bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum mechanics of particles constrained to spiral curves with application to polyene chains
Authors: Anjos Eduardo V. S. , Pavão Antonio C. , da Silva Luiz C. B. , Bastos Cristiano C.
Published: July 2024

Context

Due to advances in synthesizing lower-dimensional materials, there is the challenge of finding the wave equation that effectively describes quantum particles moving on 1D and 2D domains. Jensen and Koppe and Da Costa independently introduced a confining potential formalism showing that the effective constrained dynamics is subjected to a scalar geometry-induced potential; for the confinement to a curve, the potential depends on the curve’s curvature function.

Method

To characterize the $$\varvec{\pi }$$

π

electrons in polyenes, we follow two approaches. First, we utilize a weakened Coulomb potential associated with a spiral curve. The solution to the Schrödinger equation with Dirichlet boundary conditions yields Bessel functions, and the spectrum is obtained analytically. We employ the particle-in-a-box model in the second approach, incorporating effective mass corrections. The $$\varvec{\pi }$$

π

-$$\varvec{\pi ^{*}}$$

π

∗

transitions of polyenes were calculated in good experimental agreement with both approaches, although with different wave functions.
Complement C3a/C3aR and C5a/C5aR deposits accelerate the progression of advanced IgA nephropathy to end-stage renal disease
Authors: Wang Ying , Shang Shunlai , Jiang Shimin , Zou Guming , Gao Hongmei , Li Wenge
Published: July 2024

IgA nephropathy (IgAN) is still one of the leading causes of end-stage kidney disease (ESRD), and complement system activation is a key to the pathogenesis of IgAN. The role of complement C3a/C3aR and C5a/C5aR in late stage of IgAN remains unknown. Renal specimens of 75 IgAN patients at the stage 4 CKD were stained using immunofluorescence and immunohistochemistry. The primary outcome was a composite of end-stage renal disease (ESRD) and death. Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses. During a median follow-up of 15.0 months, 27 patients progressed to ESRD and none died. Lower eGFR [hazards ratio (HR), 0.827, 95% confidence interval (CI), 0.732–0.935; P = 0.002] and glomerular C3 deposition (HR, 3.179, 95% CI, 1.079–9.363; P = 0.036) were predictive of time to ESRD in stage 4 CKD IgAN. Higher expression of C3a (P = 0.010), C3aR (P = 0.005), C5a (P = 0.015), and C5aR (P < 0.001) was identified in ESRD group than in non-ESRD group. Glomerular C3a/C3aR and C5a/C5aR deposits were both correlated with a lower baseline eGFR, higher baseline 24 h-urinary protein (24 h-UP) and faster decline of eGFR. Besides, C3a and C5a deposits were found in patients with high S (S1) and T (T1/2) scores, respectively. Complement C3a/C3aR and C5a/C5aR in IgAN patients with stage 4 CKD may portend a faster deterioration of kidney function.
Development of Microstructure in Aluminum Single Crystal During Complex Shearing of Extruded Tube
Authors: Lejček Pavel , Školáková Andrea , Molnárová Orsolya , Habr Stanislav , Čapek Jaroslav , Čepová Marta , Málek Přemysl
Published: July 2024

The development of the microstructure during severe plastic deformation of an aluminum single crystal by complex shearing of the extruded tube (CSET) was studied in this paper. The research has demonstrated that even in a single crystal, an ultrafine-grained microstructure can be obtained during this one-step process. The size of the grains gradually changes and reaches the minimum size on the level of 1 μm at the inner surface of the resulting tube. Simultaneously, preferential orientations in individual parts of the deformed sample change in a complex way. The main mechanism affecting the final microstructure is continuous dynamic recrystallization. The microhardness also exhibits a gradient character with higher values at the inner surface of the tube compared to its center.

Graphical Abstract
Oral Administration of Limosilactobacillus reuteri KBL346 Ameliorates Influenza Virus A/PR8 Infection in Mouse
Authors: Choi Doseon , Jang Sung Jae , Choi Sueun , Park SungJun , Kim Woon-Ki , Lee Giljae , Lee Cheonghoon , Ko GwangPyo
Published: July 2024

Influenza virus infection is an important public-health concern because of its high transmissibility and potential for severe complications. To mitigate the severity and complications of influenza, probiotics containing Lactobacillus are used and generally recognized as safe. We evaluated the anti-influenza effect of Limosilactobacillus reuteri (L. reuteri) KBL346, isolated from the fecel sample of healthy South Koreans, in mice. BALB/c mice were orally administered live and heat-inactivated L. reuteri KBL346. After infection with influenza virus (A/Puerto Rico/8/34) 0.5 times the 50% lethal dose (LD50), body weight loss was improved and recovery was accelerated. Furthermore, L. reuteri KBL346 improved body weight loss and survival rate of mice infected with 4 times the LD50 of influenza virus. Heat-inactivated L. reuteri KBL346 reduced the viral titer in the lung and the plasma immunoglobulin G level. Expression levels of genes encoding inflammatory cytokines, such as interferon-γ and toll-like receptor 2 (Tlr2), were decreased in the lung tissues of mice administered L. reuteri KBL346. Live and heat-inactivated L. reuteri KBL346 increased the expression level of Adamts4, which promotes recovery after infection, and decreased that of Tlr2. The α-diversity of the gut microbiome was modulated by the administration of L. reuteri KBL346. In addition, the structure of the gut microbial community differed according to the degree of weight loss. L. reuteri KBL346 has the potential to alleviate disease severity and improve histopathological changes in mice infected with influenza A/PR8, suggesting its efficacy as a probiotic against influenza infection.
A modified cell-to-cell simulation model to predict oil-gas minimum miscibility pressure
Authors: Yang FuLin
Published: July 2024

Calculating the minimum miscibility pressure (MMP) between crude oil and carbon dioxide (CO2) is critical for optimizing injection parameters, designing schemes, and predicting production capacity in CO2 injection projects for enhancing oil recovery. However, an accurate approach for obtaining this parameter is not yet established. In order to tackle this issue, a novel approach is suggested, based on the original cell-to-cell model, to determine the MMP and the 97% oil recovery rate as the standard. Using the volume-transformed Peng-Robinson equation of state enhances the precision of fluid volume estimation, as it mainly relies on predicting fluid volume within each cell. Furthermore, to ensure a precise estimation of the ultimate oil recovery rate, it is imperative to employ a total cell count of 500 in all simulations to avoid the problem of numerical dispersion. Finally, a second-order polynomial equation more accurately predicts the infinite-cell oil recovery factor. The accuracy of the modified model is verified by comparing MMP values from five oil and gas systems in the literature. The computational results of the modified multiple-mixing-cell (MMC) approach exhibit a higher level of concordance with the MMPs in the literature. The average relative error is less than 3.96%. The improved MMC algorithm can quickly determine the miscibility mechanism and visually represent the dynamic miscibility process involving multiple oil-gas contacts in a slim tube. This study provides a theoretical and practical basis for addressing the critical scientific issues of CO2-safe storage technology.
Quantitative phosphoproteomics reveals molecular pathway network in wheat resistance to stripe rust
Authors: Gan Pengfei , Tang Chunlei , Lu Yi , Ren Chenrong , Nasab Hojjatollah Rabbani , Kun Xufeng , Wang Xiaodong , Li Liangzhuang , Kang Zhensheng , Wang Xiaojie , Wang Jianfeng
Published: July 2024

Protein phosphorylation plays an important role in immune signaling transduction in plant resistance to pathogens. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), severely devastates wheat production. Nonetheless, the molecular mechanism of wheat resistance to stripe rust remains limited. In this study, quantitative phosphoproteomics was employed to investigate the protein phosphorylation changes in wheat challenged by Pst. A total of 1537 and 2470 differentially accumulated phosphoproteins (DAPs) were identified from four early infection stage (6, 12, 18 and 24 h post-inoculation) in incompatible and compatible wheat-Pst interactions respectively. KEGG analysis revealed that Oxidative Phosphorylation, Phosphatidylinositol Signaling, and MAPK signaling processes are distinctively enriched in incompatible interaction, while Biosynthesis of secondary metabolites and RNA degradation process were significantly enriched in compatible interactions. In particular, abundant changes in phosphorylation levels of chloroplast proteins were identified, suggesting the regulatory role of photosynthesis in wheat-Pst interaction, which is further emphasized by protein-protein interaction (PPI) network analysis. Motif-x analysis identified [xxxxSPxxxx] motif, likely phosphorylation sites for defensive response-related kinases, and a new [xxxxSSxxxx] motif significantly enriched in incompatible interaction. The results shed light on the early phosphorylation events contributing to wheat resistance against Pst. Moreover, our study demonstrated that the phosphorylation levels of Nucleoside diphosphate kinase TaNAPK1 are upregulated at 12 hpi with CYR23 and at 24 hpi with CYR31. Transient silencing of TaNAPK1 was able to attenuate wheat resistance to CYR23 and CYR31. Our study provides new insights into the mechanisms underlying Pst-wheat interactions and may provide database to find potential targets for the development of new resistant varieties.
Experiment on the Hydrodynamic Characteristics of Plunging Flows in Bedrock Canyon Bends
Authors: Li Bin , Xu Haijue , Bai Yuchuan , Lu Jun
Published: July 2024

Bedrock river incision drives the evolution of the Earth's landscape and is influenced by river hydraulic power. However, the relationship between plunging flows and the curvature of bedrock canyons is poorly understood, which encouraged us to explore how the bend's curvature and undulating beds affect plunging flows. A generalized physical model was built to investigate the hydrodynamic characteristics of plunging flows in a constant curvature flume with plain and undulating beds. Our experimental findings demonstrated that plunging flows were related to secondary circulation, topography, and width‐to‐depth ratios. Plunging flows occurred when secondary circulation reached its peak, and as secondary circulation vanished, the intensity of plunging flows decreased. The undulating bed topography in the bedrock bends suppressed secondary circulation and the development of plunging flows. Bed topography may be a dominant factor in plunging flows in bedrock bends. The potential erosion area in bedrock bends was related to the intensity of plunging flows, which caused velocity inversion to increase the shear stress near the bed. With higher discharges and undulating beds, the intensity of the transverse shear stress of the riverbed near the center was greater. The potential erosion area in bedrock bends was concentrated at the center of the cross‐section around the bend apex upstream. Our experimental results can improve incision models in terms of the distribution of shear stress and flow structure in bedrock bends.
Iterative Error‐Driven Ensemble Labeling (IEDEL) Algorithm for Enhanced Data Quality Control for the Atmospheric Radiation Measurement (ARM) Program User Facility
Authors: Li Lishan , Kehoe Kenneth E. , Hu Jiaxi , Peppler Randy A. , Sockol Alyssa J. , Godine Corey A.
Published: July 2024

For over three decades, the Atmospheric Radiation Measurement (ARM) Program user facility has provided researchers with invaluable benchmark atmospheric data. Ensuring the accuracy and integrity of ARM data is vital, and to achieve this, the ARM Data Quality Office (DQO) has implemented customized quality control tests tailored to each variable, with guidance from instrument mentors. These tests are designed to pinpoint common issues, such as data exceeding valid ranges or persisting with little change over extended periods, and ARM offers tools for users to review and exclude contaminated data efficiently. However, certain quality issues, such as spikes in time series or data drift over time, sometimes evade detection by existing tests and require manual identification by data analysts and instrument mentors through visualization tools. To tackle these challenges more efficiently, the DQO has developed and implemented the Iterative Error‐Driven Ensemble Labeling (IEDEL) algorithm with unanimous voting and transfer learning techniques to efficiently generate labeled data at scale. This initiative has empowered the creation of high‐performing machine learning models, enabling real‐time monitoring of data quality issues within the ARM data and thereby enhancing data integrity and accessibility.
Development of a novel testis-on-a-chip that demonstrates reciprocal crosstalk between Sertoli and Leydig cells in testicular tissue
Authors: Park Se-Ra , Kook Myung Geun , Kim Soo-Rim , Lee Choon-Mi , Lee Jin Woo , Park Jung-Kyu , Park Chan Hum , Oh Byung-Chul , Jung YunJae , Hong In-Sun
Published: July 2024

The reciprocal crosstalk between testicular Sertoli and Leydig cells plays a vital role in supporting germ cell development and maintaining testicular characteristics and spermatogenesis. Conventional 2D and the recent 3D assay systems fail to accurately replicate the dynamic interactions between these essential endocrine cells. Furthermore, most in vitro testicular tissue models lack the ability to capture the complex multicellular nature of the testis. To address these limitations, we developed a 3D multicellular testis-on-a-chip platform that effectively demonstrates the reciprocal crosstalk between Sertoli cells and the adjacent Leydig cells while incorporating various human testicular tissue constituent cells and various natural polymers infused with blood coagulation factors. Additionally, we identified SERPINB2 as a biomarker of male reproductive toxicity that is activated in both Sertoli and Leydig cells upon exposure to various toxicants. Leveraging this finding, we designed a fluorescent reporter-conjugated toxic biomarker detection system that enables both an intuitive and quantitative assessment of material toxicity by measuring the converted fluorescence intensity. By integrating this fluorescent reporter system into the Sertoli and Leydig cells within our 3D multicellular chip platform, we successfully developed a testis-on-chip model that can be utilized to evaluate the male reproductive toxicity of potential drug candidates. This innovative approach holds promise for advancing toxicity screening and reproductive research.
PHGDH: a novel therapeutic target in cancer
Authors: Lee Chae Min , Hwang Yeseong , Kim Minki , Park Ye-Chan , Kim Hyeonhui , Fang Sungsoon
Published: July 2024

Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting enzyme in the serine biosynthesis pathway, facilitating the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Elevated PHGDH activity in diverse cancer cells is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. Ultimately, these characteristics allow PHGDH to not only influence the growth and progression of cancer but also play an important role in metastasis and drug resistance. Consequently, PHGDH has emerged as a crucial focal point in cancer research. In this review, the structural aspects of PHGDH and its involvement in one-carbon metabolism are investigated, and PHGDH is proposed as a potential therapeutic target in diverse cancers. By elucidating how PHGDH expression promotes cancer growth, the goal of this review is to provide insight into innovative treatment strategies. This paper aims to reveal how PHGDH inhibitors can overcome resistance mechanisms, contributing to the development of effective cancer treatments.
Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology
Authors: Thorel Lucie , Perréard Marion , Florent Romane , Divoux Jordane , Coffy Sophia , Vincent Audrey , Gaggioli Cédric , Guasch Géraldine , Gidrol Xavier , Weiswald Louis-Bastien , Poulain Laurent
Published: July 2024

Over the past decade, the emergence of patient-derived tumor organoids (PDTOs) has broadened the repertoire of preclinical models and progressively revolutionized three-dimensional cell culture in oncology. PDTO can be grown from patient tumor samples with high efficiency and faithfully recapitulates the histological and molecular characteristics of the original tumor. Therefore, PDTOs can serve as invaluable tools in oncology research, and their translation to clinical practice is exciting for the future of precision medicine in oncology. In this review, we provide an overview of methods for establishing PDTOs and their various applications in cancer research, starting with basic research and ending with the identification of new targets and preclinical validation of new anticancer compounds and precision medicine. Finally, we highlight the challenges associated with the clinical implementation of PDTO, such as its representativeness, success rate, assay speed, and lack of a tumor microenvironment. Technological developments and autologous cocultures of PDTOs and stromal cells are currently ongoing to meet these challenges and optimally exploit the full potential of these models. The use of PDTOs as standard tools in clinical oncology could lead to a new era of precision oncology in the coming decade.
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions
Authors: Lu Peilin , Ruan Dongxue , Huang Meiqi , Tian Mi , Zhu Kangshun , Gan Ziqi , Xiao Zecong
Published: July 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.
Dynamicity of brain network organization & their community architecture as characterizing features for classification of common mental disorders from whole-brain connectome
Authors: Sastry Nisha Chetana , Banerjee Arpan
Published: July 2024

The urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome’s modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome’s temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns’ spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.
Semiautomated experiment with a robotic system and data generation by foundation models for synthesis of polyamic acid particles
Authors: Hatakeyama-Sato Kan , Ishikawa Hiroki , Takaishi Shinya , Igarashi Yasuhiko , Nabae Yuta , Hayakawa Teruaki
Published: July 2024

A semiautomated system for synthesizing polyamic acid particles using a custom liquid-handling device and a robotic arm is proposed in this study. Integration of cameras and a multimodal large language model facilitates continuous monitoring and documentation, enhancing objectivity in synthetic experiments and enabling future advancements in experimental research.
Asset-level assessment of climate physical risk matters for adaptation finance
Authors: Bressan Giacomo , Đuranović Anja , Monasterolo Irene , Battiston Stefano
Published: July 2024

Climate physical risk assessment is crucial to inform adaptation policies and finance. However, science-based and transparent solutions to assess climate physical risks are limited, compounding the adaptation gap. This is a main limitation to fill the adaptation gap. We provide a methodology that quantifies physical risks on geolocalized productive assets, considering their exposure to chronic and acute impacts (hurricanes) across the scenarios of the Intergovernmental Panel on Climate Change. Then, we translate asset-level shocks into economic and financial losses. We apply the methodology to Mexico, a country highly exposed to physical risks, recipient of adaptation finance and foreign investments. We show that investor losses are underestimated up to 70% when neglecting asset-level information, and up to 82% when neglecting tail acute risks. Therefore, neglecting the asset-level and acute dimensions of physical risks leads to large errors in the identification of adaptation policy responses, investments and finance tools aimed to build resilience to climate change.
The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function
Authors: Kibalnyk Yana , Afanasiev Elia , Noble Ronan M. N. , Watson Adrianne E. S. , Poverennaya Irina , Dittmann Nicole L. , Alexiou Maria , Goodkey Kara , Greenwell Amanda A. , Ussher John R. , Adameyko Igor , Massey James , Graf Daniel , Bourque Stephane L. , Stratton Jo Anne , Voronova Anastassia
Published: July 2024

ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.
An outside individual option increases optimism and facilitates collaboration when groups form flexibly
Authors: Mori Ryutaro , Hanaki Nobuyuki , Kameda Tatsuya
Published: July 2024

Voluntary participation is a central yet understudied aspect of collaboration. Here, we model collaboration as people’s voluntary choices between joining an uncertain public goods provisioning in groups and pursuing a less profitable but certain individual option. First, we find that voluntariness in collaboration increases the likelihood of group success via two pathways, both contributing to form more optimistic groups: pessimistic defectors are filtered out from groups, and some individuals update their beliefs to become cooperative. Second, we reconcile these findings with existing literature that highlights the detrimental effects of an individual option. We argue that the impact of an outside individual option on collaboration depends on the “externality” of loners — the influence that those leaving the group still exert on group endeavors. Theoretically and experimentally, we show that if collaboration allows for flexible group formation, the negative externality of loners remains limited, and the presence of an individual option robustly aids collaborative success.
Linear ubiquitination regulates the KSHV replication and transcription activator protein to control infection
Authors: Luan Yi , Long Wenying , Dai Lisi , Tao Panfeng , Deng Zhifen , Xia Zongping
Published: July 2024

Like many other viruses, KSHV has two life cycle modes: the latent phase and the lytic phase. The RTA protein from KSHV is essential for lytic reactivation, but how this protein’s activity is regulated is not fully understood. Here, we report that linear ubiquitination regulates the activity of RTA during KSHV lytic reactivation and de novo infection. Overexpressing OTULIN inhibits KSHV lytic reactivation, whereas knocking down OTULIN or overexpressing HOIP enhances it. Intriguingly, we found that RTA is linearly polyubiquitinated by HOIP at K516 and K518, and these modifications control the RTA’s nuclear localization. OTULIN removes linear polyubiquitin chains from cytoplasmic RTA, preventing its nuclear import. The RTA orthologs encoded by the EB and MHV68 viruses are also linearly polyubiquitinated and regulated by OTULIN. Our study establishes that linear polyubiquitination plays a critically regulatory role in herpesvirus infection, adding virus infection to the list of biological processes known to be controlled by linear polyubiquitination.
Single-base tiled screen unveils design principles of PspCas13b for potent and off-target-free RNA silencing
Authors: Hu Wenxin , Kumar Amit , Ahmed Syed Faraz , Qi Shijiao , Ma David K. G. , Chen Honglin , Singh Gurjeet J. , Casan Joshua M. L. , Haber Michelle , Voskoboinik Ilia , McKay Matthew R. , Trapani Joseph A. , Ekert Paul G. , Fareh Mohamed
Published: July 2024

The development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer–target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.
Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly
Authors: Braxton Julian R. , Shao Hao , Tse Eric , Gestwicki Jason E. , Southworth Daniel R.
Published: July 2024

The mitochondrial chaperonin, mitochondrial heat shock protein 60 (mtHsp60), promotes the folding of newly imported and transiently misfolded proteins in the mitochondrial matrix, assisted by its co-chaperone mtHsp10. Despite its essential role in mitochondrial proteostasis, structural insights into how this chaperonin progresses through its ATP-dependent client folding cycle are not clear. Here, we determined cryo-EM structures of a hyperstable disease-associated human mtHsp60 mutant, V72I. Client density is identified in three distinct states, revealing interactions with the mtHsp60 apical domains and C termini that coordinate client positioning in the folding chamber. We further identify an asymmetric arrangement of the apical domains in the ATP state, in which an alternating up/down configuration positions interaction surfaces for simultaneous recruitment of mtHsp10 and client retention. Client is then fully encapsulated in mtHsp60–10, revealing prominent contacts at two discrete sites that potentially support maturation. These results identify distinct roles for the apical domains in coordinating client capture and progression through the chaperone cycle, supporting a conserved mechanism of group I chaperonin function.
Effect of temperature on the biological parameters of pink bollworm, Pectinophora gossypiella Saunders (Lepidoptera: Gelechiidae)
Authors: Nagaraju Madhu Tadagavadi , Mohan Kamanur Murali , Keerthi Manikyanahalli Chandrashekara , Prabhulinga Tenguri , Thube Shivaji , Shah Vivek , Elansary Hosam O. , Mousa Ihab Mohamed , El-Sheikh Mohamed A.
Published: July 2024

Pink bollworm (PBW) Pectinophora gossypiella is an important pest cotton worldwide. There are multiple factors which determines the occurrence and distribution of P. gossypiella across different cotton growing regions of the world, and one such key factor is ‘temperature’. The aim was to analyze the life history traits of PBW across varying temperature conditions. We systematically explored the biological and demographic parameters of P. gossypiella at five distinct temperatures; 20, 25, 30, 35 and 40 ± 1 °C maintaining a photoperiod of LD 16:8 h. The results revealed that the total developmental period of PBW shortens with rising temperatures, and the highest larval survival rates were observed between 30 °C and 35 °C, reaching 86.66% and 80.67%, respectively. Moreover, significant impacts were observed as the pupal weight, percent mating success, and fecundity exhibited higher values at 30 °C and 35 °C. Conversely, percent egg hatching, larval survival, and adult emergence were notably lower at 20 °C and 40 °C, respectively. Adult longevity decreased with rising temperatures, with females outliving males across all treatments. Notably, thermal stress had a persistent effect on the F1 generation, significantly affecting immature stages (egg and larvae), while its impact on reproductive potential was minimal. These findings offer valuable insights for predicting the population dynamics of P. gossypiella at the field level and developing climate-resilient management strategies in cotton.
ToF-SIMS evaluation of PEG-related mass peaks and applications in PEG detection in cosmetic products
Authors: Shen Yanjie , Son Jiyoung , Yu Xiao-Ying
Published: July 2024

Polyethylene glycols (PEGs) are used in industrial, medical, health care, and personal care applications. The cycling and disposal of synthetic polymers like PEGs pose significant environmental concerns. Detecting and monitoring PEGs in the real world calls for immediate attention. This study unveils the efficacy of time-of-flight secondary ion mass spectrometry (ToF-SIMS) as a reliable approach for precise analysis and identification of reference PEGs and PEGs used in cosmetic products. By comparing SIMS spectra, we show remarkable sensitivity in pinpointing distinctive ion peaks inherent to various PEG compounds. Moreover, the employment of principal component analysis effectively discriminates compositions among different samples. Notably, the application of SIMS two-dimensional image analysis visually portrays the spatial distribution of various PEGs as reference materials. The same is observed in authentic cosmetic products. The application of ToF-SIMS underscores its potential in distinguishing PEGs within intricate environmental context. ToF-SIMS provides an effective solution to studying emerging environmental challenges, offering straightforward sample preparation and superior detection of synthetic organics in mass spectral analysis. These features show that SIMS can serve as a promising alternative for evaluation and assessment of PEGs in terms of the source, emission, and transport of anthropogenic organics.
sUPRa is a dual-color reporter for unbiased quantification of the unfolded protein response with cellular resolution
Authors: Chakrabarty Atreyi , Newey Sarah E. , Promi Maisha M. , Agbetiameh Belinda K. , Munro Daniella , Brodersen Paul J. N. , Gothard Gemma , Mahfooz Kashif , Mengual Jose P. , Vyazovskiy Vladyslav V. , Akerman Colin J.
Published: July 2024

The unfolded protein response (UPR) maintains proteostasis upon endoplasmic reticulum (ER) stress, and is initiated by a range of physiological and pathological processes. While there have been advances in developing fluorescent reporters for monitoring individual signaling pathways of the UPR, this approach may not capture a cell’s overall UPR activity. Here we describe a novel sensor of UPR activity, sUPRa, which is designed to report the global UPR. sUPRa displays excellent response characteristics, outperforms reporters of individual UPR pathways in terms of sensitivity and kinetics, and responds to a range of different ER stress stimuli. Furthermore, sUPRa’s dual promoter and fluorescent protein design ensures that both UPR-active and inactive cells are detected, and controls for reporter copy number. Using sUPRa, we reveal UPR activation in layer 2/3 pyramidal neurons of mouse cerebral cortex following a period of sleep deprivation. sUPRa affords new opportunities for quantifying physiological UPR activity with cellular resolution.
Efficient handling of ACL policy change in SDN using reactive and proactive flow rule installation
Authors: Hussain Mudassar , Amin Rashid , Gantassi Rahma , Alshehri Asma Hassan , Frnda Jaroslav , Raza Syed Mohsan
Published: July 2024

Software-defined networking (SDN) is a pioneering network paradigm that strategically decouples the control plane from the data and management planes, thereby streamlining network administration. SDN's centralized network management makes configuring access control list (ACL) policies easier, which is important as these policies frequently change due to network application needs and topology modifications. Consequently, this action may trigger modifications at the SDN controller. In response, the controller performs computational tasks to generate updated flow rules in accordance with modified ACL policies and installs flow rules at the data plane. Existing research has investigated reactive flow rules installation that changes in ACL policies result in packet violations and network inefficiencies. Network management becomes difficult due to deleting inconsistent flow rules and computing new flow rules per modified ACL policies. The proposed solution efficiently handles ACL policy change phenomena by automatically detecting ACL policy change and accordingly detecting and deleting inconsistent flow rules along with the caching at the controller and adding new flow rules at the data plane. A comprehensive analysis of both proactive and reactive mechanisms in SDN is carried out to achieve this. To facilitate the evaluation of these mechanisms, the ACL policies are modeled using a 5-tuple structure comprising Source, Destination, Protocol, Ports, and Action. The resulting policies are then translated into a policy implementation file and transmitted to the controller. Subsequently, the controller utilizes the network topology and the ACL policies to calculate the necessary flow rules and caches these flow rules in hash table in addition to installing them at the switches. The proposed solution is simulated in Mininet Emulator using a set of ACL policies, hosts, and switches. The results are presented by varying the ACL policy at different time instances, inter-packet delay and flow timeout value. The simulation results show that the reactive flow rule installation performs better than the proactive mechanism with respect to network throughput, packet violations, successful packet delivery, normalized overhead, policy change detection time and end-to-end delay. The proposed solution, designed to be directly used on SDN controllers that support the Pyretic language, provides a flexible and efficient approach for flow rule installation. The proposed mechanism can be employed to facilitate network administrators in implementing ACL policies. It may also be integrated with network monitoring and debugging tools to analyze the effectiveness of the policy change mechanism.
DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression
Authors: Acero-Riaguas Lucía , Griso-Acevedo Ana Belén , SanLorenzo-Vaquero Alejandro , Ibáñez-Herrera Blanca , Fernandez-Diaz Sara María , Mascaraque Marta , Sánchez-Siles Rocío , López-García Iván , Benítez-Buelga Carlos , Bravo-Burguillos Elena Ruiz , Castelo Beatriz , Cebrián-Carretero José Luis , Perona Rosario , Sastre Leandro , Sastre-Perona Ana
Published: July 2024

Salivary gland squamous cell carcinomas (SG-SCCs) constitute a rare type of head and neck cancer which is linked to poor prognosis. Due to their low frequency, the molecular mechanisms responsible for their aggressiveness are poorly understood. In this work we studied the role of the phosphatase DUSP1, a negative regulator of MAPK activity, in controlling SG-SCC progression. We generated DUSP1 KO clones in A253 human cells. These clones showed a reduced ability to grow in 2D, self-renew in ECM matrices and to form tumors in immunodeficient mice. This was caused by an overactivation of the stress and apoptosis kinase JNK1/2 in DUSP1−/+ clones. Interestingly, RNAseq analysis revealed that the expression of SOX2, a well-known self-renewal gene was decreased at the mRNA and protein levels in DUSP1−/+ cells. Unexpectedly, CRISPR-KO of SOX2 did not recapitulate DUSP1−/+ phenotype, and SOX2-null cells had an enhanced ability to self-renew and to form tumors in mice. Gene expression analysis demonstrated that SOX2-null cells have a decreased squamous differentiation profile -losing TP63 expression- and an increased migratory phenotype, with an enhanced epithelial to mesenchymal transition signature. In summary, our data indicates that DUSP1 and SOX2 have opposite functions in SG-SCC, being DUSP1 necessary for tumor growth and SOX2 dispensable showing a tumor suppressor function. Our data suggest that the combined expression of SOX2 and DUSP1 could be a useful biomarker to predict progression in patients with SG-SCCs.
A particular epidemiological profile: disparities in access to contraceptive methods in Brazil during the SARS-CoV-2 (COVID-19) pandemic
Authors: Marcelino Ana C. , da Cunha Pereira Paula , Charles Charles M.’Poca , Bahamondes Luis
Published: July 2024

Our objective was to study disparities in access to contraception during the COVID-19 pandemic. We performed a cross-sectional study at the University of Campinas, Brazil using a Google questionnaire applied from December 2021 until February 2022, disseminated via snowball technique. The survey asked about sociodemographic characteristics and contraceptive use, as well as the demand for new methods and difficulties in continuing to use contraceptives during the COVID-19 pandemic. We analyzed 1018 completed questionnaires; in total, 742 (72.9%) were women aged between 20 and 39 years, 746 (73.3%) were White and 602 (59.2%) used contraceptives. During the COVID-19 pandemic, about 23% of respondents changed their method and approximately 20% of respondents looked for new methods. Among the latter, 31.3% reported some difficulty with obtaining guidance on new methods while only 5.3% of the respondents reported some difficulty with continuing their contraceptive. The main difficulty in both cases was the difficulty with getting a healthcare provider appointment. Our results point to a particular epidemiological population, of younger black and biracial women, with lower education and lower income, which suffered health disparities during the COVID-19 pandemic and found difficulties with using contraceptives and accessing family planning services.
PowerAI-Diabetes: Review of glycemic and lipid variability to predict cardiovascular events in Chinese diabetic population
Authors: Lee Sharen , Liu Tong , Chung Cheuk To , Reinhold Johannes , Vassiliou Vassilios S. , Tse Gary
Published: July 2024

The aim of this study is to review the predictive value of visit-to-visit variability in glycaemic or lipid tests for forecasting major adverse cardiovascular events (MACE) in diabetes mellitus. Data from existing studies suggests that such variability is an independent predictor of adverse outcomes in this patient cohort. This understanding is then applied to the development of PowerAI-Diabetes, a Chinese-specific artificial intelligence-enhanced predictive model for predicting the risks of major adverse cardiovascular events and diabetic complications. The model integrates an amalgam of variables including demographics, laboratory and medication information to assess the risk of MACE. Future efforts should focus on the incorporation of treatment effects and non-traditional cardiovascular risk factors, such as social determinants of health variables, to improve the performance of predictive models.
Host–guest chemistry of tridentate Lewis acids based on tribenzotriquinacene
Authors: Franke Maurice , Ens Tobin , Mix Andreas , Neumann Beate , Stammler Hans-Georg , Mitzel Norbert W.
Published: July 2024

Attaching three Lewis acid functions to the TBTQ scaffold gave tridentate acids. Their ability to complex (poly-)Lewis bases and aggregate sizes were studied by solution NMR including DOSY NMR.
Twist angle-dependent interlayer hybridized exciton lifetimes in van der Waals heterostructures
Authors: Chen Shihong , Sun Zejun , Liu Huan , Xu Haowen , Wang Chong , Han Rui , Wang Zihao , Huang Shuchun , Zhao Xiaoliang , Chen Zekai , Li Weizhou , Liu Dameng
Published: July 2024

The interlayer twist angle has a direct effect on exciton lifetimes in van der Waals heterostructures.
Chemically synthesized poly(3,4-ethylenedioxythiophene) conducting polymer as a robust electrocatalyst for highly efficient dye-sensitized solar cells
Authors: Masud  , Aftabuzzaman Md. , Zhou Haoran , Kim Saehyun , Yi Jaekyung , Park Sarah S. , Kim Youn Soo , Kim Hwan Kyu
Published: July 2024

PEDOT counter electrodes, optimized via spin-coating a DMSO-dispersed solution from scalable synthesis, were evaluated for cobalt reduction in dye-sensitized solar cells. PEDOT was a superior electrocatalyst compared to Pt.
Electrochemical selenylative ipso-annulation of N-benzylacrylamides to construct seleno-azaspiro[4.5]decadienones
Authors: Raji Reddy Chada , Islam Jannatul , Nagendraprasad Thallamapuram , Ajaykumar Uprety
Published: July 2024

Construction of seleno azaspiro[4.5]decadienones using an electrochemical approach is achieved via domino selenylation/ipso-annulation.
New diterpene lactone derivatives from Aphanamixis polystachya leaves inhibit nitric oxide production in RAW 264.7 cells
Authors: Bang Ngo Anh , Hai Yen Duong Thi , Thuy Hang Dan Thi , Yen Pham Hai , Hoang Nguyen Huy , Trang Do Thi , Dung Duong Thi , Cuc Nguyen Thi , Cuong Nguyen The , Nhiem Nguyen Xuan , Tai Bui Huu , Van Kiem Phan
Published: July 2024

Five new acyclic diterpene lactone derivatives containing two rare structural fragments a γ/δ-lactone and a furan-3-one from Aphanamixis polystachya. They inhibited NO production in LPS activated RAW264.7 cells with IC50 values of 16.8–37.7 μM.
A geminal antimony(iii)/phosphorus(iii) frustrated Lewis pair
Authors: Krieft Jonas , Trapp Pia C. , Vishnevskiy Yury V. , Neumann Beate , Stammler Hans-Georg , Lamm Jan-Hendrik , Mitzel Norbert W.
Published: July 2024

(F5C2)2SbCH2P(tBu)2 reacts in a FLP-like manner with CS2, SO2, PhNCO/S and (MePh2P)AuCl. The CS2 and AuCl adduct show secondary interactions between the Lewis acidic Sb atom and electron rich atoms, intra- and intermolecular, respectively.
A facile strategy for the construction of a phage display cyclic peptide library for the selection of functional macrocycles
Authors: Xiang Hua , Bai Liwen , Zhang Xindan , Dan Ting , Cheng Peng , Yang Xiaoqin , Ai Honglian , Li Kai , Lei Xinxiang
Published: July 2024

We have developed a display platform by integrating ortho-phthalaldehyde (OPA) onto phage particles resulting in the generation of genetically encoded cyclic peptides.
Flow pattern maps of double emulsions transporting through bifurcation microchannels
Authors: Wang Xiang , Sun Chao , Jia Shiyan , Pang Yan , Liu Zhaomiao
Published: July 2024

Flow pattern map of double emulsions considering the coupling interaction between interfaces.
Boosting the ORR kinetics of protonic ceramic fuel cells via surface decoration using nonreactive insulators
Authors: Qiu Bingbing , Zhu Kang , Yang Yi , Ye Lujuan , Zhang Lijie , Xia Changrong , Peng Ranran , Lu Yalin
Published: July 2024

By employing non-reactive insulators with different work function through impregnation methods, the direction of electron transfer is revealed to be a critical determinant of ORR kinetic changes.
Electron beam and thermal stabilities of MFM-300(M) metal–organic frameworks
Authors: Tien Eu-Pin , Cao Guanhai , Chen Yinlin , Clark Nick , Tillotson Evan , Ngo Duc-The , Carter Joseph H. , Thompson Stephen P. , Tang Chiu C. , Allen Christopher S. , Yang Sihai , Schröder Martin , Haigh Sarah J.
Published: July 2024

This work reports the thermal and electron beam stabilities of a series of isostructural metal–organic frameworks (MOFs) of type MFM-300(M) (M = Al, Ga, In, Cr).