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Plant spotted leaf (spl) mutants are useful to reveal the regulatory mechanisms of immune responses. Thus, in crop plants, their agronomic traits, especially the grain quality are usually ignored. Here, we characterized a rice spl mutant named spl-A (spotted leaf mutant from A814) that shows autoimmunity, broad-spectrum disease resistance and growth deterioration including decreased rice quality. A single nucleotide mutation of C1144T, which leads to change of the 382nd proline to serine, in the gene encoding the ATPases associated with diverse cellular activities (AAA)-type ATPase LRD6-6 is responsible for the phenotype of the spl-A mutant. Mechanistically, this mutation impairs LRD6-6 ATPase activity and disrupts its interaction with endosomal sorting complex required for transport (ESCRT)-III subunits OsSNF7.1/7.2/7.3. And thus, leading to compromise of multivesicular bodies (MVBs)-mediated vesicle trafficking and accumulation of ubiquitinated proteins in both leaves and seeds of spl-A. Therefore, the immune response of spl-A is activated, and the growth and grain quality are deteriorated. Our study identifies a new amino acid residue that important for LRD6-6 and provides new insight into our understanding of how MVBs-mediated vesicle trafficking regulates plant immunity and growth, including grain quality in rice.

BackgroundFamily socioeconomic status (FSES) serves as a significant determinant for subjective well-being. However, extant research has provided conflicting evidence on the correlation between FSES and adolescent students’ subjective well-being (SSWB).MethodsData were collected from 12,058 adolescent students (16 years of age) by the Programme for International Student Assessment (PISA) 2018. Multivariate canonical correlation and Mantel test were utilized to investigate the specific connection between FSES and SSWB. Furthermore, a Gaussian EBICglasso graph-theoretical model was used to capture the topological properties of the FSES-SSWB network and reveal the interplay among multifarious components of FSES and SSWB.ResultsFSES was positively correlated with SSWB. In the FSES-SSWB network, parental educational attainment and occupation status demonstrated the highest centrality values, thereby contributing significantly to the relationship between FSES and SSWB. However, family wealth, along with educational and cultural resources, displayed lower centrality values, signifying their weaker roles in this relationship.ConclusionOur findings suggest that symbolic capital, rather than family affluence, exerts a dominant influence on adolescent SSWB. In other words, SSWB may not be detrimentally influenced by a deficiency in monetary resources. However, it is more susceptible to being unfavorably impacted by inferior parental educational attainment and occupational standing.

Abstract Massive increases in the risks of depressive disorders and the ensuing suicide have become the overarching menace for children/adolescents. Despite global consensus to instigate psychological healthcare policy for these children/adolescents, their effects remain largely unclear neither from a small amount of official data nor from small-scale scientific studies. More importantly, in underprivileged children/adolescents in lower-middle-economic-status countries/areas, the data collection may not be as equally accessible as in developed countries/areas, thus resulting in underrepresented observations. To address these challenges, we released a large-scale and multi-center cohort dataset (n = 249,772) showing the effects of primary psychological healthcare on decreasing depression and suicidal ideation in these children/adolescents who were underrepresented in previous studies or current healthcare systems, including unattended children/adolescents, orphans, children/adolescents in especially difficult circumstances, and “left-behind” and “single-parenting” children/adolescents. We provided all individual data recording the depressive symptoms and suicide ideation that had been collected at baseline (Oct 2022) and half-year follow-up (May 2023) from practicing this psychological healthcare system.

Abstract Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). These aptamers have nanomolar affinity with the nucleocapsid protein (NP) of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also show excellent binding efficiency to the N proteins of both SARS, MERS, HCoV-OC43 and -NL63 with affinity KD values of 1.31 to 135.36 nM. Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant (BA.5) with EC50 values at 2.00 nM and 41.08 nM, respectively. The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs (−229E and -HKU1). In conclusion, we have identified six aptamers with a high pan-coronavirus antiviral activity, which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

Abstract Background Severe community-acquired pneumonia (S-CAP) is a public health threat, making it essential to identify novel biomarkers and investigate the underlying mechanisms of disease severity. Methods Here, we profiled host responses to S-CAP through proteomics analysis of plasma samples from a cohort of S-CAP patients, non-severe (NS)-CAP patients, diseases controls (DCs), and healthy controls (HCs). Then, typical differentially expressed proteins were then validated by ELISA in an independent cohort. Metabolomics analysis was further performed on both the cohort 1 and cohort 2. Then, the proteomic and metabolomic signatures were compared between the adult and child cohorts to explore the characteristics of severe pneumonia patients. Results There were clear differences between CAP patients and controls, as well as substantial differences between the S-CAP and NS-CAP. Pathway analysis of changes revealed excessive inflammation, suppressed immunity, and lipid metabolic disorders in S-CAP cases. Interestingly, comparing these signatures between the adult and child cohorts confirmed that overactive inflammation and dysregulated lipid metabolism were common features of S-CAP patients, independent of age. The change proportion of glycerophospholipids, glycerolipids, and sphingolipids were obviously different in the adult and child S-CAP cases. Conclusion The plasma multi-omics profiling revealed that excessive inflammation, suppressed humoral immunity, and disordered metabolism are involved in S-CAP pathogenesis.

Objective: To explore the potential targets for melatonin in the treatment of periodontitis through network pharmacologic analysis and experimental validation via in vivo animal models and in vitro cellular experiments. Materials and methods: In this study, we first screened melatonin targets from Pharm Mapper for putative targets, Drug Bank, and TCMSP databases for known targets. Then, disease database was searched and screened for differential expressed genes associated with periodontitis. The intersection of disease and melatonin-related genes yielded potential target genes of melatonin treatment for periodontitis. These target genes were further investigated by protein-protein interaction network and GO/KEGG enrichment analysis. In addition, the interactions between melatonin and key target genes were interrogated by molecular docking simulations. Then, we performed animal studies to validate the therapeutic effect of melatonin by injecting melatonin into the peritoneal cavity of ligation-induced periodontitis (LIP) mice. The effects of melatonin on the predicted target proteins were also analyzed using Western blot and immunofluorescence techniques. Finally, we constructed an in vitro cellular model and validated the direct effect of melatonin on the predicted targets by using qPCR. Results: We identified 8 potential target genes by network pharmacology analysis. Enrichment analysis suggests that melatonin may treat periodontitis by inhibiting the expression of three potential targets (MPO, MMP8, and MMP9). Molecular docking results showed that melatonin could effectively bind to MMP8 and MMP9. Subsequently, melatonin was further validated in a mouse LIP model to inhibit the expression of MPO, MMP8, and MMP9 in the periodontal tissue. Finally, we verified the direct effect of melatonin on the mRNA expression of MPO, MMP8, and MMP9 in an in vitro cellular model. Conclusions: Through a combination of network pharmacology and experimental validation, this study provides a more comprehensive understanding of the mechanism of melatonin to treat periodontitis. Our study suggests that MPO, MMP8, and MMP9 as key target genes of melatonin to treat periodontitis. These findings present a more comprehensive basis for further investigation into the mechanisms of pharmacological treatment of periodontitis by melatonin.

The gene delivery systems (GDS) for lung cancer (LC) has made significant progress over the past 12 years, yet, there is a great challenge in its clinical application due to low delivery efficiency. This study aims to explore research fields related to gene therapy for LC and predict future directions from a bibliometric perspective. The Web of Science Core Collection collects articles and reviews on GDS for LC published from 2010 to 2022. Comprehensive bibliometric and visual analyses were performed using CiteSpace, VOSviewer, R-Bibliometrix, and Microsoft Excel. The analysis showed that the number of publications on GDS for LC has been increasing over the past 12 years, highlighting the growing interest and research efforts in this area. A rigorous examination of keywords and research hotspots revealed that the themes such as “complex,” “transfection,” “RNA interference,” “extracellular vesicle,” “co-deliver,” “resistance,” etc. dominate the field of GDS for LC. These findings indicated that the research in GDS for LC is evolving, with a noticeable shift toward addressing challenges related to delivery efficiency, transfection methods, and overcoming resistance mechanisms in gene therapy. The comprehensive study provides an overview of the literature on GDS for LC and identifies areas that require further exploration and development. By highlighting emerging research hotspots, our bibliometric analysis offers valuable insights to scholars and researchers, aiding in the identification of gaps, and guiding future efforts toward the development of GDS with more efficiency for LC therapy.

IntroductionFood production stands as a critical global concern necessitating comprehensive investigation. This study utilizes provincial-level data from China to explore the intricate relationships between farmland transfer, agricultural loans, and grain production, with the aim of shedding light on the complexities of these dynamics.MethodsA two-way fixed effects model and instrumental variable approach are applied to assess the interplay between farmland transfer, agricultural loans, and grain production. These methods provide a robust framework for understanding the complex relationships among these variables.Results and discussionThe study reveals a notable positive correlation between farmland transfer and grain production. Conversely, agricultural loans demonstrate a significantly negative impact on grain production. However, the positive interaction term between farmland transfer and agricultural loans suggests a nuanced relationship. While profit-driven financial activities may not inherently favor grain production, they contribute to more efficient utilization of farmland resources, ultimately promoting grain production. The findings underscore the significance of continued government support for rural land system reform and active guidance of farmland transfer. It is emphasized that a moderate-scale operation of farmland is crucial for finance to play a lubricating and catalytic role. Furthermore, there is a need to guide agricultural finance towards investing in medium and long-term projects of agricultural production. Attention is also directed to preventing potential food crises arising from the phenomenon of “non- farming” associated with agricultural loans.

Premature ovarian insufficiency (POI) may lead to early menopause, fertility loss and birth defects without effective treatment. Here, we explored the efficacy and safety of gene therapy to rescue ovarian function in both natural ovarian aging and doxorubicin (Dox) induced POI mice. Sirt1 and Tgfbr2 were screened out and identified as key genes in both murine and human ovarian tissues. Then, adenovirus (AdV) was selected as a suited carrier for ovarian infection after comparison of multiple viral vectors. In both two models, murine fertility was significantly improved after AdV-Sirt1 and AdV-Tgfbr2 invention individually or in combination, without obvious side effects to themselves and their offspring. Compared with the control group, the successful pregnancy rate in the 9-month-old-AdV-Sirt1 group increased by 60 % (67 % vs 42 %). Meanwhile, the pregnancy rate in the AdV-Tgfbr2 + Dox group increased by 85 % (55.6 % vs 20 %). The biological process of ovarian follicle development and fibrosis was rescued. Our work demonstrated that AdV-Sirt1 and AdV-Tgfbr2 therapy alleviates natural ovarian aging and Dox-associated POI, which may be potentially applicable for female fertility protection.

Abstract How convective boundary‐layer (CBL) processes modify fluxes of sensible (SH) and latent (LH) heat and CO2 (Fc) in the atmospheric surface layer (ASL) remains a recalcitrant problem. Here, large eddy simulations for the CBL show that while SH in the ASL decreases linearly with height regardless of soil moisture conditions, LH and Fc decrease linearly with height over wet soils but increase with height over dry soils. This varying flux divergence/convergence is regulated by changes in asymmetric flux transport between top‐down and bottom‐up processes. Such flux divergence and convergence indicate that turbulent fluxes measured in the ASL underestimate and overestimate the “true” surface interfacial fluxes, respectively. While the non‐closure of the surface energy balance persists across all soil moisture states, it improves over drier soils due to overestimated LH. The non‐closure does not imply that Fc is always underestimated; Fc can be overestimated over dry soils despite the non‐closure issue.

Electroreduction of CO2 into formic acid (HCOOH) is of great economical value and potential for industrialization. However, it is still a substantial challenge due to the lack of efficient catalysts with simultaneously high activity, selectivity, and durability. Herein, a single‐atom bismuth loaded on N‐doped hollow carbon sphere (Bi–SA/NHCS) catalyst is reported and its catalytic activity and selectivity are modulated by changing the coordination structure of Bi center. The obtained Bi–SA/NHCS with a Bi–N3 site exhibits significantly enhanced electrocatalytic activity and selectivity of HCOOH synthesis from CO2 reduction. The HCOOH production rate achieves 16.2 mmol L−1 h−1 cm−2 at a current density of 20 mA cm−2, and its Faradaic efficiency remains 100% during a long‐term reaction. The HCOOH production rate normalized by catalyst loading is at a molar level of nearly 1.5 mol h−1 gcat−1. The production rate and Faradaic efficiency of HCOOH electrosynthesis on Bi–SA/NHCS are significantly boosted as compared with other catalysts reported in the literature. Experimental and density‐functional theory results demonstrate that the boosted activity and selectivity of HCOOH synthesis owe to the electronic structure modulation to the Bi center via threefold coordinated N‐ligands, leading to a proper binding energy of HOCO* intermediates.

ABSTRACT: With the advent of the “Big Data Era”, improving data storage density and computation speed has become more and more urgent due to the rapid growth in different types of data. Flash memory with a floating gate (FG) structure is attracting great attention owing to its advantages of miniaturization, low power consumption and reliable data storage, which is very effective in solving the problems of large data capacity and high integration density. Meanwhile, the FG memory with charge storage principle can simulate synaptic plasticity perfectly, breaking the traditional von Neumann computing architecture and can be used as an artificial synapse for neuromorphic computations inspired by the human brain. Among many candidate materials for manufacturing devices, van der Waals (vdW) materials have attracted widespread attention due to their atomic thickness, high mobility, and sustainable miniaturization properties. Owing to the arbitrary stacking ability, vdW heterostructure combines rich physics and potential 3D integration, opening up various possibilities for new functional integrated devices with low power consumption and flexible applications. This paper provides a comprehensive review of memory devices based on vdW materials with FG structure, including the working principles and typical structures of FG structure devices, with a focus on the introduction of various high-performance FG memories and their versatile applications in neuromorphic computing. Finally, the challenges of neuromorphic devices based on FG structures are also discussed. This review will shed light on the design and fabrication of vdW material-based memory devices with FG engineering, helping to promote the development of practical and promising neuromorphic computing.

In this work, a novel bamboo-like carbon nanotubes@Sn4P3@carbon (BLCNTs@Sn4P3@C) coaxial nanotubes are designed and prepared using a newly developed hydrothermal method followed by a phophidation process. The prepared Sn4P3 nanoparticles are uniformly coated and wrapped on the one-dimensional (1D) bamboo-like CNTs, which is covered by a uniform carbon layer to form a sandwich-like structure with Sn4P3 in between. The inner CNT and outer carbon can effectively maintain the structural stability and serve as the good electron conductors. Additionally, the outer carbon coating layer can effectively keep BLCNTs@Sn4P3@C nanotubes separate each other, preventing aggregation of Sn4P3 during charge/discharge when this material is used as anode for sodium ion batteries. The anode of BLCNTs@Sn4P3@C shows excellent reversible capacity and a long cycling of over 2000 cycles. The unique design of coaxial nanotubes is greatly beneficial to the electrochemical performance of Sn4P3 for sodium ion storage.

Objective: Comparative analysis of the results of the four national oral health epidemiological investigations conducted in 1983, 1995, 2005 and 2015 respectively, to understand the changes in the oral health status of the Chinese people with economic development, and provide a scientific basis for the country to formulate effective oral health defense measures. Methods: Collect the data of four large-scale oral health epidemiological investigations conducted in the past 40 years, make a retrospective summary and comparative analysis of the list below to understand the changes in Chinese oral health-related indicators such as dental caries and analyze the reason. Results: Since 1995, the preventive counseling rate was increased. Since 1983, the incidence of caries has decreased, but it has increased in children aged 5 and 12 in the last ten years. Four investigations have examined gingivitis and the situation has not improved significantly. Tooth loss was mainly concentrated in the old group, the repair rate of denture was significantly increased. There are significant differences between the gender and urban and rural distribution of oral health. Conclusions: There is an imbalance in the degree of oral health knowledge of Chinese people, and the incidence of caries and periodontal diseases is still relatively high. It is necessary to strengthen hygiene guidance for different age groups, focusing on prevention and combining prevention and treatment to jointly promote oral health.

ObjectiveTo investigate whether serum LH levels on hCG trigger day are associated with live birth rate (LBR) after fresh embryo transfer with GnRH antagonist regimen in different populations.MethodsThis study was a retrospective study. A total of 3059 fresh embryo transfers were divided into three populations: predicted normal ovarian responders (NOR) (n=2049), patients with PCOS (n=533), and predicted poor ovarian responders (POR) (n=477). Each population was stratified into three groups based on LH levels: < 25th percentile, 25–75th percentile, and > 75th percentile. The primary outcome of the study was LBR, and secondary outcomes included implantation, clinical pregnancy, and early pregnancy loss rates. Univariable and multivariable regression analyses were performed to adjust for potential confounders.ResultsIn NOR, compared to the reference group (>75th percentile), LBR was significantly lower in the < 25th percentile group (adjusted OR=0.662; 95%CI, 0.508-0.863) and 25-75th percentile group (adjusted OR=0.791; 95%CI, 0.633-0.988). In PCOS patients, LBR decreased significantly in the < 25th percentile group (41.4%) compared to the 25-75th percentile group (53.7%) and > 75th percentile group (56.1%). In addition, the LBR was lower in the < 25th percentile group (33.6%) compared with the 25-75th percentile group (43.4%) and the>75th percentile group (42.0%) in POR, but this was not statistically significant.ConclusionsHigh serum LH levels are associated with increased LBR after fresh embryo transfer in GnRH antagonist cycles, which may be attributable to higher implantation rate. LH may be a predictor of whether to schedule fresh embryo transfer in IVF cycles for better clinical outcomes.

Recurrent neural networks (RNNs) have proven to be indispensable for processing sequential and temporal data, with extensive applications in language modeling, text generation, machine translation, and time-series forecasting. Despite their versatility, RNNs are frequently beset by significant training expenses and slow convergence times, which impinge upon their deployment in edge AI applications. Reservoir computing (RC), a specialized RNN variant, is attracting increased attention as a cost-effective alternative for processing temporal and sequential data at the edge. RC’s distinctive advantage stems from its compatibility with emerging memristive hardware, which leverages the energy efficiency and reduced footprint of analog in-memory and in-sensor computing, offering a streamlined and energy-efficient solution. This review offers a comprehensive explanation of RC’s underlying principles, fabrication processes, and surveys recent progress in nano-memristive device based RC systems from the viewpoints of in-memory and in-sensor RC function. It covers a spectrum of memristive device, from established oxide-based memristive device to cutting-edge material science developments, providing readers with a lucid understanding of RC’s hardware implementation and fostering innovative designs for in-sensor RC systems. Lastly, we identify prevailing challenges and suggest viable solutions, paving the way for future advancements in in-sensor RC technology.

Purpose: Uterine fibroids occur in 40%–60% of women and are symptomatic in 30% of the patients by causing abnormal uterine bleeding, pelvic pressure, pain, and infertility. The study aims to evaluate the long-term trend of uterine fibroids mortality and disability-adjusted life years (DALYs) in China and the relative risks of age, period, and birth cohort effects.Methods: The mortality and DALYs of uterine fibroids from 1990 to 2019 were derived from the Global Burden of Disease 2019. The annual percentage change and average annual percent change (AAPC) were assessed using the Joinpoint regression. The effects of age, period, and birth cohort on death and DALYs were analyzed by the Age–Period–Cohort framework.Results: The age-standardized rates were all on the ascending trend, with the greatest increase in the age-standardized mortality rate (AAPC, 1.53; 95% CI, 1.04–2.02). The net drift was found to be 3.51% (95% CI, 2.25%–4.78%) per year for mortality and 0.34% (95% CI, 0.14%–0.53%) per year for DALYs. Significant age, period, and birth cohort effects were found for mortality and DALYs (p < 0.001 for all). The mortality risk increased overall with age, but the DALYs risk increased first and then decreased with age. The period and birth cohort risks for mortality and DALYs showed different trends.Conclusion: These secular time trends and changes of mortality and DALYs reveal the socioeconomic alterations, reform of diagnosis and therapy, and changes in social lifestyles and behaviors. Uterine fibroids are still the most common benign gynecological tumors in women, and more epidemiological investigations and social health prevention and control should be applied.

Death from acute hemorrhage is a major life-threatening. Spacer fabrics-based composite dressings have been widely concerned because of their good hemostasis and protection in wound healing, but the poor liquid absorption and compression recovery properties hinder their utilization. Herein, we report a soluble hemostatic spacer dressing based on a braided yarn of PTFE (core yarn)/carboxymethylated viscose (shell yarn) as the skin contact layer, a wrapped yarn of nylon monofilament (core yarn)/Coolmax (shell yarn) as the spacer layer, and UHMWPE yarn as the waterproof layer for wound healing. Among these, carboxymethylated viscose can stop bleeding, while PTFE has low adhesion and ensures the structural integrity of the spacer fabric. Moreover, the nylon monofilament can endow the dressing with excellent comfortability, resilience, and fatigue resistance. Coolmax can absorb blood. The as-prepared spacer dressing shows excellent mechanical, comfortable, and hemostasis properties. F2 had a hemostasis time of 5.15 min, a low coagulation index of 7.96%, a hemolysis rate of 0.98%, and a blood absorption rate of 159.09%. This work presents an integrated molding method to achieve large-scale manufacturing of spacer dressing, which is expected to guide materials design for future innovations in biomedical applications.

Abstract GSDMD is the key effector of pyroptosis, but its non-pyroptosis-related functions have seldom been reported. Here, we report that GSDMD is overexpressed in different types of tumours, including head and neck squamous-cell carcinoma, and it promotes the sensitivity of tumour cells to cisplatin. Unexpectedly, the enhanced cisplatin sensitivity is mediated by apoptosis but not pyroptosis, the well-known function of GSDMD. Furthermore, we found that GSDMD can activate the unfolded protein response by promoting the phosphorylation of eIF2α. Mechanistically, we demonstrated that GSDMD can directly bind to eIF2α and enhance the interaction between eIF2α and its upstream kinase PERK, leading to eIF2α phosphorylation. Consequently, the protein levels of ATF-4 were upregulated, downstream apoptosis-related proteins such as CHOP were activated, and apoptosis was induced. Remarkably, activation of endoplasmic-reticulum (ER) stress induced by GSDMD promotes cell apoptosis during cisplatin chemotherapy, thereby increasing the treatment sensitivity of tumours. Therefore, for the first time, our work reveals an unreported nonpyroptotic function of the classic pyroptosis protein GSDMD: it promotes cell apoptosis during cisplatin chemotherapy by inducing eIF2α phosphorylation and ER stress, which are related to the drug sensitivity of tumours. Our study also indicated that GSDMD might serve as a biomarker for cisplatin sensitivity.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a serious interstitial lung disease with a complex pathogenesis and high mortality. The development of new drugs is time-consuming and laborious; therefore, research on the new use of old drugs can save time and clinical costs and even avoid serious side effects. Nifuroxazide (NIF) was originally used to treat diarrhoea, but more recently, it has been found to have additional pharmacological effects, such as anti-tumour effects and inhibition of inflammatory diseases related to diabetic nephropathy. However, there are no reports regarding its role in pulmonary fibrosis. Methods The therapeutic effect of NIF on pulmonary fibrosis in vivo was measured by ELISA, hydroxyproline content, H&E and Masson staining, immunohistochemistry (IHC) and western blot. Immune cell content in lung tissue was also analysed by flow cytometry. NIF cytotoxicity was evaluated in NIH/3T3 cells, human pulmonary fibroblasts (HPFs), A549 cells and rat primary lung fibroblasts (RPLFs) using the MTT assay. Finally, an in vitro cell model created by transforming growth factor-β1 (TGF-β1) stimulation was assessed using different experiments (immunofluorescence, western blot and wound migration assay) to evaluate the effects of NIF on the activation of NIH/3T3 and HPF cells and the epithelial-mesenchymal transition (EMT) and migration of A549 cells. Results In vivo, intraperitoneal injection of NIF relieved and reversed pulmonary fibrosis caused by bleomycin (BLM) bronchial instillation. In addition, NIF inhibited the expression of a variety of cellular inflammatory factors and immune cells. Furthermore, NIF suppressed the activation of fibroblasts and EMT of epithelial cells induced by TGF-β1. Most importantly, we used an analytical docking experiment and thermal shift assay to further verify that NIF functions in conjunction with signal transducer and activator of transcription 3 (Stat3). Moreover, NIF inhibited the TGF-β/Smad pathway in vitro and decreased the expression of phosphorylated Stat3 in vitro and in vivo. Conclusion Taken together, we conclude that NIF inhibits and reverses pulmonary fibrosis, and these results support NIF as a viable therapeutic option for IPF treatment. Graphic Abstract

Identify risk drivers is the key condition in air pollution control, and biological effect-directed analysis is the most commented method for combing chemical identify and human health. The water-soluble organic matter contained in PM2.5 plays an important role in human health, while it is also the most difficult to identify its chemical information. Exploring the structural characteristics and pollution sources of its key toxic components is the optimized strategy to meet this question. In this study, the induction of apoptosis by the water-soluble fractions (WSF) of PM2.5 samples collected in 10 major cities in China over a period of 1 year was observed in vitro in Beas-2b cells. Organic carbon structures were examined using nuclear magnetic resonance; air potential sources were identified using δ13C and 14C isotopic markers. Apoptosis induction by WSF in PM2.5 was generally stronger in northern cities than in southern cities, and in winter than in summer. Organic compounds with aromatic and double-bond carbon structures from secondary products of motor vehicle exhausts, coal-derived emissions, and emissions derived from the burning of core residues may be primarily responsible for apoptosis induction by PM2.5. Our results will contribute to understanding the toxic substances contained in WSF and provide basic data for accurate pollution control.

This study reveals the fluid-structure interaction simulation of the ballistic impact of shear thickening fluid (STF) impregnated with ultra-high molecular weight polyethylene (UHMWPE) fiber composites. The STF/UHMWPE composites pull-out test results are fitted to obtain a similar STF rheological curve. The STF/UHMWPE composites fluid-structure interaction (FSI) model was established to reproduce the local failure and stress distribution at each stage of the ballistic impact process. The comparison of the finite element analysis (FEA) and the experimental results showed that the fitting degree of the STF/UHMWPE composites to the impact energy absorption was 94.74%. STF treatment has dual effects on the impact resistance of fabrics, increasing the friction and enhancing the thickening effect.

Heart failure (HF) is the end stage of various cardiovascular diseases, with high morbidity and mortality, and is associated with a poor prognosis. One of the primary causes of HF is aortic valve disease, manifested by progressive aortic valve stenosis (AVS), resulting in increased left ventricular load, ventricular hypertrophy, ultimately ventricular dysfunction, and HF. Early assessment of the degree of cardiomyopathy and timely intervention is expected to improve patients’ cardiac function and delay or even avoid the occurrence of HF. The Wnt signaling pathway is mainly involved in regulating myocardial insufficiency after valve stenosis. Connexin 43 protein (Cx43) is an essential target of Wnt signaling pathway that forms gap junction (GJ) structures and is widely distributed in various organs and tissues, especially in the heart. The distribution and transformation of Cx43 among cardiac cells are crucial for the development of HF. To specifically label Cx43 in vivo, we established a new Cx43-BFP-GFP mouse model with two loxp sites on both sides of the tag BFP-polyA box, which can be removed by Cre recombination. This double-reporter line endowed us with a powerful genetic tool for determining the area, spatial distribution, and functional status of Cx43. It also indicated changes in electrical conduction between cells in a steady or diseased state.

Perceived trust is a key factor affecting the behavior to donate online. In order to further explore the factors and influencing mechanisms that affect the success of medical crowdfunding projects, this paper, combined with the Stimulus-Organism-Response (S-O-R) theory, introduces the mediating variable of social presence and perceived differences in trust, and constructs a model of online users’ donation behavior to medical crowdfunding projects. We collected 437 valid samples through a questionnaire survey, and processed the data with SPSS and Amos software to test and analyze the theoretical model. The research results showed that project description and user participation have a significant positive effect on social presence; project transparency and patient identity have a significant negative effect on perceived differences in trust; social presence has a positive effect on donation behavior, while the perceived difference in trust has a negative effect; social presence and perceived differences in trust play a mediating role respectively; there is no significant effect of patient status on social presence. This study further expands the application of social presence and perceived differences in trust in medical crowdfunding, and provides a theoretical basis for the success of medical crowdfunding projects.

A thermoset polyamide resins were synthesized by citric acid and hexanediamine (CH), and was modified by oxidized glucose (OG). The effect of oxidation time and addition amount of oxidized glucose on shearing strength of plywood were characterized. Fourier transform-infrared (FT-IR) and liquid chromatography-mass spectrometry (LCMS) were used to determine the structures of the resins, the result shows that CH and OG reacted to form macromolecules. Differential Scanning Calorimeter (DSC), dynamic mechanical properties (DMA) were used to analyze its thermal properties, the results indicate that OG improved the storage module and the heat resistance. The CHOG resin exhibited a good bonding strength and water resistance, when the oxidation time is 0 min and the molar ratio of oxidized glucose to hexamethylene diamine is 1:1.6. Dry strength, 24 h wet strength and 63 °C hot water soaking wet strength of the plywood bonded with it are 1.36 MPa, 1.60 MPa, 1.49 MPa, respectively. Therefore, OG enhanced the shearing properties, and improve water resistance, which sheds new light on the preparation of bio-based wood adhesive for the manufacture of plywood.

Body cavity macrophages reside on the serous surfaces of organs and believed to participate in organ repair following injury. Here the authors show with a fate-mapping reporter system that these cells, although accumulate at the surfaces of injured liver or lung, don’t penetrate deeply into the tissue.

Abstract Problem Does aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells? Method of study A lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis. Results Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown. Conclusions AQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.

Radiological therapy/examination is the primary source of artificial radiation exposure in humans. While its application has contributed to major advances in disease diagnosis and treatment, ionizing radiation exposure is associated with ovarian damage. The use of natural products, either alone or as an adjunct, has become increasingly common for reducing the side effects of radiological therapy during disease treatment. Herein, we explored the protective effect of folic acid (FA), a widely used B vitamin, against radiation-induced ovarian injury and its mechanism of action. Female mice with normal ovarian function were randomly divided into control, FA, radiation, and radiation + FA groups. The intervention strategy included daily intragastric administration of FA (5 mg/kg) for 3 weeks prior to radiation exposure. Mice in the radiation and radiation + FA groups received a single dose of 5 Gy X-ray irradiation. Changes in the estrous cycle were then recorded, and ovarian tissues were collected. Pathophysiological changes as well as reproductive and endocrine-related indexes were determined via H&E staining, immunohistochemistry, Western blot, and ELISA. The reproductive performance and emotional symptoms of animals were also monitored. Our results indicated that FA intervention effectively alleviated ovarian damage, leading to more regular estrous cycles, lesser impairment of follicular morphology and endocrine status, as well as greater germ cell preservation. Reduced levels of oxidative stress, inflammation, and enhanced DNA repair were associated these changes. FA pre-administration improved the reproductive performance, leading to higher pregnancy rates and greater litter sizes. Further, the anxiety levels of animals were significantly reduced. Our results indicate that FA pre-administration significantly alleviates radiation-induced ovarian damage in rodents, highlighting its potential as a protective strategy against radiation exposure in the female population.

Saltmarshes can sequester atmospheric CO2 in sediments, but limited studies have quantified porewater-derived carbon exports and identified related carbon sources. Here, we estimated porewater exchange, carbon outwelling, and greenhouse gas emissions in a subtropical multi-species saltmarsh. The radon-based porewater exchange rate was estimated to be 5.60 ± 2.78 cm d-1. As the most dominant (~90%) carbon species, dissolved inorganic carbon (DIC) fluxes through porewater exchange and outwelling were 447 ± 227 and 1200 ± 61 mmol m-2 d-1, respectively, which were 1.2 and 3.2 times that of carbon burial. As most DIC can remain in the ocean for a long time, porewater-derived DIC outwelling represents another important carbon sink, in addition to carbon burial. CO2 and CH4 emissions from creek water were 54.6 ± 0.5 and 0.19 ± 0.01 mmol m-2 d-1, respectively, which could offset 16% of carbon burial. The δ13C and C/N ratios suggest that saltmarsh organic carbon mainly originates from the C3 plant Scirpus mariqueter rather than the C4 plant Spartina alterniflora. Overall, we suggest that porewater-derived DIC outwelling is an important long-term carbon sink in multi-species saltmarshes, providing a scientific basis for the protection and restoration of saltmarshes in the context of global climate change.

Abstract As the core technology in the field of aircraft, the route planning has attracted much attention. However, due to the complexity of the structure and performance constraints of the aircraft, the route planning algorithm does not have well universality, so it cannot be used in a complex environment. In the paper, a multi-constraints and dual-targets aircraft route planning model was established for the real-time requirements of space flight, the dynamic changes of flight environment with time, the accuracy requirements of positioning errors in the safety area, and the minimum turning radius constraints. Based on the directed graph and dynamic programming ideas, the model simulation and model validation were carried out with the data of F question in the “16th Graduate Mathematical Modeling Contest”. The results showed that the optimal path length obtained in data set 1 was 124.61 km, the number of corrections was 11 times, the solution time was 2.3768 seconds, the optimal path length obtained in data set 2 was 110.00 km, and the number of corrections was 12 times. The solution time was 0.0168 seconds. Multi-constraints and dual-targets aircraft route planning model can plan the flight path of the aircraft intuitively and timely, which confirmed the effectiveness of the model.

Abstract Aiming at the positioning error of the aircraft, the error accumulation to a certain extent may lead to the failure of the mission. A track correction method based on oriented graph search was proposed, and the dynamic programming idea was applied to solve the path optimization problem. Firstly, the correction points in the flight space were preprocessed, and the planning of the correction points in the flight space was transformed into a graph theory problem. It effectively solves the problem that traditional methods did not adapt well to dynamic changes in flight space. And the problem of too high complexity in the calculation space. Using the dynamic programming idea to carry out the flight path planning for the flight space, the path-correction number optimal double-objective model is comprehensively established. Finally, the oriented graph and dynamic programming ideas were used to solve the problem, and the visual analysis of the aircraft track was realized. The simulation results show that the established path-corrected optimal double-objective model can calculate an optimal track with relatively small correction times and short length.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and chronic lung disease, lacking a validated and effective therapy. Blueberry has demonstrated multiple pharmacological activities including anti-inflammatory, antioxidant, and anticancer. Therefore, the objective of this study was to investigate whether blueberry juice (BBJ) could ameliorate IPF. Experiments in vitro revealed that BBJ could significantly reduce the expressions of TGF-β1 modulated fibrotic protein, which were involved in the cascade of fibrosis in NIH/3T3 cells and human pulmonary fibroblasts. In addition, for rat primary lung fibroblasts (RPLFs), BBJ promoted the cell apoptosis along with reducing the expressions of α-SMA, vimentin, and collagen I, while increasing the E-cadherin level. Furthermore, BBJ could reverse epithelial–mesenchymal transition (EMT) phenotypic changes and inhibit cell migration, along with inducing the upregulation of E-cadherin in A549 cells. Compared with the vehicle group, BBJ treatment alleviated fibrotic pathological changes and collagen deposition in both bleomycin-induced prevention and treatment pulmonary fibrosis models. In fibrotic lung tissues, BBJ remarkably suppressed the expressions of collagen I, α-SMA, and vimentin and improved E-cadherin, which may be related to its inhibition of the TGF-β1/Smad pathway and anti-inflammation efficacy. Taken together, these findings comprehensively proved that BBJ could effectively prevent and attenuate idiopathic pulmonary fibrosis via suppressing EMT and the TGF-β1/Smad signaling pathway.

Gestational folic acid (FA) supplementation has been widely recognized for its benefits in preventing offspring defects, but its effect on postpartum females has not yet been adequately assessed. The occurrence of emotional and cognitive dysfunction is common in postpartum women, and its treatment remains limited. Considering the promising results of FA in various psychiatric disorders both in human and redents, we tested the effect of gestational FA administration on postpartum psychiatric behavioral phenotypes and the implicated brain-related mechanisms in a murine model. FA was administered orally in both the hormone-stimulated-pregnancy (HSP) model and pregnant mice at doses of 1 and 5 mg/kg. Postpartum behavioral results showed that the disorders of cognitive performance, depressive, and anxiety-related behaviors were all alleviated in the 5 mg/kg FA group. However, the general development of their offspring remained unaffected. Immunofluorescence and immunoblot results revealed that FA pretreatment significantly activated the maternal hippocampal BDNF-related pathway. Morphological studies have confirmed that FA promotes hippocampal neurogenesis. Moreover, synaptic plasticity and synaptic transmission are enhanced. All of these hippocampal changes play critical roles in rescuing neuronal function and behaviors. Thus, our data suggest that gestational FA administration has a therapeutic effect that improves cognition and reduces depression and anxiety in a murine postpartum model. This may be developed as a preventive and adjuvant therapeutic option for pregnant women.

Abstract Silicone (Si) is one type of anode materials with intriguingly high theoretical capacity. However, the severe volume change associated with the repeated lithiation and delithiation processes hampers the mechanical/electrical integrity of Si anodes and hence reduces the battery's cycle‐life. To address this issue, sequence‐defined peptoids are designed and fabricated with two tailored functional groups, “OH” and “COOH”, as cross‐linkable polymeric binders for Si anodes of LIBs. Experimental results show that both the capacity and stability of such peptoids‐bound Si anodes can be significantly improved due to the decreased cracks of Si nanoparticles. Particularly, the 15‐mer peptoid binder in Si anode can result in a much higher reversible capacity (ca. 3110 mAh g−1) after 500 cycles at 1.0 A g−1 compared to other reported binders in literature. According to the density functional theory (DFT) calculations, it is the functional groups presented on the side chains of peptoids that facilitate the formation of Si−O binding efficiency and robustness, and then maintain the integrity of the Si anode. The sequence‐designed polymers can act as a new platform for understanding the interactions between binders and Si anode materials, and promote the realization of high‐performance batteries.

Evaporation ( E ) from about 300 million lakes worldwide without plant physiological constraints directly reflects hydrological response to atmospheric forcings. However, it remains inadequately understood about what regulate spatial variability of global lake E across seasons. Here we show that vertical vapor pressure difference ( ${e_{\text{D}}}$ ) accounts for 66% of the spatial variability of annual E , followed by wind speed (16%). The ${e_{\text{D}}}$ is also the predominant factor modulating diurnal variability in E and causing greater E at night than during the daytime. As a consequence, spatial variability in nighttime E strongly regulates that in global E across seasons. Therefore, the observed widespread, heterogeneous changes in lake surface temperature that imply spatial variability in ${e_{\text{D}}}$ may have contributed to changes in global E variability.

Background: Breast cancer is the most common female cancer with considerable metastatic potential, which urges the need for developing novel potential drug candidate to inhibit tumor metastasis. Signal transducer and activator of transcription 3 (Stat3) have critical roles in cancer growth and metastasis and have been confirmed as a promising anticancer target. Here, we report our finding with pectolinarigenin, a flavonoid compound isolated from the aerial parts of Cirsium chanroenicum.Methods: The role of Pec. in cell proliferation, cell apoptosis, and cell migration and invasion in three breast cancer cells (4T1, MDA-MB-231, MCF-7) was investigated. Cell proliferation was determined by MTT assay, cell apoptosis was determined by flow cytometry, and protein expression was detected by western blotting. Tumor xenograft mice model and breast tumor metastasis model in vivo were built to further assess the effects of Pec. on 4T1 cells.Results: Intraperitoneal administrations of pectolinarigenin significantly inhibited breast cancer metastasis to lungs without affecting the tumor growth of incubated 4T1 breast cancer cells. Pectolinarigenin could also recruit CD8+ T cells to mediate tumor immune response. Furthermore, pectolinarigenin markedly impaired cancer cell migration and invasion by down-regulating phosphorylated-Stat3, and expression of matrix metalloproteinase (MMP)-2, MMP-9, while up-regulating the expression of TIMP2. We also found that pectolinarigenin inhibited breast cancer cell proliferation and induced apoptosis via mitochondrial-related apoptosis pathway, reduced mitochondrial membrane potential and the expression of Bcl-2, increased expression of Bax, and cleaved caspase-3 as well as disturbed the ROS generation.Conclusions: Pectolinarigenin might potentially be a candidate for metastasis of breast cancer by mediating Stat3 pathway.

With the rapid development of intelligent transportation, there comes huge demands for high-precision road network maps. However, due to the complex road spectral performance, it is very challenging to extract road networks with complete topologies. Based on the topological networks produced by previous road extraction methods, in this paper, we propose a Multi-conditional Generative Adversarial Network (McGAN) to obtain complete road networks by refining the imperfect road topology. The proposed McGAN, which is composed of two discriminators and a generator, takes both original remote sensing image and the initial road network produced by existing road extraction methods as input. The first discriminator employs the original spectral information to instruct the reconstruction, and the other discriminator aims to refine the road network topology. Such a structure makes the generator capable of receiving both spectral and topological information of the road region, thus producing more complete road networks compared with the initial road network. Three different datasets were used to compare McGan with several recent approaches, which showed that the proposed method significantly improved the precision and recall of the road networks, and also worked well for those road regions where previous methods could hardly obtain complete structures.

A flow biosensor for the detection of toxicity in water using the ammonia-oxidizing bacterium (AOB) Nitrosomonas europaea as a bioreceptor and a polymeric membrane ammonium-selective electrode as a transducer is described. The system is based on the inhibition effects of toxicants on the activity of AOB, which can be evaluated by measuring the ammonium consumption rates with the ammonium-selective membrane electrode. The AOB cells are immobilized on polyethersulfone membranes packed in a holder, while the membrane electrode is placed downstream in the flow cell. Two specific inhibitors of the ammonia oxidation‒allylthiourea and thioacetamide‒have been tested. The IC50 values defined as the concentration of an inhibitor causing a 50% reduction in the ammonia oxidation activity have been measured as 0.17 μM and 0.46 μM for allylthiourea and thioacetamide, respectively. The proposed sensor offers advantages of simplicity, speed and high sensitivity for measuring toxicity in water.

Rough random theory, generally applied to statistics, decision-making, and so on, is an extension of rough set theory and probability theory, in which a rough random variable is described as a random variable taking “rough variable” values. In order to extend and enrich the research area of rough random theory, in this paper, the well-known probabilistic inequalities (Markov inequality, Chebyshev inequality, Holder’s inequality, Minkowski inequality and Jensen’s inequality) are proven for rough random variables, which gives a firm theoretical support to the further development of rough random theory. Besides, considering that the critical values always act as a vital tool in engineering, science and other application fields, some significant properties of the critical values of rough random variables involving the continuity and the monotonicity are investigated deeply to provide a novel analytical approach for dealing with the rough random optimization problems.

CO _2 emissions from inland waters are commonly determined by indirect methods that are based on the product of a gas transfer coefficient and the concentration gradient at the air water interface (e.g., wind-based gas transfer models). The measurements of concentration gradient are typically collected during the day in fair weather throughout the course of a year. Direct measurements of eddy covariance CO _2 fluxes from a large inland water body (Ross Barnett reservoir, Mississippi, USA) show that CO _2 effluxes at night are approximately 70% greater than those during the day. At longer time scales, frequent synoptic weather events associated with extratropical cyclones induce CO _2 flux pulses, resulting in further increase in annual CO _2 effluxes by 16%. Therefore, CO _2 emission rates from this reservoir, if these diel and synoptic processes are under-sampled, are likely to be underestimated by approximately 40%. Our results also indicate that the CO _2 emission rates from global inland waters reported in the literature, when based on indirect methods, are likely underestimated. Field samplings and indirect modeling frameworks that estimate CO _2 emissions should account for both daytime–nighttime efflux difference and enhanced emissions during synoptic weather events. The analysis here can guide carbon emission sampling to improve regional carbon estimates.