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Pectin is a macromolecular water-soluble dietary fiber, which was widely distributed in fruits and vegetables. Pectin has various physiology functions, which has great development potential in the fields of food, medicine and health. By reviewing literature over the past 20 years, the common structures and extraction methods of pectin have been systematically summarized. Current structural studies of pectin have focused on homogalacturonans, rhamnogalacturonan-I and rhamnogalacturonan-II. Among the extraction methods, acid and aqueous extraction are the most mature technologies. Among these methods, subcritical aqueous extraction has great potential for application and popularization. Additionally, pectin plays an important role in ameliorating chronic metabolic diseases through intestinal microecology and other molecular pathways. Therefore, this article reviews the research progress in recent years on the structure, extraction methods, and the beneficial effect on the chronic diseases of pectin both domestically and internationally. Furthermore, this article summarizes the mechanism of action of pectin in improving chronic diseases and the conformational relationship between pectin structure and chronic diseases. This study would provide theoretical references for product development and industrial application of pectin.

With the current increasing global demand for low-carbon and environmentally friendly products, promoting the sustainability of closed-loop supply chains has become one of the key measures. However, consumers often do not regard remanufactured products as equivalent to new products. Therefore, this paper proposes a dynamic closed-loop supply chain that incorporates consumers' purchasing preferences to model a long-term game with product differentiation. Moreover, to enhance consumer acceptance of remanufactured products and reduce manufacturers' costs, low-carbon technologies and cost-sharing mechanisms are introduced. In this way, we construct a differential game in which the manufacturer sells new and remanufactured products through a retailer and makes decisions about the level of low-carbon technology in the remanufacturing process. Based on the theory of differential games, this paper analyzes three different power structures: the manufacturer-dominated Stackelberg game, the Nash game, and the retailer-dominated Stackelberg game. The optimal low-carbon technology level and pricing strategy are obtained by applying Pontryagin's maximum principle. The study shows that the retailer-led Stackelberg game helps retailers maximize profits, while the Nash game enables the entire closed-loop supply chain system to achieve the highest overall profits. This paper innovatively integrates low-carbon technologies into the dynamic game model of the remanufacturing process and reveals how the game behavior of supply chain participants affects the application of low-carbon technologies and the overall profit of the supply chain by comparing the cost-sharing mechanisms under different power structures. The results provide important theoretical support and practical references for closed-loop supply chain management with product differentiation.

Abstract Background Acinetobacter baumannii (AB) is a notable cause of hospital-acquired infections, with carbapenem-resistant Acinetobacter baumannii (CRAB) classified as a high-priority critical pathogen. Bacteriophage therapy is emerging as a promising alternative to combat drug-resistant bacterial infections. In this study, a lytic phage, HZY2308, was isolated from hospital sewage, and the biological properties, biosafety and anti-biofilm properties of phage HZY2308 were characterized and identified. Moreover, the antibacterial effect of phage HZY2308 in combination with antibiotics was investigated, and the apparent characteristics of phage-resistant strain AB48-R were demonstrated, which provided data support for further studies to elucidate the mechanism of generating phage resistance. Methods Phage HZY2308 was isolated by double agar plate method using clinical strain AB48 as the host bacterium. The morphology of phage HZY2308 was identified by transmission electron microscopy (TEM), and biological characteristics of phage HZY2308 were identified by host range, the efficiency of plating (EOP), sensitivity to temperature, pH, and chloroform, one-step growth curve, the optimal multiplicity of infection (MOI), and detection of endotoxin and cytotoxicity. Besides, the complete genome map of HZY2308 was constructed using CGview, and the phylogenetic tree of HZY2308 was constructed with MEGA. Additionally, the full genomic sequence of phage HZY2308 and the selected phage were compared using Easyfig. Checkerboard test of phage HZY2308 in combination with tigecycline (TGC) was performed to investigate their synergistic effect and bactericidal kinetics. The effect of HZY2308 on biofilm was investigated by semi-quantitative staining of biofilm with crystal violet, determination of bacterial activity in biofilm by 2,3-Bis (2-methoxy-4-nitro-5-sulfophenyl) -2 H-tetrazolium-5-carboxanilide (XTT) assay and observation of biofilm structure by fluorescence microscopy. Finally, Phage-resistant bacteria AB48-R were characterized by colony-forming capacity, morphology, growth curves, adsorption efficiency, and antibiotic susceptibility assays. Results A lytic phage, HZY2308, was isolated from hospital sewage, which exhibited advantageous traits such as a brief incubation period, large burst size, and robust stability. Safety assessments conducted at both genetic and cellular levels also have yielded positive outcomes. Besides, phage HZY2308 effectively inhibited AB biofilm formation and disrupted established biofilm structures. Furthermore, a synergistic antibacterial effect was noted when phage HZY2308 was combined with tigecycline. Interestingly, the phage-resistant strain, AB48-R was screened through natural selection. Compared to the wild strain AB48, the adsorption efficiency of the phage to AB48-R diminished. However, AB48-R’s sensitivity to antibiotics such as cefepime, gentamicin, amikacin, and tobramycin increased, indicating an evolutionary trade-off. Conclusions Phage HZY2308 shows strong antimicrobial potential, especially in combination with tigecycline, and the phage-resistant strain exhibits increased antibiotic sensitivity.

Abstract Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012–2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (I51R59N108 - G437) was the most common (72.6%), and the fully resistant haplotype (I51R59N108 - G437E540) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype I51R59N108 - V431A436G437G581S613 deserve more attention. In areas of high SP resistance, the intervention still reduces low birthweight and maternal anaemia. SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi).

Abstract Double-atom catalysts (DACs) have opened distinctive paradigms in the field of rapidly developing atomic catalysis owing to their great potential for promoting catalytic performance in various reaction systems. However, increasing the loading and extending the service life of metal active centres represents a considerable challenge for the efficient utilization of DACs. Here, we rationally design asymmetric nitrogen, sulfur-coordinated diatomic iron centres on highly defective nitrogen-doped carbon nanosheets (denoted A-Fe2S1N5/SNC, A: asymmetric), which possess the atomic configuration of the N2S1Fe-FeN3 moiety. The abundant defects and low-electronegativity heteroatoms in the carbon-based framework endow A-Fe2S1N5/SNC with a high loading of 6.72 wt%. Furthermore, A-Fe2S1N5/SNC has a low overpotential of 193 mV for the oxygen evolution reaction (OER) at 10 mA cm−2, outperforming commercial RuO2 catalysts. In addition, A-Fe2S1N5/SNC exhibits extraordinary stability, maintaining > 97% activity for over 2000 hours during the OER process. This work provides a practical scheme for simultaneously balancing the activity and stability of DACs towards electrocatalysis applications.

The low-salt fermented shrimp pastes with 10% (w/w) salt addition were made using acetes chinensis as the substrates and Bacillus amyloliquefaciens Y11 and Bacillus velezensis Y12 as fermentation starter cultures to investigate the impact of Bacillus amyloliquefaciens Y11 and Bacillus velezensis Y12 on the quality and bacterial community diversity. Sensory evaluation, flavor analysis, MDA content, TVB-N value, and bacterial community were examined to compare the quality and microbial diversity changes of shrimp paste fermented using single-strain and mixed-strain fermentation methods. The results revealed that shrimp paste subjected to mixed-strain fermentation using two Bacillus strains exhibited higher sensory evaluation scores, color, and flavor assessment than the single-strain and natural fermentation shrimp paste. For the shrimp paste fermented with mixed Bacillus strains, the pH was between 7.5 and 8.0, and remained relatively stable throughout the fermentation process. The MDA content decreased from 0.98 mg/kg to 0.33 mg/kg with an increased fermentation time, and the lowest TVB-N value (33.32 mg/100 g) was observed after 10 days of fermentation. Amplicon sequencing of the fermented shrimp paste indicated the addition of starter cultures had a significant impact on the relative abundance of bacterial communities in the early stage of fermentation. At the end of fermentation, the relative abundance of Alkalibacterium, Atopistipes, Staphylococcus, and Tetragonococcus was relatively high in different groups. These findings provide a theoretical foundation for utilizing Bacillus strains as fermentation agents in producing shrimp paste and other related seafood products.

In order to investigate changes in flavor substances of lightly-pickled cucumbers during storage, volatile compounds were analyzed by electronic nose and gas chromatography-ion mobility spectrometry (GC-IMS). The results showed that flavor characteristics of lightly-pickled cucumbers changed obviously during storage. A total of 56 volatile organic compounds (VOCs) were detected by GC-IMS, including 10 alcohols, 30 aldehydes, 8 ketones, 5 esters, 1 furan, 1 acid, and 1 alkane. With the extension of storage period, the relative contents of aldehydes, alcohols and ketones decreased significantly, while the contents of esters increased significantly (P1), including cis-6-nonenal, nonenal, 1-penten-3-one, isobutyraldehyde, trans-2,cis-6-nonadienal, and trans-2-octenal. Among them, trans-2-octenal increased with the relative extension of storage time, which might be the main off-flavor compound for flavor deterioration. This study can provide a theoretical basis for flavor quality evaluation of lightly-pickled cucumbers during storage.

The supercritical CO2 fracturing technology has significant potential for developing coal fracture and increasing gas permeability. Understanding its influence mechanism on coal is crucial for advancing research and practical engineering applications of this technology. In order to accurately characterize the changes of pore-fracture structures and mechanical properties of the high-rank coal under the action of supercritical CO2, taking high-rank coal from Zhongmacun Mine of Coking Coal Group as the experimental object, the changes of pore and fracture structure of the high-rank coal before and after supercritical CO2 treatment were analyzed by Brunauer-Emmet-Teller (BET) and Mercury intrusion porosimetry (MIP), and the mechanical and acoustic emission characteristics of the high-rank coal before and after supercritical CO2 treatment were tested by combining with uniaxial compression and acoustic emission experimental system. The results show that supercritical CO2 had a good effect on pore expansion and permeability enhancement of the high-rank coal. After supercritical CO2 treatment, the percentage of micro-small pore volume of the high-rank coal decreased, the percentage of medium and large pore volume increased, and the total pore volume of the high-rank coal increased after supercritical CO2 treatment. Supercritical CO2 had an obvious deteriorating effect on the mechanical properties of the high-rank coal. The uniaxial compressive strength and modulus of elasticity of the high-rank coal after supercritical CO2 treatment were significantly decreased by 70.06% and 55.56%, respectively. The acoustic emission signal activity of the high-rank coal after supercritical CO2 treatment decreased significantly, and the uniaxial compressive time, cumulative ring counts and cumulative energy of the high-rank coal were reduced by 98.68 s, 95.14×103, and 200.30 V·ms, with the decreases of 46.65%, 37.65%, and 50.03%, respectively. The proportion of accumulated ringing count and accumulated energy in the quiet period of high rank coal increased significantly, while the proportion in the slow period decreased. The proportion in the surge period of accumulated ringing count decreased, while the proportion of accumulated energy increased slightly. The research results will be conducive to promoting the mechanism research, and have certain guiding significance for the coalbed methane extraction of deep high-rank coal and CO2 underground storage.

Abstract Background Despite increases in musculoskeletal disorders (MSD) in Canada, evidence suggests utilization of chiropractic services has remained relatively stable over time. Understanding the extent to which chiropractors are consulted and factors associated with their utilization may suggest factors related to accessing care. We assessed the change in prevalence and characteristics of Canadians seeking chiropractic care across two time periods 2001–2010 and 2015–2018. Methods We used national cross-sectional data from seven cycles of the Canadian Community Health Survey between 2001 and 2018. The survey included Canadians aged 12 years and older living in private dwellings in all provinces and territories. National annual weighted prevalence and age-standardized weighted prevalence (and 95% confidence intervals) of chiropractic utilization were calculated. We calculated prevalence of chiropractic utilization stratified by demographic, socioeconomic, lifestyle and health-related variables. Crude linear trends and change in prevalence from 2001 to 2010 were assessed using linear regression models. Results The national annual prevalence of Canadians consulting a chiropractor in the previous 12 months slightly increased from 11.0% (95% CI 10.8, 11.3) in 2001 to 11.4% (95%CI 11.1, 11.7) in 2010, and in those reporting receiving regular health care from a chiropractor from 7.5% (95%CI 7.2, 7.7) in 2015 to 7.9% (95%CI 7.7, 8.2) in 2018. Prevalence of utilization varied by province, highest in the Western provinces but lowest in Atlantic provinces. The age-specific prevalence of chiropractic utilization was highest in those aged 35–49 years and remained stable over time, except for slight increase in those aged 65–79 years. A higher percentage of Canadians identifying as white, Canadian-born, in the highest quintile of household income, overweight, physically active and in excellent health reported seeking chiropractic services. The most common reported chronic conditions measured in the survey among Canadians consulting chiropractors were chronic back problems, arthritis, fibromyalgia and headaches. Conclusion The national prevalence of utilization of chiropractic services among Canadians slightly increased over time but varied by province and respondents’ socioeconomic and health characteristics. Chronic back problems were the most common reported chronic condition. This comprehensive population-based study on chiropractic utilization in Canada can be used to inform decisions concerning health human resources and access to rehabilitation care for MSD.

Abstract Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3–7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3–7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP‐CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference

Abstract Background Arginine deprivation was previously shown to inhibit retinoblastoma cell proliferation and induce cell death in vitro. However, the mechanisms by which retinoblastoma cells respond to arginine deprivation remain to be elucidated. Methods The human-derived retinoblastoma cell lines Y79 and WERI-Rb-1 were subjected to arginine depletion, and the effects on inhibiting cell growth and survival were evaluated. This study investigated potential mechanisms, including autophagy, cell cycle arrest and apoptosis. Moreover, the roles of the general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling pathways in these processes were examined. Results We demonstrated that arginine deprivation effectively inhibited the growth of retinoblastoma cells in vitro. This treatment caused an increase in the autophagic response. Additionally, prolonged arginine deprivation induced G2 cell cycle arrest and was accompanied by an increase in early apoptotic cells. Importantly, arginine depletion also induced the activation of GCN2 and the inhibition of mTOR signaling. We also discovered that the activation of SLC7A11 was regulated by GCN2 upon arginine deprivation. Knockdown of SLC7A11 rendered retinoblastoma cells partially resistant to arginine deprivation. Furthermore, we found that knockdown of GCN2 led to a decrease in the autophagic response in WERI-Rb-1 cells and arrested more cells in S phase, which was accompanied by fewer apoptotic cells. Moreover, knockdown of GCN2 induced the constant expression of ATF4 and the phosphorylation of 70S6K and 4E-BP1 regardless of arginine deprivation. Conclusions Collectively, our findings suggest that the GCN2‒SLC7A11 axis regulates cell growth and survival upon arginine deprivation through coordinating autophagy, cell cycle arrest, and apoptosis in retinoblastoma cells. This work paves the way for the development of a novel treatment for retinoblastoma.

TCP transcription factor is a plant-specific gene family which plays important roles in many developmental control pathways, regulating secondary metabolites and plant responses to abiotic and biotic stresses. Nevertheless, this gene family remains unknown in Scutellaria baicalensis. Here, by identifying and analysing all the TCP transcription factor family members based on the transcriptome of S. baicalensis, a total of 19 SbTCP genes were obtained following gene classification, the phylogenetic relationship, conserved domain structure, functional differentiation, and an expression activity analysis. Phylogenetic analysis grouped the SbTCP genes into two subfamilies; we also found that SbTCP with the same motif structure clustered together in the evolutionary tree, and these results suggest that SbTCP proteins with the same gene structure have similar functions. Gene Ontology (GO) categorised the SbTCP genes into 17 functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. After the MeJA and SA treatments, the expression of SbTCP candidate genes containing MeJA and SA promoter elements was significantly higher or lower compared with the control, indicating that these candidate SbTCP genes could respond to different concentrations of MeJA and SA treatments. These comprehensive data provide a reference for elucidating the functions of TCP transcription factor family in the growth, development, and MeJA and SA stress response of S. baicalensis, this study can create a new avenue for understanding the role of TCP gene family in S. baicalensis.

Abstract Botryosphaeria dothidea is the main fungal pathogen responsible for causing Chinese hickory (Carya cathayensis) dry rot disease, posing a serious threat to the Chinese hickory industry. Understanding the molecular basis of B. dothidea infection and the host’s resistance mechanisms is crucial for controlling and managing the ecological impact of Chinese hickory dry rot disease. This study utilized ultrastructural observations to reveal the process of B. dothidea infection and colonization in Chinese hickory, and investigated the impact of B. dothidea infection on Chinese hickory biochemical indicators and plant hormone levels. Through high-throughput transcriptome sequencing, the gene expression profiles associated with different stages of B. dothidea infection in Chinese hickory and their corresponding defense responses were described. Additionally, a series of key genes closely related to non-structural carbohydrate metabolism, hormone metabolism, and plant-pathogen interactions during B. dothidea infection in Chinese hickory were identified, including genes encoding DUF, Myb_DNA-binding, and ABC transporter proteins. These findings provide important insights into elucidating the pathogenic mechanisms of B. dothidea and the resistance genes in Chinese hickory.

Abstract Plants such as herbs, vegetables, fruits, and cereals are closely related to human life. Developing effective testing methods to ensure their safety and quantify their active components are of significant importance. Recently, nanomaterials with enzyme-like activity (known as nanozymes) have been widely developed in various assays, including colorimetric, fluorescence, chemiluminescence, and electrochemical analysis. This review presents the latest advances in analyzing phytochemicals and hazardous substances in plant samples based on nanozymes, including some active ingredients, organophosphorus pesticides, heavy metal ions, and mycotoxins. Additionally, the current shortcomings and challenges of the actual sample analysis were discussed.

Abstract Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR‐8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit‐8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR‐8/SVneo cells, respectively. To assess the expression levels of miR‐149‐3p and AKT serine/threonine kinase 1 (AKT1), quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting analysis were performed. A dual‐luciferase reporter assay was used to investigate the potential regulatory relationship between miR‐149‐3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E‐cadherin. Mechanistically, QCT downregulated the expression of miR‐149‐3p and upregulated the expression of AKT1, and miR‐149‐3p directly targets AKT1, negatively regulating its expression. Overexpression of miR‐149‐3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR‐8/SVneo cells through the miR‐149‐3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

Abstract Immune evasion represents a crucial milestone in the progression of cancer and serves as the theoretical foundation for tumor immunotherapy. In this study, we reveal a negative association between Human Papillomavirus (HPV)-encoded circular RNA, circE7, and the infiltration of CD8+ T cells in head and neck squamous cell carcinoma (HNSCC). Both in vitro and in vivo experiments demonstrate that circE7 suppresses the function and activity of T cells by downregulating the transcription of LGALS9, which encodes the galectin-9 protein. The molecular mechanism involves circE7 binding to acetyl-CoA carboxylase 1 (ACC1), promoting its dephosphorylation and thereby activating ACC1. Activated ACC1 reduces H3K27 acetylation at the LGALS9 gene promoter, leading to decreased galectin-9 expression. Notably, galectin-9 interacts with immune checkpoint molecules TIM-3 and PD-1, inhibiting the secretion of cytotoxic cytokines by T cells and promoting T cell apoptosis. Here, we demonstrate a mechanism by which HPV promotes immune evasion in HNSCC through a circE7-driven epigenetic modification and propose a potential immunotherapy strategy for HNSCC that involves the combined use of anti-PD-1 and anti-TIM-3 inhibitors.

Abstract Cisplatin (CP), a chemotherapy drug commonly used in cancers treatment, causes serious reproductive toxicity. With younger cancer patients and increasing survival rates, it is important to preserve their reproductive capacity. NME8 is highly expressed in testis and contains thioredoxin and NDPK domains, suggesting it may be a target against the CP-induced reproductive toxicity. We deleted exons 6–7 of the Nme8 in mice based on human mutation sites and observed impaired transcript splicing. In mice, Nme8 was not essential for spermatogenesis, possibly due to functional compensation by its paralog, Nme5. Nme8 expression was elevated and translocated to the nucleus in response to two weeks of CP treatment. Under CP treatment, Nme8 deficiency further impaired antioxidant capacity, induced lipid peroxidation and increased ROS level, and failed to activate autophagy, resulting in aggravated DNA damage in testes and sperm. Consequently, the proliferation and differentiation of spermatogonia and the meiosis of spermatocyte were almost completely halted, and sperm motility was impaired. Our research indicates that NME8 protects against CP-induced testis and sperm damage. This may provide new insights into the physiological functions of the Nme family and potential targets for preserving fertility in young male cancer patients.

Abstract Dopamine (DA) neurons play a crucial role in the development and manifestation of depression, as well as in response to antidepressant treatments. While the function of the predominantly distributed DA neurons in the ventral tegmental area (VTA) is well established, the contribution of a small fraction of DA neurons in the dorsal raphe nucleus (DRN) during depression remains unclear. In this study, we found that chronic unpredictable stress (CUS) induces depression-related behaviors and decreases spontaneous firing rates, excitatory and inhibitory postsynaptic currents of DA neurons in the DRN associated with reduced excitatory synaptic transmission in male and female mice. The chemogenetic inhibition of DA neurons in the DRN produces depressive phenotypes. Conversely, their activation completely reversed the anhedonic and despair behaviors induced by CUS. Furthermore, we showed that a DRN dopaminergic projecting to the dorsal bed nucleus of the stria terminalis (dBNST) selectively controls depressive behaviors by influencing the neural activity and N-methyl-D-aspartate receptor (NMDAR) mediating EPSC of calcium/calmodulin-dependent protein kinase II+ (CaMKII+) target neurons by regulating dopamine neurotransmitter and dopamine receptor 2 (DR2) in the dBNST. Overall, these findings highlight the essential role of the DRNDA → dBNSTCaMKII+ neural circuit in bi-directionally mediating stress-induced depression-related behaviors. Our findings indicate that DRN DA neurons are a key component of the neural circuitry involved in regulating depression-related behaviors, making them a potential therapeutic target for depression.

Frozen shoulder (FS) manifests as progressively worsening pain and a reduction in shoulder range of motion (ROM). Salvianolic acid B (SaB) is recently expected to be used in the treatment of fibrosis diseases including FS. We firstly demonstrate that SaB can effectively hinder the progression of oxidative stress, inflammation, and pathological fibrosis within the synovial tissue in FS, potentially leading to the reduction or reversal of capsule fibrosis and joint stiffness. For further clinical application, we design and synthesize a novel, superior, antioxidant and antibacterial CSMA-PBA/OD-DA (CPDA) hydrogel for the delivery of SaB. In vitro experiments demonstrate that the CPDA hydrogel exhibits excellent biocompatibility and rheological properties, rendering it suitable for intra-articular injections. Upon injection into the contracted joint cavity of FS model rat, the SaB-CPDA hydrogel accelerate the recovery of ROM and exhibit superior anti-fibrosis effect, presenting the promise for the treatment of FS in vivo.

Abstract Background Liver fibrosis can progress to end-stage cirrhosis and liver cancer. Mesenchymal stem cells (MSCs) were considered the most promising therapeutic strategy, but most of the MSCs injected intravenously traditionally are trapped in the lungs, rapidly reducing their survival ability. MSC spheroids cultured in 3D have shown higher tolerance to fluid shear stress and better survival than dissociated MSCs. Simulating the route of orthotopic liver transplantation, transplanting MSC spheroids into the liver via hepatic portal vein may impact superior therapeutic effects. Methods In the present study, human umbilical cord-derived MSC spheroids (hUC-MSCsp) were transplanted into rhesus monkey models of liver fibrosis via B-ultrasound-guided percutaneous portal vein puncture with minimized body invasion. The therapeutic effect is evaluated through hematology, ultrasound, and pathology. To study the effect of hUC-MSCsp on gene expression in rhesus monkeys with liver injury, transcriptome sequencing analysis was performed on the livers of rhesus monkeys. The distribution of transplanted hUC-MSCsp was traced with RNA scope technology. Results We found that hUC-MSCsp significantly restored liver function, including ALT, AST, ALB, GLOB and bilirubin. hUC-MSCsp also significantly reduced liver collagen deposition and inflammatory infiltration, and promote dismission of liver ascites. Subsequently, the therapeutic effects were further validated in TGF-β1/Smad pathway by global transcription profile. The distribution of transplanted hUC-MSCsp were also tracked, and we found that hUC-MSCsp distributed in the liver in a sphere status at 1 h after transplantation. After 16 days, the hUC-MSCsp were dispersed into dissociated cells that were predominantly distributed in the spleen, and a significant number of dissociated cells were still present in the liver. Conclusions This study reveals the distributions of transplanted hUC-MSCsp after liver portal vein transplantation, and provides a novel approach and new insights into the molecular events of potential molecular events underlying the treatment of liver fibrosis with hUC-MSCsp.

Abstract Background This study aimed to investigate the relationship between the features of endolymphatic hydrops and hearing loss in patients with Bilateral Meniere's Disease. Methods A retrospective analysis was conducted on 77 patients diagnosed with Bilateral Meniere's Disease. The features of endolymphatic hydrops in the affected ear were evaluated through gadolinium-enhanced inner ear Magnetic resonance imaging. The Spearman correlation coefficient, paired t-tests, and Wilcoxon signed-rank tests were employed for data analysis. Results The analysis revealed a significant correlation between the degree of endolymphatic hydrops and hearing loss across all frequencies(0.125–8 kHz), including the cochlear, vestibular, and overall degree of endolymphatic hydrops. The strongest correlation between the overall degree of endolymphatic hydrops and hearing loss was observed at low frequencies (r = 0.571, p

In order to explore the “double-edged sword” influence effect and boundary conditions of self-sacrificing leadership on miners’ safety performance, a hypothetical model of the theoretical relationship between self-sacrificing leadership, psychological safety, work pressure, self-efficacy and safety performance was constructed based on leadership attribution theory and resource conservation theory. A questionnaire survey was conducted for 61 managers and their corresponding 358 miners through a two-stage subordinate-leader matching method to obtain effective data, and the hypothesis model was analyzed and verified by common method bias test and Bootstrap methods. The results show that there is a significant positive effect between self-sacrificing leadership and miners’ safety performance, and psychological safety and work pressure play mediating roles through different paths, and the two different mediating paths indicate that self-sacrificing leadership has a double-edged sword effect of “sharp edge” and “wounded edge”; miners with high self-efficacy can generate more psychological safety and less work pressure under self-sacrificing leadership than miners with low self-efficacy, which can effectively improve safety performance.

Abstract Recognition of the translocation of NLRP3 to various organelles has provided new insights for understanding how the NLRP3 inflammasome is activated by different stimuli. Mitochondria have already been demonstrated to be the site of NLRP3 inflammasome activation, and the latest research suggests that NLRP3 is first recruited to mitochondria, then disassociated, and subsequently recruited to the Golgi network. Although some mitochondrial factors have been found to contribute to the recruitment of NLRP3 to mitochondria, the detailed process of NLRP3 mitochondrial translocation remains unclear. Here, we identify a previously unknown role for Signal transducer and activator of transcription-3 (STAT3) in facilitating the translocation of NLRP3 to mitochondria. STAT3 interacts with NLRP3 and undergoes phosphorylation at Ser727 in response to several NLRP3 agonists, enabling the translocation of STAT3 and thus the bound NLRP3 to mitochondria. Disruption of the interaction between STAT3 and NLRP3 impairs the mitochondrial localization of NLRP3, specifically suppressing NLRP3 inflammasome activation both in vitro and in vivo. In summary, we demonstrate that STAT3 acts as a transporter for mitochondrial translocation of NLRP3 and provide new insight into the spatial regulation of NLRP3.

Abstract Background Genetic variants in COL4A2 are less common than those of COL4A1 and their fetal clinical phenotype has not been well described to date. We present a fetus from China with an intronic variant in COL4A2 associated with a prenatal diagnosis of severe cerebral encephalomalacia and subdural hemorrhage. Methods Whole exome sequencing (WES) was applied to screen potential genetic causes. Bioinformatic analysis was performed to predict the pathogenicity of the variant. In in vitro experiment, the minigene assays were performed to assess the variant’s effect. Results In this proband, we observed ventriculomegaly, subdural hemorrhage, and extensive encephalomalacia that initially suggested cerebral hypoxic-ischemic and/or hemorrhagic lesions. WES identified a de novo heterozygous variant c.549 + 5G > A in COL4A2 gene. This novel variant leads to the skipping of exon 8, which induces the loss of 24 native amino acids, resulting in a shortened COL4A2 protein (p.Pro161_Gly184del). Conclusion Our study demonstrated that c.549 + 5G > A in COL4A2 gene is a disease-causing variant by aberrant splicing. This finding enriches the variant spectrum of COL4A2 gene, which not only improves the understanding of the fetal neurological disorders associated with hypoxic-ischemic and hemorrhagic lesions from a clinical perspective but also provides guidance on genetic diagnosis and counseling.

Abstract Background The purpose of this network meta-analysis was to assess the impact of different protective ventilatory strategies on postoperative pulmonary complications (PPCs). Methods Several databases were searched for randomized controlled trials (RCTs) that were published before October 2023 in a network meta-analysis. We assessed the effect of different lung-protective ventilation strategies on the incidence of PPCs using Bayesian network meta-analysis. Results We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low tidal volumes (LTVs) combined with iPEEP and recruitment manoeuvres (RM) was associated with significantly lower incidence of PPCs [HTVs: OR = 0.38, 95%CrI (0.19, 0.75), LTVs: OR = 0.33, 95%CrI (0.12, 0.82)], postoperative atelectasis[HTVs: OR = 0.2, 95%CrI (0.08, 0.48), LTVs: OR = 0.47, 95%CrI (0.11, 0.93)], and pneumonia[HTVs: OR = 0.22, 95%CrI (0.09, 0.48), LTVs: OR = 0.27, 95%CrI (0.08,0.89)] than was High tidal volumes (HTVs) or LTVs. LTVs combined with medium-to-high PEEP and RM were associated with significantly lower incidence of postoperative atelectasis, and pneumonia. Conclusion LTVs combined with iPEEP and RM decreased the incidence of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. Individual PEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence is moderate. Trial registration PROSPERO identifier CRD42023399485.

Abstract Background Myceliophthora heterothallica belonging to Myceliophthora is considered as an environmental fungus and has not been reported to be pathogenic or colonizing in recent literature. The present case firstly reports a ventilation-associated pneumonia caused by Myceliophthora heterothallica among the aged adult. Case presentation A 67-years-old Asian female patient suffering from a sudden disturbance of consciousness for 3 h was admitted to our hospital. Cardiac arrest occurred during emergency transport, and sinus rhythm was restored after cardiopulmonary resuscitation. Invasive mechanical ventilation was given to this patient for respiratory failure. After mechanical ventilation, the lung CT images showed multiple cuneiform nodules arranging subpleural accompanying with ground-glass opacity. On the 5th day of mechanical ventilation, Myceliophthora heterothallica was cultured from endotracheal aspirates. Two methods, namely automatic microbial identification system and internal transcribed spacer sequencing were employed to identify this fungus. The present case firstly uncovered the colonization ability and pathogenicity of Myceliophthora heterothallica in the respiratory tract. After 28d of treatment with piperacillin-tazobactam, this patient weaned from the ventilator and recovered from consciousness with lung infection disappearance. Conclusions This is the first case report of ventilation-associated pneumonia in the aged patient caused by Myceliophthora heterothallica. This current case is worth for the clinical diagnosis and treatment of Myceliophthora heterothallica infection, and also enriches new pathogenic species found of thermothelomyces species.

Abstract Background Right aortic arch (RAA) is a common congenital aortic arch abnormality. Fetuses with RAA frequently have good outcomes after birth. However, chromosomal abnormalities and genetic syndromes suggest poor prognosis for these patients. So far the underlying genetic etiology is still not identified in most RAA patients based on traditional genetic techniques and a problem is still debated whether fetuses with isolated RAA should be referred for CMA. Our study aims to investigate the genetic etiology of fetuses with right aortic arch (RAA) by chromosomal microarray analysis (CMA) and whole exome sequencing (WES) and evaluate the efficacy of CMA in fetal isolated RAA. Results Among these 153 fetuses, 99 (64.7%) with isolated RAA and 54 (35.3%) with non-isolated RAA; 25.5% (39/153) with additional intracardiac anomalies (ICA), and 19.0% (29/153) with extracardiac anomalies (ECA). Tetralogy of Fallot (n = 10) and persistent left superior vena cava (n = 11) are the most common ICA and ECA, respectively. CMA detected 15 clinically significant copy number variations (CNVs) in 14 cases (9.2%); microdeletion of 22q11.21 was the most common pathogenic CNVs (7.8%). The chromosomal abnormalities rate was higher in non-isolated RAA and RAA with ICA groups than in isolated RAA group (16.7% vs. 5.1%; 20% vs. 5.1%, both p < 0.05). From five cases further undergoing WES, a diagnostic variant in MTOR gene (c.7255G > A, de novo) was first reported in prenatal, extending the prenatal manifestation of Smith–Kingsmore syndrome (OMIM: 616638); a clinically relevant variant c.3407A > T in STAG2 was identified, being inherited from the healthy mother. Moreover, the premature birth and termination rates were higher in non-isolated RAA group than in isolated RAA group (11.1% vs. 1.0%; 37.0% vs. 2.0%, both p < 0.01). Conclusions We demonstrate that CMA and WES are useful diagnostic tools for fetal RAA, particularly non-isolated RAA, and all fetuses with RAA should be referred for CMA. The data probably aids in prenatal diagnosis and prenatal counseling of fetal RAA.

Abstract Background Accurate breed identification is essential for the conservation and sustainable use of indigenous farm animal genetic resources. In this study, we evaluated the phylogenetic relationships and genomic breed compositions of 13 sheep breeds using SNP and InDel data from whole genome sequencing. The breeds included 11 Chinese indigenous and 2 foreign commercial breeds. We compared different strategies for breed identification with respect to different marker types, i.e. SNPs, InDels, and a combination of SNPs and InDels (named SIs), different breed-informative marker detection methods, and different machine learning classification methods. Results Using WGS-based SNPs and InDels, we revealed the phylogenetic relationships between 11 Chinese indigenous and two foreign sheep breeds and quantified their purities through estimated genomic breed compositions. We found that the optimal strategy for identifying these breeds was the combination of DFI_union for breed-informative marker detection, which integrated the methods of Delta, Pairwise Wright's FST, and Informativeness for Assignment (namely DFI) by merging the breed-informative markers derived from the three methods, and KSR for breed assignment, which integrated the methods of K-Nearest Neighbor, Support Vector Machine, and Random Forest (namely KSR) by intersecting their results. Using SI markers improved the identification accuracy compared to using SNPs or InDels alone. We achieved accuracies over 97.5% when using at least the 1000 most breed-informative (MBI) SI markers and even 100% when using 5000 SI markers. Conclusions Our results provide not only an important foundation for conservation of these Chinese local sheep breeds, but also general approaches for breed identification of indigenous farm animal breeds.

Abstract Tumor cells possess complex immune evasion mechanisms to evade immune system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) to modulate immune cell functions. When a tumor is sufficiently immunogenic, it can activate cytotoxic T-cells to target and destroy it. However, tumors adapt by manipulating their metabolic pathways, particularly glucose, amino acid, and lipid metabolism, to create an immunosuppressive TME that promotes immune escape. These metabolic alterations impact the function and differentiation of non-tumor cells within the TME, such as inhibiting effector T-cell activity while expanding regulatory T-cells and myeloid-derived suppressor cells. Additionally, these changes lead to an imbalance in cytokine and chemokine secretion, further enhancing the immunosuppressive landscape. Emerging research is increasingly focusing on the regulatory roles of non-tumor cells within the TME, evaluating how their reprogrammed glucose, amino acid, and lipid metabolism influence their functional changes and ultimately aid in tumor immune evasion. Despite our incomplete understanding of the intricate metabolic interactions between tumor and non-tumor cells, the connection between these elements presents significant challenges for cancer immunotherapy. This review highlights the impact of altered glucose, amino acid, and lipid metabolism in the TME on the metabolism and function of non-tumor cells, providing new insights that could facilitate the development of novel cancer immunotherapies.

Freshwater salinization is receiving increasing global attention due to its profound influence on nitrogen cycling in aquatic ecosystems and the accessibility of water resources. However, a comprehensive understanding of the changes in river salinization and the impacts of salinity on nitrogen cycling in arid and semi-arid regions of China is currently lacking. A meta-analysis was first conducted based on previous investigations and found an intensification in river salinization that altered hydrochemical characteristics. To further analyze the impact of salinity on nitrogen metabolism processes, we evaluated rivers with long-term salinity gradients based on in situ observations. The genes and enzymes that were inhibited generally by salinity, especially those involved in nitrogen fixation and nitrification, showed low abundances in three salinity levels. The abundance of genes and enzymes with denitrification and dissimilatory nitrate reduction to ammonium functions still maintained a high proportion, especially for denitrification genes/enzymes that were enriched under medium salinity. Denitrifying bacteria exhibited various relationships with salinity, while dissimilatory nitrate reduction to ammonium bacterium (such as Hydrogenophaga and Curvibacter carrying nirB) were more inhibited by salinity, indicating that diverse denitrifying bacteria could be used to regulate nitrogen concentration. Most genera exhibited symbiotic and mutual relationships, and the highest proportion of significant positive correlations of abundant genera was found under medium salinity. This study emphasizes the role of river salinity on environment characteristics and nitrogen transformation rules, and our results are useful for improving the availability of river water resources in arid and semi-arid regions.

AIM: To quantify the severity and frequency of ocular pain in Tibetan plateau patients with dry eye, and to evaluate the related factors affecting ocular pain. METHODS: A retrospective study included 160 cases of dry eye disease (DED) patients who were treated from July 2022 to June 2023. Age, gender, occupation, illness course, anxiety, plateau duration, plateau protection, ocular surface disease index scale (OSDI), break-up time (BUT), Schirmer I test (SIT), conjunctivitis, history of ophthalmic medication, autoimmune disease, the workload of daily near vision range, smoking and overnight stay were obtained via comprehensive ophthalmic assessment, and their duration was followed up. Logistic regression analysis was used to determine the related factors affecting ocular pain. RESULTS: Totally 77.5% (124/160) of DED patients had ocular pain, of which the severity of ocular pain was mild, moderate, and severe in 30.0%, 36.3%, and 11.3% of patients, respectively. Frequency of ocular pain was reported occasional, half the time, frequent, and persistent pain in 19.4%, 36.9%, 16.9%, and 4.4%. OSDI score was 19.67±5.70 (13 to 36), and the level of pain was lowly correlated with OSDI (rs=0.316, P0.05). CONCLUSION: Ocular pain is a common complaint in high-altitude DED patients during the pandemic. Anxiety, eye protection, and adequate sleep during the epidemic period are significantly associated with the severity and frequency of ocular pain in patients with plateau DED, while symptoms of DED have relatively little influence on them.

With the intensification of population aging, chronic diseases have become one of the major public health problems facing China. Obtaining and using authoritative health information is the foundation of chronic disease management. Currently, the channels for middle-aged and elderly patients with chronic diseases to obtain health information are increasingly diversified, but incorrect and false information is prevalent, and the health information discrimination ability of this population is relatively weak. In order to promote the rational use of health information by middle-aged and elderly patients with chronic diseases, this article systematically summarizes the current research progress on health information authority identification behavior (including behaviors in two aspects: health information trust evaluation and health information adoption evaluation) among middle-aged and elderly patients with chronic diseases at home and abroad based on authority theory.

Bacillus subtilis, a gram-positive bacterium commonly found in soil, is an excellent organism for plant biocontrol. B. subtilis KRS015, an endophyte isolated from the seed of Gossypium hirsutum ‘Zhongzhimian No. 2’, has been proven based on its antagonistic activity against diverse fungal pathogens of plants, including Verticillium dahliae, a fungal pathogen of Verticillium wilt in various plants such as cotton. Here, we report the complete genome sequence of B. subtilis KRS015. The size of the KRS015 genome is 4,331,506 bp. Fifteen gene clusters for antibiotics and secondary metabolites and 412 genes involved in plant–bacterial interactions were identified in this genome. These findings qualified the potential of B. subtilis KRS015 as a biocontrol agent and may help reveal the molecular basis of its antagonistic mechanisms. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

KRS022 was isolated from the rhizosphere soil of a healthy plant in a pathogen-infested cotton field in Xinjiang, China. Previous studies have demonstrated that KRS022 possesses the ability to trigger plant immune responses, inhibit the growth of various pathogenic fungi, including Verticillium dahliae, and promote plant growth. The antagonistic properties of KRS022 primarily stem from its bioactive metabolites. In this study, the high-quality genome of KRS022 was obtained. The KRS022 genome consists of a chromosome of 6,369,026 bp with 67.09% GC content and possesses 5,830 open reading frames, of which 5,186 genes were annotated, and 119 were ncRNA genes. Additionally, 11 gene clusters of secondary metabolites biosynthesis were predicted, involved in polyketide synthase, arylpolyene, NAGGN, beta-lactone, ranthipeptide, PiPP-like, redox cofactor, and non-ribosomal peptide-synthetase clusters. It could be useful to explore the biocontrol potential of P. tohonis, implying promising application of KRS022 to biological control. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Wool quality and yield are two important economic livestock traits. However, there are relatively few molecular studies on lncRNA for improving sheep wool, so these require further exploration. In this study, we examined skin tissue from the upper scapula of Super Merino (SM) and Small-Tailed Han (STH) sheep during the growing period. The apparent difference was verified via histological examination. High-throughput RNA sequencing identified differentially expressed (DE) long non-coding (lncRNAs) and messenger RNAs (mRNAs). The target gene of DE lncRNA and DE genes were enrichment analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was used to verify randomly selected DE lncRNAs and mRNAs. Finally, the DE, RAC2, WNT11, and FZD2 genes, which were enriched in the Wnt signaling pathway, were detected via immunohistochemistry. The results showed that a total of 20,888 lncRNAs and 31,579 mRNAs were identified in the skin tissues of the two sheep species. Among these, 56 lncRNAs and 616 mRNAs were differentially expressed. Through qRT-PCR, the trends in the randomly selected DE genes’ expression were confirmed to be aligned with the RNA-seq results. GO and KEGG enrichment analysis showed that DE lncRNA target genes were enriched in GO terms as represented by epidermal and skin development and keratin filature and in KEGG terms as represented by PI3K-Akt, Ras, MAPK, and Wnt signaling pathways, which were related to hair follicle growth and development. Finally, immunohistochemistry staining results indicated that RAC2, WNT11, and FZD2 were expressed in dermal papilla (DP). The lncRNAs MSTRG.9225.1 and MSTRG.98769.1 may indirectly participate in the regulation of hair follicle growth, development, and fiber traits by regulating their respective target genes, LOC114113396(KRTAP15-1), FGF1, and IGF1. In addition, MSTRG.84658.1 may regulate the Wnt signaling pathway involved in the development of sheep hair follicles by targeting RAC2. This study provides a theoretical reference for improving sheep breeding in the future and lays a foundation for further research on the effects of MSTRG.84658.1 and the target gene RAC2 on dermal papilla cells (DPC).

Abstract Chemotherapy, the standard of care treatment for cancer patients with advanced disease, has been increasingly recognized to activate host immune responses to produce durable outcomes. Here, in colorectal adenocarcinoma (CRC) we identify oxaliplatin-induced Thioredoxin-Interacting Protein (TXNIP), a MondoA-dependent tumor suppressor gene, as a negative regulator of Growth/Differentiation Factor 15 (GDF15). GDF15 is a negative prognostic factor in CRC and promotes the differentiation of regulatory T cells (Tregs), which inhibit CD8 T-cell activation. Intriguingly, multiple models including patient-derived tumor organoids demonstrate that the loss of TXNIP and GDF15 responsiveness to oxaliplatin is associated with advanced disease or chemotherapeutic resistance, with transcriptomic or proteomic GDF15/TXNIP ratios showing potential as a prognostic biomarker. These findings illustrate a potentially common pathway where chemotherapy-induced epithelial oxidative stress drives local immune remodeling for patient benefit, with disruption of this pathway seen in refractory or advanced cases.

Under the influence of the stable snowstorm circulation situation of the typical double-resistance type warm area in northern Xinjiang, an extremely heavy snowfall event occurred in Altay, from January 6 to 12, 2024. Several meteorological stations broke the historical maximum records for the same period, resulting in avalanches in several places of the Altay Mountains. This event can be divided into three stages according to the evolution of circulation situation and snowfall characteristics. In this study, the snowfall characteristics, circulation situation, extreme causes, and model forecasting performance of the event were analyzed using the hourly observation data of national and regional meteorological stations, ERA5 reanalysis data, and CMA-GFS, CMA-MESO, CMA-TYM, ECMWF model forecast data. The results are as follows: (1) The event was characterized by several extreme features, such as long duration, large accumulated precipitation, and large hourly precipitation. The precipitation distribution was increasing from the plain areas to the mountain areas. The strong snowfall process mainly concentrated in the second and third stages. In these two stages, the increase in snow accumulation, large hourly snowfall, and high snow-to-water ratio in the mountainous areas along the northern Altay provided key meteorological conditions for the avalanches. (2) During this event, a strong polar front at 500 hPa continuously split short-wave systems, which successively moved eastward to affect Altay. The warm shear line at 850-700 hPa was maintained for a long time, accompanied by strong warm front frontogenesis. Heavy snowfall occurred in the divergence area at the exit of the polar front jet at 300 hPa, from the north of the shear line at 850 hPa to the regions near the shear line at 700 hPa. (3) In the second and third stages, the water vapor conditions in the north of Altay, especially in the northern mountains, were abnormally strong. With the effect of terrain amplification, the low-level dynamic uplift was exceptionally strong and maintained for a long time. These were the important reasons for the extremely heavy snowfall. (4) The regional model performed better than the global model in predicting heavy snowfall, but the capability to forecast extreme snowfall was still limited. ECMWF Extreme Forecast Index (EFI) forecast product and the Ensemble Average Abnormal Weather Forecast (EMAF) product were better at identifying extreme weather signals at medium-range lead time. It is suggested to strengthen the application of related products and make adjustments according to the quantitative forecast results of the model to further improve the precision service effect of forecasting and warning of extreme weather events.

In order to solve the problem of uncertainty processing and the fuzziness of index weight in the risk analysis of gas explosion, a risk assessment model of gas explosion using the Bayesian network and game theory is proposed. Firstly, the topological structure model of gas explosion is constructed based on expertise and accident-causing theories. At the same time, the subjective and objective weights of experts are determined by game theory optimization. Then, the prior probability and conditional probability of risk factors are calculated based on the fuzzy set theory. Secondly, the Bayesian inference technology is used to calculate the probability of gas explosion and the posterior probability distribution of risk factors. Finally, the sensitivity analysis and key cause chain analysis are used to find out the key risk factors and key risk paths affecting gas explosion. The case study shows that the probability of gas explosion in the working face of a coal mine in Shandong Province is 6.5%. The main ignition sources of gas explosion are electric failures, friction between rocks, blasting sparks and coal spontaneous combustion, while the main causes of gas accumulation are ventilation system failures and ventilation system design. Through sensitivity analysis, it can be seen that two factors of ventilation system failures and electric failures are the most sensitive. According to the analysis of the key causal chain, it shows that the combination of the path of electric failures→ventilation system failures→ventilation measures→gas control measures→gas transfinite and the path of electric failures→electric spark→ignition source leads to the highest possibility of gas explosion. Compared with normal conditions, the probability of gas explosion increased by 301.5%. At the same time, the combination weighting method based on game theory has comprehensive advantages in improving the objectivity and accuracy of index weights, and the evaluation results accords with the actual situation of coal mines.

Abstract Background The aim of this study was to investigate the influence of marking methods on the outcomes of body composition analysis and provide guidance for the selection of marking methods in mouse body composition analysis. Methods Male C57BL/6J mice aged 6 weeks were randomly assigned for pre‐ and post‐ ear tagging measurements. The body composition of the mice was measured using a small animal body composition analyzer, which provided measurements of the mass of fat, lean, and free fluid. Then, the mass of fat, lean and free fluid to body weight ratio was gained. Further data analysis was conducted to obtain the range and coefficient of variation in body composition measurements for each mouse. The distribution of fat and lean tissue in the mice was also analyzed by comparing the fat‐to‐lean ratio. Results (1) The mass of all body composition components in the ear tagging group was significantly lower than that in the control group. (2) There was a significant increase in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group. (3) The fat‐to‐lean ratio in the ear tagging group was significantly lower than that in the control group. Conclusions Ear tagging significantly lowered the results of body composition analysis in mice and higher the results of measurement error. Therefore, ear tagging should be avoided as much as possible when conducting body composition analysis experiments in mice.

Abstract To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP

Abstract Background and objectives Early neurological deterioration (END) post-intravenous thrombolysis significantly impacts the long-term prognosis of stroke patients. This study aimed to establish a rapid risk prediction model for unexplained END following intravenous thrombolysis. Methods This prospective study consecutively enrolled patients with acute ischemic stroke treated with recombinant tissue plasminogen activator intravenous thrombolysis at the Department of Neurology, Third People’s Hospital of Hubei Province, and Yangluo Hospital District between June 2019 and December 2022. Unexplained END was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score between admission and 24 h. A nomogram was developed and assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). The calibration was assessed using the Hosmer–Lemeshow test. Results A total of 211 patients (130 males and 110 patients aged

Abstract Bistability enables adaptive designs with tunable deflections for applications including morphing wings, robotic grippers, and consumer products. Composite laminates may be designed to exhibit bistability due to pre-strains that develop during the processing of the polymer matrix, enabling fast reconfiguration between two stable shapes. Unfortunately, designing bistable laminates is challenging because of their highly nonlinear behavior. Here, we propose the Switching Tunneling Method to address this challenge by alternating between gradient-based local minimization and tunneling search phases, with the enhancement of objective expression switching to improve numerical conditioning. Results demonstrate high effectiveness compared to existing optimizers; the Switching Tunneling Method achieves a 99% success rate in finding all energy minima across general composite layups. Additionally, our method facilitates the inverse design of variable pre-strain fields, enabling bioinspired, positive Gaussian curvatures, which are not possible with conventional pre-strain laminates. Validations through both finite element analysis and 3D printed samples confirm the optimal designs.

Abstract Background To investigate the peripapillary retinal nerve fibre layer (RNFL) thickness changes and analyse factors associated with visual recovery of G11778A Leber hereditary optic neuropathy (LHON) patients. Methods Patients diagnosed with G11778A LHON between July 2017 and December 2020 in Tongji hospital were included in this follow-up study. Patients were grouped according to disease duration. Variations in the RNFL thickness in each quadrant at different disease stages were characterised using optical coherence tomography. According to the absence or presence of significant visual acuity improvements, LHON patients of disease duration ≥ 6 months were divided into two groups. A bivariate logistic regression model was constructed to analyse the potential factors associated with spontaneous visual recovery. Results This study included 56 G11778A LHON patients (112 eyes) and 25 healthy controls (50 eyes), with a mean follow-up of 5.25 ± 1.42 months. All quadrants and mean RNFL thicknesses of LHON patients first increased and then decreased, except for the temporal RNFL. As the disease progressed, RNFL thinning slowed; however, gradual RNFL thinning occurred. Logistic regression revealed that baseline best corrected visual acuity was related to spontaneous visual recovery of LHON patients with disease duration ≥ 6 months. Conclusion The pattern of RNFL involvement could be helpful in the differential diagnosis of LHON and other optic neuropathies. LHON patients with better vision are more likely to experience some degree of spontaneous visual acuity recovery after the subacute phase.

Abstract Background Appropriate physical activity (PA) and good sleep are beneficial to maternal and fetal health. This paper sought to explore the associations of PA and sleep quality among healthy women at the first and second trimesters of pregnancy on mental health and pregnancy outcomes. Methods Totally 268 healthy pregnant women were retrospectively analyzed as study subjects, 134 each in the first trimester (FT) and second trimester (ST). Their baseline clinical data were obtained respectively at two stages of pregnancy. The PA/sleep quality of subjects were assessed through the Pregnancy Physical Activity Questionnaire-Chinese version (PPAQ-C)/Pittsburgh Sleep Quality Index (PSQI) scale. The mental health was assessed via the Hospital Anxiety and Depression Scale (HADS). The correlations of PA and sleep quality with mental health were analyzed using Spearman correlation analysis. Pregnancy outcomes of all subjects, associations of moderate intensity (MI) PA and sleep quality with adverse pregnancy outcomes, and independent influencing factors for adverse outcomes were analyzed. Results Pregnant women in the ST group exhibited higher levels of MI, worse sleep quality, and lower levels of anxiety and depression than those in the FT group. Anxiety and depression were negatively correlated with MI but positively linked with PSQI scores at the first and second trimesters. MI ≥ 7.5 MET-h/week and good sleep quality were associated with a reduced incidence of adverse pregnancy outcomes. Conclusion MI ≥ 7.5 MET-h/week and good sleep quality at the first and second trimesters of pregnancy benefit mental health and markedly reduce the occurrence of adverse pregnancy outcomes.

Abstract This study assesses the efficacy of bilateral mesh sacrospinous ligament suspension (MSSLS) compared to laparoscopic sacrocolpopexy (LSC) in patients with uterine prolapse. Ninety-eight patients with uterine prolapse were evaluated at our hospital from January 2021 to January 2023. Patients were equally divided into two groups: the study group (undergoing MSSLS) and the control group (undergoing LSC) using a random number table. Various parameters including operation time, bleeding volume, indwelling catheter time, exhaust time, hospital stay, pelvic organ prolapse stage, postoperative recurrence rate, pain severity, quality of life, pelvic floor function, impact on sexual life, complications, and recurrence rate were recorded. The study group showed significant reductions in operation time, bleeding volume, indwelling catheter time, exhaust time, and hospital stay compared to the control group (P 0.05), but six months postoperatively, these indexes were significantly lower in the study group (P 0.05), but was significantly lower in the study group six months postoperatively (P 0.05). All patients were followed up for 12–14 months, with an average follow-up time of (13.02 ± 1.36) months. The incidence of complications was significantly lower in the study group (P 0.05). MSSLS emerges as a safe and efficacious treatment for uterine prolapse, notably reducing both complications and recurrence rates, rendering it suitable for broad clinical application.

Abstract The E‐proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G‐protein‐coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt‐Sensitivity Study Cohort in northern China. These participants followed a 3‐day regular baseline diet, followed by a 7‐day low‐salt diet (3.0 g/d) and a 7‐day high‐salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14‐year follow‐up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Abstract Background Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer’s disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. Methods The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. Results The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. Conclusions DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders. Graphical Abstract Scheme depicting the possible mechanism by which DNase II deficiency induces cognitive impairment in mice. DNase II deficiency induces tau phosphorylation by regulating kinases CDK5 and CaMKII as well as phosphatase PP2A through accumulation of undigested damaged DNA in the cytoplasm of neurons. Then phosphorylated tau induces synaptic loss, neuroinflammation, and neuronal apoptosis, eventually rendering cognitive impairment in mice.