Search

Compound probiotics are capable of effectively breaking down mycotoxins, and glycyrrhizic acid (GA) exhibits hepatoprotective properties. However, the protective efficacy and the underlying mechanism of combined intervention of GA and probiotics (GAP) on ameliorating Deoxynivalenol (DON)-induced liver toxicity remains unclear. This experiment involved 120 weaned piglets, encompassing the control group, the DON group, and the GPD group (E. faecalis and S. cerevisiae + GA + DON). Results showed that GAP significantly mitigated DON-related liver damage and oxidative stress. Furthermore, GAP inhibited the Nrf2/MAPK/NF-κB pathway, ultimately decreasing liver inflammation and apoptosis. Additionally, GAP significantly enhanced the expressions of ZO-1, GLUT2, PePT1, ASCT2, Occludin and Claudin-1. Moreover, metabolomics analysis revealed that GAP modulated lipid metabolism and mitigated liver damage by elevating serum levels of metabolites, such as phosphatidylcholine, phosphatidylethanolamine, and 3-amino-4-hydroxybenzoic acid. The research provides a theoretically based framework for using GAP to combat DON-induced hepatotoxicity in piglets.

Purpose: Osteoporosis is linked to impaired function of osteoblasts, and decreased expression of METTL14 may result in abnormal differentiation of these bone-forming cells. However, the specific impact of METTL14 on osteoblast differentiation and its underlying mechanisms are not yet fully understood. Methods and results: This study discovered a positive correlation between METTL14 expression and bone formation in specimens from osteoporosis patients and ovariectomized (OVX) mice. Additionally, METTL14 targeting of SLC25A3 contributed to the restoration of mitochondrial ROS levels and mitochondrial membrane potential in osteoblasts and promoted osteoblast differentiation. Moreover, in vivo experiments showed that METTL14 enhanced bone formation, and therapeutic introduction of METTL14 countered the decrease in bone formation in OVX mice. Conclusions: Overall, these findings emphasize the crucial role of the METTL14/SLC25A3 signaling axis in osteoblast activity, suggesting that this axis could be a potential target for improving osteoporosis.

Objectives: To assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. Methods: In this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. Results: The group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the

Crocins comprise a family of hydrophilic carotenoids with pharmacological properties that are produced in significant quantities in stigma of Crocus sativus. Although the biosynthesis pathway of crocins has been sufficiently elucidated, there is a paucity of information regarding how transcription factors (TFs) regulate crocin biosynthesis in various stigma developmental stages. WRKY TFs play a role in modulating carotenoid/apocarotenoid metabolism. To provide an overview of the WRKY family in Crocus sativus (CsWRKY) and characterize candidate CsWRKY TFs involved in the biosynthesis of crocins, CsWRKY genes were identified from RNA-sequenced stigma at different developmental stages. A phylogenetic analysis was performed to characterize their evolutionary interrelatedness. A coexpression analysis of CsWRKY genes and crocin biosynthesis-related genes was performed. A quantitative real-time polymerase chain reaction was used to corroborate the expression level of CsWRKY TFs in various tissue and at different developmental stages. A total of 34 CsWRKY TFs were identified from the stigma of C. sativus. The CsWRKY TFs, together with their orthologs from Arabidopsis, were clustered into group I, II, or III following phylogenetic analysis. A correlation analysis revealed that the expressions of the TFs CsWRKY1, CsWRKY2, CsWRKY8, CsWRKY10, CsWRKY15, and CsWRKY28 were strongly related to the expression of crocin biosynthesis-related genes CsBCH, CsCCD2L, CsALDH, and CsUGT. CsWRKY2, CsWRKY15, and CsWRKY28 exhibited identical motifs and were stratified into group IId. Transcript levels of candidate CsWRKY genes were higher in stigma than in other tissues and were proportional to the crocin content.

Prior research has shown that physical activity (PA) is a crucial element for preserving and enhancing health, particularly among children and adolescents, and consistent engagement in PA offers numerous advantages for sustaining typical physical and mental well-being.PurposeHence, the primary objective of this study was to examine the relationship between sport participation, muscle-strengthening exercise (MSE), and active commuting (AC) in the co-occurrence of depression and anxiety in Chinese children and adolescents.MethodThis cross-sectional investigation occurred in various cities across the southeastern region of China between March 2021 and October 2021. A convenient sampling method was utilized. We invited children and adolescents to participate in the questionnaire survey. A total of 1,996 participants completed the questionnaires with the endorsement of their parents or guardians under the supervision of schoolteachers and headmasters. Girls comprised 47.5% of the participants, and the average age of participants was 14.8 ± 2.0 years. We conducted a logistic regression analysis, including 95% confidence intervals, to explore the association between sports participation, MSE, AC, and the co-occurrence of depression and anxiety.ResultsNo significant association was observed between weekday active commuting for travelling to and from school and MSE and the comorbidity of depression and anxiety in children and adolescents. A negative association was only detected for those who engaged in muscle-strengthening exercises 4 days a week (OR = 0.540, 95% CI = 0.345–0.845) compared to those who did not partake in such exercises.ConclusionThe present study has provided evidence of the connection between sports participation and the co-occurrence of depression and anxiety among Chinese children and adolescents. Sports participation is more likely to help adolescents relieve anxiety and depression than AC, MSE. In forthcoming research, it is imperative to delve deeper into strategies that enhance the impact of sports on the mental well-being of children and young individuals. Furthermore, optimizing the magnitude of this effect may be achievable by focusing on neurobiological, behavioral, and psychosocial mechanisms.

Ghrelin, a peptide primarily secreted in the stomach, acts via the growth hormone secretagogue receptor (GHSR). It regulates several physiological processes, such as feeding behavior, energy homeostasis, glucose and lipid metabolism, cardiovascular function, bone formation, stress response, and learning. GHSR exhibits significant expression within the central nervous system. However, numerous murine studies indicate that ghrelin is limited in its ability to enter the brain from the bloodstream and is primarily confined to specific regions, such as arcuate nucleus (ARC) and median eminence (ME). Nevertheless, the central ghrelin system plays an essential role in regulating feeding behavior. Furthermore, the role of vagal afferent fibers in regulating the functions of ghrelin remains a major topic of discussion among researchers. In recent times, numerous studies have elucidated the substantial therapeutic potential of ghrelin in most gastrointestinal (GI) diseases. This has led to the development of numerous pharmaceutical agents that target the ghrelin system, some of which are currently under examination in clinical trials. Furthermore, ghrelin is speculated to serve as a promising biomarker for GI tumors, which indicates its potential use in tumor grade and stage evaluation. This review presents a summary of recent findings in research conducted on both animals and humans, highlighting the therapeutic properties of ghrelin system in GI disorders.

Mitochondria can contact lipid droplets (LDs) to form peridroplet mitochondria (PDM) which trap fatty acids in LDs by providing ATP for triglyceride synthesis and prevent lipotoxicity. However, the role of PDM in metabolic dysfunction associated steatotic liver disease (MASLD) is not clear. Here, the features of PDM in dietary MASLD models with different severity in mice were explored. Electron microscope photographs show that LDs and mitochondria rarely come into contact with each other in normal liver. In mice fed with high-fat diet, PDM can be observed in the liver as early as the beginning of steatosis in hepatocytes. For the first time, we show that PDM in mouse liver varies with the severity of MASLD. PDM and cytosolic mitochondria were isolated from the liver tissue of MASLD and analyzed by quantitative proteomics. Compared with cytosolic mitochondria, PDM have enhanced mitochondrial respiration and ATP synthesis. Diethyldithiocarbamate (DDC) alleviates choline-deficient, L-amino acid–defined diet-induced MASLD, while increases PDM in the liver. Similarly, DDC promotes the contact of mitochondria-LDs in steatotic C3A cells in vitro. Meanwhile, DDC promotes triglyceride synthesis and improves mitochondrial dysfunction in MASLD. In addition, DDC upregulates perilipin 5 both in vivo and in vitro, which is considered as a key regulator in PDM formation. Knockout of perilipin 5 inhibits the contact of mitochondria-LDs induced by DDC in C3A cells. These results demonstrate that PDM might be associated with the progression of MASLD and the prevention of MASLD by DDC.

Abstract Thyroid cancer incidence increases worldwide annually, primarily due to factors such as ionizing radiation (IR), iodine intake, and genetics. Papillary carcinoma of the thyroid (PTC) accounts for about 80% of thyroid cancer cases. RET/PTC1 (coiled‐coil domain containing 6 [CCDC6]‐rearranged during transfection) rearrangement is a distinctive feature in over 70% of thyroid cancers who exposed to low doses of IR in Chernobyl and Hiroshima‒Nagasaki atomic bombings. This study aims to elucidate mechanism between RET/PTC1 rearrangement and IR in PTC. N‐thy‐ori‐3‐1 cells were subjected to varying doses of IR (2/1/0.5/0.2/0.1/0.05 Gy) of IR at different days, and result showed low‐dose IR‐induced RET/PTC1 rearrangement in a dose‐dependent manner. RET/PTC1 has been observed to promote PTC both in vivo and in vitro. To delineate the role of different DNA repair pathways, SCR7, RI‐1, and Olaparib were employed to inhibit non‐homologous end joining (NHEJ), homologous recombination (HR), and microhomology‐mediated end joining (MMEJ), respectively. Notably, inhibiting NHEJ enhanced HR repair efficiency and reduced IR‐induced RET/PTC1 rearrangement. Conversely, inhibiting HR increased NHEJ repair efficiency and subsequent RET/PTC1 rearrangement. The MMEJ did not show a markable role in this progress. Additionally, inhibiting DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) decreased the efficiency of NHEJ and thus reduced IR‐induced RET/PTC1 rearrangement. To conclude, the data suggest that NHEJ, rather than HR or MMEJ, is the critical cause of IR‐induced RET/PTC1 rearrangement. Targeting DNA‐PKcs to inhibit the NHEJ has emerged as a promising therapeutic strategy for addressing IR‐induced RET/PTC1 rearrangement in PTC.

Fermented total mixed ration (FTMR) is an effective method of preserving high-moisture byproducts with higher aerobic stability after fermentation. FTMR has the potential to fulfill the daily nutritional requirements of cattle and enhance their production performance. The objective of this research was to examine the influence of FTMR on lactation performance, total tract apparent digestibility, fecal microbiota communities, and fermentation profiles in lactating dairy cows. A total of 12 cows were randomly assigned into two groups: the TMR group and the FTMR group. The TMR group was fed a total mixed ration (TMR) diet, and the FTMR group was fed an FTMR diet. The FTMR did not impact milk yield in dairy cows despite a decrease in dry matter intake, which increased the efficiency of the feed. In contrast to that in the TMR group, the milk fat content in the FTMR group was greater. The FTMR group showed greater digestibility of neutral detergent fiber (NDF), organic matter (OM), dry matter (DM), crude protein (CP), and acid detergent fiber (ADF) in the total digestive tract than did the TMR group. The FTMR increased the concentration of butyrate in the fecal matter and reduced the pH of the feces. The Chao1, ACE, and Shannon indices of the archaeal community in dairy cow feces were significantly higher in cow fed the FTMR compared to those fed the TMR. LefSe analysis revealed higher levels of Oscillospira, Lactobacillus, Prevotella, and Dehalobacterium in the feces of dairy cows fed the FTMR than in those fed the TMR. However, the abundances of Roseburia, rc4-4, Bulleidia and Sharpea exhibited the opposite trend. The abundances of Halobacteria, Halobacteriales, and Halobacteriaceae, which are biomarkers for distinguishing fecal archaea in the TMR from the FTMR, were substantially greater in the feces of dairy cows that consumed the TMR than in those that consumed the FTMR. Therefore, FTMR can improve the milk fat content, total tract apparent feed digestibility efficiency, and diversity of archaea in the feces. Additionally, this work provides a theoretical basis for the feasibility of FTMR feeding for dairy cows.

ABSTRACT Regulator of G-protein signaling (RGS) proteins exhibit GTPase-accelerating protein activities to govern G-protein function. In the rice blast fungus Magnaporthe oryzae, there is a family of at least eight RGS and RGS-like proteins (MoRgs1 to MoRgs8), each exhibiting distinct or shared functions in the growth, appressorium formation, and pathogenicity. MoRgs3 recently emerged as one of the crucial regulators that senses intracellular oxidation during appressorium formation. To explore this unique regulatory mechanism of MoRgs3, we identified the nucleoside diphosphate kinase MoNdk1 that interacts with MoRgs3. MoNdk1 phosphorylates MoRgs3 under induced intracellular reactive oxygen species levels, and MoRgs3 phosphorylation is required for appressorium formation and pathogenicity. In addition, we showed that MoRgs3 phosphorylation determines its interaction with MoCrn1, a coronin-like actin-binding protein homolog, which regulates MoRgs3 internalization. Finally, we provided evidence demonstrating that MoRgs3 functions in MoMagA-mediated cAMP signaling to regulate normal appressorium induction. By revealing a novel signal perception mechanism, our studies highlighted the complexity of regulation during the appressorium function and pathogenicity of the blast fungus.IMPORTANCEWe report that MoRgs3 becomes phosphorylated in an oxidative intracellular environment during the appressorium formation stage. We found that this phosphorylation is carried out by MoNdk1, a nucleoside diphosphate kinase. In addition, this phosphorylation leads to a higher binding affinity between MoRgs3 and MoCrn1, a coronin-like actin-binding protein that was implicated in the endocytic transport of several other RGS proteins of Magnaporthe oryzae. We further found that the internalization of MoRgs3 is indispensable for its GTPase-activating protein function toward the Gα subunit MoMagA. Importantly, we characterized how such cellular regulatory events coincide with cAMP signaling-regulated appressorium formation and pathogenicity in the blast fungus. Our studies uncovered a novel intracellular reactive oxygen species signal-transducing mechanism in a model pathogenic fungus with important basic and applied implications.

ObjectiveTo explore the activation patterns in the frontal cortex of patients with post-stroke cognitive impairment during the execution of working memory tasks.Methods15 patients with post-stroke cognitive impairment, 17 patients without cognitive impairment, and 15 healthy controls of similar age and sex were included. All participants under-went immediate recall task testing and near-infrared spectroscopy imaging to measure frontal cortex activation during the task.ResultsThe healthy control group performed the best in the immediate recall task, followed by the post-stroke non-cognitive impairment group. The post-stroke cognitive impairment group had the poorest performance. The near-infrared spectroscopy results revealed that during the immediate recall task, the healthy control group primarily activated the left frontal lobe region. In contrast, post-stroke patients exhibited reduced activation in the left frontal lobe and increased activation in the right frontal cortex, particularly in the right frontopolar and orbitofrontal regions, with the post-stroke cognitive impairment group displaying the most pronounced changes.ConclusionPatients with post-stroke cognitive impairment exhibit reduced activation in the left prefrontal cortex during the working memory tasks. They rely on compensatory activation in the right prefrontal cortex, particularly in the frontopolar and orbitofrontal cortex, to successfully complete the task.

Activated sludge models are increasingly being adopted to guide the operation of wastewater treatment plants. Chemical oxygen demand (COD) is an indispensable input for such models. To ensure that the activated sludge mathematical model can adapt to various water quality conditions and minimize prediction errors, it is essential to predict the parameters of the COD components in real-time based on the actual influent COD concentrations. However, conventional methods of determining the components' contributions are too intricate and time-consuming to be really useful. In this study, the chemical oxygen demand in the actual waste water treatment plant was disassembled and analyzed. The research involved determining the proportions of each COD component, assessing the reliability of the measurement parameters, and examining potential factors affecting measurement accuracy, including weather conditions, pipeline conditions, and residents' habits. Then, a backpropagation neural network was developed which can deliver real-time predictions for five important contributors to COD in real time. In addition, using the receiver operating characteristics curve and prediction accuracy to evaluate the performance of the prediction model. For all five components, which SS, XS, SI, XA, and XH, the prediction accuracy of model was more than 80 %. The maximum deviation values of these parameters fall within the range of the actual detected values, suggesting that the model's predictions align well with real-world observations, and demonstrated prediction performance adequate for practical application in wastewater treatment. This article can provide research basis for the engineering application of activated sludge model and help for the intelligent upgrading of waste water treatment plants.

Due to the pathological production of liver disease in utility particularly complexity, the morbidity and mortality of liver disease including viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. Considering its insidious onset, rapid progression and drug resistance, finding an effective therapy is particularly worthwhile. Phyllanthus urinaria L. (P. urinaria), an ethnic medicine, can be applied at the stages of viral hepatitis, liver fibrosis/cirrhosis and HCC, which demonstrates great potential in the treatment of liver disease. Currently, there are numerous reports on the application of P. urinaria in treating liver diseases, but a detailed analysis of its metabolites and a complete summary of its pharmacological mechanism are still scarce. In this review, the phytochemical metabolites and ethnopharmacological applications of P. urinaria are summarized. Briefly, P. urinaria mainly contains flavonoids, lignans, tannins, phenolic acids, terpenoids and other metabolites. The mechanisms of P. urinaria are mainly reflected in reducing surface antigen secretion and interfering with DNA polymerase synthesis for anti-viral hepatitis activity, reducing hepatic stellate cells activity, inflammation and oxidative stress for anti-liver fibrosis/cirrhosis activity, as well as preventing tumor proliferation, invasion and angiogenesis for anti-HCC activity via relevant signaling pathways. Accordingly, this review provides insights into the future application of natural products in the trilogy of liver diseases and will provide a scientific basis for further research and rational utilization of P. urinaria.

ObjectiveExamine the effect of childhood adversity on depression in older adults and the regulatory impact that social participation has on depression.MethodsBased on 6,704 standard-compliant research subjects, single factor analysis, multiple linear regression model, and tendency score matching were used to analyze the impact of childhood adversity on depression in older adults and the regulatory effect of social participation.ResultsThe depression rate is higher among women, young age, low education, unmarried, in agricultural households, older adults with low annual income, pre-retirement work type in agriculture, non-drinking, and those with two or more chronic diseases (p

Recent regional investigations in the United States have revealed a thought-provoking perspective: household electricity consumption may act as an inferior commodity, displaying a negative correlation with wealth. This finding challenges the outcomes of various other econometric analyses and underscores the importance of scrutinizing power consumption patterns across different regional service areas. While it is commonly believed that home electricity usage decreases as income rises, this may not always hold true universally. This study focuses on power usage in Seattle, Washington households, a prominent urban economy in the Pacific Northwest. Employing dynamic error correction modeling techniques, the research demonstrates statistically significant fluctuations in domestic power usage attributed to variations in actual value, actual revenue, and cold weather. In the immediate future, energy for homes in this urban economy resembles any other commodity. However, investing in electricity for homes in Seattle may not be advisable in the long run. Home power usage in Seattle declines with each percentage point increase in actual per capita income over 1.2 %. This finding highlights the need for careful consideration and strategic planning in energy management policies for urban economies like Seattle.

Due to the diversity of postpartum depression (PPD) patients and the complexity of associated pathophysiological changes, most current animal models cannot accurately simulate PPD-like symptoms. In this study, we established a reliable animal model for PPD by inducing chronic unpredictable mild stress (CUMS) at different stages (pre-pregnancy, pregnancy, or postnatal) in female mice, followed by maternal separation (MS) from day 2–21 after delivery. The results for female mice subjected to pre-pregnancy stress were not statistically significant due to a lower conception rate. However, female mice exposed to CUMS during either the gestational or postnatal stage, followed by MS, successfully exhibited PPD-like symptoms. The models were deemed effective based on observed behavioral abnormalities, impaired hippocampal neuron functioning, and reduced serum concentrations of neurotransmitters (5-HT, GABA, and NE). Additionally, mice that underwent gestational CUMS followed by MS displayed a more dysfunctional hypothalamic-pituitary-adrenal (HPA) axis and more severe uterine inflammation. The study also investigated the impact of PPD on the behavior and neurodevelopment of adolescent offspring through behavioral tests, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and western blotting (WB). The results indicated that adolescent offspring of mothers with PPD exhibited behavioral and neurodevelopmental disorders, with male offspring being more susceptible than females. Female mice exposed to both CUMS and MS during the postnatal period had more severe adverse effects on their offspring compared to the other model groups.

The tensile and fatigue properties of a newly developed Ni-based superalloy, HAYNES® 233, were investigated. Two different manufacturing processes including hot rolling (wrought plate) and laser-powder directed energy deposition (LP-DED) were considered. In addition, specimens were tested in two heat treatment (HT) conditions, namely solution annealed (SA), and age-hardened (AH). The microstructures of the materials were characterized using a scanning electron microscope. Tensile properties of specimens were evaluated at 21 °C, 538 °C, and 871 °C along with the fatigue properties at 21 °C under two different strain amplitudes of εa = 0.005 mm/mm and εa = 0.002 mm/mm. The LP-DED material in both the SA and AH conditions showed similar tensile strengths to the wrought AH material at all test temperatures, whereas the wrought SA material showed a noticeable deficit in strength at 21 °C and 538 °C, and was only comparable at 871 °C. Fatigue results indicated that there was no significant difference in fatigue life for specimens tested at εa = 0.005 mm/mm, while differences in fatigue life were observed for specimens tested at εa = 0.002 mm/mm, where fatigue life was observed to correlate well with the size of the crystallographic facets at crack initiation sites.

Purpose: Based on social exchange theory and social cognition theory, this paper studies the effect of work-related identity discrepancy on proactive behavior of close-leadership employees through hierarchical regression analysis and examines the mediating effect of face-pressure and the moderating effect of benevolent leadership. Methods: This work surveyed 516 employees by questionnaire. The first round of survey mainly investigated employees in Changsha City, and the second round of survey mainly investigated employees' work-related identity discrepancy, face-pressure, benevolent leadership and proactive behavior in >10 regions. By tracking and matching, 396 valid questionnaires were finally obtained. Spss 22.0 was used to describe all the study variables; Mplus 7.0 is used to carry out a confirmatory factor analysis and a multi-path regression model. Results: The difference in work-related identity discrepancy had a significant negative impact on proactive behavior. Face-pressure partially mediated the relationship between work-related identity discrepancy and proactive behavior. Benevolent leadership moderated the indirect relationship between work-related identity discrepancy, proactive behavior and face-pressure. We hope that the findings and discussions from this study will spark further exploration and practical application of enterprise management theories. Conclusion: In the context of leadership change, employee identity differences in perception can affect employee proactive behavior, especially for some close-leadership employees. Face-pressure in traditional Chinese culture has a prominent place. Managers should strive to foster an open and inclusive organizational atmosphere that promotes interaction and communication among employees, reduces the impact of negative factors like face pressure, and thereby stimulates employees' work initiative and innovative spirit. This enriches and deepens our understanding within the fields of organizational behavior and cross-cultural management.

Arid pastoral ecosystems are particularly vulnerable to degradation and desertification, exacerbated by factors such as overgrazing, land use changes, and climate change impacts. Therefore, research on ecosystem health is imperative for ecosystem management and restoration in arid pastoral areas. Although ecosystem health studies have been conducted in various regions, research on ecological health assessment in arid pastoral areas of Central Asia remains limited, especially within a mountain-basin system (MBS). Taking the Chinese pastoral region of Fuyun County in Altay Prefecture, Xinjiang, as our study area, we improved an evaluation framework in terms of Vigor-Organization-Resilience-Service (VORS) based on remote sensing and GIS technology, and innovatively employed a deep learning method to assess the ecological system health status and spatiotemporal patterns for the years 2000, 2010, and 2020.Our results indicate the following: (1) The evaluation method based on deep learning can achieve a more comprehensive, efficient and objective evaluation of ecosystem health. (2) The ecosystem health index (EHI) ranged from 0.0759 to 0.5735 in 2000, 0.0798 to 0.5952 in 2010, and 0.0415 to 0.5657 in 2020. (3) The distribution pattern of EHI exhibited spatial heterogeneity, with the indexes decreasing from north to south. The highest proportion of high ecosystem health level (EHL) was found in summer pastures, followed by those in north of spring/autumn pastures and along the Irtysh and Ulungur rivers. On the other hand, the EHLs were relatively low in spring/autumn and winter pasture areas. The EHL exhibited minimal alteration between 2000 and 2010. From 2010 to 2020, areas experiencing an increase in EHL were primarily concentrated along the Ulungur River, with another part of the region focused on the interface between winter pastures and spring/autumn pastures. Based on the results, rotational grazing and grazing prohibition should be put into place for the winter pastures in the central and southern regions of the study area, as well as for the spring and autumn pastures. Meanwhile, it is recommended to plant premium, high-yield artificial forage grass alongside the Irtysh and Ulungur rivers. These findings will assist ecosystem managers in implementing effective measures to enhance ecosystem health in arid pastoral areas. Moreover, the presented evaluation framework and method enable a more objective, comprehensive, and efficient assessment of complex ecosystems, and they can be applied to ecosystem health assessments in similar regions.

H1N1 influenza virus is a significant global public health concern. Monoclonal antibodies (mAbs) targeting specific viral proteins such as hemagglutinin (HA) have become an important therapeutic strategy, offering highly specific targeting to block viral transmission and infection. This study focused on the development of mAbs targeting HA of the A/Victoria/2570/2019 (H1N1pdm09, VIC-19) strain by utilizing hybridoma technology to produce two mAbs with high binding capacity. Notably, mAb 2B2 has demonstrated a strong affinity for HA proteins in recent H1N1 influenza vaccine strains. In vitro assessments showed that both mAbs exhibited broad-spectrum hemagglutination inhibition and potent neutralizing effects against various vaccine strains of H1N1pdm09 viruses. 2B2 was also effective in animal models, offering both preventive and therapeutic protection against infections caused by recent H1N1 strains, highlighting its potential for clinical application. By individually co-cultivating each of the aforementioned mAbs with the virus in chicken embryos, four amino acid substitution sites in HA (H138Q, G140R, A141E/V, and D187E) were identified in escape mutants, three in the antigenic site Ca2, and one in Sb. The identification of such mutations is pivotal, as it compels further investigation into how these alterations could undermine the binding efficacy and neutralization capacity of antibodies, thereby impacting the design and optimization of mAb therapies and influenza vaccines. This research highlights the necessity for continuous exploration into the dynamic interaction between viral evolution and antibody response, which is vital for the formulation of robust therapeutic and preventive strategies against influenza.

Panax japonicus is an important medicinal plant, and flavonoids are one of its main secondary metabolites. In this study, the main roots, fibrous roots, stems, leaves and flowers of P. japonicus were analyzed using transcriptomics and widely targeted metabolomics. Through correlation analysis of transcription and metabolism, the flavonoid biosynthesis pathway in P. japonicus was analyzed, and the accumulation of flavonoid metabolites and the expression of related genes were investigated. Metabolomics revealed a total of 209 flavonoid metabolites in P. japonicus, among which flavonoids, flavonols, flavanones and flavanonols significantly accumulated in the flowers and leaves. Transcriptome sequencing revealed that key genes in the flavonoid pathway exhibited increased expression in the flowers and leaves. The expression patterns of key genes involved in flavonoid biosynthesis, including PjC4H, Pj4CL, PjCHS, PjCHI, PjF3H, PjF3’H, PjCYP, and PjPAL, are consistent with their upstream and downstream metabolites, demonstrating a significant positive correlation among them. In addition, the PjUGT gene is highly expressed in five tissues of P. japonicus, indicating that PjUGT is one of the key factors for the diversity of flavonoid glycosides. The WGCNA results showed that WRKY transcription factors exist widely in the candidate modules, and it was possible that PjWRKY transcription factors are involved in regulating the expression of key genes involved in flavonoid biosynthesis and the biosynthesis of flavonoid metabolites. This study reveals spatial differences in the accumulation patterns of flavonoid metabolites in different tissues and provides important clues for further understanding the regulatory mechanisms of flavonoid metabolism in P. japonicus, thus contributing to the optimization of germplasm resources of P. japonicus and the promotion of genetic diversity analysis.

Abstract DNA damage plays a significant role in the tumorigenesis and progression of the disease. Abnormal DNA repair affects the therapy and prognosis of cancer. In this study, it is demonstrated that the deubiquitinase USP25 promotes non‐homologous end joining (NHEJ), which in turn contributes to chemoresistance in cancer. It is shown that USP25 deubiquitinates SHLD2 at the K64 site, which enhances its binding with REV7 and promotes NHEJ. Furthermore, USP25 deficiency impairs NHEJ‐mediated DNA repair and reduces class switch recombination (CSR) in USP25‐deficient mice. USP25 is overexpressed in a subset of colon cancers. Depletion of USP25 sensitizes colon cancer cells to IR, 5‐Fu, and cisplatin. TRIM25 is also identified, an E3 ligase, as the enzyme responsible for degrading USP25. Downregulation of TRIM25 leads to an increase in USP25 levels, which in turn induces chemoresistance in colon cancer cells. Finally, a peptide that disrupts the USP25‐SHLD2 interaction is successfully identified, impairing NHEJ and increasing sensitivity to chemotherapy in PDX model. Overall, these findings reveal USP25 as a critical effector of SHLD2 in regulating the NHEJ repair pathway and suggest its potential as a therapeutic target for cancer therapy.

Sleep deprivation (SD) is commonplace in today’s fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer’s disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1β, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aβ42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.

Abstract Stretchable electronics have experienced remarkable progress, especially in sensors and wireless communication systems, attributed to their ability to conformably contact with rough or uneven surfaces. However, the development of complex, multifunctional, and high‐precision stretchable electronics faces substantial challenges, including instability at rigid‐soft interfaces and incompatibility with traditional high‐precision patterning technologies. Metallized electrospun nanofibers emerge as a promising conductive filler, offering exceptional stretchability, electrical conductivity, transparency, and compatibility with existing patterning technologies. Here, this review focuses on the fundamental properties, preparation processes, patterning technologies, and application scenarios of conductive stretchable composites based on metallized nanofibers. Initially, it introduces the fabrication processes of metallized electrospun nanofibers and their advantages over alternative materials. It then highlights recent progress in patterning technologies, including collector collection, vapor deposition with masks, and lithography, emphasizing their role in enhancing precision and integration. Furthermore, the review shows the broad applicability and potential influence of metallized electrospun nanofibers in various fields through their use in sensors, wireless systems, semiconductor devices, and intelligent healthcare solutions. Ultimately, this review seeks to spark further innovation and address the prevailing challenges in stretchable electronics, paving the way for future breakthroughs in this dynamic field.

E11 causes acute fulminant hepatitis in newborns. We investigated the pathological changes of different tissues from premature male twins who died due to E11 infection. The E11 expression level was higher in the liver than in other tissues. IP10 was upregulated in liver tissue in the patient group, and might be regulated by IFNAR and IRF7, whereas IFNα was regulated by IFNAR or IRF5.

ObjectivesThis study aimed to explore the value of radiomics nomogram based on computed tomography (CT) on the diagnosis of benign and malignant solitary indeterminate smoothly marginated solid pulmonary nodules (SMSPNs).MethodsThis study retrospectively reviewed 205 cases with solitary indeterminate SMSPNs on CT, including 112 cases of benign nodules and 93 cases of malignant nodules. They were divided into training (n=143) and validation (n=62) cohorts based on different CT scanners. Radiomics features of the nodules were extracted from the lung window CT images. The variance threshold method, SelectKBest, and least absolute shrinkage and selection operator were used to select the key radiomics features to construct the rad-score. Through multivariate logistic regression analysis, a nomogram was built by combining rad-score, clinical factors, and CT features. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC).ResultsA total of 19 radiomics features were selected to construct the rad-score, and the nomogram was constructed by the rad-score, one clinical factor (history of malignant tumor), and three CT features (including calcification, pleural retraction, and lobulation). The nomogram performed better than the radiomics model, clinical model, and experienced radiologists who specialized in thoracic radiology for nodule diagnosis. The AUC values of the nomogram were 0.942 in the training cohort and 0.933 in the validation cohort. The calibration curve and decision curve showed that the nomogram demonstrated good consistency and clinical applicability.ConclusionThe CT-based radiomics nomogram achieved high efficiency in the preoperative diagnosis of solitary indeterminate SMSPNs, and it is of great significance in guiding clinical decision-making.

Background. Transplantation of human-induced pluripotent stem cell (hiPSC)-derived islet organoids is a promising cell replacement therapy for type 1 diabetes (T1D). It is important to improve the efficacy of islet organoids transplantation by identifying new transplantation sites with high vascularization and sufficient accommodation to support graft survival with a high capacity for oxygen delivery. Methods. A human-induced pluripotent stem cell line (hiPSCs-L1) was generated constitutively expressing luciferase. Luciferase-expressing hiPSCs were differentiated into islet organoids. The islet organoids were transplanted into the scapular brown adipose tissue (BAT) of nonobese diabetic/severe combined immunodeficiency disease (NOD/SCID) mice as the BAT group and under the left kidney capsule (KC) of NOD/SCID mice as a control group, respectively. Bioluminescence imaging (BLI) of the organoid grafts was performed on days 1, 7, 14, 28, 35, 42, 49, 56, and 63 posttransplantation. Results. BLI signals were detected in all recipients, including both the BAT and control groups. The BLI signal gradually decreased in both BAT and KC groups. However, the graft BLI signal intensity under the left KC decreased substantially faster than that of the BAT. Furthermore, our data show that islet organoids transplanted into streptozotocin-induced diabetic mice restored normoglycemia. Positron emission tomography/MRI verified that the islet organoids were transplanted at the intended location in these diabetic mice. Immunofluorescence staining revealed the presence of functional organoid grafts, as confirmed by insulin and glucagon staining. Conclusions. Our results demonstrate that BAT is a potentially desirable site for islet organoid transplantation for T1D therapy.

As the mining depth increases, the underground space will face more serious thermal hazards. By using corn cobs, an agricultural waste, to prepare cementitious insulation materials, active insulation layers are constructed by injecting insulation materials into underground spaces using cementitious material spraying techniques. This article designed the ratios of corn cob sprayed cementitious materials and analyzed the changes in the properties of the materials obtained by adding 0–25% of corn cobs. The results of the study showed that the addition of different proportions of corn cobs improved the thermal insulation properties of the material by 6.9%-75.5% as compared to the ordinary mortar material. The mechanical properties became 25.9%-113.6% of the original. When the corn cob is wetted for more than 10 min, the fluidity of the material is sufficient to reach the minimum standard for spraying operations. Considering the comprehensive performance of the material, it is concluded that the wetting time of 30 min, the addition of corn cob 20%, the corn cob particle size of 200 mesh, and the amount of sand doping of 40% are the optimal ratios of the studied corn cob spraying cementitious materials. The study of corn cob lightweight thermal insulation spray cementitious material is of great significance for controlling the ambient temperature in deep underground space, promoting cleaner production and improving the use of environmental resources.

Background: The course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyze the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. Methods: Sequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modeling (GBMTM). Results: A total of 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n = 64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n = 140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n = 117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n = 71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. Conclusions: Four distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

Interfacial solar steam generation is recognized as a promising solution to alleviate the scarcity of freshwater resources owing to its utilization of clean solar energy alongside its high efficiency and minimal heat loss. Nonetheless, the utilization of solar energy for water evaporation encounters challenges, primarily manifested in low evaporation rates and efficiency. Herein, we introduced an approach involving the development of a biomass-based hybrid engineering hydrogel evaporator, denoted as CLC (chitosan and lignosulfonate sodium hybrid hydrogel with a carbon nanotube). The construction of this evaporator involves the straightforward blending of lignosulfonate sodium (LS) and marine polysaccharide biomass chitosan (CS) with carbon nanotubes (CNT) serving as the photothermal materials. The interaction between the sulfonic group of LS and the amino group of CS with water molecules, facilitated by hydrogen bonding and electrostatic interactions, reduces the evaporation enthalpy of water, thereby lowering the energy demand for evaporation. Furthermore, the incorporation of LS reduces the thermal conductivity of the as-prepared hydrogel and promotes photothermal management to mitigate heat loss. The CLC hydrogel demonstrates an evaporation rate of 2.48 kg m–2 h–1 and energy efficiency of 90% under one sun illumination. Moreover, the CLC hydrogel exhibits excellent antibacterial properties (98.4%), ensuring that desalinated water meets drinking standards. This high efficiency and eco-friendly biomass hydrogel with antibiological pollution characteristics and purification abilities holds great potential for widespread application of long-term seawater desalination.

In this study, the extruded Mg-Zn-Mn-Ce-Ca alloy tube with a low compression anisotropy along the ED, 45ED and TD was prepared. The effect of the second phases, initial texture and deformation behavior on this low mechanical anisotropy was investigated. The results revealed that the alloy tube contains the high content (Mg1-xZnx)11Ce phase and the low content of Mg12Ce phase. These second phases are respectively incoherent and coherent with the Mg matrix, and their influence can be ignored. Additionally, the alloy tube exhibited a weak basal fiber texture, where the c-axis was aligned along the 0° ∼ 30° tilt from TD to ED. Such a texture made the initial deformation (at 1.0% ∼ 1.6% strain) of the three samples controlled by comparable basal slip. As deformation progressed (1.6∼9.0% strain), larger amounts of ETWs nucleated and gradually approached saturation in the three samples, re-orienting the c-axis to a 0°∼±30° deviation with respect to the loading directions. Meanwhile, the prismatic 〈a〉 and pyramidal slips replaced the dominant deformation progressively until fracture. Eventually, the similar deformation mechanisms determined by the weak initial texture in the three samples contribute to the comparable strain hardening rates, resulting in the low compressive anisotropy of the alloy tube.

Emerging research suggests a potential association of progression of Alzheimer's disease (AD) with alterations in synaptic currents and mitochondrial dynamics. However, the specific associations between these pathological changes remain unclear. In this study, we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models. The investigations included behavioural tests, brain magnetic resonance imaging (MRI), liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, Nissl staining, thioflavin-S staining, enzyme-linked immunosorbent assay, Golgi-Cox staining, transmission electron microscopy (TEM), immunofluorescence staining, proteomics, adenosine triphosphate (ATP) detection, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) assessment, mitochondrial morphology analysis, electrophysiological studies, Western blotting, and molecular docking. The results revealed changes in synaptic currents, mitophagy, and mitochondrial dynamics in the AD models. Remarkably, intervention with Dengzhan Shengmai (DZSM) capsules emerged as a pivotal element in this investigation. Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention, which notably amplified the frequency and amplitude of synaptic transmission. The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions, including the hippocampal CA3, primary cingular cortex, prelimbic system, and dysgranular insular cortex. DZSM intervention led to increased IDE levels, augmented long-term potential (LTP) amplitude, and enhanced dendritic spine density and length. Moreover, DZSM intervention led to favourable changes in mitochondrial parameters, including ROS expression, MMP and ATP contents, and mitochondrial morphology. In conclusion, our findings delved into the realm of altered synaptic currents, mitophagy, and mitochondrial dynamics in AD, concurrently highlighting the therapeutic potential of DZSM intervention.

The Daniudi Gas Field is one of the typical tight sandstone gas fields in the Ordos Basin. In order to better understand the genetic types and source of natural gas and reveal the migration phase of natural gas, the geochemical analysis of light hydrocarbons in the Upper Paleozoic tight gas from the Daniudi Gas Field has been conducted in this study. The results indicate that, the C5-7 light hydrocarbons in the Upper Paleozoic tight gas are dominated by iso-alkanes, and the C6-7 light hydrocarbons display low contents of aromatics (< 10%), which are even undetectable. The C7 light hydrocarbons are dominated by methylcyclohexane (MCH) with the relative MCH contents exceeding 50%. The K1 and K2 values of natural gas from the Lower Shihezi Formation (P1x) are consistent with those from the Shanxi (P1s) and Taiyuan (C3t) formations, respectively. The δ13C1 values of the P1x gas are consistent with those of the P1s gas and significantly different from those of the C3t gas. Compared with the P1s gas, the P1x gas mainly displays lower benzene/n-hexane, benzene/cyclohexane and toluene/n-heptane ratios, as well as significantly higher n-heptane/methylcyclohexane ratios. Geochemical characteristics of light hydrocarbons and carbon and hydrogen isotopic compositions of alkanes indicate that, the Upper Paleozoic natural gas from the Daniudi Gas Field is typical coal-derived gas. The P1s and C3t gases were in-situ self-generated and self-accumulated, whereas the P1x gas was mainly derived from the underlying P1s source rocks and accumulated via vertical migration in free phase, with insignificant contributions of the C3t source rocks. Due to the effect of migration and water solution of natural gas, the deviation exists in the identification of thermal maturity for tight gas from the Daniudi Gas Field using the light hydrocarbon indexes such as heptane and isoheptane values and benzene/n-hexane ratios.

Abstract Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

Abstract Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries. Predictions for the future burden of 8 selected countries, ranks of the burden of mental disorders and correlations with Sociodemographic Index (SDI) were also estimated. During the past 3 decades, while the number of DALYs of mental disorders increased from 43.9 million (95% UI: 32.5–57.2) to 69.0 million (95% UI: 51.0–89.7), the age-standardized rates of DALYs of mental disorders remained largely consistent from 1452.2 (95% UI: 1080.16–1888.53) per 100,000 population in 1990 to 1434.82 (95% UI: 1065.02–1867.27) per 100,000 population in 2019, ranked as the eighth most significant disease burden in Asia in 2019. Depressive disorders (37.2%) were the leading contributors to the age-standardized DALY rates of mental disorders in Asia, followed by anxiety disorders (21.5%). The age-standardized DALY rates in females were higher than their male counterparts, both peaked at 30-34 years. The age-standardized DALY rates were predicted to remain stable, with the number of DALYs presented an upward trend in the future. There was no significant correlation between the burden of mental disorders and SDI. All mental disorders ranked higher in 2019, compared in 1990. To reduce this burden, urgent measures for prevention, treatment, and rehabilitation for mental disorders need to be taken by Asian governments.

Abstract Background Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. Methods We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. Results The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P

Abstract In plant immunity, a well-orchestrated cascade is initiated by the dimerization of receptor-like kinases (RLKs), followed by the phosphorylation of receptor-like cytoplasmic kinases (RLCKs) and subsequent activation of NADPH oxidases for ROS generation. Recent findings by Zhong et al. illustrated that a maize signaling module comprising ZmWAKL-ZmWIK-ZmBLK1-ZmRBOH4 governs quantitative disease resistance to grey leaf spot, a pervasive fungal disease in maize worldwide, unveiling the conservation of this signaling quartet in plant immunity.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

transformer is a switch gene for sex determination in many insects, which cooperates with transformer-2 that is expressed in both sexes to regulate female differentiation, particularly in dipterans. Zeugodacus cucurbitae (Coquillett) is a very destructive pest worldwide, however, its sex determination pathway remains largely uncharacterized. Here, we show that the female sex ratio is sharply reduced with knockdown of either transformer or transformer-2 by RNA interference in early embryos of Z. cucurbitae. Most of the males grown from the embryos with transient transformer and transformer-2 suppression mated with wild-type females and produced mixed sex progeny, with one exception that produced only female progeny, and all of the few remaining males failed to mate with wild-type females and produced no progeny. The exceptional male and those males with mating failure were XX pseudomales as determined by the detection of Y chromosome-linked Maleness-on-the-Y, indicating that most XX pseudomales are not viable. The phenotypes of transformer and transformer-2 suggest that they play a key role in regulating sex determination and are required for female sexual development of Z. cucurbitae. Our results will be beneficial to the understanding of sex determination in Z. cucurbitae and can facilitate the development of genetic sexing strains for its biological control.

Abstract Recent studies have identified a previously uncharacterized protein C11orf53 (now named POU2AF2/OCA-T1), which functions as a robust co-activator of POU2F3, the master transcription factor which is critical for both normal and neoplastic tuft cell identity and viability. Here, we demonstrate that POU2AF2 dictates opposing transcriptional regulation at distal enhance elements. Loss of POU2AF2 leads to an inhibition of active enhancer nearby genes, such as tuft cell identity genes, and a derepression of Polycomb-dependent poised enhancer nearby genes, which are critical for cell viability and differentiation. Mechanistically, depletion of POU2AF2 results in a global redistribution of the chromatin occupancy of the SWI/SNF complex, leading to a significant 3D genome structure change and a subsequent transcriptional reprogramming. Our genome-wide CRISPR screen further demonstrates that POU2AF2 depletion or SWI/SNF inhibition leads to a PTEN-dependent cell growth defect, highlighting a potential role of POU2AF2-SWI/SNF axis in small cell lung cancer (SCLC) pathogenesis. Additionally, pharmacological inhibition of SWI/SNF phenocopies POU2AF2 depletion in terms of gene expression alteration and cell viability decrease in SCLC-P subtype cells. Therefore, impeding POU2AF2-mediated transcriptional regulation represents a potential therapeutic approach for human SCLC therapy.

Abstract Accurate traffic flow forecasting is a critical component in intelligent transportation systems. However, most of the existing traffic flow prediction algorithms only consider the prediction under normal conditions, but not the influence of weather attributes on the prediction results. This study applies a hybrid deep learning model based on multi feature fusion to predict traffic flow considering weather conditions. A comparison with other representative models validates that the proposed spatial‐temporal fusion graph convolutional network (STFGCN) can achieve better performance.

Abstract Background We combined the metabolic features of 18F-FDG-PET/CT and hematological inflammatory indicators to establish a predictive model of the outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy. Results A predictive nomogram was developed based on sex, CEA, systemic immune-inflammation index (SII), mean SUV (SUVmean), and total lesion glycolysis (TLG). The nomogram presents nice discrimination that yielded an AUC of 0.76 (95% confidence interval: 0.66–0.86) to predict 1-year PFS, with a sensitivity of 63.6%, a specificity of 83.3%, a positive predictive value of 83.7%, and a negative predictive value of 62.9% in the training set. The calibration curves and DCA suggested that the nomogram had good calibration and fit, as well as promising clinical effectiveness in the training set. In addition, survival analysis indicated that patients in the low-risk group had a significantly longer mPFS than those in the high-risk group (16.8 months versus 8.4 months, P

Abstract Objectives In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization’s (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. Methods One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. Results Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. Conclusion Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.

Abstract B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated MG (TMG) and the distribution of B cells in type B TMG. The distribution of mature B cells, including Bm1–Bm5, CD19+ and CD20+ B cells and non-switched (NSMBCs) and switched (SMBCs) memory B cells, were determined in 79 patients with thymoma or TMG. Quantitative relationships between the T and TMG groups and the TMG-low and TMG-high subgroups were determined. NSMBCs and SMBCs were compared in TME and PB. Type B thymoma was more likely to develop into MG, with types B2 and B3 being especially associated with MG worsening. The percentage of CD19+ B cells in PB gradually increased, whereas the percentage of CD20+ B cells and the CD19/CD20 ratio were not altered. The (Bm2 + Bm2′)/(eBm5 + Bm5) index was significantly higher in the TMG-high than in thymoma group. The difference between SMBC/CD19+ and NSMBC/CD19+ B cell ratios was significantly lower in the thymoma than TMG group. NSMBCs assembled around tertiary lymphoid tissue in thymomas of patients with TMG. Few NSMBCs were observed in patients with thymoma alone, with these cells being diffusely distributed. MG severity in patients with TMG can be determined by measuring CD19+ B cells and Bm1-Bm5 in PB. The CD19/CD20 ratio is a marker of disease severity in TMG patients. Differences between NSMBCs and SMBCs in PB and TME of thymomas can synergistically determine MG severity in patients with TMG.

Abstract Background In sepsis, intestinal barrier dysfunction is often caused by the uncontrolled death of intestinal epithelial cells (IECs). CD4CD8αα intraepithelial lymphocytes (IELs), a subtype of CD4+ T cells residing within the intestinal epithelium, exert cytotoxicity by producing granzyme B (GrB) and perforin (Prf). Extracellular cold-inducible RNA-binding protein (eCIRP) is a recently identified alarmin which stimulates TLR4 on immune cells to induce proinflammatory responses. Here, we hypothesized that eCIRP enhances CD4CD8αα IEL cytotoxicity and induces IEC death in sepsis. Methods We subjected wild-type (WT) and CIRP−/− mice to sepsis by cecal ligation and puncture (CLP) and collected the small intestines to isolate IELs. The expression of GrB and Prf in CD4CD8αα IELs was assessed by flow cytometry. IELs isolated from WT and TLR4−/− mice were challenged with recombinant mouse CIRP (eCIRP) and assessed the expression of GrB and Prf in CD4CD8αα by flow cytometry. Organoid-derived IECs were co-cultured with eCIRP-treated CD4CD8αα cells in the presence/absence of GrB and Prf inhibitors and assessed IEC death by flow cytometry. Results We found a significant increase in the expression of GrB and Prf in CD4CD8αα IELs of septic mice compared to sham mice. We found that GrB and Prf levels in CD4CD8αα IELs were increased in the small intestines of WT septic mice, while CD4CD8αα IELs of CIRP−/− mice did not show an increase in those cytotoxic granules after sepsis. We found that eCIRP upregulated GrB and Prf in CD4CD8αα IELs isolated from WT mice but not from TLR4−/− mice. Furthermore, we also revealed that eCIRP-treated CD4CD8αα cells induced organoid-derived IEC death, which was mitigated by GrB and Prf inhibitors. Finally, histological analysis of septic mice revealed that CIRP−/− mice were protected from tissue injury and cell death in the small intestines compared to WT mice. Conclusion In sepsis, the cytotoxicity initiated by the eCIRP/TLR4 axis in CD4CD8αα IELs is associated with intestinal epithelial cell (IEC) death, which could lead to gut injury.

Abstract Background The adaptive mechanisms of agricultural pests are the key to understanding the evolution of the pests and to developing new control strategies. However, there are few studies on the genetic basis of adaptations of agricultural pests. The turnip moth, Agrotis segetum (Lepidoptera: Noctuidae) is an important underground pest that affects a wide range of host plants and has a strong capacity to adapt to new environments. It is thus a good model for studying the adaptive evolution of pest species. Results We assembled a high-quality reference genome of A. segetum using PacBio reads. Then, we constructed a variation map of A. segetum by resequencing 98 individuals collected from six natural populations in China. The analysis of the population structure showed that all individuals were divided into four well-differentiated populations, corresponding to their geographical distribution. Selective sweep analysis and environmental association studies showed that candidate genes associated with local adaptation were functionally correlated with detoxification metabolism and glucose metabolism. Conclusions Our study of A. segetum has provided insights into the genetic mechanisms of local adaptation and evolution; it has also produced genetic resources for developing new pest management strategies.

Abstract Clouds affected by solar eclipses could influence the reflection of sunlight back into space and might change local precipitation patterns. Satellite cloud retrievals have so far not taken into account the lunar shadow, hindering a reliable spaceborne assessment of the eclipse-induced cloud evolution. Here we use satellite cloud measurements during three solar eclipses between 2005 and 2016 that have been corrected for the partial lunar shadow together with large-eddy simulations to analyze the eclipse-induced cloud evolution. Our corrected data reveal that, over cooling land surfaces, shallow cumulus clouds start to disappear at very small solar obscurations (~15%). Our simulations explain that the cloud response was delayed and was initiated at even smaller solar obscurations. We demonstrate that neglecting the disappearance of clouds during a solar eclipse could lead to a considerable overestimation of the eclipse-related reduction of net incoming solar radiation. These findings should spur cloud model simulations of the direct consequences of sunlight-intercepting geoengineering proposals, for which our results serve as a unique benchmark.

Abstract As an alternative pathway for liver regeneration, liver progenitor cells and their derived ductular reaction cells increase during the progression of many chronic liver diseases. However, the mechanism underlying their hepatocyte repopulation after liver injury remains unknown. Here, we conducted progenitor cell lineage tracing in mice and found that fewer than 2% of hepatocytes were derived from liver progenitor cells after 9 weeks of injury with a choline-deficient diet supplemented with ethionine (CDE), and this percentage increased approximately three-fold after 3 weeks of recovery. We also found that the proportion of liver progenitor cells double positive for the ligand of glucocorticoid-induced tumour necrosis factor receptor (GITRL, also called Tnfsf18) and SRY-related HMG box transcription 9 (Sox9) among nonparenchymal cells increased time-dependently upon CDE injury and reduced after recovery. When GITRL was conditionally knocked out from hepatic progenitor cells, its expression in nonparenchymal cells was downregulated by approximately fifty percent, and hepatocyte repopulation increased by approximately three folds. Simultaneously, conditional knockout of GITRL reduced the proportion of liver-infiltrating CD8+ T lymphocytes and glucocorticoid-induced tumour necrosis factor receptor (GITR)-positive CD8+ T lymphocytes. Mechanistically, GITRL stimulated cell proliferation but suppressed the differentiation of liver progenitor organoids into hepatocytes, and CD8+ T cells further reduced their hepatocyte differentiation by downregulating the Wnt/β-catenin pathway. Therefore, GITRL expressed by liver progenitor cells impairs hepatocyte differentiation, thus hindering progenitor cell-mediated liver regeneration.

Bacterial cellulose (BC) hydrogel spheroid plays a significant role in diverse fields due to its spatial 3D structure and properties. In the present work, a series of BC spheroids with controllable size and shape was obtained via an in situ biosynthesis. Crucial factors for fabricating BC spheroid including inoculum concentration of 1.35 × 103 CFU/mL, shaking speeds at 100 r/min, and 48–96 h incubation time during the biosynthetic process, were comprehensively established. An operable mechanism model for tuning the size of BC spheroids from 0.4 to 5.0 mm was proposed with a fresh feeding medium strategy of dynamic culture. The resulting BC spheroids exhibit an interactive 3D network of nanofibers, a crystallinity index of 72.3 %, a specific surface area of 91.2 m2/g, and good cytocompatibility. This study reinforces the understanding of BC spheroid formation and explores new horizons for the design of BC spheroids-derived functional matrix materials for medical care.

Abstract Over the long history of evolution, nature has developed a variety of biological systems with switchable recognition functions, such as the ion transmissibility of biological membranes, which can switch their ion selectivities in response to diverse stimuli. However, developing a method in an artificial host-guest system for switchable recognition of specific guests upon the change of external stimuli is a fundamental challenge in chemistry because the order in the host-guest affinity of a given system hardly varies along with environmental conditions. Herein, we report temperature-responsive recognition of two similar gaseous guests, CO2 and C2H2, with selectivities switched by temperature change by a diffusion-regulatory mechanism, which is realized by a dynamic porous crystal featuring ultrasmall pore apertures with flip-flop locally-motive organic moiety. The dynamic local motion regulates the diffusion process of CO2 and C2H2 and amplifies their rate differences, allowing the crystal to selectively adsorb CO2 at low temperatures and C2H2 at high temperatures with separation factors of 498 (CO2/C2H2) and 181 (C2H2/CO2), respectively.