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Abstract Background This study aimed to evaluate the diagnostic abilities of the non-invasive serum biomarkers to predict liver fibrosis staging and evaluate the progress of hepatitis B. Methods We enrolled 433 patients with chronic HBV infection had complete medical data available for the study, who underwent percutaneous liver biopsy. The extent of fibrosis was assessed using the modified METAVIR score. The predictive values of the non-invasive serum biomarkers were evaluated by the areas under the receiving operator characteristics curves (AUROCs) with 95% confidence intervals. Results The proportion of males with progressive stages of liver fibrosis was relatively larger, and the average age of patients with cirrhosis stages is older than the non-cirrhotic stages. We found PLT, GGT, ALP, TB, FIB4 and GPR to be significantly associated with liver fibrosis in our cohort. GGT showed a sensitivity of 71.4% and specificity of 76.7% in distinguishing cirrhosis (F4) from non-cirrhotic stages (F1-3), with an AUROC of 0.775 (95%CI 0.711–0.840).The AUROCs of the GPR in distinguishing cirrhosis (F4) from non-cirrhotic stages (F1-3) was 0.794 (95%CI 0.734–0.853), but it had a lower sensitivity of 59.2%. Additionally, GGT, FIB4, and GPR could differentiate advanced fibrosis (F3-4) from non-advanced fibrosis (F1-2) among individuals with chronic hepatitis B, with AUROCs of 0.723 (95%CI 0.668–0.777), 0.729 (95%CI 0.675–0.782), and 0.760 (95%CI: 0.709–0.811) respectively. Conclusions GGT was a better biomarker to distinguish cirrhosis (F4) from non-cirrhotic stages (F1-3), while GPR was a better biomarker to identify advanced fibrosis (F3-4) and non-advanced fibrosis (F1-2) in patients with chronic hepatitis B.

To assess the factors that influencing the persistence of virus neutralizing antibody (VNA), and to establish prediction models to provide the appropriate timing for booster administration, a cohort of post-exposure rabies vaccine recipients was investigated. The VNA determined records from 2019 to 2023 and interrelated factors were analyzed, including gender, age, rabies immunoglobulin (RIG) administration, vaccine products, vaccination schedule, and vaccination intervals etc. The geometric mean of VNA titre within 1 month after primary vaccination with 2-1-1 schedule was statistically higher than that with 5-dose course (P = 0.031). The interaction between exposure and vaccination schedule was observed on primary vaccination, which showed that a decrease of 19.74 % (95 % CI: 5.99%–64.95 %, P = 0.008) of VNA titre among vaccinee with 5-dose and exposure III. Individuals with RIG administration produced lower VNA titres than those without RIG administration (P = 0.001). Vaccine products (Chengda, P = 0.015; human diploid cell, P = 0.026) and re-exposed time (P = 0.000) exhibited independent effects following booster vaccination. Based on the prediction model, the 99 % individual prediction intervals (IPI) of VNA titres were established at 3, 6, 12 and 18 months for the 12 characteristic populations respectively. The cases of VNA below 0.5 IU/ml first appeared at 6 months in group D of primary vaccinations and at 10 years in group F of boosters. We conclude that for primary vaccination 2-1-1 schedule is more efficient than 5-dose; the use of residual rabies immunoglobulin for distal intramuscular injection isn't recommended. The 99 % IPI of VNA titres could provide the appropriate timing for booster vaccination.

For addressing the challenges of decreased attitude and trajectory tracking accuracy and a delayed response in the flight control operations of quadcopter unmanned aerial vehicles (UAVs) under the uncertainties of model parameters and external disturbances, this study leverages the advantages of the non-causal declarative modeling language Modelica in system modeling and simulation. In addition, it incorporates the nonlinear Active Disturbance Rejection Control (ADRC) framework for disturbance observation, estimation, and compensation. A state observer is designed to mitigate the impact of external disturbances and model uncertainties through feed-forward compensation, and stability analysis is conducted. Numerical simulations for hover resistance demonstrate that, compared to the cascade proportional integral differential (PID) control strategy, PID-NLADRC reduces the maximum deviation induced by wind disturbances by ∼50% and shortens the disturbance influence time by around 40%. Simulations for different trajectories, such as planar or spatial, smooth or abrupt changes, indicate that under the PID-NLADRC control strategy, the real-time spatial distance deviation mean is reduced by 69.5%, and the peak time is shortened by 75.7%. Validation through multi-objective applications and physical experiments highlights the advantages of PID-NLADRC in terms of positioning accuracy, rapid tracking, and disturbance suppression, aligning well with the fast, precise, and robust flight control requirements of quadcopter UAVs.

Abstract Introduction Hypoxia is an important characteristic of gastric mucosal diseases, and hypoxia‐inducible factor‐1α (HIF‐1α) contributes to microenvironment disturbance and metabolic spectrum abnormalities. However, the underlying mechanism of HIF‐1α and its association with mitochondrial dysfunction in gastric mucosal lesions under hypoxia have not been fully clarified. Objectives To evaluate the effects of hypoxia‐induced HIF‐1α on the development of gastric mucosal lesions. Methods Portal hypertensive gastropathy (PHG) and gastric cancer (GC) were selected as representative diseases of benign and malignant gastric lesions, respectively. Gastric tissues from patients diagnosed with the above diseases were collected. Portal hypertension (PHT)‐induced mouse models in METTL3 mutant or NLRP3‐deficient littermates were established, and nude mouse gastric graft tumour models with relevant inhibitors were generated. The mechanisms underlying hypoxic condition, mitochondrial dysfunction and metabolic alterations in gastric mucosal lesions were further analysed. Results HIF‐1α, which can mediate mitochondrial dysfunction via upregulation of METTL3/IGF2BP3‐dependent dynamin‐related protein 1 (Drp1) N6‐methyladenosine modification to increase mitochondrial reactive oxygen species (mtROS) production, was elevated under hypoxic conditions in human and mouse portal hypertensive gastric mucosa and GC tissues. While blocking HIF‐1α with PX‐478, inhibiting Drp1‐dependent mitochondrial fission via mitochondrial division inhibitor 1 (Mdivi‐1) treatment or METTL3 mutation alleviated this process. Furthermore, HIF‐1α influenced energy metabolism by enhancing glycolysis via lactate dehydrogenase A. In addition, HIF‐1α‐induced Drp1‐dependent mitochondrial fission also enhanced glycolysis. Drp1‐dependent mitochondrial fission and enhanced glycolysis were associated with alterations in antioxidant enzyme activity and dysfunction of the mitochondrial electron transport chain, resulting in massive mtROS production, which was needed for activation of NLRP3 inflammasome to aggravate the development of the PHG and GC. Conclusions Under hypoxic conditions, HIF‐1α enhances mitochondrial dysfunction via Drp1‐dependent mitochondrial fission and influences the metabolic profile by altering glycolysis to increase mtROS production, which can trigger NLRP3 inflammasome activation and mucosal microenvironment alterations to contribute to the development of benign and malignant gastric mucosal lesions.

Background Diacetyl (DC) is widely used in the food flavoring industry and excessive occupational exposure to DC can cause serious respiratory diseases. However, there is no corresponding national standard method for the determination of DC in the air of workplace.Objective To establish a method for the determination of DC in workplace air by high performance liquid chromatography using 4-nitro-o-phenylenediamine (NPDA) as precolumn derivatization.Methods DC in the air of workplace was collected by solution absorption method. This experiment used NPDA as the derivatization reagent. By adjusting acidity of solution and optimizing concentration ration of DC/NPDA, derivatization temperature, and time, a method for the determination of DC in workplace air was proposed, and its performance indexes such as linearity, detection limit, and lower limit of quantification were obtained. Sampling efficiency was evaluated by relative comparison method, and sample stability was evaluated by sample preservation test. Accuracy and precision of the method were evaluated by standard addition recovery test with blank samples, and an interference test was carried out by adding standard samples. The established method was applied to actual samples to evaluate its adaptability.Results A combination of 60 °C for 2 h was selected for derivatization because a higher derivatization reaction temperature and a longer reaction time associated with a higher derivatization efficiency. The solution was separated by SB-C18 column (250 mm×4.6 mm, 5 μm) at 30 ℃, using a mixture of methanol and water (v/v, 65%/35%) as mobile phase with an elution flow rate of 1.0 mL·min−1, and was detected with a variable wavelength detector (λmax=257 nm) by qualitative analysis based on retention time and quantitative analysis based on external standard method. In terms of the proposed method, the linear range of detection was from 5 μg·L−1 to 2000 μg·L−1, with a correlation coefficient of 0.9999, and a detection limit of 1.3 μg·L−1, the quantitative detection of the lower limit was 4.3 μg·L−1, with a sampling volume V0 of 3.0 L, the minimum detection concentration was 4.3 μg·m−3, and the minimum quantitative concentration was 14.3 μg·m−3. The recovery rate was 99.1%-100.8%, the intra-batch precision was 0.5%-3.0%, and the inter-batch precision was 1.2%-2.0%. The average sampling efficiency of this method was 94.5%, and the sample could be stored at 4 °C for at least 14 d. The coexisting components in the air of the workplace did not interfere with the determination of DC. The DC content in the air of a flavor workplace was 5.86-8.85 mg·m−3.ConclusionA determination method for DC in workplace air by high performance liquid chromatography using NPDA as precolumn derivatization after being collected by 1.0% phosphoric acid absorbent is proposed and has the advantages of simple operation, high sensitivity, and good accuracy. With no DC loss and degradation, the method may satisfy the request for DC determination in the air of workplace.

Through an activation reaction sintering method, porous (Mo2/3Y1/3)2AlC ceramics were prepared by Mo, Y, Al, and graphite powders as raw materials. The phase composition, microstructure, element distribution, and pore structure characteristics were comprehensively studied using X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Archimedes method, and bubble point method. A detailed investigation was conducted on the influence of sintering temperature on the phase composition. Possible routes of phase transition and pore formation mechanisms during the sintering process were provided. The experimental results reveal that at 650–850 °C, transition metals react with aluminum, forming aluminum-containing intermetallics and a small amount of carbides. At 850–1250 °C, transition metals collaborate with graphite, producing transition metal carbides. Then, at 1250–1450 °C, these aluminum intermetallics interact with transition metal carbides and remaining unreacted Y, Al, and C, yielding the final product (Mo2/3Y1/3) 2AlC. Simultaneously, the pore structure alters correspondingly with the solid-phase reaction at different reaction temperatures.

Abstract Berberine (BBR) has been explored as a potential anti-liver fibrosis agent, but the underlying mechanisms are unknown. In the current study, we aimed to investigate the molecular mechanisms underlying the effect of BBR against liver fibrogenesis in thioacetamide (TAA) and carbon tetrachloride (CCl4) induced mouse liver fibrosis. In addition to i.p. injection with TAA or CCl4, mice in the treatment group received BBR intragastrically. Concurrently, combined with TAA and BBR treatment, mice in the inhibitor group were injected i.p. with ferrostatin-1 (Fer-1). Hepatic stellate cells (HSCs) were also used in the study. Our results showed that BBR obviously alleviated mouse liver fibrosis and restored mouse liver function; however, the pharmacological effects of BBR against liver fibrosis were significantly diminished by Fer-1 treatment. Mechanically, BBR impaired the autophagy–lysosome pathway (ALP) and increased cell reactive oxygen species (ROS) production in HSCs. ROS accelerated the breakdown of the iron-storage protein ferritin and sped up iron release from ferritin, which resulted in redox-active iron accumulation in HSCs. Lipid peroxidation and glutathione (GSH) depletion triggered by the Fenton reaction promoted ferroptosis and attenuated liver fibrosis. Furthermore, impaired autophagy enhanced BBR-mediated ferritin proteolysis to increase cellular ferrous overload via the ubiquitin–proteasome pathway (UPS) in HSCs and triggered HSC ferroptosis. Collectively, BBR alleviated liver fibrosis by inducing ferrous redox to activate ROS-mediated HSC ferroptosis. Our findings may be exploited clinically to provide a potential novel therapeutic strategy for liver fibrosis.

Abstract Fas/Fas ligand (FasL)-mediated cell apoptosis involves a variety of physiological and pathological processes including chronic hepatic diseases, and hepatocytes apoptosis contributes to the development of liver fibrosis following various causes. However, the mechanism of the Fas/FasL signaling and hepatocytes apoptosis in liver fibrogenesis remains unclear. The Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models were investigated. NF-κBp65 wild-type mice (p65 f/f ), hepatocytes specific NF-κBp65 deletion mice (p65Δhepa), p53-upregulated modulator of apoptosis (PUMA) wild-type (PUMA-WT) and PUMA knockout (PUMA-KO) littermate models, and primary hepatic stellate cells (HSCs) were also used. The mechanism underlying Fas/FasL-regulated hepatocytes apoptosis to drive HSCs activation in fibrosis was further analyzed. We found Fas/FasL promoted PUMA-mediated hepatocytes apoptosis via regulating autophagy signaling and NF-κBp65 phosphorylation, while inhibition of autophagy or PUMA deficiency attenuated Fas/FasL-modulated hepatocytes apoptosis and liver fibrosis. Furthermore, NF-κBp65 in hepatocytes repressed PUMA-mediated hepatocytes apoptosis via regulating the Bcl-2 family, while NF-κBp65 deficiency in hepatocytes promoted PUMA-mediated hepatocytes apoptosis and enhanced apoptosis-linked inflammatory response, which contributed to the activation of HSCs and liver fibrogenesis. These results suggest that Fas/FasL contributes to NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to enhance liver fibrogenesis, and this network could be a potential therapeutic target for liver fibrosis.

Liver cirrhosis is a form of liver fibrosis resulting from chronic hepatitis caused by various liver diseases, such as viral hepatitis, alcoholic liver damage, nonalcoholic steatohepatitis, autoimmune liver disease, and by parasitic diseases such as schistosomiasis. Liver fibrosis is the common pathological base and precursors of cirrhosis. Inflammation and disorders of lipid metabolism are key drivers in liver fibrosis. Studies have determined that parts of the arachidonic acid pathway, such as its metabolic enzymes and biologically active products, are hallmarks of inflammation, and that aberrant peroxisome proliferator-activated receptor gamma (PPARγ)-mediated regulation causes disorders of lipid metabolism. However, despite the ongoing research focus on delineating the mechanisms of liver fibrosis that underpin various chronic liver diseases, effective clinical treatments have yet to be developed. Berberine (BBR) is an isoquinoline alkaloid with multiple biological activities, such as anti-inflammatory, anti-bacterial, anti-cancer, and anti-hyperlipidemic activities. Many studies have also found that BBR acts via multiple pathways to alleviate liver fibrosis. Furthermore, the absorption of BBR is increased by nitroreductase-containing intestinal flora, and is strengthened via crosstalk with bile acid metabolism. This improves the oral bioavailability of BBR, thereby enhancing its clinical utility. The production of butyrate by intestinal anaerobic bacteria is dramatically increased by BBR, thereby amplifying butyrate-mediated alleviation of liver fibrosis. In this review, we discuss the effects of BBR on liver fibrosis and lipid metabolism, particularly the metabolism of arachidonic acid, and highlight the potential mechanisms by which BBR relieves liver fibrosis through lipid metabolism related and intestinal flora related pathways. We hope that this review will provide insights on the BBR-based treatment of liver cirrhosis and related research in this area, and we encourage further studies that increase the ability of BBR to enhance liver health.

Ni-based alloy is an ideal candidate for its application in the field of hydrogen evolution of water splitting due to its good durability, excellent catalytic properties and low hydrogen evolution overpotential. In this paper, porous Ni-Sn alloy materials were prepared by activation reaction sintering, and the pore structure was tailored by adjusting Sn content. The effects of Sn content and electrolyte temperature on the hydrogen evolution properties of porous Ni-Sn alloy electrodes in 6 mol·L−1 KOH solution were studied by electrochemical measurement methods, such as cyclic voltammetry (CV) curves, electrochemical impedance spectroscopy (ESI) and linear sweep voltammetry, and the mechanism of hydrogen evolution was further discussed. The experimental results reveal that when Sn content is 45 wt%, porous Ni-Sn alloy exhibits the best catalytic performance for hydrogen evolution with a Tafel slope of 164.69 mV·dec−1 and an overpotential of 170 mV. The tested electrode also shows good stability for hydrogen evolution in alkaline solution, and the apparent activation energy calculated at room temperature is 29.645 kJ·mol−1. The catalytic mechanism of hydrogen evolution is as follows: the addition of Sn significantly reduces the dissociation degree of M-H bonds, thereby reducing the overpotential of hydrogen evolution; with the increase of Sn content, the porous Ni-Sn electrode displays a higher electrochemical active surface area (ECSA), which makes porous Ni-Sn alloy exhibit good hydrogen evolution catalytic performance.

Abstract COX-1/PGE2 is an important protective mediator in ulcerative colitis (UC). β-arrestin1 (β-arr1), which acts as a scaffold protein, is involved in PGE2-mediated signaling pathways. However, the interaction between PGE2 and β-arr1 in maintaining mucosal barrier integrity remains unexplored. In this study, we demonstrated that COX-1 and PGE2 were significantly decreased, and EP4 mRNA was downregulated in both UC patients and mice during the injury phase. PGE2 treatment was found to alleviate mucosal injury and induce EP4 expression during dextran sulfate sodium (DSS)-induced colitis in wild-type (WT) mice. Following DSS-induced injury, β-arr1 deficient mice showed increased signs of colitis compared to β-arr1 WT mice, and the expression of PI3K and p-Akt were remarkably downregulated in β-arr1 deficient mice. In parallel, HCT116 cells transfected with β-arr1 siRNA were examined in the presence or absence of PGE2 in vitro. PGE2 treatment in the β-arr1 WT/KO DSS model and β-arr1 siRNA transfection of HCT116 cells confirmed that PGE2 upregulated β-arr1 in vivo and in vitro. Collectively, our results indicate that COX-1/PGE2/EP4 upregulates the β-arr1 mediated Akt signaling pathway to provide mucosal protection in colitis. Thus, these findings provide support for the future development and clinical application of COX-1/PGE2 in UC.

Objective. Diagnostic colonoscopy is important for diagnosing colorectal diseases, including inflammatory bowel disease and colorectal tumours. Perforation during diagnostic colonoscopy, a rare but serious complication, is a considerable factor before performing the procedure. Immediate endoluminal closure of a perforation could prevent the adverse consequences associated with general anaesthesia and surgery. This study is aimed at assessing the potential effectiveness and safety of endoscopic band ligation (EBL) in closing a colon perforation during endoscopy in a porcine model. Methods. Colon perforations were created and then subsequently closed with EBL in six porcine models. After 28 days of careful follow-up, pigs were euthanized for clinical and pathologic evaluations. Results. All colon perforations were successfully closed using EBL in pigs. The mean time of perforation closure with EBL was 244.3 seconds with one to two bands, and there were no immediate complications or clinical manifestations of peritonitis or sepsis in any animals. No pericolonic abscess or peritonitis was found during necropsy. Histopathology demonstrated reepithelialization of the mucosa at the perforation site. Conclusions. Immediate closure of perforations caused during colonoscopy with EBL is feasible and safe in a porcine model.

Abstract Objective Abnormalities in the gray matter structure of cerebral small vessel disease (CSVD) have been observed throughout the brain. However, whether cortico‐cortical connections exist between regions of gray matter atrophy in patients with CSVD has not been fully elucidated. This question was tested by comparing the gray matter covariance networks in CSVD patients with and without cognitive impairment (CI). Methods We performed multivariate modeling of the gray matter volume measurements of 61 patients with CI (CSVD‐CI), 85 patients without CI (CSVD‐NC), and 108 healthy controls using source‐based morphological analysis (SBM) to obtain gray matter structural covariance networks at the population level. Then, correlations between structural covariance networks and cognitive functions were analyzed in CSVD patients. Finally, a support vector machine (SVM) classifier was used with the gray matter covariance network as a classification feature to identify CI among the CSVD population. Results The results of the analysis of all the subjects showed that compared with healthy controls, the expression of the thalamic covariance network, cerebellum covariance network, and calcarine cortex covariance network was reduced in patients with CSVD. Moreover, CSVD‐CI patients showed a significant reduction in the expression of the thalamic covariance network, encompassing the thalamus and the parahippocampal gyrus, relative to CSVD‐NC patients, which persisted after excluding CSVD patients with thalamic lacunes. In patients with CSVD, cognitive functions were positively correlated with measures of the thalamic covariance network. More than 80% of CSVD patients with CI were correctly identified by the SVM classifier. Interpretation Our findings provide new evidence to explain the distribution state of gray matter reduction in CSVD patients, and the thalamic covariance network is the core region for early gray matter reduction during the development of CSVD disease, which is related to cognitive deficits. Reduced expression of thalamic covariance networks may provide a neuroimaging biomarker for the early identification of cognitive impairment in CSVD patients.