bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding cactus pear status for improved ecosystem services in northern Ethiopia
Authors: Meaza Hailemariam , Demissie Biadgilgn , Berhe Yemane Kahsay , Gebrehiwot Misgina , Nyssen Jan , Haile Mitiku , Gebreegzabher Amleset , Girmay Abbadi
Published: July 2024

Prickly pear (Opuntia ficus-indica) is a multipurpose plant in drylands. The objective of this study was to synthesize the livelihood benefits, survival threats and management of cactus pear in Tigray (Ethiopia). Metadata were generated from 63 available articles. Accidental interviews (n = 35) and frequent field observations were also used to substantiate the metadata. Descriptive statistics and descriptions were used to analyze the data. In the meta-analysis, cactus is a viable biological measure to maintain soil quality and moisture, as it has high water use efficiency. In addition, cactus provides an average yield of 16.20 ± 8.33 tons fruits per ha. The plant is also a source of income and a live fence in low rainfall sites. The dryland plant has bridged the food and forage gaps. The cochineal insect, which eats only cactus, was introduced for a dyeing business. However, mismanagement of the insects invaded vast cactus-rich sites at an alarming rate. The infested areas increased from 17 villages in 2011 to 139 villages in 2018 with an average damage of 3,890 ha of cactus per year. The study highlights that research institutions and Tigray government have failed to address the cochineal infestation for about 15 years. Consequently, the poor farmers received neither cactus benefits from harvesting carmine nor other ecosystem services. Therefore, we suggest that integrated pest management efforts and expansion of cactus plantations along the western escarpment in the Rift Valley improve food availability and defend the landscape against the expansion of desertification in northern Ethiopia.
Integrated transcriptomics and metabolomics provide insights into the biosynthesis of militarine in the cell suspension culture system of Bletilla striata
Authors: Li Qingqing , Xu Mengwei , Wu Fengju , Guo Ziyi , Yang Ning , Li Lin , Wen Weie , Xu Delin
Published: July 2024

Militarine is a monomer molecule with abundant and distinctive biological properties, also the lead member of secondary metabolites in Bletilla striata, while its biosynthesis mechanism is still unknown. To improve the production efficiency of militarine, sodium acetate and salicylic acid (SA) were introduced as elicitors into the suspension-cultured callus of B. striata. Subsequently, samples were taken from callus at different culturing stages to investigate the synthesis mechanisms of militarine in B. striata through integrated metabolomics and transcriptomics. Metabolomics analysis revealed that acetate ions promoted militarine synthesis, while SA had an inhibitory effect. Additionally, regulators such as ferulic acid, 2-hydroxy-3-phenylpropionic acid, and cis-beta-D-Glucosyl-2-hydroxycinnamate were identified as influencing militarine synthesis. Transcriptomics analysis indicated that the expression levels of genes involved in phenylalanine metabolism, phenylpropanoid biosynthesis, and tyrosine metabolism were correlated with militarine content. This study sheds light on the regulatory mechanism of militarine biosynthesis in plants. The results suggested that acetate ions and SA impact militarine synthesis through specific metabolic pathways and gene expression changes. This knowledge serves as a foundation for future research on militarine biosynthesis and its industrial production.
Language likely promoted peace before 100,000 ya
Authors: Wrangham Richard
Published: July 2024

Based on evidence of selection against alpha-male behavior in the earliest Homo sapiens, I suggest that by 300,000 ya (years ago) language would have been sufficiently sophisticated to contribute to peacemaking between groups. Language also influenced the social landscape of peace and war, and groups' ability to form coalitions.
Social norms, mentalising, and common knowledge, in making peace and war
Authors: Riordan Vincent
Published: July 2024

The emergence of social norms would have been dependent on the evolution of the cognitive capacity for mentalising to multiple orders of intentionality. Common knowledge is a related phenomenon that can solve coordination problems. That the same cognitive and social mechanisms should facilitate both peace and war is resonant with Girard's scapegoat hypothesis on the relationship between violence and religion.
The roots of peace
Authors: Wilson Michael L.
Published: July 2024

By focusing on peace, Glowacki provides a fresh perspective on warfare. Why did humans evolve peace? Other animals aggregate peacefully when resources are not economically defendable. The human capacity for peace may arise from two key factors: Multilevel societies and psychology shaped by within-group exchanges, which may have begun when tools enabled hominins to extract foods, including tubers and roots.
Police for peace
Authors: Rusch Hannes
Published: July 2024

Glowacki's detailed account of small-scale societies’ endogenously emerging tendencies to oscillate between phases of peace and war highlights a need for understanding better the incentives governing “internal” policing for “external” peacekeeping. Here, I sketch some of these incentives and point out a resulting dilemma which Glowacki's account leaves unresolved for the time being.
Peace is a form of cooperation, and so are the cultural technologies which make peace possible
Authors: Lie-Panis Julien , André Jean-Baptiste
Published: July 2024

While necessary parts of the puzzle, cultural technologies are insufficient to explain peace. They are a form of second-order cooperation – a cooperative interaction designed to incentivize first-order cooperation. We propose an explanation for peacemaking cultural technologies, and therefore peace, based on the reputational incentives for second-order cooperation.
How language and agriculture promote culture- and peace-promoting norms
Authors: Zentall Thomas R.
Published: July 2024

Humans are predisposed to form in-groups and out-groups that are remarkably flexible in their definition due largely to the complex language that has evolved in them. Language has allowed for the creation of shared “background stories” that can unite people who do not know each other. Second, the discovery of agriculture has resulted in the critical need to negotiate boundaries, a process that can lead to peace (but also war).
A New WENO‐Based Momentum Advection Scheme for Simulations of Ocean Mesoscale Turbulence
Authors: Silvestri Simone , Wagner Gregory L. , Campin Jean‐Michel , Constantinou Navid C. , Hill Christopher N. , Souza Andre , Ferrari Raffaele
Published: July 2024

Current eddy‐permitting and eddy‐resolving ocean models require dissipation to prevent a spurious accumulation of enstrophy at the grid scale. We introduce a new numerical scheme for momentum advection in large‐scale ocean models that involves upwinding through a weighted essentially non‐oscillatory (WENO) reconstruction. The new scheme provides implicit dissipation and thereby avoids the need for an additional explicit dissipation that may require calibration of unknown parameters. This approach uses the rotational, “vector invariant” formulation of the momentum advection operator that is widely employed by global general circulation models. A novel formulation of the WENO “smoothness indicators” is key for avoiding excessive numerical dissipation of kinetic energy and enstrophy at grid‐resolved scales. We test the new advection scheme against a standard approach that combines explicit dissipation with a dispersive discretization of the rotational advection operator in two scenarios: (a) two‐dimensional turbulence and (b) three‐dimensional baroclinic equilibration. In both cases, the solutions are stable, free from dispersive artifacts, and achieve increased “effective” resolution compared to other approaches commonly used in ocean models.
The Ionospheric Leg of the Substorm Current Wedge: Combining Iridium and Ground Magnetometers
Authors: Walker Simon James , Laundal Karl Magnus , Reistad Jone Peter , Hatch Spencer Mark , Ohma Anders , Gjerloev Jesper
Published: July 2024

Utilizing magnetic field measurements made by the Iridium satellites and by ground magnetometers in North America we calculate the full ionospheric current system and investigate the substorm current wedge. The current estimates are independent of ionospheric conductance, and are based on estimates of the divergence‐free (DF) ionospheric current from ground magnetometers and curl‐free (CF) ionospheric currents from Iridium. The DF and CF currents are represented using spherical elementary current systems (SECS), derived using a new inversion scheme that ensures the current systems' spatial scales are consistent. We present 18 substorm events and find a typical substorm current wedge (SCW) in 12 events. Our investigation of these substorms shows that during substorm expansion, equivalent field‐aligned currents (EFACs) derived with ground magnetometers are a poor proxy of the actual FAC. We also find that the intensification of the westward electrojet can occur without an intensification of the FACs. We present theoretical investigations that show that the observed deviation between FACs estimated with satellite measurements and ground‐based EFACs are consistent with the presence of a strong local enhancement of the ionospheric conductance, similar to the substorm bulge. Such enhancements of the auroral conductance can also change the ionospheric closure of pre‐existing FACs such that the ground magnetic field, and in particular the westward electrojet, changes significantly. These results demonstrate that attributing intensification of the westward electrojet to SCW current closure can yield false understanding of the ionospheric and magnetospheric state.
The Geological History of Enceladus' Cratered Terrains
Authors: Kinczyk Mallory J. , Byrne Paul K. , Patterson Gerald W.
Published: July 2024

This study presents a comprehensive assessment of the geomorphology, crater distributions, and tectonic structures within Enceladus' cratered terrains. We analyzed the distributions of impact craters and tectonic structures in seven regions of interest to inform an interpretation of the geological history of this terrain in the context of Enceladus' global evolution. We found that the tectonic structures, including both ancient, subdued troughs and young, narrow fractures, point to a cratered terrain that not only experienced early tectonic modification but also shows evidence of recent geological activity. Ancient troughs present in the equatorial cratered terrains are similar in scale and orientation to troughs present in the Leading and Trailing Hemisphere Terrains, an observation that supports possible non‐synchronous rotation of the ice shell. A dearth of impact craters in the equatorial regions as identified previously does not hold for craters <3 km in diameter in the anti‐Saturnian hemisphere. The anomalous presence of excess small craters in this region could be due to secondary or sesquinary impacts from a catastrophic event occurring at Enceladus or a neighboring moon. Finally, narrow fractures are pervasive across the cratered terrains and are most commonly oriented parallel or sub‐parallel to the most proximal cratered terrain boundary. This directionality of pervasive recent fracturing could be related to the vertical movement of an isostatically uncompensated ice shell. Enceladus' cratered terrains provide insight into the long‐term evolution of the satellite, an important component to assessing its role in Solar System evolution and its potential for habitability.
Dynamic nanomechanical characterization of cells in exosome therapy
Authors: Chen Ye , Zhang Zihan , Li Ziwei , Wu Wenjie , Lan Shihai , Yan Tianhao , Mei Kainan , Qiao Zihan , Wang Chen , Bai Chuanbiao , Li Ziyan , Wu Shangquan , Wang Jianye , Zhang Qingchuan
Published: July 2024

Exosomes derived from mesenchymal stem cells (MSCs) have been confirmed to enhance cell proliferation and improve tissue repair. Exosomes release their contents into the cytoplasmic solution of the recipient cell to mediate cell expression, which is the main pathway through which exosomes exert therapeutic effects. The corresponding process of exosome internalization mainly occurs in the early stage of treatment. However, the therapeutic effect of exosomes in the early stage remains to be further studied. We report that the three-dimensional cell traction force can intuitively reflect the ability of exosomes to enhance the cytoskeleton and cell contractility of recipient cells, serving as an effective method to characterize the therapeutic effect of exosomes. Compared with traditional biochemical methods, we can visualize the early therapeutic effect of exosomes in real time without damage by quantifying the cell traction force. Through quantitative analysis of traction forces, we found that endometrial stromal cells exhibit short-term cell roundness accompanied by greater traction force during the early stage of exosome therapy. Further experiments revealed that exosomes enhance the traction force and cytoskeleton by regulating the Rac1/RhoA signaling pathway, thereby promoting cell proliferation. This work provides an effective method for rapidly quantifying the therapeutic effects of exosomes and studying the underlying mechanisms involved.
Decoding depression: a comprehensive multi-cohort exploration of blood DNA methylation using machine learning and deep learning approaches
Authors: Sokolov Aleksandr V. , Schiöth Helgi B.
Published: July 2024

The causes of depression are complex, and the current diagnosis methods rely solely on psychiatric evaluations with no incorporation of laboratory biomarkers in clinical practices. We investigated the stability of blood DNA methylation depression signatures in six different populations using six public and two domestic cohorts (n = 1942) conducting mega-analysis and meta-analysis of the individual studies. We evaluated 12 machine learning and deep learning strategies for depression classification both in cross-validation (CV) and in hold-out tests using merged data from 8 separate batches, constructing models with both biased and unbiased feature selection. We found 1987 CpG sites related to depression in both mega- and meta-analysis at the nominal level, and the associated genes were nominally related to axon guidance and immune pathways based on enrichment analysis and eQTM data. Random forest classifiers achieved the highest performance (AUC 0.73 and 0.76) in CV and hold-out tests respectively on the batch-level processed data. In contrast, the methylation showed low predictive power (all AUCs < 0.57) for all classifiers in CV and no predictive power in hold-out tests when used with harmonized data. All models achieved significantly better performance (>14% gain in AUCs) with pre-selected features (selection bias), with some of the models (joint autoencoder-classifier) reaching AUCs of up to 0.91 in the final testing regardless of data preparation. Different algorithmic feature selection approaches may outperform limma, however, random forest models perform well regardless of the strategy. The results provide an overview over potential future biomarkers for depression and highlight many important methodological aspects for DNA methylation-based depression profiling including the use of machine learning strategies.
Effects of oxytocin receptor agonism on acquisition and expression of pair bonding in male prairie voles
Authors: Johnson Michael C. , Zweig Jonathan A. , Zhang Yangmiao , Nunez Louis , Ryabinina Olga P. , Hibert Marcel , Ryabinin Andrey E.
Published: July 2024

There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (Microtus ochrogaster), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4hr cohabitation. In contrast, while animals injected with vehicle after the 4hr cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2hr-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.
PRMT1 promotes Warburg effect by regulating the PKM2/PKM1 ratio in non-small cell lung cancer
Authors: Peng Lu , Zhao Yujiao , Tan Jiang , Hou Jingyao , Jin Xin , Liu Dong-Xu , Huang Baiqu , Lu Jun
Published: July 2024

Abnormal epigenetic modifications are involved in the regulation of Warburg effect in tumor cells. Protein arginine methyltransferases (PRMTs) mediate arginine methylation and have critical functions in cellular responses. PRMTs are deregulated in a variety of cancers, but their precise roles in Warburg effect in cancer is largely unknown. Experiments from the current study showed that PRMT1 was highly expressed under conditions of glucose sufficiency. PRMT1 induced an increase in the PKM2/PKM1 ratio through upregulation of PTBP1, in turn, promoting aerobic glycolysis in non-small cell lung cancer (NSCLC). The PRMT1 level in p53-deficient and p53-mutated NSCLC remained relatively unchanged while the expression was reduced in p53 wild-type NSCLC under conditions of glucose insufficiency. Notably, p53 activation under glucose-deficient conditions could suppress USP7 and further accelerate the polyubiquitin-dependent degradation of PRMT1. Melatonin, a hormone that inhibits glucose intake, markedly suppressed cell proliferation of p53 wild-type NSCLC, while a combination of melatonin and the USP7 inhibitor P5091 enhanced the anticancer activity in p53-deficient NSCLC. Our collective findings support a role of PRMT1 in the regulation of Warburg effect in NSCLC. Moreover, combination treatment with melatonin and the USP7 inhibitor showed good efficacy, providing a rationale for the development of PRMT1-based therapy to improve p53-deficient NSCLC outcomes.
FADD regulates adipose inflammation, adipogenesis, and adipocyte survival
Authors: Tang Jianlei , Ma Yue , Li Meilin , Liu Xiangpeng , Wang Yuting , Zhang Jie , Shu Hui , Liu Zhiwei , Zhang Chi , Fu Lei , Hu Ji , Zhang Yong , Jia Zhihao , Feng Yu
Published: July 2024

Adipose tissue, aside from adipocytes, comprises various abundant immune cells. The accumulation of low-grade chronic inflammation in adipose tissue serves as a primary cause and hallmark of insulin resistance. In this study, we investigate the physiological roles of FADD in adipose tissue inflammation, adipogenesis, and adipocyte survival. High levels of Fadd mRNA were observed in mitochondrial-rich organs, particularly brown adipose tissue. To explore its metabolic functions, we generated global Fadd knockout mice, resulting in embryonic lethality, while heterozygous knockout (Fadd+/−) mice did not show any significant changes in body weight or composition. However, Fadd+/− mice exhibited reduced respiratory exchange ratio (RER) and serum cholesterol levels, along with heightened global and adipose inflammatory responses. Furthermore, AT masses and expression levels of adipogenic and lipogenic genes were decreased in Fadd+/− mice. In cellular studies, Fadd inhibition disrupted adipogenic differentiation and suppressed the expression of adipogenic and lipogenic genes in cultured adipocytes. Additionally, Fadd overexpression caused adipocyte death in vitro with decreased RIPK1 and RIPK3 expression, while Fadd inhibition downregulated RIPK3 in iWAT in vivo. These findings collectively underscore the indispensable role of FADD in adipose inflammation, adipogenesis, and adipocyte survival.
AI-NERD: Elucidation of relaxation dynamics beyond equilibrium through AI-informed X-ray photon correlation spectroscopy
Authors: Horwath James P. , Lin Xiao-Min , He Hongrui , Zhang Qingteng , Dufresne Eric M. , Chu Miaoqi , Sankaranarayanan Subramanian K.R.S. , Chen Wei , Narayanan Suresh , Cherukara Mathew J.
Published: July 2024

Understanding and interpreting dynamics of functional materials in situ is a grand challenge in physics and materials science due to the difficulty of experimentally probing materials at varied length and time scales. X-ray photon correlation spectroscopy (XPCS) is uniquely well-suited for characterizing materials dynamics over wide-ranging time scales. However, spatial and temporal heterogeneity in material behavior can make interpretation of experimental XPCS data difficult. In this work, we have developed an unsupervised deep learning (DL) framework for automated classification of relaxation dynamics from experimental data without requiring any prior physical knowledge of the system. We demonstrate how this method can be used to accelerate exploration of large datasets to identify samples of interest, and we apply this approach to directly correlate microscopic dynamics with macroscopic properties of a model system. Importantly, this DL framework is material and process agnostic, marking a concrete step towards autonomous materials discovery.
Beta activity in human anterior cingulate cortex mediates reward biases
Authors: Xiao Jiayang , Adkinson Joshua A. , Myers John , Allawala Anusha B. , Mathura Raissa K. , Pirtle Victoria , Najera Ricardo , Provenza Nicole R. , Bartoli Eleonora , Watrous Andrew J. , Oswalt Denise , Gadot Ron , Anand Adrish , Shofty Ben , Mathew Sanjay J. , Goodman Wayne K. , Pouratian Nader , Pitkow Xaq , Bijanki Kelly R. , Hayden Benjamin , Sheth Sameer A.
Published: July 2024

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.
Analytical realization of complex thermal meta-devices
Authors: Li Weichen , Sigmund Ole , Zhang Xiaojia Shelly
Published: July 2024

Fourier’s law dictates that heat flows from warm to cold. Nevertheless, devices can be tailored to cloak obstacles or even reverse the heat flow. Mathematical transformation yields closed-form equations for graded, highly anisotropic thermal metamaterial distributions needed for obtaining such functionalities. For simple geometries, devices can be realized by regular conductor distributions; however, for complex geometries, physical realizations have so far been challenging, and sub-optimal solutions have been obtained by expensive numerical approaches. Here we suggest a straightforward and highly efficient analytical de-homogenization approach that uses optimal multi-rank laminates to provide closed-form solutions for any imaginable thermal manipulation device. We create thermal cloaks, rotators, and concentrators in complex domains with close-to-optimal performance and esthetic elegance. The devices are fabricated using metal 3D printing, and their omnidirectional thermal functionalities are investigated numerically and validated experimentally. The analytical approach enables next-generation free-form thermal meta-devices with efficient synthesis, near-optimal performance, and concise patterns.
Temporal dynamics of climate change exposure and opportunities for global marine biodiversity
Authors: Meyer Andreas Schwarz , Pigot Alex L. , Merow Cory , Kaschner Kristin , Garilao Cristina , Kesner-Reyes Kathleen , Trisos Christopher H.
Published: July 2024

Climate change is exposing marine species to unsuitable temperatures while also creating new thermally suitable habitats of varying persistence. However, understanding how these different dynamics will unfold over time remains limited. We use yearly sea surface temperature projections to estimate temporal dynamics of thermal exposure (when temperature exceeds realised species’ thermal limits) and opportunity (when temperature at a previously unsuitable site becomes suitable) for 21,696 marine species globally until 2100. Thermal opportunities are projected to arise earlier and accumulate gradually, especially in temperate and polar regions. Thermal exposure increases later and occurs more abruptly, mainly in the tropics. Assemblages tend to show either high exposure or high opportunity, but seldom both. Strong emissions reductions reduce exposure around 100-fold whereas reductions in opportunities are halved. Globally, opportunities are projected to emerge faster than exposure until mid-century when exposure increases more rapidly under a high emissions scenario. Moreover, across emissions and dispersal scenarios, 76%-97% of opportunities are projected to persist until 2100. These results indicate thermal opportunities could be a major source of marine biodiversity change, especially in the near- and mid-term. Our work provides a framework for predicting where and when thermal changes will occur to guide monitoring efforts.
Large-scale whole-exome sequencing analyses identified protein-coding variants associated with immune-mediated diseases in 350,770 adults
Authors: Yang Liu , Ou Ya-Nan , Wu Bang-Sheng , Liu Wei-Shi , Deng Yue-Ting , He Xiao-Yu , Chen Yi-Lin , Kang Jujiao , Fei Chen-Jie , Zhu Ying , Tan Lan , Dong Qiang , Feng Jianfeng , Cheng Wei , Yu Jin-Tai
Published: July 2024

The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.
Robust structural superlubricity under gigapascal pressures
Authors: Sun Taotao , Gao Enlai , Jia Xiangzheng , Bian Jinbo , Wang Zhou , Ma Ming , Zheng Quanshui , Xu Zhiping
Published: July 2024

Structural superlubricity (SSL) is a state of contact with no wear and ultralow friction. SSL has been characterized at contact with van der Waals (vdW) layered materials, while its stability under extreme loading conditions has not been assessed. By designing both self-mated and non-self-mated vdW contacts with materials chosen for their high strengths, we report outstanding robustness of SSL under very high pressures in experiments. The incommensurate self-mated vdW contact between graphite interfaces can maintain the state of SSL under a pressure no lower than 9.45 GPa, and the non-self-mated vdW contact between a tungsten tip and graphite substrate remains stable up to 3.74 GPa. Beyond this critical pressure, wear is activated, signaling the breakdown of vdW contacts and SSL. This unexpectedly strong pressure-resistance and wear-free feature of SSL breaks down the picture of progressive wear. Atomistic simulations show that lattice destruction at the vdW contact by pressure-assisted bonding triggers wear through shear-induced tearing of the single-atomic layers. The correlation between the breakdown pressure and material properties shows that the bulk modulus and the first ionization energy are the most relevant factors, indicating the combined structural and electronic effects. Impressively, the breakdown pressures defined by the SSL interface could even exceed the strength of materials in contact, demonstrating the robustness of SSL. These findings offer a fundamental understanding of wear at the vdW contacts and guide the design of SSL-enabled applications.
pH drives electron density fluctuations that enhance electric field-induced liquid flow
Authors: Pullanchery S. , Kulik S. , Schönfeldová T. , Egan C. K. , Cassone G. , Hassanali A. , Roke S.
Published: July 2024

Liquid flow along a charged interface is commonly described by classical continuum theory, which represents the electric double layer by uniformly distributed point charges. The electrophoretic mobility of hydrophobic nanodroplets in water doubles in magnitude when the pH is varied from neutral to mildly basic (pH 7 → 11). Classical continuum theory predicts that this increase in mobility is due to an increased surface charge. Here, by combining all-optical measurements of surface charge and molecular structure, as well as electronic structure calculations, we show that surface charge and molecular structure at the nanodroplet surface are identical at neutral and mildly basic pH. We propose that the force that propels the droplets originates from two factors: Negative charge on the droplet surface due to charge transfer from and within water, and anisotropic gradients in the fluctuating polarization induced by the electric field. Both charge density fluctuations couple with the external electric field, and lead to droplet flow. Replacing chloride by hydroxide doubles both the charge conductivity via the Grotthuss mechanism, and the droplet mobility. This general mechanism deeply impacts a plethora of processes in biology, chemistry, and nanotechnology and provides an explanation of how pH influences hydrodynamic phenomena and the limitations of classical continuum theory currently used to rationalize these effects.
Single-cell total-RNA profiling unveils regulatory hubs of transcription factors
Authors: Niu Yichi , Luo Jiayi , Zong Chenghang
Published: July 2024

Recent development of RNA velocity uses master equations to establish the kinetics of the life cycle of RNAs from unspliced RNA to spliced RNA (i.e., mature RNA) to degradation. To feed this kinetic analysis, simultaneous measurement of unspliced RNA and spliced RNA in single cells is greatly desired. However, the majority of single-cell RNA-seq chemistry primarily captures mature RNA species to measure gene expressions. Here, we develop a one-step total-RNA chemistry-based single-cell RNA-seq method: snapTotal-seq. We benchmark this method with multiple single-cell RNA-seq assays in their performance in kinetic analysis of cell cycle by RNA velocity. Next, with LASSO regression between transcription factors, we identify the critical regulatory hubs mediating the cell cycle dynamics. We also apply snapTotal-seq to profile the oncogene-induced senescence and identify the key regulatory hubs governing the entry of senescence. Furthermore, from the comparative analysis of unspliced RNA and spliced RNA, we identify a significant portion of genes whose expression changes occur in spliced RNA but not to the same degree in unspliced RNA, indicating these gene expression changes are mainly controlled by post-transcriptional regulation. Overall, we demonstrate that snapTotal-seq can provide enriched information about gene regulation, especially during the transition between cell states.
Laboratory infrared spectra and fragmentation chemistry of sulfur allotropes
Authors: Ferrari Piero , Berden Giel , Redlich Britta , Waters Laurens B. F. M. , Bakker Joost M.
Published: July 2024

Sulfur is one of six life-essential elements, but its path from interstellar clouds to planets and their atmospheres is not well known. Astronomical observations in dense clouds have so far been able to trace only 1 percent of cosmic sulfur, in the form of gas phase molecules and volatile ices, with the missing sulfur expected to be locked in a currently unidentified form. The high sulfur abundances inferred in icy and rocky solar system bodies indicate that an efficient pathway must exist from volatile atomic sulfur in the diffuse interstellar medium to some form of refractory sulfur. One hypothesis is the formation of sulfur allotropes, particularly of the stable S8. However, experimental information about sulfur allotropes under astrochemically relevant conditions, needed to constrain their abundance, is lacking. Here, we report the laboratory far-infrared spectra of sulfur allotropes and examine their fragmentation pathways. The spectra, including that of cold, isolated S8 with three bands at 53.5, 41.3 and 21.1 µm, form a benchmark for computational modelling, which show a near-perfect match with the experiments. The experimental fragmentation pathways of sulfur allotropes, key information for astrochemical formation/destruction models, evidence a facile fragmentation of S8. These findings suggest the presence of sulfur allotropes distributions in interstellar space or in the atmosphere of planets, dependent on the environmental conditions.
Direct observation of twisted stacking domains in the van der Waals magnet CrI3
Authors: Jang Myeongjin , Lee Sol , Cantos-Prieto Fernando , Košić Ivona , Li Yue , McCray Arthur R. C. , Jung Min-Hyoung , Yoon Jun-Yeong , Boddapati Loukya , Deepak Francis Leonard , Jeong Hu Young , Phatak Charudatta M. , Santos Elton J. G. , Navarro-Moratalla Efrén , Kim Kwanpyo
Published: July 2024

Van der Waals (vdW) stacking is a powerful technique to achieve desired properties in condensed matter systems through layer-by-layer crystal engineering. A remarkable example is the control over the twist angle between artificially-stacked vdW crystals, enabling the realization of unconventional phenomena in moiré structures ranging from superconductivity to strongly correlated magnetism. Here, we report the appearance of unusual 120° twisted faults in vdW magnet CrI3 crystals. In exfoliated samples, we observe vertical twisted domains with a thickness below 10 nm. The size and distribution of twisted domains strongly depend on the sample preparation methods, with as-synthesized unexfoliated samples showing tenfold thicker domains than exfoliated samples. Cooling induces changes in the relative populations among different twisting domains, rather than the previously assumed structural phase transition to the rhombohedral stacking. The stacking disorder induced by sample fabrication processes may explain the unresolved thickness-dependent magnetic coupling observed in CrI3.
Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model
Authors: Lin Jiajia , Jin Ming , Yang Dong , Li Zhifang , Zhang Yu , Xiao Qingquan , Wang Yin , Yu Yuyang , Zhang Xiumei , Shao Zhurui , Shi Linyu , Zhang Shu , Chen Wan-jin , Wang Ning , Wu Shiwen , Yang Hui , Xu Chunlong , Li Guoling
Published: July 2024

Duchenne muscular dystrophy (DMD) affecting 1 in 3500–5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient’s DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.
Engineering a nanoscale liposome-in-liposome for in situ biochemical synthesis and multi-stage release
Authors: Pilkington Colin P. , Gispert Ignacio , Chui Suet Y. , Seddon John. M. , Elani Yuval
Published: July 2024

Soft-matter nanoscale assemblies such as liposomes and lipid nanoparticles have the potential to deliver and release multiple cargos in an externally stimulated and site-specific manner. Such assemblies are currently structurally simplistic, comprising spherical capsules or lipid clusters. Given that form and function are intertwined, this lack of architectural complexity restricts the development of more sophisticated properties. To address this, we have devised an engineering strategy combining microfluidics and conjugation chemistry to synthesize nanosized liposomes with two discrete compartments, one within another, which we term concentrisomes. We can control the composition of each bilayer and tune both particle size and the dimensions between inner and outer membranes. We can specify the identity of encapsulated cargo within each compartment, and the biophysical features of inner and outer bilayers, allowing us to imbue each bilayer with different stimuli-responsive properties. We use these particles for multi-stage release of two payloads at defined time points, and as attolitre reactors for triggered in situ biochemical synthesis.
Adherence and persistence to tafamidis treatment among Medicare beneficiaries in the presence of a patient assistance program
Authors: Chung Haechung , Cantu Cera , Pankratova Cindi , Kemner Jason , Alvir Jose , Prasad Sapna , Chen Yong
Published: July 2024

Tafamidis is the only disease-modifying therapy approved to treat patients in the United States with transthyretin amyloid cardiomyopathy (ATTR-CM), which most commonly affects patients aged ≥ 65 years. The manufacturer operates a patient assistance program (PAP) to support access to tafamidis. This study conducted Privacy Preserving Record Linking (PPRL) using Datavant tokens to match patients across Medicare prescription drug plan (PDP) and PAP databases to evaluate the impact of PAPs on treatment exposure classification, adherence, and persistence determined using Medicare PDP data alone. We found 35% of Medicare PDP patients received tafamidis through the PAP only; 14% through both Medicare PDP and the PAP, and 51% through Medicare PDP only. Adherence and persistence were comparable between these cohorts but underestimated among patients who received ≥ 2 prescriptions through Medicare PDP and ≥ 1 through the PAP when solely using Medicare data versus pooled Medicare and PAP data (modified Medication Possession Ratio: 84% [69% ≥ 80% adherent] vs. 96% [93%]; Proportion of Days Covered: 77% [66% ≥ 80% adherent] vs. 88% [88%]; mean days to discontinuation: 186 vs. 252; total discontinuation: 13% vs. 11%). Cross-database PPRL is a valuable method to build more complete treatment journeys and reduce the risk of exposure misclassification in real-world analyses.
Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division
Authors: Dreiwi Hanan , Feliciangeli Flavia , Castro Mario , Lythe Grant , Molina-París Carmen , López-García Martín
Published: July 2024

Division and differentiation events by which cell populations with specific functions are generated often take place as part of a developmental programme, which can be represented by a sequence of compartments. A compartment is the set of cells with common characteristics; sharing, for instance, a spatial location or a phenotype. Differentiation events are transitions from one compartment to the next. Cells may also die or divide. We consider three different types of division events: (i) where both daughter cells inherit the mother’s phenotype (self-renewal), (ii) where only one of the daughters changes phenotype (asymmetric division), and (iii) where both daughters change phenotype (symmetric division). The self-renewal probability in each compartment determines whether the progeny of a single cell, moving through the sequence of compartments, is finite or grows without bound. We analyse the progeny stochastic dynamics with probability generating functions. In the case of self-renewal, by following one of the daughters after any division event, we may construct lifelines containing only one cell at any time. We analyse the number of divisions along such lines, and the compartment where lines terminate with a death event. Analysis and numerical simulations are applied to a five-compartment model of the gradual differentiation of hematopoietic stem cells and to a model of thymocyte development: from pre-double positive to single positive (SP) cells with a bifurcation to either SP4 or SP8 in the last compartment of the sequence.
The impact of tertiary lymphoid structures on tumor prognosis and the immune microenvironment in non-small cell lung cancer
Authors: Weng Yiming , Yuan Jingping , Cui Xue , Wang Jinsong , Chen Honglei , Xu Li , Chen Xinyi , Peng Min , Song Qibin
Published: July 2024

Non-small cell lung cancer (NSCLC) is a common malignancy whose prognosis and treatment outcome are influenced by many factors. Some studies have found that tertiary lymphoid structures (TLSs) in cancer may contribute to prognosis and the prediction of immunotherapy efficacy However, the combined role of TLSs in NSCLC remains unclear. We accessed The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to obtain mRNA sequencing data and clinical information as the TCGA cohort, and used our own sample of 53 advanced NSCLC as a study cohort. The samples were divided into TLS+ and TLS- groups by pathological tissue sections. Patients of the TLS+ group had a better OS (p = 0.022), PFS (p = 0.042), and DSS (p = 0.004) in the TCGA cohort, and the results were confirmed by the study cohort (PFS, p = 0.012). Furthermore, our result showed that the count and size of TLSs are closely associated with the efficacy of immunotherapy. In addition, the TLS+ group was associated with better immune status and lower tumor mutation load. In the tumor microenvironment (TME), the expression levels of CD4+ T cells and CD8+ T cells of different phenotypes were associated with TLSs. Overall, TLSs are a strong predictor of survival and immunotherapeutic efficacy in advanced NSCLC, and T cell-rich TLSs suggest a more ordered and active immune response site, which aids in the decision-making and application of immunotherapy in the clinic.
Prevalence and trends in overactive bladder among men in the United States, 2005–2020
Authors: Cheng Yu , Chen Tao , Zheng Guanghao , Song Zhen , Zhang Gan , Rao Xuepeng , Zeng Tao , Yuan Changfei
Published: July 2024

The purpose of present study was to examine the current prevalence and recent trends of overactive bladder (OAB) among US adult men and examine the correlations between OAB and several potential risk factors. The study used the nationally representative data between 2005 and 2020 from the National Health and Nutrition Examination Survey in the US. A total of 18,386 participants aged ≥ 20 years were included in the study. We divided the data into three groups: 2005–2008, 2009–2014 and 2015–2020 to investigate the trends in OAB prevalence. The weighted prevalence and corresponding 95% confidence intervals (CI) of OAB were calculated. The differences (95% CI) in prevalence between the surveys were calculated and multivariate-adjusted weighted logistic regression analysis was performed to determine the correlates of OAB. Among all US adult men, the overall prevalence of OAB increased slightly from 11.3% in 2005–2008 to 11.7% in 2009–2014 and significantly increased to 14.5% in 2015–2020 (difference, 3.2% [95% CI (1.9–4.4%)]; P < 0.05). Increases in OAB prevalence especially concentrated on those who were 40–59 years, non-Hispanic White, non-Hispanic Black and those who were overweight and obese. Older age, non-Hispanic Black, lower educational level and family poverty ratio, diabetes, depression, sleep disorder, other chronic comorbidities, less intense recreational activity, poorer health condition and unsafe food were independent risk factors of OAB. The contemporary prevalence of OAB was high, affecting 14.5% US men and the estimated overall prevalence significantly increased from 2005 to 2020. Therefore, future research should be focused to prevent and remedy this growing socioeconomic and individually troublesome malady.