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Background: Rheumatoid arthritis (RA) is an autoimmune joint disease with systemic manifestations. Emerging evidence implicates the gut microbiota in the pathophysiology of RA. However, the specific changes in the gut microbiota in RA patients remain poorly understood. Methods: We conducted a comprehensive search of PubMed, EMBASE, Web of Science, Cochrane Library, MEDLINE, Wanfang, VIP, CBM, and CNKI from the time the databases were created until October, 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in RA, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Results: Firstly, we evaluated the changes in α-diversity of gut microbes in patients with RA compared to healthy controls. Our analysis of 18 studies revealed a significant decrease in richness and evenness among RA patients. Importantly, the subgroup analysis suggested the decrease in α-diversity was more significant in treatment naïve patients rather than those who received anti-rheumatic medication. Additionally, in the subgroup analysis of 316 patients stratified by baseline disease activity, no significant differences in α-diversity were detected between groups. Discussion: Our analysis further evidence of altered α-diversity and the relative abundance of specific bacteria in RA. These findings contribute to our understanding of the role of gut microbiota dysbiosis in the pathogenesis of RA. Further research is warranted to elucidate the underlying mechanisms and explore the potential therapeutic implications of targeting the gut microbiota in RA management.

Sodium iodide (NaI) detector has wide applications in Prompt Gamma-ray Neutron Activation Analysis (PGNAA) due to its excellent detection efficiency and relatively low cost. In order to obtain the response of the detector to gamma-rays during PGNAA measurement process，a Monte Carlo model was established for the NaI detector to simulate the transport processes of neutrons and gamma-rays. Measurements and analyses were conducted on standard point sources of 60Co，137Cs，152Eu，133Ba，and 241Am，as well as a waterborne source of 137Cs. These measurements were compared with MCNP simulation calculations，and the results demonstrated agreement between the two methodologies. Then，measurements were conducted on aqueous solutions using a D-D neutron generator，and the 2.223 MeV characteristic gamma-ray produced by the H element radiative capture reaction was analyzed. The research results show that the deviations between MCNP simulation calculations of characteristic peaks for the H element and experimental measurements were consistently within 13%，demonstrating that the NaI measurement system model established by MCNP can simulate the transport processes of gamma and neutrons，laying a foundation for the subsequent optimization of the system and other related work.

Abstract Tuberculosis has been one of the most common communicable diseases raising global concerns. Accurately predicting the incidence of Tuberculosis remains challenging. Here we constructed a time-series analysis and fusion tool using multi-source data, and aimed to more accurately predict the incidence trend of tuberculosis of Anhui Province from 2013 to 2023. Random forest algorithm (RF), Feature Recursive Elimination (RFE) and Least absolute shrinkage and selection operator (LASSO) were implemented to improve the derivation of features related to infectious diseases and feature work. Based on the characteristics of infectious disease data, a model of RF-RFE-LASSO integrated particle swarm optimization multiple inputs long short term memory recurrent neural network (RRL-PSO-MiLSTM) was created to perform more accurate prediction. Results showed that the PSO-MiLSTM achieved excellent prediction results compared with common single-input and multi-input time-series models (test set MSE:42.3555, MAE: 59.3333, RMSE: 146.7237, MAPE: 2.1133, R 2 : 0.8634). PSO-MiLSTM enriches and complements the methodological research content of calibrating the time-series predictive analysis of infectious diseases using multi-source data, and can be used as a brand-new benchmark for the analysis of influencing factors and trend prediction of infectious diseases at the public health level in the future, as well as providing a reference for incidence rate prediction of infectious diseases.

Abstract In plants, recognition between resistance gene (R) and virus induces a local hypersensitive response (HR), which is accompanied by systemic acquired resistance (SAR). The dominant resistance gene N in tobacco confers resistance to tobacco mosaic virus (TMV) at both locally inoculated tissues and systemically infected tissues. However, the mechanisms underlying HR- and SAR-mediated viral inhibition are not fully revealed. In this study, we find that Nicotiana glutinosa RNA-binding protein (NgRBP) is an RNA silencing suppressor which enhances TMV-triggered HR. Stronger HR could result in stronger local and systemic RNA silencing as well as SAR. Enhanced RNA silencing in the systemically infected leaves induced by the NgRBP gene is compromised by transient expression of NahG. These results indicate that RNA silencing is activated by HR and plays a crucial role in local and systemic virus resistance. Our results reveal a crosstalk between N gene-mediated virus resistance and RNA silencing which would deepen our understanding of the established HR and SAR models.

Abstract Background Spiroplasma eriocheiris has been proved to be a pathogen causing tremor disease of Eriocheir sinensis, it is also infectious to other aquatic crustaceans, resulting in a serious threat on the sustainable development of the aquaculture industry. S. eriocheiris is a helical-shaped microbe without a cell wall, and its motility is related to the cytoskeleton protein MreB which belongs to the actin superfamily and has five MreB homologs. Results In this study, we purified MreB3, MreB4 and MreB5, and successfully prepared monoclonal antibodies. After S. eriocheiris treated with actin stabilizator Phalloidin and inhibitors A22, we found that Phalloidin and A22 affect the S. eriocheiris morphology by altering MreB expression. We confirmed that the ability of S. eriocheiris to invade E. sinensis was increased after treatment with Phalloidin, including that the morphology of E. sinensis blood lymphocytes was deteriorated, blood lymphocytes viability was decreased, peroxidase activity and cell necrosis were increased. On the contrary, the pathogenicity of S. eriocheiris decreased after treatment with A22. Conclusions Our findings suggest that the MreB protein in S. eriocheiris plays a crucial role in its morphology and pathogenicity, providing new insights into potential strategies for the prevention and control of S. eriocheiris infections.

Abstract Presenilin-associated protein (PSAP) is a mitochondrial proapoptotic protein as established in cell biology studies. It remains unknown whether it involves in neurodegenerative diseases. Here, we explored PASP expression in adult and aged human brains and its alteration relative to Alzheimer-disease (AD)-type neuropathology. In pathology-free brains, light PASP immunoreactivity (IR) occurred among largely principal neurons in the cerebrum and subcortical structures. In the brains with AD pathology, enhanced PSAP IR occurred in neuronal and neuritic profiles with a tangle-like appearance, with PSAP and pTau protein levels elevated in neocortical lysates relative to control. Neuronal/neuritic profiles with enhanced PSAP IR partially colocalized with pTau, but invariably with Amylo-Glo labelled tangles. The neuronal somata with enhanced PASP IR also showed diminished IR for casein kinase 1 delta (Ck1δ), a marker of granulovacuolar degeneration; and diminished IR for sortilin, which is normally expressed in membrane and intracellular protein sorting/trafficking organelles. In old 3xTg-AD mice with β-amyloid and pTau pathologies developed in the brain, PSAP IR in the cerebral sections exhibited no difference relative to wildtype mice. These findings indicate that PSAP upregulation is involved in the course of tangle formation especially in the human brain during aging and in AD pathogenesis.

Abstract Analogous to the condensation of Cooper pairs in superconductors, the Bose–Einstein condensation (BEC) of electron–hole pairs in semiconductors and semimetals leads to an emergence of an exotic ground state — the excitonic insulator state. In this paper, we study the electronic structure of 1T-TiSe2 utilizing angle-resolved photoemission spectroscopy and alkali-metal deposition. Alkali-metal adatoms are deposited in-situ on the sample surface, doping the system with electrons. The conduction bands of 1T-TiSe2 are thereby pushed down below the Fermi energy, which enables us to characterize its temperature dependence with precision. We found that the formation of the charge density wave (CDW) in 1T-TiSe2 at ~ 205 K is accompanied by a significant increase of the band gap, supporting the existence of excitonic pairing in the CDW state of 1T-TiSe2. More importantly, by analyzing the linewidth of the single-particle excitation spectrum, we unveiled an incoherence-to-coherence crossover at 165 K, which could be attributed to a possible exciton condensation that occurs beneath the CDW transition in 1T-TiSe2. Our results not only explain the exotic transport properties of 1T-TiSe2, but also highlight the possible existence of an excitonic condensate in this semiconducting material.

Rhinovirus (RV) is a common pathogen that causes respiratory tract infection and can cause outbreaks in hospitals and welfare institutions. A cluster of respiratory diseases occurred in a primary school in Shenyang City, Liaoning Province, China, in 2022. In this outbreak, a total of 31 students had symptoms similar to those of upper respiratory tract infection, mainly cough and sore throat. Among them, 27 throat swabs were collected and identified for respiratory pathogens by TaqMan low-density array (TLDA), quantitative real-time polymerase chain reaction (PCR), reverse transcription-nested PCR and whole-genome sequencing. Out of the 27 specimens, 24 tested positive for RV, and 21 RV viral protein 1 sequences were obtained, of which 15 (71.43%) were identified as RV-A49, while 2 RV-A20 and 4 sequences from 2 specimens were RV-A30 coinfected with RV-C15. In addition, one whole-genome sequence (WGS) of RV-A49 was obtained, and three unique amino acid mutations were found compared to 23 WGS of RV-A49 from GenBank. In conclusion, this outbreak of upper respiratory tract infection is caused by RV, mainly RV-A49.

Objective: To provide the mechanism-based pharmacotherapy of the Huatan Qushi formula (HTQS formula), for the health management and treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A rat model of NAFLD was employed to examine the efficacy and safety of the HTQS formula. In vivo active components and potential mechanisms of the HTQS formula were identified using UPLC‒MS/MS combined with network pharmacology. The influence of the HTQS formula on the dominating proteins in PI3K/Akt pathway was validated in vivo using western blot. Finally, 16S rRNA sequencing of the gut microbiome was conducted followed by targeted metabolomics detecting fecal short-chain fatty acids (SCFAs) and bile acids to determine the impact of the HTQS formula on gut microbiota. Results: The HTQS formula reduced weight gain and hepatic steatosis in NAFLD rats and decreased serum total cholesterol (TC), triglycerides, blood glucose, and insulin resistance (IR) without causing liver or kidney injury. We detected 28 components using UPLC‒MS/MS and identified 439 shared targets between NAFLD and the HTQS formula. Primarily, we focused on the PI3K/Akt signaling pathway based on protein‒protein interaction network analysis. We validated that the HTQS formula inhibited liver steatosis and inflammation by increasing the phosphorylation levels of PI3K, AKT, P27, GSK3β in the PI3K/Akt signaling pathway. 16S rRNA sequencing revealed that the HTQS formula reduced the abundance of the genus Family_XIII_AD3011_group, which was positively correlated with IR and taurodeoxycholic acid. In addition, Lachnospiraceae_UCG_010 inversely correlated with TC and five bile acids, which could be essential to the therapeutic effect of the HTQS formula against NAFLD. Conclusions: The HTQS formula proved to be an effective pharmacotherapy for NAFLD without causing liver or kidney injury. Multiple potent components of the HTQS formula could alleviate liver steatosis and lipid metabolism disorder by modulating the PI3K/Akt signaling pathway and restoring gut microbiota composition.

Based on the “unidirectional break-up and convergence” geodynamic model, this study investigates the impact of the evolution of the Tethyan domain on the formation of petroleum systems in the Sichuan super basin and explores the enrichment pattern of natural gas. The results show that, firstly, the Sichuan Basin and its surrounding areas have experienced two unidirectional rifting-aggregation cycles triggered by the Proto-Tethys Ocean and the Paleo-Tethys Ocean during the Neoproterozoic to Triassic. During Jurassic–Cenozoic, the Sichuan Basin is incorporated in the circum-Tibetan plateau basin-mountain coupled tectonic domain system. The episodic tectonic movements within the plate control the sedimentary infill styles. Second, the evolution of the Tethyan domain, paleoclimatic environment and major geological events controlled the formation and distribution of high-quality source rocks within the basin. The rift valley and intracratonic rift, passive continental margin slope, and intracratonic sags are favorable areas for the development of source rocks. Third, the evolution of the Tethyan domain, supercontinent cycles, global sea level changes, and tectono-climatic events controlled the distribution of carbonate platform and reservoir-caprock combinations. The cratonic platform margins and sub-platform internal high terrains are key areas for finding carbonate high-energy facies belts. Syndepositional paleo-uplifts and surrounding slopes, regional unconformities, and later faults zone are areas where large-scale carbonate reservoirs are distributed. The regional evaporite or shale caprock are beneficial for the large-scale preservation of oil and gas in the basin. Fourth, the spatio-temporal matching relationship of reservoir forming factors influenced by the early tectonic-sedimentary evolution pattern and the degree of later tectonic modification is the key to oil and gas enrichment. Future oil and gas exploration should focus on potential gas systems during the Sinian rift period, Cambrian pre-salt gas systems in the eastern and southern Sichuan, as well as whole oil and gas systems of Permian and Triassic.

Abstract Background Emerging evidence suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression. However, it remained unclear how the gut microbiome and neuroinflammation in the brain mutually interact or how these interactions affect brain functioning and cognition. Here we hypothesized that “gut-brain” axis mediated by microbial derived metabolites was expected to novel breakthroughs in the fields of AD research and development. Methods Multiple technologies, such as immunofluorescence, 16s rDNA sequencing, mass spectrometry-based metabolomics (LC-QQQ-MS and GC-MS), were used to reveal potential link between gut microbiota and the metabolism and cognition of the host. Results Microbial depletion induced by the antibiotics mix (ABX) verified that “gut-brain” can transmit information bidirectionally. Short-chain fatty acid-producing (SCFAs-producing) bacteria and amino acid-producing bacteria fluctuated greatly in 5×FAD mice, especially the reduction sharply of the Bifidobacteriaceae and the increase of the Lachnospiraceae family. Concentrations of several Tryptophan-kynurenine intermediates, lactic acid, CD4+ cell, and CD8+ cells were higher in serum of 5×FAD mice, whilst TCA cycle intermediates and Th1/Th2 were lower. In addition, the levels of iso-butyric acid (IBA) in feces, serum, and brain of 5×FAD mice were increased compared with WT-M mice, especially in serum. And IBA in the brain was positively correlated with Aβ and proinflammatory factors. Conclusion Together, our finding highlighted that the alternation in gut microbiota affected the effective communication between the “gut-brain” axis in 5×FAD mice by regulating the immune system, carbohydrate, and energy metabolism.

Abstract Background Lilium lancifolium is a special wild triploid species native to China and can produce abundant bulbils on its stem under natural conditions, which is very valuable to study bulbil organogenesis in plants. Although similar to the lateral and tillering principles, the molecular mechanism underlying bulbil formation has remained incompletely understood. Results The metabolome and transcriptome of L. lancifolium bulbils across four development stages were analyzed. The pairwise comparison of metabolomes across the four stages identified 17 differential hormones, predominantly auxin (IAA), cytokinin (CK), and jasmonic acid (JA). Short Time-series Expression Miner (STEM) trend analysis of differential genes revealed four significant trends across these stages. The KEGG enrichment analysis of the four clusters highlighted pathways, such as plant hormone signal transduction, which were speculated to play a crucial role in development stages. these pathways were speculated to play a crucial role in development stages. To explore the key differential expressed genes and transcription factors associated with bulbil occurrence, two periods were focused on: Ll_UN and Ll_DN, which represented the stages with and without bulbils, respectively. Through correlation analysis and qRT-PCR analysis, 11 candidate differentially expressed genes and 27 candidate transcription factors were selected. By spraying exogenous hormones to validate these candidates, LlbHLH128, LlTIFY10A, LlbHLH93, and LlMYB108, were identified as the key genes for L. lancifolium bulbils. Conclusion A regulatory network of L. lancifolium bulbil development was predicted. LlTIFY10A and LlbHLH93 might be involved in the JA and auxin signal transduction pathways, which jointly formed a regulatory network to affect the occurrence of L. lancifolium bulbil. This study not only provided more information about the differentially expressed genes and metabolites through transcriptome and metabolomics analyses, but also provided a clearer understanding of the effect of hormones on bulbil formation in lily.

Abstract This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Abstract The resistance of pests to common insecticides is a global issue that threatens food production worldwide. Diamide insecticides target insect ryanodine receptors (RyRs), causing uncontrolled calcium release from the sarcoplasmic and endoplasmic reticulum. Despite their high potency and species selectivity, several resistance mutations have emerged. Using a chimeric RyR (chiRyR) approach and cryo-electron microscopy (cryo-EM), we investigate how insect RyRs engage two different diamide insecticides from separate families: flubendiamide, a phthalic acid derivative, and tetraniliprole, an anthranilic compound. Both compounds target the same site in the transmembrane region of the RyR, albeit with different poses, and promote channel opening through coupling with the pore-forming domain. To explore the resistance mechanisms, we also solve two cryo-EM structures of chiRyR carrying the two most common resistance mutations, I4790M and G4946E, both alone and in complex with the diamide insecticide chlorantraniliprole. The resistance mutations perturb the local structure, directly reducing the binding affinity and altering the binding pose. Our findings elucidate the mode of action of different diamide insecticides, reveal the molecular mechanism of resistance mutations, and provide important clues for the development of novel pesticides that can bypass the resistance mutations.

Abstract Background In the central nervous system, type 2 vesicular monoamine transporters (VMAT2) are responsible for the reuptake of monoamines from synaptic junction back to pre-synaptic terminal vesicles. These transporters are functionally crucial as they reflect the integrity of monoamine neurons. D6-[18F]FP-(+)-DTBZ, a novel deuterated VMAT2 radioligand, has shown promise as a potential PET tracer for the diagnosis of Parkinson’s disease (PD). This study evaluates the biodistribution and dosimetry of D6-[18F]FP-(+)-DTBZ and includes a head-to-head comparison with its non-deuterated version, [18F]FP-(+)-DTBZ (AV-133), in healthy individuals and PD patients. Results The automated synthesis of D6-[18F]FP-(+)-DTBZ using the SPE method was accomplished in 35 min, yielding a high radiochemical purity (> 99%) and high radiochemical yields (35 ± 5%). The biodistribution and dosimetry study indicated an effective dose of 37.1 ± 7.2 μSv/MBq, with the liver receiving the highest radiation dose (289.6 ± 42.1 μGy/MBq), followed by pancreas (185.2 ± 29.1 μGy/MBq). Brain imaging with D6-[18F]FP-(+)-DTBZ exhibited a significantly increased uptake in VMAT2-rich regions, particularly the striatum. In a head-to-head comparison between [18F]FP-(+)-DTBZ and D6-[18F]FP-(+)-DTBZ, the latter exhibited approximately 15% higher SUVR in the caudate, putamen, and nucleus accumbens. Preliminary studies in PD patients showed a substantial reduction in VMAT2 uptake in the striatum, with the most pronounced decrease observed in the putamen (a 53% decline). Conclusions D6-[18F]FP-(+)-DTBZ is a safe and improved VMAT2-specific imaging agent, which may be suitable for diagnosing PD by evaluating changes in VMAT2 binding of monoamine neurons in the brain. Trial registration Chinese Clinical Trial Registry, ChiCTR2200057218, Registered 16 August 2021, https://www.chictr.org.cn/bin/project/edit?pid=142725 .

Abstract Background Delayed diagnosis of inflammatory bowel disease (IBD) is common, there is still no effective imaging system to distinguish Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Methods This multicenter retrospective study included IBD patients at three centers between January 2012 and May 2022. The intestinal and perianal imaging signs were evaluated. Visceral fat information from CT images was extracted, including the ratio of visceral to subcutaneous fat volume (VSR), fat distribution, and attenuation values. The valuable indicators were screened out in the derivation cohort by binary logistic regression and receiver working curve (ROC) analysis to construct an imaging report and data system for IBD (IBD-RADS), which was tested in the validation cohort. Results The derivation cohort included 606 patients (365 CD, 241 UC), and the validation cohort included 155 patients (97 CD, 58 UC). Asymmetric enhancement (AE) (OR = 87.75 [28.69, 268.4]; P

Abstract Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.

Abstract Background Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions before 20 weeks with the same spouse [1]. However, approximately 50% of RSA cases of unknown cause are classified as unexplained recurrent spontaneous abortion (URSA). Potential factors include decreased trophoblast cell migration and invasion, leading to impaired placental implantation and maintenance of the normal maternal-fetal interface. However, the mechanism of this pathogenesis remains unknown. In this study, we investigated the potential role and mechanism of KLF4 in regulating URSA by influencing the invasion and migration ability of trophoblast cells. Methods We firstly identified 817 differentially expressed genes by performing a difference analysis of the dataset GSE121950 [2] related to recurrent abortion, and intersected the top 10 genes obtained respectively by the three algorithms: DMNC, MNC, and EPC using Venn Diagram.To detect the expression levels of core genes, villi samples were obtained from normal pregnant women and patients with URSA. RT-qPCR analysis revealed a significant difference in KLF4 mRNA expression and KLF4 was then analyzed. Trophoblast cell lines HTR8 and JEG3 were used to investigate the effect of KLF4 on trophoblastic function. Wound healing and transwell assays was performed to detect the invasion and migration of trophoblast cells. The expression of epithelial-mesenchymal transition(EMT) molecules were detected by RT-qPCR and western blot. Promoter detection and epigenetic modification were detected by chromatin immunoprecipitation (ChIP) assay. Molecular nuclear localization was detected by immunofluorescence and subcellular fractionation. Miscarried mice model was used to study the effects of KLF4 on URSA induced by reduced trophoblast invasion and migration. Results KLF4 is highly expressed in the villi of patients with URSA. KLF4 inhibits the expression level of H3R2ME2a in trophoblast cells by regulating the transcriptional level and nuclear translocation of PRMT6, thereby inhibiting the possible regulatory mechanism of trophoblastic invasion and providing a potential treatment strategy for URSA in vivo. Conclusions The KLF4/PRMT6/H3R2ME2a axis regulates mechanisms associated with unexplained recurrent spontaneous abortion by regulating trophoblast function.

Glioma is the most prevalent primary malignant tumor in the central nervous system (CNS). It represents a diverse group of brain malignancies characterized by the presence of various cancer cell types as well as an array of noncancerous cells, which together form the intricate glioma tumor microenvironment (TME). Understanding the interactions between glioma cells/glioma stem cells (GSCs) and these noncancerous cells is crucial for exploring the pathogenesis and development of glioma. To invesigate these interactions requires in vitro co-culture models that closely mirror the actual TME in vivo. In this review, we summarize the two- and three-dimensional in vitro co-culture model systems for glioma-TME interactions currently available. Furthermore, we explore common glioma-TME cell interactions based on these models, including interactions of glioma cells/GSCs with endothelial cells/pericytes, microglia/macrophages, T cells, astrocytes, neurons, or other multi-cellular interactions. Together, this review provides an update on the glioma-TME interactions, offering insights into glioma pathogenesis.

Abstract Background Deep vein thrombosis (DVT) is a common and serious risk in elderly patients with knee osteoarthritis (OA), making preoperative detection crucial. Despite this, identifying OA patients at high risk for preoperative DVT and appropriately targeting them for venous ultrasound screening remains a challenge. There is limited research-based evidence on the risk factors for preoperative DVT in elderly patients with end-stage OA. We examined the incidence of and risk factors for preoperative DVT in elderly patients with end-stage OA scheduled for total knee arthroplasty. Methods We retrospectively analyzed the demographic data (age, sex, body mass index, current smoking, alcohol consumption, walking status, and Barthel index score), medical history, and laboratory test indices of 1411 patients with end-stage OA aged ≥ 60 years scheduled for total knee arthroplasty from January 2015 to December 2018. Risk factors for preoperative DVT were evaluated by univariate and multivariate logistic analyses. Receiver operating characteristic analysis was performed to determine optimal cut-off values. Results The incidence of preoperative DVT was 4.5% (63 of 1411 patients). Seven independent risk factors were correlated with preoperative DVT in the multivariate logistic regression: age (odds ratio [OR], 1.073; P = 0.002), D-dimer concentration (OR, 1.173; P = 0.003), hyperlipidemia (OR, 2.038; P = 0.045), atrial fibrillation (OR, 4.004; P = 0.033), chronic renal failure (OR, 6.732; P = 0.008), chronic obstructive pulmonary disease (COPD) (OR, 8.721; P = 0.001), and walking status (wheelchair) (OR, 2.697; P = 0.002). The optimal cut-off values for predicting preoperative DVT were 0.585 µg/mL for the D-dimer concentration (area under the curve [AUC], 0.769; P 0.585 µg/mL), high age (> 72.5 years), hyperlipidemia, atrial fibrillation, chronic renal failure, COPD, and walking status (wheelchair).

Abstract The gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures. Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes. A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome’s role in common diseases in the Chinese population and will guide personalized disease management strategies.

Abstract Myopia is a global public health concern, with a higher prevalence in women than that in male. As the relationship between sex hormone and myopia remains unclear, we aimed to reveal the relationship between sex hormone and myopia by removing the ovaries of mice and measuring changes in ocular parameters related to myopia. Lens-induced myopia (LIM) surgeries were performed on 3-week-old male mice and age-matched female mice to evaluate the effects of sex on myopia development, which indicated a high degree of myopia and rapid progression of axial elongation in male mice. Bilateral ovariectomy (OVX) performed on 4-week-old female mice induced myopic refraction status in ovariectomized mice. Although axial length elongation was larger in ovariectomized mice than that in sham control mice, the result was insignificant. To further reveal the relationship between female sex hormones and myopia, LIM combined with OVX was performed, which revealed a magnified myopic refraction status in ovariectomized mice. Nevertheless, elongation of the anterior chamber depth in the − 30 D lens-treated eyes significantly increased in LIM + OVX mice compared with the frame-treated eyes in LIM + OVX mice and − 30 D lens-treated eyes in LIM + Sham surgery mice. Sex hormones play a role in regulating myopia development in female mice.

Abstract Over the past decade, there has been a growing interest in ferritin-based vaccines due to their enhanced antigen immunogenicity and favorable safety profiles, with several vaccine candidates targeting various pathogens advancing to phase I clinical trials. Nevertheless, challenges associated with particle heterogeneity, improper assembly and unanticipated immunogenicity due to the bulky protein adaptor have impeded further advancement. To overcome these challenges, we devise a universal ferritin-adaptor delivery platform based on structural insights derived from the natural ferritinophagy complex of the human ferritin heavy chain (FTH1) and the nuclear receptor coactivator 4 (NCOA4). The engineered ferritinophagy (Fagy)-tag peptide demonstrate significantly enhanced binding affinity to the 24-mer ferritin nanoparticle, enabling efficient antigen presentation. Subsequently, we construct a self-assembling rabies virus (RABV) vaccine candidate by noncovalently conjugating the Fagy-tagged glycoprotein domain III (GDIII) of RABV to the ferritin nanoparticle, maintaining superior homogeneity, stability and immunogenicity. This vaccine candidate induces potent, rapid, and durable immune responses, and protects female mice against the authentic RABV challenge after single-dose administration. Furthermore, this universal, ferritin-based antigen conjugating strategy offers significant potential for developing vaccine against diverse pathogens and diseases.

Abstract Background The mortality rate of COVID-19 patients with critical symptoms is reported to be 40.5%. Early identification of patients with poor progression in the critical cohort is essential to timely clinical intervention and reduction of mortality. Although older age, chronic diseases, have been recognized as risk factors for COVID-19 mortality, we still lack an accurate prediction method for every patient. This study aimed to delve into the cell-free DNA fragmentomics of critically ill patients, and develop new promising biomarkers for identifying the patients with high mortality risk. Methods We utilized whole genome sequencing on the plasma cell-free DNA (cfDNA) from 33 COVID-19 patients with critical symptoms, whose outcomes were classified as survival (n = 16) and death (n = 17). Mitochondrial DNA (mtDNA) abundance and fragmentomic properties of cfDNA, including size profiles, ends motif and promoter coverages were interrogated and compared between survival and death groups. Results Significantly decreased abundance (~ 76% reduction) and dramatically shorter fragment size of cell-free mtDNA were observed in deceased patients. Likewise, the deceased patients exhibited distinct end-motif patterns of cfDNA with an enhanced preference for “CC” started motifs, which are related to the activity of nuclease DNASE1L3. Several dysregulated genes involved in the COVID-19 progression-related pathways were further inferred from promoter coverages. These informative cfDNA features enabled a high PPV of 83.3% in predicting deceased patients in the critical cohort. Conclusion The dysregulated biological processes observed in COVID-19 patients with fatal outcomes may contribute to abnormal release and modifications of plasma cfDNA. Our findings provided the feasibility of plasma cfDNA as a promising biomarker in the prognosis prediction in critically ill COVID-19 patients in clinical practice.

Improving plant resistance to Verticillium wilt (VW), which causes massive losses in Gossypium hirsutum, is a global challenge. Crop plants need to efficiently allocate their limited energy resources to maintain a balance between growth and defense. However, few transcriptional regulators specifically respond to Verticillium dahliae and the underlying mechanism has not been identified in cotton. In this study, we found that the that expression of most R2R3-MYB members in cotton is significantly changed by V. dahliae infection relative to the other MYB types. One novel R2R3-MYB transcription factor (TF) that specifically responds to V. dahliae, GhMYB3D5, was identified. GhMYB3D5 was not expressed in 15 cotton tissues under normal conditions, but it was dramatically induced by V. dahliae stress. We functionally characterized its positive role and underlying mechanism in VW resistance. Upon V. dahliae infection, the up-regulated GhMYB3D5 bound to the GhADH1 promoter and activated GhADH1 expression. In addition, GhMYB3D5 physically interacted with GhADH1 and further enhanced the transcriptional activation of GhADH1. Consequently, the transcriptional regulatory module GhMYB3D5-GhADH1 then promoted lignin accumulation by improving the transcriptional levels of genes related to lignin biosynthesis (GhPAL, GhC4H, Gh4CL, and GhPOD/GhLAC) in cotton, thereby enhancing cotton VW resistance. Our results demonstrated that the GhMYB3D5 promotes defense-induced lignin accumulation, which can be regarded as an effective way to orchestrate plant immunity and growth.

Abstract The dimension of relevant text feature space and feature weight of substation main equipment defect information is high, so it is difficult to accurately select mining features. The Natural Language Processing (NLP) medium and short‐term neural network model is used to realise the defect information text feature word segmentation in the log. After extracting the text features of defect information of main substation equipment with high categories to form the feature space; the TF‐IDF algorithm is designed to calculate the importance weight of text keywords, judge the criticality of defect information text feature vocabulary, accurately locate defect information text features, and realise defect information text feature mining. Experiments show that the algorithm has high precision for specific word segmentation of massive substation main equipment log information.

Research and development of antimicrobial technology are critical for safeguarding human life and health. Ferroelectric materials, materials with spontaneous polarization, can adjust their direction of spontaneous polarization in response to an external electric field. When subjected to this applied field, the ordered arrangement of electric dipoles within the ferroelectric material becomes disrupted. This disruption causes the bound charges on the surface to redistribute, and the released positive and negative charges react with the oxygen and water in the surrounding medium. This reaction forms active substances with powerful oxidant properties (such as OH, \begin{document}$\cdot {\text{O}}_2^ - $\end{document}). These highly oxidizing active substances can destroy the cell wall of bacterial cells, enter the cell to damage DNA, leak proteins, and render them inactive, thereby inactivating the bacteria. Ferroelectric materials are not only excellent for their piezoelectric, pyroelectric, and photovoltaic properties but also possess the unique ability to convert mechanical, thermal, and optical energy in nature into electrical and chemical energy. Coupled with their fast response speed (10−6 s) and high electromechanical coupling coefficients, the development of ferroelectric materials in conjunction with catalytic technology has emerged as a new sterilization technique. However, achieving high antimicrobial efficiencies is closely related to carrier utilization in the catalytic process and the catalyst activity. This holds true regardless of whether mechanical, thermal, or optical energy is used as the driving source to stimulate ferroelectric materials for catalytic antimicrobials. When using ferroelectric materials as catalysts, the spontaneous polarization properties of these materials can be harnessed to reduce the electron–hole pair combination rate through the internal electric field. This action increases the yield of active substances, thereby improving the efficiency of catalytic antibacterial agents. In addition, high-performance ferroelectric materials have a high internal electric field potential after polarization treatment, which can accelerate carrier separation during the catalytic process. As a result, ferroelectric materials have great potential for catalytic antimicrobial applications under environmentally friendly and safe conditions. In this review, we begin with an introduction to the ferroelectric properties of these materials and their relationship with piezoelectric and pyroelectric materials. We then summarize and organize previous work reported on the catalytic antimicrobial properties of ferroelectric materials. This summary includes discussions on photocatalytic, piezocatalytic, and pyrocatalytic antimicrobial properties and descriptions of the antimicrobial mechanisms of ferroelectric materials in different types of catalytic processes. The aim is to provide a reference for future research into the catalytic antimicrobial properties of ferroelectric materials.

Abstract Background Recent studies have found that histone-modified genes play an increasingly important role in tumor progression. Lysine(K) specific demethylase 4A (KDM4A) is a histone lysine-specific demethylase highly expressed in a variety of malignant tumors, data showed that KDM4A was negatively correlated with the Bone Morphogenetic Protein 9 (BMP9) in breast cancer. And previous experiments have demonstrated that exogenous BMP9 significantly inhibits breast cancer development. Materials and methods We detected the expression of KDM4A in breast cancer and the relationship between KDM4A and BMP9 using real-time quantitative PCR (RT-qPCR) and Western blot, and verified the interaction between KDM4A and BMP9 by ChIP experiments. At the same time, we also detected whether KDM4A had effects on the RNA and protein stability of BMP9 using actinomycin D and cycloheximide. Measurement of alpha-ketoglutarate (α-KG) level by ELISA to observe the effect of BMP9 on glutamine metabolism in breast cancer cells. Nucleoplasmic distribution of KDM4A after exogenous BMP9 treatment in breast cancer cells were observed by immunofluorescence staining and Western blot. A subcutaneous xenograft tumor model in nude mice was used to study the therapeutic effects of exogenous BMP9 and KDM4A inhibitor (JIB-04) in breast cancer. CCK-8, conoly formation, Transwell, wound healing, and immunohistochemistry were used to monitor the growth of tumor and cell function. Results We found that KDM4A was abnormally highly expressed in breast cancer, and silenced BMP9 expression by removing histone methyl groups from the BMP9 gene region. Meanwhile, KDM4A could also reduce the stability of BMP9 protein. BMP9 inhibit glutamine metabolism in breast cancer, resulting in a decrease in its product α-KG, is confirmed by ELISA. Altered nucleoplasmic distribution of KDM4A due to decreased α-KG was confirmed by immunofluorescence staining and Western blot. Animal experiments confirm that the combination of exogenous BMP9 and JIB-04 shows significantly better results in breast cancer. Conclusions KDM4A silences BMP9 expression by removing histone methyl groups from the BMP9 gene region, leading to further enhancement of glutamine metabolism, which contributes to malignant tumor progression. In addition, using JIB-04 in combination with exogenous BMP9 could inhibit the malignant progression of breast cancer cells and the growth of tumors more significantly.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Abstract Background As global aging continues to intensify, the health status of the older people requires urgent attention, and health education provides a pathway for active aging. However, the current outlook on health education for older people in rural areas of China is not optimistic. This study used Social Ecosystems Theory and explored the deep-rooted influencing factors on the acceptance of health education from the perspective of the rural older people. Methods In this study, a purposive sampling method was adopted, and eligible rural older individuals were selected from Hebi city, Henan Province, China, from March to May 2023 as the research participants. A semistructured interview method was used to explore the factors affecting the acceptance of health education by older people. The interview data were analyzed using the qualitative content analysis method to obtain relevant themes and subthemes. Results A total of 14 participants were recruited for the interviews; 8 were male, 6 were female, most had an elementary school education, and most were farmers. The results of the thematic analysis revealed a total of nine facilitators and nine barriers in micro, meso and macro levels. Among the findings, our important and unique finding is that inadequate intergenerational support somewhat hinders older adults’ exposure to health education. Conclusion There are numerous and complex facilitators of and barriers to accessing health education for rural older adults; of these, a lack of intergenerational support is particularly important. In the future, health education needs to be centered on the families of older people with the assistance of village committees so that older people and their children can learn and communicate together.

As an effective water prevention and control technology to block or reduce groundwater infiltration, water cut-off curtain has been continuously applied to underground and open pit coal mines in recent years. Influenced by quality defects such as joints and interlayer, the cut-off curtain generally needs to evaluate the anti-seepage performance by calculating the permeability coefficient, which can directly determine the anti-seepage quality of the cut-off curtain. Taking Zhanihe Open-pit Coal Mine and Yuanbaoshan Open-pit Coal Mine and Zhuxianzhuang Coal Mine as examples, the seepage coefficient of the water cut-off curtain is calculated by five methods, including the well enclosure pumping test, the complete well pumping test, the water injection test of the precipitation head, the water pressure test of the borehole and the core permeability test. The results show that there are differences in the results obtained by various calculation methods, but they can be mutually verified; the pumping test, water injection test and core permeability test are mostly used to test the permeability coefficient of the cut-off curtain in open pit coal mines, while the borehole water pressure test is more suitable for testing the seepage resistance of the grouting curtain in underground coal mines. The five calculation methods can respectively calculate the permeability coefficient of the water cut-off curtain from four different angles of point, line, surface and body, and comprehensive inspection of curtain wall seams and pouring quality. The combination of multiple methods can more comprehensively verify the permeability coefficient of the cut-off curtain.

Abstract Three-dimensional (3D) high-resolution large-volume imaging has remained a challenge. Translational rapid ultraviolet-excited sectioning tomography (TRUST) achieves rapid and cost-effective whole-organ subcellular imaging through iterative optical scanning and mechanical sectioning. However, the axial resolution is limited by the mechanical sectioning thickness or the UV light penetration depth in tissue. Here, assisted with high-and-low-frequency (HiLo) microscopy (HiLoTRUST), the optical sectioning thickness has been reduced from tens of micrometers to ~5.8 µm. In addition, HiLoTRUST has attained a finer mechanical sectioning thickness (10–15 µm) compared to TRUST (50 µm). For high-content imaging as in TRUST, we employed two additional UV light-emitting diodes (LEDs) specifically for uniform illumination. The full-color imaging ability and improved axial resolution of HiLoTRUST have been validated by two-dimensional (2D)/3D imaging of various mouse organs and human lung cancer specimens. HiLoTRUST offers a cost-effective, full-color, and high-resolution 3D imaging approach, showing its great potential in 3D histology applications.

As triboelectric nanogenerator (TENG) technology continue to evolve, its application in harsh environments has increasingly captivated the interest of researchers. However, the current research on heat-resistant triboelectric materials remains predominantly focused on the development of tribo-negative materials, with scant attention given to their equally crucial tribo-positive counterparts. In this study, the tribo-positive polyimide (PI) material with enhanced tribo-positivity is developed by integrating amide groups with electron-donating effects into the molecular chain. Furthermore, the TENG devices based on this series of tribo-positive PI materials have demonstrated an open-circuit voltage (VOC) of 242 V, a short-circuit current (ISC) of 8.13 μA, and a transferred charge (QSC) of 117 nC. Notably, these devices also demonstrate the capability to efficiently generate electricity even under elevated temperature conditions. This work not only proposes a potential molecular design strategy for developing high-performance tribo-positive PI materials applicable in TENGs, but also markedly propels the advancement of robust energy-harvesting devices engineered for operation at elevated temperatures.

Abstract By analyzing e + e − annihilation data corresponding to an integrated luminosity of 2.93 fb −1 collected at a center-of-mass energy of 3.773 GeV with the BESIII detector, the first observation of the semileptonic decays D 0 → K S 0 π − π 0 e + ν e $$ {D}^0\to {K}_S^0{\pi}^{-}{\pi}^0{e}^{+}{\nu}_e $$ and D + → K S 0 π + π − e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^{+}{\pi}^{-}{e}^{+}{\nu}_e $$ is reported. In the hypothesis that all events correspond to K 1(1270) decays, the branching fractions are measured to be B D 0 → K 1 1270 − → K S 0 π − π 0 e + ν e = 1.69 − 0.46 + 0.53 ± 0.15 × 10 − 4 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}\left(\to {K}_S^0{\pi}^{-}{\pi}^0\right){e}^{+}{\nu}_e\right)=\left({1.69}_{-0.46}^{+0.53}\pm 0.15\right)\times {10}^{-4} $$ and B D + → K ¯ 1 1270 0 → K S 0 π + π − e + ν e = 1.47 − 0.40 + 0.45 ± 0.14 × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0\left(\to {K}_S^0{\pi}^{+}{\pi}^{-}\right){e}^{+}{\nu}^e\right)=\left({1.47}_{-0.40}^{+0.45}\pm 0.14\right)\times {10}^{-4} $$ with statistical significance of 5.4σ and 5.6σ, respectively. When combined with measurements of the K 1(1270) → K + π − π decays, the absolute branching fractions are determined to be B D 0 → K 1 1270 − e + ν e = 1.08 − 0.13 − 0.10 + 0.14 + 0.08 ± 0.21 × 10 − 3 $$ \mathcal{B}\left({D}^0\to {K}_1{(1270)}^{-}{e}^{+}{\nu}_e\right)=\left({1.08}_{-0.13-0.10}^{+0.14+0.08}\pm 0.21\right)\times {10}^{-3} $$ and B D + → K ¯ 1 1270 0 e + ν e = 1.70 − 0.23 + 0.26 ± 0.13 ± 0.35 × 10 − 3 $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}_1{(1270)}^0{e}^{+}{\nu}_e\right)=\left({1.70}_{-0.23}^{+0.26}\pm 0.13\pm 0.35\right)\times {10}^{-3} $$ . The first and second uncertainties are statistical and systematic, respectively, and the third uncertainties originate from the assumed branching fractions of the K 1(1270) → Kππ decays.

Abstract Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a type of zoonoses withwidespread distribution. In 2019, a case of Q fever was diagnosed by metagenomic next-generation sequencing (mNGS) method in Xuyi County (Jiangsu province, China). The seroprevalence of previous fever patients and the molecular epidemiology of Coxiella in wild hedgehogs and harbouring ticks around the confirmed patient were detected to reveal the genetic characteristics and pathogenicity of the Coxiella strains. Four of the 90 serum samples (4.44%) were positive for specific C. burnetii IgM antibody, suggesting that local humans are at risk of Q fever. The positive rates of C. burnetii in hedgehogs and ticks were 21.9% (7/32) and 70.5% (122/173), respectively. At least 3 strains of Coxiella were found prevalent in the investigated area, including one new genotype of pathogenic C. burnetii (XYHT29) and two non-pathogenic Coxiella-like organisms (XYHT19 and XYHT3). XYHT29 carried by ticks and wild hedgehogs successfully infected mice, imposing a potential threat to local humans. XYHT19, a novel Coxiella-like microorganism, was first discovered in the world to co-infect with C. burnetii in Haemaphysalis flava. The study provided significant epidemic information that could be used for prevention and control strategies against Q fever for local public health departments and medical institutions.

Abstract Background Evidence suggests that insulin resistance (IR) is an autonomous risk factor for cardiovascular disease (CVD). Nevertheless, the association between estimated glucose disposal rate (eGDR), a novel indicator of IR, and incident CVD and mortality in chronic kidney disease (CKD) patients without diabetes remains uncertain. Methods The study included 19,906 participants from the UK Biobank who had an estimated glomerular filtration rate (eGFR)

Abstract Background GPNMB is a type I transmembrane protein, and emerging evidence supports the relationship between GPNMB and cancers. Objective Through a comprehensive pan-cancer analysis, we examined the expression levels, prognostic significance, and mutation profiles of GPNMB in different cancer types. Subsequently, utilizing in vitro experiments, we elucidated the impact of GPNMB in endometrial cancer (EC). Methods TIMER2, GEPIA2, UALCAN and cBioPortal were used to analyze the expression pattern, prognostic values, and mutation status of GPNMB. HEC-1B and Ishikawa cells were used to conduct in vitro analyses of GPNMB overexpression. GeneMANIA and TIMER2 were used to evaluate the potential functions and correlations between GPNMB expression and tumor-infiltrating immune cells in EC. Results GPNMB was found to be highly expressed in multiple cancers, where it was associated with poor prognosis. Additionally, GPNMB was downregulated at both mRNA and protein levels in EC. Overexpression of GPNMB inhibited the proliferation, migration, and invasion of HEC-1B and Ishikawa cells. Functional analysis showed that GPNMB was enriched in pathways associated with regulation of plasma lipoprotein particle levels. The expression of GPNMB was positively connected with B cell, CD8+ T cell, CD4+ T cell, Macrophage, Neutrophil, and Dendritic cell levels. Conclusion Through pan-cancer analysis, we identified the antitumor effect of GPNMB in EC and predicted the potential mechanisms between GPNMB expression and EC.

Abstract Light encodes multidimensional information, such as intensity, polarization, and spectrum. Traditional extraction of this light information requires discrete optical components by subdividing the detection area into many “one-to-one” functional pixels. The broadband photodetection of high-dimensional optical information with a single integrated on-chip detector is highly sought after, yet it poses significant challenges. In this study, we employ a metasurface-assisted graphene photodetector, enabling to simultaneously detect and differentiate various polarization states and wavelengths of broadband light (1-8 μm) at the wavelength prediction accuracy of 0.5 μm. The bipolar polarizability empowered by this design allows to decouple multidimensional information (encompassing polarization and wavelength), which can be achieved by encoding vectorial photocurrents with varying polarities and amplitudes. Furthermore, cooperative multiport metasurfaces are adopted and boosted by machine learning techniques. It enables precise spin-wavelength differentiation over an extremely broad wavelength range (1-8 μm). Our innovation offers a recipe for highly compact and high-dimensional spectral-polarization co-detection.

Abstract Background Osteoporosis (OP) is a systemic bone disease characterized by reduced bone mass and deterioration of bone microstructure, leading to increased bone fragility. Platelets can take up and release cytokines, and a high platelet count has been associated with low bone density. Obesity is strongly associated with OP, and adipose tissue can influence platelet function by secreting adipokines. However, the biological relationship between these factors remains unclear. Methods We conducted differential analysis to identify OP platelet-related plasma proteins. And, making comprehensive analysis, including functional enrichment, protein-protein interaction network analysis, and Friends analysis. The key protein, Tetranectin (TNA/CLEC3B), was identified through screening. Then, we analyzed TNA’s potential roles in osteogenic and adipogenic differentiation using multiple RNA-seq data sets and validated its effect on osteoclast differentiation and bone resorption function through in vitro experiments. Results Six OP-platelet-related proteins were identified via differential analysis. Then, we screened the key protein TNA, which was found to be highly expressed in adipose tissue. RNA-seq data suggested that TNA may promote early osteoblast differentiation. In vitro experiments showed that knockdown of TNA expression significantly increased the expression of osteoclast markers, thereby promoting osteoclast differentiation and bone resorption. Conclusions We identified TNA as a secreted protein that inhibits osteoclast differentiation and bone resorption. While, it potentially promoted early osteoblast differentiation from bioinformatic results. TNA may play a role in bone metabolism through the adipose-bone axis.

Abstract Background Cardiovascular disease continues to be the leading cause of global mortality and disability, particularly posing elevated risks in patients diagnosed with multivessel disease (MVD). Efficient risk stratification in MVD patients is crucial for improving prognosis, prompting investigation into novel biomarkers such as the triglyceride-glucose index (TyG index) and the stress hyperglycemia ratio (SHR). Methods This study enrolled a cohort comprising 679 patients diagnosed with MVD who underwent coronary angiography at Tianjin Chest Hospital. Patients were stratified into four groups based on their TyG index levels, categorized as TyG index-L and TyG index-H, and SHR levels, categorized as SHR-L and SHR-H. The primary endpoint was the occurrence of major adverse cardio-cerebral events (MACCEs). This Study conducted univariate and multivariable Cox regression analyses to assess the association between TyG index and SHR levels, both as continuous and categorical variables, in relation to MACCEs. Kaplan–Meier survival curves were employed to evaluate the correlation among patient groups. Results During a mean follow-up of 61 months, 153 cases of MACCEs were recorded. The TyG index and SHR served as independent predictors of long-term prognosis in patients with MVD, whether considered as continuous or categorical variables. Multivariable analysis revealed that patients with TyG index-H + SHR-H group exhibited the highest incidence of MACCEs (HR: 2.227; 95% CI 1.295–3.831; P = 0.004). The area under the curve (AUC) for predicting MACCEs was 0.655 for TyG index, 0.647 for SHR, and 0.674 when combined. Conclusion This study underscores the potential of the TyG index and SHR as independent and combined predictive markers for MACCEs in patients with MVD. Their integrated assessment enhances risk stratification, providing valuable insights for personalized treatment strategies aimed at optimizing patient prognosis.

Abstract The trends of diversified diets in China have generated a growing number of nutritional health problems, and healthcare investment is bearing a large burden from the diets, hindering the economic progress of the country and its residents toward affluence. This study linked the evolution of the Chinese dietary structure to changes in health expenditures and predicts future dietary patterns and their impact on health costs over the next 30 years. We found that in the past 30 years, the Chinese dietary structure has shifted towards a nutritional surplus type, and the structure of health expenditures has also shown a trend of two increases and one decrease. The consumption of plant-based foods is significant correlated with lower health expenditures, and animal-based foods show a significant impact on increase of health expenditures. Among nutrients, fat is significant correlated with increased health expenditures, whereas calorie intake is significant correlated with lower health expenditures. By 2030, the Chinese dietary structure will still evolve to a high-protein and high-fatty type. This shift will result in a decrease in per capita healthcare expenditure by 41.66 yuan and increases in household, state, personal, and total healthcare expenditures by 76.83 yuan, 18.76 billion yuan, 95.28 billion yuan, and 17.67 billion yuan, respectively. These findings demonstrate that adjusting dietary structures will bring the dual benefits of improved national health status and a favorable cycle of health expenditures.

Abstract Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Abstract Background Sedentary behavior (SB) has emerged as a significant health concern that deserves attention. This study aimed to examine the associations between prolonged sedentary behavior and the risk of all-cause and cause-specific mortality as well as to explore desirable alternatives to sitting in terms of physical activity (PA). Methods Two prospective cohort investigations were conducted using the UK Biobank and NHANES datasets, with a total of 490,659 and 33,534 participants, respectively. Cox proportional hazards regression models were used to estimate the associations between SB and the risk of all-cause and cause-specific mortality due to cancer, cardiovascular disease (CVD), respiratory diseases, and digestive diseases. In addition, we employed isotemporal substitution models to examine the protective effect of replacing sitting with various forms of PA. Results During the average follow-up times of 13.5 and 6.7 years, 36,109 and 3057 deaths were documented in the UK Biobank and NHANES, respectively. Both cohorts demonstrated that, compared with individuals sitting less than 5 h per day, individuals with longer periods of sitting had higher risks of all-cause and cause-specific mortality due to cancer, CVD, and respiratory diseases but not digestive diseases. Moreover, replacing SB per day with PA, even substituting 30 min of walking for pleasure, reduced the risk of all-cause mortality by 3.5% (hazard ratio [HR] 0.965, 95% confidence interval [CI] 0.954–0.977), whereas cause-specific mortality from cancer, CVD, and respiratory diseases was reduced by 1.6% (HR 0.984, 95% CI 0.968–1.000), 4.4% (HR 0.956, 95% CI 0.930–0.982), and 15.5% (HR 0.845, 95% CI 0.795–0.899), respectively. Furthermore, the protective effects of substitution became more pronounced as the intensity of exercise increased or the alternative duration was extended to 1 h. Conclusions SB was significantly correlated with substantially increased risks of all-cause mortality and cause-specific mortality from cancer, CVD, and respiratory diseases. However, substituting sitting with various forms of PA, even for short periods involving relatively light and relaxing physical activity, effectively reduced the risk of both overall and cause-specific mortality. Graphical Abstract

Abstract Background The long-term impacts of COVID-19 on human health are a major concern, yet comprehensive evaluations of its effects on various health conditions are lacking. Methods This study aims to evaluate the role of various diseases in relation to COVID-19 by analyzing genetic data from a large-scale population over 2,000,000 individuals. A bidirectional two-sample Mendelian randomization approach was used, with exposures including COVID-19 susceptibility, hospitalization, and severity, and outcomes encompassing 86 different diseases or traits. A reverse Mendelian randomization analysis was performed to assess the impact of these diseases on COVID-19. Results Our analysis identified causal relationships between COVID-19 susceptibility and several conditions, including breast cancer (OR = 1.0073, 95% CI = 1.0032–1.0114, p = 5 × 10 − 4), ER + breast cancer (OR = 0.5252, 95% CI = 0.3589–0.7685, p = 9 × 10 − 4), and heart failure (OR = 1.0026, 95% CI = 1.001–1.0042, p = 0.002). COVID-19 hospitalization was causally linked to heart failure (OR = 1.0017, 95% CI = 1.0006–1.0028, p = 0.002) and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). COVID-19 severity had causal effects on primary biliary cirrhosis (OR = 2.6333, 95% CI = 1.8274–3.7948, p = 2.059 × 10 − 7), celiac disease (OR = 0.0708, 95% CI = 0.0538–0.0932, p = 9.438 × 10–80), and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). Reverse MR analysis indicated that rheumatoid arthritis, diabetic nephropathy, multiple sclerosis, and total testosterone (female) influence COVID-19 outcomes. We assessed heterogeneity and horizontal pleiotropy to ensure result reliability and employed the Steiger directionality test to confirm the direction of causality. Conclusions This study provides a comprehensive analysis of the causal relationships between COVID-19 and diverse health conditions. Our findings highlight the long-term impacts of COVID-19 on human health, emphasizing the need for continuous monitoring and targeted interventions for affected individuals. Future research should explore these relationships to develop comprehensive healthcare strategies.

Abstract Background and Aim Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients’ prognoses. Methods and results Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62–2.26 vs. HR: 1.75, 95% CI: 1.43–2.16, P

Abstract Background This study investigated the clinical value of breast magnetic resonance imaging (MRI) radiomics for predicting axillary lymph node metastasis (ALNM) and to compare the discriminative abilities of different combinations of MRI sequences. Methods This study included 141 patients diagnosed with invasive breast cancer from two centers (center 1: n = 101, center 2: n = 40). Patients from center 1 were randomly divided into training set and test set 1. Patients from center 2 were assigned to the test set 2. All participants underwent preoperative MRI, and four distinct MRI sequences were obtained. The volume of interest (VOI) of the breast tumor was delineated on the dynamic contrast-enhanced (DCE) postcontrast phase 2 sequence, and the VOIs of other sequences were adjusted when required. Subsequently, radiomics features were extracted from the VOIs using an open-source package. Both single- and multisequence radiomics models were constructed using the logistic regression method in the training set. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision of the radiomics model for the test set 1 and test set 2 were calculated. Finally, the diagnostic performance of each model was compared with the diagnostic level of junior and senior radiologists. Results The single-sequence ALNM classifier derived from DCE postcontrast phase 1 had the best performance for both test set 1 (AUC = 0.891) and test set 2 (AUC = 0.619). The best-performing multisequence ALNM classifiers for both test set 1 (AUC = 0.910) and test set 2 (AUC = 0.717) were generated from DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging single-sequence ALNM classifiers. Both had a higher diagnostic level than the junior and senior radiologists. Conclusions The combination of DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging radiomics features had the best performance in predicting ALNM from breast cancer. Our study presents a well-performing and noninvasive tool for ALNM prediction in patients with breast cancer.

Abstract Using e + e − annihilation data sets corresponding to an integrated luminosity of 4.5 fb −1, collected with the BESIII detector at center-of-mass energies between 4.600 and 4.699 GeV, we report the first measurements of the absolute branching fractions B Λ c + → p K L 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0\right) $$ = (1.67 ± 0.06 ± 0.04)%, B Λ c + → p K L 0 π + π − $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^{+}{\pi}^{-}\right) $$ = (1.69 ± 0.10 ± 0.05)%, and B Λ c + → p K L 0 π 0 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{K}_L^0{\pi}^0\right) $$ = (2.02 ± 0.13 ± 0.05)%, where the first uncertainties are statistical and the second systematic. Combining with the known branching fractions of Λ c + → p K S 0 $$ {\Lambda}_c^{+}\to p{K}_S^0 $$ , Λ c + → p K S 0 π + π − $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^{+}{\pi}^{-} $$ , and Λ c + → p K S 0 π 0 $$ {\Lambda}_c^{+}\to p{K}_S^0{\pi}^0 $$ , we present the first measurements of the K S 0 $$ {K}_S^0 $$ - K L 0 $$ {K}_L^0 $$ asymmetries R Λ c + K S , L 0 X = B Λ c + → K S 0 X − B Λ c + → K L 0 X B Λ c + → K S 0 X + B Λ c + → K L 0 X $$ R\left({\Lambda}_c^{+},{K}_{S,L}^0X\right)=\frac{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)-\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)}{\mathcal{B}\left({\Lambda}_c^{+}\to {K}_S^0X\right)+\mathcal{B}\left({\Lambda}_c^{+}\to {K}_L^0X\right)} $$ in charmed baryon decays: R Λ c + p K S , L 0 = − 0.025 ± 0.031 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0\right)=-0.025\pm 0.031 $$ , R Λ c + p K S , L 0 π + π − = − 0.027 ± 0.048 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^{+}{\pi}^{-}\right)=-0.027\pm 0.048 $$ and R Λ c + p K S , L 0 π 0 = − 0.015 ± 0.046 $$ R\left({\Lambda}_c^{+},p{K}_{S,L}^0{\pi}^0\right)=-0.015\pm 0.046 $$ . No significant asymmetries with statistical significance are observed.

Abstract Background A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. Methods We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. Results Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P

Abstract Background On March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3. Case presentation A 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People's Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient's respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6–99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022). Conclusions According to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin.