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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.

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 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

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.

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.

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 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.

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.

Objectives: Coating treatment on the surface of diamond particles is an important technique to effectively overcome the problem of difficult bonding between diamond and substrate, and the thermal explosion reaction is a common surface coating technique for diamond particles. However, this technology has disadvantages such as difficulty in separating diamonds from the product and a low proportion of diamonds, which increases its complexity and production costs, greatly limiting the promotion and application of this technology. This article aims to introduce polytetrafluoroethylene (PTFE) into thermal explosion reaction technology to form a coating mainly composed of TiC on the surface of diamond particles. It is expected to optimize the coating preparation process and promote the popularization and application of thermal explosion reaction technology in the field of diamond plating, so as to improve the wear resistance and service life of the diamond tools. Methods: Using two raw material systems, Ti/carbon black/diamond and Ti/carbon black/PTFE/diamond powders, the thermal explosion reaction of Ti/carbon black/diamond is induced by the chemical furnace method, and the intense chemical reaction between PTFE and titanium at low temperature ensures that the Ti/carbon black/PTFE/diamond system directly undergoes a thermal explosion reaction. At the same time, the TiC coating can be generated on the surface of diamond particles by adjusting the ratio of raw materials and triggering the thermal explosion reaction under high temperature conditions. The macroscopic morphology of diamond particles before and after coating is observed and compared by optical microscope to roughly infer the plating condition, and the phase compositions of the coating were analyzed by X-ray diffraction. Then the scanning electron microscope and the energy dispersive spectroscopy are used to observe the surface morphology of diamond particles, determine the elemental compositions, and infer the surface reaction state. Results: The thermal explosion reaction of both raw material systems can form a TiC coating on the surface of diamond. The main phase of the binder reaction product is TiC, and the main phases of the coating on the surface of diamond particles are TiC and Ti. But for the Ti/carbon black/diamond system, the chemical furnace method is needed to induce a thermal explosion reaction. When the diamond mass fraction in the raw material is 30% or lower, the TiC coating on the surface of the diamond particles is good. When a small amount of PTFE is introduced into the Ti/carbon black/diamond system, the reaction between Ti and PTFE releases a large amount of heat, which induces the thermal explosion reaction between Ti and carbon black and synthesizes TiC, and finally forms a TiC coating on the surface of diamond particles. In addition, the system does not need the chemical furnace method to detonate. When the diamond mass fraction in the raw material is less than or equal to 60%, the diamond particle surface coated with TiC coating is good. At the same time, appropriately reducing the content of carbon black in the raw materials can enable diamond to obtain a good TiC coating on its surface even when the mass fraction of diamond is 90% or higher. Conclusions: TiC coatings are prepared on the surface of diamond particles using thermal explosion reaction technology, and the important effects of raw material compositions and PTFE additives on the formation of diamond particles' surface coating are revealed. Adding an appropriate amount of PTFE can directly induce the thermal explosion reaction, which greatly promotes the increase of the proportion of diamond in the raw material, and effectively improves the formation quality of the coating. This can greatly save binder powder, thereby reducing production costs, while obtaining loose powder products that are easy to separate from diamonds. In addition, drawing on the work of this study, other carbide materials (such as SiC) can be analogously extended for coating on the surface of diamond particles, thereby promoting the promotion and the application of thermal explosion reactions in diamond coating.

To date, some questions about medium-entropy carbide ceramics and the corresponding multi-phase carbide ceramics with the same cations and proportions remain unclear. Regarding oxidation behavior, do both have synergistic oxidation abilities and what role does entropy stabilization play in medium-entropy carbides? In this work, the oxidation behaviors of HfC–ZrC–TiC multi-phase carbide (HZT-MPC) and (Hf1/3Zr1/3Ti1/3)C medium-entropy carbide (HZT-MEC) powders were investigated. After thermogravimetry (TG) oxidation, the TG curve of HZT-MPC had a bimodal distribution. The “preferential oxidation” of HfC/ZrC occurred within HZT-MPC, followed by the formation of multi-phase oxides (HfO2, ZrO2, and TiO2). The uneven compositional distribution slowed their solid solution reactions to form Ti-doped (Hf,Zr)O2 and (Hf,Zr)TiO4. The TG curve of HZT-MEC had a single peak. A uniform compositional distribution at the atomic scale promoted the rapid interdiffusion of oxides, forming Ti-doped (Hf,Zr)O2 and (Hf,Zr)TiO4 without ZrO2, HfO2, and TiO2 after TG oxidation. Additionally, HZT-MEC had a higher onset oxidation temperature (To; 470 °C) than did HZT-MPC (430 °C), and the TG single peak of HZT-MEC was between the TG bimodal peaks of HZT-MPC. Therefore, HZT-MEC showed superior oxidation resistance compared to HZT-MPC, which was attributed to the entropy stabilization effect of HZT-MEC suppressing the “preferential oxidation” of HfC/ZrC and the “delayed oxidation” of TiC, promoting the synergistic oxidation ability of multiple principal elements.

Rheumatoid arthritis (RA), a globally increasing autoimmune disorder, is associated with increased disability rates due to the disruption of iron metabolism. Tripterygium glycoside tablets (TGTs), a Tripterygium wilfordii Hook. f. (TwHF)-based therapy, exhibit satisfactory clinical efficacy for RA treatment. However, drug-induced liver injury (DILI) remains a critical issue that hinders the clinical application of TGTs, and the molecular mechanisms underlying the efficacy and toxicity of TGTs in RA have not been fully elucidated. To address this problem, we integrated clinical multi-omics data associated with the anti-RA efficacy and DILI of TGTs with the chemical and target profiling of TGTs to perform a systematic network analysis. Subsequently, we identified effective and toxic targets following experimental validation in a collagen-induced arthritis (CIA) mouse model. Significantly different transcriptome–protein–metabolite profiles distinguishing patients with favorable TGTs responses from those with poor outcomes were identified. Intriguingly, the clinical efficacy and DILI of TGTs against RA were associated with metabolic homeostasis between iron and bone and between iron and lipids, respectively. Particularly, the signal transducer and activator of transcription 3 (STAT3)–hepcidin (HAMP)/lipocalin 2 (LCN2)–tartrate-resistant acid phosphatase type 5 (ACP5) and STAT3–HAMP–acyl-CoA synthetase long-chain family member 4 (ACSL4)–lysophosphatidylcholine acyltransferase 3 (LPCAT3) axes were identified as key drivers of the efficacy and toxicity of TGTs. TGTs play dual roles in ameliorating CIA-induced pathology and in inducing hepatic dysfunction, disruption of lipid metabolism, and hepatic lipid peroxidation. Notably, TGTs effectively reversed “iron–bone” disruptions in the inflamed joint tissues of CIA mice by inhibiting the STAT3–HAMP/LCN2–ACP5 axis, subsequently leading to “iron–lipid” disturbances in the liver tissues via modulation of the STAT3–HAMP–ACSL4–LPCAT3 axis. Additional bidirectional validation experiments were conducted using MH7A and AML12 cells to confirm the bidirectional regulatory effects of TGTs on key targets. Collectively, our data highlight the association between iron-mediated metabolic homeostasis and the clinical efficacy and toxicity of TGT in RA therapy, offering guidance for the rational clinical use of TwHF-based therapy with dual therapeutic and toxic potential.

Objective: This study aims to elucidate and quantify the composition of Jiangtang Qingre formula (JQF), delineate the absorbed components in the bloodstream, predict the major biologically active components, and identify potential targets for the treatment of diabetes mellitus (DM). Materials and Methods: The chemical composition and metabolites of JQF were elucidated using ultra-high-performance liquid chromatography (UHPLC)-linear ion trap quadrupole-orbitrap high-resolution mass spectrometry (MS). The various components of JQF were concurrently determined using UHPLC-triple–quadrupole MS. Network pharmacological analysis was employed to explore the bioactive components and potential therapeutic targets in DM. Results: A total of 63 compounds were identified and provisionally characterized, with flavones, organic acids, and alkaloids emerging as the major chemical constituents. A robust analytical method that enables the simultaneous quantification of 24 representative components was successfully developed. The contents of 11 batches of samples were assessed. Ten prototype components were identified in rat plasma. The pathways associated with the efficacy of JQF in DM treatment were linked to signal transduction, endocrine and immune systems, lipid metabolism, and amino acid metabolism. Conclusion: This study systematically and comprehensively characterized the major chemical components and patterns in JQF, laying the groundwork for understanding its pharmacodynamic mechanisms and clinical applications.

Abstract Although overall survival data are still premature, the PROpel study found radiological progression-free survival (PFS) benefits of abiraterone and olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC). However, for patients who have not been genetically tested or lack BRCA1/2 mutations (BRCAm), this combination therapy has been questioned as a first-line conventional treatment for mCRPC, mainly due to significant health economics and side effects. In our retrospective study, we found that treatment with low-dose abiraterone plus olaparib as a late-line treatment for mCRPC could lead to prostate-specific antigen (PSA) and symptom PFS in selective cases even without BRCAm. The median PSA–PFS was 8 months (IQR: 6.5–11.5), with a median follow-up duration of 39.0 months (IQR: 27.5–64.5). Gene tests were conducted in all patients, identifying non-BRCA mutations through ctDNA testing (24%), tumor tissue testing (12%), or both (64%). Adverse events occurred in 72% of patients, with 16% experiencing Grade ≥ 3 events. Common adverse events included anemia (64%), decreased appetite (48%), and fatigue (25%). Our findings support low-dose abiraterone plus olaparib as a potential option for mCRPC patients without BRCAm, offering manageable safety and efficacy profiles.

Abstract Objective To investigate the clinical significance of using 3D printing guides in modified unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fractures (OVCF), and to explore a new method for preventing paravertebral vein leakage during PVP in conjunction with a previous study of the optimal puncture-side bone cement/vertebral volume ratio(PSBCV/VV%). Methods This retrospective study analyzed 99 patients who underwent unilateral puncture PVP between January 2023 and December 2023. Patients were divided into a guide plate group (46 patients) and a conventional group (53 patients). The guide plate group underwent modified unilateral puncture PVP with the guidance of 3D printing guides, while the conventional group underwent unilateral puncture PVP using the conventional pedicle approach. The distribution of bone cement, surgical outcomes, and the occurrence of cement leakage into paravertebral veins were observed in both groups. Results The guide plate group had significantly shorter operating time and required fewer fluoroscopies compared to the conventional group. The amount of bone cement volume (BCV) used in the guide plate group was higher, but the amount of bone cement volume on the puncture side(PSBCV), the PSBCV/VV%, and the rate of paravertebral vein leakage were lower in the guide plate group compared to the conventional group (P

Abstract Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd−/−) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Abstract This single-arm phase 2 trial (ChiCTR2100046715) examined previously untreated patients with advanced esophageal squamous cell carcinoma (ESCC) who received four cycles of paclitaxel with carboplatin every 3 weeks. Toripalimab was infused intravenously every 3 weeks for 12 months, or until disease progression or intolerable toxicity. Radiotherapy that encompassed the primary lesions and metastases commenced in the third cycle. The median progression-free survival time was 9.8 months (95% confidence interval [CI]: 6.8–not estimable) in the intent-to-treat population, failing to meet the pre-specified primary endpoints. Secondary endpoints included an objective response rate of 45.5%, a disease control rate of 57.6%, and a median duration of response of 11.5 months (interquartile range, 6.4–15.0). The 1-year progression-free survival and overall survival rates were 41.9% (95% CI: 27.7–63.5) and 69.7% (95% CI: 55.7–87.3), respectively. Lymphopenia was the most frequent grade ≥3 adverse event (82%), and an esophageal fistula developed in three patients (9.1%). No treatment-related deaths occurred. In prespecified exploratory biomarker analysis, higher densities of CD8 + T cells, CD11c+ dendritic cells, and CD68+ macrophages correlated with improved tumor response and prognosis. Radiotherapy supplementation to first-line chemo-immunotherapy for treatment-naive advanced ESCC demonstrated some antitumor activity and manageable safety profiles, warranting further randomized controlled trials.

This is an article in the field of ceramics and composites. In this article, the effects of IOT and polyvinyl alcohol (PVA) fiber (PF) on the compressive strength, four-point flexural strength, flexural toughness, pore structure of cement-based composites were studied and discussed in detail. The conversion relationship between compressive strength and four-point flexural strength was established. The results showed that the incorporation of IOT had an enhanced effect on the mechanical properties, and this enhanced effect showed a trend of first increasing and then decreasing with the increase in the substitution rate of IOT. However, when PF was added, the mechanical properties under the combined effect of PF and IOT were further improved and showed good toughness. In addition, the internal pores of the matrix with IOT substitution rate of 40% and PF were obviously reduced. Thus, it was concluded that the cement-based composite material had good mechanical properties when the 40% IOT was combined with PF.

Abstract Biological networks serve a crucial role in elucidating intricate biological processes. While interspecies environmental interactions have been extensively studied, the exploration of gene interactions within species, particularly among individual microorganisms, is less developed. The increasing amount of microbiome genomic data necessitates a more nuanced analysis of microbial genome structures and functions. In this context, we introduce a complex structure using higher-order network theory, “Solid Motif Structures (SMS)”, via a hierarchical biological network analysis of genomes within the same genus, effectively linking microbial genome structure with its function. Leveraging 162 high-quality genomes of Microcystis, a key freshwater cyanobacterium within microbial ecosystems, we established a genome structure network. Employing deep learning techniques, such as adaptive graph encoder, we uncovered 27 critical functional subnetworks and their associated SMSs. Incorporating metagenomic data from seven geographically distinct lakes, we conducted an investigation into Microcystis’ functional stability under varying environmental conditions, unveiling unique functional interaction models for each lake. Our work compiles these insights into an extensive resource repository, providing novel perspectives on the functional dynamics within Microcystis. This research offers a hierarchical network analysis framework for understanding interactions between microbial genome structures and functions within the same genus.

【Objective】E/W band millimeter-wave frequency covers 60~110 GHz, with abundant frequency band resources and potential for high-capacity transmission. Compared with lasers, E/W band millimeter-wave beam is wider, with advantages of directionality, anti-interference and ease of alignment, making it a promising frequency band for long-distance wireless communication at sea. However, the characteristics of near-sea surface channels such as atmospheric absorption and multipath at the sea surface limit the transmission distance of E/W-band millimeter waves, resulting in bottlenecks in E/W-band millimeter wave transmission near-sea surface. This paper focuses on the direction of long-distance millimeter-wave wireless transmission at sea, using microwave photonics technology to propose an ultra-wideband millimeter-wave modulation and demodulation system architecture to improve the millimeter-wave frequency conversion and modulation performance. We then study the optimal high-order modulation format in near-sea surface long-distance transmission systems to achieve high-capacity long-distance transmission.【Methods】The power amplifier in long-distance communication systems can introduce nonlinear distortion to the signal. It analyzes the factors affecting the performance of high-order modulation formats such as Amplitude Phase Shift Keying (APSK) and Quadrature Amplitude Modulation (QAM) due to the nonlinear characteristics of solid-state power amplifiers. The optimal distribution, Euclidean distance and inner and outer radius ratio of 16APSK signals have been studied. By the equivalent power experiments, the nonlinear resistance of 16QAM and 16APSK signals are compared and analyzed.【Results】The millimeter-wave long-distance transmission experiment is carried out for performance investigation. It proves that the APSK modulation format is more suitable for long-distance transmission system than QAM format.【Conclusion】Based on the 16APSK modulation format, the performance of 16 Gbit/s, equivalent 34 km long-distance transmission are achieved in the experiment, providing high-value technical means for long-distance high-capacity transmission at sea.

Abstract Background This study details a case of a patient with advanced lung adenocarcinoma harboring an exon 19 deletion in the EGFR gene. Method A 46-year-old female patient was diagnosed with stage IVb left lung adenocarcinoma, with multiple bone and lymph node metastases. Following the identification of tumor-specific antigen peptides, the patient received a combination treatment of immunotherapy (TSA-DC-CTL) and oral osimertinib. Peripheral blood circulating immune cells and circulating tumor cells (CTCs) were monitored before and after treatment. PET-CT and CT scans were used to assess the tumor response to treatment. Results A significant increase in total lymphocyte percentage and decrease in the number of CTCs in the patient was observed. Imaging studies showed a notable reduction in tumor metastases. Conclusion This report demonstrates the safety and efficacy of TSA-DC-CTL cell immunotherapy combined with osimertinib in the treatment of a patient with advanced lung adenocarcinoma with an EGFR exon 19 deletions. This study describes a promising new treatment option for patients with advanced lung cancer with EGFR mutations.

Abstract Background Insulin resistance (IR) has been linked to the development of gout. The triglyceride glycemic (TyG) index is a useful biomarker of IR, and the evidences between TyG and gout are limited. Therefore, this study aimed to examine the association between the TyG index and gout in the United States (U.S). Methods The cross-sectional study was conducted among adults with complete TyG index and gout data in the 2007–2017 National Health and Nutrition Examination Survey (NHANES). The TyG index was calculated as fasting triglycerides (mg/dl) * fasting glucose (mg/dl)/2. Gout was assessed by self-report questionnaire (MCQ160n). Weighted chi-squared and weighted Student’s t-test were used to assess group differences. Weighted multivariable logistic regression analysis, subgroup analysis, and interaction tests were used to examine the TyG index and gout association. Results The final participants were 11,768; 5910 (50.32%) were female, 7784 (73.26%) were 18–60 years old, 5232 (69.63%) were white, and 573 (5.12%) had gout. After adjusting for all covariates, the TyG index was positively associated with gout; each unit increase in TyG index was associated with 40% higher odds of gout (odds ratio (OR), 1.40; 95% CI: 1.82–2.66; p 0.05). Conclusions In this large cross-sectional study, our results suggested that a higher TyG index was associated with an increased likelihood of gout in U.S. adults. Our findings highlight that the TyG index is a reliable biomarker of IR; management of IR among adults may prevent or alleviate the development of gout; meanwhile, the TyG index may be a simple and cost-effective method to detect gout.

Objectives Cervical alignment and range of motion (ROM) changes after cervical spine surgery are related to cervical biomechanical and functions. Few studies compared these parameters between posterior laminoplasty and anterior 3‐level hybrid surgery incorporating anterior cervical discectomy and fusion (ACDF) with cervical disc replacement (CDR). This study is aimed to detect the differences of cervical alignment and ROM changes of the two surgeries in a matched‐cohort study. Methods From January 2018 and May 2020, 51 patients who underwent 3‐level hybrid surgery incorporating ACDF with ACDR were included. A 1:1 match of the patients who underwent cervical laminoplasty based on age, gender, duration of symptoms, body mass index, and cervical alignment type was utilized as control group. General data (operative time, blood loss, etc.), Japanese Orthopaedic Association (JOA) score, VAS (Visual Analog Score), NDI (The Neck Disability Index), cervical sagittal alignment, and cervical range of motion (ROM) were recorded and compared. Results Both groups gained significant improvement in JOA, VAS, NDI scores postoperatively (p

ObjectiveTo evaluate the safety of co-vaccination with domestic 23-valent pneumococcal polysaccharide vaccine (PPSV23) and split influenza virus vaccine (sFlu) in key populations aged 3 years and older and to provide a reference for formulating co-vaccination strategies. MethodsThe study participants were 5 502 healthy and unhealthy (with chronic diseases) volunteers (including 2 072 children aged 3 – < 8 years, 1 598 residents aged 8 – < 60 years, and 1 832 elderly aged 60 years and older) vaccinated simultaneously with one dose of PPSV23 (intramuscular injection into the deltoid muscle of the left upper arm) and one dose of sFlu (into the right upper arm) in 8 cities of Anhui province from October 2021 to February 2023. Active surveillance for adverse reactions within 28 days of co-vaccination with PPSV23 and sFlu was conducted among participants through active reporting via the Ark Immunization mobile application and telephone or home interviews by health care workers. Reported current/historic chronic diseases and observed adverse events after co-vaccination were categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) and the Guiding Principles for the Classification of Adverse Events in Clinical Trials of Preventive Vaccines issued by the National Medical Products Administration. ResultsThe prevalence of underlying chronic diseases was 1.45%, 100.00%, and 37.61% in participants aged 3 – < 8, 8 – < 60, and ≥ 60 years, respectively. All adverse events occurred within 7 days of co-vaccination, with an incidence rate of 2.67%. The incidence rates of grade 1, 2, and 3 adverse events were 1.62%, 0.93%, and 0.13%, respectively. The incidence rates of local and systemic adverse events were 2.25% and 1.00%, respectively. Local reactions were mainly pain at the vaccination site, while systemic reactions were mainly fever. The incidence of local adverse events was higher for PPSV23 than for sFlu when administered at the same time. The incidence rates of adverse reactions in participants aged 3 – < 8, 8 – < 60, and 60 years and older were 2.03%, 3.25%, and 2.89%, respectively, without significant difference (χ2 = 5.741, P > 0.05). The grades of adverse reactions in the participants of the three age groups were mainly grade 1 and 2. The overall incidence rate of adverse reactions in healthy participants was 2.32% and that in unhealthy participants was 3.15%, without significant difference between the two groups (χ2 = 3.530, P > 0.05). There were no significant differences in the incidence and severity of adverse events between the healthy and unhealthy participants aged 3 – < 8 years and 60 years and older (P > 0.05). ConclusionSimultaneous vaccination with domestic PPSV23 and sFlu has shown good safety in key populations of different ages, health status and simultaneous vaccination with the two vaccines is recommended.