TDP-43 ameliorates aging-related cartilage degradation through preventing chondrocyte senescence.

Senescent chondrocytes or signaling mechanisms leading to senescence are promising new therapeutic approaches for ameliorating cartilage degradation. Herein, we show that the transactive response DNA/RNA-binding protein (TDP-43) regulates chondrocyte senescence and ameliorates cartilage degradation. First, a significant decrease in TDP-43 was observed in 16-month-old mice compared with younger mice. Immunohistochemistry (IHC) analysis of mouse articular cartilage showed that p21, p16, p53, and matrix metalloprotein-13 (MMP13) were increased, but laminB1 and Collagen type II alpha1 1 chain (Col2a1) were decreased in 16-month-old mice. Furthermore, TDP-43 levels were decreased in vivo following D-galactose (D-gal) induction. Therefore, we investigated the role of TDP-43 in the senescent chondrocytes. ATDC5 cells were induced to overexpress TDP-43. Western blot analysis showed increased expression of laminB1, Ki67, and PCNA but decreased expression of p21, p16, p53, and MMP13. Senescence-associated-ß-galactosidase (SA-ß-Gal) assay, γH2AX staining, and EdU were performed to assess changes in chondrocytes, showing weaker SA-ß-Gal and γH2AX staining but stronger EdU and Alican Blue staining. However, TDP-43 deficiency had opposing effects, and similar to D-gal stimulation results. Taken together, our data verified that TDP-43 negatively correlated with senescence markers, positively correlated with cell proliferation markers, and could alleviate cartilage degradation induced by D-gal. This may be an essential mechanism of cellular senescence and cartilage degradation.

The underlying mechanisms by which boron mitigated copper toxicity in Citrus sinensis leaves revealed by integrated analysis of transcriptome, metabolome, and physiology.

Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) µM CuCl2 and 2.5 (B2.5) or 25 (B25) µM HBO3 for 24 weeks. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 µM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 µM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars, and increased the concentrations of starch, glucose, fructose, and total nonstructural carbohydrates (TNC) in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350; and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, and some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites, and genes that might lead to Cu tolerance in leaves.

Assessing Thoracic Vertebral Bone Mineral Density (T8-T10) for Osteoporosis Diagnosis During CT Lung Cancer Screening in Older Adults.

Introduction: Osteoporosis diagnosis often utilizes quantitative computed tomography (QCT). This study explored the validity of applying lumbar bone mineral density (LBMD) standards to thoracic vertebrae (T8-T10) for osteoporosis detection during CT lung cancer screenings. This study investigated the utility of thoracic BMD (BMD-T8-T10) for detecting osteoporosis in older persons during CT lung cancer screening. Methods: We studied 701 participants who underwent QCT scans for both LBMD and BMD-T8-T10. Osteoporosis was diagnosed using ACR criteria based on LBMD. We determined BMD-T8-T10 thresholds via a receiver operating characteristic (ROC) curve and translated BMD-T8+T9+T10 to LBMD (TTBMD) using linear regression. Kappa test was used to evaluate the accuracy of BMD-T8-T10 thresholds and TTBMD in diagnosing osteoporosis. Results: Raw BMD-T8-T10 poorly identified osteoporosis (kappa = 0.51). ROC curve analysis identified BMD-T8-T10 thresholds for osteopenia (138 mg/cm3) and osteoporosis (97 mg/cm3) with areas under the curve of 0.97 and 0.99, respectively. We normalized BMD-T8-T10 to TTBMD based on the formula: TTBMD = 0.9 × BMD-T8-T10 - 2.56. These thresholds (kappa = 0.74) and TTBMD performed well in detecting osteoporosis/osteopenia (kappa = 0.74). Conclusion: Both calculating BMD-T8-T10 threshold (138.0 mg/cm3 for osteopenia and 97 mg/cm3 for osteoporosis) and normalizing BMD-T8-T10 to LBMD demonstrated good performance in identifying osteoporosis in older adults during CT lung cancer screening.

Molecular mechanism of regulating tat protein expression of pingganjiedu TCM in the treatment of AIDS based on network pharmacology.

AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS.

Specially Structured AgCuTi Foil Enables High-Strength and Defect-Free Brazing of Sapphire and Ti6Al4V Alloys: The Microstructure and Fracture Characteristics.

A novel AgCuTi brazing foil with a unique microstructure was developed, which could achieve strong vacuum brazing of Ti6Al4V (TC4) and sapphire. The brazing foil was composed of Ag solid solution (Ag(s,s)), Cu solid solution (Cu(s,s)), and layered Ti-rich phases, and had a low liquidus temperature of 790 °C and a narrow melting range of 16 °C, facilitating the defect-free joining of TC4 and sapphire. The sapphire/TC4 joint fabricated by using this novel AgCuTi brazing foil exhibited an outstanding average shear strength of up to 132.2 MPa, which was the highest value ever reported. The sapphire/TC4 joint had a characteristic structure, featuring a brazing seam reinforced by TiCu particles and a thin Ti3(Cu,Al)3O reaction layer of about 1.3 µm. The fracture mechanism of the sapphire/TC4 joint was revealed. The crack originated at the brazing seam with TiCu particles, then propagated through the Ti3(Cu,Al)3O reaction layer, detached the reaction layer from the sapphire, and finally penetrated into the sapphire. This study offers valuable insights into the design of active brazing alloys and reliable metal-ceramic bonding.

Development and Validation of Diagnostic Models for Transcriptomic Signature Genes for Multiple Tissues in Osteoarthritis.

Background: Progress in research on expression profiles in osteoarthritis (OA) has been limited to individual tissues within the joint, such as the synovium, cartilage, or meniscus. This study aimed to comprehensively analyze the common gene expression characteristics of various structures in OA and construct a diagnostic model. Methods: Three datasets were selected: synovium, meniscus, and knee joint cartilage. Modular clustering and differential analysis of genes were used for further functional analyses and the construction of protein networks. Signature genes with the highest diagnostic potential were identified and verified using external gene datasets. The expression of these genes was validated in clinical samples by Real-time (RT)-qPCR and immunohistochemistry (IHC) staining. This study investigated the status of immune cells in OA by examining their infiltration. Results: The merged OA dataset included 438 DEGs clustered into seven modules using WGCNA. The intersection of these DEGs with WGCNA modules identified 190 genes. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms, nine signature genes were identified (CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3), each demonstrating substantial diagnostic potential (areas under the curve from 0.701 to 0.925). Furthermore, dysregulation of various immune cells has also been observed. Conclusion: CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3 demonstrated significant diagnostic efficacy in OA and are involved in immune cell infiltration.

Super-Durable, Tough Shape-Memory Polymeric Materials Woven from Interlocking Rigid-Flexible Chains.

Developing advanced engineering polymers that combine high strength and toughness represents not only a necessary path to excellence but also a major technical challenge. Here for the first time a rigid-flexible interlocking polymer (RFIP) is reported featuring remarkable mechanical properties, consisting of flexible polyurethane (PU) and rigid polyimide (PI) chains cleverly woven together around the copper(I) ions center. By rationally weaving PI, PU chains, and copper(I) ions, RFIP exhibits ultra-high strength (twice that of unwoven polymers, 91.4 ± 3.3 MPa), toughness (448.0 ± 14.2 MJ m-3), fatigue resistance (recoverable after 10 000 cyclic stretches), and shape memory properties. Simulation results and characterization analysis together support the correlation between microstructure and macroscopic features, confirming the greater cohesive energy of the interwoven network and providing insights into strengthening toughening mechanisms. The essence of weaving on the atomic and molecular levels is fused to obtain brilliant and valuable mechanical properties, opening new perspectives in designing robust and stable polymers.

Harnessing cytokines to optimize chimeric antigen receptor-T cell therapy for gastric cancer: Current advances and innovative strategies.

Enormous patients with gastric cancer (GC) are insensitive to chemotherapy and targeted therapy without the chance of radical surgery, so immunotherapy may supply a novel choice for them. Chimeric antigen receptor (CAR)-T cell therapy has the advantages of higher specificity, stronger lethality, and longer-lasting efficacy, and it has the potential for GC in the future. However, its application still faces numerous obstacles in terms of accuracy, efficacy, and safety. Cytokines can mediate the migration, proliferation, and survival of immune cells, regulate the duration and strength of immune responses, and are involved in the occurrence of severe side effects in CAR-T cell therapy. The expression levels of specific cytokines are associated with the genesis, invasion, metastasis, and prognosis of GC. Applications of cytokines and their receptors in CAR-T cell therapy have emerged, and various cytokines and their receptors have contributed to improving CAR-T cell anti-tumor capabilities. Large amounts of central cytokines in this therapy include chemokines, interleukins (ILs), transforming growth factor-ß (TGF-ß), and colony-stimulating factors (CSFs). Meanwhile, researchers have explored the combination therapy in treating GC, and several approaches applied to other malignancies can also be considered as references. Therefore, our review comprehensively outlines the biological functions and clinical significance of cytokines and summarizes current advances and innovative strategies for harnessing cytokines to optimize CAR-T cell therapy for GC.

Fecal microbiota from patients with Parkinson's disease intensifies inflammation and neurodegeneration in A53T mice.

AIMS: We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms. METHODS: We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice. RESULTS: The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of α-Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF-κB/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice. CONCLUSION: The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.

Molecular Mechanism of ARF5-AHL15-Mediated Auxin-Induced Embryogenic Cell Formation in Apples.

The somatic embryo (SE) has bipolar characteristics, which is an ideal material for large-scale microproduction of woody plants represented by apples, and the somatic embryo is also an excellent receptor for genetic transformation. The formation of embryogenic cells is a prerequisite for somatic embryogenesis to occur. The embryogenic cells of apples cannot be obtained without induction of exogenous auxin, but how the auxin pathway regulates this process remains unknown. In this study, via RNA sequencing, MdARF5 and MdAHL15 were identified as differentially expressed genes involved in this process. Overexpression of MdARF5 and MdAHL15 induced the formation and proliferation of embryogenic cells and thus substantially shortened the induction cycle and improved the somatic embryo proliferation efficiency. A yeast one-hybrid assay showed that MdARF5 can directly bind to the promoter of MdAHL15. ß-Glucuronidase (GUS) and dual-luciferase reporter assays revealed that MdARF5 activation of MdAHL15 transcription was substantial. In conclusion, our results suggest that MdAHL15 is induced by auxin and promotes the formation of embryogenic cells in early somatic embryogenesis via the positive regulation of MdARF5 in apples. The results will provide a theoretical basis for somatic embryogenesis-based development, reproduction, and transgenic breeding in apples.

Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury.

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury.

The non-negligible non-specific adsorption of oligonucleotides in target-immobilized Mag-SELEX.

Target-immobilized magnetic beads-based Systematic Evolution of Ligands by Exponential Enrichment (target-immobilized Mag-SELEX) has emerged as a powerful tool for aptamer selection owing to its convenience, efficiency, and versatility. However, in this study we systematically investigated non-specific adsorption in target-immobilized Mag-SELEX and found that the non-specific adsorption of the oligonucleotides to target-labeled magnetic beads was comparable to that of the screening libraries, indicating a substantial portion of captured sequences likely stem from non-specific adsorption. Longer nucleic acid sequences (80 nt and above, such as polyA80 and yeast tRNA) were found to attenuate this non-specific adsorption, with more complex higher-order structures demonstrating greater efficacy, while dNTP and short sequences such as primer sequences (20 nt), polyT(59), or polyA(59), did not possess this capability. Various evidence suggested that hydrophobic interactions and other weak interactions may be the primary underlying cause of non-specific adsorption. Additionally, surface modification of magnetic beads with polar molecule polyethylene glycol (PEG) also yielded a significant reduction in non-specific adsorption. In conclusion, our research underscores the critical importance of closely monitoring non-specific adsorption in target-immobilized Mag-SELEX.

Dynamic regulation of alternative polyadenylation by PQBP1 during neurogenesis.

Alternative polyadenylation (APA) is a critical post-transcriptional process that generates mRNA isoforms with distinct 3' untranslated regions (3' UTRs), thereby regulating mRNA localization, stability, and translational efficiency. Cell-type-specific APA extensively shapes the diversity of the cellular transcriptome, particularly during cell fate transition. Despite its recognized significance, the precise regulatory mechanisms governing cell-type-specific APA remain unclear. In this study, we uncover PQBP1 as an emerging APA regulator that actively maintains cell-specific APA profiles in neural progenitor cells (NPCs) and delicately manages the equilibrium between NPC proliferation and differentiation. Multi-omics analysis shows that PQBP1 directly interacts with the upstream UGUA elements, impeding the recruitment of the CFIm complex and influencing polyadenylation site selection within genes associated with the cell cycle. Our findings elucidate the molecular mechanism by which PQBP1 orchestrates dynamic APA changes during neurogenesis, providing valuable insights into the precise regulation of cell-type-specific APA and the underlying pathogenic mechanisms in neurodevelopmental disorders.

Fracturing Construction Curves and Fracture Geometries of Coals in the Southern Qinshui Basin, China: Implication for Coalbed Methane Productivity.

Hydraulic fracturing technology has become a common practice to enhance the permeability of coal seams, and its effectiveness significantly impacts the productivity of coalbed methane (CBM) wells. In this study, multiple data sets, including fracturing reports, productivity data, and microseismic monitoring, were utilized to analyze the factors influencing fracturing effectiveness and gas well production at the southern margin of the Qinshui Basin, China, especially the Zhengzhuang and Fanzhuang blocks. Statistics revealed that the fracturing displacement, liquid consumption, and sand consumption were 8 m3/min, 17.69-1386.52 m3 (averaging 728.42 m3), and 28.5-46.1 m3 (averaging 40 m3), respectively. There were differences in the types of fracturing curves among blocks or well groups, and the natural fracture system was identified as the key factor affecting their characteristics. The coal seams with high density of microfractures in Zhengzhuang reduce the fracture threshold of reservoirs during hydraulic fracturing, resulting in a lower fracture response ratio than that of Fanzhuang (71.0 vs 80.3%). Well groups with higher microfracture width in coal seams (Group-ZC and DS) experienced a further reduction in fracture response (averaging 67.2 vs 80.3%), and the connection of hydraulic fractures (HFs) with these high-permeability microfractures lead to an increase in the proportion of fluctuating fracturing curves (averaging 52.2 vs 33.6%). Regional structural features and fracturing effectiveness jointly affected the production of CBM wells. The productivity in Zhengzhuang was lower than that in Fanzhuang due to the highly developed faults and deeply buried coal seams. Shallow coal seams with a high width of microfractures and a low-stress environment were easily supported by a proppant, forming a complex HF network and yielding a high productivity (Group-ZC and DS). For other deeper well groups, proppant migration became unfavorable once high-angle and complex branch HF clusters formed in coal seams, leading to local low-efficiency wells and fluctuating fracturing curves.

Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.

BACKGROUND: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. METHODS AND FINDINGS: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. CONCLUSIONS: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

A robust ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of 10 components in glutathione cycle.

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.

Analysis of the usage and awareness of child safety seats for children aged 0-6 in Leshan City, Sichuan Province, China.

Objective: To investigate the current situation of child safety seat use and children's cognition of safe riding in Leshan City, and to provide a basis for the promotion and application of child safety seats in Leshan City. Methods: From November 2021 to February 2022, a total of 500 car-owning families who visited or were hospitalized in the department of pediatrics of our hospital were surveyed by self-filling questionnaire method. Through the investigation of personal situation, family situation, travel habits, use of child safety seat, cognition of safe riding, etc., the influencing factors of possession and use of child safety seat and cognition were analyzed. Results: The ownership rate of car seats was 57.8%, the use rate was 47.6%, and the always use rate was 18.8% among all families with children surveyed. There were no statistically significant differences in the use rate and always use rate of child safety seats among different genders of children, parents' education background, and car ownership price. The use rate and constant use rate of child safety seats in urban households were significantly higher than those in rural areas. When the main driver was the mother, the use rate of child safety seats was higher, and the difference was statistically significant. From the perspective of cognition, the use rate and constant use rate of the child safety seat of parents with correct cognition were 64.5% and 25.7% respectively, while the use rate and constant use rate of the child safety seat of parents with incorrect cognition were only 11.1% and 4.3%, which were significantly lower than those with correct cognition, and the difference was statistically significant. In terms of cognition, 10.4% of parents think it is safe for children to sit in the back seat with adults in their arms, and 9.0% of family members think it is safe for children to sit in the back seat with seat belts alone. Conclusions: At present, the ownership rate, utilization rate, and parents' correct cognition of child safety seats in Leshan City are all at a low level, and there is a lack of regional legal guidance, so the safety situation of children in cars is worrying. To effectively improve the use of child safety seats, the promotion of child safety seats should be promoted from three aspects: improving parents' cognition, forming good traffic habits, and legal guidance.

Mitogenomes of museum specimens provide new insight into species classification and recently reduced diversity of highly endangered Nomascus gibbons.

Our findings reveal that the western black crested gibbon (Nomascus concolor) did not divide into different subspecies, and the relatively low level of genetic diversity emphasizes the importance of monitoring this indicator for vulnerable wildlife. Meanwhile, phylogeographic analysis of the Nomascus genus shows a north-to-south trend of ancestral geographic distribution.

Advances in multiparametric magnetic resonance imaging combined with biomarkers for the diagnosis of high-grade prostate cancer.

Clinical decisions based on the test results for prostate-specific antigen often result in overdiagnosis and overtreatment. Multiparametric magnetic resonance imaging (mpMRI) can be used to identify high-grade prostate cancer (HGPCa; Gleason score ≥3 + 4); however, certain limitations remain such as inter-reader variability and false negatives. The combination of mpMRI and prostate cancer (PCa) biomarkers (prostate-specific antigen density, Proclarix, TMPRSS2:ERG gene fusion, Michigan prostate score, ExoDX prostate intelliscore, four kallikrein score, select molecular diagnosis, prostate health index, and prostate health index density) demonstrates high accuracy in the diagnosis of HGPCa, ensuring that patients avoid unnecessary prostate biopsies with a low leakage rate. This manuscript describes the characteristics and diagnostic performance of each biomarker alone and in combination with mpMRI, with the intension to provide a basis for decision-making in the diagnosis and treatment of HGPCa. Additionally, we explored the applicability of the combination protocol to the Asian population.