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Abstract Charge density waves (CDWs) in transition metal dichalcogenides are the subject of growing scientific interest due to their rich interplay with exotic phases of matter and their potential technological applications. Here, using density functional theory with advanced meta-generalized gradient approximations (meta-GGAs) and linear response time-dependent density functional theory (TDDFT) with state-of-the-art exchange-correlation kernels, we investigate the electronic, vibrational, and optical properties in 1T-TiSe2 with and without CDW. In both bulk and monolayer TiSe2, the electronic bands and phonon dispersions in either normal or CDW (semiconducting) phase are described well via meta-GGAs, which separate the valence and conduction bands just as HSE06 does but with significantly more computational feasibility. The experimentally observed humps of electron energy loss spectroscopy are successfully reproduced in TDDFT. Our work opens the door to simulating these complexities in CDW compounds from first principles by revealing meta-GGAs as an accurate low-cost alternative to HSE06.

Abstract The global burden of hepatitis B virus (HBV) infection remains high, with chronic hepatitis B (CHB) patients facing a significantly increased risk of developing cirrhosis and hepatocellular carcinoma (HCC). The ultimate objective of antiviral therapy is to achieve a sterilizing cure for HBV. This necessitates the elimination of intrahepatic covalently closed circular DNA (cccDNA) and the complete eradication of integrated HBV DNA. This review aims to summarize the oncogenetic role of HBV integration and the significance of clearing HBV integration in sterilizing cure. It specifically focuses on the molecular mechanisms through which HBV integration leads to HCC, including modulation of the expression of proto-oncogenes and tumor suppressor genes, induction of chromosomal instability, and expression of truncated mutant HBV proteins. The review also highlights the impact of antiviral therapy in reducing HBV integration and preventing HBV-related HCC. Additionally, the review offers insights into future objectives for the treatment of CHB. Current strategies for HBV DNA integration inhibition and elimination include mainly antiviral therapies, RNA interference and gene editing technologies. Overall, HBV integration deserves further investigation and can potentially serve as a biomarker for CHB and HBV-related HCC.

Object detection in road scenarios is crucial for intelligent transport systems and autonomous driving, but complex traffic conditions pose significant challenges. This paper introduces Z-You Only Look Once version 8 small (Z-YOLOv8s), designed to improve both accuracy and real-time efficiency under real-world uncertainties. By incorporating Revisiting Perspective Vision Transformer (RepViT) and C2f into the YOLOv8s framework, and integrating the Large Selective Kernel Network (LSKNet), the model enhances spatial feature extraction. Additionally, the YOLOv8s backbone is optimized with Space-to-Depth Convolution (SPD-Conv) for better small object detection. The Softpool-Spatial Pyramid Pooling Fast (SoftPool-SPPF) module ensures precise characteristic information preservation. Z-YOLOv8s improves mean average precision (mAP)@0.5 on the Berkeley Deep Drive 100 K (BDD100K) and Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) datasets by 7.3 % and 3.8 %, respectively. It also achieves accuracy increases of 5.7 % and 6.5 % in Average Precision (AP)-Small, and a real-time detection speed of 78.41 frames per second (FPS) on the BDD100K. Z-YOLOv8s balances detection precision and processing speed more effectively than other detectors, as demonstrated by experimental results and comparisons.

Abstract Previous studies have found associations between the incidence of metabolic syndrome (MetS) and exposure to air pollution or road traffic noise. However, investigations on environmental co-exposures are limited. This study aimed to investigate the association between co-exposure to air pollution and road traffic noise and MetS and its subcomponents. Participants living in Taipei City who underwent at least two health checkups between 2010 and 2016 were included in the study. Data were sourced from the MJ Health database, a longitudinal, large-scale cohort in Taiwan. The monthly traffic noise exposure (Lden and Lnight) was computed using a dynamic noise map. Monthly fine particulate data at one kilometer resolution were computed from satellite imagery data. Cox proportional hazards regression models with month as the underlying time scale were used to estimate hazard ratios (HRs) for the impact of PM2.5 and road traffic noise exposure on the risk of developing MetS or its subcomponents. Data from 10,773 participants were included. We found significant positive associations between incident MetS and PM2.5 (HR: 1.88; 95% CI 1.67, 2.12), Lden (HR: 1.10; 95% CI 1.06, 1.15), and Lnight (HR: 1.07; 95% CI 1.02, 1.13) in single exposure models. Results further showed significant associations with an elevated risk of incident MetS in co-exposure models, with HRs of 1.91 (95% CI 1.69, 2.16) and 1.11 (95% CI 1.06, 1.16) for co-exposure to PM2.5 and Lden, and 1.90 (95% CI 1.68, 2.14) and 1.08 (95% CI 1.02, 1.13) for co-exposure to PM2.5 and Lnight. The HRs for the co-exposure models were higher than those for models with only a single exposure. This study provides evidence that PM2.5 and noise exposure may elevate the risk of incident MetS and its components in both single and co-exposure models. Therefore, preventive approaches to mitigate the risk of MetS and its subcomponents should consider reducing exposure to PM2.5 and noise pollution.

BackgroundBronchopulmonary dysplasia (BPD) is the most prevalent chronic lung disease in preterm infants. Studies have shown that Ureaplasma urealyticum (UU) infection is linked to its pathogenesis. However, it remains controversial whether UU colonization in preterm infants increases the risk of developing BPD.ObjectiveThis study aimed to conduct a systematic review and meta-analysis to summarize the correlation between UU and BPD.MethodsWe searched PubMed, Embase, the Cochrane Library, Web of Science, Wanfang Database, Chinese National Knowledge Infrastructure Database, Chinese Science and Technique Journal Database, and the China Biology Medicine disc from their inception to March 15, 2024. We included cohort and case-control studies investigating the association between UU infections and BPD in preterm infants, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for quality assessment. The outcome was defined as the continued need for oxygen or respiratory support at 28 days after birth (BPD28) or at 36 weeks postmenstrual age (BPD36). Considering the potential publication bias in observational studies, we used a random-effects meta-analysis model, assessed heterogeneity (I2), performed subgroup analyses, evaluated publication bias, and graded the quality of evidence.ResultsThe meta-analysis included 36 cohort studies encompassing 5,991 participants. Among these, 20 reported on BPD28, 13 on BPD36, and 3 on both. The results indicated a significant association between UU colonization and BPD28 (odds ratio (OR): 2.26, 95% confidence interval (CI): 1.78–2.85, P

Background: Mycobacterium tilburgii is a nonculturable, nontuberculous mycobacterium that occasionally causes serious infections in individuals with immune deficiencies. Owing to its nonculturable nature, its antimicrobial susceptibility has not been assessed, and the optimal treatment regimen is unclear. Herein, we report a case of disseminated M. tilburgii infection in a person with AIDS, identified using metagenomics next-generation sequencing (mNGS) and polymerase chain reaction (PCR). Case presentation: A 33-year-old man presented with a 3-month history of abdominal pain, lymphadenopathy, intermittent night hot flashes, night sweats, and weight loss. No pathogen was detected during initial routine investigations. M. tilburgii was subsequently identified in a left cervical lymph node sample using mNGS. Furthermore, M. tilburgii infection was detected in a bone marrow sample based on PCR of 16S rRNA and hsp65 gene sequencing. The person was treated with a combination of moxifloxacin, clarithromycin, ethambutol, rifabutin, and amikacin. The laboratory results improved, and the patient's symptoms resolved. Conclusion: M. tilburgii may be missed in diagnostic tests because it cannot be grown using routine culture techniques. Early diagnosis and timely and effective treatment are critical in patients with M. tilburgii infection; therefore, molecular techniques are recommended for patients with suspected M. tilburgii infection.

Summary: Many countries and commercial organizations have shown great interest in constructing a Martian base. In situ resource utilization (ISRU) provides a cost-effective way to achieve this ambitious goal. In this article, we proposed to use Martian soil simulant to produce a fiber to satisfy material requirement for the construction of Martian base. The composition, melting behavior, and fiber forming process of the soil simulant was studied, and continuous fiber with maximum strength of 1320 MPa and elastic modulus of 99 GPa was obtained on a spinning facility. The findings of this study demonstrate the feasibility of ISRU to prepare Martian fiber from the soil on the Mars, offering a new way to obtain key materials for the construction of a Martian base.

Invasive Spartina alterniflora (S. alterniflora) has significant impacts on sediment biogeochemical cycling in the tidal wetlands of estuaries and coasts. However, the impact of exotic Spartina alterniflora invasion on greenhouse gases (GHGs) production dynamics in sediments remain limited. Here, we investigated the dynamics of sediment physicochemical properties, GHGs production rates, and microbial gene abundances in a native Cyperus malacensis habitat and three invasive S. alterniflora habitats (6-, 10-, and 14-year) in the Minjiang River Estuary, China. The methane (CH4), carbon dioxide (CO2), and nitrous oxide (N2O) production rates varied both spatially and seasonally, while microbial gene abundances (bacterial and fungal gene abundances) and organic matter (TOC and TN) only varied spatially. GHGs production rates were also characterized by higher values in surface sediment (0–10 cm) compared to subsurface sediment (10–20 cm) and by seasonal variations with higher values in summer than in winter. S. alterniflora invasion can significantly increase CH4 and CO2 production rates, organic matter, and microbial gene abundances (p < 0.05). Temperature, organic matter and microbial gene abundances were the most dominating factor controlling the spatio-temporal variations of CH4 and CO2 production rates. Overall, our findings highlighted the significant role of S. alterniflora invasion in regulating GHGs production rates in coastal wetland sediments and provided fundamental data for estimating GHGs emissions and carbon sequestration in the complex tidal wetlands.

Huaier, derived from the fungus on Sophora japonica trees, is a fruiting body belonging to Polyporaceae family. Traditionally, it has been utilized for treating hemorrhoids and rectal bleeding. As a medicine food homology herb, its remarkable immune-regulating properties have led to widespread adoption in digestive system tumors in recent years. Currently, over 502 compounds, excluding polysaccharides, have been isolated from Huaier exhibiting diverse biological activities and medicinal value. Clinically, Huaier has demonstrated effectiveness against digestive system tumors. Mechanistic studies suggested that Huaier may exert its antitumor effects by bolstering immunity, inducing tumor cell death, inhibiting tumor proliferation, migration, invasion, metastasis, and dampening inflammatory cancer transformation. The abundance of active ingredients underscores Huaier's potential as an anticancer agent. Both its clinical application and mechanistic investigations highlight its significant promise in addressing digestive system tumors.

Abstract 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that can cause gastrointestinal ulcers by affecting dopamine levels. Therefore, MPTP has been considered a toxic substance that causes gastric ulcer disease in experimental animals. In this study, tree shrews were used as the animal model of gastric mucosa injury, and MPTP was intraperitoneally injected at a lower MPTP dosage 2 mg/kg/day for 13 weeks, while tree shrews were not injected as the control group. Under the light microscope, local congestion or diffuse bleeding points of gastric mucosa and multiple redness and swelling bleeding symptoms on the inner wall were observed in the treatment group, as well as immune cell infiltration was found in HE staining, but no such phenomenon was observed in the control group. In order to explore the molecular basis of changes in MPTP induced gastric mucosa injury, the transcriptome and proteome data of gastric mucosa were analyzed. We observed significant differences in mRNA and protein expression levels under the influence of MPTP. The changes in mRNA and proteins are related to increased immune infiltration, cellular processes and angiogenesis. More differentially expressed genes play a role in immune function, especially the candidate genes RPL4 and ANXA1 with significant signal and core role. There are also differentially expressed genes that play a role in mucosal injury and shedding, especially candidate genes GAST and DDC with certain signaling and corresponding functions. Understanding the factors and molecular basis that affect the expression of related genes is crucial for coping with Emotionality gastric mucosa injury disease and developing new treatment methods to establish the ability to resist disease.

Abstract Background HBV infection is the leading risk factor for HCC. HBV infection has been confirmed to be associated with the exhaustion status of CD8+ T cells and immunotherapeutic efficacy in HCC. In this study, we aimed to investigate the prognostic value of the CD8+ T-cell exhaustion signature and immunotherapy response in patients with HBV-related HCC. Methods We identified different clusters of HBV-related HCC cells by single-cell RNA sequencing (scRNA-seq) and identified CD8+ T-cell exhaustion-related genes (TERGs) by pseudotime analysis. We conducted differential expression analysis and LASSO Cox regression to detect genes and construct a CD8+ T-cell exhaustion index (TEI). We next combined the TEI with other clinicopathological factors to design a prognostic nomogram for HCC patients. We also analysed the difference in the TEI between the non-responder and responder groups during anti-PD-L1 therapy. In addition, we investigated how HBV induces CD8+ T lymphocyte exhaustion through the inhibition of tyrosine metabolism in HCC using gene set enrichment analysis and RT‒qPCR. Results A CD8+ T-cell exhaustion index (TEI) was established with 5 TERGs (EEF1E1, GAGE1, CHORDC1, IKBIP and MAGOH). An AFP level > 500 ng, vascular invasion, histologic grade (G3-G4), advanced TNM stage and poor five-year prognosis were related to a higher TEI score, while HBV infection was related to a lower TEI score. Among those receiving anti-PD-L1 therapy, responders had lower TEIs than non-responders did. The TEI also serves as an independent prognostic factor for HCC, and the nomogram incorporating the TEI, TNM stage, and vascular invasion exhibited excellent predictive value for the prognosis in HCC patients. RT‒qPCR revealed that among the tyrosine metabolism-associated genes, TAT (tyrosine aminotransferase) and HGD (homogentisate 1,2 dioxygenase) were expressed at lower levels in HBV-HCC than in non-HBV HCC. Conclusion Generally, we established a novel TEI model by comprehensively analysing the progression of CD8+ T-cell exhaustion, which shows promise for predicting the clinical prognosis and potential immunotherapeutic efficacy in HBV-related HCC patients.

ABSTRACTDuring disaster response, it is very important to obtain the information of collapsed building distribution accurately and quickly. However, limited by some practical factors, existed methods often suffer from the contradiction between the accuracy and efficiency of building damage extraction. This paper proposed a simple and effective framework to rapid recognize collapsed building objects using pre-disaster building distribution maps and post-disaster quasi-panchromatic remote sensing images. The proposed method is validated using several historical disasters in the xBD dataset and tested using three cases of earthquakes in terms of both effectiveness and efficiency. In addition, we have verified that the texture information of optical remote sensing images can be used as the main basis to judge whether a building is collapsed or not, so the panchromatic images are sufficient to enable the deep learning model to correctly recognize collapsed buildings. The experimental results indicate that using quasi-panchromatic images can alleviate the influence of style variations and diverse roof colors present in multi-spectral images on the model’s generalization performance, resulting in an average overall accuracy improvement of 2.4%. Additionally, the reduced data volume leads to an improvement in inference efficiency.

Introduction Preterm birth complications and neonatal asphyxia are the leading causes of neonatal mortality worldwide. Surviving preterm and asphyxiated newborns can develop neurological sequelae; therefore, timely and appropriate neonatal resuscitation is important to decrease neonatal mortality and disability rates. There are very few systematic studies on neonatal resuscitation in China, and its prognosis remains unclear. We established an online registry for neonatal resuscitation in Shenzhen based on Utstein’s model and designed a prospective, multicentre, open, observational cohort study to address many of the limitations of existing studies. The aim of this study is to explore the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen.Methods and analysis This prospective, multicentre, open, observational cohort study will be conducted between January 2024 and December 2026 and will include >1500 newborns resuscitated at birth by positive pressure ventilation at five hospitals in Shenzhen, located in the south-central coastal area of Guangdong province, China. Maternal and infant information, resuscitation information, hospitalisation information and follow-up information will be collected. Maternal and infant information, resuscitation information and hospitalisation information will be collected from the clinical records of the patients. Follow-up information will include the results of follow-up examinations and outcomes, which will be recorded using the WeChat applet ‘Resuscitation Follow-up’. These data will be provided by the neonatal guardians through the applet on their mobile phones. This study will provide a more comprehensive understanding of the implementation and management, risk factors and outcomes of neonatal resuscitation in Shenzhen; the findings will ultimately contribute to the reduction of neonatal mortality and disability rates in Shenzhen.Ethics and dissemination Our protocol has been approved by the Medical Ethics Committee of Shenzhen Luohu People’s Hospital (2023-LHQRMYY-KYLL-048). We will present the study results at academic conferences and peer-reviewed paediatrics journals.Trial registration number ChiCTR2300077368.

Invasive Spartina alterniflora has significant impacts on sediment carbon pool and turnover in the tidal wetlands of estuaries and coasts. Yet, how this exotic S. alterniflora affects sediment organic carbon mineralization dynamics remains poorly understood. In this study, sediment geochemical properties, organic carbon fractions, and mineralization dynamics were examined in a native Cyperus malaccensis habitat and three invasive S. alterniflora habitats (6-, 10-, and 14-year-old) in summer and winter. We found that invasive S. alterniflora generally increased sediment total organic carbon and their labile fraction contents. The organic carbon mineralization rates and cumulative carbon mineralization amounts were significantly influenced by invasive S. alterniflora, and their values increased with this exotic plant invasion chronosequences. The mineralization rates and cumulative mineralization amounts were also characterized by higher values in surface sediment (0 – 10 cm depth) compared to subsurface sediment (10 – 20 cm depth) and by seasonal variations with higher values in summer than in winter. The sediment organic carbon labile fractions, rather than total organic carbon, were the most important factor affecting carbon mineralization dynamics. The cumulative carbon mineralization amounts exhibited an excellent fit to the first-order kinetic equation (R2 ≥ 0.93). The changes in modeled kinetic parameters (potential carbon mineralization amounts (C0) and carbon mineralization rate constant (k)) among these four habitats were similar to carbon mineralization rates, implying invasive S. alterniflora promoted the availabilities of organic compounds for microbial respiration metabolism. Overall, our findings highlighted the importance of S. alterniflora invasion in accelerating organic carbon decomposition and carbon dioxide release potential, although it also increases carbon accumulation.

BackgroundElevated international normalized ratio of prothrombin time (PT-INR) is one of the key characteristics of acute-on-chronic liver failure (ACLF). Whether the staging of PT-INR has the ability to screen out subgroups of ACLF patients who would be more eligible for artificial liver support system (ALSS) treatment has not been studied in detail.MethodsA previous study enrolled patients receiving ALSS treatment with regional citrate anticoagulation from January 2018 to December 2019. Patients with different PT-INR intervals were retrospectively enrolled: 1.3 ≤ PT-INR

Abstract Three‐dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D‐RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D‐RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D‐RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor‐dependent and vendor‐independent software platforms were used to analyze the 3D‐RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D‐RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D‐RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D‐RV values should be stratified by sex, age, race, and vendor.

BackgroundFungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest.ObjectivesThis study aimed to provide evidence for the early warning and management of fungal infections.MethodsWe analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed.ResultsA total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053–1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015–1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855–0.970) were an independent risk factor for empirical antifungal therapy.ConclusionThe most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.

Summary: Background: Hepatocellular carcinoma (HCC) is a highly prevalent and deadly type of cancer, and although pharmacotherapy remains the cornerstone of treatment, therapeutic outcomes are often unsatisfactory. Pharmacological inhibition of mammalian target of rapamycin (mTOR) has been closely associated with HCC regression. Methods: Herein, we covalently conjugated AZD8055, a potent mTORC1/2 blocker, with a small panel of unsaturated fatty acids via a dynamically activating linkage to enable aqueous self-assembly of prodrug conjugates to form mTOR nanoblockers. Cell-based experiments were carried out to evaluate the effects of the nanoblocker against hepatocellular carcinoma (HCC) cells. The orthotopic and subcutaneous HCC mouse models were established to examine its antitumour activity. Findings: Among several fatty acids as promoieties, linoleic acid-conjugated self-assembling nanoblocker exhibited optimal size distribution and superior physiochemical properties. Compared with free agents, PEGylated AZD8055 nanoblocker (termed AZD NB) was pharmacokinetically optimized after intravenous administration. In vivo investigations confirmed that AZD NB significantly suppressed tumour outgrowth in subcutaneous HCCLM3 xenograft, Hepatoma-22, and orthotopic Hepa1-6 liver tumour models. Strikingly, treatment with AZD NB, but not free agent, increased intratumour infiltration of IFN-γ+CD8+ T cells and CD8+ memory T cells, suggesting a potential role of the mTOR nanoblocker to remodel the tumour microenvironment. Overall, a single conjugation with fatty acid transformed a hydrophobic mTOR blocker into a systemically injectable nanomedicine, representing a facile and generalizable strategy for improving the therapeutic index of mTOR inhibition-based cancer therapy. Interpretation: The mTOR inhibition by chemically engineered nanoblocker presented here had enhanced efficacy against tumours compared with the pristine drug and thus has the potential to improve the survival outcomes of patients with HCC. Additionally, this new nanosystem derived from co-assembling of small-molecule prodrug entities can serve as a delivery platform for the synergistic co-administration of distinct pharmaceutical agents. Funding: This work was supported by the National Natural Science Foundation of China (32171368,81721091), the Zhejiang Provincial Natural Science Foundation of China (LZ21H180001), the Jinan Provincial Laboratory Research Project of Microecological Biomedicine (JNL-2022039c and JNL-2022010B), State Key Laboratory for Diagnosis and Treatment of Infectious Diseases (zz202310), and Natural Science Foundation of Shandong Province (ZR2023ZD59).

Background: Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention. Methods: The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor–Immune System Interactions Database (TISIDB), and validated through western blot experiments. Results: Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B ( APOB ) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A ( HNF4A ) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells. Conclusion: Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB . Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

Abstract Background The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. Methods A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. Results In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-β (IFN-β) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. Conclusions Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Abstract Background Helicobacter pylori lipopolysaccharide (LPS) structures vary among strains of different geographic origin. The aim of this study was to characterize the LPS O-antigen profiles of H. pylori strains isolated from Southwest China, and to further analyze the association of Lewis antigen expression with clinical outcomes and antibiotic resistance. Results A total of 71 H. pylori isolates from Southwest China were included for LPS profiling by silver staining and Western blotting after SDS-PAGE electrophoresis. We demonstrated that all the clinical isolates had the conserved lipid A and core-oligosaccharide, whereas the O-antigen domains varied significantly among the isolates. Compared with the common presence of the glucan/heptan moiety in LPS O-antigen structure of European strains, the clinical isolates in this study appeared to lack the glucan/heptan moiety. The expression frequency of Lex, Ley, Lea, and Leb was 66.2% (47/71), 84.5% (60/71), 56.3% (40/71), and 31.0% (22/71), respectively. In total, the expression of type II Lex and/or Ley was observed in 69 (97.2%) isolates, while type I Lea and/or Leb were expressed in 49 (69.0%) isolates. No association of Lewis antigen expression with clinical outcomes or with antibiotic resistance was observed. Conclusions H. pylori strains from Southwest China tend to produce heptan-deficient LPS and are more likely to express type I Lewis antigens as compared with Western strains. This may suggest that H. pylori evolves to change its LPS structure for adaptation to different hosts.

Abstract Background Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims to reveal the contributions of NRCAM to LCSC function and HCC metastasis, and further explore its mechanism in detail. Methods 117 HCC and 29 non-HCC patients with focal liver lesions were collected and analyzed to assess the association between NRCAM and HCC metastasis. Single-cell RNA sequencing (scRNA-seq) was used to explore the biological characteristics of cells with high NRCAM expression in metastatic HCC. The role and mechanism of NRCAM in LCSC dissemination and metastasis was explored in vitro and in vivo using MYC-driven LCSC organoids from murine liver cells. Results Serum NRCAM is associated with HCC metastasis and poor prognosis. A scRNA-seq analysis identified that NRCAM was highly expressed in LCSCs with MYC activation in metastatic HCC. Moreover, NRCAM facilitated LCSC migration and invasion, which was confirmed in MYC-driven LCSC organoids. The in vivo tumor allografts demonstrated that NRCAM mediated intra-hepatic/lung HCC metastasis by enhancing the ability of LCSCs to escape from tumors into the bloodstream. Nrcam expression inhibition in LCSCs blocked HCC metastasis. Mechanistically, NRCAM activated epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) through the MACF1 mediated β-catenin signaling pathway in LCSCs. Conclusions LCSCs typified by high NRCAM expression have a strong ability to invade and migrate, which is an important factor leading to HCC metastasis.

To explore the development of coal seam fractures around gas extraction borehole and the issue of self-ignition caused by air leakage, a combination of theoretical analysis, field testing, and laboratory experiments was used. The distribution characteristics of cracks in the crushed zone after borehole excavation were analyzed. An in-situ test using SF6 tracer gas was conducted to measure air leakage in the gas extraction borehole, revealing the law of air leakage around the gas extraction borehole during the process of gas pre-extraction. Using a program for temperature increase and gas chromatography combined experiment, the self-ignition characteristic parameters of coal under different air supply rates were studied as a research object of the 215 working face in a certain mine, and the functional relationship formula between oxygen consumption rate, CO generation rate, and coal temperature and air supply rate was obtained. The results showed that the main ways of air leakage around the gas extraction borehole were side leakage of roadway coal wall, drilling fracture leakage, and sealing section leakage. The minimum air leakage rate around the gas extraction borehole was quantitatively obtained between 0.19 m/min and 0.68 m/min, with an average air leakage rate of 0.41 m/min, and the range of air leakage in the borehole was greater than 4.35 m. The air supply rate had a promoting effect on the natural characteristics parameters of coal.

Abstract Epstein‒Barr virus (EBV) is a DNA virus that belongs to the human B lymphotropic herpesvirus family and is highly prevalent in the human population. Once infected, a host can experience latent infection because EBV evades the immune system, leading to hosts harboring the virus for their lifetime. EBV is associated with many diseases and causes significant challenges to human health. This review first offers a description of the natural history of EBV infection, clarifies the interaction between EBV and the immune system, and finally focuses on several major types of diseases caused by EBV infection.

Beat-by-beat monitoring of hemodynamic parameters in the left ventricle contributes to the early diagnosis and treatment of heart failure, valvular heart disease, and other cardiovascular diseases. Current accurate measurement methods for ventricular hemodynamic parameters are inconvenient for monitoring hemodynamic indexes in daily life. The objective of this study is to propose a method for estimating intraventricular hemodynamic parameters in a beat-to-beat style based on non-invasive PCG (phonocardiogram) and PPG (photoplethysmography) signals. Three beagle dogs were used as subjects. PCG, PPG, electrocardiogram (ECG), and invasive blood pressure signals in the left ventricle were synchronously collected while epinephrine medicine was injected into the veins to produce hemodynamic variations. Various doses of epinephrine were used to produce hemodynamic variations. A total of 40 records (over 12,000 cardiac cycles) were obtained. A deep neural network was built to simultaneously estimate four hemodynamic parameters of one cardiac cycle by inputting the PCGs and PPGs of the cardiac cycle. The outputs of the network were four hemodynamic parameters: left ventricular systolic blood pressure (SBP), left ventricular diastolic blood pressure (DBP), maximum rate of left ventricular pressure rise (MRR), and maximum rate of left ventricular pressure decline (MRD). The model built in this study consisted of a residual convolutional module and a bidirectional recurrent neural network module which learnt the local features and context relations, respectively. The training mode of the network followed a regression model, and the loss function was set as mean square error. When the network was trained and tested on one subject using a five-fold validation scheme, the performances were very good. The average correlation coefficients (CCs) between the estimated values and measured values were generally greater than 0.90 for SBP, DBP, MRR, and MRD. However, when the network was trained with one subject’s data and tested with another subject’s data, the performance degraded somewhat. The average CCs reduced from over 0.9 to 0.7 for SBP, DBP, and MRD; however, MRR had higher consistency, with the average CC reducing from over 0.9 to about 0.85 only. The generalizability across subjects could be improved if individual differences were considered. The performance indicates the possibility that hemodynamic parameters could be estimated by PCG and PPG signals collected on the body surface. With the rapid development of wearable devices, it has up-and-coming applications for self-monitoring in home healthcare environments.

Bone morphogenetic proteins (BMPs) are a group of growth factors belonging to the transforming growth factor β(TGF-β) family. While initially recognized for their role in bone formation, BMPs have emerged as significant players in liver diseases. Among BMPs with various physiological activities, this comprehensive review aims to delve into the involvement of BMP9 specifically in liver diseases and provide insights into the complex BMP signaling pathway. Through an enhanced understanding of BMP9, we anticipate the discovery of new therapeutic options and potential strategies for managing liver diseases.

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients’ progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels.

Introduction: Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high short-term mortality. ACLF has been increasingly studied in recent years; however, a bibliometric analysis of the entire ACLF field has not been conducted. This study assesses current global trends and hotspots in ACLF research. Materials and methods: The core Web of Science database was searched for all ACLF-related publications conducted during 2012–2022. The data included information on the author, country, author keywords, publication year, citation frequency, and references. Microsoft Excel was used to collate the data and calculate percentages. VOSviewer software was used for citation and density visualization analysis. Histogram rendering was performed using GraphPad Prism Version 8.0 and R software was used to supplement the analysis. Result: A total of 1609 ACLF-related articles from 67 different countries were identified. China contributed the most literature, followed by the United States. However, Chinese literature only had the 4th highest number of citations, indicating that cooperation with other countries needs to be strengthened. The Journal of Hepatology had the highest number of ACLF-related citations. Prognosis was one of the most common author keywords, which may highlight current research hotspots. Bacterial infection was a common keyword and was closely related to prognosis. Conclusion: This bibliometric analysis suggests that future research hotspots will focus on the interplay among bacterial infection, organ failure, and prognosis.

Urban heat islands will occur if city neighborhoods contain insufficient green spaces to create a comfortable environment, and residents' health will be adversely affected. Current satellite imagery can only effectively identify large-scale green spaces and cannot capture street trees or potted plants within three-dimensional building spaces. In this study, we used a deep convolutional neural network semantic segmentation model on Google Street View to extract environmental features at the neighborhood level in Taipei City, Taiwan, including the green vegetation index (GVI), building view factor, and sky view factor. Monthly temperature data from 2018 to 2021 with a 0.01° spatial resolution were used. We applied a linear mixed-effects model and geographically weighted regression to explore the association between pedestrian-level green spaces and ambient temperature, controlling for seasons, land use information, and traffic volume. Their results indicated that a higher GVI was significantly associated with lower ambient temperatures and temperature differences. Locations with higher traffic flows or specific land uses, such as religious or governmental, are associated with higher ambient temperatures. In conclusion, the GVI from street-view imagery at the community level can improve the understanding of urban green spaces and evaluate their effects in association with other social and environmental indicators.

IntroductionThe healing of tendon-bone injuries is very difficult, often resulting in poor biomechanical performance and unsatisfactory functional recovery. The tendon-bone insertion has a complex four distinct layers structure, and previous studies have often focused on promoting the regeneration of the fibrocartilage layer, neglecting the role of its bone end repair in tendon-bone healing. This study focuses on the role of treadmill training in promoting bone regeneration at the tendon-bone insertion and its related mechanisms.MethodsAfter establishing the tendon-bone insertion injury model, the effect of treadmill training on tendon-bone healing was verified by Micro CT and HE staining; then the effect of CX3CL1 on osteoclast differentiation was verified by TRAP staining and cell culture; and finally the functional recovery of the mice was verified by biomechanical testing and behavioral test.ResultsTreadmill training suppresses the secretion of CX3CL1 and inhibits the differentiation of local osteoclasts after tendon-bone injury, ultimately reducing osteolysis and promoting tendon bone healing.DiscussionOur research has found the interaction between treadmill training and the CX3CL1-C3CR1 axis, providing a certain theoretical basis for rehabilitation training.

Solar wind can directly interact with the lunar surface and bring a space weathering effect. Some solar wind protons can be scattered as energetic neutral atoms (ENAs), which include rich information of the solar wind–surface interaction. However, people still know little about the ENA truth on the lunar ground due to the lack of in situ measurements. Different from the previous in-orbit measurements, here we present the first ground-based ENA measurements by the Chang’E-4 rover and find a good correlation between the mean ENA energy and the solar wind energy. Moreover, the loss rate of ENA energy can strongly depend on both the solar wind energy and the solar zenith angle (SZA), in which the energy loss rate can be enhanced by 73% when the solar wind energy increases from 400 to 1400 eV and can be reduced by 32% when the SZA increases from 57° to 71°. Combined with numerical simulations by SDTrimSP code, we propose that the solar wind protons can penetrate deeper into the lunar surface with a longer path length when the solar wind energy is higher or the SZA is lower, which results in a larger energy loss rate for the scattered ENAs. Our results provide an important constraint for the solar wind–surface research and have general implications in studying the surficial space weathering of the Moon and other airless bodies.

In order to improve the efficiency of submarine pipeline inspection, and manage inspection data more reasonably and effectively, so as to analyze and predict pipeline health status more scientifically, an efficient and intelligent submarine pipeline inspection management platform was constructed by using WebGIS and 3D visualization technology. The platform has functions such as automatic management of job flow, visual monitoring of job site, intelligent analysis and visual display of inspection data. The results of applications show that the platform is advanced and reliable, and can enable the submarine pipeline inspection system to be automated, visualized and intelligent. The improvement and promotion of the platform will be of great significance to ensure the high efficiency and low fault operation of China′s submarine pipelines.

Abstract Background Stem cells play a therapeutic role mainly through immunoregulation. However, the immunomodulatory function of stem cells may be affected by inflammation-related factors in patients’ serum. Therefore, this study aims to investigate the possible mechanism by which acute-on-chronic liver failure (ACLF) patient serum influences the efficacy of hUC-MSCs. Methods The serum of surviving and dead ACLF patients was collected to culture hUC-MSCs in vitro, and the hUC-MSCs cultured in the serum of ACLF patients were used to treat acute liver failure (ALF) rats. The therapeutic effect on the rats was evaluated by a survival curve, the transaminase level and liver histopathology. The expression of cytokines in hUC-MSCs was detected by Q-PCR and ELISA. Results Serum pretreatment reduced the therapeutic effect of hUC-MSCs on ALF, especially pretreatment in the serum from dead ACLF patients. After hUC-MSCs were cultured in the serum of surviving or dead ACLF patients, the most differentially expressed factor was IL-8. Interfering with the expression of IL-8 in hUC-MSCs can improve the therapeutic effect of hUC-MSCs on ALF. The high level of IL-1β in the serum of dead ACLF patients causes the increased expression of IL-8 in hUC-MSCs through the activation of the NF-κB signaling pathway. Meanwhile, we found that the neutralizing IL-1β in serum from dead ACLF patients can improve the therapeutic effect of hUC-MSCs on ALF. Conclusion The high level of IL-1β in ACLF serum can promote the expression of IL-8 in hUC-MSCs through the NF-κB signaling pathway, thus reducing the effect of hUC-MSCs on ALF.

Abstract Expansive soil exhibits remarkable characteristics of water absorption expansion and water loss shrinkage, rendering it susceptible to cracking under the alternating dry–wet environments of nature. The generation and development of cracks in expansive soil can result in catastrophic engineering accidents such as landslides. Vegetation protection is an important approach to stabilizing expansive soil slopes and fulfilling ecological protection requirements. In this study, through indoor experiments and theoretical analysis methods, the effects of Cynodon dactylon roots on the crack development and shear strength of expansive soil subjected to dry–wet cycles were analyzed, and the relationship between the crack development and shear strength decay in root-doped expansive soil was explored. Furthermore, the mechanism of vegetative root system action was elucidated. The results show that the Cynodon dactylon root system exerts a significant inhibitory effect on crack development in expansive soil. The crack indexes of root-doped expansive soil exhibit significant phase characteristics during the process of dry–wet cycles. The crack-blocking and reinforcing effect of the root system becomes pronounced as the root-to-soil mass ratio increases and the root diameter decreased. Moreover, the process of crack development in expansive soil is accompanied by a decrease in soil shear strength. The quantitative relationship between crack development and shear strength decay can serve as a basis for predicting the stability of slope soil. Overall, the results highlight the potential of vegetation-based approaches in protecting slopes with expansive soils and have practical implications for ecological protection and engineering design in areas with expansive soils.

Introduction: The prevalence of visual impairment and ocular diseases changes over time. This measure can help general practitioners in anticipating common eye disorders that may require ophthalmological referrals to government hospitals. This study aimed to evaluate the prevalence of visual impairment and ocular diseases in an outpatient ophthalmology clinic in a public hospital and the types of investigations frequently conducted to diagnose these diseases. Methods: A cross-sectional prospective study was conducted over three weeks in the eye clinic of the University of Malaya Medical Centre. The electronic medical records of all patients who attended the outpatient clinic were assessed to collect data on sex, age, type of visit, visual acuity, ocular presentation, investigations conducted and diagnosis of eye diseases. Visual impairment and blindness were categorised as per the World Health Organization criteria. Results: Among 1002 patients, 327 had visual impairments (32.63%), and nine had blindness (0.9%). Cataracts were the most common ocular disease diagnosed (n=294, 29.74%), followed by glaucoma (n=123, 12.28%) and diabetic retinopathy (n=84, 8.38%). Optical coherence tomography was the most common investigation performed (n=272, 64.9%), followed by Humphrey visual field testing (n=53,12.6%). Conclusion: Untreated refractive error is the leading cause of visual impairment in children, while cataract, glaucoma and diabetic retinopathy are the main contributors to visual impairment and blindness in elderly individuals. Our study highlights the urgent need for general practitioners to recognise avoidable visual impairment in all age groups to help prevent blindness.

Lakes on the Qinghai Tibet Plateau (QTP) are widely distributed spatially, and they are mostly seasonally frozen. Due to global warming, the thickness and phenology of the lake ice has been changing, which profoundly affects the regional climate evolution. There are a few studies about lake ice in alpine regions, but the understanding of climatological characteristics of lake ice on the QTP is still limited. Based on a field experiment in the winter of 2022, the thermal conductivity of Qinghai Lake ice was determined as 1.64 W·m−1·°C−1. Airborne radar ice thickness data, meteorological observations, and remote sensing images were used to evaluate a quasi-steady ice model (Leppäranta model) performance of the lake. This is an analytic model of lake ice thickness and phenology. The long-term (1979–2017) ice history of the lake was simulated. The results showed that the modeled mean ice thickness was 0.35 m with a trend of −0.002 m·a−1, and the average freeze-up start (FUS) and break-up end (BUE) were 30 December and 5 April, respectively, which are close to the field and satellite observations. The simulated trend of the maximum ice thickness from 1979 to 2017 (0.004 m·a−1) was slightly higher than the observed result (0.003 m·a−1). The simulated trend was 0.20 d·a−1 for the FUS, −0.34 d·a−1 for the BUE, and −0.54 d·a−1 for the ice duration (ID). Correlation and detrending analysis were adopted for the contribution of meteorological factors. In the winters of 1979–2017, downward longwave radiation and air temperature were the two main factors that had the best correlation with lake ice thickness. In a detrending analysis, air temperature, downward longwave radiation, and solar radiation contributed the most to the average thickness variability, with contributions of 42%, 49%, and −48%, respectively, and to the maximum thickness variability, with contributions of 41%, 45%, and −48%, respectively. If the six meteorological factors (air temperature, downward longwave radiation, solar radiation, wind speed, pressure, and specific humidity) are detrending, ice thickness variability will increase 83% on average and 87% at maximum. Specific humidity, wind, and air pressure had a poor correlation with ice thickness. The findings in this study give insights into the long-term evolutionary trajectory of Qinghai Lake ice cover and serve as a point of reference for investigating other lakes in the QTP during cold seasons.

(1) Background: This study evaluates the effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in improving gait in post-stroke hemiplegic patients, using wearable sensor technology for objective gait analysis. (2) Methods: A total of 72 stroke patients were randomized into control, sham stimulation, and LF-rTMS groups, with all receiving standard medical treatment. The LF-rTMS group underwent stimulation on the unaffected hemisphere for 6 weeks. Key metrics including the Fugl-Meyer Assessment Lower Extremity (FMA-LE), Berg Balance Scale (BBS), Modified Barthel Index (MBI), and gait parameters were measured before and after treatment. (3) Results: The LF-rTMS group showed significant improvements in the FMA-LE, BBS, MBI, and various gait parameters compared to the control and sham groups (p < 0.05). Specifically, the FMA-LE scores improved by an average of 5 points (from 15 ± 3 to 20 ± 2), the BBS scores increased by 8 points (from 35 ± 5 to 43 ± 4), the MBI scores rose by 10 points (from 50 ± 8 to 60 ± 7), and notable enhancements in gait parameters were observed: the gait cycle time was reduced from 2.05 ± 0.51 s to 1.02 ± 0.11 s, the stride length increased from 0.56 ± 0.04 m to 0.97 ± 0.08 m, and the walking speed improved from 35.95 ± 7.14 cm/s to 75.03 ± 11.36 cm/s (all p < 0.001). No adverse events were reported. The control and sham groups exhibited improvements but were not as significant. (4) Conclusions: LF-rTMS on the unaffected hemisphere significantly enhances lower-limb function, balance, and daily living activities in subacute stroke patients, with the gait parameters showing a notable improvement. Wearable sensor technology proves effective in providing detailed, objective gait analysis, offering valuable insights for clinical applications in stroke rehabilitation.