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Inland wetlands might be an important "carbon sink", and the chronosequence development of newly formed inland wetlands offers a natural and suitable opportunity for studying the dynamic effect of plant and microbial necromass carbon (PlantC and MNC) on the soil organic carbon (SOC) stabilization. The space-for-time chronosequence approach was used and plots were established in the three ages of newly formed inland wetlands (2, 5, and 16 years). Soil samples were collected in the surface (0-10 cm) and subsurface soil (20-30 cm). Results showed that accumulation of SOC, PlantC, and MNC were significantly larger in the surface than those in the subsurface soil. Moreover, MNC stocks were more abundant than PlantC in the wetland ecosystem both in the surface and subsurface soil. During the chronosequence development, dynamics of SOC and its components accumulation were similar to MNC, both exhibiting an increasing and then decreasing trend in the surface and subsurface soil, except for free particulate organic carbon in the subsurface soil. Structural equation models revealed that changes of MNC affected by environmental variables were the main cause of MAOC dynamics both in the surface and subsurface soil, suggesting that contribution of MNC to MAOC would be the key way of carbon stabilization in the newly formed inland wetlands. Furthermore, MNC accumulation in the surface soil was closely linked to pH, CEC, and soil texture, while in the subsurface soil affected by soil nutrients (TN and NH 4 + -N). Particularly, despite the decreasing SOC stocks in the 16-year wetland, the stability has significantly enhanced due to the increasing persistent individual amino sugars. This study provides new information on the dynamics of SOC accumulation and highlights the significance of MNC on the SOC sequestration in the newly formed inland wetlands, which is important for the understanding of wetland SOC stock dynamics and stabilization mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To explore the association between smoking, genetic susceptibility and early menopause (EM) and clarify the potential mechanisms underlying this relationship., Design: An observational and Transcriptome-wide association analysis (TWAS) study., Setting: UK Biobank and public summary statistics., Population: 139 869 women with full baseline and menopause data, and no gynaecological surgery history., Methods: Adjusted modified Poisson regression models were developed to determine the smoking and genetic risk effects on EM. TWAS was used to identify gene expression between smoking and EM, with Mendelian randomisation (MR) to infer causality. Enrichment analysis explored regulatory networks of transcription factors, microRNAs and potential therapeutic targets. Small molecule drugs were predicted using drug-gene interaction analysis., Main Outcome Measures: EM prevalence and common gene expression patterns., Results: Women with over 30 pack-years of smoking had about 1.5 times higher EM risk, with RRs of 1.39 (95%CI, 1.23-1.56), 1.45 (1.33-1.59) and 1.45 (1.36-1.55) in the low, intermediate and high genetic risk groups. TWAS identified hub genes such as IMMP2L, BMPR2 and HMGN1. MR confirmed daily cigarette consumption as a causal factor in early menopause. Several potential therapeutic targets (e.g., SP600125, INCB18424 and ruxolitinib) were identified., Conclusions: Smoking reduction significantly lowered the risk of EM. Hub genes and therapeutic targets identified provided new avenues for mitigating harmful effects of smoking., (© 2024 John Wiley & Sons Ltd.)

Exosomes have emerged as significant biomarkers for multiple diseases, including cancers. Circular RNAs (circRNAs), abundant in exosomes, are involved in regulating cancer development. However, the regulatory function and the underlying molecular mechanism of hsa_circ_0006906 (circSCP2) in colorectal cancer (CRC) metastasis remain unclear. A competing endogenous RNA microarray was used to analyze circRNA expression in serum exosomes in patients with CRC at early and late stages. circSCP2 expression was evaluated using qRT-PCR. The biological functions of circSCP2 in CRC were assessed through in vitro and in vivo experiments. The molecular mechanism of circSCP2 was explored using western blotting, RNA pulldown, RNA immunoprecipitation, luciferase assays, and relative rescue experiments. circSCP2 expression was significantly elevated in CRC tissues, with higher levels in serum exosomes correlating with advanced TNM stages. circSCP2 knockdown inhibited CRC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Mechanistically, circSCP2 sponged miR-92a-1-5p to increase insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) expression. Additionally, circSCP2 directly bound to and stabilized polypyrimidine tract binding protein 1 (PTBP1) by inhibiting protein ubiquitination, resulting in IGF2BP1 mRNA stabilization and enhanced CRC migration and invasion. Our findings demonstrate that circSCP2 regulates the miR-92a-1-5p/IGF2BP1 pathway, promotes PTBP1/IGF2BP1 interaction, and accelerates CRC progression. Exosomal circSCP2 is a promising circulating biomarker for CRC prognosis and needs further therapeutic investigation., Competing Interests: Declarations. Ethics approval and consent to participate: The animal study was approved and performed in compliance with the guidance suggestion of Animal Care Committee of Sir Run Run Shaw Hospital and carried out under the guidelines of the Guide for the Care and Use of Laboratory Animals of the China National Institutes of Health. The collection of clinical specimens was approved by the Ethics Committee of Sir Run Shaw Hospital after informed consent was obtained from each patient. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aim: Infection caused by Aspergillus species poses a growing global concern, yet their prevalence in Southeast China lacks comprehensive documentation. This retrospective analysis aims to elucidate the epidemiological role and antifungal susceptibilities of Aspergillus species at Huashan Hospital of Fudan University, Shanghai, China., Methods: Data spanning from 2018 to 2022, encompassing demographic, clinical, and laboratory information on Aspergillus species isolates were analyzed. The isolates were subjected to susceptibility testing using YeastOne TM broth microdilution system., Results: A total of 253 Aspergillus isolates were identified, with A. fumigatus (57.71%) being the predominant species, followed by A. niger (26.88%), A. flavus (10.67%), and A. terreus (3.95%). Notably, the highest number of isolates originated from the Department of Infectious Disease (28.06%), with sputum (54.94%) being the primary source of isolation, where A. fumigatus was the dominant species. Gastrointestinal disorder (23.90%), hepatic disorder (9.09%), and diabetes (8.30%) were identified as the most prevalent underlying conditions, with A. fumigatus being the most abundant species in each case, accounting for 65.08%, 82.60%, and 73.91%, respectively, followed by A. flavus . Non-wild-type (NWT) Aspergillus isolates exhibited higher resistance against amphotericin B (AMB) compared to triazoles. Specifically, A. fumigatus showed greater resistance to AMB, with only 23.28% of isolates being susceptible, while the majority of isolates were susceptible to triazoles like itraconazole (ITR) and posaconazole (POS). POS demonstrated the highest efficacy against all species. Sequencing revealed mutations in the promoter region of the cyp51A gene and at positions Y121F and E247K in A, fumigatus which confer resistance to ITR, voriconazole (VRC), and POS., Conclusion: These findings contribute to a better understanding of the epidemiology and antifungal resistance pattern of Aspergillus species in the region, providing valuable insights for the management of Aspergillus -related infections., Competing Interests: The authors declare no conflicts of interest., (© 2024 Hussain et al.)

Despite extensive global attention on microplastic pollution, our understanding of the pathways underlying microplastic translocation, accumulation, and their potential impacts on ecosystems and human health through the food chain remains incomplete. To investigate the translocation and accumulation of microplastics from insects to mammals, we developed a novel oral exposure model that Tenebrio molitor larvae (yellow mealworms, invertebrate terrestrial insects) were firstly orally exposed to both micro and nanometer-sized plastics (M/NPs), and subsequently fed as a food source to mice (mammals). Our results provide clear evidence that micro/nanoplastics (M/NPs) do indeed translocate through the food chain, from lower to higher trophic levels. Fluorescence microscopy and tissue quantification revealed the accumulation of M/NPs in the digestive, somatic, and circulatory systems of the larvae. Specifically, the food chain transferred M/NPs were later detected in the digestive, respiratory, and urinary systems of mice, showcasing strong fluorescent signals in vital organs such as the lungs, liver, intestines, brain, and kidneys, as well as in embryos. These findings highlight the intricate dynamics of M/NPs contamination, emphasizing their ability to traverse biological barriers, accumulate in organisms, and potentially impact embryonic development via food chain transfer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study estimated the effect of changing trends in drug- and firearm-related mortality on life expectancy in the U.S. over the last two decades., Study Design: Retrospective cross-sectional study., Methods: We used national vital registration data from CDC WONDER, stratified by sex, to estimate the mortality rate due to accidental and intentional poisoning (ICD Codes X40-X49, X60-X69, Y10-Y19 and X85), and firearm deaths (ICD codes W32-W34, X72-X74, X93-X95, Y22-Y24) for the period 2000-2020. We applied standard life table methods to all cause mortality rates with and without these mortality causes to estimate the life expectancy at each age over this period., Results: In 2020, mortality due to drugs and firearms combined reduced male life expectancy by1.67 years compared to 0.67 years in 2000, and without the effect of these two causes of death, male life expectancy in 2019 would have been 78.02 years. For women, drugs and firearm-related mortality reduced life expectancy by 0.20 years in 2000 and 0.63 years in 2020, and female life expectancy would have been 82.25 years in 2019 without the retarding effect of these two preventable causes., Conclusions: Drug- and firearm-related deaths have increased so rapidly, especially among younger populations, that life expectancy at birth is significantly reduced by these causes of death. Without urgent action to tackle these preventable causes of death, US life expectancy will continue to stagnate and may even decline, even without the effect of COVID-19., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Postpartum haemorrhage (PPH) is a serious complication of pregnancy. In this study, patients with PPH were treated with blood component transfusion, and the effectiveness of blood component transfusion and its influence on coagulation function were analysed. This retrospective randomised controlled study evaluated the clinical data of patients with PPH who were admitted to the Department of Blood Transfusion at the First Affiliated Hospital of Xiamen University, from January 2021 to December 2021. In 2021, 84 patients received treatment at this hospital. Patients transfused with a 1:1 ratio of red blood cells (RBC) to cryoprecipitate showed a significant improvement in coagulation levels compared to pretreatment. The combination of RBC, plasma, and cryoprecipitate in a reasonable proportion effectively improves coagulation function in haemorrhage puerperae, showing a good clinical treatment effect. It is worth promoting. Key Words: Postpartum, Blood component transfusion, Coagulation, Resuscitation rate.

With the rapid development of energy vehicles, the demand for high-safety and high-energy-density battery systems, such as solid-state lithium metal batteries, is becoming increasingly urgent. Polyethylene oxide (PEO), as a commonly used electrolyte in solid-state batteries, has the advantages of easy processing and good interface compatibility but also faces the issue of poor ionic conductivity. In this study, we have enhanced the mechanical properties and ion conductivity of PEO electrolytes significantly, stabilizing electrochemical cycling, utilizing positively charged MXene as a modifying material for PEO solid electrolytes and leveraging stronger electrostatic forces. With these enhanced properties, the modified solid electrolyte in Li/Li cells demonstrates excellent cycling stability of over 430 h at 0.1 mA cm -2 . Furthermore, the Li/LiFePO 4 cells show excellent cycling performance, and the capacity retention rate is 92.1%.

Macrophages are fundamental cellular components of atherosclerotic plaques, and inhibition of macrophage inflammation can delay the development of atherosclerotic plaques. Sodium danshensu (SDSS) can inhibit inflammatory responses and thus delay atherosclerosis, but the specific mechanism remains unclear. The effect of SDSS in inhibiting atherosclerosis was confirmed by observing and detecting atherosclerotic plaque area, morphology and lipid levels in the aorta. The mechanism by which SDSS attenuated atherosclerotic plaques was elucidated by in vivo and in vitro detection of inflammation-related mRNA and protein expression. In addition, bioinformatics analysis, RT-qPCR and dual-luciferase assays were used to predict and validate the potential miRNAs of SDSS to attenuate atherosclerosis. miR-200a-2p mimic and inhibitor were then compared for their effects on the efficacy of SDSS. SDSS inhibited atherosclerotic plaque formation and suppressed the expression of MEKK3, TNF-α, and IL-1β as well as nuclear factor-κB (NF-κB) phosphorylation and nuclear translocation to attenuate inflammatory responses. Bioinformatic predictions combined with RT-qPCR results and dual-luciferase assays indicated that miR-200a-3p negatively regulated MEKK3 expression by directly targeting the 3'UTR region of MEKK3, thereby blocking MEKK3. Further studies showed that miR-200a-3p inhibitor, but not miR-200a-3p mimic, reversed the beneficial effects of SDSS on inflammation. SDSS inhibited macrophage inflammation by modulating the miR-200a-3p/MEKK3/NF-κB signaling pathway., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Numerous viruses that propagate through the respiratory tract may be initially engulfed by macrophages (M φ s) within the alveoli, where they complete their first replication cycle and subsequently infect the adjacent epithelial cells. This process can lead to significant pathological damage to tissues and organs, leading to various diseases. As essential components in host antiviral immune systems, M φ s can be polarized into pro-inflammatory M1 M φ s or anti-inflammatory M2 M φ s, a process involving multiple signaling pathways and molecular mechanisms that yield diverse phenotypic and functional features in response to various stimuli. In general, when infected by a virus, M1 macrophages secrete pro-inflammatory cytokines to play an antiviral role, while M2 macrophages play an anti-inflammatory role to promote the replication of the virus. However, recent studies have shown that some viruses may exhibit the opposite trend. Viruses have evolved various strategies to disrupt M φ polarization for efficient replication and transmission. Notably, various factors, such as mechanical softness, the altered pH value of the endolysosomal system, and the homeostasis between M1/M2 M φ s populations, contribute to crucial events in the viral replication cycle. Here, we summarize the regulation of M φ polarization, virus-induced alterations in M φ polarization, and the antiviral mechanisms associated with these changes. Collectively, this review provides insights into recent advances regarding M φ polarization in host antiviral immune responses, which will contribute to the development of precise prevention strategies as well as management approaches to disease incidence and transmission.

Background: Antimicrobial resistance and bacterial hypermucoviscosity, associated with escalating production of capsules, constitute major challenges for the clinical management of Klebsiella pneumoniae (K. pneumoniae) infections. This study investigates the association and underlying mechanism between ceftazidime-avibactam (CAZ-AVI) resistance and bacterial hypermucoviscosity in Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp)., Results: The proportion of CAZ-AVI-sensitive clinical isolates exhibiting the hypermucoviscous phenotype was significantly lower than that of the resistant strains (5.6% vs. 46.7%, P < 0.001). To further verify the correlation and molecular mechanism between CAZ-AVI resistance and hypermucoviscosity, 10 CAZ-AVI-resistant isolates were generated through in vitro resistance selection from CAZ-AVI-sensitive KPC-Kp. The results showed the same association as it showed in the clinical isolates, with four out of ten induced CAZ-AVI-resistant isolates transitioning from negative to positive in the string tests. Comparative genomic analysis identified diverse mutations in the wzc gene, crucial for capsule polysaccharide (CPS) synthesis, in all four CAZ-AVI-resistant hypermucoviscous KPC-Kp strains compared to the parent strains. However, these mutations were absent in the other six KPC-Kp strains that did not exhibit induced hypermucoviscosity. Cloning of the wzc gene variants and their expression in wild-type strains confirmed that mutations in the wzc gene can induce bacterial hypermucoviscosity and heightened virulence, however, they do not confer resistance to CAZ-AVI., Conclusions: These results indicated that resistance to CAZ-AVI in KPC-Kp isolates may be accompanied by the acquisition of hypermucoviscosity, with mutations in the wzc gene often involving in this process., (© 2024. The Author(s).)

To investigate the dynamic changes and potential correlations between microbial diversity and volatile organic compounds (VOCs) during Chinese medium-temperature Daqu (MTD) manufacturing at different key stages, in this study, high-throughput sequencing (HTS) and gas chromatography-ion mobility spectrometry (GC-IMS) were employed to analyze the microbial diversity and VOCs of MTD, respectively. The results showed that Weissella , Staphylococcus , Thermoactinomyces , Kroppenstedtia , and Lactobacillus were the dominant bacterial genera, while Aspergillus , Alternaria , Thermoascus , Thermomyces , Wickerhamomyces , and Saccharomyces were the dominant fungal genera. A total of 61 VOCs were detected by GC-IMS, among which, 13 differential VOCs (VIP > 1) were identified, that could be used as potential biomarkers to judge the fermentation stage of MTD. Kroppenstedtia and Saccharopolyspora were positively correlated with 3-methyl-2-butenal and 2,2,4,6,6-pentamethylheptane-D, respectively, and both of these were positively correlated with butanal-D. Acetobacter , Streptomyces , and lactic acid bacteria (LAB) including Leuconostoc , Pediococcus , Weissella , and Lactobacillus were negatively correlated with their associated VOCs, while fungi were generally positively correlated with VOCs. Wickerhamomyces , Saccharomyces , and Candida were positively correlated with butan-2-one-M. This study provides a theoretical basis for explaining the mechanisms of MTD flavor formation and screening functional microorganisms to improve the quality of MTD.

Pyraclostrobin, a typical representative of strobilurin fungicides, is extensively used in agriculture to control fungi and is often detected in water bodies and food. However, the comprehensive toxicological molecular mechanism of pyraclostrobin requires further study. To assess the toxic effects and underlying mechanisms of pyraclostrobin on aquatic organisms, zebrafish embryos were exposed to pyraclostrobin (20, 40, and 60 μg/L) until 96 h post fertilization (hpf). These results indicated that exposure to pyraclostrobin induces morphological alterations, including spinal curvature, shortened body length, and smaller eyes. Furthermore, heart developmental malformations, such as pericardial edema and bradycardia, were observed. This indicated severe cardiotoxicity induced by pyraclostrobin in zebrafish embryos, which was confirmed by the dysregulation of genes related to heart development. Besides, our findings also demonstrated that pyraclostrobin enhanced the contents of reactive oxygen species (ROS) and malondialdehyde (MDA), up-regulated catalase (CAT) activity, but inhibited superoxide dismutase (SOD) activity. Subsequently, the NF-κb signaling pathway was further studied, and the results indicated that the up-regulation of tnf-α, tlr-4, and myd88 activated the NF-κb signaling pathway and up-regulated the relative expression level of pro-inflammatory cytokines, such as cc-chemokine, ifn-γ, and cxcl-clc. Collectively, this study revealed that pyraclostrobin exposure induces developmental toxicity and cardiotoxicity, which may result from a combination of oxidative stress and inflammatory responses. These findings provide a basis for continued evaluation of the effects and ecological risks of pyraclostrobin on the early development of aquatic organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims/Background The evaluation of health-related quality of life in patients undergoing maintenance haemodialysis has garnered increasing attention. The modified creatinine index, a surrogate marker for muscle mass, has been linked to various clinical outcomes. However, the relationship between modified creatinine index and health-related quality of life in maintenance haemodialysis patients remains unclear. This study aims to elucidate the association between modified creatinine index and health-related quality of life in individuals receiving maintenance haemodialysis. Methods This cross-sectional study included 217 maintenance haemodialysis patients. Health-related quality of life was assessed using the Kidney Disease Quality of Life Instrument. Collected data included general patient information, laboratory results, and haemodialysis-related parameters. The modified creatinine index was calculated based on gender, age, single-pool Kt/V (spKt/V), and pre-dialysis serum creatinine levels. Multiple linear regression models and smooth curve fitting were used to investigate the relationship between modified creatinine index and health-related quality of life. Subgroup analyses and interaction tests were performed to identify potential effect modifiers. Results The 217 maintenance haemodialysis patients had a mean age of 53.66±13.15 years and a median dialysis vintage of 39 (25-84) months; 120 (55.30%) were male. The mean health-related quality of life score was 55.76±10.33, and the mean modified creatinine index was 22.72±2.95 mg/kg/day. After adjusting for confounding factors, an increase in modified creatinine index was associated with an improvement in health-related quality of life (β=0.55, 95% CI: 0.04, 1.06, p = 0.033). No nonlinear relationship was identified between modified creatinine index and health-related quality of life by smooth curve fitting. Subgroup and interaction analyses indicated that the relationship between modified creatinine index and health-related quality of life was stable and not significantly influenced by age, gender, dialysis vintage, diabetes status, or body mass index ( p > 0.05). Conclusion Modified creatinine index is positively correlated with health-related quality of life in maintenance haemodialysis patients, suggesting its potential utility in evaluating patient quality of life. Modified creatinine index could be clinically useful to improve the predictability of health-related quality of life in maintenance haemodialysis patients.

Cell-passage-adapted strains of African swine fever virus (ASFV) typically exhibit substantial genomic alterations and attenuated virulence in pigs. We have indicated that the human embryonic kidney (HEK293T) cells-adapted ASFV strain underwent genetic alterations and the I7L gene in the right variable region was deleted compared with the ASFV HLJ/2018 strain (ASFV-WT). A recent study has revealed that the deletion of the I7L-I11L genes results in attenuation of virulent ASFV in vivo, but the underlying mechanism remains largely unknown. Therefore, we hypothesized that the deletion of the I7L gene may be related to the pathogenicity of ASFV in pigs. We generated the I7L gene-deleted ASFV mutant (ASFV-ΔI7L) and found that the I7L gene deletion does not influence the replication of ASFV in primary porcine alveolar macrophages (PAMs). Using transcriptome sequencing analysis, we identified that the differentially expressed genes in the PAMs infected with ASFV-ΔI7L were mainly involved in antiviral immune responses induced by interferon gamma (IFN-γ) compared with those in the ASFV-WT-infected PAMs. Meanwhile, we further confirmed that the I7L protein (pI7L) suppressed the IFN-γ-triggered JAK-STAT signaling pathway. Mechanistically, pI7L interacts with STAT1 and inhibits its phosphorylation and homodimerization, which depends on the tyrosine at position 98 (Y98) of pI7L, thereby preventing the nuclear translocation of STAT1 and leading to the decreased production of IFN-γ-stimulated genes. Importantly, ASFV-ΔI7L exhibited reduced replication and virulence compared with ASFV-WT in pigs, likely due to the increased production of IFN-γ-stimulated genes, indicating that pI7L is involved in the virulence of ASFV. Taken together, our findings demonstrate that pI7L is associated with pathogenicity and antagonizes the IFN-γ-triggered JAK-STAT signaling pathway via inhibiting the phosphorylation and homodimerization of STAT1 depending on the Y98 residue of pI7L and the Src homology 2 domain of STAT1, which provides more information for understanding the immunoevasion strategies and designing the live attenuated vaccines against ASFV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recently, there has been a burgeoning interest in flexible shear force sensors capable of precisely detecting both magnitude and direction. Despite considerable efforts, the challenge of achieving accurate direction recognition persists, primarily due to the inherent structural characteristics and sensing mechanisms. Here, we present a shear force sensor constructed by a magnetically induced assembled Ni/PDMS composite membrane, which is magnetized and integrated with a three-axis Hall sensor, facilitating its ability to simultaneously monitor both shear force magnitude (0.7-87 mN) and direction (0-360°). The cilia-inspired shear force magnetic sensor (CISFMS) exhibits admirable attributes, including exceptional flexibility, high sensitivity (0.76 mN -1 ), an exceedingly low detection limit (1° and 0.7 mN), and remarkable durability (over 10,000 bending cycles). Further, our results demonstrate the capacity of the CISFMS in detecting tactile properties, fluid velocity, and direction, offering substantial potential for future developments in wearable electronics.

The cross-modal remote sensing image-text retrieval (CMRSITR) is a lively research topic in the remote sensing (RS) community. Benefiting from the large pretrained image-text models, many successful CMRSITR methods have been proposed in recent years. Although their performance is attractive, there are still some challenges. First, fine-tuning large pretrained models requires a significant amount of computational resources. Second, most large models are pretrained by natural images, which reduces their effectiveness in processing RS images. To tackle these challenges, we propose a new CMRSITR network named context and uncertainty-aware prompt (CUP). First, prompt tuning theory is introduced into CUP to eliminate the burden of optimization resources. By training the prompt tokens rather than all parameters, the large model's knowledge can be transferred to CMRSITR tasks with small trainable parameters. Second, considering the differences between natural-image-based prior clues and RS images, apart from adopting the free-prompt tokens, we develop a prompt generation module (PGM) to produce the RS-oriented prompt tokens. The specific prompt tokens are rich in object-level messages of RS images, which help CUP narrow the gaps between natural large models and RS images. Third, we further design an uncertainty estimation module (UEM) to whittle down the uncertainties caused by the model and data. This way, can not only the semantic misalignment and intraclass diversity imbalance problems be mitigated but also the RS clues can be deeply explored. Competitive experimental results counted on three public benchmark datasets demonstrate that our CUP can achieve competitive performance in the CMRSITR task compared with many existing methods. Our source codes are available at: https://github.com/TangXu-Group/Cross-modal-remote-sensing-image-and-text-retrieval-models/tree/main/CUP.

The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention., (© 2024. The Author(s).)

Background: Brassica napus L. (B. napus) is susceptible to waterlogging stress during different cultivation periods. Therefore, it is crucial to enhance the resistance to waterlogging stress to achieve a high and stable yield of B. napus., Results: Here we observed significant differences in the responses of two B. napus varieties in root under waterlogging stress. The sensitive variety (23651) exhibited a more pronounced and rapid reduction in cell wall thickness and root integrity compared with the tolerant variety (Santana) under waterlogging stress. By module clustering analysis based on transcriptome data, we identified that cell wall polysaccharide metabolism responded to waterlogging stress in root. It was found that pectin content was significantly reduced in the sensitive variety compared with the tolerant variety. Furthermore, transcriptome analysis revealed that the expression of two homologous genes encoding polygalacturonase-inhibiting protein 2 (PGIP2), involved in polysaccharide metabolic pathways, was highly upregulated in root of the tolerant variety under waterlogging stress. BnaPGIP2s probably confer waterlogging resistance by inhibiting the activity of polygalacturonases (PGs), which in turn reduces the degradation of the pectin backbone polygalacturonic acid., Conclusions: Our findings demonstrate that cell wall polysaccharides in root plays a vital role in response to the waterlogging stress and provide a theoretical foundation for breeding waterlogging resistance in B. napus varieties., (© 2024. The Author(s).)

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR , and all ST1486 non-hv-CRAB-BSI lacked adeG . The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

Aircraft ducts play an indispensable role in various systems of an aircraft. The regular inspection and maintenance of aircraft ducts are of great significance for preventing potential failures and ensuring the normal operation of the aircraft. Traditional manual inspection methods are costly and inefficient, especially under low-light conditions. To address these issues, we propose a new defect detection model called LESM-YOLO. In this study, we integrate a lighting enhancement module to improve the accuracy and recognition of the model under low-light conditions. Additionally, to reduce the model's parameter count, we employ space-to-depth convolution, making the model more lightweight and suitable for deployment on edge detection devices. Furthermore, we introduce Mixed Local Channel Attention (MLCA), which balances complexity and accuracy by combining local channel and spatial attention mechanisms, enhancing the overall performance of the model and improving the accuracy and robustness of defect detection. Finally, we compare the proposed model with other existing models to validate the effectiveness of LESM-YOLO. The test results show that our proposed model achieves an mAP of 96.3%, a 5.4% improvement over the original model, while maintaining a detection speed of 138.7, meeting real-time monitoring requirements. The model proposed in this paper provides valuable technical support for the detection of dark defects in aircraft ducts.

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities., (© 2024. The Author(s).)

This article investigates an event-triggered interval observer (ETIO) fault detection and isolation method for multiagent systems. First, an event-triggered mechanism is developed to reduce unnecessary communication transmission. Then, a distributed ETIO is designed by combining an interval observer and the proposed event-triggered mechanism. Furthermore, for achieving the desired tradeoff between the robustness to disturbances and the sensitivity to faults, the ETIO is formulated as a multiobjective optimization with l 1 / H ∞ performance. Second, a bank of ETIOs are interpreted to isolate the faulty agent on a local agent using only the output information from itself and its neighbors. Comparison result with the existing method is given to highlight the superiority of our methodology. Finally, the multiunmanned aerial vehicles system is utilized as the case research, and specific simulation results are presented.

It is well-known that proteins after administration into biological environments adsorb on the surface of nanoparticles (NPs). The biological identity could be determined by protein corona, but whether and how the preadsorbed molecules impact the composition of the corona and immunological response have rarely been reported. Here, the effects of preadsorbed chymotrypsin (Chy) on forming protein corona and subsequent immunological response are reported. We find that preadsorbed Chy on the surface of AuNPs results in a protein corona with enriched immunoglobulins and reduced human serum albumin protein, which further affect the polarization of macrophages into specific phenotypes. Our study suggests that the protein surrounding the nanoparticles could affect the protein corona and immunological response, which may direct the preparation of multifunctional nanomedicine for future studies., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Purpose: Calf muscles play an important role in marathon race, and the incidence of injury is high in this process. This study prospectively quantified diffusion tensor metrics, muscle fat fraction (MFF) and cross-sectional area (CSA) of calf muscles induced by endurance exercise in amateur marathoners, and the potential mechanisms underlying the changes in these parameters were analyzed., Method: In this prospective study, 35 marathoners (27 males, 8 females; mean age (standard deviation, SD), 38.92 (4.83) years) and 26 controls (18 males, 8 females; mean age (SD), 38.35 (6.75) years) underwent magnetic resonance imaging (MRI) from September 2022 to March 2023. The diffusion tensor eigenvalues (λ1, λ2, λ3), radial diffusivity (RD), fractional anisotropy (FA), MFF and CSA of calf muscles were compared between marathoners and controls. A binary logistic regression model with gender correction was performed analyze the relationship between marathon exercise and DTI parameters, CSA and MFF of calf muscles., Results: Interobserver agreement was good (κ = 0.71). The results of binary logistic regression model with gender correction showed that the regression coefficients of FA values in anterior group of calf (AC), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG) were negative, and the odds ratios (OR) were 0.33, 0.45, 0.35, 0.05, respectively (P < 0.05). The OR of RD in SOL and λ2 in external group of calf (EC) were relatively higher, 3.74 and 3.26, respectively (P < 0.05). CSA was greater in SOL of marathoners, with an OR value of 1.00(P < 0.05). The MFF in AC and LG was lower in marathoners and OR of two indexes were -0.69 and -0.59, respectively (P < 0.05)., Conclusions: Diffusion tensor imaging (DTI) combined with chemical shift-encoded sequence can noninvasively detect and quantify the adaptive changes of calf muscle morphology, microstructure and tissue composition induced by long-term running training in amateur marathoners., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The concentration of antimicrobial agents in environments like water and food has increased rapidly, which led to a rapid increase in antimicrobial resistance levels in the environment. Monitoring of bacterial resistance levels is considered as a necessary means to control the bacterial resistance. Reference standards are critical for antimicrobial susceptibility testing. CLSI M45 A3 standard defines pathogenic microorganisms that cause infections less frequently than those covered by CLSI M02, M07, and M100 as Infrequently Isolated or Fastidious Bacteria and specifies antimicrobial susceptibility testing methods. Our study investigated the epidemiology and antimicrobial susceptibility testing data of Infrequently Isolated or Fastidious Bacteria strains isolated from blood specimens in 70 hospitals in Guangdong Province between 2017 and 2021. We defined testing methods other than those specified in CLSI M45 A3 as "Non-Standardized." The proportion of standardized antimicrobial susceptibility testing for penicillin increased significantly ( Corynebacterium spp. 17.4% vs. 50.0% p  < 0.05; Micrococcus spp. 50.0% vs. 77.8% p  < 0.05; Abiotrophia spp. and Granulicatella spp. 21.4% vs. 90.9% p  < 0.001), while for cefotaxime ( Corynebacterium spp. 0.0% vs. 45.2% p  < 0.05; Abiotrophia spp. and Granulicatella spp. 0.0% vs. 14.3% p  = 0.515) and vancomycin increased finitely. Non-standardized methods were used for all other antimicrobials. Due to limitations in the economic and medical environment, some clinical laboratories are unable to fully comply with CLSI M45 A3 standard. We recommend that CLSI should add breakpoints for disk diffusion method to improve the standardization of antimicrobial susceptibility testing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yang, Haque, Chen, Guo, Li, Yao, Zhuo, Wang, Wang, Li, Lin, Xiao and Zhuo.)

Ethnopharmacological Relevance: Tiaogan Daozhuo Formula (TGDZF) is a common formulation against atherosclerosis, however, there is limited understanding of its therapeutic mechanism., Aim of This Study: To examine the effectiveness of TGDZF in the treatment of atherosclerosis and to explore its mechanisms., Materials and Methods: In ApoE -/- mice, atherosclerosis was induced by a high-fat diet for 12 weeks and treated with TGDZF at different doses. The efficacy of TGDZF in alleviating atherosclerosis was evaluated by small animal ultrasound and histological methods. Lipid levels were measured by biochemical methods. The capacity of cholesterol efflux was tested with a cholesterol efflux assay in peritoneal macrophage, and the expression of AMPKα1, PPARγ, LXRα, and ABCA1 was examined at mRNA and protein levels. Meanwhile, RAW264.7-derived macrophages were induced into foam cells by ox-LDL, and different doses of TGDZF-conducting serum were administered. Similarly, we examined differences in intracellular lipid accumulation, cholesterol efflux rate, and AMPKα1, PPARγ, LXRα, and ABCA1 levels following drug intervention. Finally, changes in the downstream molecules were evaluated following the inhibition of AMPK by compound C or PPARγ silencing by small interfering RNA., Results: TGDZF administration reduced aortic plaque area and lipid accumulation in aortic plaque and hepatocytes, and improved the serum lipid profiles of ApoE -/- mice. Further study revealed that its efficacy was accompanied by an increase in cholesterol efflux rate and the expression of PPARγ, LXRα, and ABCA1 mRNA and protein, as well as the promotion of AMPKα1 phosphorylation. Moreover, similar results were caused by the intervention of TGDZF-containing serum in vitro experiments. Inhibition of AMPK and PPARγ partially blocked the regulatory effect of TGDZF, respectively., Conclusions: TGDZF alleviated atherosclerosis and promoted cholesterol efflux from macrophages by activating the AMPK-PPARγ-LXRα-ABCA1 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to develop novel rapid-acting antidepressants with sustained efficacy and favorable safety profiles. We designed and synthesized a series of fluorine-containing scopolamine analogues and evaluated their antidepressant potential. In vitro cytotoxicity assays showed that most of these compounds exhibited minimal toxicity against neuronal and non-neuronal mammalian cell lines (IC 50 > 100 μM). The antidepressant activities of the compounds were evaluated using the tail suspension test, and S -3a was identified as a lead compound with potent and sustained antidepressant effects. Behaviorally, S -3a alleviated depressive symptoms in mice and displayed a higher cognitive safety margin than scopolamine. Toxicological assessments confirmed S -3a 's safety, while pharmacokinetics showed a rapid clearance (half-life: 16.6 min). Mechanistically, S -3a antagonized M 1 receptors and elevated BDNF levels, suggesting its potential as an antidepressant for further exploration.

Plastics biodegradation by insect larvae is considered as a new strategy for plastic wastes treatment. To uncover the biodegradation of a more complex chemical polymer of melamine formaldehyde (MF) by insect larvae, two worm species of yellow mealworm Tenebrio molitor and superworm Zophobas atratus were fed on MF foam as sole diet for 45 days with sole bran diet as control. Although the MF foam consumption by yellow mealworms of 0.38 mg/d/g-larvae was almost 40% higher than that by superworms of 0.28 mg/d/g-larvae, a similar decrease of survival rates in both species were obtained at about 58%, indicating the adverse effects on their growth. Depolymerization and biodegradation of MF foam occurred in both larval guts, but was more extensive in yellow mealworms. MF foam sole diet influenced gut bacterial and fungal microbiomes of both larvae species, which were assessed by Illumina MiSeq on day 45. Compared to the bran-fed group, both gut bacterial and fungal communities significantly changed in MF-fed groups, but differed in the two larvae species. The results demonstrated a strong association between the distinctive gut microbiome and MF foam degradation, such as unclassified Enterobacteriaceae, Hyphopichia and Issatchenkia. However, sole MF foam diet negatively influenced worms, like lower survival rates and gut abnormalities. In summary, MF foam could be degraded by both yellow mealworms and superworms, albeit with adverse effects. Gut microbes were strongly associated to MF foam degradation, especially the gut fungi., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Drug development for atherosclerosis, the underlying pathological state of ischemic cardiovascular diseases, has posed a longstanding challenge. Saponins, classified as steroid or triterpenoid glycosides, have shown promising therapeutic potential in the treatment of atherosclerosis. Through an exhaustive examination of scientific literature spanning from May 2013 to May 2023, we identified 82 references evaluating 37 types of saponins in terms of their prospective impacts on atherosclerosis. These studies suggest that saponins have the potential to ameliorate atherosclerosis by regulating lipid metabolism, inhibiting inflammation, suppressing apoptosis, reducing oxidative stress, and modulating smooth muscle cell proliferation and migration, as well as regulating gut microbiota, autophagy, endothelial senescence, and angiogenesis. Notably, ginsenosides exhibit significant potential and manifest essential pharmacological attributes, including lipid-lowering, anti-inflammatory, anti-apoptotic, and anti-oxidative stress effects. This review provides a comprehensive examination of the pharmacological attributes of saponins in atherosclerosis, with particular emphasis on their role in the regulation of lipid metabolism regulation and anti-inflammatory effects. Thus, saponins may warrant further investigation as a potential therapy for atherosclerosis. However, due to various reasons such as low oral bioavailability, the clinical application of saponins in the treatment of atherosclerosis still needs further exploration., (© 2024 John Wiley & Sons Ltd.)

VarCards, an online database, combines comprehensive variant- and gene-level annotation data to streamline genetic counselling for coding variants. Recognising the increasing clinical relevance of non-coding variations, there has been an accelerated development of bioinformatics tools dedicated to interpreting non-coding variations, including single-nucleotide variants and copy number variations. Regrettably, most tools remain as either locally installed databases or command-line tools dispersed across diverse online platforms. Such a landscape poses inconveniences and challenges for genetic counsellors seeking to utilise these resources without advanced bioinformatics expertise. Consequently, we developed VarCards2, which incorporates nearly nine billion artificially generated single-nucleotide variants (including those from mitochondrial DNA) and compiles vital annotation information for genetic counselling based on ACMG-AMP variant-interpretation guidelines. These annotations include (I) functional effects; (II) minor allele frequencies; (III) comprehensive function and pathogenicity predictions covering all potential variants, such as non-synonymous substitutions, non-canonical splicing variants, and non-coding variations and (IV) gene-level information. Furthermore, VarCards2 incorporates 368 820 266 documented short insertions and deletions and 2 773 555 documented copy number variations, complemented by their corresponding annotation and prediction tools. In conclusion, VarCards2, by integrating over 150 variant- and gene-level annotation sources, significantly enhances the efficiency of genetic counselling and can be freely accessed at http://www.genemed.tech/varcards2/., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Substantial evidence shown that the age at onset (AAO) of Parkinson's disease (PD) is a major determinant of clinical heterogeneity. However, the mechanisms underlying heterogeneity in the AAO remain unclear. To investigate the risk factors with the AAO of PD, a total of 3156 patients with PD from the UK Biobank were included in this study. We evaluated the effects of polygenic risk scores (PRS), nongenetic risk factors, and their interaction on the AAO using Mann-Whitney U tests and regression analyses. We further identified the genes interacting with nongenetic risk factors for the AAO using genome-wide environment interaction studies. We newly found physical activity (P < 0.0001) was positively associated with AAO and excessive daytime sleepiness (P < 0.0001) was negatively associated with AAO, and reproduced the positive associations of smoking and non-steroidal anti-inflammatory drug intake and the negative association of family history with AAO. In the dose-dependent analyses, smoking duration (P = 1.95 × 10 -6 ), coffee consumption (P = 0.0150), and tea consumption (P = 0.0008) were positively associated with AAO. Individuals with higher PRS had younger AAO (P = 3.91 × 10 -5 ). In addition, we observed a significant interaction between the PRS and smoking for AAO (P = 0.0316). Specifically, several genes, including ANGPT1 (P = 7.17 × 10 -7 ) and PLEKHA6 (P = 4.87 × 10 -6 ), may influence the positive relationship between smoking and AAO. Our data suggests that genetic and nongenetic risk factors are associated with the AAO of PD and that there is an interaction between the two., (© 2024. The Author(s).)

Background: Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown., Methods: We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein-protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing., Findings: We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants (CSVs) and NCSVs contributed to an equal proportion of patients with NDD (0.76% vs. 0.82%). The candidate genes carrying NCSVs were associated with glutamatergic synapse and chromatin remodelling. Minigene successfully validated 59 of 79 (74.68%) NCSVs that led to abnormal splicing in 40 candidate genes, and 9 of the genes (ARID1B, KAT6B, TCF4, SMARCA2, SHANK3, PDHA1, WDR45, SCN2A, SYNGAP1) harboured recurrent NCSVs with the same variant present in more than two unrelated patients with NDD. Moreover, 36 of 59 (61.02%) NCSVs are novel clinically relevant variants, including 34 unreported and 2 clinically conflicting interpretations or of uncertain significance NCSVs in the ClinVar database., Interpretation: This study highlights the common pathology and clinical importance of NCSVs in unsolved patients with NDD., Funding: The present study was funded by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Hunan Youth Science and Technology Innovation Talent Project, the Provincial Natural Science Foundation of Hunan, The Scientific Research Program of FuRong laboratory, and the Natural Science Project of the University of Anhui Province., Competing Interests: Declaration of interests The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Answer sorting and filtering are two closely related steps for determining the answer to a question. Answer sorting is designed to produce an ordered list of scores based on Top-k and contextual criteria. Answer filtering optimizes the selection according to other criteria, such as the range of time constraints the user expects. However, the unclear number of answers and time constraints, as well as the high score of false positive results, indicate that the traditional sorting and selection methods cannot guarantee the quality of answers to multi-answer questions. Therefore, this study proposes MATQA, a component based on multi-answer temporal question reasoning, using a re-validation framework to convert the Top-k answer list output by the QA system into a clear number of answer combinations, and a new multi-answer based evaluation index is proposed for this output form. First, the highly correlated subgraph is selected by calculating the scores of the boot node and the related fact node. Second, the subgraph attention inference module is introduced to determine the initial answer with the highest probability. Finally, the alternative answers are clustered at the semantic level and the time constraint level. Meanwhile, the candidate answers with similar types and high scores but do not satisfy the semantic constraints or the time constraints are eliminated to ensure the number and accuracy of final answers. Experiments on the multi-answer TimeQuestions dataset demonstrate the effectiveness of the answer combinations output by MATQA., Competing Interests: The authors declare there are no competing interests., (©2023 Yao et al.)

Lithiophilic substrates have been shown to improve the electrochemical performance of lithium metal anodes. The MXene-BN/Cu 3D current collector was prepared by a filtration method. The artificial solid electrolyte interface (SEI) layer composed of Li 3 N and LiF was formed on the surface of MXene-BN/Cu during the Li deposition process. Volume changes can be effectively relieved by this special 3D structure. The artificial SEI film reduced the critical dendrite growth length, inhibited Li dendrite growth, and stabilized the electrochemical cycle. MXene-BN/Cu exhibited highly reversible cycling properties during lithium metal deposition with a high Coulombic efficiency of ∼ 98.0% over 500 cycles. Furthermore, LiBH 4 was produced during the Li deposition process. This study presents a promising strategy for developing dendrite-free Li anodes for use in lithium metal batteries.

Ovarian mesenchymal cells (oMCs) constitute a distinct microenvironment that supports folliculogenesis under physiological conditions. Supplementation of exogenous non-ovarian mesenchymal-related cells has been reported to be an efficient approach to improve ovarian functions. However, the development and cellular and molecular characteristics of endogenous oMCs remain largely unexplored. In this study, we surveyed the single-cell transcriptomic landscape to dissect the cellular and molecular changes associated with the aging of oMCs in mice. Our results showed that the oMCs were composed of five ovarian differentiated MC (odMC) populations and one ovarian mesenchymal progenitor (oMP) cell population. These cells could differentiate into various odMCs via an oMP-derived route to construct the ovarian stroma structures. Comparative analysis revealed that ovarian aging was associated with decreased quantity of oMP cells and reduced quality of odMCs. Based on the findings of bioinformatics analysis, we designed different strategies involving supplementation with young oMCs to examine their effects on female fertility and health. Our functional investigations revealed that oMCs supplementation prior to ovarian senescence was the optimal method to improve female fertility and extend the reproductive lifespan of aged females in the long-term., (© 2023. Science China Press.)

As one of the most important phthalates, di-isononyl phthalate (DINP) has been widely used as a common plasticizer in the food and personal care products sectors. In our previous study, we found that DINP can induce autophagy of ovarian granulosa cells; while the underlying mechanism is unclear. In the study, we showed that DINP exposure could induce autophagy of ovarian granulosa cells and KGN cells, accompanied with the increase in the mRNA and protein level of DDIT4. Furthermore, overexpression of DDIT4 were shown to induce autophagy of KGN cells; while knockdown of DDIT4 inhibited DINP-induced autophagy, implying that DDIT4 played an important role in DINP-induced autophagy of ovarian granulosa cells. There were three putative binding sites of transcription factor ATF4 in the promoter region of DDIT4 gene, suggesting that DDIT4 might be regulated by ATF4. Herein, we found that overexpression of ATF4 could upregulate the expression of DDIT4 in KGN cells, while knockdown of ATF4 inhibited its expression. Subsequently, ATF4 was identified to bind to the promoter region of DDIT4 gene and promote its transcription. The expression of ATF4 was also increased in the DINP-exposed granulosa cells, and ATF4 overexpression promoted autophagy of KGN cells; whereas knockdown of ATF4 alleviated DINP-induced upregulation of DDIT4 and autophagy of the cells. Taken together, DINP triggered autophagy of ovarian granulosa cells through activating ATF4/DDIT4 signals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Can potential mechanisms involved in the likely concurrence of diminished ovarian reserve (DOR) and miscarriage be identified using genetic data?, Summary Answer: Concurrence between ovarian reserve and spontaneous miscarriage was observed, and may be attributed to shared genetic risk loci enriched in antigen processing and presentation and autoimmune disease pathways., What Is Known Already: Previous studies have shown that lower serum anti-Müllerian hormone (AMH) levels are associated with increased risk of embryo aneuploidy and spontaneous miscarriage, although findings have not been consistent across all studies. A recent meta-analysis suggested that the association between DOR and miscarriage may not be causal, but rather a result of shared underlying causes such as clinical conditions or past exposure. Motivated by this hypothesis, we conducted the present analysis to explore the concurrence between DOR and miscarriage, and to investigate potential mechanisms using genetic data., Study Design, Size, Duration: Three data sources were used in the study: the clinical IVF data were retrospectively collected from an academically affiliated Reproductive Medicine Center (17 786 cycles included); the epidemiological data from the UK Biobank (UKB), which is a large-scale, population-based, prospective cohort study (35 316 white women included), were analyzed; and individual-level genotype data from the UKB were extracted for further analysis., Participants/materials, Setting, Methods: There were three modules of analysis. First, clinical IVF data were used to test the association between ovarian reserve biomarkers and the subsequent early spontaneous miscarriage risk. Second, the UKB data were used to test the association of spontaneous miscarriage history and early menopause. Third, individual-level genotype data from the UKB were analyzed to identify specific pleiotropic genes which affect the development of miscarriage and menopause., Main Results and the Role of Chance: In the analysis of clinical IVF data, the risk of early spontaneous miscarriage was 1.57 times higher in the group with AMH < 1.1 ng/ml group (P < 0.001), 1.62 times for antral follicular count <5 (P < 0.001), and 1.39 times for FSH ≥10 mIU/ml (P < 0.001) in comparison with normal ovarian reserve groups. In the analysis of UKB data, participants with a history of three or more miscarriages had a one-third higher risk of experiencing early menopause (odds ratio: 1.30, 95% CI 1.13-1.49, P < 0.001), compared with participants without spontaneous miscarriage history. We identified 158 shared genetic risk loci that affect both miscarriage and menopause, which enrichment analysis showed were involved in antigen processing and presentation and autoimmune disease pathways., Limitations, Reasons for Caution: The analyses of the UKB data were restricted to participants of European ancestry, as 94.6% of the cohort were of white ethnicity. Further studies are needed in non-white populations. Additionally, maternal age at the time of spontaneous miscarriage was not available in the UKB cohort, therefore we adjusted for age at baseline assessment in the models instead. It is known that miscarriage rate in IVF is higher compared to natural conception, highlighting a need for caution when generalizing our findings from the IVF cohort to the general population., Wider Implications of the Findings: Our findings have implications for IVF clinicians in terms of patient counseling on the prognosis of IVF treatment, as well as for genetic counseling regarding miscarriage. Our results highlight the importance of further research on the shared genetic architecture and common pathophysiological basis of DOR and miscarriage, which may lead to new therapeutic opportunities., Study Funding/competing Interest(s): This work was supported by the Hunan Youth Science and Technology Innovation Talent Project (2020RC3060), the International Postdoctoral Exchange Fellowship Program (Talent-Introduction Program, YJ20220220), the fellowship of China Postdoctoral Science Foundation (2022M723564), and the Natural Science Foundation of Hunan Province, China (2023JJ41016). This work has been accepted for poster presentation at the 39th Annual Meeting of ESHRE, Copenhagen, Denmark, 25-28 June 2023 (Poster number: P-477). The authors declare no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Bronchopulmonary dysplasia (BPD) is the predominant chronic disorder in preterm neonates. This study explored impacts of miR-34c-5p carried by bone marrow stromal cells-secreted extracellular vesicles (BMSC-EVs) on BPD progression., Methods: A BPD mouse model was established, followed by measurement of miR-34c-5p, OTUD3, and PTEN expression. EVs were isolated from BMSCs transfected with miR-34c-5p mimic or mimic NC and intratracheally injected into mice. CD31 and Ki67 expression was detected and the pathological changes of lung tissues and lung function indexes were observed for mice. A neonatal human pulmonary microvascular endothelial cell (HPMEC) model was developed with hyperoxia, followed by co-culture with extracted EVs and ectopic experiments for measurement of cell viability, migration, and angiogenesis. IL-4, IL-13, IL-1β, and IL-6 levels were measured in cell supernatants and lung tissues. Dual-luciferase reporter, ubiquitination, Co-IP, and RIP assays were adopted to determine the relationship among miR-34c-5p, OTUD3, and PTEN., Results: Lung tissues of BPD mice had downregulated miR-34c-5p expression and upregulated OTUD3 and PTEN expression. BMSC-EVs and BMSC-EVs-miR-34c-5p treatment improved lung injury and alveolar structure, decreased lung resistance and IL-4, IL-13, IL-1β, and IL-6 levels, and elevated dynamic lung compliance in BPD mice, as well as enhanced proliferation, angiogenesis, and migration and restrained inflammation in HPMECs. Mechanistically, miR-34c-5p negatively targeted OTUD3 which restrained ubiquitination to promote PTEN protein stabilization. Upregulation of OTUD3 or PTEN negated the changes in the proliferation, angiogenesis, migration, and inflammation of hyperoxia-treated HPMECs induced by BMSC-EVs-miR-34c-5p., Conclusion: BMSC-EVs-miR-34c-5p alleviated lung injury and inflammation in hyperoxia-induced BPD by blocking the OTUD3/PTEN axis.

Accurately obtaining soil water and organic matter content is of great significance for improving soil qua-lity in croplands with medium to low yield. We explored the estimation effect of fractional order differentiation (FOD) combined with different spectral indices on soil water and organic matter content in medium and low yield croplands of Ningxia Yellow River Irrigation Area. After root mean square transformation of field measured hyperspectral reflectance, we used 0-2 FOD (with a step length of 0.25) to construct difference index (DI), ratio index (RI), product index (PI), sum index (SI), generalized difference index (GDI), and nitrogen planar domain index (NPDI) and to select the optimal spectral index based on the correlation coefficients between six spectral indices with soil water and organic matter contents. We constructed a model for estimating soil water and organic matter content based on partial least squares regression (PLSR) and support vector machine (SVM). The results showed that the correlation between soil water and organic matter content and spectral information was effectively improved after FOD transformation compared with the original spectrum, with maximum increases of 0.1785 and 0.1713, respectively. The soil water content sensitive bands were mainly in the range of 400-630 and 1350-1940 nm, while the sensitive bands of organic matter content were mainly at 460-850, 1530-1910, and 2060-2310 nm. The accuracy of SVM model was significantly higher than that of PLSR, and the soil water content estimation model based on 1.75-order NPDI-SVM reached the highest precision, with a validation determination coefficient ( R p 2 ) of 0.970, root mean square error (RMSE) of 1.615, and relative percent deviation (RPD) of 4.211. The organic matter content estimation model based on 0.5 order DI-SVM had the best performance, with R p 2 , RMSE and RPD of 0.983, 0.701 and 5.307, respectively. Our results could provide data and technological support for soil water and nutrient monitoring, quality improvement, and graphics creating in similar area with medium to low yield fields.

Soil microbiota, which plays a fundamental role in ecosystem functioning, is sensitive to environmental changes. Studying soil microbial ecological patterns can help to understand the consequences of environmental disturbances on soil microbiota and hence ecosystem services. The different habitats with critical environmental gradients generated through the restoration of coal-mining subsidence areas provide an ideal area to explore the response of soil microbiota to environmental changes. Here, based on high-throughput sequencing, we revealed the patterns of soil bacterial and fungal communities in habitats with different land-use types (wetland, farmland, and grassland) and with different restored times which were generated during the ecological restoration of a typical coal-mining subsidence area in Jining City, China. The α-diversity of bacterial was higher in wetland than in farmland and grassland, while that of fungi had no discrepancy among the three habitats. The β-diversity of bacterial community in the grassland was lower than in the farmland, and fungal community was significant different in all three habitats, showing wetland, grassland, and farmland from high to low. The β-diversity of the bacterial community decreased with restoration time while that of the fungal community had no significant change in the longer-restoration-time area. Furthermore, soil electrical conductivity was the most important driver for both bacterial and fungal communities. Based on the taxonomic difference among different habitats, we identified a group of biomarkers for each habitat. The study contributes to understand the microbial patterns during the ecological restoration of coal-mining subsidence areas, which has implications for the efficient ecological restoration of subsidence areas., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer at the histological level. Despite the emergence of new biological technology, advanced-stage HCC remains largely incurable. The prediction of a cancer biomarker is a key problem for targeted therapy in the disease., Methods: We performed a miRNA-gene integrated analysis to identify differentially expressed miRNAs (DEMs) and genes (DEGs) of HCC. The DEM-DEG interaction network was constructed and analyzed. Gene ontology enrichment and survival analyses were also performed in this study., Results: By the analysis of healthy and tumor samples, we found that 94 DEGs and 25 DEMs were significantly differentially expressed in different datasets. Gene ontology enrichment analysis showed that these 94 DEGs were significantly enriched in the term "Liver" with a statistical p -value of 1.71 × 10 -26 . Function enrichment analysis indicated that these genes were significantly overrepresented in the term "monocarboxylic acid metabolic process" with a p -value = 2.94 × 10 -18 . Two sets (fourteen genes and five miRNAs) were screened by a miRNA-gene integrated analysis of their interaction network. The statistical analysis of these molecules showed that five genes (CLEC4G, GLS2, H2AFZ, STMN1, TUBA1B) and two miRNAs (hsa-miR-326 and has-miR-331-5p) have significant effects on the survival prognosis of patients., Conclusion: We believe that our study could provide critical clinical biomarkers for the targeted therapy of HCC.

Background: China has one of the highest hepatitis B virus (HBV) disease burdens worldwide and tracking progress toward the 2030 HBV elimination targets is essential. This study aimed to assess the impact of biomedical interventions (i.e., adult vaccination, screening and treatment) on the adult HBV epidemic, estimate the time for HBV elimination, and evaluate the cost-effectiveness of the interventions in China., Methods: A deterministic compartmental model was developed to project the HBV epidemic from 2022 to 2050 and estimate the time to meet elimination targets under four intervention scenarios. Cost-effectiveness was calculated using incremental cost per quality-adjusted life year (QALY) gained, i.e., average cost-effectiveness ratio (CER)., Results: Under the status quo, there will be 42.09-45.42 million adults living with HBV in 2050 and 11.04-14.36 million HBV-related deaths cumulatively from 2022 to 2050. Universal vaccination would cumulatively avert 3.44-3.95 million new cases at a cost of US$1027-1261/QALY gained. The comprehensive strategy would cumulatively avert 4.67-5.24 million new chronic cases and 1.39-1.85 million deaths, expediting the realization of the elimination targets forward to 2049. This strategy was also cost-effective with an average CER of US$20,796-26,685/QALY and a saved healthcare cost of US$16.10-26.84 per person., Conclusion: China is not on track to meet the elimination targets but comprehensive biomedical interventions can accelerate the realization of the targets. A comprehensive strategy is cost-effective and cost-saving, which should be promoted in primary care infrastructures. Universal adult vaccination may be appropriate in the near future considering practical feasibility., (© 2023. The Author(s).)

With the development of underwater technology and the increasing demand for ocean development, more and more intelligent equipment is being applied to underwater scientific missions. Specifically, autonomous underwater vehicle (AUV) clusters are being used for their flexibility and the advantages of carrying communication and detection units, often performing underwater tasks in formation. In order to locate AUVs with high precision, we introduce an unmanned surface vehicle (USV) with global positioning system (GPS) and propose a USV-AUV network. Furthermore, we propose an ultra-short baseline (USBL) acoustic cooperative location scheme with an orthogonal array, which is based on underwater communication with sonar. Based on the derivation of the Fisher information matrix formula under Cartesian parameters, we analyze the positioning accuracy of AUVs in different positions under the USBL positioning mode to derive the optimal array of the AUV formation. In addition, we propose a USV path planning scheme based on Dubins path planning functions to assist in locating the AUV formation. The simulation results verify that the proposed scheme can ensure the positioning accuracy of the AUV formation and help underwater research missions.

Background: Drug overdose deaths in the USA have increased rapidly in the past 20 years, and understanding patterns and trends in mortality is essential to develop policy responses. This study aimed to determine whether cohort patterns in mortality due to drug overdose have changed in the past two decades and assess these patterns by race and sex., Methods: The national records of accidental drug overdose death were extracted from Centers for Disease Control and Prevention, National Center for Health Statistics Mortality Data for 2000-2020. Age-period-cohort analysis was performed to examine independent effects of age, period and birth cohort on accidental drug overdose mortality., Findings: The number of accidental drug overdose deaths increased by 622% between 2000 and 2020, and age-standardized mortality rates increased nearly four-fold in both men and women. Age-period-cohort decomposition found rapid increases in mortality since 2012 in men and women, with higher mortality risk in cohorts born after 1990. The fastest increase occurred in Black Americans since 2012, and Americans of all races born after 1975 had significantly higher mortality risk, with mortality risk increasing rapidly in more recent cohorts. The peak of mortality has shifted from the 40-59 age group to the 30-40 year age group in the past decade., Interpretation: The burden of drug overdose mortality has shifted to younger Americans, and a new generation of Americans are at significantly higher and rapidly increasing risk of overdose death. Urgent action is needed to prevent an entire generation of young people being consigned to decades of preventable mortality., Funding: None., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

China's goal to achieve carbon (C) neutrality by 2060 requires scaling up photovoltaic (PV) and wind power from 1 to 10-15 PWh year -1 (refs.  1-5 ). Following the historical rates of renewable installation 1 , a recent high-resolution energy-system model 6 and forecasts based on China's 14th Five-year Energy Development (CFED) 7 , however, only indicate that the capacity will reach 5-9.5 PWh year -1 by 2060. Here we show that, by individually optimizing the deployment of 3,844 new utility-scale PV and wind power plants coordinated with ultra-high-voltage (UHV) transmission and energy storage and accounting for power-load flexibility and learning dynamics, the capacity of PV and wind power can be increased from 9 PWh year -1 (corresponding to the CFED path) to 15 PWh year -1 , accompanied by a reduction in the average abatement cost from US$97 to US$6 per tonne of carbon dioxide (tCO 2 ). To achieve this, annualized investment in PV and wind power should ramp up from US$77 billion in 2020 (current level) to US$127 billion in the 2020s and further to US$426 billion year -1 in the 2050s. The large-scale deployment of PV and wind power increases income for residents in the poorest regions as co-benefits. Our results highlight the importance of upgrading power systems by building energy storage, expanding transmission capacity and adjusting power load at the demand side to reduce the economic cost of deploying PV and wind power to achieve carbon neutrality in China., (© 2023. The Author(s).)

Non-coding variants in the human genome significantly influence human traits and complex diseases via their regulation and modification effects. Hence, an increasing number of computational methods are developed to predict the effects of variants in human non-coding sequences. However, it is difficult for inexperienced users to select appropriate computational methods from dozens of available methods. To solve this issue, we assessed 12 performance metrics of 24 methods on four independent non-coding variant benchmark datasets: (1) rare germline variants from clinical relevant sequence variants (ClinVar), (2) rare somatic variants from Catalogue Of Somatic Mutations In Cancer (COSMIC), (3) common regulatory variants from curated expression quantitative trait locus (eQTL) data, and (4) disease-associated common variants from curated genome-wide association studies (GWAS). All 24 tested methods performed differently under various conditions, indicating varying strengths and weaknesses under different scenarios. Importantly, the performance of existing methods was acceptable for rare germline variants from ClinVar with the area under the receiver operating characteristic curve (AUROC) of 0.4481-0.8033 and poor for rare somatic variants from COSMIC (AUROC = 0.4984-0.7131), common regulatory variants from curated eQTL data (AUROC = 0.4837-0.6472), and disease-associated common variants from curated GWAS (AUROC = 0.4766-0.5188). We also compared the prediction performance of 24 methods for non-coding de novo mutations in autism spectrum disorder, and found that the combined annotation-dependent depletion (CADD) and context-dependent tolerance score (CDTS) methods showed better performance. Summarily, we assessed the performance of 24 computational methods under diverse scenarios, providing preliminary advice for proper tool selection and guiding the development of new techniques in interpreting non-coding variants., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Chlorprenaline hydrochloride (CLOR) is a typical representative of β-adrenergic agonists that may be used illegally as a livestock feed additive and may have adverse impacts on the environment. In the present study, zebrafish embryos were exposed to CLOR to investigate its developmental toxicity and neurotoxicity. The results demonstrated that CLOR exposure led to adverse effects on developing zebrafish, such as morphological changes, a high heart rate, and increased body length, resulting in developmental toxicity. Moreover, the up-regulation of activities of superoxide dismutase (SOD) and catalase (CAT) and the enhancement of malondialdehyde (MDA) content illustrated that CLOR exposure activated oxidative stress in exposed zebrafish embryos. Meanwhile, CLOR exposure also caused alterations in locomotive behavior in zebrafish embryos, including an increase in acetylcholinesterase (AChE) activity. Quantitative polymerase chain reaction (QPCR) results showed that the transcription of genes related to the central nervous system (CNS) development, namely, mbp, syn2a, α1-tubulin, gap43, shha, and elavl3, indicated that CLOR exposure could lead to neurotoxicity in zebrafish embryos. These results showed that CLOR exposure could cause developmental neurotoxicity in the early stages of zebrafish development and that CLOR might induce neurotoxicity by altering the expression of neuro-developmental genes, elevating AChE activity, and activating oxidative stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Atherosclerosis, the main pathological basis of cardiovascular disease, is a chronic inflammatory disease that severely affects the quality of human life. Resveratrol (Res) is a natural polyphenol that is a major component of many herbs and foods. The present study analyzed resveratrol from the perspective of visualization and bibliometric analysis and found that resveratrol is closely related to the inflammatory response in cardiovascular diseases (associated with atherosclerosis). To explore the specific molecular mechanism of resveratrol, network pharmacology and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used, in which HIF-1 α signaling may be a key pathway in the treatment of AS. Furthermore, we induced the polarization of macrophage RAW264.7 to M1 type to generate inflammatory response by the combination of lipopolysaccharide (LPS) (200 ng/mL) + interferon- γ (IFN- γ ) (2.5 ng/mL). LPS and IFN- γ increased the inflammatory factor levels of IL-1 β , TNF- α , and IL-6 in RAW264.7, and the proportion of M1-type macrophages also increased, but the expression of inflammatory factors decreased after resveratrol administration, which confirmed the anti-inflammatory effect of resveratrol in AS. In addition, we found that resveratrol downregulated the protein expression of toll-like receptor 4 (TLR4)/NF- κ B/hypoxia inducible factor-1 alpha (HIF-1 α ). In conclusion, resveratrol has a significant anti-inflammatory effect, alleviates HIF-1 α -mediated angiogenesis, and prevents the progression of AS through the TLR4/NF- κ B signaling pathway., Competing Interests: The authors declare that the paper was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin Guo et al.)