Direct and rapid thermal shock for recycling spent graphite in lithium-ion batteries.

Due to the rapid increase in the number of spent lithium-ion batteries, there has been a growing interest in the recovery of degraded graphite. In this work, a rapid thermal shock (RTS) strategy is proposed to regenerate spent graphite for use in lithium-ion batteries. The results of structural and morphological characterization demonstrate that the graphite is well regenerated by the RTS process. Additionally, an amorphous carbon layer forms and coats onto the surface of the graphite, contributing to excellent rate performance. The regenerated graphite (RG-1000) displays excellent rate performance, with capacities of 413 mAh g-1 at 50 mA g-1 and 102.1 mAh g-1 at 1000 mA g-1, respectively. Furthermore, it demonstrates long-term cycle stability, maintaining a capacity of 80 mAh g-1 at 1000 mA g-1 with a capacity retention of 78.4 % after 600 cycles. This RTS method enables rapid and efficient regeneration of spent graphite anodes for lithium-ion batteries, providing a facile and environmentally friendly strategy for their direct regeneration.

Osteopontin drives neuroinflammation and cell loss in MAPT-N279K frontotemporal dementia patient neurons.

Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, which we further characterized by single nucleus RNA sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.

Effects of Perineal Warm Compresses during the Second Stage of Labor on Reducing Perineal Trauma and Relieving Postpartum Perineal Pain in Primiparous Women: A Systematic Review and Meta-Analyses.

Non-pharmaceutical midwifery techniques, including perineal warm compresses, to improve maternal outcomes remain controversial. The aims of this study are to assess the effects of perineal warm compresses on reducing perineal trauma and postpartum perineal pain relief. This systematic review included randomized controlled trials (RCTs). We searched seven bibliographic databases, three RCT register websites, and two dissertation databases for publications from inception to 15 March 2023. Chinese and English publications were included. Two independent reviewers conducted the risk of bias assessment, data extraction, and the evaluation of the certainty of the evidence utilizing the Cochrane risk of bias 2.0 assessment criteria, the Review Manager 5.4, and the online GRADEpro tool, respectively. Seven RCTs involving 1362 primiparous women were included. The combined results demonstrated a statistically significant reduction in the second-, third- and/or fourth- degree perineal lacerations, the incidence of episiotomy, and the relief of the short-term perineal pain postpartum (within two days). There was a potential favorable effect on improving the integrity of the perineum. However, the results did not show a statistically significant supportive effect on reducing first-degree perineal lacerations and the rate of perineal lacerations requiring sutures. In summary, perineal warm compresses effectively reduced the second-, third-/or fourth-degree perineal trauma and decreased the short-term perineal pain after birth.

Superconductivity in Ca-intercalated bilayer graphene: C2CaC2.

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

Inflammatory liver diseases and susceptibility to sepsis.

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis.

Collective effects of rising average temperatures and heat events on oviparous embryos.

Survival of the immobile embryo in response to rising temperature is important to determine a species' vulnerability to climate change. However, the collective effects of 2 key thermal characteristics associated with climate change (i.e., rising average temperature and acute heat events) on embryonic survival remain largely unexplored. We used empirical measurements and niche modeling to investigate how chronic and acute heat stress independently and collectively influence the embryonic survival of lizards across latitudes. We collected and bred lizards from 5 latitudes and incubated their eggs across a range of temperatures to quantify population-specific responses to chronic and acute heat stress. Using an embryonic development model parameterized with measured embryonic heat tolerances, we further identified a collective impact of embryonic chronic and acute heat tolerances on embryonic survival. We also incorporated embryonic chronic and acute heat tolerance in hybrid species distribution models to determine species' range shifts under climate change. Embryos' tolerance of chronic heat (T-chronic) remained consistent across latitudes, whereas their tolerance of acute heat (T-acute) was higher at high latitudes than at low latitudes. Tolerance of acute heat exerted a more pronounced influence than tolerance of chronic heat. In species distribution models, climate change led to the most significant habitat loss for each population and species in its low-latitude distribution. Consequently, habitat for populations across all latitudes will shift toward high latitudes. Our study also highlights the importance of considering embryonic survival under chronic and acute heat stresses to predict species' vulnerability to climate change.

Efectos colectivos del aumento de las temperaturas promedio y los eventos de calor en embriones ovíparos Resumen La supervivencia de los embriones inmóviles en respuesta al incremento de temperatura es importante para determinar la vulnerabilidad de las especies al cambio climático. Sin embargo, los efectos colectivos de dos características térmicas claves asociadas con el cambio climático (i. e., aumento de temperatura promedio y eventos de calor agudo) sobre la supervivencia embrionaria permanecen en gran parte inexplorados. Utilizamos mediciones empíricas y modelos de nicho para investigar cómo el estrés térmico crónico y agudo influye de forma independiente y colectiva en la supervivencia embrionaria de los lagartos en todas las latitudes. Recolectamos y criamos lagartos de cinco latitudes e incubamos sus huevos en un rango de temperaturas para cuantificar las respuestas específicas de la población al estrés por calor crónico y agudo. Posteriormente, mediante un modelo de desarrollo embrionario parametrizado con mediciones de tolerancia embrionaria al calor, identificamos un impacto colectivo de las tolerancias embrionarias al calor agudo y crónico en la supervivencia embrionaria. También incorporamos la tolerancia embrionaria crónica y aguda al calor en modelos de distribución de especies híbridas para determinar los cambios de distribución de las especies bajo el cambio climático. La tolerancia embrionaria al calor crónico (T­crónico) permaneció constante, mientras que la tolerancia al calor agudo (T­agudo) fue mayor en latitudes altas que en latitudes bajas. La tolerancia al calor agudo ejerció una influencia más pronunciada que la tolerancia al calor crónico. En los modelos de distribución de especies, el cambio climático provocó la pérdida de hábitat más significativa para cada población y especie en su distribución de latitudes bajas. En consecuencia, el hábitat para poblaciones en todas las latitudes se desplazará a latitudes altas. Nuestro estudio también resalta la importancia de considerar la supervivencia embrionaria bajo estrés térmico crónico y agudo para predecir la vulnerabilidad de las especies al cambio climático.

Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases.

AGT (angiotensinogen) is the unique precursor for the generation of all the peptides of the renin-angiotensin system, but it has received relatively scant attention compared to many other renin-angiotensin system components. Focus on AGT has increased recently, particularly with the evolution of drugs to target the synthesis of the protein. AGT is a noninhibitory serpin that has several conserved domains in addition to the angiotensin II sequences at the N terminus. Increased study is needed on the structure-function relationship to resolve many unknowns regarding AGT metabolism. Constitutive whole-body genetic deletion of Agt in mice leads to multiple developmental defects creating a challenge to use these mice for mechanistic studies. This has been overcome by creating Agt-floxed mice to enable the development of cell-specific deficiencies that have provided considerable insight into a range of cardiovascular and associated diseases. This has been augmented by the recent development of pharmacological approaches targeting hepatocytes in humans to promote protracted inhibition of AGT synthesis. Genetic deletion or pharmacological inhibition of Agt has been demonstrated to be beneficial in a spectrum of diseases experimentally, including hypertension, atherosclerosis, aortic and superior mesenteric artery aneurysms, myocardial dysfunction, and hepatic steatosis. This review summarizes the findings of recent studies utilizing AGT manipulation as a therapeutic approach.

Nudifloside, a Secoiridoid Glucoside Derived from Callicarpa nudiflora, Inhibits Endothelial-to-Mesenchymal Transition and Angiogenesis in Endothelial Cells by Suppressing Ezrin Phosphorylation.

Callicarpa nudiflora is a traditional folk medicine in China used for eliminating stasis to subdue swelling. Several compounds from Callicarpa nudiflora have been proved to show anti-inflammatory, haemostasis, hepatitis, and anti-proliferative effects. Tumor endothelial cells play crucial roles in tumor-induced angiogenesis. Recently, it was demonstrated that ECs may be the important source of cancer associated fibroblasts (CAFs) through endothelial to mesenchymal transition (EndoMT). In this study, we evaluated the effects of nudifloside (NDF), a secoiridoid glucoside from Callicarpa Nudiflora, on TGF-ß1-induced EndoMT and VEGF-induced angiogenesis, and the underlying mechanisms were also involved. It was found that NDF significantly inhibited enhanced migration, invasion and F-actin assembly in endothelial cells (ECs) exposed in TGF-ß1. NDF obviously reversed expression of several biomarkers associated with EndoMT and recovered the morphological characteristics of ECs and tube-like structure induced by TGF-ß1. Furthermore, treatment of NDF resulted in a significant destruction of VEGF-induced angiogenesis in vitro and ex vivo. Data from co-immunoprecipitation assay provided the evidence that Ezrin phosphorylation and the interaction with binding protein can be inhibited by NDF, which can be confirmed by data from Ezrin silencing assay. Collectively, the application of NDF inhibited TGF-ß1-induced EndoMT and VEGF-induced angiogenesis in ECs by reducing Ezrin phosphorylation.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

MNDA expression and its value in differential diagnosis of B-cell non-Hodgkin lymphomas: a comprehensive analysis of a large series of 1293 cases.

AIMS: MNDA (myeloid nuclear differentiation antigen) has been considered as a potential diagnostic marker for marginal zone lymphoma (MZL), but its utility in distinguishing MZL from other B-cell non-Hodgkin lymphomas (B-NHLs) and its clinicopathologic relevance in diffuse large B-cell lymphoma (DLBCL) are ambiguous. We comprehensively investigated MNDA expression in a large series of B-NHLs and evaluated its diagnostic value. METHODS: MNDA expression in a cohort of 1293 cases of B-NHLs and 338  cases of reactive lymphoid hyperplasia (RLH) was determined using immunohistochemistry and compared among different types of B-NHL. The clinicopathologic relevance of MNDA in DLBCL was investigated. RESULTS: MNDA was highly expressed in MZLs (437/663, 65.9%), compared with the confined staining in marginal zone B-cells in RLH; whereas neoplastic cells with plasmacytic differentiation lost MNDA expression. MNDA expression was significantly higher in mantle cell lymphoma (MCL, 79.6%, p = 0.006), whereas lower in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL, 44.8%, p = 0.001) and lymphoplasmacytic lymphoma (LPL, 25%, p = 0.016), and dramatically lower in follicular lymphoma (FL, 5.2%, p < 0.001), compared with MZL. 29.6% (63/213) of DLBCLs were positive for MNDA. The cases in non-GCB group exhibited a higher rate of MNDA positivity (39.8%) compared to those in GCB group (16.3%) (p < 0.001), and MNDA staining was more frequently observed in DLBCLs with BCL2/MYC double-expression (50%) than those without BCL2/MYC double-expression (24.8%) (p = 0.001). Furthermore, there was a significant correlation between MNDA and CD5 expression in DLBCL (p = 0.036). CONCLUSIONS: MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

Fraxetin pretreatment alleviates cisplatin-induced kidney injury by antagonizing autophagy and apoptosis via mTORC1 activation.

Cisplatin-induced kidney injury (CKI) is a common complication of chemotherapy. Fraxetin, derived from Fraxinus bungeana A. DC. bark, has antioxidant, anti-inflammatory, and anti-fibrotic effects. This study aims to investigate fraxetin's effects on CKI and its underlying mechanism in vivo and in vitro. Tubular epithelial cells (TECs) and mice were exposed to cisplatin with and without fraxetin preconditioning assess fraxetin's role in CKI. TECs autophagy was observed using transmission electron microscopy. Apoptosis levels in animal tissues were measured using TUNEL staining. The protective mechanism of fraxetin was explored through pharmacological and genetic regulation of mTORC1. Molecular docking was used to identify potential binding sites between fraxetin and mTORC1. The results indicated that fraxetin pretreatment reduced cisplatin-induced kidney injury in a time- and concentration-dependent way. Fraxetin also decreased autophagy in TECs, as observed through electron microscopy. Tissue staining confirmed that fraxetin pretreatment significantly reduced cisplatin-induced apoptosis. Inhibition of mTORC1 using rapamycin or siRNA reversed the protective effects of fraxetin on apoptosis and autophagy in cisplatin-treated TECs, while activation of mTORC1 enhanced fraxetin's protective effect. Molecular docking analysis revealed that fraxetin can bind to HEAT-repeats binding site on mTORC1 protein. In  summary, fraxetin pretreatment alleviates CKI by antagonizing autophagy and apoptosis via mTORC1 activation. This provides evidence for the potential therapeutic application of fraxetin in CKI.

Accuracy of cone-beam breast computed tomography for assessing breast cancer tumor size-comparison with breast magnetic resonance imaging.

Background: Accurate preoperative assessment of tumor size is important in developing a surgical plan for breast cancer. The purpose of this study was to evaluate the accuracy of cone-beam breast computed tomography (CBBCT) and magnetic resonance imaging (MRI) in the assessment of tumor size and to analyze the factors influencing the discordance. Methods: In this retrospective study, patients with breast cancer who underwent preoperative contrast-enhanced CBBCT (CE-CBBCT) and dynamic contrast-enhanced MRI (DCE-MRI) and received a complete pathologic diagnosis from August 2020 to December 2021 were included, using the pathological result as the gold standard. Two radiologists assessed the CBBCT and MRI features and measured the tumor size with a 2-week washout period. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were used to assess inter-observer reproducibility and agreement based on CBBCT, MRI and pathology. Univariate analyses of differences in clinical, pathological and CBBCT/MRI features between the concordant and discordant groups was performed using the t-test, Mann-Whitney U-test, Chi-squared test and Fisher's exact test. Multivariate analyses were used to identify factors associated with discordance of CBBCT/MRI with pathology. Results: A total of 115 female breast cancer patients (115 lesions) were included. All patients had a single malignant tumor of the unilateral breast. The reproducibility and the agreement ranged from moderate to excellent (ICC =0.607-0.983). Receiver operating characteristic (ROC) analyses showed that the cut-off values of CBBCT-pathology and MRI-pathology discordance were 2.25 and 2.65 cm, respectively. CBBCT/MRI-pathology concordance was significantly associated with the extent of pathology, lesion type, presence of calcification, human epidermal growth factor receptor 2 (HER2) status and fatty infiltration (P<0.05). In lesions containing calcification, the difference of CBBCT-pathology was significantly smaller than MRI-pathology (P=0.021). Non-mass enhancement (NME) was the main predictor of CBBCT- or MRI-pathology discordance [odds ratio (OR) =3.293-6.469, P<0.05], and HER2 positivity was a predictor of CBBCT-pathology discordance (OR =3.514, P=0.019). Conclusions: CBBCT and MRI have comparable accuracy in measurement of tumor size, and CBBCT is advantageous in assessing the size of calcified lesions. NME and HER2 positivity are significant predictors of CBBCT-pathology discordance. This suggests that CBBCT might serve as an alternative imaging technique to assess tumor size when patients do not tolerate MRI.

Highly Sensitive and Selective Toluene Gas Sensors Based on ZnO Nanoflowers Decorated with Bimetallic AuPt.

Efficient sensors for toluene detecting are urgently needed to meet people's growing demands for both environment and personal health. Metal oxide semiconductor (MOS)-based sensors have become brilliant candidates for the detection of toluene because of their superior performance over gas sensing. However, gas sensors based on pure MOS have certain limitations in selectivity, operating temperature, and long-term stability, which hinders their further practical applications. Noble metals (including Ag, Au, Pt, Pd, etc.) have the ability to enhance the performance of MOS-based sensors via surface functionalization. Herein, ZnO nanoflowers (ZNFs) modified with bimetallic AuPt are prepared for toluene detection through hydrothermal method. The response of a AuPt@ZNF-based gas sensor can reach 69.7 at 175 °C, which is 30 times, 9 times, and 10 times higher than that of the original ZNFs, Au@ZNFs, and Pt@ZNFs, respectively. Furthermore, the sensor also has a lower optimal operating temperature (175 °C), good stability (94% of previous response after one month), and high selectivity towards toluene, which is the result of the combined influence of the electronic and chemical sensitization of noble metals, as well as the unique synergistic effect of the AuPt alloy. In summary, AuPt@ZNF-based sensors can be further applied in toluene detection in practical applications.

Mechanism of tartaric acid mediated dissipation and biotransformation of tetrabromobisphenol A and its derivatives in soil.

Biotransformation is a major dissipation process of tetrabromobisphenol A and its derivatives (TBBPAs) in soil. The biotransformation and ultimate environmental fate of TBBPAs have been widely studied, yet the effect of root exudates (especially low-molecular weight organic acids (LMWOAs)) on the fate of TBBPAs is poorly documented. Herein, the biotransformation behavior and mechanism of TBBPAs in bacteriome driven by LMWOAs were comprehensively investigated. Tartaric acid (TTA) was found to be the main component of LMWOAs in root exudates of Helianthus annus in the presence of TBBPAs, and was identified to play a key role in driving shaping bacteriome. TTA promoted shift of the dominant genus in soil bacteriome from Saccharibacteria_genera_incertae_sedis to Gemmatimonas, with a noteworthy increase of 24.90-34.65% in relative abundance of Gemmatimonas. A total of 28 conversion products were successfully identified, and ß-scission was the principal biotransformation pathway for TBBPAs. TTA facilitated the emergence of novel conversion products, including 2,4-dibromophenol, 3,5-dibromo-4-hydroxyacetophenone, para-hydroxyacetophenone, and tribromobisphenol A. These products were formed via oxidative skeletal cleavage and debromination pathways. Additionally, bisphenol A was observed during the conversion of derivatives. This study provides a comprehensive understanding about biotransformation of TBBPAs driven by TTA in soil bacteriome, offering new insights into LMWOAs-driven biotransformation mechanisms.

Role of regulatory T cells in mouse lung development.

Regulatory T cells (Tregs) constitute a specialized subset of T cells with dual immunoregulatory and modulatory functions. Recent studies have reported that Tregs mediate immune responses and regulate the development and repair processes in non-lymphoid tissues, including bone and cardiac muscle. Additionally, Tregs facilitate the repair and regeneration of damaged lung tissues. However, limited studies have examined the role of Tregs in pulmonary development. This study aimed to evaluate the role of Tregs in pulmonary development by investigating the dynamic alterations in Tregs and their hallmark cellular factor Forkhead box P3 (Foxp3) at various stages of murine lung development and establishing a murine model of anti-CD25 antibody-induced Treg depletion. During the early stages of murine lung development, especially the canalicular and saccular stages, the levels of Treg abundance and expression of Foxp3 and transforming growth factor-ß (TGF-ß) were upregulated. This coincided with the proliferation period of alveolar epithelial cells and vascular endothelial cells, indicating an adaptation to the dynamic lung developmental processes. Furthermore, the depletion of Tregs disrupted lung tissue morphology and downregulated lung development-related factors, such as surfactant protein C (SFTPC), vascular endothelial growth factor A (VEGFA) and platelet endothelial cell adhesion molecule-1 (PECAM1/CD31). These findings suggest that Tregs promote murine lung development.

CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-ß1/Smad2/3 signaling in mouse viral myocarditis.

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

Hepatitis C Attributable Healthcare Costs and Mortality among Immigrants: A Population-Based Matched Cohort Study.

Background: Data on the economic burden of chronic hepatitis C (CHC) among immigrants are limited. Our objective was to estimate the CHC-attributable mortality and healthcare costs among immigrants in Ontario, Canada. Methods: We conducted a population-based matched cohort study among immigrants diagnosed with CHC between May 31, 2003, and December 31, 2018, using linked health administrative data. Immigrants with CHC (exposed) were matched 1 : 1 to immigrants without CHC (unexposed) using a combination of hard (index date, sex, and age) and propensity-score matching. Net costs (2020 Canadian dollars) collected from the healthcare payer perspective were calculated using a phase-of-care approach and used to estimate long-term costs adjusted for survival. Results: We matched 5,575 exposed individuals with unexposed controls, achieving a balanced match. The mean age was 47 years, and 52% was male. On average, 10.5% of exposed and 3.5% of unexposed individuals died 15 years postindex (relative risk = 2.9; 95% confidence interval (CI): 2.6-3.5). The net 30-day costs per person were $88 (95% CI: 55 to 122) for the prediagnosis, $324 (95% CI: 291 to 356) for the initial phase, $1,016 (95% CI: 900 to 1,132) for the late phase, and $975 (95% CI: -25 to 1,974) for the terminal phase. The mean net healthcare cost adjusted for survival at 15 years was $90,448. Conclusions: Compared to unexposed immigrants, immigrants infected with CHC have higher mortality rates and greater healthcare costs. These findings will support the planning of HCV elimination efforts among key risk groups in the province.

The contact force between lunar-based equipment and lunar soil.

Lunar-based equipment plays a vital role in the exploration of the moon because it undertakes the tasks of moving, transporting, digging, and so on. In order to control the gait of lunar-based equipment more precisely and guarantee mobile stability, the contact mechanism between its foot and lunar soil is worthy of in-depth study. In this paper, a contact model is proposed to predict the stress, strain, and displacement both on the contact surface and in the lunar soil when the foot is under vertical load. The axial stress in the proposed contact model is verified through the experiment and its accuracy in the lunar equipment is verified through simulation. The error is in a reasonable range and the influence depth of load conforms to the experiment results. This paper provides a relatively accurate model to describe the contact force between the lunar-based equipment's foot and the lunar soil and will promote the research of lunar exploration.

Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.