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Abstract Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC–MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops.

Abstract Hair cell bundles consist of stereocilia arranged in rows of increasing heights, connected by tip links that transmit sound-induced forces to shorter stereocilia tips. Auditory mechanotransduction channel complexes, composed of proteins TMC1/2, TMIE, CIB2, and LHFPL5, are located at the tips of shorter stereocilia. While most components can interact with the tip link in vitro, their ability to maintain the channel complexes at the tip link in vivo is uncertain. Return, using mouse models, we show that an additional component, LOXHD1, is essential for keeping TMC1-pore forming subunits at the tip link but is dispensable for TMC2. Using SUB-immunogold-SEM, we showed that TMC1 localizes near the tip link but mislocalizes without LOXHD1. LOXHD1 selectively interacts with TMC1, CIB2, LHFPL5, and tip-link protein PCDH15. Our results demonstrate that TMC1-driven mature auditory channels require LOXHD1 to stay connected to the tip link and remain functional, while TMC2-driven developmental channels do not.

Abstract Electron microscopy paired with immunogold labeling is the most precise tool for protein localization. However, these methods are either cumbersome, resulting in small sample numbers and restricted quantification, or limited to identifying protein epitopes external to the membrane. Here, we introduce SUB-immunogold-SEM, a scanning electron microscopy technique that detects intracellular protein epitopes proximal to the membrane. We identify four critical sample preparation factors contributing to the method’s sensitivity. We validate its efficacy through precise localization and high-powered quantification of cytoskeletal and transmembrane protein distribution. We evaluate the capabilities of SUB-immunogold-SEM on cells with highly differentiated apical surfaces: (i) auditory hair cells, revealing the presence of nanoscale MYO15A-L rings at the tip of stereocilia; and (ii) respiratory multiciliate cells, mapping the distribution of the SARS-CoV-2 receptor ACE2 along the motile cilia. SUB-immunogold-SEM extends the application of SEM-based nanoscale protein localization to the detection of intracellular epitopes on the exposed surfaces of any cell.

Rapeseed meal is a promising food ingredient, but its utilization is limited by the presence of some potentially harmful ingredients, such as glucosinolates. Fermentation is a cost-effective method of detoxication but a food-grade starter culture with glucosinolates degradation capacity is required. In this study, 46 strains of lactic acid bacteria from traditional paocai brines were screened for their ability to glucosinolate degradation. The results showed that more than 50% of the strains significantly degraded glucosinolates. Two strains of Lactiplantibacillus (p7 and s7) with high capacity of glucosinolates degradation through producing enzymes were identified. Then, an optimized condition for rapeseed meal fermentation by p7 was established to degrade glucosinolates, which can achieve about 80% degradation. UPLC/Q-TOF-MS analysis showed that the degradation rate of individual glucosinolates was different and the degradation rate of gluconapin and progoitrin in rapeseed meal can reach more than 90%. Meanwhile, fermentation with p7 can improve safety of rapeseed meal by inhibiting the growth of Enterobacteriaceae and improve its nutritional properties by degrading phytic acid. The in vitro digestion experiments showed that the content of glucosinolates in rapeseed meal decreased significantly during gastric digestion. Meanwhile, fermentation with p7 can greatly improve the release of soluble protein and increase the contents of free essential amino acids, such as lysine (increased by 12 folds) and methionine (increased by 10 folds).

Wheat bran, a principal byproduct of flour milling, stands as an abundant source of dietary fiber, yet its economic potential remains under-exploited in current forage applications. Arabinoxylan (AX), constituting the core of dietary fiber, emerges as a versatile compound with multifaceted functionalities. Its nutritional significance, coupled with its role in cereal food processing, has prompted a surge of studies focusing on the valorization of wheat bran AX. Moreover, the hydrolyzed derivative, arabinoxylan oligosaccharides (AXOS), demonstrates prebiotic and antioxidant properties, offering potential avenues to mitigate the risk of chronic diseases. This review summarizes current knowledge on the valorization of wheat bran AX in terms of the processing and nutritional properties of AX. Moreover, multiple novel applications of AX in the materials area, including biodegradable food packaging films, delivery of bioactive substances as nanoparticles, and the manufacture of food emulsifiers, are also highlighted to extend the utilization of AX. This review underscores the immense potential of wheat bran AX, advocating for its exploitation not only as a nutritional asset but also as a primary ingredient in advanced materials. The synthesis of nutritional and materials perspectives accentuates the multifaceted utility of wheat bran AX, thereby paving the way for sustainable valorization pathways. By unraveling the latent potential within AX, this paper advocates for the holistic and sustainable utilization of wheat bran in diverse, value-added applications.

Abstract Background Early detection of colorectal cancer (CRC) significantly enhances patient outcomes. Conventional CRC screening tools, like endoscopy and stool-based tests, have constraints due to their invasiveness or suboptimal patient adherence. Recently, liquid biopsy employing plasma cell-free DNA (cfDNA) has emerged as a potential noninvasive screening technique for various malignancies. Methods In this research, we harnessed the Mutation Capsule Plus (MCP) technology to profile an array of genomic characteristics from cfDNA procured from a single blood draw. This profiling encompassed DNA methylation, the 5’ end motif, copy number variation (CNV), and genetic mutations. An integrated model built upon selected multiomics biomarkers was trained using a cohort of 93 CRC patients and 96 healthy controls. Results This model was subsequently validated in another cohort comprising 89 CRC patients and 95 healthy controls. Remarkably, the model achieved an area under the curve (AUC) of 0.981 (95% confidence interval (CI), 0.965–0.998) in the validation set, boasting a sensitivity of 92.1% (95% CI, 84.5%-96.8%) and a specificity of 94.7% (95% CI, 88.1%-98.3%). These numbers surpassed the performance of any single genomic feature. Importantly, the sensitivities reached 80% for stage I, 89.2% for stage II, and were 100% for stages III and IV. Conclusion Our findings underscore the clinical potential of our multiomics liquid biopsy test, indicating its prospective role as a noninvasive method for early-stage CRC detection. This multiomics approach holds promise for further refinement and broader clinical application.

Abstract Introduction The EQ Health and Wellbeing (EQ-HWB) is a new questionnaire for measuring quality of life (QoL) from a broad perspective. The items of the EQ-HWB were derived based on a ‘qualitative review’ of literature, which reported primarily on Western studies. It can be argued that the QoL is a cultural-related concept and therefore people from China have a different understanding of the QoL. This study aimed to explore whether Chinese citizens could understand the EQ-HWB’s candidate items and what they thought of those items. In doing so, we wanted to examine the face validity of the candidate items and explore if further cultural adaptation is necessary. Methods This research was part of the E-QALY project, in which 36 candidate items were selected for the EQ-HWB from a 97-item pool. In China, three interviewers investigated the face validity of these EQ-HWB candidate items in semi-structured qualitative face-to-face interviews. Respondents were invited to report ‘problems’ with regard to the interpretation of the items and these problems were grouped into themes. We explored to what extent those themes related to specific cultural aspects in China. We also classified the rates of reported problems for each item into three groups: 1) less than 20%, 2) from 20–50%, and 3) over 50%. Results For 17 items the rate of reported problems was less than 20%, 15 items fell into the second group (with 20 − 50%) and for 4 items the rate of problems reported was more than 50%. The thematic analysis revealed eight themes: ambiguous problems in the interpretation of 16 items; difficult to understand (11); contained a complex negative expression (10); examples used seemed inappropriate (7); misleading connotation in Chinese (2); long and complex (2); complex response options (1); and use of non-colloquial language (1). Discussion Our research shows that EQ-HWB candidate items require careful examination to make them more comprehensible. Most of the reported problem themes were generic problems related to the items, and only a few face validity issues appeared to relate to specific cultural aspects in China, even though most of the items were based on Western studies. Our findings are reassuring for the instrument’s international application, especially in China.

Abstract Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

Abstract On a global note, oral health plays a critical role in improving the overall human health. In this vein, dental-related issues with dentin exposure often facilitate the risk of developing various oral-related diseases in gums and teeth. Several oral-based ailments include gums-associated (gingivitis or periodontitis), tooth-based (dental caries, root infection, enamel erosion, and edentulous or total tooth loss), as well as miscellaneous diseases in the buccal or oral cavity (bad breath, mouth sores, and oral cancer). Although established conventional treatment modalities have been available to improve oral health, these therapeutic options suffer from several limitations, such as fail to eradicate bacterial biofilms, deprived regeneration of dental pulp cells, and poor remineralization of teeth, resulting in dental emergencies. To this end, the advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources. This review presents a comprehensive overview of different nanoarchitectured composites for improving overall oral health. Initially, we emphasize various oral-related diseases, providing detailed pathological circumstances and their effects on human health along with deficiencies of the conventional therapeutic modalities. Further, the importance of various nanostructured components is emphasized, highlighting their predominant actions in solving crucial dental issues, such as anti-bacterial, remineralization, and tissue regeneration abilities. In addition to an emphasis on the synthesis of different nanostructures, various nano-therapeutic solutions from diverse sources are discussed, including natural (plant, animal, and marine)-based components and other synthetic (organic- and inorganic-) architectures, as well as their composites for improving oral health. Finally, we summarize the article with an interesting outlook on overcoming the challenges of translating these innovative platforms to clinics. Graphical abstract

Abstract The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

Abstract Background Virtual reality (VR) and augmented reality (AR) are emerging technologies that can be used for cardiopulmonary resuscitation (CPR) training. Compared to traditional face-to-face training, VR/AR-based training has the potential to reach a wider audience, but there is debate regarding its effectiveness in improving CPR quality. Therefore, we conducted a meta-analysis to assess the effectiveness of VR/AR training compared with face-to-face training. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, and Wanfang databases from the inception of these databases up until December 1, 2023, for randomized controlled trials (RCTs) comparing VR- and AR-based CPR training to traditional face-to-face training. Cochrane's tool for assessing bias in RCTs was used to assess the methodological quality of the included studies. We pooled the data using a random-effects model with Review Manager 5.4, and assessed publication bias with Stata 11.0. Results Nine RCTs (involving 855 participants) were included, of which three were of low risk of bias. Meta-analyses showed no significant differences between VR/AR-based CPR training and face-to-face CPR training in terms of chest compression depth (mean difference [MD], -0.66 mm; 95% confidence interval [CI], -6.34 to 5.02 mm; P = 0.82), chest compression rate (MD, 3.60 compressions per minute; 95% CI, -1.21 to 8.41 compressions per minute; P = 0.14), overall CPR performance score (standardized mean difference, -0.05; 95% CI, -0.93 to 0.83; P = 0.91), as well as the proportion of participants meeting CPR depth criteria (risk ratio [RR], 0.79; 95% CI, 0.53 to 1.18; P = 0.26) and rate criteria (RR, 0.99; 95% CI, 0.72 to 1.35; P = 0.93). The Egger regression test showed no evidence of publication bias. Conclusions Our study showed evidence that VR/AR-based training was as effective as traditional face-to-face CPR training. Nevertheless, there was substantial heterogeneity among the included studies, which reduced confidence in the findings. Future studies need to establish standardized VR/AR-based CPR training protocols, evaluate the cost-effectiveness of this approach, and assess its impact on actual CPR performance in real-life scenarios and patient outcomes. Trial registration CRD42023482286.

Abstract To assess the health utility value (HUV) of Rheumatoid Arthritis (RA) patients and its influencing factors in China. A cross-sectional survey was conducted in 8 tertiary hospitals across four capital-cities. The demographic characteristics, patient-reported outcomes including the HUV got by EQ-5D-5L, clinical characteristics, and clinician-reported outcomes of 171 RA patients were collected both from themselves and their physicians. Both the univariate and multivariate analyses were used to assess the potential factors of EQ-5D-5L HUV of the patients. The mean age of the patients was 50.7 years, with female being 64.9% (n = 111). The mean HUV and EQ visual analogue scale score of all patients were 0.586 and 47.3, respectively. The univariate analysis showed that the patients who were female, older, living in rural areas, with lower education level, advanced disease stage, higher the patient's assessment of arthritis pain visual analogue scale (PtAAP-VAS), the patient's global assessment of disease activity visual analogue scale (PtGADA-VAS), and the Physician’s global assessment of disease activity visual analogue scale (PhGADA-VAS) scores had significantly lower EQ-5D-5L HUVs. The multivariate analysis further suggested that older age, female, higher body mass index and higher PtGADA-VAS score were statistically significantly related to lower HUVs. The study provided the HUVs for RA patients with different characteristics and outcomes, which could be used in the economic evaluation of interventions for the RA patients. The identified factors could also assist the health care managing and improving the health-related quality of life on RA patients.

Abstract Background Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. Methods 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1–2, and the moderate neuromuscular block group maintained TOF = 1–2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. Results MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg−1·h−1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), μg·kg−1·min−1, P

Abstract To assess the efficacy of stent grafts (SGs) in managing central venous obstruction disease (CVOD) in hemodialysis (HD) patients with arteriovenous (AV) access, and to identify predictive factors influencing the SG treatment outcomes. HD subjects with CVOD who underwent SGs placement at our center between August 2018 and June 2022 were enrolled. Survival curve analysis using the Kaplan–Meier method and log-rank test was performed. Cox proportional hazards regression analysis was employed to identify predictive factors associated with outcomes. A total of 59 SG implantation procedures for CVOD were analyzed, comprising 30 cases of stenosis and 29 cases of occlusion. The access circuit primary patency (ACPP) at 6, 12, and 24 months post-SG placement were 80.9%, 53.8%, and 31.4%, respectively, while, the target lesion primary patency (TLPP) were 91.3%, 67.6%, and 44.5%, respectively. Subgroup analysis revealed higher TLPP in the stenosis group compared to the occlusion group, although the difference was not statistically significant (P = 0.165). The TLPP was significantly improved by SG placement in those who had antecedent balloon dilations (P

Abstract Background Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. Case presentation The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. Conclusion Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

Abstract Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.

The current trend of increasing the precision lifetime of high-performance bearings forces scientists and engineers to optimize the heat treatment and processing technology to endure higher fatigue frequencies from rolling/sliding motion. In this study, the influences of two crucial factors, hardness and spherical carbides, on the wear behavior of AISI 52100 bearing steel were investigated using elaborate heat treatments to control the variables. The results showed that avoiding excessive hardness and improving the content of spherical carbides could reduce the wear volume during sliding friction and enhance wear resistance. On the one hand, high hardness is correlated to high carbon concentration and high micro-plastic strain in the martensite matrix, inducing the propagation of microcracks and formation of large-size shallow micro-pitting, which accelerates wear loss. On the other hand, spherical carbides effectively inhibit severe plastic deformation of the martensite matrix, which inhibits the wear loss caused by micro-cutting and decreases the formation of wear debris. In this case, densely distributed carbides can improve the wear performance.

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

Abstract This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs.

Abstract Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients’ health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient’ health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants. Methods A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL. Results A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well. Conclusion Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.

Logistics is playing a significant role in supporting economic growth and material security during the epidemic period and it has been experiencing a rapid development in recent years. With the issues of personalisation and cost, the economy and society ask for higher requirements for logistics storage systems. The rational design of the functional area layout is an essential step to improve the operational efficiency of the logistics warehousing system. In reality, due to warehouse design and equipment application, there has been a gradual increase in irregular warehouses. By taking an irregular warehouse as an example, combining the operation status quo, this paper clarifies the functional area settings and constructs a 0–1 integer planning model based on the grid and systematic layout planning method with constraints, such as the unique functional attributes of the grid. We optimised the genetic algorithm based on the warehouse irregularity factor and the grids factor, and then solve it through MATLAB. Finally, by using the Flexsim software, simulation metrics were selected for evaluation, the method feasibility is verified.

Neighborhood relationships play a pivotal role in rough set theory, addressing the limitations of equivalence relations. This article focuses on defining upper and lower approximation operators using neighborhood relationships and exploring their properties in terms of serialization, inverse serialization, reflexivity, symmetry, transitivity, and Euclidean relations. Furthermore, a necessary and sufficient condition for the upper approximation operator to function as a topological closure operator is derived. Overall, this research sheds light on the significance of neighborhood relationships and their implications within rough set theory.

Abstract Background Prior research has reaffirmed lifestyle risk behaviors to cluster among adolescents. However, the lifestyle cluster effect on suicidal thoughts and behaviors (STBs) was unclear among adolescents in low- and middle-income countries (LMICs). No comparison of such associations was conducted across nations. Methods Data from 45 LMICs were obtained from the Global School-based Student Health Survey (GSHS) between 2009 and 2019. Lifestyle behavior factors were collected through a structured questionnaire. Suicidal ideation, plan, and attempt were ascertained by three single-item questions. Lifestyle risk scores were calculated via a sufficient dimension reduction technique, and lifestyle risk clusters were constructed using a latent class analysis. Generalized linear mixed models with odds ratio (OR) and 95% confidence interval (CI) were used to estimate the lifestyle-STB associations. Results A total of 229,041 adolescents were included in the final analysis. The weighted prevalence of suicidal ideation, plan, and attempt was 7.37%, 5.81%, and 4.59%, respectively. Compared with the favorable lifestyle group, the unfavorable group had 1.48-, 1.53-, and 3.11-fold greater odds of suicidal ideation (OR = 1.48, 95%CI: 1.30–1.69), plan (OR = 1.53, 95%CI 1.34–1.75), and attempt (OR = 3.11, 95%CI 2.64–3.65). Four clusters of lifestyle risk behaviors were identified, namely healthy lifestyles (H–L), insufficient intake of vegetables and fruit (V-F), frequent consumption of soft drinks and fast food (D-F), and tobacco smoking and alcohol drinking (S-A) clusters. Compared with H–L cluster, V-F cluster was associated with 43% and 42% higher odds of suicidal ideation and plan, followed by S-A cluster (26% for ideation and 20% for plan), but not significant in D-F cluster (P > 0.05). D-F cluster was associated with 2.85-fold increased odds of suicidal attempt, followed by V-F cluster (2.43-fold) and S-A cluster (1.18-fold). Conclusions Clustering of lifestyle risk behaviors is informative for risk stratification of STBs in resource-poor settings. Lifestyle-oriented suicide prevention efforts should be initiated among school-attending adolescents in LMICs.

Abstract The Chinese traditional educational primer San Zi Jing (三字经) was immensely appreciated by Western missionaries, who frequently leveraged it to spur Chinese-language learning or to decipher Chinese thought. Walter Henry Medhurst (1796–1857), affiliated with the London Missionary Society (LMS), translated and reconstructed biblical scriptures into the format and style of the Chinese-language San Zi Jing, henceforth referred to as the “disguised San Zi Jing” in this article. The disguised San Zi Jing was initially published in Batavia in 1823 and reprinted in several locations, occasionally with minor modifications to its content. First, this study examines the complex qualities of the original San Zi Jing, which made it an ideal translation target, and the unique natures of the disguised San Zi Jing, which served as the ultimate translation product. Second, referencing Edward Said’s traveling theory, a diachronic investigation finds that the disguised San Zi Jing traveled in four stages, from Nanyang to Lingnan to Jiangnan and finally across Pan-China (more regions of China). Last, the article examines the indigenization process of the disguised San Zi Jing in space and content over time and analyzes the power dynamics underlying indigenization. The study contributes to translation history studies as well as studies of Christianity in China.

Background: Stomach adenocarcinoma (STAD) is one of the most common malignancies. Infection of helicobacter pylori (H. pylori) is a major risk factor that leads to the development of STAD. This study constructed a risk model based on the H. pylori-related macrophages for predicting STAD prognosis. Methods: The single-cell RNA sequencing (scRNA-seq) dataset and the clinic information and RNA-seq datasets of STAD patients were collected for establishing a prognostic model and for validation. The “Seurat” and “harmony” packages were used to process the scRNA-seq data. Key gene modules were sectioned using the “limma” package and the “WGCNA” package. Kaplan-Meier (KM) and Receiver Operating Characteristic Curve (ROC) analyses were performed with “survminer” package. The “GSVA” package was employed for single sample gene set enrichment analysis (ssGSEA). Cell migration and invasion were measured by carrying out wound healing and trans-well assays. Results: A total of 17397 were screened and classified into 8 cell type clusters, among which the macrophage cluster was closely associated with the H. pylori infection. Macrophages were further categorized into four subtypes (including C1, C2, C3, and C4), and highly variable genes of macrophage subtype C4 could serve as an indicator of the prognosis of STAD. Subsequently, we developed a RiskScore model based on six H. pylori -associated genes (TNFRSF1B, CTLA4, ABCA1, IKBIP, AKAP5, and NPC2) and observed that the high-risk patients exhibited poor prognosis, higher suppressive immune infiltration, and were closely associated with cancer activation-related pathways. Furthermore, a nomogram combining the RiskScore was developed to accurately predict the survival of STAD patients. ABCA1 in the RiskScore model significantly affected the migration and invasion of tumor cells. Conclusion: The gene expression profile served as an indicator of the survival for patients with STAD and addressed the clinical significance of using H. pylori-associated genes to treat STAD. The current findings provided novel understandings for the clinical evaluation and management of STAD.

Colorectal cancer (CRC) is a malignant tumor with a high incidence, ranking first among gastrointestinal malignancies. We investigated the impact of polyphyllin I (PPI), a natural compound found in Paris polyphylla, on CRC. PPI has been documented to exhibit anticancer activity against various tumors. This study aimed to assess the effects of PPI on colorectal cancer and explore its potential mechanisms. Our research demonstrated that PPI inhibited proliferation, promoted apoptosis, and induced G2 cell-cycle arrest in a dose-dependent manner. Additionally, our results indicated that PPI suppressed Notch signaling by downregulating the Notch1 receptor, its ligand Jagged1, and the downstream target Hes1 expression. Furthermore, we confirmed the antitumor effect of PPI on patient-derived organoids. In conclusion, our study indicates that PPI impedes the growth of colon cancer by suppressing the Notch signaling pathway.

BackgroundBronchiolitis and pneumonia are both significant lower respiratory tract infections with a profound impact on children’s health. The purpose of this study is to explore the economic burden and related influence factors of pediatric patients with bronchiolitis and pneumonia in China.MethodsA face-to-face interview was employed for the investigation of hospitalized patients (≤5 years old) with bronchiolitis and pneumonia, along with their guardians from January to October 2019. Demographic and costs were collected from Shanghai, Zhengzhou, and Kunming, representing three regions with different levels of economic development in China. Multiple linear regression analysis was used to explore factors associated with the economic burden of the diseases.ResultsA total of 338 patients with bronchiolitis and 529 patients with pneumonia were included in the analysis. The average hospitalization and total cost for patients with bronchiolitis are 4,162 CNY and 5,748 CNY, respectively, while those with pneumonia are 6,096 CNY and 7,783 CNY. Patients from Shanghai, both bronchiolitis and pneumonia, exhibited the lowest cost expenditures, with average total costs of 3,531 CNY and 3,488 CNY, respectively. Multiple regression analysis indicated that, among bronchiolitis patients, factors such as region, medical insurance, relationship, loss of work time, and length of stay were found to be significantly associated with both hospitalization cost and total cost (p

ABSTRACT: Mycoplasma synoviae (MS) is an essential pathogenic mycoplasma in poultry worldwide, posing a serious threat to the poultry industry's health. Timely detection is imperative for early diagnosis, prevention, and control of MS infection. Current laboratory methods for MS detection are generally complicated, time-consuming, and require sophisticated equipment. Therefore, a simple and rapid method is urgently needed. This study developed a novel real-time fluorescence-based recombinase-aided amplification (RF-RAA) technique for detecting MS nucleic acids, enabling target gene amplification within 20 min at 39°C. The RF-RAA outcomes are interpretable in 2 modalities: real-time fluorescence monitoring employing a temperature-controlled fluorescence detector or direct visual inspection facilitated by a portable blue light transilluminator. This method exhibits robust specificity, demonstrating no cross-reactivity with various common poultry pathogens, and achieves high sensitivity, detecting as low as 10 copies/μL for the standard plasmid. Seventy-one clinical samples of chicken throat swabs were detected by RF-RAA and real-time fluorescence quantitative polymerase chain reaction (qPCR) methods. The diagnostic coincidence rates of qPCR with RF-RAA (fluorescence monitoring) and RF-RAA (visual observation) were determined to be 100% and 97.2% (69/71), respectively. In conclusion, the RF-RAA method developed in this study provides a rapid and visually observable approach for MS detection, offering a novel technique to diagnosing MS infection, especially in resource-limited settings.

Abstract Tissue‐engineered extraction products, such as apoptotic extracellular vesicles (ApoEVs), significantly promote tissue regeneration, endowing them with the potential to improve osseointegration. However, there is an urgent need to determine how to effectively load these materials onto a material surface to maximize their function. Considering that all such products have a phospholipid bilayer, a phospholipid‐modified implant coating is designed that can effectively load tissue‐engineered products with a phospholipid bilayer structure. ApoEVs are effectively loaded onto the surface and the osteogenic effect improved, achieving good osseointegration. In vitro experiments show that this material improves angiogenesis by promoting macrophage M1 polarization and NO secretion in the early stages. In vivo experiments show that after implantation, it effectively improve the peri‐implant vascularization of the implant, thereby improving the new bone formation ability and osseointegration. This study provides a universal solution for loading vesicular tissue‐engineered products onto an implant surface and validates its ability to improve bone fusion using ApoEVs as an example while exploring its mechanism.

Abstract Excellent castability, significantly refined microstructure, and good mechanical properties make eutectic high‐entropy alloys (EHEAs) a natural fit for rapid solidification processes, e.g., additive manufacturing. Previous investigations have focused on developing EHEAs through trial and error and mixing known binary eutectic materials. However, eutectic compositions obtained from near‐equilibrium conditions do not guarantee a fully eutectic microstructure under rapid solidifications. In this work, a thermodynamically guided high‐throughput framework is proposed to design EHEAs for rapid solidification. Empirical formulas derived from past experimental observations and thermodynamic computations are applied and considered phase growth kinetics under rapid solidification (skewed phase diagram). The designed alloy candidate, Co25.6Fe17.9Ni22.4Cr19.1Ta8.9Al6.1 (wt.%), contains nanostructured eutectic lamellar and shows a high Vickers hardness of 675 Hv. In addition to this specific composition, the alloy design toolbox enables the development of new EHEAs for rapid solidification without the limitation of previous knowledge.

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P < 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P < 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P < 0.05), while malondialdehyde increased significantly (P < 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P < 0.05), total bile acid secretion decreased significantly (P < 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P < 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P < 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.

ABSTRACT Riverine islands are widespread alluvium wetlands developed in large rivers, and bacterial communities are crucial to their ecological function, yet their assembly processes are rarely addressed. The ecosystem services provided by the middle and the lower Yangtze are primarily threatened by pollution discharge from agricultural land use, and resource overutilization (e.g., embankments), respectively. Here, we assessed bacterial community assembly processes and their drivers within riverine islands in the middle Yangtze River (MR islands) and those in the lower reach (LR islands). A significant distance–decay relationship was observed, although the turnover rate was lower than that of the terrestrial ecosystem with less connectivity. Deterministic and stochastic processes jointly shaped community patterns, and the influence of stochastic increased from 26% in MR islands to 59% for those in LR islands. Meanwhile, the bacterial community in MR islands was controlled more by inorganic nitrogen availability, whereas those in LR islands were governed by pH and EC, although those factors explained a limited fraction of variation in the bacterial community. Potential indicator taxa (affiliated with Nocardioides and Lysobacter) characterized the waterway transport pollution. Overall, our study demonstrated that bacterial community dissimilarity and the importance of dispersal limitation increased concurrently along the flow direction, while distinct local factors further determined bacterial community compositions by selecting habitat-specificity taxa and particularly metabolism function. These findings enhanced our understanding of the mechanisms driving changes in bacterial communities of riverine islands subject to increased anthropogenic impacts.IMPORTANCERivers are among the most threatened ecosystems globally and face multiple stressors related to human activity. However, linkages between microbial diversity patterns and assembly processes in rivers remain unclear, especially in riverine islands developed in large rivers. Our findings reveal that distinct factors result in divergent bacterial community compositions and functional profiles in the riverine islands in the middle Yangtze and those in the lower Yangtze, with substantial differentiation in deterministic and stochastic processes that jointly contribute to bacterial community assemblages. Additionally, keystone species may play important metabolic roles in coping with human-related disturbances. This study provides an improved understanding of relationships between microbial diversity patterns and ecosystem functions under environmental changes in large river ecosystems.

The Hippo pathway plays a central role in tissue development and homeostasis. However, the function of Hippo in pancreatic endocrine development remains obscure. Here, we generated novel conditional genetically engineered mouse models to examine the roles of Hippo pathway-mediated YAP1/TAZ inhibition in the development stages of endocrine specification and differentiation. While YAP1 protein was localized to the nuclei in bipotent progenitor cells, Neurogenin 3 expressing endocrine progenitors completely lost YAP1 expression. Using genetically engineered mouse models, we found that inactivation of YAP1 requires both an intact Hippo pathway and Neurogenin 3 protein. Gene deletion of Lats1 and 2 kinases (Lats1&2) in endocrine progenitor cells of developing mouse pancreas using Neurog3Cre blocked endocrine progenitor cell differentiation and specification, resulting in reduced islets size and a disorganized pancreas at birth. Loss of Lats1&2 in Neurogenin 3 expressing cells activated YAP1/TAZ transcriptional activity and recruited macrophages to the developing pancreas. These defects were rescued by deletion of Yap1/Wwtr1 genes, suggesting that tight regulation of YAP1/TAZ by Hippo signaling is crucial for pancreatic endocrine specification. In contrast, deletion of Lats1&2 using β-cell-specific Ins1CreER resulted in a phenotypically normal pancreas, indicating that Lats1&2 are indispensable for differentiation of endocrine progenitors but not for that of β-cells. Our results demonstrate that loss of YAP1/TAZ expression in the pancreatic endocrine compartment is not a passive consequence of endocrine specification. Rather, Hippo pathway-mediated inhibition of YAP1/TAZ in endocrine progenitors is a prerequisite for endocrine specification and differentiation.

BackgroundThe global prevalence of infertility is 9%, with male factors potentially accounting for 40% to 60% of cases. Conventional treatments can be ineffective, invasive, costly, and linked to adverse effects and high risks. Previous studies have shown that, Chinese herbal medicine (CHM) can regulate the hypothalamus-pituitary-testis axis, improve sperm abnormalities and quality, mitigate oxidative stress, and decrease DNA fragmentation index (DFI). Yet, the evidence backing the use of Chinese herbal medicine (CHM) for treating male factor infertility lacks conviction due to study design limitations, and there remains a scarcity of studies on the live birth rate following CHM treatment for male factor infertility. Here, we describe the rationale and design of a randomized waitlist-controlled trial to evaluate the effect of CHM on the live birth rate among males with infertility.MethodsThis study is a single-center, randomized, waitlist-controlled study. A total of 250 couples diagnosed with male factor infertility will be enrolled in this study and then randomly allocated into two groups in a 1:1 ratio. Male participants in CHM group (treatment group) will receive CHM once a day for 3 months. Male participants in the waitlist group (control group) will not receive any treatment for 3 months. After 3 months, participants in both groups need to be followed up for another 12 months. The primary outcome will be the live birth rate; secondary outcomes include semen quality parameters, DFI and pregnancy related outcomes. Safety will also be assessed.DiscussionThe purpose of this trial is to explore the effects and safety of CHM on the live birth rate among couples dealing with male factor infertility. The outcome of this trial may provide a viable treatment option for male factor infertility.Trial registrationChinese Clinical Trial Registry: ChiCTR2200064416. Registered on 7 October 2022, https://www.chictr.org.cn.

BackgroundSnijders Blok-Campeau syndrome (SNIBCPS) is a rare genetic disorder characterized by facial abnormalities, hypotonia, macrocephaly, and global developmental delay (GDD) caused by mutations in CHD3 gene. There is limited information on SNIBCPS and few studies on its pathogenic gene CHD3.MethodsWe utilized whole-exome sequencing, in vitro minigene splicing assay analysis, and construction of protein models to validate the suspected pathogenic mutation. In addition, the PubMed database was searched using the keywords “Snijders Blok-Campeau syndrome,” “CHD3,” or “SNIBCPS” to summarize the gene mutations and clinical phenotypic characteristics of children with SNIBCPS.ResultsWe identified a non-frameshift variant c.3592_c.3606delGCCAAGAGAAAGATG, a splice site variant c.1708-1G>T, and two missense variants, c. 2954G>C (p.Arg985Pro) and c.3371C>T (p.A1124V), in CHD3 variants with SNIBCPS. Importantly, the c.3592_c.3606delGCCAAGAGAAAGATG, c.1708-1G>T, and c.3371C > T (p.A1124V) loci were not reported, and the children in this study also had phenotypic features of unibrow, transverse palmar creases, tracheal bronchus, and hypomelanosis of Ito (HI). The c.1708-1G>T classical splicing mutation leads to abnormal shearing of mRNA, forming a truncated protein that ultimately affects gene function.ConclusionOur findings have expanded the spectrum of genetic variants and clinical features in children with SNIBCPS. Splicing analysis of CHD3 is an important method to understand the pathogenesis of spliced cells.

The twin boundary (TB) is a planar defect that both destroys the integrity of the crystal and significantly deteriorates the performance of semiconductor devices. However, limited research exists on the initial crystal nucleus kinetics of TB, which is a crucial aspect for a comprehensively understanding the twinning mechanism. Here, the nucleation kinetics process of TB has been thoroughly studied regarding crystal morphology, growth interface at the atomic scale, and first-principle calculations in β-Ga2O3. The nucleation kinetics process of TB originates from the smooth interface growth mode of (100)-B, which requires a significant degree of supercooling. During the crystal growth, the large degree of supercooling in front of the (100)-B plane at the three-phase boundary (TPB) leads to nucleation of TB. The twin type of β-Ga2O3 is recognized as twin-B among the two thermodynamically equivalent structures. It is a glide reflection twin whose glide process initiates with a 1/4 length of the [001] vector and then with a 1/2 length of the [010] vector. This study has developed the nucleation kinetics of TB, thus enriching the theory of crystal defects. The revealed relationship between TB and the smooth interface growth mode holds great significance for guiding the suppression of twins.

Abstract Public concern regarding safety policies serious consequences is anticipated to persist over an extended duration. A study examining a case of rapid public health policy adaptation in China during the COVID-19 epidemic was conducted by gathering public opinion data from major social media platforms. A systematic approach to comprehend public opinion was developed. Five fundamental elements and four dimensions were delineated. An indicator system was established utilizing the K-means text clustering model. Public prediction, expectation, and their evolution underlying public concern were elucidated employing TF–IDF text mining models. The HMM elucidated the way public opinion influences policy adjustments. The findings underscore that public concern regarding enduring events undergoes temporal shifts, mirroring the evolution of public opinion towards policy. Public opinion aroused by both the original event and derived events collaboratively influence policy adjustments. In China, public opinion serves as a mechanism for policy feedback and oversight; notably, negative public sentiment plays a pivotal role in expediting policy transitions. These findings aid in refining policies to mitigate emergencies through a feedback loop, thereby averting the emergence of safety risks such as social unrest prompted by public opinion.

Abstract Background Patient satisfaction is an important outcome domain of patient-centered care. Medical humanization follows the patient-centered principle and provides a more holistic view to treat patients. The COVID-19 pandemic posed significant barriers to maintaining medical humanization. However, empirical study on the relationship between medical humanization and patient satisfaction is clearly absent. Objectives We examined the mediation effects of communication on the relationship between medical humanization and patient satisfaction when faced with a huge public health crisis like the COVID-19 pandemic, and the moderation effect of medical institutional trust on the mediation models. Methods A cross-sectional survey study was performed. A final sample size of 1445 patients was surveyed on medical humanization, communication, patient satisfaction and medical institutional trust. Results All correlations were significantly positive across the main variables (r = 0.35–0.67, p

Abstract Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Abstract A wealth of proteogenomic data has been generated using cancer samples to deepen our understanding of the mechanisms of cancer and how biological networks are altered in association with somatic mutation of tumor suppressor genes, such as TP53 and PTEN. To generate functional signatures of TP53 or PTEN loss, we profiled the RNA and phosphoproteomes of the MCF10A epithelial cell line, along with its congenic TP53- or PTEN-knockout derivatives, upon perturbation with the monofunctional DNA alkylating agent methyl methanesulfonate (MMS) vs. mock treatment. To enable quantitative and reproducible mass spectrometry data generation, the cell lines were SILAC-labeled (stable isotope labeling with amino acids in cell culture), and the experimental design included label swapping and biological replicates. All data are publicly available and may be used to advance our understanding of the TP53 and PTEN tumor suppressor genes and to provide functional signatures for bioinformatic analyses of proteogenomic datasets.

Germinated brown rice is a staple food with high nutritional value and market prospects. Gamma-Aminobutyric Acid (GABA), abundantly present in germinated brown rice, has attracted significant attention due to its multiple active functions on the human body. This study aimed to enrich GABA in germinated brown rice by using static magnetic field pretreatment and NaCl, CaCl2 and KCl stress. After selecting Nanjing9108, which had the highest GABA content among the nine cultivars, a single-factor experiment was conducted and optimized the pretreatment condition as 10 mT static magnetic field for 40 min. Under this condition, the GABA content in brown rice germinated for 36 h was 66.35 mg/100 g, which was 13.88% higher than the control group. Simultaneously, the germination rate and early growth of germinated brown rice were also promoted. The optimal combination of culture medium for GABA enrichment obtained by response surface experimental design was NaCl 37.23 mmol/L, CaCl2 4.71 mmol/L, and KCl 5.75 mmol/L, with a GABA content of 69.783 mg/100 g. Under this condition, the changes in nutrients and the expression of glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T) related genes during the 0-48 h germination process of brown rice were studied. The relative expression of GAD was promoted and the relative expression of GABA-T was inhibited, resulting in the accumulation of GABA. This indicates that the combination of static magnetic field and salt treatment is an effective method to increase the GABA content in germinated brown rice.

The distribution warehouse in the field of trade express is still dominated by manual operation, which has disadvantages in terms of accuracy, timeliness and economy. Choosing intelligent logistics equipment that can meet different operation links and reasonably setting the number of logistics equipment will help to improve the warehouse operation efficiency and reduce the warehouse operation cost. This paper proposes a multi-objective optimization method to solve this problem. We build a collaborative optimization model of multi-type logistics equipment selection and quantity decision to meet the whole process of intelligent distribution warehouse. The model takes the total equipment cost, return on investment and warehouse operation efficiency as the optimization objectives, and considers the constraints of workload satisfaction, equipment utilization, area occupation and selection rules. We use genetic algorithm combined with penalty function to solve the model. The example shows that this method can meet the requirements of intelligent warehouse operation, and realize the economic selection and quantity decision of logistics equipment for loading and unloading, storage, sorting, palletizing and film winding. And furthermore, it is concluded that the shelf access operation can be completed by both loading and unloading equipment, and the total cost is better.

Abstract Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the four most common driver mutations of this disease. Similarly, sorted ductal cells carrying these genetic mutations can also form PDAC, thus experimentally proving that PDACs can originate from both human acinar and ductal cells. RNA-seq analysis reveal the transcriptional shift from normal acinar cells towards PDACs with enhanced proliferation, metabolic rewiring, down-regulation of MHC molecules, and alterations in the coagulation and complement cascade. By comparing PDAC-like cells with normal pancreas and PDAC samples, we identify a group of genes with elevated expression during early transformation which represent potential early diagnostic biomarkers.

Abstract Background Parturients are prone to postdural puncture headache (PDPH) after epidural puncture. Cerebral venous sinus thrombosis (CVST) is a fatal complication of PDPH. The main symptom of both is headache, however, the mechanism is not similar. For persistent PDPH, early differential diagnosis from CVST is essential. Optic nerve sheath diameter (ONSD) measurements can be used to identify changes in intracranial pressure as an auxiliary tool to distinguish the cause of headache. Case presentation The dura of a 32-year-old woman undergoing cesarean section was accidentally penetrated while administering epidural anesthesia, and the patient developed PDPH the subsequent day. The patient refused epidural blood patch (EBP) treatment and was discharged after conservative treatment. Fourteen days post-discharge, she was readmitted for a seizure. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) indicated low cranial pressure syndrome and superior sagittal sinus thrombosis with acute infarction. The next morning, the EBP was performed with 15 ml autologous blood. Subsequently, the headache symptoms decreased during the day and worsened at night. ONSD measurement suggested dilation of the optic nerve sheath, and subsequently, the patient showed intracranial hypertension with papilledema. After dehydration and anticoagulant treatment, the patient’s symptoms were relieved and she was discharged from the hospital 49 days later. Conclusions Headache is the main symptom of PDPH and cerebral venous thrombosis, which are difficult to distinguish. ONSD measurement may help to estimate the intracranial pressure, and early measurement may be helpful for women with PDPH to avoid serious complications, such as CVST.

In this study, a W–1%ZrC spherical powder for additive manufacturing was successfully fabricated by spray granulation combined with radio frequency (RF) plasma spheroidization. 3 μm tungsten powder and the nano-sized ZrC powder were spray granulated into a porous agglomerated powder and then spheroidized to form a dense spherical powder by RF plasma. Spherical W–ZrC powder with a narrow particle size distribution and a uniform distribution of Zr element was obtained, whose flowability and apparent density was 7.5 s/50g and 9.36 g/cm3, respectively. Furthermore, ZrC enters the tungsten grains after plasma spheroidization, which causes dislocations in the tungsten grain. The spherical W–ZrC composite powder is expected to suppress the crack formation of W parts during the laser powder bed fusion process.

Objective: Despite continuous progress in treatment, recurrence and metastasis limit further improvement in the prognosis of breast cancer (BC) patients. Our aim was to search for a crucial prognostic biomarker of BC. Materials and methods: Patient data were selected from The Cancer Genome Atlas (TCGA) and GTEx databases. Several online public databases, including Gene Expression Profiling Interactive Analysis (GEPIA), miRWalk, miRDB, and LncBase Predicted v.2, were used to identify potential upstream miRNAs and lncRNAs. These findings were validated through in vitro experiments. Results: A total of 1, 097 invasive BC samples and 572 normal breast tissues (including 113 samples from TCGA and 459 samples from GTEx) were collected for the study. CCT4 was not only significantly overexpressed in BC compared with normal breast tissues but also had important prognostic significance (P

Multi-material additive manufacturing holds immense potential for performance and functionality enhancement. Past research efforts primarily focused on the horizontal interface (perpendicular to the sample build direction) during the laser-powder bed fusion (LPBF) of multi-materials, whereas a few studies demonstrated that the vertical interface (parallel to the sample build direction) is in fact the main obstacle towards high-integrity multi-material fabrication in a three-dimensional space. In this work, facilitated by our own patented powder spreading device, we explored the mechanisms behind defect formation along both the horizontal and vertical interfaces during the LPBF production of 316L stainless steel and K220 copper multi-materials. High-fidelity fluid dynamics simulations were also conducted to rationalise the experimental observations. A practical process parameter optimisation approach is also proposed at the end, with the aim of mitigating those large defects currently occurring near the vertical interface.

Background: Cardiovascular diseases (CVDs) remain the leading cause of global mortality, with dyslipidemia recognized as a significant risk factor. Dyslipidemia, characterized by elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), is associated with an increased lifetime risk of CVD. Although alfalfa’s cholesterol-lowering effects have been demonstrated in animal models, clinical trial data supporting its efficacy in human dyslipidemia treatment are limited. Methods: A randomized controlled trial was conducted from September 20, 2021, to January 12, 2023, involving patients diagnosed with dyslipidemia. Approved by the China Ethics Committee of Registering Clinical Trials, the study included multiple sites in China. Eligible participants were adults aged 18 years or older, meeting criteria from the Chinese Guidelines for the Prevention and Treatment of Adult Blood Lipid Disorders. Participants were randomly assigned to either a health education-only group or a combined alfalfa powder supplementation and health education group for a three-month intervention period. Results: A total of 160 eligible patients were enrolled and randomized into two groups: the Alfalfa group (n = 80) and the Education group (n = 80). The intervention resulted in significant improvements in key lipid parameters in the Alfalfa group, including reductions in TC, LDL-C, and Apo A1 levels. Although changes in HDL-C levels were not significantly different between the groups, the Alfalfa group exhibited a larger increase. Serum lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the combined intervention did not significantly alter the overall blood lipid metabolome but identified fifteen regulated differential metabolites, with the glycerophospholipid metabolism pathway significantly affecting lipid metabolism levels. Conclusion: Supplementation with alfalfa powder combined with health education significantly reduced TC, LDL-C, and Apo A1 levels in patients with dyslipidemia. KEGG pathway analysis suggests an association between the glycerophospholipid metabolism pathway and dyslipidemia. Further research is warranted to validate these findings and explore the underlying mechanisms.

As the global population ages, the incidence of Parkinson's Disease (PD) continues to rise, imposing significant social and economic burdens. Mangiferin (MGF), a polyphenolic, bioactive compound has been shown to play a role in the prevention and treatment of PD. This study investigates the neuroprotective effects of MGF in an MPTP-induced zebrafish model of PD through transcriptome analysis. Initially, optimal concentrations for modeling were determined using various MPTP and MGF combinations. The zebrafish were then divided into control, MPTP-treated, and MGF co-treated groups. Subsequent evaluations included hatching rates, mortality rates, growth and development conditions, spontaneous motor abilities, as well as measurements of enzymatic activities of SOD, CAT, and levels of GSH. Ultimately, the therapeutic efficacy of MGF on the PD model in zebrafish was assessed through transcriptome sequencing. The results demonstrated that MPTP treatment induced PD-associated symptoms in zebrafish, while MGF treatment significantly improved the motor abilities and survival rates of the PD model zebrafish, effectively reducing oxidative stress and ameliorating PD symptoms. Transcriptome sequencing further revealed that MGF may mitigate mitochondrial-related oxidative stress in PD zebrafish by modulating the expression of critical genes including lrrk2, vps35, atp13a, dnajc6, and uchl1. Differential gene expression analysis indicated that these genes are primarily involved in vital signaling pathways, such as neuroactive ligand-receptor interaction, and the calcium signaling pathway. In summary, our study provides robust scientific evidence supporting MGF as a potential therapeutic candidate for PD by preserving mitochondrial homeostasis and elucidating its mechanisms of action.

Cigarette smoke (CS) is a prevalent chemical indoor air contaminant known to be the primary cause of EMT during airway remodeling in COPD. While some evidence indicates the involvement of SMAD4 in EMT across certain diseases, its specific role in CS-induced EMT in airway remodeling associated with COPD is not established. In our research, we observed a substantial upregulation in SMAD4 expression, O-GlcNAcylation and EMT in patients with COPD, as well as in vitro and in vivo COPD models induced by CS, than those of the controls. Downregulation of SMAD4 resulted in a reduction in CS-induced EMT in vitro and in vivo. As a post-translational modification of proteins, O-GlcNAcylation is dynamically controlled by the duo of enzymes: O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and O-GlcNAcase (OGA). We further discovered the enhancement of O-GlcNAcylation levels induced by CS was due to an elevated OGT expression, as the expression of OGA remained unchanged. Using an OGT inhibitor (OSMI-1) counteracted the effects of SMAD4 on EMT. Whereas, overexpressing OGT increased SMAD4 expression and promoted EMT. OGT-mediated SMAD4 O-GlcNAcylation shielded SMAD4 from proteasomal degradation by reducing its ubiquitination, thereby aiding in SMAD4 stabilization in response to EMT induced by CS. Overall, this research uncovers a fresh pathway for CS-induced EMT in the airway remodeling of COPD and offers valuable insights.