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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.

Objective The current study investigated the effects of mulberry 1-deoxynijirimycin (DNJ) on the digestion ability, intestinal morphology, and intestinal barrier of rabbits. Methods A total of 36 New Zealand White rabbits (male) about 45 days old (mean body weight of 1.05±0.04 kg) were reared and commercial diets were employed, and afterwards divided into three groups (n = 12) with different levels of DNJ extract additive in feed: T0 (0 g/kg), T1 (0.35 g/kg), T2 (0.7 g/kg) for 28 d. Results The results demonstrated that T2 decreased the average daily gain (p

AbstractContext Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection.Objective To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality.Materials and methods A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an in vitro model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1’s safe dosage. Groups for each model were: in vivo—a control group, a CLP-induced sepsis group, and a CLP + NGR1 treatment group (30 mg/kg/d for 3 d); in vitro—a control group, a LPS-induced sepsis group, and a LPS + NGR1 treatment group (4 μM for 30 min). NGR1’s effects on survival, intestinal function, mitochondrial quality, and mitochondrial dynamic-related protein (Drp1) were evaluated.Results Sepsis resulted in approximately 60% mortality within 7 days post-CLP, with significant reductions in intestinal microvascular perfusion and increases in vascular leakage. Severe mitochondrial quality imbalance was observed in IMVECs. NGR1 (IC50 is 854.1 μM at 30 min) targeted Drp1, inhibiting mitochondrial translocation, preventing mitochondrial fragmentation and restoring IMVEC morphology and function, thus protecting against intestinal barrier dysfunction, vascular permeability, microcirculatory flow, and improving sepsis prognosis.Discussion and conclusions Drp1-mediated mitochondrial quality imbalance is a potential therapeutic target for sepsis. Small molecule natural drugs like NGR1 targeting Drp1 may offer new directions for organ protection following sepsis. Future research should focus on clinical trials to evaluate NGR1’s efficacy across various patient populations, potentially leading to novel treatments for sepsis.

Abstract Baseline IL-6 levels have been found to be non-predictive of subsequent outcomes following tocilizumab treatment, highlighting the need for more reliable predictive markers. To address this, a retrospective analysis was conducted on the clinical profiles, diagnostic tests, and follow-up prognoses of 60 patients with severe or critical COVID-19, all of whom were identified as experiencing a cytokine storm and subsequently received tocilizumab treatment. Among the patients, the overall survival rate during follow-up was 80%, with further analysis revealing that advanced age was an independent risk factor for adverse outcomes. Following tocilizumab administration, a statistically significant increase in IL-6 and D-dimer levels was observed, while markers such as C-reactive protein (CRP), procalcitonin (PCT), and fibrinogen demonstrated reductions compared to pre-treatment values. Specifically, IL-6 levels initially surged briefly after tocilizumab intervention before gradually diminishing. To assess the prognostic utility of IL-6, the Receiver Operating Characteristic (ROC) curve was employed, which yielded an area under the curve (AUC) of 0.812, indicating strong predictive capability, with a sensitivity of 100% and a specificity of 53.49%. The optimal cut-off value for IL-6 was identified at 147.79 pg/mL. In conclusion, IL-6 levels tend to rise transiently following tocilizumab therapy, before gradually declining. These post-treatment IL-6 measurements may serve as a valuable biomarker for assessing prognosis in patients undergoing this treatment.

Abstract Heart failure (HF) is the leading cause of death in patients with maintenance hemodialysis (MHD). Biomarkers has an important guiding role in the early diagnosis, risk stratification, and prognostic assessment of HF. Increasing studies have indicated that long non-coding RNAs (lncRNAs) have played an indispensable role in the regulatory network of HF. This study was aiming to explore the expression profiles of lncRNAs in patients treated with MHD developing heart failure. Peripheral blood mononuclear cells were isolated from 4 hemodialysis patients with reduced ejection fraction (HFrEF) and 4 hemodialysis patients with preserved ejection fraction (HFpEF), respectively. The expression profile analysis of lncRNAs was performed by using Illumina Novaseq 6000 sequencer. Quantitative real time polymerase chain reaction (qRT-PCR) was used to verify the expression of representative differentially expressed lncRNAs. Based on lncRNA-miRNA-mRNA-KEGG network analysis, the potential role of candidate lncRNAs and their association with the severity of HF were further evaluated. In total, 1,429 differentially expressed lncRNAs were found between patients with HFrEF and patients with HFpEF, of which 613 were up-regulated and 816 were down-regulated (P

Abstract Background Premature ventricular beats increase the cardiac load in pregnant women, leading to symptoms, such as palpitations. In severe instances, they may reduce placental perfusion, potentially causing intrauterine distress and developmental delays in the fetus, which could result in miscarriage or stillbirth. Fluoroscopy-less ablation offers significant advantages for pregnant women, including reduced radiation exposure, enhanced treatment precision, and a lower incidence of postprocedure complications. Case Presentation This case describes how radiofrequency catheter ablation was used on a pregnant Chinese woman who was identified with frequent ventricular premature beats originating from the high septal margin trabeculae carneae of the right ventricle. The rarity of this premature beat focus poses challenges for electrophysiology mapping and ablation; however, the ablation ultimately succeeded. In this case report, the clinical manifestations, electrocardiogram, ablation procedure, and patient prognosis are reported and discussed. Conclusion X-ray free ablation clearly reduces radiation exposure while maintaining a high success rate and safety of the ablation procedure.

Abstract Objective To determine the incidence of secondary vertebral compression fracture (SVCF) after percutaneous vertebral augmentation (PVA) and its correlative risk factors, and to provide theoretical evidence for clinical practice. Methods A retrospective analysis of 288 cases of PVA completed in our hospital from June 2020 to June 2023 was performed, and the patients were divided into the non-secondary vertebral compression fracture group (N-SVCF group) and the secondary vertebral compression fracture group (SVCF group) according to whether SVCF occurred during the postoperative follow-up review. Gender, age, body mass index (BMI), T value of bone mineral density (BMD-T), underlying diseases (hypertension, diabetes mellitus, coronary heart disease, chronic obstructive pulmonary disease), intravertebral vacuum cleft (IVC), amount of bone cement injected, classification of cement diffusion, anterior vertebral recovery ratio, local Cobb angle correction rate, leakage of bone cement into the intervertebral space, and fat infiltration rate (FIR) of paraspinal muscles were collected from the patients. The incidence and risk factors of SVCF after PVA were evaluated using univariate and multivariate logistic regression analysis, and the predictive value of the independent risk factors was evaluated using receiver operating characteristic curve (ROC) to determine the cut-off points at which they were meaningful for the development of SVCF. Results In our study, the incidence of SVCF was 14.60% (42/288) in 288 patients who underwent PVA. Univariate analysis showed that age, BMI, fat infiltration rate of paraspinal muscles, cement leakage into the intervertebral space, unilateral/bilateral pedicle puncture approach and presence of IVC were statistically different between N-SVCF and SVCF (P

Abstract Background Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs. Methods Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels. Results We uncovered that LC-BrMs exhibited a significantly greater intra-tumor heterogeneity. We also observed that mutations in a subset of genes were almost always shared by both primary lung cancers and LC-BrM lesions, including TTN, TP53, MUC16, LRP1B, RYR2, and EGFR. In addition, the genome-wide landscape of somatic copy number alterations was similar between primary lung cancers and LC-BrM lesions. Nevertheless, several regions of focal amplification were significantly enriched in LC-BrMs, including 5p15.33 and 20q13.33. Intriguingly, integrated analyses of transcriptomic, proteomic, and metabolomic data revealed mitochondrial-specific metabolism was activated but tumor immune microenvironment was suppressed in LC-BrMs. Subsequently, we validated our results by conducting real-time quantitative reverse transcription PCR experiments, immunohistochemistry, and multiplexed immunofluorescence staining of patients’ paired tumor specimens. Therapeutically, targeting oxidative phosphorylation with gamitrinib in patient-derived organoids of LC-BrMs induced apoptosis and inhibited cell proliferation. The combination of gamitrinib plus anti-PD-1 immunotherapy significantly improved survival of mice bearing LC-BrMs. Patients with a higher expression of mitochondrial metabolism genes but a lower expression of immune genes in their LC-BrM lesions tended to have a worse survival outcome. Conclusions In conclusion, our findings not only provide comprehensive and integrated perspectives of molecular underpinnings of LC-BrMs but also contribute to the development of a potential, rationale-based combinatorial therapeutic strategy with the goal of translating it into clinical trials for patients with LC-BrMs.

Abstract Late complications of radiotherapy can include a variety of issues, such as xerostomia, dysphagia, taste changes, digestive and absorption dysfunction. These late complications can seriously impact the nutritional status and quality of life of patients following radiotherapy, and may even adversely affect tumor control and patient survival. Comprehensive nutritional management strategies should be implemented to address these late complications. For radiation-induced xerostomia, salivary stimulant drugs, saliva substitutes, and hyperbaric oxygen therapy have demonstrated efficacy in alleviating dry mouth symptoms. The management of post-radiation trismus remains challenging, with functional training, including active jaw exercises, passive motor devices, and splints, being the primary interventions. In the case of radiation-induced dysphagia, a multidisciplinary team approach is recommended, incorporating malnutrition risk assessment, personalized nutritional treatment, nursing care, rehabilitation training, and patient education. Protecting normal organs, such as the tongue and oral cavity, during radiotherapy planning can help prevent and mitigate taste changes, which can be further managed with zinc supplements, oral care, and lactoferrin supplementation. For post-radiation digestive and absorption dysfunction, a comprehensive assessment of the patient's nutritional status, site of gastrointestinal injury, and potential complications (e.g., bleeding, perforation) is crucial in guiding the selection of appropriate nutritional support, ranging from enteral nutrition as the first-line approach to supplemental or even exclusive parenteral nutrition. Surgical intervention may be necessary in some cases. By implementing these multifaceted nutritional management strategies, healthcare professionals can optimize the care of cancer patients undergoing radiotherapy and mitigate the adverse impact of late radiation complications on their overall well-being and treatment outcomes.

Abstract To investigate the difference in preoperative retinal function in patients with type 2 diabetes cataract (DC) without obvious retinopathy and to explore the clinical application of full blood glucose management for improving the postoperative vision in DC patients. This was a retrospective analysis in which we estimated the changes in visual electrophysiology (N75, P100, photopic flash electroretinogram(FERG), and scotopic FERG, paraoptic retinal nerve fibre layer thickness (pRNFL) and paraoptic radial capillary network blood flow density (ppVD) of type 2 diabetes (T2DM) patients at different phases of disease progression along with fasting blood glucose (FBG) and glycosylated haemoglobin (HbAlC) levels before and after DC surgery at Ziyang Central Hospital from January 2020 to December 2022. Additionally, trends in the above data throughout the entire process of glucose management intervention were examined. As the course of T2DM progressed, FBG and HbA1c increased, the N75 and P100 latency periods of patients gradually increased, and the values of photopic FERG, scotopic FERG, pRNFL, and ppVD gradually decreased at each postoperative time point. Moreover, the best corrected visual acuity(BCVA) of patients after surgery gradually decreased (P

Abstract Elicitation through abiotic stress, including heavy metals, is a new natural product drug discovery technique. In this research, three compounds 1, 2, and 6, were achieved by triggering zinc and nickel on marine Sphingomonas sp. and Streptomyces sp., which were absent in normal culture. Compound 5 was obtained for the first time from marine bacteria. All compounds showed potent antibacterial activity against Staphylococcus aureus and bactericidal effect at 300 µm, but 6 was more active. The potent compound 6 production was further enhanced through response surface methodology by optimizing the condition consisting of nickel 1 mM ions, 20 mg/L sucrose, 30 mg/L salt and culture time 14 days. Under these conditions, the SM-6 production was enhanced with a yield of 6.3 mg/L, which was absent in the normal culture. Further transcriptome analysis of compound 6 unveiled its antibacterial activity on S. aureus by modulating heat shock protein genes, disrupting protein folding and synthesis, and perturbing cellular redox balance, leading to a comprehensive inhibition of normal bacterial growth. In addition, ADMET has shown that all compounds are safe for cardiac and hepatotoxicity. To determine the anti-bacterial mechanism, all compounds were docked with PBP2a and DNA gyrase enzyme, and TLR-4 protein for predicting vaccine construct, and the best docking score was achieved against PBP2a enzyme with the highest score of −10.2 for compound 6. In-silico cloning was carried out to ensure the expression of proteins generated and were cloned using S.aureus as a host. The simulation studies have shown that both SM-6-PBP2a and TLR-4-PBP2a complex are stable with the system. This study presents a new approach to anti-bacterial drug discovery from microorganisms through heavy metals triggering and enhancing the compound production through response surface methodology.

Abstract Objective To evaluate the benefits of volumetric modulated arc therapy (VMAT) based on multicriteria optimization (MCO) for gastric cancer patients, particularly the protection of serial organs at risk (OARs) that overlap with the target volume. Methods MCO and single-criterion optimization (SCO) VMAT plans were conducted among 30 gastric cancer patients, with a prescription dose of 50.4 Gy delivered in 28 fractions. All treatment plans underwent review, and a comparison was made between the active planning time and different dose-volume parameters. Results Both the MCO and SCO VMAT plans achieved the target dose coverage, with no significant difference in the conformity index (CI) for the planning target volume (PTV), at median CI values of 0.887 and 0.891, respectively (P = 0.417). The MCO plans showed a slight but significant increase in the homogeneity index of the PTV, with a median increase of 0.029 (P

Abstract Topological pumps reveal topological insights of adiabatic mode evolution, in which adiabaticity plays a crucial role. However, the adiabatic infimum, i.e., the possible shortest evolution duration of an adiabatic topological pumping process, has remained elusive. In this study, we report the approach of adiabatic infimum in topological pumps in photonic waveguides based on the lithium niobate-on-insulator (LNOI) platform. Besides the most common way to achieve adiabaticity by slowing down the evolution of the system, the adiabaticity of a topological pump is also contingent on an effective Berry connection between instant eigenstates, which can be controlled by the selection of specific pump loops. Specifically, we develop a strategy to identify a pump loop with a minimized effective Berry connection, corresponding to the adiabatic infimum of a topological pump. As such, it is experimentally demonstrated that topological pumps can happen even with rapid evolution speed, at which the conventional pump would completely fail. The adiabatic infimum accelerates the topological pumps from the constraints of slow evolution and facilitates the design of compact topological devices.

Abstract Objective The present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population. Methods The study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE). Results A retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p

Abstract Background An atypical type A thymoma variant was recently added to the World Health Organization classification of type A thymoma in 2015. This novel form of type A thymoma presents with hypercellularity, increased mitotic activity, and necrosis. In particular, necrosis seems to be related to postoperative recurrence and metastasis, but the clinical significance of these changes still needs to be studied. Case presentation A 76-year-old man underwent thoracoscopic surgery for tumour resection due to an anterior mediastinal mass. Pathological examination revealed that the tumour invaded the surrounding thymic tissue. Cells were arranged in nest-like and whirl-like patterns, accompanied by prominent comedo-like necrosis, increased cell density, mild atypia, and a mitotic count of 4–6 per 10 high-power fields. Immunohistochemistry revealed positive expression of cytokeratin 19 and P63 in the tumour cells. Lymphocytes in the background were positive for CD3 and CD5, did not express terminal deoxynucleotide transferase, CD20, or CD117, and had an MIB-1 labelling index(LI) value of 15%. On the basis of these findings, the tumour was finally diagnosed as an atypical type A thymoma variant. Conclusions We report a case of atypical type A thymoma and review the literature to enhance our understanding of and provide accumulated pathological data on this rare disease.

Abstract The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P

Abstract Mung bean (Vigna radiata L.), a widely cultivated legume, belongs to the Fabaceae family’s Papilionoideae subfamily. Although Phosphatidylethanolamine-binding protein (PEBP) genes have been identified in several plant species, their presence and function in mung bean remain largely unexplored. In this study, we identified seven VrPEBP genes from mung bean and classified them into four clades: FT, MFT, TFL and FT-like. Cis-regulatory element analysis revealed that VrPEBP genes may play a role in light, hormone, and stress responses. Quantitative real-time PCR (qRT-PCR) analysis indicated that VrPEBPs were constitutively expressed in various tissues. However, tissue-specific expression patterns were observed among VrPEBP genes. Under short-day (SD) conditions, VrFT1 and VrMFT1 exhibited significantly higher expression levels than under long-day (LD) conditions at 8 and 4 h, respectively. Conversely, VrTFL2 and VrTFL3 showed significantly higher expression levels under LD conditions compared to SD conditions at 8 and 12 h, respectively. The varied expression patterns of these genes under different photoperiod suggest their potential involvement in the photoperiodic regulation of flowering in mung bean. Additionally, phenotypic analysis of transgenic Arabidopsis plants overexpressing VrFT1 revealed higher expression levels under SD conditions and predicted its role in promoting flowering. These results provide valuable insights into the evolution and function of PEBP genes in mung bean and lay the foundation for further research on their regulatory mechanisms and potential applications in mung bean improvement.

In China's coal mine backfill mining projects, certain mines demonstrate an extensive filling distance that exceeds 3000 m. However, there are few researches concerning the theoretical underpinnings for slurry long-distance pipeline transportation. Gangue particles suspending in filling slurry is the prerequisite for successful long-distance pipeline transportation. This paper conducts theoretical researches on the heightened sensitivity issue of particle settling within coal-based solid waste filling slurry (CSWFS) for long-distance pipeline transportation, which can easily lead to unstable slurry concentration then pipe blockage or bursting accidents. The mechanical model for particle settling and critical non-settling particle diameter for long-distance pipeline transportation are developed based on the ''solid-liquid two-phase carrier suspension fluid'', and reveal the intrinsical mechanism of particle settling within CSWFS for long-distance pipeline transportation. Through the calculation of the mechanical model for critical non-settling particle diameter and particle settling, coupled with the particle diameter screening experiment, the value of critical non-settling particle diameter is determined to be 0.0067 m, and the density of solid-liquid two-phase carrier suspension fluid is 1712.37 kg/m3. The CSWFS is classified as a semi-stable slurry, lacking time-dependent suspending state required for long-distance pipeline transportation, which could lead to pipe blockage accidents. Further research into effective methods is urgently required to ensure adequate safety and adaptability for long-distance pipeline transportation of CSWFS.

Abstract Cryo-electron microscopy (cryo-EM) is one of the most powerful experimental methods for macromolecular structure determination. However, accurate DNA/RNA structure modeling from cryo-EM maps is still challenging especially for protein-DNA/RNA or multi-chain DNA/RNA complexes. Here we propose a deep learning-based method for accurate de novo structure determination of DNA/RNA from cryo-EM maps at

Abstract Background Osteonecrosis of the femoral head (ONFH) significantly impacts young and middle-aged adults, with steroid use implicated in many cases. Traditional treatments have limited efficacy, prompting a shift towards innovative approaches, such as stem cell therapy, offering less invasive regenerative solutions. Methods Using bibliometric analysis from 1997 to 2023, we identified 392 articles on stem cell therapy for ONFH from the Web of Science Core Collection and analysed them using VOSviewer and CiteSpace to identify key trends and research directions. Results From 1997 to 2023, stem cell therapy for ONFH research expanded significantly, with 392 articles evidencing global collaboration, particularly from China, the United States and South Korea. The field is characterised by 158 core authors across 26 clusters and contributions from 417 institutions in 104 research clusters, with Shanghai Jiao Tong University as a notable leader. This research is disseminated through 23 journal clusters, emphasising interdisciplinary work, with Clinical Orthopaedics and Related Research among the most influential journals. Key findings include the identification of the most influential papers, highlighting advances, such as use of autologous mesenchymal stem cells (MSCs) and innovative delivery mechanisms. High-frequency keyword analysis further mapped the evolution of the field, from basic mechanisms to advanced therapies, underscoring a trend towards more targeted stem cell treatments for ONFH. Conclusion Stem cell therapy for ONFH has advanced significantly, showcasing a successful transition from basic research to clinical practice, particularly highlighted by developments in use of autologous MSCs and delivery methods. Future research will focus on refining therapies through exosome technology, targeted modulation of stress and inflammation and integration with surgical techniques, with the aim of tailored patient care and improved ONFH outcomes.

Abstract Osteosarcoma (OS) is a cancerous tumor, and its development is greatly influenced by long non-coding RNA (lncRNA). Endoplasmic reticulum stress (ERS) is an essential biological defense process in cells and contributes to the progression of tumors. However, the exact mechanisms remain elusive. This study aims to develop a signature of lncRNAs associated with ERS in OS. This signature will guide the prognosis prediction and the determination of appropriate treatment strategies. The UCSC Xena database collected transcriptional and clinical data of OS and muscle, after identifying ERS differentially expressed genes, we utilized correlation analysis to determine the endoplasmic reticulum stress lncRNAs (ERLs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were utilized to develop an ERLs signature. To clarify the fundamental mechanisms controlling gene expression in low and high-risk groups, Gene Set Variation Analysis (GSVA) were conducted. In addition, the distinction between the two groups regarding drug sensitivity and immune-related activity was investigated to determine the immunotherapy effects. Utilizing RT-qPCR, the expression of model lncRNAs in OS cell lines was ascertained. The functional analysis of LINC02298 was carried out through in vitro experiments and pan-cancer analysis. This study successfully constructed an ERLs prognostic signature for OS, which comprised 5 lncRNAs (AC023157.3, AL031673.1, LINC02298, LINC02328, SNHG26). The risk signature predicted overall survival in patients with OS and was confirmed by assessing the validation and whole cohorts. Further, it was discovered that individuals classified as high-risk displayed suppressed immune activation, decreased infiltration of immune cells, and decreased responsiveness to immunotherapy. The RT-qPCR showed that the constructed risk prognosis model is reliable. Experimental validation has demonstrated that LINC02298 can promote OS cells’ invasion, migration, and proliferation. In addition, LINC02298 exhibited significant differential expression in many types of cancer. Moreover, LINC02298 is an important biomarker in a variety of tumors. This study established a novel ERLs signature, which successfully predicted the prognosis of OS. The function of LINC02298 in OS was elucidated via in vitro experiments. Therefore, it offers new opportunities for predicting the clinical prognosis of OS and establishes the basis for targeted therapy in OS.

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 Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p

Abstract The Qinling Mountains in China frequently experience geological disasters, with large‐scale landslides being particularly prominent, causing severe economic losses to the local area. To gain a comprehensive understanding of the geological disaters distribution in the region, we conducted extensive research on the entire Qinling Mountains, covering an area of approximately 380,000 km2. By employing methods such as literature review, data collection, and interpretation of remote sensing images, we have successfully created a database of landslides. The inventory of landslides includes a total of 169,888 large‐scale landslides, covering a combined area of approximately 1575 km2. The average size of these landslides is approximately 92,734 m2. The scale of these landslides varies widely, with the smallest individual landslide covering an area of 166.25 m2 and the largest reaching 12.9 km2. Upon examining areas with frequent landslides, it was observed that landslides are usually densely distributed along riverbanks or within valleys. Landslide development is also dense in areas prone to frequent historical earthquakes. This comprehensive database provides essential data to support the analysis of spatial distribution patterns of large‐scale landslides in the Qinling Mountains. It also facilitates landslide assessments and serves as a reference for the prevention and control of landslide disasters in the area.

Abstract Background We aimed to clarify the controversial relationship between levels of high-sensitivity C-reactive protein (hs-CRP) and severity of depression in men and women. Methods Medical records were retrospectively analyzed for 1,236 inpatients at our medical center who were diagnosed with depression at discharge between January 2018 and August 2022. Depression severity was assessed during hospitalization using the 24-item Hamilton Depression Rating Scale. Potential associations between severity scores and hs-CRP levels were explored using multivariate linear regression as well as smooth curve fitting to detect non-linear patterns. Results In male patients, hs-CRP levels between 2.00 mg/L and 10.00 mg/L showed a non-linear association with depression severity overall (fully adjusted β = 1.69, 95% CI 0.65 to 2.72), as well as with severity of specific symptoms such as hopelessness, sluggishness, and cognitive disturbance. In female patients, hs-CRP levels showed a linear association with severity of cognitive disturbance (fully adjusted β = 0.07, 95% CI 0.01 to 0.12). These results remained significant after adjusting for age, body mass index, diabetes, hypertension, history of drinking, history of smoking, and estradiol levels. Discussion Levels of hs-CRP show sex-specific associations with depression severity, particularly levels between 2.00 and 10.00 mg/L in men. These findings may help develop personalized anti-inflammatory treatments for depression, particularly for men with hs-CRP levels of 2.00–10.00 mg/L.

Abstract The effect of bolt support in mining roadways with fractured or weak surrounding rock is poor, and the roof easily loses stability. Studying the support control technology of bolts on fractured surrounding rock is necessary. Based on the theories of pressure arches and combined arch support, the bolt anchorage and anchorage effect angle are proposed a model is established, and the optimal bolt anchorage is calculated. The influence of related factors on the bolt anchorage and the scope of bolt action are analysed via numerical simulation and experimental methods. The pretightening force of the bolts and the spacing between the rows of bolts are positively correlated and negatively correlated with the bolt anchorage, respectively. The compression zone conforms to the reinforced arch state when the bolt end is anchored. The experimental work shows that the maximum spacing a of the anchor rods and the length L of the anchor rods in the surrounding rock satisfy 4.28a

Abstract Objectives Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. Methods A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. Results Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172–2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689–0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). Conclusion The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.

Abstract Background To compare the therapeutic effects of right vertical infra-axillary thoracotomy (RVIAT) and Standard Median Sternotomy (SMS) in the repair of atrial septal defect (ASD) and ventricular septal defect (VSD), and to evaluate the safety and effectiveness of right subaxillary incision technique in the surgical treatment of common congenital heart disease (CHD) in children. Methods Data of children diagnosed with ASD repair or VSD repair at our center from September 2019 to September 2022 were collected. Based on propensity score matching, 214 children (107 in the RVIAT group and 107 in the SMS group) who completed ASD repair surgery and 242 children (121 in the RVIAT group and 121 in the SMS group) who completed VSD repair surgery were selected for the study. The perioperative and follow-up data of the two surgical approaches were compared to evaluate clinical efficacy. Results There was no statistically significant difference (p > 0.05) between the two surgical approaches in terms of surgical time, aortic occlusion time, total amount of ultrafiltration fluid, ICU stay time, and hospital stay; The intraoperative blood loss and total postoperative drainage fluid in the RVIAT group were lower than those in the SMS group (p

This study investigates the utilization of artificial intelligence (AI) for feature engineering in the education sector, highlighting its potential to enhance individualized learning and improve academic outcomes. The correlation analysis, performed using a correlation matrix of the feature set, indicated that specific pairings of characteristics exhibit a strong association, resulting in the ineffectiveness of conventional models. In order to tackle this issue, we utilized three sophisticated machine learning methodologies: Adaptive Lasso (ALasso), Artificial Neural Networks (ANN), and Support Vector Regression (SVR). The ALasso model discovered several influential characteristics, namely Gender (X5), Education (X1), Hours of Work (X4), and Marital Status (X6), that significantly affect salaries. Subsequently, a comparative evaluation of these methods was conducted using Root Mean Squared Error (RMSE) and Mean Absolute Error (MAE). The results demonstrated that SVR outperformed the other techniques, with the most optimal RMSE of 0.595 and MAE of 0.423. These findings emphasize the significance of using data-driven strategies in policymaking and propose further investigation into the use of AI methods in various educational contexts to improve the identification of features and the performance of models.

Abstract Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Objective The first deepwater and deep-stratum gas field was recently discovered in the Baodao 21-1 area of the Qiongdongnan Basin, which is of great significance for petroleum exploration in the deep-water area of the South China Sea. Methods Based on the newly acquired drilling-seismic data, the sedimentary characteristics of the Third Member of the Upper Oligocene Lingshui Formation and their significance in hydrocarbon exploration were analyzed in the Baodao 21-1 area. Results Bidirectional sediment provenances controlled the deposition of the Third Member of the Lingshui Formation, resulting in the early deposition of fan delta in the adjacent uplands and the late deposition of braided river delta fed by sediment sources of the Hainan Uplift on the northwest and the Shenhu Uplift on the northeast. In addition, the routes of sediment transport between steep and gentle slopes show great variability. The evolution of the sedimentary system in the Third Member of the Lingshui Formation can be divided into three stages, including the fan delta deposition in the early stage, the fan delta and braided river delta depositions in the middle stage, and the braided river delta deposition in the late stage. Correspondingly, the sediment provenances changed from the adjacent highlands in the early stage, to both adjacent highlands and Shenhu Uplift in the middle stage, and finally to both Hainan Uplift and Shenhu Uplift in the late stage. The Baodao 21-1 area is close to the hydrocarbon kitchen of the Yacheng Formation and it contains the No.12-1 Fault-Fracture systems and the tectonic-lithologic traps, favoring the petroleum accumulation. Conclusion The discovery of the Baodao 21-1 gas field is a breakthrough in deepwater petroleum exploration in China, pointing out that the fracture transition zone of marine basins is a key area for future deepwater exploration.

Background: To delineate the levels of serum Hepatitis B virus (HBV) RNA in patients with HBV-related hepatocellular carcinoma (HCC) and study comparisons with those of individuals afflicted with cirrhosis. Methods: Adult patients diagnosed with HBV-related cirrhosis or HCC (initial diagnosis) were enrolled in the cross-sectional study. Serum HBV DNA level was quantified through a real-time polymerase chain reaction assay with a lower limit of quantification (LLQ) of 20 IU/ml. Additionally, serum HBV RNA was quantified employing RNA real-time fluorescence thermostatic amplification detection technology with LLQ of 100 copies/ml. Propensity score matching (PSM) was conducted to ensure balance in between-group confounders. Results: A total of 187 patients (47 with HCC and 140 with cirrhosis) were recruited, among whom 140 (74.9%) had undergone antiviral therapy prior to their inclusion, with varying durations. Serum HBV RNA was detectable in 89.4% of HCC patients at the time of carcinoma diagnosis. After PSM, individuals with HCC exhibited significantly elevated levels of serum HBV DNA and HBV RNA compared to those with cirrhosis (median lgHBV RNA 3.1 vs 2.0 copies/ml, P = 0.001). Subgroup analysis, including 38 patients who exhibited ultrasensitive HBV DNA negativity, revealed similar results (median lgHBV RNA 3.0 vs 0.0 copies/ml, P < 0.001). Conclusions: Serum HBV RNA levels were significantly higher in HBV-related HCC patients compared to cirrhotic patients. The presence of serum HBV RNA positivity or elevated levels was associated with the onset of HCC.

Abstract Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition caused by long-term corticosteroid use, leading to impaired blood flow and bone cell death. The disruption of cellular processes and promotion of apoptosis by endoplasmic reticulum stress (ERS) is implicated in the pathogenesis of SONFH. We identified ERS-associated genes in SONFH and investigated their potential as therapeutic targets. We analysed the GSE123568 GEO dataset to identify differentially expressed genes (DEGs) related to ERS in SONFH. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, identified hub genes by protein-protein interaction (PPI) analyses, and evaluated their functions by gene set enrichment analysis (GSEA). We constructed mRNA–miRNA networks, identified potential therapeutics, and assessed immune cell infiltration. We performed cross-validation using the GEO dataset GSE74089, qRT-PCR on clinical samples from patients with SONFH and controls, and a receiver operating characteristic (ROC) curve analysis to assess the diagnostic performance of the hub genes. We identified 195 ERS-related genes in SONFH, which were primarily involved in oxidative stress, immune responses, and metabolic pathways. The PPI network suggested CXCL8, STAT3, IL1B, TLR4, PTGS2, TLR2, CASP1, CYBB, CAT, and HOMX1 to be key hub genes, which were shown by GSEA to be involved in biological pathways related to metabolism, immune modulation, and cellular integrity. We also identified 261 microRNAs (miRNAs) as well as drugs such as dibenziodolium and N-acetyl-L-cysteine that modulated inflammatory responses in SONFH. Twenty-two immune cell subtypes showed significant correlations, such as a positive correlation between activated mast cells and Tregs, and patients with SONFH had fewer dendritic cells than controls. The hub genes CYBB and TLR4 showed significant correlations with M1 macrophages and CD8 T cells, respectively. Cross-validation and qRT-PCR confirmed the upregulation of STAT3, IL1B, TLR2, and CASP1 in patients with SONFH, validating the bioinformatics findings. An ROC curve analysis confirmed the diagnostic potential of the hub genes. The top 10 hub genes show promise as ERS-related diagnostic biomarkers for SONFH. We discovered that 261 miRNAs, including hsa-miR-23, influence these genes and identified potential therapeutics such as dibenziodolium and simvastatin. Immune profiling indicated altered immune functions in SONFH, with significant correlations among immune cell types. Validation confirmed the upregulation of STAT3, IL1B, TLR2 and CASP1, which had diagnostic potential. The findings suggest potential diagnostic markers and therapeutic targets for SONFH.

Abstract To test the reliability and validity of the “Defeat Scale” and explore whether the scale is suitable for use in surveys of college athletes. A total of 226 athletes from five universities in China were selected for evaluation using the defeat scale. Factor analysis and correlation analysis were used to explore the reliability and validity of the defeat scale. Exploratory factor analysis showed that two factors could be extracted from this scale, namely a sense of decadence and a sense of low achievement. Confirmatory factor analysis showed that the model fit of the two factors was excellent (X2/DF = 2.809, RMSEA = 0.092, SRMR = 0.054, NFI = 0.891, IFI = 0.927, CFI = 0.926, GFI = 0.919, TLI = 0.910) . The convergent validity AVE values are 0.579 and 0.505 respectively, AVE > 0.5, and the combined reliability is 0.946 and 0.746 respectively. Both > 0.7 indicate good convergence effect. The arithmetic square roots of AVE, 0.760 and 0.710, are both higher than the absolute value of the correlation coefficient between the two dimensions, 0.30, indicating good discriminant validity; and the Cronbach's alpha coefficient of defeat is 0.931, and the Spearman-Brown coefficient is 0.888. The defeat scale has good reliability and validity among college athletes.

Abstract Background Intracranial aneurysm (IA) is a severe cerebrovascular disease, and effective gene therapy and drug interventions for its treatment are still lacking. Oxidative stress (OS) is closely associated with the IA, but the key regulatory genes involved are still unclear. Through multiomics analysis and experimental validation, we identified two diagnostic markers for IA associated with OS. Methods In this study, we first analyzed the IA dataset GSE75436 and conducted a joint analysis of oxidative stress-related genes (ORGs). Differential analysis, functional enrichment analysis, immune infiltration, WGCNA, PPI, LASSO, and other methods were used to identify IA diagnostic markers related to OS. Next, the functions of TLR4 and ALOX5 expression in IA and their potential targeted therapeutic drugs were analyzed. We also performed single-cell sequencing of patient IA and control (superficial temporal artery, STA) tissues. 23,342 cells were captured from 2 IA and 3 STA samples obtained from our center. Cell clustering and annotation were conducted using R software to observe the distribution of TLR4 and ALOX5 expression in IAs. Finally, the expression of TLR4 and ALOX5 were validated in IA patients and in an elastase-induced mouse IA model using experiments such as WB and immunofluorescence. Results Through bioinformatics analysis, we identified 16 key ORGs associated with IA pathogenesis. Further screening revealed that ALOX5 and TLR4 were highly expressed to activate a series of inflammatory responses and reduce the production of myocytes. Methotrexate (MTX) may be a potential targeted drug. Single-cell analysis revealed a notable increase in immune cells in the IA group, with ALOX5 and TLR4 primarily localized to monocytes/macrophages. Validation through patient samples and mouse models confirmed high expression of ALOX5 and TLR4 in IAs. Conclusions Bioinformatics analysis indicated that ALOX5 and TLR4 are the most significant ORGs associated with the pathogenesis of IA. Single-cell sequencing and experiments revealed that the high expression of ALOX5 and TLR4 are closely related to IA. These two genes are promising new targets for IA therapy.

Abstract Background This study assessed the global trends and burden of severe chest injury, including rib fractures, lung contusions, and heart injuries from 1990 to 2019. Herein, we predicted the burden patterns and temporal trends of severe chest injuries to provide epidemiological evidence globally and in China. Methods In our analysis, the age-standardized incidence rate (ASIR), prevalence rate (ASPR), and years lived with disability rate (ASYR) of severe chest injury were analyzed by gender, age, sociodemographic index, and geographical region between 1990 and 2019 using data from the Global Burden of Disease study 2019. Trends were depicted by calculating the estimated annual percentage changes (EAPCs). The impact of age, period, and cohort factors was assessed using an Age-Period-Cohort model. Autoregressive integrated moving average (ARIMA) model was employed to predict severe chest injury trends from 2020 to 2050. Results In 2019, the global number of severe chest injury cases reached 7.95 million, with the highest incidence rate observed in Central Europe (209.61). Afghanistan had the highest ASIRs at 277.52, while North Korea had the lowest ASIRs at 41.02. From 1990 to 2019, the Syrian Arab Republic saw significant increases in ASIR, ASPR, and ASYR, with EAPCs of 10.4%, 9.31%, and 10.3%, respectively. Burundi experienced a decrease in ASIR with an EAPC of − 6.85% (95% confidence interval [CI] − 11.11, − 2.37), while Liberia’s ASPR and ASYR declined with EAPCs of − 3.22% (95% CI − 4.73, − 1.69) and − 5.67% (95% CI − 8.00, − 3.28), respectively. Falls and road injuries remained the most common causes. The relative risk of severe chest injury by age, period, and cohort demonstrated a complex effect globally and in China. The ARIMA model forecasted a steady increase in global numbers from 2020 to 2050, while in China, it forecasted an increase in incidence, a decrease in ASIR and ASYR, and an increase in ASPR. Conclusions This study provides a groundbreaking analysis of global severe chest injury, shedding light on its measures and impact. These findings highlight the need for timely, specialized care and addressing regional disparities to mitigate the severe chest injury burden.

Abstract Background Atrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias, strongly associated with neutrophils. However, the underlying mechanism remain unclear. This study aims to explore the interaction between neutrophils and atrial myocytes in the pathogenesis of AF. Methods Patch-clamp was employed to record the action potential duration (APD) and ion channels in HL-1 cells. Flow cytometry was used to assess the differentiation of neutrophils. The mRNA and protein levels of CACNA1C, CACNA2D, and CACNB2 in HL-1 cells were detected. Results High-frequency electrical stimulation resulted in a shortening of the APD in HL-1 cells. Flow cytometry demonstrated that neutrophils were polarized into N1 phenotype when cultured with stimulated HL-1 cells medium. Compared to control neutrophils conditioned medium (CM), cocultured with TNF-α knockout neutrophils CM prolonged APD and the L-type Ca (2+) channel (LTCC) of HL-1 cells. Additionally, the expression of CACNA2D, CACNB2 and CACNA1C in HL-1 cells were upregulated. Compared with CACNA1C siRNA-transfected HL-1 cells treated with TNF-α siRNA-transfected neutrophils CM, the APD and LTCC of CACNA1C siRNA-transfected HL-1 cells were shortened in control N1 neutrophil CM. The APD and LTCC of control HL-1 cells were also shortened in control N1 neutrophil CM, but prolonged in TNF-α siRNA-transfected neutrophils CM. Conclusion These findings suggest that neutrophils were polarized into N1 phenotype in AF, TNF-α released from N1 neutrophils contributes to the pathogenesis of AF, via decreasing the APD and LTCC in atrial myocytes through down-regulation of CACNA1C expression.

Abstract Black soldier fly larvae (BSFL) could convert a variety of organic wastes, including spent mushroom substrate (SMS) and wet distiller’s grains (WDG). Nevertheless, little is known about the conversion of these wastes by BSFL. Thus, this study investigates the conversion of SMS and WDG in five different proportions by BSFL. This study demonstrates that BSFL can convert SMS, WDG, and their mixtures. It can also encourage the humification of the substrate, increasing the amount of element in the residues. It is evident that there were differences in the carbon and nitrogen element fractionation mode as well as the microbial community present in the residue. The microbial community of the substrate and the physiochemical parameters are intimately related to this. Although the mixture treated with BSFL helps to generate a residue with more humus, it might not be stable.

Abstract On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

Abstract Background Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. Methods Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. Results The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. Conclusions In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Abstract Maladaptive changes of metabolic patterns in the lumbar dorsal root ganglion (DRG) are critical for nociceptive hypersensitivity genesis. The accumulation of branched-chain amino acids (BCAAs) in DRG has been implicated in mechanical allodynia and thermal hyperalgesia, but the exact mechanism is not fully understood. This study aimed to explore how BCAA catabolism in DRG modulates pain sensitization. Wildtype male mice were fed a high-fat diet (HFD) for 8 weeks. Adult PP2Cmfl/fl mice of both sexes were intrathecally injected with pAAV9-hSyn-Cre to delete the mitochondrial targeted 2 C-type serine/threonine protein phosphatase (PP2Cm) in DRG neurons. Here, we reported that BCAA catabolism was impaired in the lumbar 4–5 (L4-L5) DRGs of mice fed a high-fat diet (HFD). Conditional deletion of PP2Cm in DRG neurons led to mechanical allodynia, heat and cold hyperalgesia. Mechanistically, the genetic knockout of PP2Cm resulted in the upregulation of C-C chemokine ligand 5/C-C chemokine receptor 5 (CCL5/CCR5) axis and an increase in transient receptor potential ankyrin 1 (TRPA1) expression. Blocking the CCL5/CCR5 signaling or TRPA1 alleviated pain behaviors induced by PP2Cm deletion. Thus, targeting BCAA catabolism in DRG neurons may be a potential management strategy for pain sensitization.

Abstract Insect’s resilience to adverse conditions poses a significant challenge for integrated pest control. This has resulted in huge economic losses to agriculture and forestry production as well as a range of severe ecological issues. As a physiological mechanism of insects, digestive physiology plays an important role in the process of adaptation to stress factors. However, there has been no systematic review of what stresses insects can adapt to through digestive physiology and how digestive physiology is involved in insect adaptation to stresses. In this review, the potential link between digestive physiology and adaptation of insects to biotic and abiotic stresses, including plant defense mechanisms, chemical insecticides, and entomopathogenic microorganisms, is analyzed. We point to that digestive physiology composed of digestive enzymes and gut microbial communities is an important strategy for insects to resist plant physical defense (e.g., hemicellulose, pectin, and microfibers), chemical defense (e.g., azadirachtin, diterpenoid acids, and phenolic glycosides), chemical insecticide stress, and entomopathogenic microorganism infection. In addition, the primary function of the digestive physiology in insects is to ensure energy supply during biotic and abiotic stress, assist in the metabolism of exogenous toxins (e.g., anti-insect proteins, primary metabolites, secondary metabolites, and insecticides), and improve their innate immunity against entomopathogenic microorganisms. This review is helpful to elucidate the mechanism of pest adaptation to adversity, and provide a breakthrough point for analyzing the causes of pest outbreaks. Graphical abstract

Abstract To evaluate the changes of choroidal thickness (CT) and blood flow related to myopia, and its effects of vascular endothelial growth factor (VEGFA) on choroidal vessels in myopia. Subjects were included and divided into emmetropia (EM), non-high myopia (Non-HM) and high myopia (HM) groups. we measured choroidal thickness (CT), choriocapillaris vessel density (VD), and VEGFA content in tears in humans (137 subjects for CT, VD and 84 for tear) and detected the role of VEGFA in the choroid in form-deprivation myopia (FDM) in guinea pigs. Twenty-four guinea pigs were divided into control and FDM groups, and the expression changes of choroidal vessels and VEGFA were observed and compared using immunohistochemistry and Western blotting. Twenty-one guinea pigs were divided into control, FDM + Vehicle and FDM + Conbercept groups. The changes of diopter, axis length and choroidal vessels after intravitreal injection of Conbercept were observed. There were significant differences in CT and VD among the three groups (p

Abstract The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients’ quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.

Abstract Background Early identification of children at high risk of developing myopia is essential to prevent myopia progression by introducing timely interventions. However, missing data and measurement error (ME) are common challenges in risk prediction modelling that can introduce bias in myopia prediction. Methods We explore four imputation methods to address missing data and ME: single imputation (SI), multiple imputation under missing at random (MI-MAR), multiple imputation with calibration procedure (MI-ME), and multiple imputation under missing not at random (MI-MNAR). We compare four machine-learning models (Decision Tree, Naive Bayes, Random Forest, and Xgboost) and three statistical models (logistic regression, stepwise logistic regression, and least absolute shrinkage and selection operator logistic regression) in myopia risk prediction. We apply these models to the Shanghai Jinshan Myopia Cohort Study and also conduct a simulation study to investigate the impact of missing mechanisms, the degree of ME, and the importance of predictors on model performance. Model performance is evaluated using the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Results Our findings indicate that in scenarios with missing data and ME, using MI-ME in combination with logistic regression yields the best prediction results. In scenarios without ME, employing MI-MAR to handle missing data outperforms SI regardless of the missing mechanisms. When ME has a greater impact on prediction than missing data, the relative advantage of MI-MAR diminishes, and MI-ME becomes more superior. Furthermore, our results demonstrate that statistical models exhibit better prediction performance than machine-learning models. Conclusion MI-ME emerges as a reliable method for handling missing data and ME in important predictors for early-onset myopia risk prediction.

Abstract Optical wireless communication (OWC) stands out as one of the most promising technologies in the sixth-generation (6G) mobile networks. The establishment of high-quality optical links between transmitters and receivers plays a crucial role in OWC performances. Here, by a compact beam splitter composed of a metasurface and a fiber array, we proposed a wide-angle (~120°) OWC optical link scheme that can parallelly support up to 144 communication users. Utilizing high-speed optical module sources and wavelength division multiplexing technique, we demonstrated each user can achieve a communication speed of 200 Gbps which enables the entire system to support ultra-high communication capacity exceeding 28 Tbps. Furthermore, utilizing the metasurface polarization multiplexing, we implemented a full range wide-angle OWC without blind area nor crosstalk among users. Our OWC scheme simultaneously possesses the advantages of high-speed, wide communication area and multi-user parallel communications, paving the way for revolutionary high-performance OWC in the future.

Abstract Background Depression is often linked to inflammation in the brain. Researchers have been exploring ways to reduce this inflammation to improve depression symptoms. One potential target is a protein called RIPK1, which is known to contribute to brain inflammation. However, it’s unclear how RIPK1 influences depression. Our study aims to determine whether RIPK1 inhibition could alleviate neuroinflammation-associated depression and elucidate its underlying mechanisms. Methods To investigate our research objectives, we established a neuroinflammation mouse model by administering LPS. Behavioral and biochemical assessments were conducted on these mice. The findings were subsequently validated through in vitro experiments. Results Using LPS-induced depression models, we investigated RIPK1’s role, observing depressive-like behaviors accompanied by elevated cytokines, IBA-1, GFAP levels, and increased inflammatory signaling molecules and NO/H2O2. Remarkably, Necrostatin (Nec-1 S), a RIPK1 inhibitor, mitigated these changes. We further found altered expression and phosphorylation of eIF4E, PI3K/AKT/mTOR, and synaptic proteins in hippocampal tissues, BV2, and N2a cells post-LPS treatment, which Nec-1 S also ameliorated. Importantly, eIF4E inhibition reversed some of the beneficial effects of Nec-1 S, suggesting a complex interaction between RIPK1 and eIF4E in LPS-induced neuroinflammation. Moreover, citronellol, a RIPK1 agonist, significantly altered eIF4E phosphorylation, indicating RIPK1’s potential upstream regulatory role in eIF4E and its contribution to neuroinflammation-associated depression. Conclusion These findings propose RIPK1 as a pivotal mediator in regulating neuroinflammation and neural plasticity, highlighting its significance as a potential therapeutic target for depression.

This study aims to explore the changes in the vitreous proteomics of form deprivation myopia (FDM) in guinea pigs, in order to reveal the molecular mechanisms involved in the onset and development of myopia. The myopia model in guinea pigs was successfully established by covering one eye of the guinea pigs with a latex bead sac for 4 weeks. This study used 4D data-independent acquisition proteomics technology to analyze vitreous body samples from both the FDM group and the control group. The goal of the proteomics analysis was to identify differences in protein expression within the vitreous body of FDM guinea pigs. Myopia was successfully induced in the FDM group after 4 weeks of modeling. A total of 6298 proteins were identified, among which 348 were differentially expressed proteins (DEPs), with 81 upregulated and 267 downregulated. These DEPs were subjected to in-depth bioinformatics analyses, including Gene Ontology, the Eukaryotic Orthologous Groups, and the Kyoto Encyclopedia of Genes and Genomes. These analyses revealed significant involvement in cellular processes, metabolic pathways, biological regulation, cytoskeletal organization, and cell movement. Our results indicate that calcium signaling plays a critical role in mediating eye changes associated with form deprivation, which may bear similarities to mechanisms observed in neurodegenerative diseases. A total of 348 DEPs related to the development and progression of myopia were identified. These changes involve key biological processes, including protein degradation, cell adhesion, and transport, especially alterations in calcium signaling pathways. Stromal interaction molecule 1 (STIM1) is an important biological marker of FDM, which was confirmed by Western blot, immunohistochemistry and ELISA. Our study found clear differences in the expression of proteins in the vitreous during the development of myopic guinea pigs, especially those related to calcium signaling pathway. Our study offers new insights into the pathogenesis of myopia, particularly changes related to protein metabolism pathways.

In this paper, bathymetry retrieval is combined with the Depth Invariant Index (DII) substrate cluster to acquire more accurate water depth. DIIs are calculated through the selected samples that are in bright and dark pixels firstly. Then, substrates are clustered with DIIs by using the K-MEANS cluster algorithm. Last, in-situ data and Genetic Algorithm (GA) are applied to solve the models’ parameters of the Stumpf model and the Legleiter model. The feasibility of this method is investigated in the Xia Shan Reservoir, Shandong Province, China. The experimental results show that (1) When there are various bottom types in the study area, the substrates cluster before bathymetry retrieval can significantly improve the retrieval accuracy. For example, in the without cluster case, the R2 values are both around 0.72 in the GF-2 image and the R2 values are both 0.53 in the Sentienl-2 image, and the minimum RMSE and RRMSE values are 1.09 m and 19.36 % respectively. When substrates are clustered into two clusters and three clusters, R2 values have all increased and RMSE and RRMSE values decreased. (2) Clustering substrates into more clusters may not necessarily improve retrieval accuracy. For our research area, it’s better to divide the substrate into two clusters. For the two clusters case, the bathymetry result using the Legleiter model has a higher retrieval accuracy, which RMSE is 0.76 m, R2 is 0.9 and RRMSE is 11.76 %. Compared with the three clusters case, the bathymetry retrieval accuracy of the two clusters case improves more obviously.

Ralstonia solanacearum usually infects the vascular bundle system through the roots of host plants, causing bacterial wilt and leading to irreversible wilting and death of plants. Bacterial wilt is a devastating soil-borne bacterial disease. At present, it has been one of the main diseases restricting the production of Solanaceae crops in China. Type Ⅲ secretion system (T3SS) plays an important role in the pathogenesis of R. solanacearum, using T3SS to inject large amounts of Type Ⅲ effectors (T3Es) into host cells to interfere with the immune response of the host. Scholars at home and abroad are committed to exploring how R. solanacearum interferes with host cells and regulates host immune function by identifying target proteins in the host. Therefore, the identification of host proteins that can be targeted by T3Es is helpful to understand the biological function of R. solanacearum T3Es, the pathogenic process of R. solanacearum, and to explore the R. solanacearum resistance-related proteins and their mechanism of action in hosts. Although most of the functions of T3Es are still unknown, so far, it has been reported that R. solanacearum T3Es can regulate host resistance to bacterial wilt by interfering with plant innate immunity, inducing plant hypersensitivity response and affecting plant metabolism and hormone signal transduction through a variety of molecular mechanisms. In this review, we summarize the current research progress on the characteristics and functional identification methods of T3Es of R. solanacearum, and its research progress in participating in the regulation of pathogenicity and plant immunity mechanism of R. solanacearum, which can provide an in-depth understanding of the pathogenic mechanism of R. solanacearum and the response mechanism of the host immune system. The mechanism of interaction between R. solanacearum T3Es and the host are prospected, which will provide an effective reference for the analysis of the host resistance mechanism induced by R. solanacearum and the prevention and control of bacterial wilt.