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Abstract The existence of flaws seriously weakens the rock strength, directly affects the crack expansion morphology, and indirectly affects the slope stability. In this study, uniaxial compression tests were carried out on double-flawed granite to investigate the effects of flaw angle on its compressive strength and crack coalescence based on DIC technology and PFC2D numerical simulation. The result indicates that the UCS values of flawed specimens at angles of 15°, 30°, 45°, and 60° are approximately 25.5–51.7% lower than that of the intact specimen. The failure strength of the double-flawed sample increases with the increase of flaw inclination angle, and the fracture morphology shifts from no expansion to split expansion. When the flaw tip strain of each flaw sample exceeded 0.6%, the stress concentration was generated at the flaw tip, and the sample began to appear macroscopic large cracks. DIC technique can well observe the crack initiation and propagation process, recording inclined shear strain bands at flaw tips, tensile strain bands in the middle of flaws, and tensile shear O-shaped strain ring in rock bridge areas. Numerical simulations using PFC2D software were carried out and showed a good agreement with the physical results. In addition, the effect of structural inclination on specimen failure strength is clearly explained by the theory of compressive damage based on the projected size of flaws. The deformation of rock mass is not a simple material deformation but is composed of material deformation and structural deformation. These experimental and numerical results enhance our understanding of crack initiation and coalescence characteristics, aiding in the analysis of rock structure stability in scenarios such as excavated underground openings, slopes, and tunneling construction, where pre-existing cracks or step-path fractures are pivotal to structural integrity.

Abstract Background The correlation between the triglyceride-glucose (TyG) index and mortality in the general population remains controversial, with inconsistent conclusions emerging from different studies. Objective This study aims to investigate whether there is an association between the TyG index and mortality in the general population in the United States, and to explore whether a new index combining the TyG index with systemic inflammation indicators can better predict all-cause and cardiovascular mortality risks in the general population than using the TyG index alone. Methods Calculate the systemic inflammation indicators and TyG index for each participant based on their complete blood count, as well as their triglyceride and glucose levels in a fasting state. TyG-inflammation indices were obtained by multiplying the TyG index with systemic inflammation indicators (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI). Based on the weighted Cox proportional hazards model, assess whether the TyG and TyG-Inflammation indices are associated with mortality risk in the general population. Restricted cubic splines (RCS) are used to clarify the dose-response relationship between the TyG and TyG-Inflammation indices and mortality, and to visualize the results. Time-dependent receiver operating characteristic (ROC) curves are used to evaluate the accuracy of the TyG and TyG-Inflammation indices in predicting adverse outcomes. Results This study included 17,118 participants. Over a median follow-up period of 125 months, 2595 patients died. The TyG index was not found to be related to mortality after adjusting for potentially confounding factors. However, the TyG-inflammation indices in the highest quartile (Q4), except for TyG-lgPLR, were significantly associated with both all-cause and cardiovascular mortality, compared to those in the lowest quartile (Q1). Among them, TyG-MLR and TyG-lgSII showed the strongest correlations with all-cause mortality and cardiovascular mortality. Specifically, compared to their respective lowest quartiles (Q1), participants in the highest quartile (Q4) of TyG-MLR had a 48% increased risk of all-cause mortality (95% CI: 1.23–1.77, P for trend

Abstract Observational and genetic studies have reported the relationship between dyslexia and Alzheimer’s disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes. First, we selected 42 dyslexia genetic variants from a large-scale genome-wide association studies (GWAS) dataset and extracted their corresponding GWAS summary statistics from AD, VD, LBD, and FTD. Second, we selected four MR methods, including inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO. Heterogeneity, horizontal pleiotropy, and leave-one-out sensitivity analysis were then used to evaluate the reliability of all causal estimates. We also conducted multivariable MR (MVMR) and mediation analysis to assess the potential mediating role of cognitive performance (CP) or educational achievement (EA) on the causal association between dyslexia and AD. Two MVMR methods, including MV IVW and MV-Egger, and two-step MR were used to perform the analysis. Using IVW, we found a significant causal association between increased dyslexia and increased risk of AD (OR = 1.15, 95% CI: 1.04–1.28, P = 0.006), but not VD, LBD, FTD, or its four subtypes. MR-PRESSO further supported the statistically significant association between dyslexia and AD (OR = 1.15, 95% CI: 1.05–1.27, P = 0.006). All sensitivity analyses confirmed the reliability of causal estimates. Using MV IVW and mediation analysis, we found no causal relationship between dyslexia and AD after adjusting for CP but not EA, CP mediated the total effect of dyslexia on AD with a proportion of 46.32%. We provide genetic evidence to support a causal effect of increased dyslexia on increased risk of AD, which was largely mediated by CP. Reading activity may be a potential intervention strategy for AD by improving cognitive function.

Shaped charge liner (SCL) has been extensively applied in oil recovery and defense industries. Achieving superior penetration capability through optimizing SCL structures presents a substantial challenge due to intricate rate-dependent processes involving detonation-driven liner collapse, high-speed jet stretching, and penetration. This study introduces an innovative optimization strategy for SCL structures that employs jet penetration efficiency as the primary objective function. The strategy combines experimentally validated finite element method with machine learning (FEM-ML). We propose a novel jet penetration efficiency index derived from enhanced cutoff velocity and shape characteristics of the jet via machine learning. This index effectively evaluates the jet penetration performance. Furthermore, a multi-model fusion based on a machine learning optimization method, called XGBOOST-MFO, is put forward to optimize SCL structure over a large input space. The strategy's feasibility is demonstrated through the optimization of copper SCL implemented via the FEM-ML strategy. Finally, this strategy is extended to optimize the structure of the recently emerging CrMnFeCoNi high-entropy alloy conical liners and hemispherical copper liners. Therefore, the strategy can provide helpful guidance for the engineering design of SCL.

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 Radiomics offers a noninvasive avenue for predicting clinicopathological factors. However, thorough investigations into a robust breast cancer outcome-predicting model and its biological significance remain limited. This study develops a robust radiomic model for prognosis prediction, and further excavates its biological foundation and transferring prediction performance. We retrospectively collected preoperative dynamic contrast-enhanced MRI data from three distinct breast cancer patient cohorts. In FUSCC cohort (n = 466), Lasso was used to select features correlated with patient prognosis and multivariate Cox regression was utilized to integrate these features and build the radiomic risk model, while multiomic analysis was conducted to investigate the model’s biological implications. DUKE cohort (n = 619) and I-SPY1 cohort (n = 128) were used to test the performance of the radiomic signature in outcome prediction. A thirteen-feature radiomic signature was identified in the FUSCC cohort training set and validated in the FUSCC cohort testing set, DUKE cohort and I-SPY1 cohort for predicting relapse-free survival (RFS) and overall survival (OS) (RFS: p = 0.013, p = 0.024 and p = 0.035; OS: p = 0.036, p = 0.005 and p = 0.027 in the three cohorts). Multiomic analysis uncovered metabolic dysregulation underlying the radiomic signature (ATP metabolic process: NES = 1.84, p-adjust = 0.02; cholesterol biosynthesis: NES = 1.79, p-adjust = 0.01). Regarding the therapeutic implications, the radiomic signature exhibited value when combining clinical factors for predicting the pathological complete response to neoadjuvant chemotherapy (DUKE cohort, AUC = 0.72; I-SPY1 cohort, AUC = 0.73). In conclusion, our study identified a breast cancer outcome-predicting radiomic signature in a multicenter radio-multiomic study, along with its correlations with multiomic features in prognostic risk assessment, laying the groundwork for future prospective clinical trials in personalized risk stratification and precision therapy.

Abstract Acquiring multi-dimensional optical information, such as intensity, spectrum, polarization, and phase, can significantly enhance the performance of photodetectors. Incorporating these dimensions allows for improved image contrast, enhanced recognition capabilities, reduced interference, and better adaptation to complex environments. However, the challenge lies in obtaining these dimensions on a single photodetector. Here we propose a misaligned unipolar barrier photodetector based on van der Waals heterojunction to address this issue. This structure enables spectral detection by switching between two absorbing layers with different cut-off wavelengths for dual-band detection. For polarization detection, anisotropic semiconductors like black phosphorus and black arsenic phosphorus inherently possess polarization-detection capabilities without additional complex elements. By manipulating the crystal direction of these materials during heterojunction fabrication, the device becomes sensitive to incident light at different polarization angles. This research showcases the potential of the misaligned unipolar barrier photodetector in capturing multi-dimensional optical information, paving the way for next-generation photodetectors.

Abstract Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by early metastasis, rapid tumor growth and poor prognosis. In recent decades, the epidemiology, initiation and mutation characteristics of SCLC, as well as abnormal signaling pathways contributing to its progression, have been widely studied. Despite extensive investigation, fewer drugs have been approved for SCLC. Recent advancements in multi-omics studies have revealed diverse classifications of SCLC that are featured by distinct characteristics and therapeutic vulnerabilities. With the accumulation of SCLC samples, different subtypes of SCLC and specific treatments for these subtypes were further explored. The identification of different molecular subtypes has opened up novel avenues for the treatment of SCLC; however, the inconsistent and uncertain classification of SCLC has hindered the translation from basic research to clinical applications. Therefore, a comprehensives review is essential to conclude these emerging subtypes and related drugs targeting specific therapeutic vulnerabilities within abnormal signaling pathways. In this current review, we summarized the epidemiology, risk factors, mutation characteristics of and classification, related molecular pathways and treatments for SCLC. We hope that this review will facilitate the translation of molecular subtyping of SCLC from theory to clinical application.

Abstract The development of highly efficient and durable alkaline hydrogen evolution reaction (HER) catalysts is crucial for achieving high-performance practical anion exchange membrane water electrolyzer (AEMWE) at ampere-level current density. Herein, we report a design concept by employing Ga single atoms as an electronic bridge to stabilize the Ru clusters for boosting alkaline HER performance in practical AEMWE. Experimental and theoretical results collectively reveal that the bridged Ga sites trigger strong metal-support interaction for the homogeneous distribution of Ru clusters with high density, as well as optimize the Ru–H bond strength due to the electron transfer between Ru and Ga for enhanced intrinsic HER activity. Moreover, the oxophilic Ga sites near the Ru clusters tend to adsorb the hydroxyl species and accelerate the water dissociation for sufficient proton supplement in an alkaline medium. The Ru–GaSA/N–C catalyst exhibits a low overpotential of 4 ± 1 mV (10 mA cm−2) and high mass activity of 9.3 ± 0.5 A mg−1 Ru at −0.05 V vs RHE. In particular, the Ru–GaSA/N–C-based AEMWE in 1 M KOH delivers a voltage of only 1.74 V to reach an industrial current density of 1 A cm−2, and can steadily operate at 1 A cm−2 for more than 170 h.

Objective: To predict and validate the antidepressant pharmacodynamic components and mechanism of action of Hemerocallis citrina Baroni (H.citrina) and to determine the optimal extraction process of H.citrina. Methods: The key active ingredients, action targets and key signaling pathways of H.citrina were selected by network pharmacology. HPLC fingerprints of H.citrina were established, and similarity evaluation was conducted on 15 batches of H.citrina fingerprints from Suqian, Jiangsu Province. The common peak and the antidepressant active components in the fingerprints were identified. The key antidepressant index components of H.citrina were determined based on the results of the fingerprints and molecular docking. An orthogonal experiment was conducted to optimize the extraction process of H.citrina. Results: According to the result of topology analysis,10 key antidepressant active ingredients in H.citrina were identified, such as isoeugenol, rutin and hyperoside. The protein-protein interaction (PPI) network of H.citrina and depressive disorder targets were constructed and cluster analysis was applied, resulted to that the active ingredient targets on 10 key proteins such as SRC, TP53, HSP90AA1. Enrichment analysis of the gene ontology (GO) function and Kyoto Encyclopedia of genes and genomes (KEGG) signaling pathway for the key anti-inflammatory targets of H.citrina were applied and 10 key KEGG signal pathways were obtained, including the cancer pathway, PI3K/Akt signaling pathway, neuroactive ligand-receptor interaction signaling pathway and so on. The HPLC fingerprints of 15 batches of H.citrina were established, and 15 common peaks were obtained. Among them, four key components of antidepressant were identified: Nechlorogenic acid, rutin, hyperoside and quercetin. Molecular docking results showed that the docking binding energies of the above components to the target were all less than −5 kcal/mol. The transfer rate of the components (total flavonoids, neochlorogenic acid and rutin) and solid yield of H. citrina were used as indicators. The extraction process of H.citrina was optimized as the ratio of material-liquid 1:10 (g/mL), the extraction process was twice, and the extraction time was 1 hour. The optimized process resulted in a transfer rate of 72.12%±0.61% for total flavonoids, 68.11%±0.65% for neochlorogenic acid, 63.40%±1.59% for rutin, and a solid yield of 52.62%±0.15%. Conclusion: Through the organic combination of network pharmacology and fingerprint, the antidepressant index components from H.citrina were screened out for extraction technology research. The optimized H.citrina extraction process of H.citrina was stable and feasible, providing a theoretical basis for the development of research on H. citrina as an antidepressant functional food.

In this study, aiming at fulfilling the requirement of polarization acquisition and utilization, a method for active deception jamming recognition based on the time-varying polarization-conversion metasurface is investigated. First, an anisotropic phase-modulated metasurface supporting 3-bit phase quantization in the 9.6～10.1 GHz frequency band is designed. By optimizing the periodical phase coding, the polarization state can be converted on demand. And then, loading the polarization-conversion metasurface on a single polarization radar antenna so that the polarization states of the antenna can change along a specific trajectory. By extracting the difference in the polarization domain between target and active deception jamming, the active deception jamming could be distinguished from the radar echo. The simulation results show that under the constraints of three different polarization trajectories, the active deception jamming and targets exhibit a significant clustering effect, and the identification effect is stable. Compared with jamming identification methods that rely on dual-polarization or full-polarization radar systems, the proposed method has both low cost and high efficiency, which has great application potential in radar anti-jamming.

Liver fibrosis is an important step in the transformation of chronic liver disease into cirrhosis and liver cancer, and structural changes and functional disorders of liver sinusoidal endothelial cells (LSECs) are early events in the occurrence of liver fibrosis. Therefore, it is necessary to identify the key regulatory genes of endothelial dysfunction in the process of liver fibrosis to provide a reference for the diagnosis and treatment of liver fibrosis. In this study, we identified 230 common differentially expressed genes (Co-DEGs) by analyzing transcriptomic data of primary LSECs from three different liver fibrosis mouse models (carbon tetrachloride; choline-deficient, l-amino acid-defined diet; and nonalcoholic steatohepatitis). Enrichment analysis revealed that the Co-DEGs were mainly involved in regulating the inflammatory response, immune response, angiogenesis, formation and degradation of the extracellular matrix, and mediating chemokine-related pathways. A Venn diagram analysis was used to identify 17 key genes related to the progression of liver cirrhosis. Regression analysis using the Lasso–Cox method identified genes related to prognosis among these key genes: SOX4, LGALS3, SERPINE2, CD52, and LPXN. In mouse models of liver fibrosis (bile duct ligation and carbon tetrachloride), all five key genes were upregulated in fibrotic livers. This study identified key regulatory genes for endothelial dysfunction in liver fibrosis, namely SOX4, LGALS3, SERPINE2, CD52, and LPXN, which will provide new targets for the development of therapeutic strategies targeting endothelial dysfunction in LSECs and liver fibrosis.

Background Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Abstract Background Antibiotic resistance is a serious global public health issue. However, there are few reports on trends in antimicrobial susceptibility in Chinese neonates, and most of the existing evidence has been derived from adult studies. We aimed to assess the trends in antimicrobial susceptibility of common pathogens in full-term neonates with invasive bacterial infections (IBIs) in China. Methods This cross-sectional survey study analyzed the antimicrobial susceptibility in Chinese neonates with IBIs from 17 hospitals, spanning from January 2012 to December 2021. Joinpoint regression model was applied to illustrate the trends and calculate the average annual percentage change (AAPC). Using Mantel-Haenszel linear-by-linear association chi-square test, we further compared the antibiotic minimum inhibitory concentrations (MICs) by pathogens between 2019 and 2021 to provide precise estimates of changes. Results The proportion of Escherichia coli with extended-spectrum-beta-lactamase-negative strains increased from 0.0 to 88.5% (AAPC = 62.4%, 95% confidence interval (CI): 44.3%, 82.9%), with two breakpoints in 2014 and 2018 (p-trend

Abstract China’s higher education system is shifting from quantitative expansion to connotative development to advance its quality. Since 2015, Chinese governments have been implementing a strategic policy for higher education called “double first-class”, which aims to promote a number of Chinese top universities to construct world-class universities or to establish world-class disciplines. “Double first-class” universities have received a large amount of educational resources through this policy. Taking advantage of resources efficiently is an important element in promoting the development of higher quality higher education. However, research on resource allocation in China’s “double first-class” universities is incomplete. Current research has not clarified the level of resource allocation efficiency or the factors affecting China’s “double first-class” universities. With the help of the superefficient data envelopment analysis (DEA)-Malmquist–Tobit model, this study actively explores the current status of the resource allocation efficiency of China’s “double first-class” universities to fill this gap in the field. Specifically, the development level and change trend of the resource allocation efficiency of 13 “double first-class” universities in China from 2015 to 2019 were measured with the help of the superefficient DEA-Malmquist model. The internal and external factors affecting the resource allocation efficiency of “double first-class” universities are also analysed with the help of the Tobit model. The overall level of resource allocation efficiency of “double first-class” universities is high, but the internal variability is large. From the perspective of efficiency decomposition, it is found that both technical efficiency change (EFch) and technical progress efficiency (TEch) play important roles in improving the total factor productivity (TFP) of resource allocation. Compared with TEch, EFch plays a more significant pulling role. This study confirms that the factors affecting resource allocation efficiency are complex. Among them, the regional economic environment, faculty title structure, and degree of international exchange have significant roles in promoting the resource allocation efficiency of “double first-class” universities, but local financial support and the time of policy implementation have certain negative effects.

Abstract Rabies is a lethal disease caused by the rabies virus (RABV), which causes acute neurological infections in mammals, including human beings. We previously reported that an mRNA vaccine (LVRNA001) encoding the rabies virus’s glycoprotein induced strong protective immune responses to rabies in mice and dogs. Here, we further evaluate the safety of LVRNA001. First, we performed a confirmative efficacy study in dogs, which showed that LVRNA001 fully protected the animals from the virus, both pre- and post-infection. Moreover, using pre- and post-exposure prophylaxis murine models, we showed that LVRNA001, built from the CTN-1 strain, was able to protect against various representative RABV strains from the China I–VII clades. To evaluate the safety of the vaccine, chronic and reproductive toxicity studies were performed with cynomolgus macaques and rats, respectively. In a repeated-dose chronic toxicity study, vaccinated monkeys displayed no significant alterations in body weight, temperature, or hematological and biochemical markers. Lymphocyte subset measurement and histopathological examination showed that no toxicity was associated with the vaccine. The immunogenicity study in cynomolgus macaques demonstrated that LVRNA001 promoted the generation of neutralizing antibodies and Th1-biased immune response. Evaluation of reproductive toxicity in rats revealed that administration of LVRNA001 had no significant effects on fertility, maternal performance, reproductive processes, and postnatal outcomes. In conclusion, LVRNA001 can provide efficient protection against rabies virus infection in dogs and mice, and toxicity studies showed no significant vaccine-related adverse effects, suggesting that LVRNA001 is a promising and safe vaccine candidate for rabies prophylaxis and therapy.

Abstract Background By combining high-frequency and contrast-enhanced ultrasound (CEUS), the position of the severed end of a finger extensor tendon injury and the injury classification can be determined as part of a comprehensive preoperative evaluation in clinical practice. However, there have been no reports of high-frequency ultrasound combined with CEUS for the preoperative diagnosis of human finger extensor tendon injury. Cases presentation One case of complete rupture of the extensor tendon was diagnosed by ultrasound, which was completely consistent with the surgery; one case of incomplete rupture was ultimately confirmed clinically; and one case of distal phalangeal bone base avulsion fracture with tendon contusion and missed diagnosis on the first radiographic examination was confirmed by follow-up radiographic examination. Conclusions Different types of finger extensor tendon injuries exhibit distinctive contrast-enhanced ultrasonography findings. Combined high-frequency and contrast-enhanced ultrasound can accurately locate the position of the severed end of the finger extensor tendon injury before surgery while observing the contrast agent filling area to clarify injury classification, providing a reliable imaging basis for clinical practice and ultimately developing personalized diagnosis and treatment plans for patients to ensure minimal trauma and pain, as well as optimal treatment effects.

Abstract Background Crohn’s disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). Methods This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow’s hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients’ medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. Results EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach’s α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman’s coefficient, which demonstrated a significant correlation with the IBDQ (P

Abstract Background The taxonomy of Taxus Linn. remains controversial due to its continuous phenotypic variation and unstable topology, thus adversely affecting the formulation of scientific conservation strategies for this genus. Recently, a new ecotype, known as Qinling type, is mainly distributed in the Qinling Mountains and belongs to a monophyletic group. Here, we employed multiple methods including leaf phenotype comparison (leaf shapes and microstructure), DNA barcoding identification (ITS + trnL-trnF + rbcL), and niche analysis to ascertain the taxonomic status of the Qinling type. Results Multiple comparisons revealed significant differences in the morphological characters (length, width, and length/width ratio) among the Qinling type and other Taxus species. Leaf anatomical analysis indicated that only the Qinling type and T. cuspidata had no papilla under the midvein or tannins in the epicuticle. Phylogenetic analysis of Taxus indicated that the Qinling type belonged to a monophyletic group. Moreover, the Qinling type had formed a relatively independent niche, it was mainly distributed around the Qinling Mountains, Ta-pa Mountains, and Taihang Mountains, situated at an elevation below 1500 m. Conclusions Four characters, namely leaf curvature, margin taper, papillation on midvein, and edges were put forward as primary indexes for distinguishing Taxus species. The ecotype Qingling type represented an independent evolutionary lineage and formed a unique ecological niche. Therefore, we suggested that the Qingling type should be treated as a novel species and named it Taxus qinlingensis Y. F. Wen & X. T. Wu, sp. nov.

Abstract Background To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection. Methods This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission. Results We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms. Conclusion Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes.

Background: Emerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of

ABSTRACTPre-treatment processing technology plays a crucial role in the overall freshwater fish processing procedure, and automatic head and tail cutting stands out as a significant pre-treatment technique within the industry. The system for removing the head and tail of freshwater fish comprised a Cartesian coordinate manipulator, a fish transfer device, a control system, and an image acquisition device. In the vision system, five image segmentation methods were utilized for fish head and tail image segmentation comparison tests. These methods include U-Net (U-shaped Deep Neural Network), DeeplabV3, PSPNet (Pyramid Scene Parsing Network), FastSCNN (Fast Semantic Segmentation Network), and ICNet (Image Cascade Network), all of which were employed to evaluate their performance. Among the tested segmentation methods, the ICNet demonstrated the most excellent segmentation capability. The experimental results indicated a segmentation accuracy of 99.01%, a mean intersection over union (MIoU) of 82.50%, and an image processing time of 15.25 ms. The results showed that the fish head and tail were successfully cut off using this model for recognition with a circular knife. Consequently, the segmentation model employed in the machine vision system within this study has demonstrated successful applicability in automatically cutting the heads and tails of freshwater fish of various sizes.

Abstract Introduction Patients with systemic lupus erythematosus (SLE) have variable treatment pathways, including antimalarials, glucocorticoids, immunosuppressants, and/or biologics. This study describes differences in clinical outcomes when initiating belimumab (BEL) before and after immunosuppressant use. Methods This real-world, retrospective cohort study (GSK Study 217536) used de-identified administrative claims data from January 2015 to December 2022 in the Komodo Health Database. Adults with moderate/severe SLE initiating BEL (index date) were identified from January 2017 to May 2022, allowing a ≥ 24-month baseline period. Patients were stratified into those initiating BEL before immunosuppressant use (no immunosuppressant use within 24 months before index) and those initiating BEL after immunosuppressant use (one immunosuppressant used within 24 months before index). Oral glucocorticoid (OGC) use, SLE flares, new organ damage, and all-cause healthcare resource utilization (HCRU) were analyzed descriptively over a 24-month follow-up. Results Baseline SLE severity was similar for patients initiating BEL before (n = 2295) versus after (n = 4114) immunosuppressant use (moderate, 83.1% vs 79.0%; severe, 16.8% vs 21.0%). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates and OGC use. Post-index, patients initiating BEL before versus after immunosuppressant use discontinued their OGC sooner (moderate baseline SLE, 4.5 vs 8.9 months; severe baseline SLE, 6.2 vs 11.6 months). Patients initiating BEL before versus after immunosuppressant use had lower SLE flare rates per person-year at all time points (especially severe flare rates in patients with severe baseline SLE, 0.70 vs 1.48 through 24 months post-index). Median time to new organ damage occurrence was longer in patients initiating BEL before versus after immunosuppressant use (moderate baseline SLE, 32.1 vs 26.7 months; severe baseline SLE, 22.7 vs 21.6 months). All-cause HCRU was similar between cohorts. Conclusions These results suggest that patients initiating BEL before versus after immunosuppressant use had more favorable outcomes.

In order to study the chemical constituents from Chloranthus henryi and their antitumor activities in vitro. The chemical constituents of ethyl acetate fraction, extracted with 95% ethanol from C. henryi were isolated and purified by silica gel column chromatography, reversed phase column chromatography, Sephadex LH-20 column chromatography and preparation liquid chromatography, and their structures were identified by the physicochemical properties, spectral data combined with relevant literatures. The cytotoxic activities of these compounds were evaluated by MTT method. The results were as follows: (1) Twelve compounds were isolated and identified as pipercyclobutanamide C (1), chololactone A (2), sarcanolide B (3), oxacol A (4), chloramultiol D (5), chlorasessilifol B (6), chlorajaponol (7), tianmushanol (8), spicachlorantins B (9), spicachlorantins A (10), serrachlorin A (11), chloramultiols A (12). Among them, Compound 1 was identified as a new compound, and except for Compound 8, all the other compounds were isolated from the C. henryi for the first time. (2) The cytotoxic activity test results showed that only compounds 2 and 7 had good inhibitory effects on HeLa cells in vitro, while the other compounds showed no inhibition effects. The IC50 of the two compounds were (4.50±0.27) μmol·L-1 and (4.25±0.08) μmol·L-1 respectively. In conclusion, the study enriches the chemical constituents of C. henryi, and provides a reference for the further exploration and utilization of this Chloranthus herb plants.

Abstract Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Abstract Background Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore. Methods We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan–Meier plotter database and clinical breast cancer tissue samples. Results We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo. Conclusions Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.

Abstract Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.

Abstract Background Collagen (COL) genes, play a key role in tumor invasion and metastasis, are involved in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. However, studies focusing on the diagnostic value of the COL4 family in stomach adenocarcinoma (STAD) are currently lacking. Methods The TCGA database was employed to retrieve the clinical features and RNA sequencing expression profiles of patients with STAD. We conducted an investigation to examine the expression disparities between STAD and adjacent normal tissues. Kaplan-Meier survival analysis was utilized to assess their prognostic significance, while Spearman correlation analysis was employed to determine their association with immune checkpoint genes and immunomodulatory molecules. Furthermore, GO and KEGG analyses were performed on the COL4s-related genes, revealing potential biological pathways through gene set enrichment analysis (GSEA). Subsequently, we explored the extent of immune infiltration of the COL4 family in STAD using the TIMER database. Lastly, the expression levels of the COL4 family in STAD were further validated through quantitative PCR (qPCR) and western blot techniques. Results The expression levels of COL4A1/2 were significantly upregulated, while COL4A5/6 were conspicuously downregulated in STAD. The survival analysis revealed that the upregulated COL4s indicated poorer overall survival, first progression and post-progression survival outcomes. Additionally, our findings demonstrated a positive correlation between the expressions of COL4A1/2/3/4 and the infiltration of immune cells, including CD8 + T cells, dendritic cells, macrophages, neutrophils and CD4 + T cells. Further correlation analysis uncovered a favorable association between the expression of COL4A1/2/3/4 and various crucial immunomodulatory molecules, immunological checkpoint molecules, and chemokines. Quantitative PCR analysis confirmed that the expression patterns of COL4A1/3/4/6 genes aligned with the finding from the TCGA database. However, gastric cancer cells exhibited downregulation of COL4A2. Consistently, the protein level of COL4A1 was elevated, whereas the protein level of COL4A2 was reduced in the gastric cancer cell lines. Conclusion COL4s could potentially serve as biomarkers for diagnosing and predicting the prognosis of STAD.

To solve the problems in restoring sedimentary facies and predicting reservoirs in loose gas-bearing sediment, based on seismic sedimentologic analysis of the first 9-component S-wave 3D seismic dataset of China, a fourth-order isochronous stratigraphic framework was set up and then sedimentary facies and reservoirs in the Pleistocene Qigequan Formation in Taidong area of Qaidam Basin were studied by seismic geomorphology and seismic lithology. The study method and thought are as following. Firstly, techniques of phase rotation, frequency decomposition and fusion, and stratal slicing were applied to the 9-component S-wave seismic data to restore sedimentary facies of major marker beds based on sedimentary models reflected by satellite images. Then, techniques of seismic attribute extraction, principal component analysis, and random fitting were applied to calculate the reservoir thickness and physical parameters of a key sandbody, and the results are satisfactory and confirmed by blind testing wells. Study results reveal that the dominant sedimentary facies in the Qigequan Formation within the study area are delta front and shallow lake. The RGB fused slices indicate that there are two cycles with three sets of underwater distributary channel systems in one period. Among them, sandstones in the distributary channels of middle-low Qigequan Formation are thick and broad with superior physical properties, which are favorable reservoirs. The reservoir permeability is also affected by diagenesis. Distributary channel sandstone reservoirs extend further to the west of Sebei-1 gas field, which provides a basis to expand exploration to the western peripheral area.

Abstract Objectives To investigate whether reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with deep learning reconstruction (DLR) can improve the accuracy of evaluating muscle invasion using VI-RADS. Methods Eighty-six bladder cancer participants who were evaluated by conventional full field-of-view (fFOV) DWI, standard rFOV (rFOVSTA) DWI, and fast rFOV with DLR (rFOVDLR) DWI were included in this prospective study. Tumors were categorized according to the vesical imaging reporting and data system (VI-RADS). Qualitative image quality scoring, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC value were evaluated. Friedman test with post hoc test revealed the difference across the three DWIs. Receiver operating characteristic analysis was performed to calculate the areas under the curve (AUCs). Results The AUC of the rFOVSTA DWI and rFOVDLR DWI were higher than that of fFOV DWI. rFOVDLR DWI reduced the acquisition time from 5:02 min to 3:25 min, and showed higher scores in overall image quality with higher CNR and SNR, compared to rFOVSTA DWI (p 0.05). Conclusions rFOV DWI with DLR can improve the diagnostic accuracy of fFOV DWI for evaluating muscle invasion. Applying DLR to rFOV DWI reduced the acquisition time and improved overall image quality while maintaining ADC value and diagnostic accuracy. Critical relevance statement The diagnostic performance and image quality of full field-of-view DWI, reduced field-of-view (rFOV) DWI with and without DLR were compared. DLR would benefit the wide clinical application of rFOV DWI by reducing the acquisition time and improving the image quality. Key Points Deep learning reconstruction (DLR) can reduce scan time and improve image quality. Reduced field-of-view (rFOV) diffusion-weighted imaging (DWI) with DLR showed better diagnostic performances than full field-of-view DWI. There was no difference of diagnostic accuracy between rFOV DWI with DLR and standard rFOV DWI. Graphical Abstract

Abstract Background Growth differentiation factor‐15 (GDF‐15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF‐15 and pre‐eclampsia (PE). Method The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF‐15 were measured by using enzyme‐linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF‐15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs). Results MOM of GDF‐15 in PE participants was higher compared with controls (1.588 vs. 1.000, p 1) had a 4.74‐fold (95% CI = 2.23–10.08, p

Introduction The aim of the study is the regulatory effect of MicroRNA-210 (MiR- 210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. Methods Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRTPCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. Results Our results showed that MiR-210 mRNA levels were significantly downregulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro , MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. Conclusions MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future.

Abstract Backgrounds Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. Methods We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. Results Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Abstract Background Cervical cancer is a prevalent malignancy of the female reproductive system. Cervical intraepithelial neoplasia (CIN) is a precursor lesion for CC. Various studies have examined circulating microRNAs (miRNAs) as potential early diagnostic markers for CC and CIN. However, the findings have been inconclusive. Therefore, it is necessary to evaluate the diagnostic accuracy and identify potential sources of variability among these studies. Methods: The PubMed, Cochrane Library, Embase, and Web of Science databases were searched to identify relevant literature. Then, Stata 14.0 was utilized to calculate summary estimates for diagnostic parameters, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic (ROC). To scrutinize the heterogeneity, the Cochran-Q test and I2 statistic were utilized. As significant heterogeneity was observed, the random effects model was chosen. To explore potential sources of the heterogeneity, subgroup and regression analyses were conducted. Results: We analysed 12 articles reporting on 24 studies involving 1817 patients and 1731 healthy controls. The pooled sensitivity was 0.77 (95% CI 0.73–0.81), the specificity was 0.81 (95% CI 0.73–0.86), the PLR was 3.99 (95% CI 2.81–5.65), the NLR was 0.28 (95% CI 0.23–0.35), the DOR was 14.18 (95% CI 8.47–23.73), and the area under the curve (AUC) was 0.85 (95% CI 0.81–0.87). Subgroup analysis revealed that multiple miRNAs can improve diagnostic performance; the pooled sensitivity of multiple miRNAs was 0.78 (95% CI 0.68–0.86), the specificity was 0.85 (95% CI 0.78–0.90), and the AUC was 0.89 (95% CI 0.86–0.91). Conclusion: This study suggested that circulating microRNAs may be biomarkers for early CC diagnosis.

Thermal boundary conditions of the turbine disk cavity system are of great importance in the design of secondary air systems in aero-engines. This study aims to investigate the complex heat transfer mechanisms of a rotating turbine disk under high-speed conditions. A high-speed rotating free-disk model with Dorfman empirical solutions is developed to evaluate the heat transfer performance considering various factors. Specifically, the influence of compressibility, variable properties, and heat dissipation is determined using theoretical and numerical analyses. In particular, a novel combined solution method is proposed to simplify the complex heat transfer problem. The results indicate that the heat transfer performance of a free disk is primarily influenced by the rotating Mach number, rotating Reynolds number, Rossby number, and wall temperature ratio. The heat transfer temperature and Nusselt number of the free disk are strongly correlated with the rotating Mach number and rotating Reynolds number. Analysis reveals that heat dissipation is a critical factor affecting the accurate evaluation of the heat transfer performance of the turbine disk. Thus, the combined solution method can serve as a reference for future investigations of flow and heat transfer in high-speed rotating turbine disk cavity systems in aero-engines.

Introduction Apoptosis and chronic inflammation are the main phenotypes in chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke exposure is the leading risk factor for COPD, which causes aberrant airway epithelial structure and function. As a non-classical calpain, the molecular function of calpain5 (CAPN5) in COPD remains unclear. This study investigated the role of CAPN5 in mediating cigarette smoke extract (CSE)-induced apoptosis and inflammation. Methods Immunohistochemistry (IHC) and Western blotting (WB) were performed to detect the location and expression of CAPN5. In vitro, BEAS-2B cells were transfected with CAPN5 siRNA or CAPN5 plasmid, followed by phosphatebuffered saline (PBS) or cigarette smoke extract (CSE) treatment. The protein expression levels of CAPN5, NF-κB p65, p-p65, IκBα, p-IκBα and apoptosis proteins (BCL-2, BAX) were measured by WB. Flow cytometry (FCM) was performed to analyze the cell apoptosis index. Results CAPN5 was mainly expressed in the airway epithelium and significantly decreased in the COPD-smoker and emphysema-mouse groups. Silencing CAPN5 significantly decreased the protein expression of BCL-2, IκBα, and increased p-p65 and BAX protein expression. Additionally, an increased apoptosis index was detected after silencing CAPN5. Moreover, overexpression of CAPN5 partly inhibited IκBα degradation and p65 activation, and reduced CSE-induced inflammation and apoptosis. Conclusions These combined results indicate that CAPN5 could protect against CSEinduced apoptosis and inflammation, which may provide a potential therapeutic target for smoking-related COPD.

To explore the dynamic behavior of magnetic abrasive particles in the grinding process of pipe fittings, the grinding process of magnetic abrasive particles was simulated using discrete elements. The changes in motion trajectory and grinding force with the speed of pipe fittings and the processing gap were analyzed. Single abrasive particle ball motion and magnetic particle grinding test were conducted to verify the accuracy of the magnetic field force model and the feasibility of visualizing the particle kinematic behavior. The results show that as the speed of the pipe fittings increases, the magnetic abrasive particles move outside the processing area due to centrifugal force, and the larger the processing gap, the easier they are "thrown away". Before reaching the critical rotation speed, the grinding force decreases, and material removal efficiency increases with the increase in pipe rotation speed. When the pipe rotation speed increases from 400 r/min to the critical rotation speed and the machining gaps are 2 mm and 4 mm, the grinding forces decrease by 5.4 μN and 2.3 μN respectively, leading to a significant improvement in material removal efficiency. However, with a machining gap of 6 mm, the grinding force changes little, and when the rotation speed exceeds the critical rotation speed of 650 r/min, material removal efficiency decreases. Additionally, the material removal amount increases with the increase in pipe rotation speed before reaching the critical rotation speed, but increasing the processing gap reduces the critical rotation speed. The change in material removal amount aligns with the simulation results, validating the reliability of the simulation analysis.

Abstract Secondary lung injury after SCI is a major cause of patient mortality, with apoptosis playing a key role. This study aimed to explore the impact of treadmill training and miR145-5p on the MAPK/Erk signaling pathway and apoptosis in rats with complete SCI. SD rats were used to establish T10 segmental complete SCI models and underwent treadmill training 3, 7, or 14 days postinjury. Various techniques including arterial blood gas analysis, lung wet/dry weight ratio, HE staining, immunofluorescence staining, immunohistochemical staining, qRT-PCR, and Western blotting were employed to assess alterations in lung function and the expression levels of crucial apoptosis-related factors. In order to elucidate the specific mechanism, the impact of miR145-5p on the MAPK/Erk pathway and its role in apoptosis in lung cells were confirmed through miR145-5p overexpression and knockdown experiments. Following spinal cord injury (SCI), an increase in apoptosis, activation of the MAPK/Erk pathway, and impairment of lung function were observed in SCI rats. Conversely, treadmill training resulted in a reduction in alveolar cell apoptosis, suppression of the MAPK/Erk pathway, and enhancement of lung function. The gene MAP3K3 was identified as a target of miR145-5p. The influence of miR145-5p on the MAPK/Erk pathway and its impact on apoptosis in alveolar cells were confirmed through the manipulation of miR145-5p expression levels. The upregulation of miR145-5p in spinal cord injury (SCI) rats led to a reduction in MAP3K3 protein expression within lung tissues, thereby inhibiting the MAPK/Erk signaling pathway and decreasing apoptosis. Contrarily, rats with miR145-5p knockdown undergoing treadmill training exhibited an increase in miR145-5p expression levels, resulting in the inhibition of MAP3K3 protein expression in lung tissues, suppression of the MAPK/Erk pathway, and mitigation of lung cell apoptosis. Ultimately, the findings suggest that treadmill training may attenuate apoptosis in lung cells post-spinal cord injury by modulating the MAP3K3 protein through miR145-5p to regulate the MAPK/Erk signaling pathway.

Abstract Background Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. Methods We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α (HIF-1α) and LAMC1 expression were explored. Results LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion, while overexpression of LAMC1 in U251 cells leads to the opposite trend. Most TCGA solid cancers including glioma showed enhancement of HIF-1α expression. High HIF-1α expression leads to adverse prognosis in gliomas, besides, HIF-1α expression was positively related to LAMC1. Mechanistically, HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O2)-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. Conclusions High expression of LAMC1 in some solid tumors including gliomas suggests a poor prognosis. The hypoxic microenvironment in gliomas activates the HIF-1α/LAMC1 signaling, thereby promoting tumor progression. Targeted intervention on the HIF-1α/LAMC1 signaling attenuates cell growth and invasion, suggesting a new strategy for glioma treatment.

Abstract The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal–organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Abstract This research aimed to investigate effects of different yeast culture (YC) levels on in vitro fermentation characteristics and bacterial and fungal community under high concentrate diet. A total of 5 groups were included in the experiment: control group without YC (CON), YC1 (0.5% YC proportion of substrate dry matter), YC2 (1%), YC3 (1.5%) and YC4 (2%). After 48 h of fermentation, the incubation fluids and residues were collected to analyze the ruminal fermentation parameters and bacterial and fungal community. Results showed that the ruminal fluid pH of YC2 and YC4 groups was higher (P

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

Abstract Background The Vesical Imaging-Reporting and Data System (VI-RADS) has demonstrated effectiveness in predicting muscle invasion in bladder cancer before treatment. The urgent need currently is to evaluate the muscle invasion status after neoadjuvant chemotherapy (NAC) for bladder cancer. This study aims to ascertain the accuracy of VI-RADS in detecting muscle invasion post-NAC treatment and assess its diagnostic performance across readers with varying experience levels. Methods In this retrospective study, patients with muscle-invasive bladder cancer who underwent magnetic resonance imaging (MRI) after NAC from September 2015 to September 2018 were included. VI-RADS scores were independently assessed by five radiologists, consisting of three experienced in bladder MRI and two inexperienced radiologists. Comparison of VI-RADS scores was made with postoperative histopathological diagnosis. Receiver operating characteristic curve analysis (ROC) was used for evaluating diagnostic performance, calculating sensitivity, specificity, and area under ROC (AUC)). Interobserver agreement was assessed using the weighted kappa statistic. Results The final analysis included 46 patients (mean age: 61 years ± 9 [standard deviation]; age range: 39–70 years; 42 men). The pooled AUC for predicting muscle invasion was 0.945 (95% confidence interval (CI): 0.893–0.977) for experienced readers, and 0.910 (95% CI: 0.831–0.959) for inexperienced readers, and 0.932 (95% CI: 0.892–0.961) for all readers. At an optimal cut-off value ≥ 4, pooled sensitivity and specificity were 74.1% (range: 66.0–80.9%) and 94.1% (range: 88.6–97.7%) for experienced readers, and 63.9% (range: 59.6–68.1%) and 86.4% (range: 84.1–88.6%) for inexperienced readers. Interobserver agreement ranged from substantial to excellent between all readers (k = 0.79–0.92). Conclusions VI-RADS accurately assesses muscle invasion in bladder cancer patients after NAC and exhibits good diagnostic performance across readers with different experience levels.

Abstract Biological nitrogen fixation by free-living bacteria and rhizobial symbiosis with legumes plays a key role in sustainable crop production. Here, we study how different crop combinations influence the interaction between peanut plants and their rhizosphere microbiota via metabolite deposition and functional responses of free-living and symbiotic nitrogen-fixing bacteria. Based on a long-term (8 year) diversified cropping field experiment, we find that peanut co-cultured with maize and oilseed rape lead to specific changes in peanut rhizosphere metabolite profiles and bacterial functions and nodulation. Flavonoids and coumarins accumulate due to the activation of phenylpropanoid biosynthesis pathways in peanuts. These changes enhance the growth and nitrogen fixation activity of free-living bacterial isolates, and root nodulation by symbiotic Bradyrhizobium isolates. Peanut plant root metabolites interact with Bradyrhizobium isolates contributing to initiate nodulation. Our findings demonstrate that tailored intercropping could be used to improve soil nitrogen availability through changes in the rhizosphere microbiome and its functions.

Abstract Statins, the first‐line medication for dyslipidemia, are linked to an increased risk of type 2 diabetes. But exactly how statins cause diabetes is yet unknown. In this study, a developed short‐term statin therapy on hyperlipidemia mice show that hepatic insulin resistance is a cause of statin‐induced diabetes. Statin medication raises the expression of progesterone and adiponectin receptor 9 (PAQR9) in liver, which inhibits insulin signaling through degradation of protein phosphatase, Mg2+/Mn2+ dependent 1 (PPM1α) to activate ERK pathway. STIP1 homology and U‐box containing protein 1 (STUB1) is found to mediate ubiquitination of PPM1α promoted by PAQR9. On the other hand, decreased activity of hepatocyte nuclear factor 4 alpha (HNF4α) seems to be the cause of PAQR9 expression under statin therapy. The interventions on PAQR9, including deletion of PAQR9, caloric restriction and HNF4α activation, are all effective treatments for statin‐induced diabetes, while liver specific over‐expression of PPM1α is another possible tactic. The results reveal the importance of HNF4α‐PAQR9‐STUB1‐PPM1α axis in controlling the statin‐induced hepatic insulin resistance, offering a fresh insight into the molecular mechanisms underlying statin therapy.

Anti-tubular basement membrane (anti-TBM) antibody nephritis is a rare type of tubulointerstitial nephritis associated with progressive decline in kidney function. It is characterized histopathologically by tubular atrophy and dilation, interstitial fibrosis, lymphocyte and macrophage-predominant cellular infiltration, and linear deposition of IgG and complement along the tubular basement membrane. We herein present a case of a 69-year-old male who was recently diagnosed with chronic lymphocytic leukemia (CLL) and was referred for evaluation of kidney failure, ultimately diagnosed as anti-TBM antibody nephritis progressing into end-stage kidney disease (ESKD). This case report highlights the management challenges of anti-TBM antibody nephritis as a rare kidney disorder.

Background: Premature ovarian insufficiency (POI), a modifiable cause of infertility with substantial implications for women's well-being, prompts the exploration of efficacious adjunctive treatments. Acupuncture emerges as a promising therapeutic avenue; however, the nuanced effects of acupuncture in POI warrant more comprehensive investigation. The intricate mechanisms dictating individualized responses remain elusive. This trial seeks to assess the effectiveness of acupuncture as an adjunctive treatment for POI, concurrently delving into the impact of transcriptome analysis on peripheral blood to unravel the underpinnings of these individual variations. The overarching objective is to enrich our comprehension of acupuncture's therapeutic potential in the context of POI, with a view to advancing holistic patient care. Methods/design: Constituting an open-label, nested case-control study, this research endeavors to enroll 108 women diagnosed with POI. Participants will be randomly assigned in a 1:1 ratio to either the study group or the control group, each comprising 54 subjects. Ten patients from each group meeting specific criteria will partake in transcriptome analysis. An additional 10 subjects meeting the study criteria will form a healthy control group. The study group will exclusively undergo acupuncture treatment, while the control group will solely receive Fenmutong. Acupuncture sessions, administered thrice weekly across three menstrual cycles from the fifth day of menstruation, constitute the intervention. Primary outcome measurement rests on Follicle-Stimulating Hormone (FSH) levels, supplemented by secondary assessments encompassing biometric features, hormone biomarkers, anxiety and depression scores, and transcriptome analysis. Baseline measurements precede intervention, with post-intervention evaluations following. The study endeavors to discern specific genes linked to individualized responses to acupuncture. Data analysis, employing SPSS 25.0 software, incorporates a meticulous examination of peripheral blood samples for transcriptome analysis. The investigation aspires to shed light on genetic determinants influencing the effects of acupuncture on women with POI, thereby fostering elevated standards in patient care and management. Discussion: This study pivots on the principal objective of scrutinizing the efficacy of acupuncture as an adjunctive treatment for POI. Beyond effectiveness, it undertakes an exploration of the intricate mechanisms underlying the diverse responses exhibited by individuals in the context of acupuncture, augmenting the depth of understanding in this therapeutic domain.

Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.