Search

Abstract Background Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury. Methods We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis. Results Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1β and IL-1β in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion. Conclusions These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients. Graphical Abstract

Abstract Chemodynamic therapy represents a novel tumor therapeutic modality via triggering catalytic reactions in tumors to yield highly toxic reactive oxygen species (ROS). Nevertheless, low efficiency catalytic ability, potential systemic toxicity and inefficient tumor targeting, have hindered the efficacy of chemodynamic therapy. Herein, a rationally designed catalytic nanoplatform, composed of folate acid conjugated liposomes loaded with copper peroxide (CP) and chloroquine (CQ; a clinical drug) (denoted as CC@LPF), could power maximal tumor cytotoxicity, mechanistically via maneuvering endogenous and exogenous copper for a highly efficient catalytic reaction. Despite a massive autophagosome accumulation elicited by CP-powered autophagic initiation and CQ-induced autolysosomal blockage, the robust ROS, but not aberrant autophagy, underlies the synergistic tumor inhibition. Otherwise, this combined mode also elicits an early onset, above all, long-term high-level existence of immunogenic cell death markers, associated with ROS and aberrant autophagy -triggered endoplasmic reticulum stress. Besides, CC@LPF, with tumor targeting capability and selective tumor cytotoxicity, could elicit intratumor dendritic cells (mainly attributed to CQ) and tumor infiltrating CD8+ T cells, upon combining with PD-L1 therapeutic antibody, further induce significant anti-tumor effect. Collectively, the rationally designed nanoplatform, CC@LPF, could enhance tumor chemoimmunotherapy via deploying endogenous plus exogenous copper and remodeling tumor microenvironment. Graphical abstract

Introduction:: Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Objectives:: Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. Methods:: We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. Results:: The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. Conclusions:: These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography.

Abstract Various low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

Abstract Soft magnetic materials with stable permeability up to hundreds of megahertz (MHz) are urgently needed for integrated transformers and inductors, which are crucial in the more-than-Moore era. However, traditional frequency-stable soft magnetic ferrites suffer from low saturation magnetization and temperature instability, making them unsuitable for integrated circuits. Herein, we fabricate a frequency-stable soft magnetic composite featuring a magnetic vortex structure via cold-sintering, where ultrafine FeSiAl particles are magnetically isolated and covalently bonded by Al2SiO5/SiO2/Fe2(MoO4)3 multilayered heterostructure. This construction results in an ultrastable permeability of 13 up to 1 gigahertz (GHz), relatively large saturation magnetization of 105 Am2/kg and low coercivity of 48 A/m, which we ascribe to the elimination of domain walls associated with almost uniform single-vortex structures, as observed by Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the ultimate compressive strength has been simultaneously increased up to 337.1 MPa attributed to the epitaxially grown interfaces between particles. This study deepens our understanding on the characteristics of magnetic vortices and provides alternative concept for designing integrated magnetic devices.

Abstract Recent progress on the signatures of pressure-induced high-temperature superconductivity in Ruddlesden–Popper (RP) nickelates (La n+1Ni n O3n+1) has attracted growing interest in both theoretical calculations and experimental efforts. The fabrication of high-quality single-crystalline RP nickelate thin films is critical for possible reducing the superconducting transition pressure and advancing applications in microelectronics in the future. In this study, we report the observations of an active phase transition in RP nickelate films induced by misfit strain. We found that RP nickelate films favor the perovskite structure (n = ∞) under tensile strains, while compressive strains stabilize the La3Ni2O7 (n = 2) phase. The selection of distinct phases is governed by the strain dependent formation energy and electronic configuration. In compressively strained La3Ni2O7, we experimentally determined the e g splitting energy is ~0.2 eV and electrons prefer to occupy in-plane orbitals. First-principles calculations unveil a robust coupling between strain effects and the valence state of Ni ions in RP nickelates, suggesting a dual driving force for the inevitable phase co-existence transition in RP nickelates. Our work underscores the sensitivity of RP nickelate formation to epitaxial strain, presenting a significant challenge in fabricating pure-phase RP nickelate films. Therefore, special attention to stacking defects and grain boundaries between different RP phases is essential when discussing the pressure-induced superconductivity in RP nickelates.

During shield tunneling construction, a significant amount of waste muck is generated, presenting challenges due to its high volume, complex composition, and difficult disposal. Effectively managing this muck has become a pressing issue in shield tunneling projects. This study uses the Nanjing Metro Line 5 shield tunneling project as a case study, employing shield tunneling muck to prepare eco-grouting materials. The research investigates the operational and mechanical properties of these grouting materials. Optimal slurry densities and mixing ratios for two types of shield tunneling muck were proposed, and the curing mechanism of grouting materials was analyzed. These eco-grouting materials are then applied in real engineering projects, and their efficacy is verified through surface subsidence monitoring. The findings reveal that a slurry density of 1.65 for Line 5 muck and 1.55 for Line 9 muck, mixed in a 2:1 ratio, result in composite slurries with superior comprehensive performance concerning apparent density, consistency, setting time, water permeability rate, stone formation rate, compressive strength, and water-land strength ratio. The increased content of C-S-H and AFt in these composite slurries effectively fills internal voids, thereby enhancing material performance. The maximum surface settlement during muck grouting construction is approximately 20 mm, significantly less than the approximately 25 mm observed with conventional grouting materials, underscoring the superior effectiveness of eco-grouting materials in shield tunneling.

GlcNAc2-epimerase myopathy is a rare autosomal recessive myopathy characterized by distal involvement in the lower extremities. Our study reprogrammed human-induced pluripotent stem cells from peripheral blood mononuclear cells of a patient with GNE gene deep intronic variant c.862 + 870C>T and c.478C>T compound heterozygous mutations that co-segregated with the disease. The generated iPSCs express pluripotent cell markers with no mycoplasma contamination. Additionally, these iPSCs demonstrated pluripotency, the capacity to differentiate into the three germ layers, and maintained normal karyotypes. Importantly, we identified that these iPSCs possess the same specific mutations as the patient, making them a robust model for studying GNE myopathy and developing potential therapeutic interventions.

Introduction The Agatston coronary artery calcification score (CACS) is an assessment index for coronary artery calcification (CAC). This study aims to explore the characteristics of CAC in end-stage kidney disease (ESKD) patients and establish a predictive model to assess the risk of severe CAC in patients.Methods CACS of ESKD patients was assessed using an electrocardiogram-gated coronary computed tomography (CT) scan with the Agatston scoring method. A predictive nomogram model was established based on stepwise regression. An independent validation cohort comprised of patients with ESKD from multicentres.Results 369 ESKD patients were enrolled in the training set, and 127 patients were included in the validation set. In the training set, the patients were divided into three subgroups: no calcification (CACS = 0, n = 98), mild calcification (0 400, n = 130). Among the four coronary branches, the left anterior descending branch (LAD) accounted for the highest proportion of calcification. Stepwise regression analysis showed that age, dialysis vintage, β-receptor blocker, calcium-phosphorus product (Ca × P), and alkaline phosphatase (ALP) level were independent risk factors for severe CAC. A nomogram that predicts the risk of severe CAC in ESKD patients has been internally and externally validated, demonstrating high sensitivity and specificity.Conclusion CAC is both prevalent and severe in ESKD patients. In the four branches of the coronary arteries, LAD calcification is the most common. Our validated nomogram model, based on clinical risk factors, can help predict the risk of severe coronary calcification in ESKD patients who cannot undergo coronary CT analysis.

Abstract Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop‐CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop‐CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child–Pugh grades and the Model for End‐stage Liver Disease and Sodium (MELD‐Na) scores in the test and validation cohort. The EuroQol 5‐D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop‐CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Given the dual roles in immune function and metabolism, the liver emerge as a compelling candidate to bridge host defense and metabolic adjustments during pathogen infections in teleosts. In order to dissect the roles of the liver in the immune response of Sebastes schlegelii, we conducted an investigation into the activities of SOD, CAT and GPX4, performed a systematic analysis of circRNA, miRNA and mRNA expression profiles, as well as constructed circRNA-miRNA-mRNA regulatory networks in the liver of S. schlegelii following Aeromonas salmonicida infection were performed in the present study. The present results demonstrated the content of SOD, CAT and GPX4 increased significantly at early infection stage to protect the liver tissue from excessive damage. Additionally, 622 circRNA-miRNAs pairs, 78 miRNA-mRNA pairs and 327 circRNA-miRNA-mRNA pairs were identified in our study. These differently expressed circRNAs and miRNAs were found to be associated with the regulation of LMNB1, DMBT1, NAMPT, IFIT1, CELSRs, PYGL. GO and KEGG enrichment analysis revealed that these differently expressed genes were involved in TLR signal pathway, RLRs signal pathway, PPAR signal pathway, shedding light on antibacterial ceRNA networks within the liver of S. schlegelii post A. hydrophila post infection, which provides new insights into the immune mechanisms of teleost.

IntroductionStudies on the effect of vaccine type and two other vaccines other than inactivated vaccines approved in China on in vitro fertilization (IVF) pregnancy outcomes are rare. To complement and confirm the existing findings, this research aimed to investigate whether there are adverse effects of different vaccine types in females and males on reproductive function and clinical pregnancy.MethodsThis retrospective study enrolled 6,455 fresh embryo transfer cycles at the First Affiliated Hospital of Zhengzhou University between May 1, 2021, and October 31, 2022. The primary outcome is the clinical pregnancy rate (CPR). At the same time, the secondary results are the number of oocytes retrieved, two pronuclei (2PN) rate, blastocyst formation rate, high-quality blastocyst rate, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DNA fragment index (DFI) rate).ResultsIn the comparison of ovarian stimulation indicators, no statistically significant differences (P > 0.05) were found in Gn days, endometrial thickness, 2PN rate, metaphase 2 (MII) rate, high-quality embryo rate, and blastocyst formation rate. No significant differences (P>0.05) were found in age, body mass index (BMI), education level, and semen parameters (volume, density, sperm count, forward motility rate, total motility rate, immobility rate, and DFI rate) in these four groups. The multivariate regression model showed that neither the types of vaccines nor the vaccination status of both infertile couples significantly affected clinical pregnancy.DiscussionThe type of vaccine does not appear to have an unfavorable effect on ovarian stimulation, embryo development, semen parameters, and clinical pregnancy.

The compound known as Sodium arsenite (NaAsO2), which is a prevalent type of inorganic arsenic found in the environment, has been strongly associated with liver fibrosis (LF), a key characteristic of nonalcoholic fatty liver disease (NAFLD), which has been demonstrated in our previous study. Our previous research has shown that exposure to NaAsO2 triggers the activation of hepatic stellate cells (HSCs), a crucial event in the development of LF. However, the molecular mechanism is still unknown. N6-methyladenosine (m6A) modification is the most crucial post-transcriptional modification in liver disease. Nevertheless, the precise function of m6A alteration in triggering HSCs and initiating LF caused by NaAsO2 remains unknown. Here, we found that NaAsO2 induced LF and HSCs activation through TGF-β/Smad signaling, which could be reversed by TGF-β1 knockdown. Furthermore, NaAsO2 treatment enhanced the m6A modification level both in vivo and in vitro. Significantly, NaAsO2 promoted the specific interaction of METTL14 and IGF2BP2 with TGF-β1 and enhanced the TGF-β1 mRNA stability. Notably, NaAsO2-induced TGF-β/Smad pathway and HSC-t6 cells activation might be avoided by limiting METTL14/IGF2BP2-mediated m6A modification. Our findings showed that the NaAsO2-induced activation of HSCs and LF is made possible by the METTL14/IGF2BP2-mediated m6A methylation of TGF-β1, which may open up new therapeutic options for LF brought on by environmental hazards.

Abstract Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.

Abstract Harvesting biomechanical energy from cardiac motion is an attractive power source for implantable bioelectronic devices. Here, we report a battery-free, transcatheter, self-powered intracardiac pacemaker based on the coupled effect of triboelectrification and electrostatic induction for the treatment of arrhythmia in large animal models. We show that the capsule-shaped device (1.75 g, 1.52 cc) can be integrated with a delivery catheter for implanting in the right ventricle of a swine through the intravenous route, which effectively converts cardiac motion energy to electricity and maintains endocardial pacing function during the three-week follow-up period. We measure in vivo open circuit voltage and short circuit current of the self-powered intracardiac pacemaker of about 6.0 V and 0.2 μA, respectively. This approach exhibits up-to-date progress in self-powered medical devices and it may overcome the inherent energy shortcomings of implantable pacemakers and other bioelectronic devices for therapy and sensing.

Nicotinamide adenine dinucleotide (NAD+) is an essential metabolite that plays a crucial role in diverse biological processes, including energy metabolism, gene expression, DNA repair, and mitochondrial function. An aberrant NAD+ level mediates the development of cardiovascular dysfunction and diseases. Both in vivo and in vitro studies have demonstrated that nicotinamide mononucleotide (NMN), as a NAD+ precursor, alleviates the development of cardiovascular diseases such as heart failure, atherosclerosis, and myocardial ischemia/reperfusion injury. Importantly, NMN has suggested pharmacological activities mostly through its involvement in NAD+ biosynthesis. Several clinical studies have been conducted to investigate the efficacy and safety of NMN supplementation, indicating its potential role in cardiovascular protection without significant adverse effects. In this review, we systematically summarize the impact of NMN as a nutraceutical and potential therapeutic drug on cardiovascular diseases and emphasize the correlation between NMN supplementation and cardiovascular protection.

Following the recent report by Dasenbrock-Gammon et al. [Nature 615, 244–250 (2023)] of near-ambient superconductivity in nitrogen-doped lutetium trihydride (LuH3−δNε), significant debate has emerged surrounding the composition and interpretation of the observed sharp resistance drop. Here, we meticulously revisit these claims through comprehensive characterization and investigations. We definitively identify the reported material as lutetium dihydride (LuH2), resolving the ambiguity surrounding its composition. Under similar conditions (270–295 K and 1–2 GPa), we replicate the reported sharp decrease in electrical resistance with a 30% success rate, aligning with the observations by Dasenbrock-Gammon et al. However, our extensive investigations reveal this phenomenon to be a novel pressure-induced metal-to-metal transition intrinsic to LuH2, distinct from superconductivity. Intriguingly, nitrogen doping exerts minimal impact on this transition. Our work not only elucidates the fundamental properties of LuH2 and LuH3, but also critically challenges the notion of superconductivity in these lutetium hydride systems. These findings pave the way for future research on lutetium hydride systems, while emphasizing the crucial importance of rigorous verification in claims of ambient-temperature superconductivity.

IntroductionAs a systemic autoimmune disorder, the prognosis of rheumatoid arthritis (RA) is intricately linked to inflammation. This study aimed to investigate the association between the advanced lung cancer inflammation index (ALI), a comprehensive indicator of inflammation combined with nutritional status, and all-cause and cardiovascular mortality among patients diagnosed with RA.MethodsThe 2,305 RA patients from NHANES (2001–2018) included in the analysis were categorized into three groups according to ALI tertiles. Weighted Kaplan–Meier and multivariate COX regression analyses evaluated the relationship between ALI and mortality. The time-dependent characteristic curve (ROC) was used to assess the prediction accuracy of ALI.ResultsDuring a median follow-up of 7.92 years, 591 participants died from all causes, including 197 from cardiovascular diseases. Increased ALI was associated with a decreased probability of death. The full COX model revealed lower all-cause mortality hazard risks in the T2 (HR: 0.67, 95%CI: 0.54–0.83) and T3 (HR: 0.47 95%CI: 0.33–0.67, p for tend

This study delves into the efficiency and structure of the social organization network involved in flood disaster management in China’s Guangdong-Hong Kong-Macao Greater Bay Area (GBA). Leveraging the global knowledge graph, we analyzed social media data and news reports to identify the pivotal roles and interactions of various social organization types in flood disaster governance. The empirical findings underscore the central role of national public social organizations, evidenced by their high frequency of news coverage and mentions. Meanwhile, International Social Organizations and Local Public Social Organizations exhibit growing influence and participation. As China shifts toward a comprehensive disaster reduction strategy, the study observes increased diversity and decentralization among these organizations, with non-governmental organizations and volunteer groups playing vital roles in resource mobilization, information dissemination, and disaster coordination. Network analysis unveils evolving interaction patterns and co-occurrence frequencies among social organizations, reflecting the evolving roles of different organization types in disaster relief. This research aims to provide actionable insights to enhance the effectiveness of social organizations in disaster management, contributing to the establishment of a more resilient and efficient disaster management framework in the GBA.

Three representative purple fleshed sweet potato varieties, Taizishu NO.1, Violet and Vietnamese purple sweet potato were selected as materials. Sensory evaluation, moisture content, starch content, sugar content were explored after baking, steaming and microwave with Pushu NO.32 as the control. Combining with correlation analysis and partial least squares regression (PLSR), the correlations of consumer sensory evaluation and physicochemical property were explored. The sensory evaluation results showed that, Taizishu No.1 obtained the highest score. The sweetness and texture were the driving attributes which could determine consumer preference. The cooking method significantly affected the sensory quality of purple sweet potato. Moisture and starch content of purple sweet potato were decreased after cooking while content of reducing sugar and total sugar were increased. Moreover, sucrose and maltose content increased, while glucose and fructose showed different changes with different varieties and cooking methods. Steaming facilitated water retention and roasting was good for high temperature saccharification during ripening. The correlation analysis showed that the sensory evaluation score was significantly positively correlated with water content and reducing sugar (fructose and glucose) (P

Abstract. Cardiovascular diseases, including heart failure, coronary artery disease, atherosclerosis, aneurysm, thrombosis, and hypertension, are a great economic burden and threat to human health and are the major cause of death worldwide. Recently, researchers have begun to appreciate the role of microbial ecosystems within the human body in contributing to metabolic and cardiovascular disorders. Accumulating evidence has demonstrated that the gut microbiota is closely associated with the occurrence and development of cardiovascular diseases. The gut microbiota functions as an endocrine organ that secretes bioactive metabolites that participate in the maintenance of cardiovascular homeostasis, and their dysfunction can directly influence the progression of cardiovascular disease. This review summarizes the current literature demonstrating the role of the gut microbiota in the development of cardiovascular diseases. We also highlight the mechanism by which well-documented gut microbiota-derived metabolites, especially trimethylamine N-oxide, short-chain fatty acids, and phenylacetylglutamine, promote or inhibit the pathogenesis of cardiovascular diseases. We also discuss the therapeutic potential of altering the gut microbiota and microbiota-derived metabolites to improve or prevent cardiovascular diseases.

Abstract Objective Sjögren’s syndrome (SS) is a rare disease with unclear diagnostic criteria among the children and adolescents. The purpose of this study is to describe the clinical features of pediatric Sjögren’s syndrome and validate with Japanese diagnostic guidelines criteria of 2018. Methods We conducted a retrospective analysis of the clinical data of a cohort of 54 patients with pediatric Sjögren’s syndrome admitted to our hospital over a total of 10 years from September 2013 to September 2022. Results The ratio of females to males was 49:5 among the 54 children (34 cases of primary SS and 20 cases of secondary SS), the average age of onset of symptoms for the first time was 9.9 years, and the average age at diagnosis was 10.2 years. In terms of subjective symptoms, 7 cases (13.0%) presented with dry mouth and 5 cases (9.3%) reported dry eyes. The positive rates were 9.3% for Schirmer I test, 70.4% for salivary gland function test, and 55.6% for salivary gland ultrasonography. The positive rates were 94.4% for Anti-Ro/SSA antibodies, 66.7% for Anti-La/SSB antibodies, 88.9% for ANA, 59.3% for RF, and the elevation rate of IgG was 63.0%. Among the EULAR Sjögren’s syndrome disease activity index (ESSDAI) domains, the biological, constitutional, glandular, cutaneous, and lymphadenopathy domains were most involved. Treatment consisted of glucocorticoids in 88.9% of the patients in our study and hydroxychloroquine in 92.6%. As per the Japanese version of the clinical practice guidance for Sjögren’s Syndrome in pediatric patients (2018), 5 cases were identified as Definite SS, 35 cases as Probable SS, and 14 cases as Possible SS. With respect to primary and secondary SS, there was essentially no significant difference between the groups in any of the above aspects. Conclusions Patients with pediatric SS presented with a wide spectrum of clinical features, a low prevalence of reported symptoms of dry mouth and dry eyes, and various clinical manifestations with multi-system involvement. These are similar to other pediatric study cohorts in terms of epidemiology, auxiliary investigation results, disease activity scores, and treatment. The coincidence between our study and the Japanese version of the clinical practice guidance for Sjögren’s Syndrome in pediatric patients (2018) is good for the diagnosis of pediatric SS.

Abstract. Background:. There are limited data on the resource utilization of total knee arthroplasty (TKA) in China. This study aimed to examine the length of stay (LOS) and inpatient charges of TKA in China, and to investigate their determinants. Methods:. We included patients undergoing primary TKA in the Hospital Quality Monitoring System in China between 2013 and 2019. LOS and inpatient charges were obtained, and their associated factors were further assessed using multivariable linear regression. Results:. A total of 184,363 TKAs were included. The LOS decreased from 10.8 days in 2013 to 9.3 days in 2019. The admission-to-surgery interval decreased from 4.6 to 4.2 days. The mean inpatient charges were 61,208.3 Chinese Yuan. Inpatient charges reached a peak in 2016, after which a gradual decrease was observed. Implant and material charges accounted for a dominating percentage, but they exhibited a downward trend, whereas labor-related charges gradually increased. Single marital status, non-osteoarthritis indication, and comorbidity were associated with longer LOS and higher inpatient charges. Female sex and younger age were associated with higher inpatient charges. There were apparent varieties of LOS and inpatient charges among provincial or non-provincial hospitals, hospitals with various TKA volume, or in different geographic regions. Conclusions:. The LOS following TKA in China appeared to be long, but it was shortened during the time period of 2013 to 2019. The inpatient charges dominated by implant and material charges exhibited a downward trend. However, there were apparent sociodemographic and hospital-related discrepancies of resource utilization. The observed statistics can lead to more efficient resource utilization of TKA in China.

Abstract. In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and immunosuppression. In recent years, with the development of regenerative medicine, the decellularization-recellularization strategy seems to be a promising and attractive method to resolve these difficulties. The decellularized extracellular matrix contains no cells and genetic materials, while retaining the complex ultrastructure, and it can be used as a scaffold for cell seeding and subsequent transplantation, thereby promoting the regeneration of diseased or damaged tissues and organs. This review provided an overview of decellularization-recellularization technique, and mainly concentrated on the application of decellularization-recellularization technique in the field of plastic and reconstructive surgery, including the remodeling of skin, nose, ears, face, and limbs. Finally, we proposed the challenges in and the direction of future development of decellularization-recellularization technique in plastic surgery.

Background: The challenge of emerging antimicrobial resistance and variation in antibiotic use across provinces in China call for knowledge on antibiotic utilization at the regional level. This study aims to evaluate the long-term trends and patterns of antibiotic usage in Xinjiang Province, the largest provincial-level division located in the northwest of China, aiming to provide evidence in enhancing provincial antimicrobial stewardship (AMS) and developing policy measures to optimize regional antimicrobial use. Methods: This was an ecological study with temporal trend analysis on inpatient antibiotic utilization, with antibiotic use data from 92 public hospitals covered by Xinjiang’s Center for Antibacterial Surveillance from 2012 to 2022. Antibiotic use was measured by the number of daily defined doses per 100 patient days (DDDs/100 pds). Patterns of antibiotic use were described by Anatomical Therapeutic Chemical (ATC) subgroups and the Access, Watch, Reserve (AWaRe) classification. The Average Annual Percent Change (AAPC) of antibiotic use and the corresponding 95% confidence intervals (CIs) were calculated to describe the trend of antibiotic use over time. Joinpoint regression was performed using the Weighted Bayesian Information Criteria (WBIC) model with a parametric method. A pairwise comparison between secondary and tertiary hospitals was conducted to explore disparities in antibiotic use across hospital levels. The most commonly used antibiotics were also analyzed. Results: The total inpatient antibiotic use in Xinjiang was 27.6 DDDs/100 patient days in 2022, with a significant decreasing trend during 2012–2022 (AAPC, −2.0%; 95% CI, −3.6% to −0.4%). The Watch group antibiotics were the most used AWaRe category, with the Access-to-Watch ratio decreasing significantly from 46.4% to 24.4% (AAPC, −6.8%; 95% CI, −8.4% to −5.1%). No significant difference was found in the trend of total antibiotic use between secondary and tertiary hospitals, but there were disparities across hospital levels in subgroups. Third-generation cephalosporins, second-generation cephalosporins, and fluoroquinolones remained the top three antibiotic class throughout the study period. The number of antibiotics accounting for 90% of the total antibiotic use decreased from 34 antibiotics in 2012 to 18 antibiotics in 2022. Conclusions: The decreasing trend of inpatient antibiotic use in Xinjiang’s public hospitals reflects the effects of continuous AMS implementation. Patterns of antibiotic use underscore the need for further efforts on evidence-based antibiotic selection and for analyses on the appropriateness of antibiotic use.

Abstract. Background:. Perturbations in bone marrow mesenchymal stem cell (BMSC) differentiation play an important role in steroid-induced osteonecrosis of the femoral head (SONFH). At present, studies on SONFH concentrate upon the balance within BMSC osteogenic and adipogenic differentiation. However, BMSC apoptosis as well as proliferation are important prerequisites in their differentiation. The hedgehog (HH) signaling pathway regulates bone cell apoptosis. Baicalin (BA), a well-known compound in traditional Chinese medicine, can affect the proliferation and apoptosis of numerous cell types via HH signaling. However, the potential role and mechanisms of BA on BMSCs are unclear. Thus, we aimed to explore the role of BA in dexamethasone (Dex)-induced BMSC apoptosis in this study. Methods:. Primary BMSCs were treated with 10–6 mol/L Dex alone or with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA for 24 hours followed by co-treatment with 5.0 μmol/L, 10.0 μmol/L, or 50.0 μmol/L BA and 10–6 mol/L Dex. Cell viability was assayed through the Cell Counting Kit-8 (CCK-8). Cell apoptosis was evaluated using Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining followed by flow cytometry. The imaging and counting, respectively, of Hochest 33342/PI-stained cells were used to assess the morphological characteristics and proportion of apoptotic cells. To quantify the apoptosis-related proteins (e.g., apoptosis regulator BAX [Bax], B-cell lymphoma 2 [Bcl-2], caspase-3, and cleaved caspase-3) and HH signaling pathway proteins, western blotting was used. A HH-signaling pathway inhibitor was used to demonstrate that BA exerts its anti-apoptotic effects via the HH signaling pathway. Results:. The results of CCK-8, Hoechst 33342/PI-staining, and flow cytometry showed that BA did not significantly promote cell proliferation (CCK-8: 0 μmol/L, 100%; 2.5 μmol/L, 98.58%; 5.0 μmol/L, 95.18%; 10.0 μmol/L, 98.11%; 50.0 μmol/L, 99.38%, F = 2.33, P > 0.05), but it did attenuate the effect of Dex on apoptosis (Hoechst 33342/PI-staining: Dex+ 50.0 μmol/L BA, 12.27% vs. Dex, 39.27%, t = 20.62; flow cytometry: Dex + 50.0 μmol/L BA, 12.68% vs. Dex, 37.43%, t = 11.56; Both P

Abstract. Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator -1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.

Abstract. Background:. Despite the advent of innovative knee prosthesis design, a consistent first-option knee implant design in total knee arthroplasty (TKA) remained unsettled. This study aimed to compare the clinical effects among posterior-stabilized (PS), cruciate-retaining (CR), bi-cruciate substituting (BCS), and bi-cruciate retaining designs for primary TKA. Methods:. Electronic databases were systematically searched to identify eligible randomized controlled trials (RCTs) and cohort studies from inception up to July 30, 2021. The primary outcomes were the range of knee motion (ROM), and the secondary outcomes were the patient-reported outcome measures (PROMs) and complication and revision rates. Confidence in evidence was assessed using Confidence in Network Meta-Analysis. The Bayesian network meta-analysis was performed for synthesis. Results:. A total of 15 RCTs and 18 cohort studies involving 3520 knees were included. The heterogeneity and inconsistency were acceptable. There was a significant difference in ROM at the early follow-up when PS was compared with CR (mean difference [MD] = 3.17, 95% confidence interval [CI] 0.07, 7.18) and BCS was compared with CR (MD = 9.69, 95% CI 2.18, 17.51). But at the long-term follow-up, there was no significant difference in ROM in any one knee implant compared with the others. No significant increase was found in the PROMs and complication and revision rates at the final follow-up time. Conclusions:. At early follow-up after TKA, PS and BCS knee implants significantly outperform the CR knee implant in ROM. But in the long run, the available evidence suggests different knee prostheses could make no difference in clinical outcomes after TKA with extended follow-up.

Abstract Background This retrospective study aimed to investigate the most suitable endometrial thickness (EMT) on the day of embryo transfer that could reduce ectopic pregnancy rate (EPR) and improve clinical pregnancy rate (CPR) in fresh embryo transfer patients with early follicular phase long-acting regimen. Methods A total of 11,738 IVF/ICSI cycles, comprising 4,489 non-clinical pregnancies, 7,121 intrauterine pregnancies, and 128 ectopic pregnancy cycles after fresh embryo transfer, recorded between September 2017 and December 2020. Clinical pregnancy (CP) and ectopic pregnancy (EP) were the primary outcomes. Multivariate logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for EP and CP. Patients were divided into three groups based on the EMT (6–10 mm, 11–15 mm, and 16–20 mm). CPR and EPR per millimeter of EMT were drawn into a line chart, and three groups were analyzed by Chi-square test. Results After controlling for potential confounders, EMT had a significant effect on CP (aOR = 1.07; 95% CI, 1.05–1.08; P = 0.00) and EP (aOR = 0.88; 95% CI, 0.82–0.94; P = 0.00). With the increase of EMT, CPR increased and EPR decreased. Pearson correlation coefficients were r = 0.708 (P = 0.00) and r =-0.558 (P = 0.03), respectively. Significant differenceswere detected in the CPRs and EPRs (all P = 0.00). The CPR in the 6–10 mm group (54.88%) was significantly lower than that in the 11–15 mm group (64.23%) and the 16–20 mm group (64.40%) (P = 0.00). The EPR in the 6–10 mm group (2.72%) was significantly higher than that in the other two groups (1.60% and 0.97%, P = 0.00). The difference in CPR and EPR between the 11–15 mm group and the 16–20 mm group was not statistically significant, which indicated that EMT ≥ 11 mm simultaneously reduced the EPR and increased the CPR. Conclusions EMT was inversely proportional to EPR and directly proportional to CPR in fresh embryo transfer cycles. The EMT ≥ 11 mm on the day of embryo transfer could simultaneously achieve lower EPR and higher CPR. Accordingly, more attention should be given to the EMT of women who underwent ART treatment.

Abstract. Background:. Stroke is the leading cause of death in China, and predicting the stroke burden could provide essential information guiding the setting of medium- and long-term health policies and priorities. The study aimed to project trends associated with stroke burden in China through 2050, not only in terms of incidence and mortality but also for prevalence and disability-adjusted life years (DALYs). Methods:. Data on stroke rates in incidence, prevalence, deaths, and DALYs in China between 1990 and 2019 were obtained from a recent Global Burden of Disease study. Demographic-specific trends in rates over time were estimated using three models: the loglinear model, the Lee-Carter model, and a functional time series model. The mean absolute percentage error and the root mean squared error were used for model selection. Projections up to 2050 were estimated using the best fitting model. United Nations population data were used to project the absolute numbers through 2050. Results:. From 2019 to 2050, the crude rates for all measures of the stroke burden are projected to increase continuously among both men and women. We project that compared with those in 2019, the incidence, prevalence, deaths, and DALYs because of stroke in China in 2050 will increase by 55.58%, 119.16%, 72.15%, and 20.04%, respectively; the corresponding increases in number were 2.19, 34.27, 1.58, and 9.21 million. The age-standardized rate is projected to substantially decline for incidence (8.94%), death (40.37%), and DALYs (43.47%), but the age-standardized prevalence rate is predicted to increase by 10.82%. By 2050, the burden of stroke among the population aged ≥65 years will increase significantly: by 104.70% for incidence, by 218.48% for prevalence, by 100.00% for death, and by 58.93% for DALYs. Conclusions:. With the aging population in China increasing over the next three decades, the burden of stroke will be markedly increased. Continuous efforts are needed to improve stroke health care and secondary prevention, especially for older adults.

Abstract. Background:. Patellofemoral joint (PFJ) degeneration has traditionally been regarded as a contraindication to unicompartmental knee arthroplasty (UKA). More recently, some researchers have proposed that PFJ degeneration can be ignored in medial UKA, and others have proposed that this change should be reviewed in PFJ degenerative facets and severity. This study aimed to systematically evaluate the effect of PFJ degeneration on patient-reported outcome measures (PROMs) and revision rates after medial UKA. Methods:. Electronic databases (PubMed, Embase, Web of Science, etc.) were searched for studies assessing the influence of PFJ degeneration on medial UKA. A random-effects meta-analysis was conducted for the Oxford knee score (OKS), Knee society score (KSS), and revision rates and stratified by PFJ degenerative facets (medial/lateral/trochlear/unspecified), severe PFJ degeneration (bone exposed), and bearing type (mobile/fixed). Heterogeneity was assessed by the Cochran Q test statistic and chi-squared tests with the I-squared statistic. Results:. A total of 34 articles with 7007 knees (2267 with PFJ degeneration) were included (5762 mobile-bearing and 1145 fixed-bearing and 100 unspecified). Slight to moderate degenerative changes in the medial and trochlear facets did not decrease the OKS and KSS, and only lateral facets significantly decreased the OKS (mean difference [MD] = −2.18, P

Abstract. Background:. There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension. Methods:. The study cohort comprised 25,433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD. Results:. During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10–1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10–1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07–1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03–1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association. Conclusions:. NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.

Antimicrobial peptides (AMPs) are an important part of the innate immune defense system; they can effectively kill viruses, fungi, and bacteria, preventing infection (and even sepsis). AMPs also have other functional roles in immune regulation, anti-tumor activity, angiogenesis, and wound healing. Liver-expressed antimicrobial peptide 2 (LEAP-2) is an AMP that has been extensively studied in mammals, birds, and fishes. The earliest fish LEAP-2 study reported the cloning of LEAP-2A and LEAP-2B of rainbow trout. So far, LEAP-2 has been studied in various fishes, including blunt snout bream, grass carp, golden pompano, ayu, and large yellow croaker. These studies found that LEAP-2 generally contains four highly conserved cysteine residues and two disulfide bonds; it can disrupt the structural integrity of bacterial cell membrane, revealing its antibacterial activity with an important role in the innate immune system of fishes. Russian sturgeon (Acipenser gueldenstaedtii) is cultivated on a certain scale in China, and Aeromonas hydrophila is its main pathogen. Hemorrhagic ascites and tissue hemorrhage appear after infection, causing huge economic losses to Russian sturgeon aquaculture. As an important innate immunity component, LEAP-2 research is of great significance. At present, studies on AgLEAP-2 have not been reported. To study the molecular characteristics and the transcriptional expression patterns of AgLEAP-2, as well as its antibacterial activity in vitro, the full-length AgLEAP-2 cDNA sequence was obtained by RACE. AgLEAP-2 was cloned and its sequence characteristics were analyzed by bioinformatics. The qRT-PCR method was used to detect AgLEAP-2 in 13 different tissues (liver, intestine, spleen, head kidney, blood, gill, skin, ovary, brain, heart, stomach, metanephros, and muscle) of healthy Russian sturgeon, and the AgLEAP-2 transcriptional expression pattern in immune tissues after infection with A. hydrophila. The AgLEAP-2 prokaryotic expression vector was constructed and the recombinant AgLEAP-2 protein (designated rAgLEAP-2) was purified. The antibacterial activity of rAgLEAP-2 was preliminarily detected by the agar dilution method. The results showed that the full-length cDNA of the AgLEAP-2 gene was 622 bp in length, of which the 5'-UTR was 184 bp, the 3'-UTR was 192 bp, and the ORF was 246 bp in length, encoding an 81-amino acid peptide. The molecular mass of the rAgLEAP-2 protein was predicted to be 11.2 kDa, and the theoretical isoelectric point was 9.15. AgLEAP-2 contained a signal peptide (1~25 aa) and a mature peptide (26~81 aa). The mature peptide contained four conserved cysteine residues and formed a core structure is consistent with two disulfide bonds between the Cys58-Cys69 and Cys64-Cys74. The AgLEAP-2 structure agreed with the LEAP-2 family characteristics. Moreover, the results showed that the AgLEAP-2 sequence was highly evolutionary conserved. Amino acid sequence alignment and phylogenetic analysis showed that AgLEAP-2 was clustered into a clade with the LEAP-2C of fishes, with the highest similarity with the LEAP-2C of Yangtze sturgeon and Chinese sturgeon. The qRT-PCR analysis showed that AgLEAP-2 was widely expressed in all healthy tissues, with the highest expression level in the liver, followed by the intestine and muscle, with the lowest expression in the gill. The expression patterns of LEAP-2 in different fish species were slightly different, with the highest expression level in the liver of Russian sturgeon and the intestine of large yellow croaker. The similar LEAP-2 expression patterns in different species suggested that its functions may be consistent, although it also had tissue and species specificity. The AgLEAP-2 expression reached its maximum within 72 h in the liver, spleen, head kidney, gill, and blood immune tissues. Among them, the expression AgLEAP-2 changed most significantly on the gill, which increased 5 000-fold compared with 0 h. The highest relative expression level was observed in the spleen at 72 h, corresponding to a 1500-fold induction relative to 0 h, and in the intestine at 48 h, with a 900-fold induction compared to 0 h kept constant until 72 h. In addition, the rAgLEAP-2 protein exhibited good antibacterial effects against both Gram-positive bacteria (Streptococcus sp. and S. aureus) and Gram-negative bacteria (E. coli, Vibrio anguillarum, and Shewanella spp.) in a dose-dependent manner in vitro. The rAgLEAP-2 protein at 500 μg/mL could inhibit the growth of most bacteria, significantly reducing the number of colonies on the plate. In conclusion, cloning and homology analysis revealed that AgLEAP-2 was closely related to LEAP-2C. AgLEAP-2 plays an important role in the immune response of Russian sturgeon against bacterial infection, and the rAgLEAP-2 protein could inhibit the growth of Gram-positive and Gram-negative bacteria in vitro. This study enhanced our current understanding of the nonspecific immune response in fish and provided a research basis for further studies on the antibacterial mechanism of LEAP-2 found in Russian sturgeon.

INTRODUCTION: Energy, as a core element supporting the functioning of modern society, is vital to the development of the rural collective economy. With the upgrading of the agrarian industrial structure and the improvement of rural electrification levels, the energy demand gradually increases. Therefore, for China's rural collective economy, an in-depth study of the forecasting and risk assessment of the energy market has essential theoretical and practical value for scientific planning of resource allocation and improving energy utilization efficiency. OBJECTIVES: This study aims to reveal the development trend and key influencing factors through an in-depth analysis of China's rural collective economy's energy market and to make scientific forecasts of the future development of the energy market. At the same time, through risk assessment, it proposes risk prevention and resolution countermeasures of the energy market for the rural collective economy to provide decision support for rural energy security and sustainable development. METHODS: This study adopts a comprehensive analysis approach, combining historical data, policy literature analysis, and expert interviews. First, a comprehensive analytical framework is established by combing the development history of the rural collective economy energy market over the past few years. Second, quantitative analysis models and numerical simulations are used to analyze the key factors affecting the energy market. Finally, expert interviews are conducted to obtain the views of experts in related fields on the future development and risks of the energy market to improve the research conclusions further. RESULTS: The results of the study show that the energy market of China's rural collective economy will show a trend of gradual growth, but it also faces multiple risk challenges, including market price fluctuations, policy adjustments, and an imbalance between supply and demand. In the future, with the deepening of green energy policies, rural collective economies will pay more attention to the application of clean and renewable energy. CONCLUSION: To summarize, this study provides a scientific reference for the energy strategy decision-making of rural collective economies by forecasting and assessing the risk of the energy market based on China's rural collaborative economies. In the future, it is necessary to pay more attention to the improvement of the policy system to promote the development of green energy, as well as the establishment of a sound market regulatory mechanism to reduce the uncertainty of the energy market and provide solid support for the sustainable development of the rural collective economy.

Di-2-ethylhexyl phthalate (DEHP), as a common endocrine disrupting chemicals, can induce toxicity to reproductive system. However, the mechanism remains to be explored. In our study, DEHP exposure induced testicular injury in rats. The high throughput transcriptional sequencing was performed to identify differentially expressed genes (DEGs) between the treatment and control groups. KEGG analysis revealed that DEGs were enriched in apoptosis, PPARα, and ER stress pathway. DEHP up-regulated the expression of PPARα, Bax, Bim, caspase-4. GRP78, PERK, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. This view has also been confirmed in TM3 and TM4 cells. In vitro, after pre-treatment with GW6471 (an inhibitor of PPARα) or GSK (an inhibitor of PERK), the apoptosis was inhibited and mitochondrial dysfunction was improved. Moreover, the improvement of mitochondrial dysfunction decreased the expression of PERK pathway by using SS-31(a protective agent for mitochondrial function). Interestingly, ER stress promoted the accumulation of ROS by ERO1L (the downstream of CHOP during ER stress), and the ROS further aggravated the ER stress, thus forming a feedback loop during the apoptosis. In this process, a vicious cycle consisting of PERK, eIF2α, ATF4, CHOP, ERO1L, ROS was involved. Taken together, our results suggested that mitochondrial dysfunction and ER stress-ROS feedback loop caused by PPARα activation played a crucial role in DEHP-induced apoptosis. This work provides insight into the mechanism of DEHP-induced reproductive toxicity.

AbstractCalciphylaxis is a rare cutaneous vascular disease that manifests with intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and microvessel thrombosis. Currently, there are no standardized guidelines for this disease. Recent studies have recognized a high prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategy with intravenous and local hAMSC application. In order to investigate the therapeutic mechanism of hAMSCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status, quality of life and skin biopsy were followed up. Polymerase chain reaction (PCR) was performed to determine the distribution of hAMSCs in multiple tissues including lung, kidney and muscle after infusion of hAMSCs for 24 h, 1 week and 1 month in mice aiming to investigate whether hAMSCs retain locally active roles after intravenous administration. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration over one-year period. Skin biopsy pathology suggested regenerative tissues after 1 month hAMSC application and full epidermal regeneration after 20 months hAMSC treatment. PCR analysis indicated that hAMSCs were homing in lung, kidney and muscle tissues of mice even until tail vein injection of hAMSCs for 1 month. We propose that hypercoagulability is a promising therapeutic target of calciphylaxis patients, which can be effectively improved by hAMSC treatment.

AbstractIntroduction Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices.Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested.Results The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased.Conclusions Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment.

Abstract. Wearable technology, which can continuously and remotely monitor physiological and behavioral parameters by incorporated into clothing or worn as an accessory, introduces a new era for ubiquitous health care. With big data technology, wearable data can be analyzed to help long-term cardiovascular care. This review summarizes the recent developments of wearable technology related to cardiovascular care, highlighting the most common wearable devices and their accuracy. We also examined the application of these devices in cardiovascular healthcare, such as the early detection of arrhythmias, measuring blood pressure, and detecting prevalent diabetes. We provide an overview of the challenges that hinder the widespread application of wearable devices, such as inadequate device accuracy, data redundancy, concerns associated with data security, and lack of meaningful criteria, and offer potential solutions. Finally, the future research direction for cardiovascular care using wearable devices is discussed.

Abstract Background Joint contracture causes a decrease in range of motion (ROM), which severely affects activities of daily living of patients. We have investigated the effectiveness of a multidisciplinary rehabilitation on joint contracture by rat model. Methods We used 60 Wistar rats in this study. The rats were divided into five groups as follows: group 1 was the normal control group; except the group 1, we created left hind limb knee joint contracture using Nagai method for other four groups. The joint contracture modeling group 2 was the model control group for monitoring the spontaneous recovery, and other three groups were given different rehabilitation treatments; for example, group 3 was treadmill running group; group 4 was medication group; group 5 was treadmill running plus medication group. The left hind limbs knee joint ROM and the femoral blood flow indicators (FBFI) including PS, ED, RI, and PI were measured right before and after the 4 weeks of rehabilitation. Result After 4 weeks of rehabilitation treatments, the measured values of ROM and FBFI are compared with the corresponding values of group 2. Firstly, we did not see clear difference in the values of ROM and FBFI for group 2 before and after 4 weeks spontaneous recovery. The improvement of left lower limb ROM for group 4 and group 5 as compared to the group 2 was statistically significant (p

Abstract. The clinical efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in reducing major cardiovascular adverse events related to atherosclerotic cardiovascular disease (ASCVD) has been well established in recent large randomized outcome trials. Although the cardiovascular and all-cause mortality benefit of PCSK9i remains inconclusive, current cholesterol management guidelines have been modified toward more aggressive goals for lowering low-density lipoprotein cholesterol (LDL-C). Consequently, the emerging concept of “the lower the better” has become the paradigm of ASCVD prevention. However, there is evidence from observational studies of a U-shaped association between baseline LDL-C levels and all-cause mortality in population-based cohorts. Among East Asian populations, low LDL-C was associated with an increased risk for hemorrhagic stroke in patients not on antithrombotic therapy. Accumulating evidence showed that low LDL-C was associated with an enhanced bleeding risk in patients on dual antiplatelet therapy following percutaneous coronary intervention. Additionally, low LDL-C was associated with a higher risk for incident atrial fibrillation and thereby, a possible increase in the risk for intracranial hemorrhage after initiation of anticoagulation therapy. The mechanism of low-LDL-C-related bleeding risk has not been fully elucidated. This review summarizes recent evidence of low-LDL-C-related bleeding risk in patients on antithrombotic therapy and discusses potential measures for reducing this risk, underscoring the importance of carefully weighing the pros and cons of aggressive LDL-C lowering in patients on antithrombotic therapy.

Drought and salt stress are important limiting factors that affect crop growth and yield. As a newly recognized plant hormone, melatonin can participate in the regulation of plant stress tolerance and enhance the tolerance of plants to adversity. In this study, the effects of melatonin (150 µmol·L−1) on agronomic traits, osmotic adjustment substances, antioxidant enzyme activities, and reactive oxygen species content in C. esculentus under different salt (0 and 200 mmol·L−1 NaCl), drought (70% field capacity, 50% field capacity), and salt–drought (200 mmol·L−1 NaCl + 50% field capacity) stress conditions were determined using a pot experiment. Spraying with 150 µmol·L−1 of melatonin effectively improved the plant height, number of blades, biomass, and root growth of C. esculentus seedlings under salt, drought, and combined stress. In addition, this treatment also increased the relative water content, superoxide dismutase, peroxidase, and catalase activities, and soluble sugar content of the blades and decreased the relative electroconductivity conductivity and proline, malondialdehyde, hydrogen peroxide, and superoxide anion contents. A comprehensive analysis showed that spraying the plants with exogenous melatonin could increase the activity of antioxidant enzymes and the accumulation of osmotic adjustment substances in C. esculentus blades under salt and drought stress, effectively remove excessive reactive oxygen species, alleviate oxidative damage, and enhance the ability of C. esculentus to resist salt and drought stress.

Background: We investigated the mediating role of personality compatibility, couple communication, and sexual life in the psychological resilience and marital satisfaction of women with breast cancer. Methods: This is a cross-sectional survey. From March 2022 to June 2022, we enrolled 212 women with breast cancer from a tertiary tumor hospital in Xinjiang, China using a convenient sampling method. The basic information of patients was collected. The marriage quality and psychological resilience were assessed with the Enrich Marital Inventory and Connor-Davidson resilience scale, respectively. Counting data are expressed using the number and frequency while measuring data are presented using mean ± standard deviation. Statistical tests included one-way ANOVA and t-test. Pearson correlation was performed. The mediating effects were analyzed using the Baron and Kenny stepwise method. Results: The mean marriage quality score of women with breast cancer in marital satisfaction was 31.38 ± 8.36, in couple communication was 31.28 ± 7.15, in sexual life was 31.16 ± 7.76, in personality compatibility was 29.61 ± 7.32, and in psychological resilience was 53.60 ± 12.05, all of which were lower than the corresponding female norms. Correlation analysis showed that the three factors of psychological resilience (tenacity, strength, and optimism) of women with breast cancer were positively correlated with marital quality (marital satisfaction, personality compatibility, couple communication, and sexual life). The mediating effects of personality compatibility, couple communication, and sexual life on psychological resilience and marital satisfaction of women with breast cancer were significant (p < 0.001). Their effect values accounted for 48.6%, 63.1%, and 64.4% of the total effects, respectively. Conclusions: The level of psychological resilience and marital satisfaction of women with breast cancer is low. Psychological resilience can not only directly affect the marital satisfaction of women with breast cancer, but also indirectly affect marital quality through personality compatibility, couple communication, and sexual life. Medical workers should pay attention to the psychological status and marital satisfaction of women with breast cancer.