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38096271

The impact of estimation methods for alcohol-attributable mortality on long-term trends for the general population and by educational level in Finland and Italy (Turin).

This paper assesses the impact of estimation methods for general and education-specific trends in alcohol-attributable mortality (AAM), and develops an alternative method that can be used when the data available for study is limited.

38096272

Penumbral thoughts: Contents of consciousness upon waking.

Thoughts shape our experience, choice, and behaviour throughout the day. Yet the content of 'penumbral thoughts'-first thoughts upon waking-has received very little research attention. Across seven independent samples (total N = 829), we used recall and reflection methods, solicited the same day, to understand what individuals think as they regain consciousness. These penumbral thoughts show remarkable thematic consistency: individuals were most likely to reflect on their somatic or psychological state, focus on temporal orientation, and prioritise waking actions. Survey results demonstrate that temporal and spatial orientation are dominated by the current time and the day ahead, rather than the past or other future timescales. Our results provide some insight into the order of priority in consciousness. We conclude that establishing one's temporal position is important to the daily process of 'rebooting' conscious awareness.

38096274

EU policies undermine environmental targets.

38096273

Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells.

Circulating tumor cells (CTCs) are the "seeds" for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and treatment.

38096275

Light-gated channelrhodopsin sparks proton-induced calcium release in guard cells.

Although there has been long-standing recognition that stimuli-induced cytosolic pH alterations coincide with changes in calcium ion (Ca²⁺) levels, the interdependence between protons (H⁺) and Ca²⁺ remains poorly understood. We addressed this topic using the light-gated channelrhodopsin <i>Hc</i>KCR2 from the pseudofungus <i>Hyphochytrium catenoides</i>, which operates as a H⁺ conductive, Ca²⁺ impermeable ion channel on the plasma membrane of plant cells. Light activation of <i>Hc</i>KCR2 in <i>Arabidopsis</i> guard cells evokes a transient cytoplasmic acidification that sparks Ca²⁺ release from the endoplasmic reticulum. A H⁺-induced cytosolic Ca²⁺ signal results in membrane depolarization through the activation of Ca²⁺-dependent SLAC1/SLAH3 anion channels, which enabled us to remotely control stomatal movement. Our study suggests a H⁺-induced Ca²⁺ release mechanism in plant cells and establishes <i>Hc</i>KCR2 as a tool to dissect the molecular basis of plant intracellular pH and Ca²⁺ signaling.

38096276

Immunotherapies for Alzheimer's disease.

Antibodies targeting amyloid-β aggregates slow decline in Alzheimer's disease.

38096277

Tracing the origin of virulence.

Microbial genomes from ancient chickens uncover the drivers of pathogenicity.

38096278

The history of the Coast Salish "woolly dogs".

DNA and traditional knowledge reveal the history of an extinct dog bred for its wool.

38096280

Chasing an equation for awareness<b>Putting Ourselves Back in the Equation</b> <i>George Musser</i> Farrar, Straus and Giroux, 2023. 336 pp.

A writer seeks connections between consciousness and fundamental physics.

38096281

Third Pole needs more than legal protection.

38096279

Securing success for the Nature Restoration Laws.

38096282

The drivers of massive star evolution.

An elusive population of stripped binary stars is finally revealed.

38096283

Runners-Up.

38096286

Extreme drought threatens the Amazon.

38096285

Microbiome diversity protects against pathogens by nutrient blocking.

The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.

38096284

Iodine oxoacids enhance nucleation of sulfuric acid particles in the atmosphere.

The main nucleating vapor in the atmosphere is thought to be sulfuric acid (H₂SO₄), stabilized by ammonia (NH₃). However, in marine and polar regions, NH₃ is generally low, and H₂SO₄ is frequently found together with iodine oxoacids [HIO<i>_x</i>, i.e., iodic acid (HIO₃) and iodous acid (HIO₂)]. In experiments performed with the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber, we investigated the interplay of H₂SO₄ and HIO<i>_x</i> during atmospheric particle nucleation. We found that HIO<i>_x</i> greatly enhances H₂SO₄(-NH₃) nucleation through two different interactions. First, HIO₃ strongly binds with H₂SO₄ in charged clusters so they drive particle nucleation synergistically. Second, HIO₂ substitutes for NH₃, forming strongly bound H₂SO₄-HIO₂ acid-base pairs in molecular clusters. Global observations imply that HIO<i>_x</i> is enhancing H₂SO₄(-NH₃) nucleation rates 10- to 10,000-fold in marine and polar regions.

38096287

Solar-powered clothes, for the heat and cold.

A wearable device allows the human body to adapt to changes in ambient temperature.

38096288

No room at the table.

The gut microbiota prevents infection by crowding out pathogens.

38096289

A challenging move.

38096290

Multifaceted SOX2-chromatin interaction underpins pluripotency progression in early embryos.

Pioneer transcription factors (TFs), such as OCT4 and SOX2, play crucial roles in pluripotency regulation. However, the master TF-governed pluripotency regulatory circuitry was largely inferred from cultured cells. In this work, we investigated SOX2 binding from embryonic day 3.5 (E3.5) to E7.5 in the mouse. In E3.5 inner cell mass (ICM), SOX2 regulates the ICM-trophectoderm program but is dispensable for opening global enhancers. Instead, SOX2 occupies preaccessible enhancers in part opened by early-stage expressing TFs TFAP2C and NR5A2. SOX2 then widely redistributes when cells adopt naive and formative pluripotency by opening enhancers or poising them for rapid future activation. Hence, multifaceted pioneer TF-enhancer interaction underpins pluripotency progression in embryos, including a distinctive state in E3.5 ICM that bridges totipotency and pluripotency.

38096291

Obesity meets its match.

Blockbuster weight loss drugs show promise for a wider range of health benefits.

38096293

Breakdowns of the Year.

What went wrong in the world of science.

38096294

In Science Journals.

Highlights from the <i>Science</i> family of journals.

38096297

Their budget bursting, U.S. particle physicists dream small.

New effort to study big bang afterglow heads to-do list.

38096292

The history of Coast Salish "woolly dogs" revealed by ancient genomics and Indigenous Knowledge.

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired "woolly dogs" that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton," collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.

38096298

Florida law blocks hiring of Chinese students.

Top officials would have to approve job offers to research staff-and process remains opaque.

38096295

More questions than answers.

Weight loss and obesity have been challenging topics in science and public health for decades. While scientists have pursued understanding through studies of metabolism and the microbiome, public health scholars have shown that social factors such as poverty and inadequate health care are also major contributors. And though it is true that excess weight carries with it numerous comorbidities that lower life expectancy and add costs to the health care system, studies also show that it is possible to be overweight and healthy. That doesn't change the fact that obesity can be associated with poor mental health, in part because of the corrosive societal stigma that associates being overweight with mental weakness, not biochemistry.

38096299

Universities uneasy with plan to disclose misconduct findings.

Transparency could benefit, but some see a threat to privacy.

38096300

What does it mean to trust a technology?

A survey published in October 2023 revealed what seemed to be a paradox. Over the past decade, self-driving vehicles have improved immeasurably, but public trust in the technology is low and falling. Only 37% of Americans said they would be comfortable riding in a self- driving vehicle, down from 39% in 2022 and 41% in 2021. Those that have used the technology express more enthusiasm, but the rest have seemingly had their confidence shaken by the failure of the technology to live up to its hype.

38096301

Do tiny black holes from cosmic dawn hide within giant stars?

Idea could account for universe's mysterious dark matter.

38096302

Dinosaur extinction researcher guilty of research misconduct.

But Robert DePalma did not commit fraud in paper claiming asteroid hit in springtime, university report finds.

38096303

Object lessons<b>So Much Stuff: How Humans Discovered Tools, Invented Meaning, and Made More of Everything</b> <i>Chip Colwell</i> University of Chicago Press, 2023. 304 pp.

An anthropologist confronts the history and ubiquity of human-made items.

38096304

Proposed FDA rule on lab tests sparks debate.

Scientists divided over whether increased regulation would protect patients or limit access.

38096305

Self-sustaining personal all-day thermoregulatory clothing using only sunlight.

The human body must stay within a certain temperature range for comfort and safety. However, challenges for thermoregulatory clothing exist for harsh application scenarios, such as full day/night cycles, frigid polar regions, and space travel. We developed a flexible and sustainable personal thermoregulatory clothing system by integrating a flexible organic photovoltaic (OPV) module to directly acquire energy from sunlight and bidirectional electrocaloric (EC) devices. The flexible OPV-EC thermoregulatory clothing (OETC) can extend the human thermal comfort zone from 22°-28°C to 12.5°-37.6°C with a fast thermoregulation rate. The low energy consumption and high efficiency of the EC device allows for 24 hours of controllable and dual-mode thermoregulation with 12 hours of sunlight energy input. This self-powered wearable thermoregulatory platform has a simple structure, compact design, high efficiency, and strong self-adaptability with sunlight as the sole energy source.

38096306

News at a glance.

38096307

Erratum for the Research Article "Agriculture and hot temperatures interactively erode the nest success of habitat generalist birds across the United States" by K. S. Lauck <i>et al</i>.

38096308

Estimating the number of required nurses in different types of hospitals: An application of the workload indicators of staffing needs (WISNS) method.

Health system performance depends on the availability, accessibility, acceptability, and quality of health workforces. Policymakers seek whether the number of nurses is optimally matched based on patients' needs. This study aimed to assess the workforce stock, workload activities, activity standards, and workload pressure to determine the number of required nurses in different types of hospitals in Iran.

38096309

Frequentist model averaging for analysis of dose-response in epidemiologic studies with complex exposure uncertainty.

In epidemiologic studies, association estimates of an exposure with disease outcomes are often biased when the uncertainties of exposure are ignored. Consequently, corresponding confidence intervals (CIs) will not have correct coverage. This issue is particularly problematic when exposures must be reconstructed from physical measurements, for example, for environmental or occupational radiation doses that were received by a study population for which radiation doses cannot be measured directly. To incorporate complex uncertainties in reconstructed exposures, the two-dimensional Monte Carlo (2DMC) dose estimation method has been proposed and used in various dose reconstruction efforts. The 2DMC method generates multiple exposure realizations from dosimetry models that incorporate various sources of errors to reflect the uncertainty of the dose distribution as well as the uncertainties in individual doses in the exposed population. Traditional measurement-error model approaches, typically based on using mean doses in the dose-exposure analysis, do not fully account exposure uncertainties. A recently developed statistical approach that overcomes many of these limitations by analyzing multiple exposure realizations in relation to disease risk is Bayesian model averaging (BMA). The analytic advantage of the BMA is its ability to better accommodate complex exposure uncertainty in the risk estimation, but a practical. Drawback is its significant computational complexity. In this present paper, we propose a novel frequentist model averaging (FMA) approach which has all the analytical advantages of the BMA method but is much simpler to implement and computationally faster. We show in simulations that, like BMA, FMA yields 95% confidence intervals for association parameters that close to 95% coverage rate. In simulations, the FMA has shorter length of CIs than those of another frequentist approach, the corrected information matrix (CIM) method. We illustrate the similarities in performance of BMA and FMA from a study of exposures from radioactive fallout in Kazakhstan.

38096310

Research on distribution network fault processing technology based on knowledge of graph.

Safety and reliability are the basis of the development of a distribution network. To analyze the risk transmission process in the distribution network and ensure the safe and reliable operation of the power system, this paper intends to use the knowledge graph method to realize the risk analysis of the distribution network information system. Firstly, the knowledge graph method is used to extract and integrate the risk knowledge of the multi-dimensional information collected by the distribution network. Secondly, the knowledge graph model of distribution network risk analysis is constructed, and the multi-dimensional distribution network fault handling and knowledge graph construction oriented to the feeder and platform area are designed. The distribution line parameters of the low-voltage distribution network model, neutral point grounding mode, and different fault types are analyzed, and the non-planned island is searched based on the knowledge graph adjacency matrix. Finally, combined with the simulation experiment, it is verified that the proposed method can effectively depict the information risk process of the distribution network. The structure of this paper starts from the multi-node complex distribution network, combined with a knowledge graph and deep learning method, which can solve the distribution network fault more quickly.

38096311

Attitudes towards LGBTQ+ individuals among Thai medical students.

The global population of individuals with gender diversity or LGBTQ+ people is on the rise. However, negative attitudes towards LGBTQ+ individuals persist, even among healthcare professionals, creating barriers to healthcare access. These attitudes are influenced by cultural variations worldwide and necessitate investigation across diverse cultures and settings.

38096312

Burial leakage: A human accustomed groundwater contaminant sources and health hazards study near cemeteries in Benin City, Nigeria.

This study was carried out to assess the levels of physico-chemical parameters that could be impacted by burial leakage and associated human health risks in Benin City, Nigeria. A total of thirty groundwater samples were collected from two cemeteries and analysed for pH, alkalinity, chloride, sulphate, nitrate, phosphate, ammonia- N, calcium, sodium, potassium, BOD₅, COD, Mn, Cd, Cu, Ni, Pb, Zn and Fe. The concentrations of the parameters were compared to national and international standards. The results revealed that the groundwater is highly acidic in nature. Principal component analysis (PCA) revealed that except for alkalinity, all other parameters characterised contributed significantly to various principal components (PC) with eigenvalues ≥ 1. Moreover, the significance of the PC depicted decomposition of the body corpse and associated burial materials. Water quality index (WQI), heavy metal evaluation index (HEI) and Nemerov pollution index (NI) indicated that groundwater from the study area is of poor quality, and highly contaminated by heavy metals. We determined the Chronic health risk through exposure by calculating the hazard quotient (HQ) and hazard index (HI), for both children and adults. For the oral exposure, approximately 33% of samples suggest the high category of chronic risk for children while the medium category was indicated for adults. We found that oral exposure showed relatively higher risk than dermal exposure, and chronic risk for children and adults ranged from low to negligible. However, the carcinogenic risk of Ni and Pb via oral exposure route suggests, very high risk for Ni and medium risk for Pb. In consideration that long term exposure to low concentrations of some heavy metals (including Pb, Cd, and Ni) could result in different manifestations of cancer, we recommend that residents of these areas should find an alternative source of water for drinking and other domestic uses.

38096313

A comprehensive framework for advanced protein classification and function prediction using synergistic approaches: Integrating bispectral analysis, machine learning, and deep learning.

Proteins are fundamental components of diverse cellular systems and play crucial roles in a variety of disease processes. Consequently, it is crucial to comprehend their structure, function, and intricate interconnections. Classifying proteins into families or groups with comparable structural and functional characteristics is a crucial aspect of this comprehension. This classification is crucial for evolutionary research, predicting protein function, and identifying potential therapeutic targets. Sequence alignment and structure-based alignment are frequently ineffective techniques for identifying protein families.This study addresses the need for a more efficient and accurate technique for feature extraction and protein classification. The research proposes a novel method that integrates bispectrum characteristics, deep learning techniques, and machine learning algorithms to overcome the limitations of conventional methods. The proposed method uses numbers to represent protein sequences, utilizes bispectrum analysis, uses different topologies for convolutional neural networks to pull out features, and chooses robust features to classify protein families. The goal is to outperform existing methods for identifying protein families, thereby enhancing classification metrics. The materials consist of numerous protein datasets, whereas the methods incorporate bispectrum characteristics and deep learning strategies. The results of this study demonstrate that the proposed method for identifying protein families is superior to conventional approaches. Significantly enhanced quality metrics demonstrated the efficacy of the combined bispectrum and deep learning approaches. These findings have the potential to advance the field of protein biology and facilitate pharmaceutical innovation. In conclusion, this study presents a novel method that employs bispectrum characteristics and deep learning techniques to improve the precision and efficiency of protein family identification. The demonstrated advancements in classification metrics demonstrate this method's applicability to numerous scientific disciplines. This furthers our understanding of protein function and its implications for disease and treatment.

38096314

Evidence suggesting that reindeer mothers allonurse according to the direct reciprocity and generalized reciprocity decision rules.

Allonursing is the nursing of the offspring of other mothers. Cooperation is an emergent property of evolved decision rules. Cooperation can be explained by at least three evolved decision rules: 1) direct reciprocity, i.e. help someone who previously helped you, 2) kin discrimination, i.e. preferentially direct help to kin than to non-kin, and 3) generalized reciprocity, i.e. help anyone if helped by someone. We assessed if semi-domesticated reindeer, Rangifer tarandus, mothers allonursed according to the decision rules of direct reciprocity, generalized reciprocity and kin discrimination over 2 years. To assess if reindeer mothers allonursed according to the direct reciprocity decision rule, we predicted that mothers should give more help to those who previously helped them more often. To assess if reindeer mothers allonursed according to the kin discrimination decision rule, we predicted that help given should increase as pairwise genetic relatedness increased. To assess if reindeer mothers allonursed according to the generalized reciprocity decision rule, we predicted that the overall number of help given by reindeer mothers should increase as the overall number of help received by reindeer mothers increased. The number of help given i) increased as the number of help received from the same partner increased in the 2012 group but not in both 2013 groups, ii) was not influenced by relatedness, and iii) was not influenced by an interaction between the number of help received from the same partner and relatedness. iv) The overall number of help given increased as the overall number of help received increased. The results did not support the prediction that reindeer mothers allonursed according to the kin discrimination decision rule. The results suggest that reindeer mothers may allonurse according to the direct reciprocity and generalized reciprocity decision rules.

38096315

Impact of digital finance on enterprise green innovation: From the perspective of information asymmetry, consumer demand and factor market distortions.

The study endeavors to empirically assess the influence of digital finance on promoting enterprise green innovation, while simultaneously probing its underlying mechanisms, by leveraging panel data from a sample of 2071 China A-share listed firms over an extensive time frame spanning from 2011 to 2021. The findings demonstrate that digital finance plays a crucial role in promoting enterprise green innovation, and that both the coverage breadth and usage depth of digital finance have a significant effect on enterprise green innovation, but the digitization level of digital finance also has a non-significant effect on enterprise green innovation, and the conclusions hold even after multiple robustness tests and consideration of endogeneity issues. Furthermore, heterogeneity analysis reveals that digital finance is only has a significant promoting effect on green innovation of SMEs, and high-tech enterprises. After conducting the mechanism analysis, it has been noted that digital finance serves as a facilitator in promoting green innovation in enterprises by reducing information asymmetry, stimulating consumer demand, and attenuating the distortion of regional factor markets. Intellectual property protection and environmental governance will strengthen the positive impact of digital finance on enterprises' green innovation. The research results provide policy implications for the green development of digital finance enabling enterprises.

38096316

Priority healthcare needs amongst people experiencing homelessness in Dublin, Ireland: A qualitative evaluation of community expert experiences and opinions.

In light of evidence that housing-related disparities in mortality are worsening over time, this study aimed to explore the perspectives of experts working in homeless health and addiction services on priority healthcare needs amongst people experiencing homelessness in Dublin, Ireland, a city facing problematic increases in homelessness. As part of a larger qualitative study, a series of semi-structured interviews were carried out with 19 community experts followed by inductive thematic framework analysis to identify emergent themes and sub-themes relating to priority healthcare needs. At the societal level, community experts identified a need to promote a culture that values health equity. At the policy level, accelerating action in addressing health inequalities was recommended with an emphasis on strategic planning, Housing First, social support options, interagency collaboration, improved data linkage and sharing, and auditing. At the health services level, removing barriers to access will require the provision of more and safer mental health, addiction, women-centred, and general practice services; resolved care pathways in relation to crisis points and multi-morbidity; expanded trauma-informed education and training and hospital-led Inclusion Health programmes; and outreach programmes and peer support for chronic disease management. The voices of people experiencing homelessness, including representatives from specific homeless groups such as migrants, youth, and the elderly, must be thoroughly embedded into health and social service design and delivery to facilitate impactful change.

38096318

Rural-urban disparities in nutritional status among ever-married women in Bangladesh: A Blinder-Oaxaca decomposition approach.

This study aims to investigate socioeconomic disparities in nutritional status among ever-married women in Bangladesh and to break down urban-rural differences in the underlying causes of undernutrition. We utilized data from the Bangladesh Demographic and Health Survey 2017-18, a sample size of 18328 ever-married women, including 5170 from urban residences, and 13159 from rural residences. To explore socioeconomic inequality, we employed a concentration indexing measure, while a multiple binary logistic regression model was carried out to identify the determinants associated with the outcome variable. A Blinder-Oaxaca decomposition analysis was performed to decompose the urban-rural gap in women's nutritional status using associated factors. The prevalence of undernutrition among ever-married women in Bangladesh was 12 percent. Notably, this percentage varied by region, with urban residents accounting for 8.6% and rural residents accounting for 13.3%. Our findings confirmed that undernutrition was more prevalent among women with lower wealth indexes in Bangladesh, as indicated by the concentration index (CIX = -0.26). The multivariable analysis investigating the determinants of undernutrition status among ever-married women, with a focus on residence revealed significant associations with respondent age, education, marital status, mass media access, wealth status, and division. According to the Blinder-Oaxaca decomposition and its extension, the prevalence was significantly higher in rural residences of Bangladesh than in urban residences, and the endowment effect explained 86 percent of the total urban-rural difference in undernutrition prevalence. The results of this study indicate that the factors that influence women's nutritional status in rural areas play a significant role in the gap, and the majority of the gap is caused by education and economic position. In order to effectively promote maternal health policies in Bangladesh, intervention techniques should be created that are aimed at the population, that is, the poorest and least educated.

38096317

Optimized strategy for real-time qPCR detection of Onchocerca volvulus DNA in pooled Simulium sp. blackfly vectors.

Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease.

38096319

Human arm endpoint-impedance in rhythmic human-robot interaction exhibits cyclic variations.

Estimating the human endpoint-impedance interacting with a physical environment provides insights into goal-directed human movements during physical interactions. This work examined the endpoint-impedance of the upper limb during a hybrid ball-bouncing task with simulated haptic feedback while participants manipulated an admittance-controlled robot. Two experiments implemented a force-perturbation method to estimate the endpoint parameters of 31 participants. Experimental conditions of the ball-bouncing task were simulated in a digital environment. One experiment studied the influence of the target height, while the other explored the impedance at three cyclic phases of the rhythmic movement induced by the task. The participants' performances were analyzed and clustered to establish a potential influence of endpoint impedance on performance in the ball-bouncing task. Results showed that endpoint-impedance parameters ranged from 45 to 445 N/m, 2.2 to 17.5 Ns/m, and 227 to 893 g for the stiffness, damping, and mass, respectively. Results did not support such a critical role of endpoint impedance in performance. Nevertheless, the three endpoint-impedance parameters described significant variations throughout the arm cycle. The stiffness is linked to a quasi-linear increase, with a maximum value reached before the ball impacts. The observed damping and mass cyclic variations seemed to be caused by geometric and kinematic variations. Although this study reveals rapid and within-cycles variations of endpoint-impedance parameters, no direct relationship between endpoint-impedance values and performance levels in ball-bouncing could be found.

38096320

Differences in eye movements for face recognition between Canadian and Chinese participants are not modulated by social orientation.

Face recognition strategies do not generalize across individuals. Many studies have reported robust cultural differences between West Europeans/North Americans and East Asians in eye movement strategies during face recognition. The social orientation hypothesis posits that individualistic vs. collectivistic (IND/COL) value systems, respectively defining West European/North American and East Asian societies, would be at the root of many cultural differences in visual perception. Whether social orientation is also responsible for such cultural contrast in face recognition remains to be clarified. To this aim, we conducted two experiments with West European/North American and Chinese observers. In Experiment 1, we probed the existence of a link between IND/COL social values and eye movements during face recognition, by using an IND/COL priming paradigm. In Experiment 2, we dissected the latter relationship in greater depth, by using two IND/COL questionnaires, including subdimensions to those concepts. In both studies, cultural differences in fixation patterns were revealed between West European/North American and East Asian observers. Priming IND/COL values did not modulate eye movement visual sampling strategies, and only specific subdimensions of the IND/COL questionnaires were associated with distinct eye-movement patterns. Altogether, we show that the typical contrast between IND/COL cannot fully account for cultural differences in eye movement strategies for face recognition. Cultural differences in eye movements for faces might originate from mechanisms distinct from social orientation.

38096321

Applications of natural language processing at emergency department triage: A narrative review.

Natural language processing (NLP) uses various computational methods to analyse and understand human language, and has been applied to data acquired at Emergency Department (ED) triage to predict various outcomes. The objective of this scoping review is to evaluate how NLP has been applied to data acquired at ED triage, assess if NLP based models outperform humans or current risk stratification techniques when predicting outcomes, and assess if incorporating free-text improve predictive performance of models when compared to predictive models that use only structured data.

38096322

Exploring the nexus between physical environments, resident preferences, and usage frequency of community centers: Evidence from two Korean neighborhoods in Seoul.

Community centers offer a public space for physical activities, attracting residents with diverse interests and abilities, and promoting social interaction and connection, which in turn enhances individuals' physical and mental fitness and fosters a sense of community. When exploring the correlation between community space accessibility and usage frequency, it is crucial to consider empirical evidence and resident preferences. Nevertheless, the role of physical environments in determining community center usage frequency, while also considering residents' inclination for effortless access, remains unclear. This study investigated the impact of resident preferences and satisfaction with the accessibility of community centers and physical environments on usage frequency, addressing a gap in previous research. Structural equation models were utilized to analyze a household drop-off survey consisting of 186 residents gathered from two neighborhoods in Korea. The results revealed that while the preference for easy access to community centers did not have a substantial effect on their usage frequency, satisfaction with easy access to such centers was positively linked to usage frequency. Furthermore, the perception of physical environments as being walkable and having a diverse range of amenities was associated with a higher frequency of community center usage. These findings have policy implications as they can help increase the usage frequency of community centers and enhance overall well-being in regenerated neighborhoods.

38096323

The impact of total factor mobility on rural-urban symbiosis: Evidence from 27 Chinese provinces.

The rational flow and optimal allocation of urban and rural factors is the key to solving the problem of unbalanced and insufficient urban and rural development. This study draws on the theory of ecological symbiosis to examine the mechanism of factor flow and urban-rural symbiosis. It analyzes panel data from 27 Chinese provinces and autonomous regions between 2010 and 2020 to empirically demonstrate the influence of labor, capital, technology, and land mobility on urban-rural symbiosis. The study found that: (1) The relationship between the total factor flow and urban-rural symbiosis is U-shaped nonlinear, and the time when cities feed the development of rural areas has come; (2) The impact of labor factor flow on urban-rural symbiosis exhibits an inverted U-shaped relationship, the impact of capital factor flow displays a positive U-shaped relationship, the impact of land factor flow shows an inverted U-shaped relationship, and the impact of technical factor flow on urban-rural symbiotic development is not significant. (3) The factor flow exerts a region-oriented impact on the level of urban-rural symbiosis. In developed areas, total factor flow does not affect urban-rural symbiosis, but the level of labor flow and the urban-rural symbiosis demonstrates an inverted U-shaped relationship, the flow of technological factors has a U-shaped impact on the urban-rural symbiosis level, the flow of land factors and the urban-rural symbiosis show an inverted U-shaped relationship, and the flow of capital factors has no impact on the urban-rural symbiosis relationship. In underdeveloped areas, the impact of the total factor flow on urban-rural symbiosis shows a significantly positive U-shaped characteristic, the labor mobility level and urban-rural symbiosis show an inverted U-shaped relationship, the flow of capital factors has a U-shaped impact on the urban-rural symbiosis level, and the flow of lands and technology does not have a remarkable impact on urban-rural symbiosis in underdeveloped areas.

38096324

Deep learning-based idiomatic expression recognition for the Amharic language.

Idiomatic expressions are built into all languages and are common in ordinary conversation. Idioms are difficult to understand because they cannot be deduced directly from the source word. Previous studies reported that idiomatic expression affects many Natural language processing tasks in the Amharic language. However, most natural language processing models used with the Amharic language, such as machine translation, semantic analysis, sentiment analysis, information retrieval, question answering, and next-word prediction, do not consider idiomatic expressions. As a result, in this paper, we proposed a convolutional neural network (CNN) with a FastText embedding model for detecting idioms in an Amharic text. We collected 1700 idiomatic and 1600 non-idiomatic expressions from Amharic books to test the proposed model's performance. The proposed model is then evaluated using this dataset. We employed an 80 by 10,10 splitting ratio to train, validate, and test the proposed idiomatic recognition model. The proposed model's learning accuracy across the training dataset is 98%, and the model achieves 80% accuracy on the testing dataset. We compared the proposed model to machine learning models like K-Nearest Neighbor (KNN), Support Vector Machine (SVM), and Random Forest classifiers. According to the experimental results, the proposed model produces promising results.

38096326

Expanding the UTAUT2 framework to determine the drivers of mobile shopping behaviour among older adults.

In the current severe aging of the population, the problem of "digital divide" of the elderly has become increasingly prominent, and the elderly market represents a vast demographic that is increasingly becoming an important customer segment for mobile shopping in the future. However, there is currently insufficient attention given to the research on mobile shopping behavior among older adults. This study tries to answer what are the driving factors of mobile phone shopping behavior among the elderly? The purpose of this study is to analyze the factors that drive the elderly's mobile phone shopping behavior, and to establish a mobile phone shopping acceptance model for the elderly to predict the factors of the elderly's behavioral intention of using smart phones. Based on the second edition of Unified Theory of Acceptance and Use of Technology theory (UTAUT 2), this study proposed a mobile phone shopping acceptance model for the elderly. The study collected valid data from 389 Chinese elderly people through questionnaires and analyzed them using structural equation models. The results showed that utilitarian, anxiety, trust, performance expectancy, effort expectancy, social influence, facilitating conditions and habit directly impact the older adults' intention to engage in mobile shopping. Additionally, facilitating conditions, habit and the older adults' intention to engage in mobile shopping act as driving factors for actual use behavior. This study further expands the UTAUT theoretical model, provides a theoretical basis for the research of mobile shopping behavior of the elderly, and enricues the application groups and fields of the UTAUT theoretical model. The results of this study provide inspiration for the development, design and marketing of age-appropriate mobile shopping products, and contribute to the realization and further adoption of age-appropriate mobile shopping, and also contribute to promoting the active aging of the elderly.

38096325

Demonstrating the importance of porcine reproductive and respiratory syndrome virus papain-like protease 2 deubiquitinating activity in viral replication by structure-guided mutagenesis.

Deubiquitination of cellular substrates by viral proteases is a mechanism used to interfere with host cellular signaling processes, shared between members of the coronavirus- and arterivirus families. In the case of Arteriviruses, deubiquitinating and polyprotein processing activities are accomplished by the virus-encoded papain-like protease 2 (PLP2). Several studies have implicated the deubiquitinating activity of the porcine reproductive and respiratory syndrome virus (PRRSV) PLP2 in the downregulation of cellular interferon production, however to date, the only arterivirus PLP2 structure described is that of equine arteritis virus (EAV), a distantly related virus. Here we describe the first crystal structure of the PRRSV PLP2 domain both in the presence and absence of its ubiquitin substrate, which reveals unique structural differences in this viral domain compared to PLP2 from EAV. To probe the role of PRRSV PLP2 deubiquitinating activity in host immune evasion, we selectively removed this activity from the domain by mutagenesis and found that the viral domain could no longer downregulate cellular interferon production. Interestingly, unlike EAV, and also unlike the situation for MERS-CoV, we found that recombinant PRRSV carrying PLP2 DUB-specific mutations faces significant selective pressure to revert to wild-type virus in MARC-145 cells, suggesting that the PLP2 DUB activity, which in PRRSV is present as three different versions of viral protein nsp2 expressed during infection, is critically important for PRRSV replication.

38096327

Friendship interventions for children with neurodevelopmental needs: A systematic review and meta-analysis.

Children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual disability (ID), and social (pragmatic) communication disorder (SPCD) experience difficulties with social functioning due to differences in their social, emotional and cognitive skills. Previous systematic reviews have focussed on specific aspects of social functioning rather than broader peer functioning and friendships.

38096328

Design and experiment of a shovel-tooth removal end-effector for abnormal plants in hybrid rape breeding based on MBD-DEM coupling.

In view of the problem that removing abnormal plants in breeding rape requires a large amount of labor and is inefficient, combined with the planting requirements of breeding rape, a shovel-tooth end-effector was designed, and a shovel-tooth removal test bench was built. A simulation model based on MBD (Multibody Dynamics)-DEM (Discrete Element Method) coupling was constructed. Then we conducted a Box-Behnken test with four factors and three levels. Taking the angle of soil penetration, speed of soil penetration, depth of soil penetration and speed of shovel-tooth gathering as the test factors, the soil penetration force and shovel-tooth gathering force as the test indicators. The mathematical regression model between test indicators and test factor was established. After optimizing the parameters of the model, the best combination of parameters with low soil penetration force and low shovel-tooth gathering force was obtained: angle of soil penetration of 84°, speed of soil penetration of 9 cm/s, depth of soil penetration of 8cm, and speed of shovel-tooth gathering of 6 cm/s. The simulation model was validated by field experiments. The average soil penetration force and average shovel-tooth gathering force of the three groups of pull-out tests were 34.8 N and 763.0 N, respectively. The removal rates were 96%, 92%, and 94%, all greater than 90%, indicating that the removal effect of the shovel-tooth end-effector was good, and the parameters were reasonably designed. The results can serve as reference for the design of rape abnormal plants removal device and the operation of MBD-DEM coupling simulation end-effector.

38096329

A Mendelian randomization study on the causal association of circulating cytokines with colorectal cancer.

Circulating cytokines have been associated with colorectal cancer (CRC). However, their causal correlation remains undetermined. This investigation uses genetic data to evaluate the mechanism that links circulating cytokines and CRC via Mendelian Randomization (MR).

38096331

Research on the synergetic development of producer services and manufacturing in northwest China's inland central cities-A case study of Lanzhou.

Under the post Ford flexible production organization system, the existence of specialized division of labor has made the forward and backward connections between the producer services as an intermediate input and the manufacturing increasingly close. With the proposal of the "Belt and Road" and the deepening of "The development of the western region in China", the northwest region plays an increasingly important role in China's regional development strategy, and the economic transformation, especially the transformation and upgrading of the manufacturing, and it is crucial to its completion of the strategic mission entrusted by the state. Taking Lanzhou City as a case area, based on the measurement of the cooperative development level of producer services and manufacturing, this paper explores the internal law of the synergetic development of producer services and manufacturing in the northwest inland central city. The study found: The overall synergy development level of producer services and manufacturing in Lanzhou has been significantly improved in the dynamic evolution process, and two industries are in the transition stage from the primary coordinated development to the intermediate coordinated development at present. The spatial layout of producer services and manufacturing in Lanzhou City has certain spatial proximity, and the overall presents a "center-periphery" spatial pattern with the main urban area as the main component. From the perspective of the synergistic development of producer services and manufacturing in Lanzhou, the two industries have initially formed an interactive relationship of two-way promotion at present, but there is a significant asymmetry in the two-way promoting effect of the two industries.

38096330

Comparison of yeast-derived commercial feed additives on Salmonella Enteritidis survival and microbiota populations in rooster cecal in vitro incubations.

Yeast-derived products have become more of an interest in the poultry industry as of late because of their use in modulating the gastrointestinal tract (GIT) microbiome to both improve production parameters and prevent infection. This study aimed to evaluate the effects of various yeast-derived products on Salmonella enterica inoculation in un in vitro rooster cecal incubations and associated effects on the cecal microbiome. Cecal contents were obtained from 53-wk old White Leghorn H & N Nick Chick roosters (n = 3) fed a wheat-based, commercial-type basal diet. Cecal contents were diluted 1:3000 in anaerobic dilution solution (ADS) in an anaerobic chamber, with 20 mL aliquoted to each serum bottle. There were three controls (n = 3): basal diet only, diluted cecal contents only, and basal diet and diluted cecal contents; and five treatments containing the basal diet and diluted cecal contents (n = 3): Citristim® (ADM), ImmunoWall® (ICC), Maxi-Gen Plus® (CBS Bio Platforms), Hilyses® (ICC), and Original XPC® (Diamond V). All treatments were applied at a rate of 2.5 kg/tonne or less. All groups were inoculated with a nalidixic acid-resistant strain of Salmonella Enteritidis at 10^7 CFU/mL and incubated at 37 deg C. Samples were collected at 0, 24, and 48 h for S. Enteritidis enumeration and 16S rDNA microbial sequencing. Salmonella data were log-transformed and analyzed in a two-way ANOVA with means separated using Tukey's HSD (P≤0.05). Genomic DNA was extracted, and resulting libraries were prepared and sequenced using an Illumina MiSeq. Sequencing data were analyzed in QIIME2 (2021.4) with diversity metrics (alpha and beta), and an analysis of the composition of microbiomes (ANCOM) was performed. Main effects were considered significant at P≤0.05, with pairwise differences considered significant at Q≤0.05. There was an interaction of treatment and time on the enumeration of Salmonella where treatments of Citristim, Immunowall, Hilyses, and XPC reduced Salmonella by 1 log CFU/mL compared to the controls. At 48 h, each yeast product treatment reduced Salmonella by 3 log CFU/mL compared to the controls. There was no main effect of treatment on the alpha diversity metrics, richness, or evenness (P > 0.05). Treatment affected the beta diversity, abundance, and phylogenetic differences, but there were no pairwise differences (P>0.05, Q>0.05). Using ANCOM at the genus level, the taxa Synergistes, Alloprevotella, Sutterella, and Megasphaera abundance were significantly different (W = 154,147,145,140, respectively). These results demonstrate the potential of these yeast-derived products to reduce foodborne pathogens, such as Salmonella Enteriditis, in vitro, without negatively disrupting the cecal microbiome.

38096332

Evaluation of PPP-ABS investment environment based on combined weighting of level difference maximization and TOPSIS method.

Asset-backed securitization (ABS) is currently used to refinance public-private partnership (PPP) projects in the infrastructure field. To stimulate the investors' enthusiasm, this study evaluated the investment environment of PPP projects asset-backed securitization (PPP-ABS). Firstly, we established a PPP-ABS investment environment evaluation indicator system based on the literature review and the practice of PPP-ABS. Then, the optimal weights of each indicator were determined by the combined weighting of level difference maximization method, where the subjective weights were determined by the AHP method, and the objective weights were determined by the entropy method. Finally, we evaluated the PPP-ABS investment environment from 2015 to 2022 with the technique for order preference by similarity to ideal solution (TOPSIS) method. The final valuation results are consistent with the actual situation. The results showed that the PPP-ABS investment environment exhibits a stable and upward trend. Under the overall guidance of the government, the approval process, information disclosure and supervisory systems have continued to improve, the number of ABS products issued has continued to grow, and the overall market risk is controllable. However, some problems still need to be solved and improved, including inadequate accounting and tax systems, insufficient liquidity in the secondary market, and the recovery of economic development in the post-COVID-19 era. This study fills the research gap in PPP-ABS. It proves the rationality and feasibility of PPP-ABS and is expected to provide a reference for investors' decision-making and promote the sustainable and healthy development of PPP-ABS.

38096333

A molecular sieve with ultrafast adsorption kinetics for propylene separation.

The design of molecular sieves is vital for gas separation, but it suffers from a long-standing issue of slow adsorption kinetics due to the intrinsic contradiction between molecular sieving and diffusion within restricted nanopores. We report a molecular sieve ZU-609 with local sieving channels that feature molecular sieving gates and rapid diffusion channels. The precise cross-section cut-off of molecular sieving gates enable the exclusion of propane from propylene. The co-existed large channels constituted by sulfonic anions and helically arranged metal-organic architectures allow the fast adsorption kinetics of propylene, and the measured propylene diffusion coefficient in ZU-609 is one to two orders of magnitude higher than previous molecular sieves. Propylene with 99.9% purity is obtained through breakthrough experiments with a productivity of 32.2 L kg^-1.

38096334

Electrophotocatalytic perfluoroalkylation by LMCT excitation of Ag(II) perfluoroalkyl carboxylates.

Molecular Ag(II) complexes are super-oxidizing photoredox catalysts capable of generating radicals from redox reticent substrates. Herein, we exploit the electrophilicity of Ag(II) centers in [Ag(bpy)₂(TFA)][OTf] and Ag(bpy)(TFA)₂ complexes to activate trifluoroacetate (TFA) by visible-light-induced homolysis. The resulting trifluoromethyl radicals may react with a variety of arenes to forge C(sp²)-CF₃ bonds. This methodology is general and extends to other perfluoroalkyl carboxylates of higher chain length (R_FCO₂^-; R_F = CF₂CF₃ or CF₂CF₂CF₃). The photoredox reaction may be rendered electrophotocatalytic by regenerating the Ag(II) complexes electrochemically during irradiation. Electrophotocatalytic perfluoroalkylation of arenes at turnover numbers exceeding 20 is accomplished by photoexciting the Ag(II)-TFA ligand-to-metal charge transfer (LMCT) state followed by electrochemical re-oxidation of the Ag(I) photoproduct back to the Ag(II) photoreactant.

38096335

Treatment of an Ulnar Fracture Bone Defect Using Heterotopic Bone Autograft: A Case Report.

Autologous bone grafting has wide applications for the treatment of bony defects. Generally, cancellous or corticocancellous bone grafts are used depending on the characteristics and size of the bony defect and wound bed. The use of heterotopic bone as a potential source of bone graft has not been widely reported. We present a 56-year-old right-hand-dominant male victim of dog mauling who sustained a right ulnar fracture with a 5-cm bony defect, treated with the use of heterotopic bone autograft.

38096336

Patellar Tendon Rupture During Postoperative Physiotherapy for Crouch Gait: A Case Report.

A 14-year-old adolescent girl with spastic diplegic cerebral palsy underwent bilateral distal femur extension osteotomy and patellar tendon plication. Two and a half months after surgery, during physiotherapy, she sustained mid-substance tear of the left patellar tendon. The girl was successfully managed with patellar tendon repair and augmentation with tensor fascia lata autograft.

38096337

Erratum: Chronic Volar Distal Radial Ulnar Joint Dislocation: A Case Report with Proposed Treatment Algorithm.

38096338

Intraoperative Ultrasound for Extracting Deep-Seated Radio-Opaque Foreign Body from Calf: A Case Report.

A 50-year-old man presented with chronic refractory symptoms of radiating leg pain with muscle cramps because of a retained bullet in the calf after being shot in 1990. Radiographs confirmed the bullet lodged in posterolateral aspect of calf abutting proximal fibula. An intraoperative point-of-care ultrasound aided in accurate localization of bullet, thereby facilitating precise planning of surgical incision and subsequent removal.

38096339

A Sarcoma Masquerading as a Pseudotumor After Total Hip Arthroplasty: A Case Report.

There is an increasing emphasis on adverse reactions to metal debris around prosthetic hip implants. We present a case report of a patient with increasing pain around a previous total hip arthroplasty and magnetic resonance imaging findings consistent with a pseudotumor. Serum metal ion levels were not elevated and initial biopsy findings inconclusive. The patient was diagnosed with an extraskeletal chondrosarcoma after revision total hip arthroplasty and subsequently underwent external hemipelvectomy with negative margins.

38096340

Complete Repair of Osteonecrosis of the Femoral Head After Basicervical Femoral Neck Rotational Osteotomy: A Case Report.

We present a 28-year-old female patient who developed left hip pain and was diagnosed with osteonecrosis of the femoral head (ARCO stage II). The patient underwent a basicervical femoral neck rotational osteotomy (BFNRO) combining surgical hip dislocation technique and extended retinacular soft-tissue flap technique. She was followed up for 53 months and exhibited complete repair of the necrotic area, with normal hip range of motion, gait, and excellent hip functional scores.

38096358

Identification and surveillance of rare relapse-initiating stem cells during complete remission post-transplantation.

Relapse following complete remission (CR) remains the main cause of mortality after allogeneic stem cell transplantation for hematological malignancies and therefore improved biomarkers for early prediction of relapse remains a critical goal towards development and assessment of preemptive relapse treatment. Since the significance of cancer stem cells as a source of relapses remains unclear, we investigated whether mutational screening for persistence of rare cancer stem cells would enhance measurable residual disease (MRD) and early relapse-prediction post-transplantation. In a retrospective study of relapse patients and continuous-CR patients with myelodysplastic syndromes and related myeloid malignancies, combined flow cytometric cell sorting and mutational screening for persistence of rare relapse-initiating stem cells was performed in bone marrow at multiple CR time points post-transplantation. In 25 CR samples from 15 patients that later relapsed, only 9 samples were MRD-positive in mononuclear cells (MNCs) whereas flowcytometric sorted hematopoietic stem and progenitor cells (HSPCs) were MRD-positive in all samples, and always with a higher variant allele frequency than in MNCs (mean 97-fold). MRD-positivity in HSPCs preceded MNCs in multiple sequential samples, in some cases preceding relapse by more than 2 years. In distinction, in 13 patients in long-term continuous-CR, HSPCs remained MRD-negative. Enhanced MRD-sensitivity was also observed in total CD34+ cells, but HSPCs were always more clonally involved (mean 8-fold).In conclusion, identification of relapse-initiating cancer stem cells and mutational MRD-screening for their persistence consistently enhances MRD-sensitivity and earlier prediction of relapse after allogeneic stem cell transplantation.

38096359

One-Pot Synthesis of Cereblon Proteolysis Targeting Chimeras via Photoinduced C(sp²)-C(sp³) Cross Coupling and Amide Formation for Proteolysis Targeting Chimera Library Synthesis.

In this study, a one-pot synthesis via photoinduced C(sp²)-C(sp³) coupling followed by amide formation to access proteolysis targeting chimeras (PROTACs) was developed. The described protocol was studied on cereblon (CRBN)-based E3-ligase binders and (+)-JQ-1, a bromodomain inhibitor, to generate BET (bromodomain and extra terminal domain) targeting protein degraders. The generated PROTACs were profiled in vitro and tested for their degradation ability with several potent candidates identified. Upfront, the individual reactions of the one-pot transformation were carefully optimized for CRBN binder functionalization and multiple heterobifunctional linker moieties were designed and synthesized. Separate scopes detailing the C(sp²)-C(sp³) coupling and one-pot PROTAC synthesis are described in this report as well as a library miniaturization study showing the high-throughput compatibility. Overall, the developed protocol provides rapid access to PROTACs in a single process, thereby allowing efficient generation of CRBN-based PROTAC libraries.

38096360

Potent Half-Sandwich 16-/18-Electron Iridium(III) and Ruthenium(II) Anticancer Complexes with Readily Available Amine-Imine Ligands.

The synthesis and biological evaluation of stable 16-electron half-sandwich complexes have remained scarce. We herein present the different coordination modes (16-electron or 18-electron) between half-sandwich iridium(III) complexes and ruthenium(II) complexes derived from the same amine-imine ligands chelating hybrid sp³-N/sp²-N donors. The 16-electron iridium(III) and 18-electron ruthenium(II) complexes with different counteranions were obtained and identified by various techniques. The promising cytotoxicity of these complexes against A549 lung cancer cells, cisplatin-resistant A549/DPP cells, cervical carcinoma HeLa cells, and human hepatocellular liver carcinoma HepG2 cells was observed with IC₅₀ values ranging from 5.4 to 16.3 &#956;M. Moreover, these complexes showed a certain selectivity (selectivity index: 2.1-3.7) toward A549 cells and BEAS-2B normal cells. The variation of metal center, counteranion, 16/18-electron coordination mode, and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The mechanism of action study showed that these complexes could target mitochondria, induce the depolarization of the mitochondrial membrane, and promote the generation of intracellular reactive oxygen species (ROS). Further, the induction of cell apoptosis and the perturbation of the cell cycle in the G₀/G₁ phase were also observed for these complexes. Overall, it seems that the redox mechanism dominated the anticancer efficacy of these complexes.

38096362

Probing Chemical Complexity of Amyloid Plaques in Alzheimer's Disease Mice using Hyperspectral Raman Imaging.

One of the distinctive pathological features of Alzheimer's disease (AD) is the deposition of amyloid plaques within the brain of affected individuals. These plaques have traditionally been investigated using labeling techniques such as immunohistochemical imaging. However, the use of labeling can disrupt the structural integrity of the molecules being analyzed. Hence, it is imperative to employ label-free imaging methods for noninvasive examination of amyloid deposits in their native form, thereby providing more relevant information pertaining to AD. This study presents compelling evidence that label-free and nondestructive confocal Raman imaging is a highly effective approach for the identification and chemical characterization of amyloid plaques within cortical regions of an arcAβ mouse model of AD. Furthermore, this investigation elucidates how the spatial correlation of Raman signals can be exploited to identify robust Raman marker bands and discern proteins and lipids from amyloid plaques. Finally, this study uncovers the existence of distinct types of amyloid plaques in the arcAβ mouse brain, exhibiting significant disparities in terms of not only shape and size but also molecular composition.

38096361

Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promote eosinophilia and arterial thrombosis.

Increased eosinophil counts are associated with cardiovascular disease and may be an independent predictor of major cardiovascular events. However, the causality and underlying mechanisms are poorly understood. GWAS have shown an association of a common LNK variant (R262W, T allele) with eosinophilia and atherothrombotic disorders. LNK(TT) reduces LNK function and Lnk-deficient mice display accelerated atherosclerosis and thrombosis. This study was undertaken to assess the role of eosinophils in arterial thrombosis in mice with hematopoietic Lnk deficiency. Hematopoietic Lnk deficiency increased circulating and activated eosinophils, JAK/STAT signaling in eosinophils and carotid arterial thrombosis with increased eosinophil abundance and extracellular trap formation (EETosis) in thrombi. Depletion of eosinophils by anti-Siglec-F antibody or by the ∆dbIGata1 mutation eliminated eosinophils in thrombi and markedly reduced thrombosis in mice with hematopoietic Lnk deficiency but not in control mice. Eosinophil depletion reduced neutrophil abundance and NETosis in thrombi without altering circulating neutrophil counts. To assess the role of Lnk specifically in eosinophils, we crossed Lnkf/f mice with eoCre mice. Lnk∆eos mice displayed isolated eosinophilia, increased eosinophil activation and accelerated arterial thrombosis associated with increased EETosis and NETosis in thrombi. DNase I infusion abolished EETs and NETs in thrombi and reversed the accelerated thrombosis. Human iPSC-derived LNK(TT) eosinophils showed increased activation and EETosis relative to isogenic LNK(CC) eosinophils, demonstrating human relevance. These studies show a direct link between eosinophilia, EETosis and atherothrombosis in hematopoietic Lnk deficiency and an essential role of eosinophil LNK in suppression of arterial thrombosis.

38096364

Reducing Facial Stereotype Bias in Consequential Social Judgments: Intervention Success With White Male Faces.

Initial impressions of others based on facial appearances are often inaccurate yet can lead to dire outcomes. Across four studies, adult participants underwent a counterstereotype training to reduce their reliance on facial appearance in consequential social judgments of White male faces. In Studies 1 and 2, trustworthiness and sentencing judgments among control participants predicted whether real-world inmates were sentenced to death versus life in prison, but these relationships were diminished among trained participants. In Study 3, a sequential priming paradigm demonstrated that the training was able to abolish the relationship between even automatically and implicitly perceived trustworthiness and the inmates' life-or-death sentences. Study 4 extended these results to realistic decision-making, showing that training reduced the impact of facial trustworthiness on sentencing decisions even in the presence of decision-relevant information. Overall, our findings suggest that a counterstereotype intervention can mitigate the potentially harmful effects of relying on facial appearance in consequential social judgments.

38096363

A p53 score derived from TP53 CRISPR/Cas9 HMCLs predicts survival and reveals major role of BAX in BH3 mimetics response.

To establish a strict p53-dependent gene expression profile, TP53-/- clones were derived from TP53+/+ and TP53-/mut t(4;14) human myeloma cell lines (HMCLs) using CRISPR/Cas9 technology. From the 17 dysregulated genes shared between the TP53-/- clones from TP53+/+ HMCLs, we established a functional p53 score, involving 13 genes specifically downregulated upon p53 silencing. This functional score segregated clones and myeloma cell lines, as well as other cancer cell lines according to their TP53 status. The score was efficient to identify myeloma patient samples with biallelic TP53 inactivation and was predictive of overall survival in MMRF-coMMpass and CASSIOPEA cohorts. At the functional level, we showed that among the 13 genes, p53-regulated BAX expression correlated to, and directly impacted, the MCL1 BH3 mimetic S63845 sensitivity of myeloma cells by decreasing MCL1-BAX complexes. However, resistance to S63845 was overcome by combining MCL1 and BCL2 BH3 mimetics which displayed synergistic efficacy. BH3 mimetics combination was efficient in 97% of patient samples with or without del17p. Nevertheless, scRNAseq analysis showed that myeloma cells surviving to the combination had lower p53 score, showing that myeloma cells with higher p53 score were more sensitive to BH3 mimetics. Taken together, we established a functional p53 score that identifies myeloma cells with biallelic TP53 invalidation, demonstrated that p53-regulated BAX is critical for optimal cell response to BH3 mimetics, and showed that MCL1 and BCL2 BH3 mimetics combination may be of interest for patients with biallelic TP53 invalidation, for whom there is still an unmet medical need.

38096365

Teclistamab in relapsed or refractory AL amyloidosis, a multinational retrospective case series.

Teclistamab shows promising results in R/R AL amyloidosis, with VGPR or better in 88% of patients and involved FLC < 10 mg/L in 76%. We observed a 35% rate of severe infections and no cardiac or kidney related events.

38096366

Synthesis, Optimization, and Structure-Activity Relationships of Nicotinamide Phosphoribosyltransferase (NAMPT) Positive Allosteric Modulators (N-PAMs).

Depletion of nicotinamide adenine dinucleotide (NAD⁺) is associated with aging and disease, spurring the study of dietary supplements to replenish NAD⁺. The catabolism of NAD⁺ to nicotinamide (NAM) requires the salvage of NAM to replenish cellular NAD⁺, which relies on the rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT). Pharmacological activation of NAMPT provides an alternative to dietary supplements. Screening for activators of NAMPT identified small molecule NAMPT positive allosteric modulators (N-PAMs). N-PAMs bind to the rear channel of NAMPT increasing enzyme activity and alleviating feedback inhibition by NAM and NAD⁺. Synthesis of over 70 N-PAMs provided an excellent correlation between rear channel binding affinity and potency for enzyme activation, confirming the mechanism of allosteric activation via binding to the rear channel. The mechanism accounts for higher binding affinity leading to loss of efficacy. Enzyme activation translated directly to elevation of NAD⁺ measured in cells. Optimization led to an orally bioavailable N-PAM.

38096367

Practice Trends and Job Satisfaction of Dental Therapists in Canada: Results from a National Survey.

The objective of this research was to evaluate the practice trends, clinical services and job satisfaction of dental therapists in Canada. Licenced Canadian dental therapists were recruited to participate in this cross-sectional study. A total of 124 dental therapists completed the survey (~68% response rate), with 57.3% of respondents being over the age of 50. Most respondents were actively engaged in full-time clinical practice in private dental offices. Indigenous dental therapists were significantly more likely to work outside of private dental offices providing care for Indigenous communities. Just over half of respondents were compensated by an annual salary, with the highest proportion of full-time practitioners earning between $75,000 and $99,000 per year. Dental therapists who were active in clinical practice performed a wide range of preventive, diagnostic, and treatment services consistent with their scope of practice. This research demonstrates that Canadian dental therapists are highly engaged and satisfied with their profession. Dental therapists can facilitate improved access to oral health care in less accessible areas of Canada; however, compensation packages and incentives to work in these less accessible areas must be addressed, as well as legal and regulatory requirements to ensure that dental therapists are licenced providers throughout Canada.

38096368

Cell crosstalk within lymphoma tumor microenvironment: follicular lymphoma as a paradigm.

Follicular lymphoma (FL) is an indolent yet incurable germinal center B-cell lymphoma retaining a characteristic follicular architecture. FL tumor B cells are highly dependent on direct and indirect interactions with a specific and complex tumor microenvironment (TME). Great progress has been recently made in describing the heterogeneity and dynamics of FL-TME and in depicting how tumor clonal and functional heterogeneity rely on the integration of TME-related signals. Specifically, FL-TME is enriched for exhausted cytotoxic T cells, immunosuppressive regulatory T cells of various origins, and follicular helper T cells overexpressing B cell and TME reprogramming factors. FL stromal cells have also emerged as crucial determinants of tumor growth and remodeling, with a key role for deregulated chemokines and extracellular matrix composition. Finally, tumor associated macrophages play a dual function, contributing to FL cell phagocytosis and to FL cell survival through BCR long-lasting activation. The resulting tumor-permissive niches show additional layers of site-to-site and kinetic heterogeneity, which raise questions about the niche of FL-committed precursor cells supporting early lymphomagenesis, clonal evolution, relapse, and transformation. In turn, FL B cell genetic and non-genetic determinants drive the reprogramming of FL immune and stromal TME. Therefore, offering a functional picture of the dynamic crosstalk between FL cells and TME holds the promise of identifying the mechanisms of therapy resistance, stratifying patients, and developing new therapeutic approaches capable of eradicating FL disease in its different ecosystems.

38096369

Low-frequency inherited complement receptor variants are associated with purpura fulminans.

Extreme disease phenotypes can provide key insights into the pathophysiology of common conditions, but studying these patients is challenging due to their rarity and the limited statistical power of existing methods. Herein, we used a novel approach to pathway-based mutational burden testing, the rare variant trend test (RVTT), to investigate genetic risk factors for an extreme form of sepsis-induced coagulopathy, infectious purpura fulminans (PF). In addition to prospective patient sample collection, we electronically screened over 10.4 million medical records from four large hospital systems and identified historical cases of PF for which archived specimens were available to perform germline whole exome sequencing. We found a significantly increased burden of rare, putatively function-altering variants in the complement system in patients with PF compared to unselected patients with sepsis (p=0.01). A multivariable logistic regression analysis found that the number of complement system variants per patient was independently associated with PF after controlling for age, sex, and disease acuity (p=0.01). Functional characterization of PF-associated variants in the immunomodulatory complement receptors CR3 and CR4 revealed that they result in partial or complete loss of anti-inflammatory CR3 function and/or gain of pro-inflammatory CR4 function. Taken together, these findings suggest that inherited defects in CR3 and CR4 predispose to the maladaptive hyperinflammation that characterizes severe sepsis with coagulopathy.

38096370

Nucleic acid sensing promotes inflammatory monocyte migration through biased coagulation factor VIIa signaling.

Protease activated receptors (PARs) are cleaved by coagulation proteases and thereby connect hemostasis with innate immune responses. Signaling of the tissue factor (TF) complex with FVIIa via PAR2 stimulates extracellular signal-regulated kinase (ERK) activation and cancer cell migration, but functions of cell autonomous TF-FVIIa signaling in immune cells are unknown. Here we show that myeloid cell expression of FVII but not of FX is crucial for inflammatory cell recruitment to the alveolar space after challenge with the double stranded viral RNA mimic Poly(I:C). In line with these data, genetically modified mice completely resistant to PAR2 cleavage but not FXa-resistant PAR2 mutant mice are protected from lung inflammation. Poly(I:C) stimulated migration of monocytes/macrophages is dependent on ERK activation and mitochondrial antiviral signaling (MAVS), but independent of toll-like receptor (TLR) 3. Monocyte/ macrophage synthesized FVIIa cleaving PAR2 is required for integrin αMβ2-dependent migration on fibrinogen, but not for integrin β1-dependent migration on fibronectin. To further dissect the downstream signaling pathway, we generated PAR2S365/T368A mutant mice deficient in β-arrestin recruitment and ERK scaffolding. This mutation reduces cytosolic, but not nuclear ERK phosphorylation by Poly(I:C) stimulation and prevents macrophage migration on fibrinogen, but not fibronectin following stimulation with Poly(I:C) or CpG-B, a single stranded DNA TLR9 agonist. In addition, PAR2S365/T368A mutant mice display markedly reduced immune cell recruitment to the alveolar space after Poly(I:C) challenge. These results identify TF-FVIIa-PAR2-β-arrestin biased signaling as a driver for lung infiltration in response to viral nucleic acids and suggest potential therapeutic interventions specifically targeting TF-VIIa signaling in thrombo-inflammation.

38096372

Impact of folic acid supplementation on the epigenetic profile in healthy unfortified individuals - a randomized intervention trial.

Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of folic acid. We conducted a randomized intervention trial to test the influence of folic acid supplementation on DNA methylation in an unfortified population in Germany. A total of 16 healthy male volunteers (age range 23-61&#8201;y) were randomized to receive either 400&#8201;&#956;g (<i>n</i>&#8201;=&#8201;9) or 800&#8201;&#956;g (<i>n</i>&#8201;=&#8201;7) folic acid supplements daily for 8&#8201;weeks. Infinium Human Methylation 450K BeadChip Microarrays were used to assay site-specific DNA methylation across the genome. Microarray analyses were conducted on PBL DNA. We estimated several epigenetic clocks and mean DNA methylation across all autosomal probes on the array. AgeAccel was estimated as the residual variation in each metric. In virtually all participants, both serum and red blood cell (RBC) folate increased successively throughout the trial period. Participants with a larger increase in RBC folate had a larger increase in DNAmAge AgeAccel (Spearman Rho: 0.56, <i>p</i>-value&#8201;=&#8201;0.03). No notable changes in the methylome resulting from the folic acid supplementation emerged. In this population with adequate folate levels derived from diet, an increase in RBC folate had a modest impact on the epigenetic clock predicting chronologic age.

38096371

Mezigdomide is effective alone and in combination with Menin inhibition in pre-clinical models of KMT2A-r and NPM1c AML.

Small molecules that target the MENIN-KMT2A protein-protein interaction (Menin inhibitors) have recently entered clinical trials in lysine methyltransferase 2A (KMT2A, MLL1) rearranged (KMT2A-r) and nucleophosmin mutant (NPM1c) acute myeloid leukemia (AML) and are demonstrating encouraging results. However, rationally chosen combination therapy is needed to improve responses and prevent resistance. We have previously identified IKZF1/IKAROS as a target in KMT2A-r AML and shown in preclinical models that IKAROS protein degradation with lenalidomide or iberdomide has modest single-agent activity yet can synergize with Menin inhibitors. Recently, the novel IKAROS degrader mezigdomide was developed with greatly enhanced IKAROS protein degradation. In this study we show that mezigdomide has increased preclinical activity in vitro as a single-agent in KMT2A-r and NPM1c AML cell lines, including sensitivity in cell lines resistant to lenalidomide and iberdomide. Further, we demonstrate that mezigdomide has the greatest capacity to synergize with and induce apoptosis in combination with Menin inhibitors, including in MEN1 mutant models. We show that the superior activity of mezigdomide compared to lenalidomide or iberdomide is due to its increased depth, rate, and duration of IKAROS protein degradation. Single-agent mezigdomide was efficacious in five patient derived xenograft (PDX) models of KMT2A-r and one NPM1c AML. The combination of mezigdomide with the Menin inhibitor VTP-50469 increased survival and prevented and overcame MEN1 mutations that mediate resistance in patients receiving Menin inhibitor monotherapy. These results support prioritization of mezigdomide for early phase clinical trials in KMT2A-r and NPM1c AML, either as a single-agent or in combination with Menin inhibitors.

38096374

Coalescence-Induced Droplet Jumping on Superhydrophobic Surfaces with Annular Wedge-Shaped Micropillar Arrays.

The coalescence-induced droplet jumping on superhydrophobic surfaces has extensive application potential in water harvesting, thermal management of electronic devices, and microfluidics. The rational design of the surface structure can influence the interaction between the droplet and the surface, thereby controlling the velocity and direction of the droplet's jumping. In this study, we fabricate the superhydrophobic surface with annular wedge-shaped micropillar arrays, examine the dynamic behavior of condensate droplets on the surface, and measure the temporal and spatial variations of droplet density, average radius, and surface coverage with wedge-shaped micropillars of varying sizes. In addition, the energy analysis of the coalescence-induced droplet jumping reveals that the two primary factors influencing the jumping are the relative size and position of the droplets and micropillars. Further numerical simulations find that the wedge-shaped micropillars cause an asymmetric distribution of pressure within the droplet and at the solid-liquid contact surface, which generates an unbalanced force driving the droplet in the gradient direction of the wedge-shaped micropillar, causing the droplet to jump off the surface with both vertical and gradient-direction velocities. The capacity of the wedge-shaped micropillar surface to transport droplets in the gradient direction increases and then decreases as the relative size of the droplets and micropillars increases. The relative position of the droplet center-of-mass line perpendicular to the bottom edge of the wedge micropillars' trapezoidal shape is more favorable for droplet transport. This work reveals the influence mechanism of surface structure on the velocity and direction of droplet jumping, and the results can guide the microstructure design of superhydrophobic surfaces, which has significant implications for the application of droplet jumping.

38096373

Genomic analyses reveal poaching hotspots and illegal trade in pangolins from Africa to Asia.

The white-bellied pangolin (<i>Phataginus tricuspis</i>) is the world's most trafficked mammal and is at risk of extinction. Reducing the illegal wildlife trade requires an understanding of its origins. Using a genomic approach for tracing confiscations and analyzing 111 samples collected from known geographic localities in Africa and 643 seized scales from Asia between 2012 and 2018, we found that poaching pressures shifted over time from West to Central Africa. Recently, Cameroon's southern border has emerged as a site of intense poaching. Using data from seizures representing nearly 1 million African pangolins, we identified Nigeria as one important hub for trafficking, where scales are amassed and transshipped to markets in Asia. This origin-to-destination approach offers new opportunities to disrupt the illegal wildlife trade and to guide anti-trafficking measures.

38096375

Low voltage-driven high-performance thermal switching in antiferroelectric PbZrO₃ thin films.

Effective control of heat transfer is vital for energy saving and carbon emission reduction. In contrast to achievements in electrical conduction, active control of heat transfer is much more challenging. Ferroelectrics are promising candidates for thermal switching as a result of their tunable domain structures. However, switching ratios in ferroelectrics are low (&lt;1.2). We report that high-quality antiferroelectric PbZrO₃ epitaxial thin films exhibit high-contrast (&gt;2.2), fast-speed (&lt;150 nanoseconds), and long-lifetime (&gt;10⁷) thermal switching under a small voltage (&lt;10 V). In situ reciprocal space mapping and atomistic modelings reveal that the field-driven antiferroelectric-ferroelectric phase transition induces a substantial change of primitive cell size, which modulates phonon-phonon scattering phase space drastically and results in high switching ratio. These results advance the concept of thermal transport control in ferroic materials.

38096376

Emission and coherent control of Levitons in graphene.

Flying qubits encode quantum information in propagating modes instead of stationary discrete states. Although photonic flying qubits are available, the weak interaction between photons limits the efficiency of conditional quantum gates. Conversely, electronic flying qubits can use Coulomb interactions, but the weaker quantum coherence in conventional semiconductors has hindered their realization. In this work, we engineered on-demand injection of a single electronic flying qubit state and its manipulation over the Bloch sphere. The flying qubit is a Leviton propagating in quantum Hall edge channels of a high-mobility graphene monolayer. Although single-shot qubit readout and two-qubit operations are still needed for a viable manipulation of flying qubits, the coherent manipulation of an itinerant electronic state at the single-electron level presents a highly promising alternative to conventional qubits.

38096377

Characterization of the Reversible Intersystem Crossing Dynamics of Organic Photocatalysts Using Transient Absorption Spectroscopy and Time-Resolved Fluorescence Spectroscopy.

Thermally activated delayed fluorescence (TADF) emitters are molecules of interest as homogeneous organic photocatalysts (OPCs) for photoredox chemistry. Here, three classes of OPC candidates are studied in dichloromethane (DCM) or N,N-dimethylformamide (DMF) solutions, using transient absorption spectroscopy and time-resolved fluorescence spectroscopy. These OPCs are benzophenones with either carbazole (2Cz-BP and 2tCz-BP) or phenoxazine/phenothiazine (2PXZ-BP and 2PTZ-BP) appended groups and the dicyanobenzene derivative 4DP-IPN. Dual lifetimes of the S₁ state populations are observed, consistent with reverse intersystem crossing (RISC) and TADF emission. Example fluorescence lifetimes in DCM are (5.18 &#177; 0.01) ns and (6.22 &#177; 1.27) &#956;s for 2Cz-BP, (1.38 &#177; 0.01) ns and (0.32 &#177; 0.01) &#956;s for 2PXZ-BP, and (2.97 &#177; 0.01) ns and (62.0 &#177; 5.8) &#956;s for 4DP-IPN. From ground state bleach recoveries and time-correlated single photon counting measurements, triplet quantum yields in DCM are estimated to be 0.62 &#177; 0.16, 0.04 &#177; 0.01, and 0.83 &#177; 0.02 for 2Cz-BP, 2PXZ-BP, and 4DP-IPN, respectively. 4DP-IPN displays similar photophysical behavior to the previously studied OPC 4Cz-IPN. Independent of the choice of solvent, 4DP-IPN, 2Cz-BP, and 2tCz-BP are shown to be TADF emitters, whereas emission by 2PXZ-BP and 2PTZ-BP depends on the molecular environment, with TADF emission enhanced in aggregates compared to monomers. Behavior of this type is representative of aggregation-induced emission luminogens (AIEgens).

38096378

Parsing 20 Years of Public Data by AI Maps Trends in Proteomics and Forecasts Technology.

The trends of the last 20 years in biotechnology were revealed using artificial intelligence and natural language processing (NLP) of publicly available data. Implementing this "science-of-science" approach, we capture convergent trends in the field of proteomics in both technology development and application across the phylogenetic tree of life. With major gaps in our knowledge about protein composition, structure, and location over time, we report trends in persistent, popular approaches and emerging technologies across 94 ideas from a corpus of 29 journals in PubMed over two decades. New metrics for clusters of these ideas reveal the progression and popularity of emerging approaches like single-cell, spatial, compositional, and chemical proteomics designed to better capture protein-level chemistry and biology. This analysis of the proteomics literature with advanced analytic tools quantifies the Rate of Rise for a next generation of technologies to better define, quantify, and visualize the multiple dimensions of the proteome that will transform our ability to measure and understand proteins in the coming decade.

38096379

How to Provide Nitrite Robustly for Anaerobic Ammonium Oxidation in Mainstream Nitrogen Removal.

Innovation in decarbonizing wastewater treatment is urgent in response to global climate change. The practical implementation of anaerobic ammonium oxidation (anammox) treating domestic wastewater is the key to reconciling carbon-neutral management of wastewater treatment with sustainable development. Nitrite availability is the prerequisite of the anammox reaction, but how to achieve robust nitrite supply and accumulation for mainstream systems remains elusive. This work presents a state-of-the-art review on the recent advances in nitrite supply for mainstream anammox, paying special attention to available pathways (forward-going (from ammonium to nitrite) and backward-going (from nitrate to nitrite)), key controlling strategies, and physiological and ecological characteristics of functional microorganisms involved in nitrite supply. First, we comprehensively assessed the mainstream nitrite-oxidizing bacteria control methods, outlining that these technologies are transitioning to technologies possessing multiple selective pressures (such as intermittent aeration and membrane-aerated biological reactor), integrating side stream treatment (such as free ammonia/free nitrous acid suppression in recirculated sludge treatment), and maintaining high activity of ammonia-oxidizing bacteria and anammox bacteria for competing oxygen and nitrite with nitrite-oxidizing bacteria. We then highlight emerging strategies of nitrite supply, including the nitrite production driven by novel ammonia-oxidizing microbes (ammonia-oxidizing archaea and complete ammonia oxidation bacteria) and nitrate reduction pathways (partial denitrification and nitrate-dependent anaerobic methane oxidation). The resources requirement of different mainstream nitrite supply pathways is analyzed, and a hybrid nitrite supply pathway by combining partial nitrification and nitrate reduction is encouraged. Moreover, data-driven modeling of a mainstream nitrite supply process as well as proactive microbiome management is proposed in the hope of achieving mainstream nitrite supply in practical application. Finally, the existing challenges and further perspectives are highlighted, i.e., investigation of nitrite-supplying bacteria, the scaling-up of hybrid nitrite supply technologies from laboratory to practical implementation under real conditions, and the data-driven management for the stable performance of mainstream nitrite supply. The fundamental insights in this review aim to inspire and advance our understanding about how to provide nitrite robustly for mainstream anammox and shed light on important obstacles warranting further settlement.

38096380

Triple B←N Lewis Pair-Functionalized Triazatruxenes with Large Stokes Shifts.

A novel class of multiple B&#8592;N Lewis pair-functionalized polycyclic aromatic hydrocarbons with different BR₂ groups (R = Cl or Et) directly attached at positions 1, 6, and 11 of triazatruxene was synthesized. The triazatruxene backbone of <b>4</b> displays a bowl shape, and its molecular skeleton shows a highly twisted propeller-like structure with <i>C</i>₃ symmetry. The introduction of B&#8592;N Lewis pairs not only results in a large decrease in the HOMO-LUMO gap but also lowers the LUMO to -3.00 eV. Both compounds show excellent stability with large Stokes shifts of &#8804;8234 cm^-1 and solvatochromic emission in solvents of different polarities.

38096381

Catalytic Reductive Recyclization of Functionalized Isoxazoline <i>N</i>-Oxides to Pyrrolizidine-3-ones.

Pyrrolizidine is among the saturated <i>N</i>-heterocyclic scaffolds most frequently found in natural products and pharmaceutically relevant substances. Herein, a strategy for the synthesis of polysubstituted pyrrolizidine-3-ones by catalytic reductive domino-type recyclization of properly functionalized isoxazoline <i>N</i>-oxides was developed. The process is diastereoselective, and one diastereomer (out of four possible ones) is predominant in many of the studied cases. Using the developed method, modifications of potent GSK's PDE4 inhibitor and MSD's potent hNK₁ antagonist were prepared.

38096382

Base-Promoted Synthesis of <i>S</i>-Arylisothiazolones via Intramolecular Dehydrative Cyclization of &#945;-Keto-<i>N</i>-acylsulfoximines.

A base (Et₃N)-promoted synthesis of 1,4-diarylisothiazolones from &#945;-keto-<i>N</i>-acylsulfoximines has been achieved. The reaction proceeds via &#945;-hydrogen abstraction from sulfoximine, followed by an intramolecular nucleophilic attack at the keto carbonyl to form a <i>tert</i>-hydroxy isothiazolone intermediate. The 1,4-substituted isothiazolone is obtained after dehydration via an E1cB path. This one-pot synthesis of isothiazolinones has a broad substrate scope, has a high atom economy, and provides products with good yields. The &#916;<i>E</i>_LUMO-HOMO is calculated using <i>Gaussian 16</i> at the B3LYP/6-31G(d,p) level of theory.

38096383

Metal-Free Oxidative Formation of Aryl Esters by Catalytic Coupling of Acyl and Sulfonyl Chlorides with Arylboronic Acids.

A practical and efficient synthesis of aryl esters was developed through metal-free oxidation. This reaction employs stable and readily available acyl or sulfonyl chlorides and arylboronic acids as the starting materials and proceeds under mild reaction conditions without additional precious metal catalysts. This new strategy exhibits broad substrate tolerance and operational simplicity and gives diverse aryl esters in moderate to high yields.

38096384

Ancient chicken remains reveal the origins of virulence in Marek's disease virus.

The pronounced growth in livestock populations since the 1950s has altered the epidemiological and evolutionary trajectory of their associated pathogens. For example, Marek's disease virus (MDV), which causes lymphoid tumors in chickens, has experienced a marked increase in virulence over the past century. Today, MDV infections kill &gt;90% of unvaccinated birds, and controlling it costs more than US$1 billion annually. By sequencing MDV genomes derived from archeological chickens, we demonstrate that it has been circulating for at least 1000 years. We functionally tested the <i>Meq</i> oncogene, one of 49 viral genes positively selected in modern strains, demonstrating that ancient MDV was likely incapable of driving tumor formation. Our results demonstrate the power of ancient DNA approaches to trace the molecular basis of virulence in economically relevant pathogens.

38096385

HIV vaccines induce CD8⁺ T cells with low antigen receptor sensitivity.

Current HIV vaccines designed to stimulate CD8⁺ T cells have failed to induce immunologic control upon infection. The functions of vaccine-induced HIV-specific CD8⁺ T cells were investigated here in detail. Cytotoxic capacity was significantly lower than in HIV controllers and was not a consequence of low frequency or unaccumulated functional cytotoxic proteins. Low cytotoxic capacity was attributable to impaired degranulation in response to the low antigen levels present on HIV-infected targets. The vaccine-induced T cell receptor (TCR) repertoire was polyclonal and transduction of these TCRs conferred the same reduced functions. These results define a mechanism accounting for poor antiviral activity induced by these vaccines and suggest that an effective CD8⁺ T cell response may require a vaccination strategy that drives further TCR clonal selection.

38096387

[Hydrodynamics of dental dentinal fluid].

Dentinal fluid is very close in its physical and mechanical properties and composition to blood plasma, which makes it a potentially aggressive biological environment for modern adhesive systems. An in-depth study of the physiological processes of the functioning of tooth dentin remains relevant in order to solve problems associated with its artificial restoration.

38096386

Positioning for lumbar puncture in newborn infants.

Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes.

38096388

[Development of osteoplastic gene-activated 3D matrices based on adenoviral vectors].

Gene therapy is one of the most promising approaches in regenerative medicine for the restoration of extensive bone defects in dentistry and maxillofacial surgery. Matrices obtained using three-dimensional printing from bioresorbable polymers, impregnated with adenoviral constructs with genes for osteoinductive factors, can ensure safe and effective formation of bone tissue.