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This study examines the hot deformation behavior of Mo-14Re alloy at various true strains (15%, 35%, 65%) and strain rates (0.01 s−1, 10 s−1) at a temperature of 1400K. The findings indicate that dynamic recovery (DRV) and dynamic recrystallization (DRX) occur concomitantly as strain increases at a low strain rate of 0.01 s−1, with DRV being the predominant softening mechanism. At a strain of 65%, DRX emerges as the primary softening process. Conversely, under high strain rates of 10 s−1, DRX is inhibited, and the Mo-14Re alloy experiences work hardening due to an increase in dislocation density. Microscopic analysis shows that the high-density dislocations facilitate the continued nucleation and growth of recrystallized grains at low strain rates. At high strain rates, tangled dislocations hinder dislocation motion and recrystallization. Regarding texture evolution, stronger {100}//CD and weaker {111}//CD fiber texture is observed at low strain rates of 0.01 s−1, while stronger {111}//CD and weaker {100}//CD fiber texture forms at high strain rates of 10 s−1, with enhanced texture intensity. Mechanistic analysis confirms the activation of the {110}, {112}, and {123} dislocation slip systems at elevated temperatures, with the {123} system being the most dominant.

Abstract Background Malaria-associated acute lung injury/acute respiratory distress syndrome (MA-ALI/ARDS) is a fatal complication of Plasmodium falciparum infection that is partially triggered by macrophage recruitment and polarization. As reported, copper exposure increases the risk of malaria infection, and copper accumulation-induced cuproptosis triggers M1 macrophage polarization. It is thus hypothesized that cuproptosis could act as a critical mediator in the pathogenesis of MA-ALI/ARDS, but its underlying mechanism remains unclear. The present study aimed to explore the role of cuproptosis in the severity of murine MA-ALI/ARDS. Methods We utilized an experimental model of MA-ALI/ARDS using female C57BL/6 mice with P. berghei ANKA infection, and treated these animals with the potent copper ion carrier disulfiram (DSF) or copper ion chelator tetrathiomolybdate (TTM). The RAW 264.7 macrophages, which were stimulated with infected red blood cells (iRBCs) in vitro, were also targeted with DSF-CuCl2 or TTM-CuCl2 to further investigate the underlying mechanism. Results Our findings showed a dramatic elevation in the amount of copper and the expression of SLC31A1 (a copper influx transporter) and FDX1 (a key positive regulator of cuproptosis) but displayed a notable reduction in the expression of ATP7A (a copper efflux transporter) in the lung tissue of experimental MA-ALI/ARDS mice. Compared to the P. berghei ANKA-infected control group, mice that were administered DSF exhibited a remarkable increase in parasitemia/lung parasite burden, total protein concentrations in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio, vascular leakage, and pathological changes in lung tissue. Strikingly, the experimental MA-ALI/ARDS mice with DSF treatment also demonstrated dramatically elevated copper levels, expression of SLC31A1 and FDX1, numbers of CD86+, CD68+, SLC31A1+-CD68+, and FDX1+-CD68+ macrophages, and messenger RNA (mRNA) levels of pro-inflammatory cytokines (tumor necrosis factor [TNF-α] and inducible nitric oxide synthase [iNOS]) in lung tissue, but showed a remarkable decrease in body weight, survival time, expression of ATP7A, number of CD206+ macrophages, and mRNA levels of anti-inflammatory cytokines (transforming growth factor beta [TGF-β] and interleukin 10 [IL-10]). In contrast, TTM treatment reversed these changes in the infected mice. Similarly, the in vitro experiment showed a notable elevation in the mRNA levels of SLC31A1, FDX1, CD86, TNF-α, and iNOS in iRBC-stimulated RAW 264.7 cells targeted with DSF-CuCl2, but triggered a remarkable decline in the mRNA levels of ATP7A, CD206, TGF-β, and IL-10. In contrast, TTM-CuCl2 treatment also reversed these trends in the iRBC-stimulated RAW 264.7 cells. Conclusions Our data demonstrate that the activation of cuproptosis with DSF aggravated the severity of MA-ALI/ARDS by partially inducing M1 polarization of pulmonary macrophages, while inhibition of cuproptosis with TTM contrarily ameliorated the severity of MA-ALI/ARDS by promoting macrophage M2 polarization. Our findings suggest that blockage of cuproptosis could be a potential therapeutic strategy for treatment of MA-ALI/ARDS. Graphical Abstract

Abstract The Chinese mitten crab (Eriocheir sinensis) holds significant importance as a popular aquaculture food source; however, there are concerns about its potential contamination with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) from both food and aquatic environment. To assess the associated health risks and identify potential sources of contamination in crabs, a comprehensive investigation was conducted, including a total of 70 samples from the crab food web. The results demonstrated that crabs predominantly exhibited elevated concentrations of PCBs and dl-PCBs, with mean concentrations of 12 207 ± 11 962 pg g-1 and 554 ± 203 pg g-1, respectively, while PCDD/Fs concentrations were comparatively lower at 20 ± 17 pg g-1. The accumulation of PCBs in crabs significantly surpassed that of PCDD/Fs. The material balance of PCDD/Fs and PCBs in the crab food web was estimated, indicating that sediments and feeds likely constitute the two primary sources of PCDD/Fs and PCBs in crabs. The monthly intake of PCDD/Fs and PCBs through crab consumption accounted for 30% of the dietary intake, which was well below the provisional tolerable monthly intake (PTMI) limit. The weekly intake of PCDD/Fs and PCBs for adults consuming one crab (100 g) does not pose health risks and the recommended weekly intake of white crabmeat and brown crabmeat is 443 g and 21 g, respectively.

Abstract Background We aimed to characterize the associations between physical activity levels and the risk of developing age-related diseases in the Coronary Artery Risk Development in Young Adults (CARDIA) study and used Mendelian randomization (MR) to assess whether there are causal relationships between physical activity levels and the risk of developing 8 age-related diseases (coronary atherosclerosis, ischemic heart disease, angina, Alzheimer’s disease, hypertension, type 2 diabetes, hyperlipidemia, and venous thromboembolism). Methods Based on the data available in the CARDIA, we obtained data related to five disease states: coronary heart disease, hypertension, diabetes, hyperlipidemia, and venous thromboembolism. Binary logistic regression analysis estimated the multivariable-adjusted associations between different physical activity statuses and diseases. For the MR study, we used summary-level data from a recently published genome-wide association study on physical activity (including vigorous physical activity and accelerometer-based physical activity) conducted with participants from the UK Biobank study. We selected the above 8 age-related diseases as our outcomes. Results In the CARDIA-based analysis, the risk of developing coronary heart disease [OR (95% CI): 0.562 (0.397–0.795)], hypertension [OR (95% CI): 0.703 (0.601–0.821)], diabetes [OR (95% CI): 0.783 (0.620–0.988)], and hyperlipidemia [OR (95% CI): 0.792 (0.662–0.949)] was negatively related to physical activity status when participants achieved the physical activity target. Our MR results support a negative causal association between genetically determined vigorous physical activity levels and the risk of developing 3 age-related diseases, namely, angina, hypertension and type 2 diabetes. Moreover, our results also support a negative causal association between genetically determined accelerometer-based physical activity levels and the risk of developing angina. Conclusions Promotion of physical activity is likely to prevent specific age-related diseases.

Abstract Background Insulin resistance and diabetes are associated with an increased risk of frailty, and frailty is associated with cardiovascular disease and premature mortality. We aim to investigate the impact of long‐term insulin resistance trajectories on future frailty and cardiovascular risk among young adults. Methods In total, 3168 participants with a 30‐year follow‐up period. The baseline period covered the first 15 years as the exposure period. Insulin resistance was determined using the homeostasis model assessment for insulin resistance (HOMA‐IR), and three trajectories (low, moderate, and high) were constructed. The subsequent 15 years constituted the event accrual period. Frailty was assessed using a deficit accumulation mode, and cardiovascular outcomes were obtained from the 15‐year event accrual period. Results The mean age of all 3168 participants was 41.0 (37.0–43.0) years, with 1750 (55.2%) being women. Participants in the high level of insulin resistance trajectory had an increased prevalence of frailty (OR: 1.55, 95% CI: 1.05–2.30, P = 0.028). Although no statistically significant associations were observed after full adjustment, single‐factor analysis indicated association between the moderate and high trajectories and frailty progression. Additionally, participants with high level of insulin resistance trajectory were associated with an increased risk of cardiovascular disease, coronary heart disease, and stroke. A notable correlation between HOMA‐IR trajectory and cardiovascular diseases was still discernible within the subgroup where the frailty index ≥0.12 (HR: 2.12, 95% CI: 1.17–3.83, P = 0.013) (P for interaction >0.05). Conclusions Long‐term high level of insulin resistance is associated with high prevalence of frailty, and an increased risk of cardiovascular events. Emphasizing the importance of early prevention and intervention for abnormal glucose metabolism in young adults to prevent frailty and cardiovascular disease.

Abstract Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction. Graphical Abstract

Abstract Having correct distribution network topology information is essential for system state estimation, line loss analysis, electricity theft detection and fault location. At present, with continuous deployment of smart sensors, a large amount of monitoring data is collected, which enables refined management for distribution network. A data‐driven low voltage (LV) distribution network topology identification method is proposed, which realises transformer‐customer pairing and customer phase identification for distribution network with relatively balanced power supplies. Firstly, an integrated similarity coefficient of voltage curve is proposed, which can reflect the neighbourhood relationship within stations while increase the distinction between stations; the K‐Nearest Neighbour (KNN) algorithm is used to propagate the service transformer labels to complete transformer‐customer association. Then, the influence of power fluctuation on voltage curve is analysed and a dynamic sliding window model is adopted to search for voltage segments with significantly difference among three phase feeders to formulate a voltage time series to identify customer phase. Finally, the results are corrected and verified based on the principle of network power balance. The proposed algorithm is tested in two different real substations in China and Europe and shows high accuracy and robustness especially in distribution network with relatively balanced power supplies.

N,N′-Substituted p-phenylenediamines (PPDs) are widely used as antioxidants in the rubber industry and are released into the environment in large quantities during the production and use of rubber products. We quantified PPDs and PPD quinone derivatives (PPD-Qs) in rubber consumer products, including car tires, rubber belts, rubber gloves, rubber cables, and rubber hoses, to obtain information on the degree of weathering over time during their use. Additionally, we investigated the occurrences and sources of PPDs and PPD-Qs in dust samples collected from four typical urban environments (roads, parking lots, automotive repair shops, and residences). The detected compounds included the highly toxic N-(1,3-dimethylbutyl)-N′-phenyl-1,4-phenylenediamine quinone, which can cause acute mortality of coho salmon (Oncorhynchus kisutch). Concentrations of PPDs in the automotive repair shops reached 56.0 μg/g, and were much higher than in the other environments, while the residential samples had the lowest contaminant concentrations. In road and residential samples, N,N′-di-2-naphthyl-p-phenylenediamine accounted for 17 %–30 % of the PPDs, and may have originated from different sources. We preliminarily identified 32 transformation products, and 11 of these were N,N′-di-2-naphthyl-p-phenylenediamine transformation products. The average daily intakes of PPDs and PPD-Qs were calculated to assess the health risks of dust exposure in each environment. Workers had high total intakes of PPD [60.3 ng/(kg day)] and PPD-Qs [20.1 ng/(kg day)], and were at some risk of occupational exposure. These results improve our understanding of the environmental occurrences, sources, transformation, and health risks of PPDs and PPD-Qs.

In the context of the modern dynamic socio-economic environment, career-related issues are becoming relevant to psychological and pedagogical sciences as it is professional development that enables people to realize their abilities, capabilities, and needs. Career orientation should be identified as early as possible in order to obtain significant achievements. An important issue is related to career orientation predictors, which determine future achievements and career choice. The study discusses conceptual provisions and methodological approaches to assessing the career orientations of college students with different levels of self-efficacy. The purpose of the research is to study theoretical and methodological approaches and aspects of the psychological assessment of self-efficacy as a personality predictor of the career orientations of college students. The study was conducted with the participation of a representative sample of 558 third-year students aged 18 to 20 on the campus of the Ural State College named after I. Polzunov (Ekaterinburg) (average age is 18.7 years). The practical significance of the study arises from the possibility to use the results obtained in order to implement programs aimed at improving self-efficacy in adolescents. The research is of practical value for organizational psychologists, educational psychologists, and teachers.

Abstract Podocytes are specialized terminally differentiated cells in the glomerulus that are the primary target cells in many glomerular diseases. However, the current podocyte cell lines suffer from prolonged in vitro differentiation and limited survival time, which impede research progress. Therefore, it is necessary to establish a cell line that exhibits superior performance and characteristics. We propose a simple protocol to obtain an immortalized mouse podocyte cell (MPC) line from suckling mouse kidneys. Primary podocytes were cultured in vitro and infected with the SV40 tsA58 gene to obtain immortalized MPCs. The podocytes were characterized using Western blotting and quantitative real-time PCR. Podocyte injury was examined using the Cell Counting Kit-8 assay and flow cytometry. First, we successfully isolated an MPC line and identified 39 °C as the optimal differentiation temperature. Compared to undifferentiated MPCs, the expression of WT1 and synaptopodin was upregulated in differentiated MPCs. Second, the MPCs ceased proliferating at a nonpermissive temperature after day 4, and podocyte-specific proteins were expressed normally after at least 15 passages. Finally, podocyte injury models were induced to simulate podocyte injury in vitro. In summary, we provide a simple and popularized protocol to establish a conditionally immortalized MPC, which is a powerful tool for the study of podocytes.

This study comprehensively investigates the impact of varying red-to-blue light ratios on the growth of Spanish lettuce. The research considers various factors such as growth morphology, photosynthetic parameters, and chlorophyll fluorescence. Lettuce was cultivated in an environment with a photosynthetic photon flux density (PPFD) of 200 ± 20 μmol/m2/s and a photoperiod of 16 h per day. The experiment incorporated eight distinct light treatment methodologies, with the red-to-blue light ratios ranging from 2:8 (R2B8) to 9:1 (R9B1). The data implies that during the initial 20 days of growth, groups exposed to a higher proportion of red light demonstrated superior growth. In particular, the R9B1 group exhibited the highest increase in plant height. The photosynthetic performance of leaves (net photosynthetic rate, stomatal conductance, and transpiration rate) showed a tendency to rise with a decreasing red-to-blue ratio within a particular range, peaking at R3B7. However, both the dry matter content and fresh weight were relatively lower under the R3B7 light quality ratio. The results indicate that cultivating lettuce under the R8B2 ratio led to optimal outcomes. This group significantly outperformed the other test groups in terms of weight and exhibited higher photosynthetic rates. Despite exhibiting lower stomatal conductance, this group reduced energy consumption and ultimately achieved the highest overall weight.

Abstract Background Medical consortiums have been extensively established to facilitate the integration of health resources and bridge the technical gap among member institutions. However, some commonly appropriate technologies remain stagnant in subordinate hospitals, although they have been routinely applied in leading hospitals. Besides, the mechanism underlying differences in clinicians’ adoption behavior at different levels of institutions was unknown. Therefore, this study aimed to investigate the differences in influencing mechanisms of clinicians’ hepatic contrast-enhanced ultrasound technology (CEUS) utilization behavior between leading and subordinate hospitals within medical consortiums, thus providing clues for expanding effective and appropriate technologies within integrated care systems. Methods A self-designed scale was developed based on the theory of planned behavior (TPB). A multistage sampling method was applied to investigate clinicians who were aware of CEUS and worked in liver disease-related departments within the sampled medical institutions. The final sample size was 289. AMOS 24.0 software was used to construct multi-group structural equation modeling (SEM) to validate the hypotheses and determine the mechanism of hepatic CEUS utilization. Results It revealed that behavioral intention significantly influenced adoption behavior, regardless of whether it was in leading hospitals or subordinate hospitals (β = 0.283, p

Abstract Rapeseed is a critical cash crop globally, and understanding its distribution can assist in refined agricultural management, ensuring a sustainable vegetable oil supply, and informing government decisions. China is the leading consumer and third-largest producer of rapeseed. However, there is a lack of widely available, long-term, and large-scale remotely sensed maps on rapeseed cultivation in China. Here this study utilizes multi-source data such as satellite images, GLDAS environmental variables, land cover maps, and terrain data to create the China annual rapeseed maps at 30 m spatial resolution from 2000 to 2022 (CARM30). Our product was validated using independent samples and showed average F1 scores of 0.869 and 0.971 for winter and spring rapeseed. The CARM30 has high spatial consistency with existing 10 m and 20 m rapeseed maps. Additionally, the CARM30-derived rapeseed planted area was significantly correlated with agricultural statistics (R2 = 0.65–0.86; p

Tibetan Plateau is one of the most typical areas of biodiversity in the world because of its unique environmental and regional units, which breed unique biological communities and concentrate on many unique and rare wild animals and plants. Research on Chironomidae in the Tibetan Plateau is relatively weak. At present, the identification of Chironomidae species mainly depends on male adults, while identification of larvae and pupae is relatively difficult and there is less research on them.During the investigations of insect diversity in the Tibetan Plateau, larval and pupal stages of Orthocladius nitidoscutellatus Lundström, 1915 and Psectrocladius nevalis Akhrorov, 1977 were described and illustrated. Matching and identification of larval and pupal stages were based on DNA barcodes. Neighbour-joining trees were reconstructed, based on known Orthocladius and Psectrocladius COI DNA barcodes, respectively.

Abstract Esophageal squamous cell carcinoma (ESCC) remains an important health concern in developing countries. Patients with advanced ESCC have a poor prognosis and survival rate, and achieving early diagnosis remains a challenge. Metabolic biomarkers are gradually gaining attention as early diagnostic biomarkers. Hence, this multicenter study comprehensively evaluated metabolism dysregulation in ESCC through an integrated research strategy to identify key metabolite biomarkers of ESCC. First, the metabolic profiles were examined in tissue and serum samples from the discovery cohort (n = 162; ESCC patients, n = 81; healthy volunteers, n = 81), and ESCC tissue-induced metabolite alterations were observed in the serum. Afterward, RNA sequencing of tissue samples (n = 46) was performed, followed by an integrated analysis of metabolomics and transcriptomics. The potential biomarkers for ESCC were further identified by censoring gene-metabolite regulatory networks. The diagnostic value of the identified biomarkers was validated in a validation cohort (n = 220), and the biological function was verified. A total of 457 dysregulated metabolites were identified in the serum, of which 36 were induced by tumor tissues. The integrated analyses revealed significant alterations in the purine salvage pathway, wherein the abundance of hypoxanthine/xanthine exhibited a positive correlation with HPRT1 expression and tumor size. A diagnostic model was developed using two purine salvage–associated metabolites. This model could accurately discriminate patients with ESCC from normal individuals, with an area under the curve (AUC) (95% confidence interval (CI): 0.680–0.843) of 0.765 in the external cohort. Hypoxanthine and HPRT1 exerted a synergistic effect in terms of promoting ESCC progression. These findings are anticipated to provide valuable support in developing novel diagnostic approaches for early ESCC and enhance our comprehension of the metabolic mechanisms underlying this disease.

Muscle is one of the important quality of fish. However, there is still a lack of sufficient understanding of the mechanism of muscle growth regulation in fish. In this study, the expression patterns of 10 reported muscle development related genes are analyzed in zebrafish during growth or under water flow stress. Myogenic regulatory factors (MyoD, MyoG, MRF4), myostatin regulatory genes (Mstna, Mstnb) and myoblast development-related genes (Pax7, Prmt5, Desmin, MYHC) are significantly increased expression at somite stage and muscle effect stage embryos in zebrafish. The mRNA levels of the muscle development related genes are up-regulated in 7-day fries and 30-day juvenile of zebrafish. And there are differences in the expression levels of seven muscle development related genes (MyoD, Myf5, MyoG, Mstna, Mstnb, Desmin, MYHC) between the large and small individuals of 20-day-old zebrafish. Results indicated that short-term water flow stressing can promote zebrafish muscle growth, while prolonged water flow stress may lead to motor fatigue and affect growth in zebrafish. This research provides a foundation for further exploration of the growth regulation mechanism in fish, and is helpful on fish farming.

Precocial Eriocheir sinensis, showing advanced sexual maturity, are a serious impediment to crab industry. The aim of this study was to identify miRNAs and its related pathways involved in regulation of precocity in E. sinensis. High-throughput sequencing was used to evaluate hepatopancreas of precocious and normal E. sinensis at the same period. A total of 101 differentially expressed miRNAs were identified as candidate target genes. KEGG analysis revealed retinol metabolism may contribute to the regulation of gonadogenesis. Aldehyde dehydrogenase 1 family member A1 (aldh1a1) was identified as the core gene in the retinol metabolism by gene expression, and subsequently, gene cloning was performed to further explore its function. The aldh1a1 gene was 1740 bp, including a 189 bp 5′ untranslated region (UTR), 75 bp 3′ UTR and a 1476 bp open-reading frame, encoding 491 amino acids. The corresponding protein is 87.98 % homologous in Portunus trituberculatus. The expression of aldh1a1 was highest in ovary, and then in the hepatopancreas. In addition, dual-luciferase reporter assay indicated that there was negative correlation between NW_020868524.1_2213 and aldh1a1. NW_020868524.1_2213 agomir treatment in the normal group increased testosterone and estradiol levels significantly, down-regulated aldh1a1 expression, and activated the retinol metabolism. By contrast, the administration of NW_020868524.1_2213 antagomir after a short-term induction of retinol resulted in increase in aldh1a1 expression, decrease in sex hormone levels, and inhibition in retinol metabolism. In short, NW_020868524.1_2213 in the hepatopancreas could activate the retinol metabolic pathway via aldh1a1, thus regulating precocious and gonadal development in E. sinensis. These findings would provide a potential pathway for decreasing crab precocity in practice.

ABSTRACTThe immobilization of enzymes is an important strategy to improve their stability and reusability. However, it often comes with a trade off of reduced biological activity and catalytic efficiency. In this study, a composite hydrogel based on corn stalk carboxymethyl cellulose, acrylic acid, and mesoporous silica SBA-15 was developed as a support for the immobilization of lipase from Pseudomonas S.P. (PSL). The surface morphology and functional properties of the composite hydrogels were investigated by scanning electron microscopy, Fourier transform infrared, X-ray diffraction and simultaneous thermal analyzer, respectively. The composite hydrogel materials had a large number of mesopores and macropores were present in the wall of the hydrogel sheet. The hydrogel had a network structure that reduced the diffusion resistance of the substrate and improved the accessibility of the enzyme. The immobilized PSL exhibited high enantioselectivity (E value: 88.2) and enzyme activity (316.8 µmol/g/min) in the preparation of (S)-ibuprofen by enzymatic hydrolytic resolution of racemic ibuprofen ethyl ester. This prepared novel composite hydrogel is a promising supporting matrix for the immobilization of enzymes.

Background This study aims to undertake a comprehensive assessment of the effectiveness and safety profile of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in the management of primary membranous nephropathy (PMN), within the context of a prospective clinical investigation.Methods A multicenter, open-label clinical trial was executed on patients diagnosed with PMN. These individuals were subjected to MFSD therapy for a duration of at least 24 months, with primary outcome of clinical remission rates. The Cox regression analysis was employed to discern the pertinent risk factors exerting influence on the efficacy of MFSD treatment, with scrupulous monitoring of any adverse events.Results The study comprised 198 participants in total. Following 24 months of treatment, the remission rate was 58.6% (116/198). Among the subgroup of 130 participants subjected to a 36-month follow-up, the remission rate reached 70% (91/130). Subgroup analysis revealed that neither a history of immunosuppressive therapy (HIST) nor an age threshold of ≥60 years exhibited a statistically significant impact on the remission rate at the 24-month mark (p > .05). Multivariate Cox regression analyses elucidated HIST, nephrotic syndrome, or mass proteinuria, and a high-risk classification as noteworthy risk factors in the context of MFSD treatment. Remarkably, no fatalities resulting from side effects were documented throughout the study’s duration.Conclusions This trial establishes the efficacy of MFSD as a treatment modality for membranous nephropathy. MFSD demonstrates a favorable side effect profile, and remission rates are consistent across patients, irrespective of HIST and age categories.

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine’s protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

Study region: Upstream of the Heilongjiang River, located in Northeast Asia, is the transboundary river between China and Russia. Study focus: Using long-term hydrological records provided by the Mohe station in combination with multiple statistical approaches, we investigate how river ice phenology of the Heilongjiang River has varied during the period 1957–2016, and quantitatively assess the individual contribution of changes in different climatic factors to such variation in river ice phenology. New insights for the region: We show the later occurrence for newly formed ice date, ice-on date, and freeze-up date and the earlier occurrence for beak-up date and ice-off date, ultimately leading to a decrease in persistence of river ice in the Heilongjiang River. River ice phenology exhibits a general lag response to climate change, with ranging from 1 to 5 months. Further attribution analysis that explicitly considers time-lag effect suggests that climate change plays a dominant role in regulating river ice phenology. More specifically, compared to other climatic factors, air pressure and maximum and minimum temperature changes have larger contributions to variation in river ice phenology, particularly for the delay of formation time. These findings provide technical basis and beneficial reference to the development of regional river management strategies involved in climate change adaptation framework.

BackgroundSepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infection, yet the potential causal relationship between the immunophenotype and sepsis remains unclear.MethodsGenetic variants associated with the immunophenotype served as instrumental variables (IVs) in Mendelian randomization (MR) to elucidate the causal impact of the immunophenotype on three sepsis outcomes. Additionally, a two-step MR analysis was conducted to identify significant potential mediators between the immunophenotype and three sepsis outcomes.ResultsOur MR analysis demonstrated a significant association between the immunophenotype and sepsis outcome, with 36, 36, and 45 the immunophenotype associated with the susceptibility, severity, and mortality of sepsis, respectively. Specifically, our analysis highlighted the CD14+ CD16+ monocyte phenotype as a significant factor across all three sepsis outcomes, with odds ratios (ORs) and corresponding confidence intervals (CIs) indicating its impact on sepsis (OR = 1.047, CI: 1.001-1.096), sepsis in Critical Care Units (OR = 1.139, CI: 1.014-1.279), and sepsis-related 28-day mortality (OR = 1.218, CI: 1.104-1.334). Mediation analyses identified seven cytokines as significant mediators among 91 potential cytokines, including interleukin-5 (IL-5), S100A12, TNF-related apoptosis-inducing ligand (TRAIL), T-cell surface glycoprotein CD6 isoform, cystatin D, interleukin-18 (IL-18), and urokinase-type plasminogen activator (uPA). Furthermore, reverse MR analysis revealed no causal effect of sepsis outcomes on the immunophenotype.ConclusionOur MR study suggests that the immunophenotype is significantly associated with the susceptibility, severity, and mortality of patient with sepsis, providing, for the first time, robust evidence of significant associations between immune traits and their potential risks. This information is invaluable for clinicians and patients in making informed decisions and merits further attention.

Summary: The role of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), and triglyceride-glucose index (TyG index) in predicting all-cause and cause-specific mortalities remains elusive. This study included 384,420 adults from the Shanghai cohort and the UK Biobank (UKB) cohort. After multivariable adjustment in the Cox models, FPG ≥7.0 mmol/L or HbA1c ≥ 6.5% increased the risk of all-cause mortality, FPG ≥5.6 mmol/L or HbA1c ≥ 6.5% increased CVD-related mortality, and higher or lower TyG index increased all-cause and CVD-related mortalities in the Shanghai cohort; FPG ≥5.6 mmol/L, HbA1c ≥ 5.7%, TyG index

The purpose of this study is to explore the interaction between dietary methionine and taurine levels on growth performance, the profiles of amino acids, protein metabolism, and how taurine spares methionine of Chinese mitten crab (Eriocheir sinensis). The crabs were divided into six groups which were fed six diets formulated with two Tau levels (0 and 0.4%) and three Met levels (0.6%, 0.9% and 1.2%). The results showed that the weight gain rate and specific growth rate were the highest in the crabs fed 0.4% Tau and 0.6% Met. Crabs fed 1.2% Met had the highest survival rate and lowest feed conversion ratio. Furthermore, the hepatopancreas and muscle amino acid content were significantly influenced by the interactive effects of Met and Tau (P < 0.05). Moreover, interactive effects of dietary methionine and taurine were significantly observed in the expressions of amino acid metabolism-related genes (P < 0.05). Additionally, crabs fed 1.2% Met and 0% Tau had the highest activities of cysteine decarboxylase (CSD) and cysteine dioxygenase (CDO). In conclusion, the addition of appropriate amount of taurine to the diet can reduce the requirement of methionine for Chinese mitten crab by regulating the activities of CSD and CDO. At the same time, the addition of methionine and taurine could affect the amino acids metabolism. Therefore, the diet formula of Chinese mitten crab needs to consider the metabolism of sulfur-containing amino acids.

The multi-axle emergency rescue vehicle has dangerous driving conditions, high body height, and large weight, and the coupling of each subsystem of the chassis is more complicated. In order to solve the coordination problem between the vehicle suspension system and the steering system, the vehicle can drive more smoothly on uneven road surfaces and improve the riding comfort of passengers. A sliding mode dual robust coupled collaborative control strategy is proposed to address the impact of the multi-axis steering system and active suspension system on driving smoothness and handling stability of emergency rescue vehicles. The active suspension system and multi-axle steering system are synergistically controlled. Firstly, an active suspension sliding mode variable structure controller is designed to improve vehicle ride comfort. Secondly, A new dual robust controller is proposed to realize the handling stability of the vehicle’s all-wheel steering system. Thirdly, the coupling cooperative controller of the active suspension system and all-wheel steering system is designed and simulated under different working conditions. The experimental results show that the root-mean-square values of body roll angle, body roll angle acceleration, and yaw angle acceleration with cooperative control are reduced by 26.58%, 30.54%, and 21.92% respectively; moreover, the lateral acceleration and vertical acceleration of the vehicle body are effectively reduced. The use of cooperative control effectively improves the ride comfort and handling stability of the vehicle.

SARS-CoV-2 evolves gradually to cause COVID-19 epidemic. One of driving forces of SARS-CoV-2 evolution might be activation of apolipoprotein B mRNA editing catalytic subunit-like protein 3 (APOBEC3) by inflammatory factors. Here, we aimed to elucidate the effect of the APOBEC3-related viral mutations on the infectivity and immune evasion of SARS-CoV-2. The APOBEC3-related C > U mutations ranked as the second most common mutation types in the SARS-CoV-2 genome. mRNA expression of APOBEC3A (A3A), APOBEC3B (A3B), and APOBEC3G (A3G) in peripheral blood cells increased with disease severity. A3B, a critical member of the APOBEC3 family, was significantly upregulated in both severe and moderate COVID-19 patients and positively associated with neutrophil proportion and COVID-19 severity. We identified USP18 protein, a key molecule centralizing the protein-protein interaction network of key APOBEC3 proteins. Furthermore, mRNA expression of USP18 was significantly correlated to ACE2 and TMPRSS2 expression in the tissue of upper airways. Knockdown of USP18 mRNA significantly decreased A3B expression. Ectopic expression of A3B gene increased SARS-CoV-2 infectivity. C > U mutations at S371F, S373L, and S375F significantly conferred with the immune escape of SARS-CoV-2. Thus, APOBEC3, whose expression are upregulated by inflammatory factors, might promote SARS-CoV-2 evolution and spread via upregulating USP18 level and facilitating the immune escape. A3B and USP18 might be therapeutic targets for interfering with SARS-CoV-2 evolution.

Study area: China Study focus: Drought is an extremely serious disaster, typically characterized by slow onset, long duration, and cumulative impacts on multifaceted aspects. Developing a combined index that integrates its various characteristics can help deepen our understanding of drought evolution and provide accurate references for farmers to take drought mitigation measures. In this study, we proposed a Modified version of the Type Response-Aided Drought Index (MTRADI), simultaneously considering the various responses of different vegetation and the slow-varying properties of drought development. New hydrological insights for the regions: The suitability of MTRADI was evaluated through correlation analysis with Palmer Drought Severity Index (PDSI) and qualitative comparison with Meteorological Drought Composite Index (MCI) maps. The MTRADI achieved significantly higher correlation coefficients with the PDSI, outperforming other combined drought indices. Based on the run theory, Mann-Kendall (MK) test, and Sen’s slope, drought characteristics and trends in mainland China during 2001–2020 were analyzed and the results show that drought frequency and severity are relatively higher in eastern Inner Mongolia, North China Plain, and Northeast of China. Furthermore, areas with significant wetting trends are observed to be mainly distributed near the Hu line, indicating that the water conditions in China are gradually improving at the transition zone of arid and humid climate regions.

Abstract Background Targeted drugs are the main methods of RCC treatment. However, drug resistance is common in RCC patients, in-depth study of the drug-resistant mechanism is essential. Methods We constructed sunitinib resistant and Twist overexpressed A498 cells, and studied its mechanisms in vitro and in vivo. Results In cell research, we found that either sunitinib resistance or Twist overexpression can activate Wnt/β-catenin and EMT signaling pathway, and the sunitinib resistance may work through β-catenin/TWIST/TCF4 trimer. In zebrafish research, we confirmed the similarity of Twist overexpression and sunitinib resistance, and the promoting effect of Twist overexpression on drug resistance. Conclusions Sunitinib resistance and Twist overexpression can activate Wnt/β-catenin signaling pathway and EMT to promote the growth and metastasis of RCC cells.

The operational trajectory of a skilled operator holds significant guiding implications for the motion control of unmanned excavators. This study collects and analyzes the operational trajectories of experienced operators under specific working conditions, acquires standardized data, and proposes fluctuation judgment data in terms of joint motion speed and angle values at specific stages. Utilizing standardized data, a motion control trajectory is generated and combined with the Lagrange function and MPC algorithm to achieve decoupling of the four composite motions of excavators. Simulation verification and experimental comparison are conducted using the MPC algorithm. By adopting MPC motion control without altering the structure, hydraulic system, or electrical system of the experimental object, operating efficiency reaches 108.1% compared to that of skilled operators while significantly reducing fluctuations in operation trajectory. The average reduction in relative standard deviation and maximum fluctuation value, by 29.3% and 3.14deg/s respectively, signifies enhancements in velocity stability and position stability of over 36.2% and 12.85deg respectively, thereby presenting a novel approach for controlling work devices on unmanned excavators.

Purposes In this paper, research on various stages of the data life cycle and various security governance technologies has been conducted to achieve data security governance progress by searching and analyzing related technical literatures. Motheds First, the importance of strengthening research on data security governance is analyzed by introducing the status quo of data security governance. Second, the theory of the whole data life cycle is expounded in detail, and the different stages of the data life cycle are given. Third, the data security governance technologies and their applications in different life cycle stages such as data preparation, use, storage, and destruction are systematicalhy summarized. At last, the challenges and future research directions of data security governance are analyzed and prospected. Conclusions Strengthening data security governance is of great significance, whether for the privacy protection of personal information, or for the development of the data industry itself, or even for the information security of the country.

Emerging evidence suggested that zinc finger protein 831 (ZNF831) was associated with immune activity and stem cell regulation in breast cancer. Whereas, the roles and molecular mechanisms of ZNF831 in oncogenesis remain unclear. ZNF831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not mutation. Ectopic over-expression of ZNF831 suppressed breast cancer cell proliferation and colony formation and promoted apoptosis in vitro, while knockdown of ZNF831 resulted in an opposite phenotype. Anti-proliferation effect of ZNF831 was verified in vivo. Bioinformatic analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT pathway. ChIP and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of STAT3. As a result, the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic progression. Augmentation of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell lines. Furthermore, ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell lines. Our findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer, suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

Abstract DNA, or deoxyribonucleic acid, is a powerful molecule that plays a fundamental role in storing and processing genetic information of all living organisms. In recent years, scientists have harnessed hybridization powers between DNA molecules to perform various computing tasks in DNA computing and DNA storage. Unlike specific hybridization, non-specific hybridization provides a natural way to measure similarity between the objects represented by different DNA sequences. We utilize such property to build an instance-based learning model which recognizes an object by its similarity with other samples. The handwriting digit images in MNIST dataset are encoded by DNA sequences using a deep learning encoder. And the reverse complement sequence of a query image is used to hybridize with the training instance sequences. Simulation results by NUPACK show that this classification model by DNA could achieve 95% accuracy on average. Wet-lab experiments also validate the predicted yield is consistent with the hybridization strength. Our work proves that it is feasible to build an effective instance-based classification model for practical application.

Baling Tieshan Reservoir is one of the important artificial inland lakes in Hunan Province, with abundant aquatic resources, including high-quality fish species such as organic bighead carp. In order to further utilize the resource advantages of Baling Tieshan Reservoir and create a high-quality brand, this experiment analysis the biological characteristics and excellent traits of Baling Tieshan organic bighead carp (BTOBC) through techniques such as gene cloning, qRT-PCR, and paraffin section, and provides experimental basis for improving the quality of BOTBC. Pond-cultured bighead carp (PCBC) was used as a control for comparison. The findings reveal that BTOBC exhibits excellent traits in terms of body color, body shape and meat quality, which better meets the market and consumers' demands. Analysis of muscle nutrient composition and observation of muscle fiber histomorphology demonstrate a higher muscle fat proportion, and umami amino acid (AA) content, higher muscle fiber density, enhanced taste in BTOBC. Blood index and liver histology observation indicate that BTOBC has relatively healthier physiological conditions. mRNA expression detection of umami taste receptor genes T1r1 and T1r3 in various tissues shows that the meat of BTOBC has a more delicious taste. This study provides a comprehensive understanding of the nutritional characteristics of BTOBC and explores its excellent traits, which can serve as a reference for subsequent processing, comprehensive utilization, and healthy breeding in the reservoir area. Moreover, it offers a scientific basis for the rational use of reservoir resources and the sustainable development of reservoir fisheries.

Objective This study aimed to develop an individual WeChat Mini Program to provide pharmaceutical care to better manage cancer pain patients and to evaluate its feasibility and the differences in analgesic efficacy, medication adherence and safety versus conventional pharmacy interventions. Methods In this parallel randomized clinical trial, 42 cancer pain patients were equally allocated into the experimental group and the control group. The experimental group received individualized pharmaceutical care based on the “Yao Nin You Wo” WeChat Mini Program, while the control group received conventional care during the 4-week period. Main outcomes contained pain scores, medication adherence, incidences and relief rates of breakthrough pain, and incidences of adverse events. Relief rates of pain were also calculated according to pain scores. Results At the beginning of intervention, none of the pain scores and medication adherence showed relevant differences between the two groups (all P > .05). After intervention, the experimental group had significantly lower pain scores compared to the control group ( P = .003). Breakthrough pain of both groups was alleviate; not only the incidence of breakthrough pain considerably was lower at 4 weeks than at baseline, but the relief rate of breakthrough in the experimental group was higher than that in the control group. Compared with the control group, the medication adherence rate of the experimental group was significantly improved ( P = .02). Types of adverse events that happened in experimental and groups were similar, but the total incidence of adverse events in the experimental group was lower than that in the control group. Conclusions WeChat Mini Program is a useful and facilitative tool with the potential to improve cancer pain self-management ability in discharged patients. In addition, pharmacists could play a key role through the Mini Program to connect with patients successfully by providing personalized pharmaceutical services.

The control precision of the working device has always been a challenging aspect in unmanned excavator research due to the adoption of a triangular drive mode and a complex hydraulic system in the working mechanism. The article focuses on the research of autonomous control for the downward motion of a robotic arm in an unmanned excavator equipped with a regeneration valve. The study aims to achieve precise tracking of fast movement trajectories during operator manipulation, utilizing Model Predictive Control (MPC). Furthermore, the exceptional disturbance rejection capability of the MPC algorithm is demonstrated through interference application. A comprehensive model considering mechanical, hydraulic, and electrical factors is established for the excavator boom. The MPC algorithm is applied to achieve precise control over the boom descent process, providing a foundation for motion control in unmanned excavators. This article presents a theoretical analysis to elucidate the robustness principle of MPC in the descent control of uncertain dynamic arms. By incorporating real parameters, we successfully track predetermined planned paths at different speeds and validate them on a 20-ton hydraulic excavator. The results demonstrate that the MPC control algorithm accurately manipulates the boom descent motion while exhibiting excellent disturbance rejection performance. Compared to PID control algorithms, MPC offers wider target adaptability range and better disturbance rejection performance, making it suitable for rapid application in controlling working devices of unmanned excavators.

Background: Primary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear. Methods: Serum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury. RNA-seq was used to screen the possible targets of MFSD, and the effect of MFSD targeting IL-6/STAT3 was further verified by combining the experimental results. Finally, the efficacy of tocilizumab in PHN rats was observed. Results: Serum IL-6 levels were significantly higher in PMN patients than in healthy subjects. These levels significantly decreased in patients in remission after MFSD treatment. MFSD treatment improved laboratory indicators in PHN rats, as well as glomerular filtration barrier damage and podocyte marker protein expression. Renal transcriptome changes showed that MFSD-targeted differential genes were enriched in JAK/STAT and cytokine-related pathways. MFSD inhibits the IL6/STAT3 pathway in podocytes. Additionally, MFSD significantly reduced serum levels of IL-6 and other cytokines in PHN rats. However, treatment of PHN with tocilizumab did not achieve the expected effect. Conclusion: The IL-6/STAT3 signaling pathway is activated in podocytes of experimental membranous nephropathy. MFSD alleviates podocyte damage by inhibiting the IL-6/STAT3 pathway.

Oxidative stress in muscles is closely related to the occurrence of insulin resistance, muscle weakness and atrophy, age-related sarcopenia, and cancer. Aldehydes, a primary oxidation intermediate of polyunsaturated fatty acids, have been proven to be an important trigger for oxidative stress. However, the potential role of linoleic acid (LA) as a donor for volatile aldehydes to trigger oxidative stress has not been reported. Here, we reported that excessive dietary LA caused muscle redox imbalance and volatile aldehydes containing hexanal, 2-hexenal, and nonanal were the main metabolites leading to oxidative stress. Importantly, we identified 5-lipoxygenase (5-LOX) as a key enzyme mediating LA peroxidation in crustaceans for the first time. The inhibition of 5-LOX significantly suppressed the content of aldehydes produced by excessive LA. Mechanistically, the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway facilitated the translocation of 5-LOX from the nucleus to the cytoplasm, where 5-LOX oxidized LA, leading to oxidative stress through the generation of aldehydes. This study suggests that 5-LOX is a potential target to prevent the production of harmful aldehydes.

LncRNAs are an essential type of non-coding RNAs, which have been reported to be involved in various human pathological conditions. Increasing evidence suggests that drugs can regulate lncRNAs expression, which makes it possible to develop lncRNAs as therapeutic targets. Thus, developing in-silico methods to predict lncRNA-drug associations (LDAs) is a critical step for developing lncRNA-based therapies. In this study, we predict LDAs by using graph convolutional networks (GCN) and graph attention networks (GAT) based on lncRNA and drug similarity networks. Results show that our proposed method achieves good performance (average AUCs > 0.92) on five datasets. In addition, case studies and KEGG functional enrichment analysis further prove that the model can effectively identify novel LDAs. On the whole, this study provides a deep learning-based framework for predicting novel LDAs, which will accelerate the lncRNA-targeted drug development process.

With the rapid development of power grid, the structure and technology of the secondary system in substations are also constantly innovating. The new generation of intelligent substations has achieved online monitoring functions for secondary equipment, making some state variables of relay protection equipment become observable indicators. Based on this, this paper proposes a novel relay protection equipment status evaluation strategy. Firstly, considering the fuzziness and uncertainty of the boundary division of relay protection evaluation levels, a relay protection risk assessment method based on normal cloud model has been proposed. Then, due to the particularity of historical statistical data, a weight calculation method combining analytical hierarchy process (AHP) and entropy weight method is adopted to eliminate subjective factors in the weight calculation process. Meanwhile, the equipment operation risk level was determined by calculating the certainty of the corresponding evaluation level for each indicator. Finally, in case study, the proposed method is used to evaluate the status of relay protection equipment, and the feasibility and accuracy of this method are verified through the analysis of the results.

Cloud contamination is a common problem in Earth observation that hinders various remote sensing applications. To address this problem, recent studies have employed deep neural networks and multi-modal data fusion to reconstruct cloud-free optical imagery. However, this task faces many challenges, such as: (1) the scarcity of suitable multi-modal datasets; (2) the ineffective use of feature correlations; and (3) the limited applicability of existing models. To overcome these challenges, this study proposes a novel solution that fuses high-spatial SAR and low-spatial optical data to reconstruct high-quality cloud-free multi-spectral optical products. First, a curated benchmark dataset, named SMILE-CR, is created with a realistic cloud simulation strategy. The SMILE-CR serves as a global and multi-modal cloud removal dataset for the Landsat-8 sensor, with Sentinel-1 and MODIS data as additional supplementary data. Second, a Transformer-based cloud removal network, abbreviated as CRformer, is developed with two novel modules: multi-head dense and sparse attention and multi-scale gated-dconv feed-forward network. The CRformer achieves global attention while suppressing the weak correlations and enhancing the multi-scale cloud features by filtering out invalid features. The performance of the proposed method is evaluated through extensive experiments. The results show that the CRformer surpasses the state-of-the-art cloud removal methods with significant improvements in both quantitative and qualitative metrics. The fusion of MODIS and Sentinel-1 data is shown to be effective and necessary in reconstructing Landsat-8 observations. Moreover, the CRformer model can be readily applied to reconstruct time-series cloud-free Landsat-8 products in Wuhan city, which can improve the average accuracy of land cover mapping by over 3%.

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Purpose: The pathophysiological mechanisms underlying migraine remain elusive, with oxidative stress hypothesized as a potential etiological factor. The Oxidative Balance Score (OBS) is a comprehensive tool for assessing the impact of diet and lifestyle on oxidative stress, thereby gauging an individual's overall antioxidant capacity. In this cross-sectional study, we explored the correlation between OBS and migraine prevalence among a cohort of US adults. Methods: We analyzed data from 6195 participants aged 20 years and above, drawn from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. We employed multiple logistic regression, coupled with sensitivity analyses, to investigate the relationship between OBS and migraine. Subsequent subgroup analyses and interaction tests were performed to assess the consistency of this association across the population. Results: Multiple logistic regression revealed an inverse relationship between OBS and the likelihood of experiencing migraines. Specifically, individuals in the highest OBS quartile exhibited a significantly reduced migraine risk compared to those in the lowest quartile (OR = 0.98, 95% Confidence Interval (CI): 0.97–0.99, P = 0.0001). Furthermore, restricted cubic spline curves indicated a non-linear association between dietary OBS and migraine incidence (non-linear P = 0.0258). Discussion: Our findings suggest that adherence to an antioxidant-rich diet may be an effective strategy for mitigating migraine, potentially by influencing oxidative balance.

Abstract N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmt ft/ft). We show that female Asmt ft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmt ft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a “higher resilience”. Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmt ft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.

Abstract Aerobic glycolysis, a typical phenotype in human tumors, is associated with tumor progression and chemotherapy resistance. The present study demonstrated that cisplatin-resistant oral squamous cell carcinoma (OSCC) cells exerted a stronger glycolysis ability, which was associated with hexokinase 2 (HK2) overexpression. Additionally, the tumor growth of OSCC cells was delayed in vivo and the glycolysis was notably decreased following HK2 knockdown. The natural compound screening revealed that gastrodin could be an effective candidate for OSCC therapy since it inhibited HK2-mediated glucose metabolism and promoted endogenous OSCC cell apoptosis. Furthermore, gastrodin could bind to protein kinase B (Akt) and suppress its activity, thus downregulating HK2 at the transcriptional level. Additionally, S-phase kinase-associated protein 2 (Skp2) was highly expressed in OSCC cells, while K63-linked ubiquitination of Akt was inhibited in Skp2-depleted cisplatin-resistant OSCC cells. Gastrodin could also inhibit the cisplatin resistance of OSCC cells in vivo, particularly when combined with the Skp2 inhibitor, SZL P1-41. Overall, the aforementioned finding suggested that targeting the Skp2-Akt axis could be a potential therapeutic strategy for treating OSCC and overcoming chemoresistance.

Normally, proper fermentation can be an efficient and widely used method to improve feed quality in animal rearing; however, the studies on crustaceans, especially Eriocheir sinensis, remain limited. This study aimed to investigate whether feed fermentation could meliorate dietary nutritional value and benefit E. sinensis rearing. First, non-fermented feed (NFD) and fermented feed (FD) were produced and assessed, respectively. Then, the “Y” maze feed choice behavior test (180 times; 30 times, 6 rounds) was conducted to assess the attractiveness of these 2 feeds for crabs. Finally, a total of 80 crabs (44.10 ± 0.80 g) were randomly assigned into 2 groups with 4 replicates, and fed the experimental diets for 8 weeks to evaluate the effects of each feed on growth, antioxidant capacity, meat flavor, and intestinal microbiota. In this study, FD showed higher levels of crude protein (P

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host's ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.