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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.

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.

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 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 Dryocosmus kuriphilus, commonly known as the chestnut gall wasp, belongs to the family Cynipidae and is native to China. It is a highly invasive insect species causing serious damage to chestnut trees and has rapidly spread to various continents, including Europe, North America, and Oceania. The D. kuriphilus has become one of the important pests of chestnut plants in the world and is listed as a quarantine object by the European and Mediterranean Plant Protection Organization (EPPO). In this study, we used PacBio long reads, Illumina short reads, and Hi-C sequencing data to construct a chromosome-level assembly of the D. kuriphilus genome. The assembled genome includes 14,729 contigs with a total length of 2.28 Gb and a contig N50 of 0.8 Mb. With Hi-C technology, 2.17 Gb (95.02%) of contigs were anchored and oriented into the 10 pseudochromosomes with the scaffold N50 of 198.8 Mb and the scaffold N90 of 158.8 Mb. In total, 24,086 protein-coding genes were predicted in the assembled D. kuriphilus genome as the reference gene set. A total of 1.82 Gb repeats (occupying 79.7% of the genome), including 1.42 Gb of transposable elements and 0.40 Gb of tandem repeats, were identified in D. kuriphilus genome. In the evaluation of completeness, the BUSCO analysis determined a level of 98.1% completeness for the assembled genome sequences based on the Insecta database (OrthoDB version 10). The high-quality genome assembly of D. kuriphilus will not only provide a valuable reference for the study of its evolutionary history and genetic structure but also facilitate the research of host-pest interactions and invasiveness. Moreover, this genome assembly will promote in the development of effective management strategies to mitigate the economic and ecological impacts of this invasive pest on chestnut trees and ecosystems.

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.

Objective To explore the role of the exemplary demonstration course “Basic Neurosurgery Operations and Surgical Approaches” in improving the teaching quality of standardized training of neurosurgery. Methods A total of 42 graduate students who participated in the course from September 2021 to December 2023 were selected, matched 1:1 with their counterparts who did not participate in the course. All trainees were required to complete a same questionnaire survey. The basic data, questionnaire scores of the two groups were compared, and statistical descriptions of the satisfaction and course evaluation of the participating students were performed. Statistical tests including t-test, Mann-Whitney test, Dunn′s multiple comparison tests and Chi-square test were applied using Graphpad Prism 10.0. Results There were no significant differences in educational background and age distribution between the two groups indicating comparability. The questionnaire scores of the students who participated in the course[7.0(6.0-9.0) points] were significantly higher than those of the students who did not participate in the course[3.5(2.0-5.0) points] (P＜0.000 1). This score advantage applied to students who participated in the course in the school year from 2021 to 2023, and there was no statistical difference in questionnaire scores among students who participated in the course across the three years. Additionally, 88.1% of the students who participated in the course expressed a high satisfaction and 90.5% of them considered the course was very practical for training of clinical skills. Conclusions The exemplary demonstration course “Basic Neurosurgery Operations and Surgical Approaches”may improve learning outcomes of surgical approaches and support the clinical training of neurosurgery graduates.

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.

Abstract Objective To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. Patients and methods The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. Results About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470–21.569), PR (OR = 7.690, 95%CI: 3.974–16.129, Her-2 (OR = 10.489, 95%CI: 2.779–23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031–0.377 were significant independent risk factors affecting AR expression. Conclusions AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

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

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 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.

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 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.

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 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 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 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 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 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.

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.

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.

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.

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).

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.

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.

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.

Information literacy is an essential twenty-first-century skill for students. Most students face difficulty in discerning online information while searching, evaluating, and utilizing it effectively. Appropriate information evaluating framework, such as RADAR (relevance, authority, date, appearance, and reason for writing), has been recommended to enhance students' accuracy in identifying information. Research suggests that the effectiveness of the learning framework can be enhanced in the gamification context by using graphic organizers (e.g. concept maps) to help students organize and analyze information. Therefore, this study proposed a concept mapping-based information evaluating framework in the gamification context to teach information identification skills in an elementary school. A quasi-experimental study was conducted with the experimental group class (35 students) using the concept mapping-based information evaluating framework (CM-IEF), and the control group (35 students) using the conventional information evaluating framework (C-IEF). According to the study's findings, students in the experimental group had more significant increases in learning achievement, self-efficacy, and information discernment skills. However, there was no significant difference in learning motivation. Furthermore, the learning behavior of both groups was analyzed from the lag sequential analysis and interview. The study suggests that larger sample sizes and longer durations could be explored in the future.

The wall-associated kinase (WAK) gene family encodes functional cell wall-related proteins. These genes are widely presented in plants and serve as the receptors of plant cell membranes, which perceive the external environment changes and activate signaling pathways to participate in plant growth, development, defense, and stress response. However, the WAK gene family and the encoded proteins in soybean (Glycine max (L.) Merr) have not been systematically investigated. In this study, the soybean WAK genes (GmWAK) were identified based on genome-wide sequence information, the basic characteristics, chromosome location, gene replication, expression pattern, and responses to stress were comprehensively analyzed. A total of 74 GmWAK genes were identified and mapped to 19 different chromosomes in the soybean genome. Seventy-four GmWAK genes were divided into four groups, and GmWAK genes in the same group shared similar gene structures and conserved motifs. Thirty-seven duplicate pairs were identified in 74 GmWAK genes. Segmental duplication (SD) was critical in soybean WAK gene family expansion, and purification selection occurred during evolution. The promoter cis-element analysis displayed many hormone- and stress-related response elements in the promoter regions of GmWAK genes. GmWAK genes were diversely expressed in different organs and tissues, with most actively responding to cold, heat, salt, drought, and heavy metal stresses, suggesting that GmWAK genes could exhibit relevant roles in various bioprocesses.

ObjectivesTo explore the acute intervention effects of tissue flossing on chronic knee pain (CKP) in boxers.MethodsEighteen boxers with CKP (12 male/6 female) were randomly divided into an experimental group (EG) with tissue flossing (n = 9) and a control group (CG) (n = 9). The visual analog scale (VAS), Lysholm knee function score, flexion range of motion (ROM), maximal isometric extensor muscle strength, and stability of the knee were measured pre- and post-intervention (EG: 3-minute tissue flossing, CG: rest).ResultsVAS (F = 15.849, p = 0.001, η2p = 0.498) and Lysholm knee function (F = 9.327, p = 0.008, η2p = 0.357) significantly improved more in the EG than in the CG. There was a significant difference for maximal isometric extensor muscle strength (F = 17.769, p = 0.001, η2p = 0.542) and knee stability (F = 13.844, p = 0.002, η2p = 0.464) but no significant difference for ROM (F = 1.218, p = 0.287, η2p = 0.075) between the EG and CG.ConclusionTissue flossing can reduce knee pain, improve knee function, increase knee extensor strength, and improve knee stability in boxers with CKP.

Dissolved organic matter (DOM) released by straw returning for decomposition interacts with selenium (Se) in soil, which affects the speciation distribution of Se and its bioavailability. However, the relative mechanisms involved are slightly understood. This study investigated the effects of straw-derived DOM on two levels of exogenous selenite (low-Se and high-Se treatments) in two types of soil with distinct pH. Interactions between DOM and Se were revealed through three-dimensional excitation emission matrix (3D-EEM) fluorescence spectroscopy and two-dimensional correlation spectroscopy (2D-COS). Results showed that straw amendment significantly enhanced selenite bioavailability in alkaline Lou soil regardless of Se application rates (p

BackgroundAtrial fibrillation (AF) is a prevalent cardiac arrhythmia, with ventricular rate control being a critical therapeutic target. However, the optimal range for ventricular rate control remains unclear. Additionally, the relationship between different levels of ventricular rate control and cardiac remodeling in patients with atrial fibrillation remains unclear.ObjectiveThis study aims to explore the relationship between different levels of heart rate control and cardiac remodeling in patients with early persistent atrial fibrillation.MethodsA bi-center prospective cohort study was conducted, enrolling patients with newly diagnosed persistent AF and rapid ventricular rates, yet with a normal cardiac size, from March 2019–May 2020 at the people's hospital of Chongqing Hechuan and the First Affiliated Hospital of Zhengzhou University. Patients were divided into four groups based on their average ventricular rate levels from 24 h Holter monitoring: Group I (40 ≤ average rate

BackgroundTherapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. In recent years, the safety and efficacy of hypothermia combining thrombolysis or mechanical thrombectomy have attracted widespread attention. The primary objective of the study was to evaluate the effectiveness and safety of hypothermia by combining reperfusion therapy in acute ischemic stroke patients.MethodsA systematic search was performed in PubMed, EMBASE, Cochrane Library, and the Clinical Trial Registries on articles published until May 2024. The full-text articles were thoroughly reviewed, and relevant information regarding study characteristics and outcomes was extracted. Mantel–Haenszel (M–H) random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). In addition, subgroup analyses were performed focusing on the different hypothermia modalities and duration.ResultsAfter screening 2,265 articles, 10 studies were included in the present analysis with a total sample size of 785. Forest plots of clinical outcomes were as follows: modified Rankin Scale (mRS) ≤2 at 3 months (RR = 1.28, 95% CI 1.01–1.61, p = 0.04), mortality within 3 months (RR = 0.95, 95% CI 0.69–1.29, p = 0.73), total complications (RR = 1.02, 95% CI 0.89–1.16, p = 0.77) and pneumonia (RR = 1.35, 95% CI 0.76–2.40, p = 0.31). Subgroup analyses indicated a mild protective effect of selective cerebral hypothermia; however, the difference in mortality between the hypothermia and control groups was not statistically significant (RR = 0.88, 95% CI 0.57–1.35, p = 0.55). Patients undergoing hypothermia for 24–48 h experienced a higher rate of overall complications (RR = 1.37, 95% CI 1.01–1.86, p = 0.04) and pneumonia (RR = 2.84, 95% CI 1.05–7.66, p = 0.04).ConclusionThe preliminary evidence supports the safety and feasibility of hypothermia combined with reperfusion therapy, which should be further investigated in randomized controlled studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024556625.

Objectives: N7-methylguanosine (m7G) modification is closely related to the occurrence of human diseases, but its roles in sepsis remain unclear. This study aimed to explore the patterns of lethality-related m7G regulatory factor-mediated RNA methylation modification and immune microenvironment regulatory features in sepsis. Methods: Three sepsis-related datasets (E-MTAB-4421 and E-MTAB-4451 as training sets and GSE185263 as a validation set) were collected, and differentially expressed m7G-related genes were analyzed between survivors and non-survivors. Lethality-related m7G signature genes were then screened using machine learning methods, followed by the construction of a survival recognition model. Additionally, differences in immune cell distribution were determined and differentially expressed genes (DEGs) between different subtypes were analyzed. Weighted gene co-expression network analysis (WGCNA) was used to select important modules and related hub genes. Results: In total, 10 differentially expressed m7G-related genes were identified between the survivors and non-survivors, and after further analysis, EIF4G3, EIF4E3, NSUN2, NUDT4, and GEMIN5 were identified as the optimal lethality-related m7G genes. A survival status diagnostic model was then constructed with a combined AUC of 0.678. Fifteen types of immune cells were significantly different between survivors and non-survivors. Sepsis samples were classified into two subtypes, with 22 types of immune cells showing significant differences. Subsequently, 1707 DEGs were identified between the two subtypes, which were significantly enriched in 91 GO terms and 16 KEGG pathways. Finally, the green module with |correlation| > 0.3 was found to be closely related to the subtypes and survival status; further, the top10 hub genes were obtained. Conclusion: The constructed survival status diagnostic model based on the five lethality-related m7G signature genes may help predict the survival status of patients, and the 10 hub genes obtained may be potential therapeutic targets for sepsis.

Aging-related lipid metabolic disorder is related to oxidative stress. Selenium (Se)-enriched Cardamine violifolia (SEC) is known for its excellent antioxidant function. The objective of this study was to evaluate the effects of SEC on antioxidant capacity and lipid metabolism in the liver of aged laying hens. A total of 450 sixty-five-wk-old Roman laying hens were randomly divided into 5 treatments: a basal diet (without Se supplementation, CON) and basal diets supplemented with 0.3 mg/kg Se from sodium selenite (SS), 0.3 mg/kg Se from Se-enriched yeast (SEY), 0.3 mg/kg Se from SEC (SEC), or 0.3 mg/kg Se from SEC and 0.3 mg/kg Se from SEY (SEC + SEY). The experiment lasted for 8 wk. The results showed that dietary SEC + SEY supplementation decreased (P < 0.05) triglyceride (in the plasma and liver) and total cholesterol levels (in the plasma), and increased (P < 0.05) HDL-C concentration in plasma compared to CON diet. Compared with CON diet, SEC and/or SEY supplementation decreased (P < 0.05) the mRNA expression of hepatic ACC, FAS and HMGCR, and increased (P < 0.05) PPARα, VTG-II, Apo-VLDL II and ApoB expression. Dietary SEC + SEY and SEY supplementation increased (P < 0.05) Se content in egg yolk and breast muscle compared to CON diet. Dietary SEC, SEY or SEC + SEY supplementation increased (P < 0.05) the activity of antioxidant enzymes (GSH-PX, T-AOC and T-SOD) in the plasma and liver and decreased (P < 0.05) MDA content in the plasma compared to CON diet. Dietary Se supplementation promoted (P < 0.05) mRNA expression of Nrf2 in the liver. In contrast, dietary SEY and SEC supplementation resulted in a decrease (P < 0.05) of hepatic Keap1 mRNA expression compared to CON diet. Dietary SEC + SEY and/or SEC supplementation increased (P < 0.05) mRNA expression of Selenof, GPX1 and GPX4 in the liver compared with CON diet. In conclusion, dietary SEC (0.3 mg/kg Se) or SEC (0.3 mg/kg Se) + SEY (0.3 mg/kg Se) improved the antioxidant capacity and the lipid metabolism in the liver of aged laying hens, which might be associated with regulating Nrf2/Keap1 signaling pathway.

This study aimed to investigate the effects of the in-ovo injection of Yu Ping Feng polysaccharides (YPF) on the immunological development, hatchability, growth performance, intestinal tissue development, intestinal IgA+ cell distribution, and intestinal secretory IgA (SIgA) production in broiler chicken. Herein, 800 chicken embryos were randomly divided into Astragalus polysaccharide (APS), Atractylodes macrocephala polysaccharide (ATR), YPF, and normal saline (control) injection groups—polysaccharide injection, 0.5 mL of 4 mg/mL polysaccharide; normal saline injection, 0.5 mL. The related indexes of hatched chicks were detected, and there were 5 repeats in each group. Compared with the other three groups, the in-ovo YPF injection did not affect the hatching rate of chicken embryos; however, the initial body weight of hatchlings significantly increased and the feed conversion ratio decreased. Additionally, at each time point, the intestinal villus height (VH) of the chicks in the YPF group increased, whereas no notable difference was observed in the crypt depth (CD), resulting in a higher VH/CD ratio. Furthermore, the YPF group exhibited a statistically significant increase in intestinal IgA+ cell count and flushing fluid SIgA level throughout various time periods compared with those in the other three groups. Additionally, the expression of intestinal mucosal immune cytokines, including interleukin (IL)-2, IL-4, IL-6, and interferon-γ, were markedly increased in the duodenum and ileum of the YPF group. Moreover, the analysis of immune development revealed that their serum levels in the polysaccharide-injected groups were also increased, with the YPF groups exhibiting superior performance than the APS and ATR groups and encouraging the development of T and B lymphocytes in the spleen and peripheral blood mononuclear cells. Altogether, the findings of this study demonstrate that the in-ovo injection of YPF can improve the growth performance, intestinal tissue development, and immune system of the broiler chicks.

Background Anti-programmed cell death 1 (PD-1) antibody combined with chemotherapy simultaneously is regarded as the standard treatment for patients with advanced non-small cell lung cancer (NSCLC) by current clinical guidelines. Different immune statuses induced by chemotherapy considerably affect the synergistic effects of the chemo-anti-PD-1 combination. Therefore, it is necessary to determine the optimal timing of combination treatment administration.Methods The dynamic immune status induced by chemotherapy was observed in paired peripheral blood samples of patients with NSCLC using flow cytometry and RNA sequencing. Ex vivo studies and metastatic lung carcinoma mouse models were used to evaluate immune activity and explore the optimal combination timing. A multicenter prospective clinical study of 170 patients with advanced NSCLC was performed to assess clinical responses, and systemic immunity was assessed using omics approaches.Results PD-1 expression on CD8+ T cells was downregulated on day 1 (D1) and D2, but recovered on D3 after chemotherapy administration, which is regulated by the calcium influx-P65 signaling pathway. Programmed cell death 1 ligand 1 expression in myeloid-derived suppressor cells was markedly reduced on D3. RNA sequencing analysis showed that T-cell function began to gradually recover on D3 rather than on D1. In addition, ex vivo and in vivo studies have shown that anti-PD-1 treatment on D3 after chemotherapy may enhance the antitumor response and considerably inhibit tumor growth. Finally, in clinical practice, a 3-day-delay sequential combination enhanced the objective response rate (ORR, 68%) and disease control rate (DCR, 98%) compared with the simultaneous combination (ORR=37%; DCR=81%), and prolonged progression-free survival to a greater extent than the simultaneous combination. The new T-cell receptor clones were effectively expanded, and CD8+ T-cell activity was similarly recovered.Conclusions A 3-day-delay sequential combination might increase antitumor responses and clinical benefits compared with the simultaneous combination.

Double-stranded RNA (dsRNA) has emerged as key player in gene silencing for the past two decades. Tailor-made dsRNA is now recognized a versatile raw material, suitable for a wide range of applications in biopesticide formulations, including insect control to pesticide resistance management. The mechanism of RNA interference (RNAi) acts at the messenger RNA (mRNA) level, utilizing a sequence-dependent approach that makes it unique in term of effectiveness and specificity compared to conventional agrochemicals. Two primary categories of small RNAs, known as short interfering RNAs (siRNAs) and microRNAs (miRNAs), function in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Furthermore, the application of RNAi in crop protection can be achieved by employing plant-incorporated protectants through plant transformation, but also by non-transformative strategies such as the use of formulations of sprayable RNAs as direct control agents, resistance factor repressors or developmental disruptors. This review explores the agricultural applications of RNAi, delving into its successes in pest-insect control and considering its broader potential for managing plant pathogens, nematodes, and pests. Additionally, the use of RNAi as a tool for addressing pesticide-resistant weeds and insects is reviewed, along with an evaluation of production costs and environmental implications.

ABSTRACT Immunotherapy is a pivotal approach in the treatment of lung cancer. Although HLA‐E is a potential target for tumor immunotherapy, its role in lung cancer remains unclear. Previous studies have identified the transcription factor IRF5 as a characteristic gene of M1‐like macrophages, highlighting its crucial role in promoting antitumor immune responses. In this study, we developed an engineered M1‐like macrophage exosomes expressing IRF5 (IRF5 M1‐exos) and demonstrated their ability to inhibit proliferation, migration, and invasion of lung cancer cells. Moreover, our experiments using a nude mouse model revealed that IRF5 M1‐exos exerted potent therapeutic effects by effectively suppressing tumor growth. Notably, the mechanism by which IRF5 exerts its antitumor function through HLA‐E regulation in lung cancer has not been fully elucidated. Here, we identified HLA‐E as a downstream target gene of IRF5 and demonstrated that the overexpression of HLA‐E can counteract the tumor‐promoting effects induced by si‐IRF5 M1‐exos. These results suggest that M1 macrophage‐derived exosomes, enriched with the transcription factor IRF5, exhibit potent antitumor activity by up‐regulating HLA‐E in lung cancer cells. Therefore, IRF5 M1‐exos represent an attractive therapeutic strategy for lung cancer.

Background: Primary aldosteronism (PA) is a prevalent cause of endocrine hypertension characterized by an excess of aldosterone that can induce proinflammatory, prooxidant and profibrotic effects on the heart. Emerging evidence indicates a heightened incidence of atrial fibrillation (AF) in patients with PA, suggesting a significant association between the two conditions. However, the underlying mechanisms remain unclear. The purpose of this study was to investigate the molecular networks associated with the development of both PA and AF. Methods: Datasets were obtained from the Gene Expression Omnibus database. Hub genes were identified by enrichment and protein–protein interaction analysis. These hub genes were subsequently validated via two independent external datasets: GSE60042 (PA microarray dataset) and GSE41177 (AF microarray dataset). Following the identification of shared genes, quantitative real-time polymerase chain reaction (qPCR) was employed to verify the reliability of the dataset and to further confirm the presence of shared genes in clinical samples. Results: The results of the common gene analysis revealed that immune and inflammatory responses may be shared features in the pathophysiology of PA and AF. One hub gene, specifically tumor necrosis factor superfamily member 10 (TNFSF10), was identified through various analyses and subsequently validated via qPCR. Compared with that in healthy controls, the expression level of TNFSF10 was lower in PA patients with AF. Conclusion: Our findings indicate that TNFSF10 may play a role in the pathophysiology of AF complications associated with PA conditions, suggesting that it could serve as a potential target for the diagnosis or treatment of PA patients complicated with AF.

Purpose: To observe the clinical features of the paracentral acute middle maculopathy (PAMM) and to investigate the changes in perfusion density of superficial capillary plexus (SCP) and deep capillary plexus (DCP) in PAMM by optical coherence tomography angiography (OCTA). Methods: Twelve patients (12 eyes) diagnosed with PAMM and 13 healthy participants (13 eyes) were enrolled. The clinical features of 12 PAMM patients were recorded. The perfusion density of SCP and DCP in the parafovea and perifovea (divided into Temporal, Superior, Nasal, and Inferior) was measured by OCTA in PAMM and healthy eyes. Automated macular maps, including SCP and DCP, were also performed. Results: The mean age of patients was 48.08 (range 14–72) years. The best corrected visual acuity (BCVA) was from finger count (FC) to 1.0. Risk factors included hypertension, diabetes mellitus, COVID-19, etc. The patients had signs of retinal vascular disease except for one patient with isolated PAMM. A spectral-domain OCT image of the PAMM eye showed hyperreflectivity in the inner nuclear layer (INL). Compared with healthy eyes, SCP and DCP in PAMM eyes were significantly reduced in all sectors (all p < 0.05) in the parafovea and perifovea. The average perfusion density of SCP in parafovea and perifovea in PAMM eyes were 46.94±4.34% vs 52.21±3.98 % (p = 0.002), 44.01±3.95% vs 50.51±3.14 (p = 0.000) in healthy eyes. The average perfusion density of DCP in parafovea and perifovea in PAMM eyes were 51.22±4.16% vs 57.15±3.87 % (p = 0.002), 47.375±6.23% vs 54.27±5.33 % (p = 0.002) in healthy eyes. Conclusion: PAMM often accompanies concurrent ocular and systemic diseases. OCTA results confirm that the perfusion density of SCP and DCP in the parafovea and perifovea significantly reduced in PAMM patients.

BackgroundBenign Paroxysmal Positional Vertigo (BPPV) is the most common cause of peripheral vertigo, with frequent recurrence, particularly pronounced among middle-aged and elderly populations, significantly affecting patients’ quality of life. This study aimed to identify predictive factors for recurrence in middle-aged and older patients with BPPV and to develop a nomogram prediction model based on these predictors.MethodsThis retrospective study included 582 participants aged ≥45 years who were selected from the electronic medical records system of the First Hospital of Changsha between March 2021 and March 2024. Randomly chosen participants (n = 407, 70%) constituted the training group, whereas the remaining participants (n = 175, 30%) formed the validation group. This study used LASSO binomial regression to select the most predictive variables. A predictor-based nomogram was developed to calculate the risk of BPPV recurrence. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves with 1,000 bootstrap resampling validations. Decision curve analysis (DCA) was conducted to assess the clinical usefulness of the nomogram.ResultsAccording to findings from least absolute shrinkage and selection operator (LASSO) binomial regression and logistic regression screening, older age, higher levels of uric acid (UA) and homocysteine (HCY), diabetes, migraine, anxiety, and insomnia were identified as independent factors associated with an increased recurrence risk of BPPV. A nomogram model for predicting recurrence risk was developed based on these predictors. The nomogram achieved an AUC (C-statistic) of 0.8974 (95% CI: 0.8603–0.9345) in the training group and 0.8829 (95% CI: 0.8253–0.9406) in the validation group. Calibration curves, after 1,000 bootstrap resamples, demonstrated good agreement between the predicted and actual probabilities in the development and validation cohorts. DCA indicated that the nomogram had clinical utility.ConclusionThe nomogram model incorporating age, UA, HCY, diabetes, migraine, anxiety status, and insomnia demonstrated a strong predictive capability for estimating the probability of BPPV recurrence in middle-aged and elderly patients. This tool is valuable for identifying individuals at high risk of BPPV recurrence and can aid physicians in making informed treatment decisions aimed at reducing recurrence rates.