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Abstract Extreme myopia (EM), defined as a spherical equivalent (SE) ≤ −10.00 diopters (D), is one of the leading causes of sight impairment. Known EM-associated variants only explain limited risk and are inadequate for clinical decision-making. To discover risk genes, we performed a whole-exome sequencing (WES) on 449 EM individuals and 9606 controls. We find a significant excess of rare protein-truncating variants (PTVs) in EM cases, enriched in the retrograde vesicle-mediated transport pathway. Employing single-cell RNA-sequencing (scRNA-seq) and a single-cell polygenic burden score (scPBS), we pinpointed PI16 + /SFRP4+ fibroblasts as the most relevant cell type. We observed that KDELR3 is highly expressed in scleral fibroblast and involved in scleral extracellular matrix (ECM) organization. The zebrafish model revealed that kdelr3 downregulation leads to elongated ocular axial length and increased lens diameter. Together, our study provides insight into the genetics of EM in humans and highlights KDELR3’s role in EM pathogenesis.

Abstract Background Meloidogyne incognita is one of the most important plant-parasitic nematodes and causes tremendous losses to the agricultural economy. Light is an important living factor for plants and pathogenic organisms, and sufficient light promotes root-knot nematode infection, but the underlying mechanism is still unclear. Results Expression level and genetic analyses revealed that the photoreceptor genes PHY, CRY, and PHOT have a negative impact on nematode infection. Interestingly, ELONGATED HYPOCOTYL5 (HY5), a downstream gene involved in the regulation of light signaling, is associated with photoreceptor-mediated negative regulation of root-knot nematode resistance. ChIP and yeast one-hybrid assays supported that HY5 participates in plant-to-root-knot nematode responses by directly binding to the SWEET negative regulatory factors involved in root-knot nematode resistance. Conclusions This study elucidates the important role of light signaling pathways in plant resistance to nematodes, providing a new perspective for RKN resistance research.

Abstract Dry reforming of methane (DRM) is a highly endothermic process, with its development hindered by the harsh thermocatalytic conditions required. We propose an innovative DRM approach utilizing a 16 W pulsed laser in combination with a cost-effective Mo2C catalyst, enabling DRM under milder conditions. The pulsed laser serves a dual function by inducing localized high temperatures and generating *CH plasma on the Mo2C surface. This activates CH4 and CO2, significantly accelerating the DRM reaction. Notably, the laser directly generates *CH plasma from CH4 through thermionic emission and cascade ionization, bypassing the traditional step-by-step dehydrogenation process and eliminating the rate-limiting step of methane cracking. This method maintains a carbon-oxygen balanced environment, thus preventing the deactivation of the Mo2C catalyst due to CO2 oxidation. The laser-catalytic DRM achieves high yields of H2 (14300.8 mmol h−1 g−1) and CO (14949.9 mmol h−1 g−1) with satisfactory energy efficiency (0.98 mmol kJ−1), providing a promising alternative for high-energy-consuming catalytic systems.

Abstract Background The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. Results A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3−/−) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. Conclusion Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract Graphical Abstract

Abstract Accurate segmentation of multiple organs in the head, neck, chest, and abdomen from medical images is an essential step in computer-aided diagnosis, surgical navigation, and radiation therapy. In the past few years, with a data-driven feature extraction approach and end-to-end training, automatic deep learning-based multi-organ segmentation methods have far outperformed traditional methods and become a new research topic. This review systematically summarizes the latest research in this field. We searched Google Scholar for papers published from January 1, 2016 to December 31, 2023, using keywords “multi-organ segmentation” and “deep learning”, resulting in 327 papers. We followed the PRISMA guidelines for paper selection, and 195 studies were deemed to be within the scope of this review. We summarized the two main aspects involved in multi-organ segmentation: datasets and methods. Regarding datasets, we provided an overview of existing public datasets and conducted an in-depth analysis. Concerning methods, we categorized existing approaches into three major classes: fully supervised, weakly supervised and semi-supervised, based on whether they require complete label information. We summarized the achievements of these methods in terms of segmentation accuracy. In the discussion and conclusion section, we outlined and summarized the current trends in multi-organ segmentation.

Abstract Background Standardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye. Methods This retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0–12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl’s ratio (SR) were also determined using an optical quality analysis system. Results The average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6–10 mm and 10–12 mm circles than males. Age-related changes in CD were evident, except in the 2–6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P

Abstract Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor β-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction.

Abstract Background To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. Methods The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. Results The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. Conclusions Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR.

Abstract Motivated by recent experimental observations of opposite Chern numbers in R-type twisted MoTe2 and WSe2 homobilayers, we perform large-scale density-functional-theory calculations with machine learning force fields to investigate moiré band topology across a range of twist angles in both materials. We find that the Chern numbers of the moiré frontier bands change sign as a function of twist angle, and this change is driven by the competition between moiré ferroelectricity and piezoelectricity. Our large-scale calculations, enabled by machine learning methods, reveal crucial insights into interactions across different scales in twisted bilayer systems. The interplay between atomic-level relaxation effects and moiré-scale electrostatic potential variation opens new avenues for the design of intertwined topological and correlated states, including the possibility of mimicking higher Landau level physics in the absence of magnetic field.

Soybean cyst nematode (Heterodera glycines, soybean cyst nematode [SCN]) disease adversely affects the yield of soybean and leads to billions of dollars in losses every year. To control the disease, it is necessary to study the resistance genes of the plant and their mechanisms. Isoflavonoids are secondary metabolites of the phenylalanine pathway, and they are synthesized in soybean. They are essential in plant response to biotic and abiotic stresses. In this study, we reported that phenylalanine ammonia-lyase (PAL) genes GmPALs involved in isoflavonoid biosynthesis, can positively regulate soybean resistance to SCN. Our previous study demonstrated that the expression of GmPAL genes in the resistant cultivar Huipizhi (HPZ) heidou are strongly induced by SCN. PAL is the rate-limiting enzyme that catalyzes the first step of phenylpropanoid metabolism, and it responds to biotic or abiotic stresses. Here, we demonstrate that the resistance of soybeans against SCN is suppressed by PAL inhibitor l-α-(aminooxy)-β-phenylpropionic acid (L-AOPP) treatment. Overexpression of eight GmPAL genes caused diapause of nematodes in transgenic roots. In a petiole-feeding bioassay, we identified that two isoflavones, daidzein and genistein, could enhance resistance against SCN and suppress nematode development. This study thus reveals GmPAL-mediated resistance against SCN, information that has good application potential. The role of isoflavones in soybean resistance provides new information for the control of SCN. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract The spatial response mechanism of hydrology and water quality of large river-connected lakes is very complicated. In this study, we developed a spatial response analysis method that couples wavelet correlation analysis (WTC) with self-organizing maps (SOM), revealing the spatial response and variation of water level and water quality in Poyang Lake, China's largest river-connected lake, over the past decade. The results show that: (1) there was significant spatial heterogeneity in water level and quality during the dry seasons (2010–2018) compared to other hydrological stages. (2) We identified a more pronounced difference in response of water level and quality between northern and southern parts of Poyang Lake. As the distance increases from the northern lake outlet, the impact of rising water levels on water quality deterioration intensified during the dry seasons. (3) The complex spatial heterogeneity of water level and quality response in the dry seasons is primarily influenced by water level fluctuations from the northern region and the cumulative pollutant entering the lake from the south, which particularly leads to the reversal of the response in the central area of Poyang Lake. The results of this study can contribute to scientific decision-making regarding water environment zoning management in large river-connected lakes amidst complex environment conditions.

Abstract To address the issues of probiotic activity loss during storage and feeding, as well as the limited efficacy of single probiotics, a solution was devised by embedding a mixture of Bacillus coagulans SN‐8 (SN‐8) and Saccharomyces boulardii SN‐6 (SN‐6) in a gel. The initial step involved screening the probiotic microcapsules' preparation method and wall material. Using sodium alginate and β‐cyclodextrin as composite wall material and chitosan as the outer coating material allowed for an embedding rate of 82.11% in composite probiotic microcapsules prepared by the air atomization method. Next, in vitro, simulated digestion experiments were conducted to determine the number of viable bacteria and the release rate of the microcapsules. The results showed that compared to the free strain, the mixed probiotic microcapsules retained a survival rate of 67.5% after 3 h of simulated gastric juice exposure and 70.56% after 42 days of storage at 4°C. This demonstrated higher survival rates and storage stability. The prepared probiotic microcapsules were then administered to dairy cows. 16S rDNA gene sequencing showed that consumption of the microcapsules reduced the number of harmful bacteria, such as Paeniclostridium, in the intestinal tract of dairy cows while accelerating the growth of beneficial bacteria, such as Bifidobacterium. In particular, this resulted in a significant improvement in the lactation performance of the cows, with a 4.5% increase in milk fat content, a 92.5% increase in milk protein content, and a 3.5% increase in milk urea nitrogen content (6.75 mL/dL). In conclusion, probiotic microcapsules can effectively regulate intestinal flora, improving milk production, and quality in dairy cows.

Abstract The fuel injection performance and spray characteristics of the high‐pressure common rail (HPCR) system at low temperatures are investigated with experiment. The effects of environmental temperature, common rail pressure, and fuel injection pulse width on the injection quantity and spray characteristics are discussed. The fuel injection quantity at −30°C decreases by about 10% compared to the target fuel quantity. For the different target fuel quantity, the decrease of fuel injection quantity with temperature is the same under different rail pressures. The impact of temperature change on fuel injection quantity is relatively greater when the fuel injection pulse width is small. At the same common rail pressure and injector control pulse width, the injection quantity of −35# diesel is greater than that of −10# diesel for the same temperature condition. The low‐temperature fluidity can ensure normal diesel supply and injection in the fuel supply system. When the viscosity of diesel fuel rises and fluidity deteriorates in a low‐temperature environment, the spray beam produced by the same spray pressure becomes difficult to spread, and the spray penetration distance and cone angle decrease. The spray penetration distance differs by about 2.2 mm between the two temperatures. At low temperatures, the viscosity of diesel fuel rises and the fluidity deteriorates. The minimum injection pressure of the spray increases, and the spray angle is relatively small.

Abstract Background Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. Methods We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. Results This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. Conclusion Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

In agricultural ecosystems, incorporation of crop residues has been practiced as a recycling approach for sustaining soil organic matter (SOM) and soil fertility. However, how crop residue amendments in different forms (direct straw return, converted as manure and pyrolyzed as biochar) affect soil organic carbon (SOC) pools and SOM composition is not well known. In this study, a short-term (2015–2019) field experiment in paddy soil was conducted with a one-time maize residue amendment, consistently in a single doses of 10 Mg ha−1 organic carbon (OC) equivalent, in three forms: air-dried straw (CS), cattle manure (CM) and biochar (CB). No residue amendment (CK) was used as control. Topsoil organic matter changes were analysed using 13C isotopic tracing, biomarker analysis, and solid-state 13C nuclear magnetic resonance spectroscopy in combination with soil aggregate density/size fractionation. After four cropping cycles following amendment, SOC content was unchanged under CS and CM but increased by 24% under CB; However, the OC pool ratio of particulate organic matter (POM) to mineral-associated organic matter (MAOM) significantly increased under all amendments compared to CK. The δ13C values indicated that maize-derived OC was preserved the most in the POM within the macroaggregates, particularly under CB. Regarding the molecular composition, all residue amendments increased the abundance ratio of plant- to microbe-derived lipids. Plant-derived lipids were primarily concentrated in macroaggregates, whereas microbial lipids were more prevalent in the silt–clay fractions. Lignin phenols were significantly enriched only in microaggregates under CS relative to CK. Overall, SOM changes in the paddy topsoil following crop residue amendment in different forms were depicted by OC pool redistribution and molecular composition alteration. The study highlighted that biochar amendment, instead of straw or manure, greatly enhanced SOC accumulation by promoting macro-aggregation, which in turn preserved plant-derived carbon through the direct input of the persistent char in a rice paddy.

IntroductionWith the widespread use of social media, the behavior and mindset of users have been transformed, leading to a gradual increase in lurking users, which can impede the sustainable development of social media platforms. In this study, we aim to investigate the impact of intrinsic and extrinsic motivational factors on social media users’ anxiety, social media fatigue, and lurking behavior.MethodologyFor the confirmation of these phenomena and to validate the theories, a structural equation model was constructed based on the SSO (Stressor-Strain-Outcome) theoretical framework. The model was then tested and validated with data from 836 valid online surveys. These data were analyzed using SPSS 27.0 and AMOS 24.0 software.ResultsThe results indicate that intrinsic motivations (such as social comparison and privacy concerns) and extrinsic motivations (including information overload, functional overload, and social overload) are positively associated with users’ lurking behavior through the mediating effects of social media fatigue and anxiety. Additionally, for the mediator variables, social media fatigue was found to be positively associated with anxiety.DiscussionThese findings underscore the importance of social media platforms considering both intrinsic and extrinsic motivational factors to mitigate user anxiety and social media fatigue. By addressing these factors, platforms can foster user satisfaction and increase engagement, ultimately contributing to the sustainable development of social media platforms.

Reactive carbonyl and oxygen species (RCS/ROS), often generated as metabolic byproducts, particularly under conditions of pathology, can cause direct damage to proteins, lipids, and nucleic acids. Glyoxal oxidases (Gloxs) oxidize aldehydes to carboxylic acids, generating hydrogen peroxide (H2O2). Although best characterized for their roles in lignin degradation, Glox in plant fungal pathogens are known to contribute to virulence, however, the mechanism underlying such effects are unclear. Here, we show that Glox in the insect pathogenic fungus, Metarhizium acridum, is highly expressed in mycelia and during formation of infection structures (appressoria), with the enzyme localizing to the cell membrane. MaGlox targeted gene disruption mutants showed RCS and ROS accumulation, resulting in cell toxicity, induction of apoptosis and increased autophagy, inhibiting normal fungal growth and development. The ability of the MaGlox mutant to scavenge RCS was significantly reduced, and the mutant exhibited increased susceptibility to aldehydes, oxidative and cell wall perturbing agents but not toward osmotic stress, with altered cell wall contents. The ΔMaGlox mutant was impaired in its ability to penetrate the host cuticle and evade host immune defense resulting in attenuated pathogenicity. Overexpression of MaGlox promoted fungal growth and conidial germination, increased tolerance to H2O2, but had little to other phenotypic effects. Transcriptomic analyses revealed downregulation of genes related to cell wall synthesis, conidiation, stress tolerance, and host cuticle penetration in the ΔMaGlox mutant. These findings demonstrate that MaGlox-mediated scavenging of RCS is required for virulence, and contributes to normal fungal growth and development, stress resistance.

Environmental pollution has long been a global concern, and the development of fintech has led to radical changes in the financial industry, while finance plays a very important role in environmental governance. We use the number of fintech companies to create a city fintech index, and with the data of 827 listed companies in heavily polluting industries from 2011 to 2020, we study the impact of fintech development on enterprise environmental investment. We find that fintech can significantly increase the environmental investment of heavily polluting enterprises, while increasing the size of enterprise green bonds and improving the green cognition of executives are two important influence mechanisms. Heterogeneity analysis found that the impact of fintech on Southern enterprises and state-owned enterprises is more significant. Further analysis shows that fintech can significantly reduce the carbon emissions of heavily polluting enterprises and increase the number of green invention patents. The results of the study provide a useful reference for the government to promote the implementation of fintech policies and explore new ways to modernize pollution management.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that can participate in biological processes such as gene expression, growth, and development. However, little has been explored about the function of circRNAs in the development of Apis cerana larval guts. By using our previously gained deep sequencing data from the guts of A. cerana worker larvae at 4-, 5-, and 6-day-old (Ac4, Ac5, and Ac6 groups), the expression pattern and regulatory role of circular RNAs (circRNAs) during the development process was comprehensively investigated, with a focus on differentially expressed circRNAs (DEcircRNAs) relevant to immunity pathways and developmental signaling pathways, followed by validation of the binding relationships among a key competing endogenous RNA (ceRNA) axis. Here, 224 (158) DEcircRNAs were detected in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group. It’s suggested that 172 (123) parental genes of DEcircRNAs were involved in 26 (20) GO terms such as developmental process and metabolic process and 138 (136) KEGG pathways like Hippo and Wnt signaling pathways. Additionally, ceRNA network analysis indicated that 21 (11) DEcircRNAs could target seven (three) DEmiRNAs, further targeting 324 (198) DEmRNAs. These DEmRNAs can be annotated to 33 (26) GO terms and 168 (200) KEGG pathways, including 12 (16) cellular and humoral immune pathways (endocytosis, lysosome, Jak-STAT, etc.) and 10 (nine) developmental signaling pathways (Hippo, mTOR, Hedgehog, etc.). Interestingly, DEcircRNAs in these two comparison groups could target the same ace-miR-6001-y, forming complex sub-networks. The results of PCR and Sanger sequencing confirmed the back-splicing sites within four randomly selected DEcircRNAs. RT-qPCR detection of these four DEcircRNAs verified the reliability of the used transcriptome data. The results of dual-luciferase reporter assay verified the binding relationships between novel_circ_001627 and ace-miR-6001-y and between ace-miR-6001-y and apterous-like. Our data demonstrated that DEcircRNAs were likely to modulate the developmental process of the A. cerana worker larval guts via regulation of parental gene transcription and ceRNA network, and novel_circ_001627/ace-miR-6001-y/apterous-like was a potential regulatory axis in the larval gut development. Findings from this work offer a basis and a candidate ceRNA axis for illustrating the circRNA-modulated mechanisms underlying the A. cerana larval guts.

Background & Aims: Recent studies demonstrated the importance of fibrosis in promoting an immunosuppressive liver microenvironment and thereby aggressive hepatocellular carcinoma (HCC) growth and resistance to immune checkpoint blockade (ICB), particularly via monocyte-to-monocytic myeloid-derived suppressor cell (M-MDSC) differentiation triggered by hepatic stellate cells (HSCs). We thus aimed to identify druggable targets in these immunosuppressive myeloid cells for HCC therapy. Methods: M-MDSC signature genes were identified by integrated transcriptomic analysis of a human HSC-monocyte culture system and tumor-surrounding fibrotic livers of patients with HCC. Mechanistic and functional studies were conducted using in vitro-generated and patient-derived M-MDSCs. The therapeutic efficacy of a M-MDSC targeting approach was determined in fibrosis-associated HCC mouse models. Results: We uncovered over-expression of protein phosphatase 1 regulatory subunit 15A (PPP1R15A), a myeloid cell-enriched endoplasmic reticulum stress modulator, in human M-MDSCs that correlated with poor prognosis and ICB non-responsiveness in patients with HCC. Blocking TGF-β signaling reduced PPP1R15A expression in HSC-induced M-MDSCs, whereas treatment of monocytes by TGF-β upregulated PPP1R15A, which in turn promoted ARG1 and S100A8/9 expression in M-MDSCs and reduced T-cell proliferation. Consistently, lentiviral-mediated knockdown of Ppp1r15a in vivo significantly reduced ARG1+S100A8/9+ M-MDSCs in fibrotic liver, leading to elevated intratumoral IFN-γ+GZMB+CD8+ T cells and enhanced anti-tumor efficacy of ICB. Notably, pharmacological inhibition of PPP1R15A by Sephin1 reduced the immunosuppressive potential but increased the maturation status of fibrotic HCC patient-derived M-MDSCs. Conclusions: PPP1R15A+ M-MDSC cells are involved in immunosuppression in HCC development and represent a novel potential target for therapies. Impact and implications: Our cross-species analysis has identified PPP1R15A as a therapeutic target governing the anti-T-cell activities of fibrosis-associated M-MDSCs (monocytic myeloid-derived suppressor cells). The results from the preclinical models show that specific inhibition of PPP1R15A can break the immunosuppressive barrier to restrict hepatocellular carcinoma growth and enhance the efficacy of immune checkpoint blockade. PPP1R15A may also function as a prognostic and/or predictive biomarker in patients with hepatocellular carcinoma.

Abstract Aim Nurses play a crucial role within medical institutions, maintaining direct interaction with patient data. Despite this, there is a scarcity of tools for evaluating nurses' perspectives on patient information security. This study aimed to translate the Information Security Attitude Questionnaire into Chinese and validate its reliability and validity among clinical nurses. Design A cross‐sectional design. Methods A total of 728 clinical nurses from three hospitals in China participated in this study. The Information Security Attitude Questionnaire (ISA‐Q) was translated into Chinese utilizing the Brislin two‐way translation method. The reliability was assessed through internal consistency coefficient and test–retest reliability. The validity was determined through the Delphi expert consultation method and factor analysis. Results The Chinese version of ISA‐Q consists of 30 items. Cronbach's α coefficient of the questionnaire was 0.930, and Cronbach's α coefficient of the six dimensions ranged from 0.781 to 0.938. The split‐half reliability and test–retest reliability were 0.797 and 0.848, respectively. The content validity index (S‐CVI) was 0.962. Exploratory factor analysis revealed a 6‐factor structure supported by eigenvalues, total variance interpretation, and scree plots, accounting for a cumulative variance contribution rate of 69.436%. Confirmatory factor analysis further validated the 6‐factor structure, demonstrating an appropriate model fit. Conclusion The robust reliability and validity exhibited by the Chinese version of ISA‐Q establish it as a dependable tool for evaluating the information security attitudes of clinical nurses. Implications for Nursing Practice The Chinese iteration of the ISA‐Q questionnaire offers a profound insight into the information security attitudes held by clinical nurses. This understanding serves as a foundation for nursing managers to develop targeted intervention strategies aimed at fortifying nurses' information security attitudes, thereby enhancing patient safety.

BackgroundThis study aims to investigate the independent causal relation between height, screen time, physical activity, sleep and myopia.MethodsInstrumental variables (IVs) for exposures and outcome were obtained from the largest publicly available genome-wide association studies (GWAS) databases. First, we performed a bidirectional univariate MR analysis using primarily the inverse variance weighted method (IVW) with height, screen time, physical activity and sleep as the exposure and myopia as the outcome to investigate the causal relationship between exposures and myopia. Sensitivity analysis was used to demonstrate its robustness. Then the multivariable MR (MVMR) and MR-based mediation approach was further used to estimate the mediating effect of potential confounders (education and time outdoors) on causality.ResultsThe results of univariate MR analysis showed that taller height (OR = 1.009, 95% CI = 1.005–1.012, p = 3.71 × 10−7), longer time on computer (OR = 1.048, 95% CI = 1.029–1.047, p = 3.87 × 10−7) and less moderate physical activity (OR = 0.976, 95% CI = 0.96–0.991 p = 2.37 × 10−3) had a total effect on the increased risk of developing myopia. Meanwhile our results did not have sufficient evidence to support the causal relationship between chronotype (p = 0.637), sleep duration (p = 0.952) and myopia. After adjusting for education, only taller height remains an independent risk factor for myopia. After adjusting for education, the causal relationship between height, screen and myopia still had statistical significance. A reverse causal relationship was not found in our study. Most of the sensitivity analyses showed consistent results with those of the IVW method.ConclusionOur MR study revealed that genetically predicted taller height, longer time on computer, less moderate physical activity increased the risk of myopia. After full adjustment for confounders, only height remained independently associated with myopia. As a complement to observational studies, the results of our analysis provide strong evidence for the improvement of myopia risk factors and provide a theoretical basis for future measures to prevent and control myopia in adolescents.

PurposeTo construct and validate a computed tomography (CT) radiomics model for differentiating lung neuroendocrine neoplasm (LNEN) from lung adenocarcinoma (LADC) manifesting as a peripheral solid nodule (PSN) to aid in early clinical decision-making.MethodsA total of 445 patients with pathologically confirmed LNEN and LADC from June 2016 to July 2023 were retrospectively included from five medical centers. Those patients were split into the training set (n = 316; 158 LNEN) and external test set (n = 129; 43 LNEN), the former including the cross-validation (CV) training set and CV test set using ten-fold CV. The support vector machine (SVM) classifier was used to develop the semantic, radiomics and merged models. The diagnostic performances were evaluated by the area under the receiver operating characteristic curve (AUC) and compared by Delong test. Preoperative neuron-specific enolase (NSE) levels were collected as a clinical predictor.ResultsIn the training set, the AUCs of the radiomics model (0.878 [95% CI: 0.836, 0.915]) and merged model (0.884 [95% CI: 0.844, 0.919]) significantly outperformed the semantic model (0.718 [95% CI: 0.663, 0.769], p both

ABSTRACT This study aimed to assess the in vitro efficacy of ceftazidime-avibactam (CZA) in combination with various antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae (CRKP). We selected 59 clinical CRKP isolates containing distinct drug resistance mechanisms. The minimum inhibitory concentrations (MICs) of meropenem (MEM), colistin (COL), eravacycline (ERA), amikacin (AK), fosfomycin (FOS), and aztreonam (ATM), both individually and in combination with CZA, were tested using the checkerboard method. The interactions of antimicrobial agent combinations were assessed by fractional inhibitory concentration index (FICI) and susceptible breakpoint index (SBPI). The time-kill curve assay was employed to dynamically evaluate the effects of these drugs alone and in combination format. In the checkerboard assay, the combination of CZA+MEM showed the highest level of synergistic effect against both KPC-producing and carbapenemase-non-producing isolates, with synergy rates of 91.3% and 100%, respectively. Following closely was the combination of FOS+CZA . For metallo-beta-lactamases (MBLs) producing strains, ATM+CZA displayed complete synergy, while the combination of MEM+CZA showed a synergy rate of only 57.14% for NDM-producing strains and 91.67% for IMP-producing strains. In the time-kill assay, MEM+CZA also demonstrated significant synergistic effects against the two KPC-2-producing isolates (Y070 and L70), the two carbapenemase-non-producing isolates (Y083 and L093), and the NDM-1-producing strain L13, with reductions in log10 CFU/mL exceeding 10 compared to the control. Against the IMP-producing strain Y047, ATM+CZA exhibited the highest synergistic effect, resulting in a log10 CFU/mL reduction of 10.43 compared to the control. The combination of CZA and MEM exhibited good synergistic effects against KPC-producing and non-enzyme-producing strains, followed by the FOS+CZA combination. Among MBL-producing strains, ATM+CZA demonstrated the most pronounced synergistic effect. However, the combinations of CZA with ERA, AK, and COL show irrelevant effects against the tested clinical isolates.IMPORTANCEOur study confirmed the efficacy of the combination CZA+MEM against KPC-producing and non-carbapenemase-producing strains. For metalloenzyme-producing strains, CZA+ATM demonstrated the most significant synergy. Additionally, CZA exhibited a notable synergy effect when combined with FOS. These combination therapies present promising new options for the treatment of CRKP infection.

Members of bZIP gene family play crucial roles in various biological processes, including plant growth and development, stress response, and light signal transduction. Despite their significance, there is limited information on the function of the bZIP gene family in peanuts. In this investigation, we identified a total of 99 bZIP gene family members in the peanut genome, distributed across 20 chromosomes. Phylogenetic tree analysis categorized the peanut bZIP gene family into 10 groups, with groups I, D, A and S being the most widely distributed. Transcriptome analysis of peanut pods revealed that 10 bZIP family genes exhibited significant induction in response to light, suggesting their potential involvement in light signal transduction in peanuts. Within the peanut bZIP family, group H comprises six genes AhbZIP13, AhbZIP63, AhbZIP39, AhbZIP44, AhbZIP91 and AhbZIP96. Particularly, the expression of the AhbZIP63 (AhHYH) gene significantly increased under light induction, indicating a pivotal role in light signal transduction. DAP-seq analysis of AhbZIP63 (AhHYH) demonstrated its direct regulation of genes associated with UV response and cellular response to nutrient levels.

Abstract Background Elabela, a recently discovered hormonal peptide containing 32 amino acids, is a ligand for the apelin receptor. It can lower blood pressure and attenuate renal fibrosis. However, the clinicopathological relationship between Elabela level and renal damage caused by benign hypertension (BHT) and malignant hypertension (MHT) has not been elucidated. Therefore, we investigated the clinicopathological correlation between serum Elabela level and renal damage caused by BHT and MHT. Methods The participants comprised 50 patients and 25 age-matched healthy adults. The 50 patients were separated into two groups: MHT (n = 25) and BHT groups (n = 25). We analyzed their medical histories, demographics, and clinical examinations, including physical and laboratory tests. Results The results showed that serum Elabela level decreased gradually with a continuous increase in blood pressure from the healthy control group, BHT, to MHT. Moreover, Elabela levels negatively correlated with BMI (R = − 0.27, P = 0.02), SBP (r = − 0.64, P

Highlights The reaction mechanisms of hydrogen evolution reaction (HER) on various crystal surfaces of zinc anode have been systematically investigated by first-principle calculations. Both the thermodynamic and kinetic aspects of HER have been studied to reveal the relative HER activity of several crystal surface of zinc anode. The generalized coordination number of surface Zn atoms are proposed as a key descriptor of HER activity of Zn anode.

Abstract Background Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer, with a high mortality rate and poor prognosis. Mutated or dysregulated transcription factors (TFs) are significantly associated with carcinogenesis. The aim of this study was to develop a TF-related prognostic risk model to predict the prognosis and guide the treatment of HCC patients. Methods RNA sequencing data were obtained from the TCGA database. The ICGC and GEO databases were used as validation datasets. The consensus clustering algorithm was used to classify the molecular subtypes of TFs. Kaplan‒Meier survival analysis and receiver operating characteristic (ROC) analysis were applied to evaluate the prognostic value of the model. The immunogenic landscape differences of molecular subtypes were evaluated by the TIMER and xCell algorithms. Autodock analysis was used to predict possible binding sites of trametinib to TFs. RT‒PCR was used to verify the effect of trametinib on the expression of core TFs. Results According to the differential expression of TFs, HCC samples were divided into two clusters (C1 and C2). The survival time, signaling pathways, abundance of immune cell infiltration and responses to chemotherapy and immunotherapy were significantly different between C1 and C2. Nine TFs with potential prognostic value, including HMGB2, ESR1, HMGA1, MYBL2, TCF19, E2F1, FOXM1, CENPA and ZIC2, were identified by Cox regression analysis. HCC patients in the high-risk group had a poor prognosis compared with those in the low-risk group (p

The gas pipeline network constitutes a critical component of urban infrastructure. Emergencies, such as leaks or explosions, can lead to severe casualties, extensive property damage, and long-lasting effects on societal and environmental safety. The genesis of such emergencies typically involves a complex interplay among various risk factors. Therefore, the meticulous identification of these risk factors and the effective modeling of their interrelations are crucial for assessing the risks associated with such emergencies and enhancing urban safety. In this research, we initially developed a specialized dataset tailored specifically to analyze emergencies within gas pipeline networks. Recognizing the significance of unstructured domain-specific knowledge, we introduced an innovative approach Fusing expert knowledge and pre-trained model. This approach facilitates the fusion of domain experts’ knowledge into the process of risk factor identification and extraction in different steps, ensuring a thorough and precise determination and filtration of risk factors. Subsequently, a network depicting the associations between risk factors was established, drawing on their co-occurrence relationships, followed by a quantitative analysis of this network. Supported by real-world gas network management and emergency cause investigations, the methods proposed in this study provide strong support for gas network safety management and emergency decision-making.

Abstract Background The lateral profile is an important indicator of facial attractiveness. This study explored the general characteristics of the forehead profile and protrusion, and their relationship with related factors in structure and development. Methods Four hundred fourteen Chinese participants in the Yangtze River Delta region were involved. Including 206 males (17.15 ± 7.68 years old) and 208 females (18.35 ± 8.06 years old); 94 children (8.54 ± 2.21 years old, ranging from 4 to 12 years old), 166 adolescents (14.83 ± 1.50 years old, ranging from 13 to 17 years old), and 154 adults (25.52 ± 4.89, 18 years or older). The frontal section of the forehead was used to explore its shape. The straight distance between the vertical line of the FH plane through the nasal root point and its parallel line, which is tangential to the forehead, indicates the forehead prominence. Frontal sinus width was measured using the method described by Mahmood. Results The general shape of the forehead was straight and slightly bulged near the eyebrow arch in males but rounder in females. The average forehead protrusion in males was higher than that in females in adults. Significant differences in forehead protrusion between the dentoskeletal classifications and growth phases were notable. Frontal protrusion significantly correlated with frontal sinus depth, especially in males, adults, Class I, and those whose convex points were located in the lower section of the forehead. Conclusions Age, race, and sex affect the forehead protrusion and frontal sinus width. Forehead protrusion may be an indicator of dentoskeletal deformities in the early stage. And dentoskeletal deformities may impair the correlation between the frontal sinuses and forehead protrusion during development. Trial registration This retrospective, cross-sectional study was reviewed and approved by the Research Ethical Committee (T2020008), and registered at ClinicalTrial.gov with an identified number (ChiCTR2100041913).

We propose a cost-effective and memory-aware end-to-end learning scheme utilizing bi-directional gated recurrent unit (bi-GRU) for geometric constellation shaping (GCS) under the first-order regular perturbation (FRP) auxiliary channel. The performance of the proposed system has been numerically verified at a 32 GBd 5-channel wavelength division multiplexing (WDM) 64 quadrature amplitude modulation (QAM) 800 km optical coherent communication system. Results show that the proposed bi-GRU based GCS scheme can achieve a performance gain over square 64QAM in mutual information (MI) with 0.12 bits/symbol and a Q-factor gain of 0.4 dB at optimal launched optical power. When transmission distance is extended to 1280 km, a generalized mutual information (GMI) gain of 0.136 bits/symbol is observed. Additionally, compared with the bi-directional long short-term memory (bi-LSTM) based GCS, the proposed bi-GRU scheme has lower computation complexity with similar system performance.

Abstract N‐glycosylation has important implications for the physicochemical properties and biochemical activity of breast milk proteins. However, an in‐depth characterization of site‐specific N‐glycans in breast milk serum proteins is lacking. In this study, 875 site‐specific N‐glycans attached to 114 serum glycoproteins from breast colostrum (BC) and 427 site‐specific N‐glycans attached to 60 serum glycoproteins from breast mature milk (BM) were identified and quantified using label‐free site‐specific glycoproteomics. Among them, 24 site‐specific N‐glycans mapping to 11 N‐glycosites on 9 glycoproteins were significantly increased, and 76 site‐specific N‐glycans mapping to 19 N‐glycosites on 13 glycoproteins were significantly decreased. Gene ontology annotation analysis showed that BC and BM serum N‐glycoproteins were mainly enriched in complement activation, classical pathway, extracellular exosome part, and immunoglobulin receptor binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that BC and BM serum N‐glycoproteins were mainly involved in the PI3K‐Akt signaling pathway. Additionally, breast milk serum N‐glycoproteins carried fucosylated core structures as well as Lewis and sialylated branch structures that may contribute to neonatal retinal homeostasis. These results provide a molecular basis for understanding the unique biological activities of breast milk serum N‐glycoproteins.

To address the problem of difficult performance assessment of train control on-board system after recovery from failures, we have proposed a resilience assessment methodology that uses reliability as an indicator of system resilience. Since the system failures are time-dependent, we adopted the Discrete Time Bayesian Network method to obtain the system's reliability before and after failure. Subsequently, we used an exponential recovery model to quantify the system's performance curve during the recovery phase, and finally utilized the resilient triangle area method to quantify its resilience size. Analyzing the CTCS3-300T train control on-board system, we found that the resilience of the system with cold standby redundancy design and hot standby redundancy design were 89.44 % and 87.34 %, respectively, indicating a slight decrease in system performance after recovery from failures compared to pre-failure levels. At that time, it was necessary to adjust operational plans based on actual conditions to avoid greater impact on the railway network. This paper realizes performance resilience of train control on-board system after failure recovery, which can be applied to similar systems and provide theoretical references for realizing intelligent maintenance of the high-speed train.

Objectives: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC. Methods: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0. Results: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate. Conclusions: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

This paper aims to accurately assess and effectively manage various security risks in the community and overcome the challenges faced by traditional models in handling large amounts of features and high-dimensional data. Hence, this paper utilizes the back propagation neural network (BPNN) to optimize the security risk assessment model. A key challenge of researching community security risk assessment lies in accurately identifying and predicting a range of potential security threats. These threats may encompass natural disasters, public health crises, accidents, and social security issues. The intricate interplay of these risk factors, combined with the dynamic nature of community environments, presents difficulties for traditional risk assessment methodologies to address effectively. Initially, this paper delves into the factors influencing safety incidents within communities and establishes a comprehensive system of safety risk assessment indicators. Leveraging the adaptable and generalizable nature of the BPNN model, the paper proceeds to optimize the BPNN model, enhancing the security risk assessment model through this optimization. Subsequent comparison experiments with traditional models validate the rationality and effectiveness of the proposed model, with hidden layer nodes set at various levels like 10, 15, 20, 25, 30, and 35. These traditional models include Convolutional Neural Network (CNN), Long Short-Term Memory Network (LSTM), Bidirectional Encoder Representations from Transformers (BERT), Generative Pre-trained Transformer (GPT), and eXtreme Gradient Boosting (XGBOOST). Experimental findings demonstrate that with 20 hidden layer nodes, the optimized model achieves a remarkable final recognition accuracy of 99.1 %. Moreover, the optimized model exhibits significantly lower final function loss compared to models with different node numbers. Increasing the number of hidden layer nodes may diminish the optimized model's fit and accuracy. Comparison with traditional models reveals that the average accuracy of the optimized model in community risk identification reaches 98.5 %, with a maximum accuracy of 99.6 %. This marks an improvement of 9%–11 % in recognition accuracy across various risk factors compared to traditional models. Regarding system response time and resource utilization, the optimized model exhibits a response time ranging from 100 ms to 120 ms and consistently lower resource utilization rates across all scenarios, underscoring its efficiency in community security risk assessment. In conclusion, this experiment sheds light on the underlying mechanisms and patterns of community safety risk formation, offering novel perspectives and methodologies for researching community safety risk assessment. The paper concludes by presenting recommendations and strategies for addressing community safety risks based on experimental analysis.

Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.

The active thickness of the translational landslides plays a pivotal role in evaluating its hazards and simulating its instability. Existing techniques have difficulties in estimating the accurate active thickness due to the limitations of observation conditions and imaging geometry, leading to deviations in failure simulations. To overcome these challenges, this study proposes an enhanced method that utilizes multi-orbit Interferometric Synthetic Aperture Radar (InSAR) observations to estimate the active thickness of the translational landslides and subsequently conduct more accurate instability simulations. The method involves integrating multi-orbit InSAR imaging parameters with the spatial geometry of the landslide to establish a slope coordinate system. This system enables the projection of one-dimensional InSAR Line Of Sight (LOS) displacements onto the three-dimensional displacements of the landslide. Subsequently, the active thickness is estimated by combining InSAR three-dimensional displacements with the mass conservation method. Finally, the estimated thickness is incorporated into the geological model construction to simulate the dynamic movement of the landslide. The method was applied to the Xiongba translational landslide in Gongga County, Tibet Autonomous Region, China. The results show that the deformation is mainly concentrated at its forefront, with maximum three-dimensional deformation rates of 4.7 m/a, 2.3 m/a, and 1.24 m/a. The landslide encompasses an estimated area of around 5.33 square kilometers, and its active thickness varies from 0 to 106.59 m. The maximum displacement distance reaches 1469.76 m, with a peak velocity of 60.37 m/s. The proposed method provides scientific support for assessing, analyzing, and preventing landslide disasters.

BackgroundStrengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China.MethodsA community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled.ResultsThe results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p

AimsThe high salinity of soil, nutrient scarcity, and poor aggregate structure limit the exploitation and utilization of coastal mudflat resources and the sustainable development of saline soil agriculture. In this paper, the effects of applying exogenous organic acids combined with biological substrate on the composition and diversity of soil bacterial community were studied in moderately saline mudflats in Jiangsu Province.MethodsA combination of three exogenous organic acids (humic acid, fulvic acid, and citric acid) and four biological substrates (cottonseed hull, cow manure, grass charcoal, and pine needle) was set up set up on a coastal saline mudflat planted with a salt-tolerant forage grass, sweet sorghum. A total of 120 kg ha−1 of organic acids and 5,000 kg ha−1 of substrates were used, plus two treatments, CK without application of organic acids and substrates and CK0 in bare ground, for a total of 14 treatments.ResultsNo significant difference was found in the alpha diversity of soil bacterial community among all treatments (p ≥ 0.05), with the fulvic acid composite pine needle (FPN) treatment showing the largest increase in each index. The beta diversity differed significantly (p

Peripheral nerve injury disease is a prevalent traumatic condition in current medical practice. Despite the present treatment approaches, encompassing surgical sutures, autologous nerve or allograft nerve transplantation, tissue engineering techniques, and others, an effective clinical treatment method still needs to be discovered. Exploring novel treatment methods to improve peripheral nerve regeneration requires more effort in investigating the cellular and molecular mechanisms involved. Many factors are associated with the regeneration of injured peripheral nerves, including the cross-sectional area of the injured nerve, the length of the nerve gap defect, and various cellular and molecular factors such as Schwann cells, inflammation factors, kinases, and growth factors. As crucial mediators of cellular communication, kinases exert regulatory control over numerous signaling cascades, thereby participating in various vital biological processes, including peripheral nerve regeneration after nerve injury. In this review, we examined diverse kinase classifications, distinct nerve injury types, and the intricate mechanisms involved in peripheral nerve regeneration. Then we stressed the significance of kinases in regulating autophagy, inflammatory response, apoptosis, cell cycle, oxidative processes, and other aspects in establishing conductive microenvironments for nerve tissue regeneration. Finally, we briefly discussed the functional roles of kinases in different types of cells involved in peripheral nerve regeneration.

In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis-infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem–loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA–gene axis for further investigation.

This study utilizes the Weather Research and Forecasting (WRF) to comparatively analyze the impact of three vertical grid resolution (VGR) enhancement schemes on the simulation of super typhoon Lekima under two different horizontal resolutions. The relationship between structural changes and typhoon intensity is explored from the perspective of the simulated three-dimensional thermodynamic and dynamic structure of the typhoon. The main conclusions obtained are as follows: Typhoon track simulation is not sensitive to the setting of VGR, while intensity simulation is greatly affected by it. Increasing VGR in the lower layer can enhance the simulated intensity of the typhoon, but when VGR enhancement is made in the middle layer, the simulated typhoon intensity decreases. For VGR enhancement in the upper levels, it is only when coupled with a simultaneous increase in horizontal resolution that the simulated typhoon intensity is enhanced. Different VGR enhancement schemes result in significant differences in the simulated thermodynamic and dynamic structures of the typhoon, which is a crucial factor causing variations in simulated typhoon intensity. In terms of dynamics, increasing VGR in the lower layer reduces the hydrostatic stability of the lower troposphere, which enhances convection and improves its symmetry. This leads to strengthened inflow and outflow activities of the typhoon, resulting in a stronger simulated typhoon with a tighter and straighter eyewall. In terms of thermal structure, increasing VGR in both the lower and upper levels enhances the warm core of the typhoon, thereby increasing its simulated intensity. However, the warm core simulated with upper layer enhancement extends to a higher altitude. This may be related to two different heating mechanisms, where lower layer VGR enhancement has a more pronounced effect on changes in boundary layer latent heat flux, while upper layer VGR enhancement promotes more sinking of high-entropy air from higher levels.

Abstract Ferroptosis is a recently discovered form of regulated cell death characterized by its distinct dependence on iron and the peroxidation of lipids within cellular membranes. Ferroptosis plays a crucial role in physiological and pathological situations and has attracted the attention of numerous scientists. Ferroptosis suppressive protein 1 (FSP1) is one of the main regulators that negatively regulates ferroptosis through the GPX4‐independent FSP1–CoQ10–NAD(P)H axis and is a potential therapeutic target for ferroptosis‐related diseases. However, the crystal structure of FSP1 has not been resolved, which hinders the development of therapeutic strategies targeting FSP1. To unravel this puzzle, we purified the human FSP1 (hFSP1) protein using the baculovirus eukaryotic cell expression system and solved its crystal structure at a resolution of 1.75 Å. Furthermore, we evaluated the oxidoreductase activity of hFSP1 with NADH as the substrate and identified E156 as the key amino acid in maintaining hFSP1 activity. Interestingly, our results indicated that hFSP1 exists and functions in a monomeric state. Mutagenesis analysis revealed the critical role of the C‐terminal domain in the binding of substrate. These findings significantly enhance our understanding of the functional mechanism of FSP1 and provide a precise model for further drug development.

Introduction: Depression is a complex psychiatric disorder with substantial societal impact. While current antidepressants offer moderate efficacy, their adverse effects and limited understanding of depression’s pathophysiology hinder the development of more effective treatments. Amidst this complexity, the role of neuroinflammation, a recognized but poorly understood associate of depression, has gained increasing attention. This study investigates hydroxytyrosol (HT), an olive-derived phenolic antioxidant, for its antidepressant and anti-neuroinflammatory properties based on mitochondrial protection.Methods:In vitro studies on neuronal injury models, the protective effect of HT on mitochondrial ultrastructure from inflammatory damage was investigated in combination with high-resolution imaging of mitochondrial substructures. In animal models, depressive-like behaviors of chronic restraint stress (CRS) mice and chronic unpredictable mild stress (CUMS) rats were examined to investigate the alleviating effects of HT. Targeted metabolomics and RNA-Seq in CUMS rats were used to analyze the potential antidepressant pathways of HT.Results: HT protected mitochondrial ultrastructure from inflammatory damage, thus exerting neuroprotective effects in neuronal injury models. Moreover, HT reduced depressive-like behaviors in mice and rats exposed to CRS and CUMS, respectively. HT’s influence in the CRS model included alleviating hippocampal neuronal damage and modulating cytokine production, mitochondrial dysfunction, and brain-derived neurotrophic factor (BDNF) signaling. Targeted metabolomics in CUMS rats revealed HT’s effect on neurotransmitter levels and tryptophan-kynurenine metabolism. RNA-Seq data underscored HT’s antidepressant mechanism through the BDNF/TrkB signaling pathways, key in nerve fiber functions, myelin formation, microglial differentiation, and neural regeneration.Discussion: The findings underscore HT’s potential as an anti-neuroinflammatory treatment for depression, shedding light on its antidepressant effects and its relevance in nutritional psychiatry. Further investigations are warranted to comprehensively delineate its mechanisms and optimize its clinical application in depression treatment.

The modularity of carbohydrate-active enzymes facilitates that enzymes with different functions have similar fragments. However, because of the complex structure of the enzyme active sites and the epistatic effects of various mutations on enzyme activity, it is difficult to design enzymes with multiple mutation sites using conventional methods. In this study, we designed multi-point mutants by fragment replacement in the donor-acceptor binding pocket of Actinobacillus pleuropneumoniae N-glycosyltransferase (ApNGT) to obtain novel properties. Candidate fragments were selected from a customized glycosyltransferase database. The stability and substrate-binding energy of the three fragment replacement mutants were calculated in comparison with wild-type ApNGT, and mutants with top-ranking stability and middle-ranking substrate-binding energy were chosen for priority experimental verification. We found that a mutant called F13, which increased the glycosylation efficiency of the natural substrate by 1.44 times, the relative conversion of UDP-galactose by 14.2 times, and the relative conversion of UDP-xylose from almost 0 to 78.6%. Most importantly, F13 mutant acquired an entirely new property, the ability to utilize UDP-glucuronic acid. On one hand, this work shows that replacing similar fragments in the donor-acceptor binding pocket of the enzyme might provide new ideas for designing mutants with new properties; on the other hand, F13 mutant is expected to play an important role in targeted drug delivery.

Abstract CRISPR based technologies have been used for fast and sensitive detection of pathogens. To test the possibility of CRISPR based detection strategy in Pseudomonas aeruginosa infections, a combined method of recombinase polymerase amplification followed by Cas12a-mediated detection via fluorescence reader or lateral flow biosensor (named Cas12a-RCFL) has been established in this study. The Cas12a-RCFL can detect as low as 50 CFU/mL Pseudomonas aeruginosa. The whole detection process can be finished within one hour with satisfied detection specificity. Cas12a-RCFL also shows good sensitivity of detecting Pseudomonas aeruginosa inStaphylococcus aureus and Acinetobacter baumannii contaminated samples. For the detection of 22 clinical samples, Cas12a-RCFL matches with PCR sequencing result exactly without DNA purification. This Cas12a-RCFL is rapid and sensitive with low cost, which shows good quality to be adopted as a point-of-care testing method.

Abstract Background Myopia has recently emerged as a significant threat to global public health. The high and pathological myopia in children and adolescents could result in irreversible damage to eye tissues and severe impairment of visual function without timely control. Posterior scleral reinforcement (PSR) can effectively control the progression of high myopia by limiting posterior scleral expansion, improving retrobulbar vascular perfusion, thereby stabilizing the axial length and refraction of the eye. Moreover, orthokeratology and low concentrations of atropine are also effective in slowing myopia progression. Case presentation A female child was diagnosed with binocular congenital myopia and amblyopia at the age of 3 and the patient’s vision had never been rectified with spectacles at the first consultation. The patient’s ophthalmological findings suggested, high refractive error with low best corrected visual acuity, longer axial length beyond the standard level of her age, and fundus examination suggesting posterior scleral staphyloma with weakened hemodynamics of the posterior ciliary artery. Thereby, PSR was performed to improve fundus health and the combination of orthokeratology and 0.01% atropine were performed to control the development of myopia. Following up to 8 years of clinical treatment and observations, the progression of myopia could be well controlled and fundus health was stable. Conclusion In this report, 8-year of clinical observation indicated that PSR could improve choroidal thickness and hemodynamic parameters of the retrobulbar vessels, postoperative orthokeratology combined with 0.01% atropine treatment strategy may be a good choice for myopia control effectively.