Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention.

To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1-2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer-Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer-Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.

Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling. We genetically and chemically fuse functional synNotch ligands to ECM proteins and ECM-derived materials. We also generate tissues with microscale precision over four distinct reporter phenotypes by culturing cells with two orthogonal synNotch programs on surfaces microcontact-printed with two synNotch ligands. Finally, we showcase applications in tissue engineering by co-transdifferentiating fibroblasts into skeletal muscle or endothelial cell precursors in user-defined micropatterns. These technologies provide avenues for spatially controlling cellular phenotypes in mammalian tissues.

The effect of physical exercise therapy on autism spectrum disorder:a systematic review and meta-analysis.

BACKGROUND: Physical Exercise Therapy (PET) is increasingly applied in the treatment of Autism Spectrum Disorders (ASD), yet the empirical evidence supporting its efficacy remains ambiguous. This systematic review and meta-analysis aimed to investigate the effectiveness of PET for individuals with ASD, providing evidence-based support for clinical and scientific research. METHODS: We systematically searched four international databases (Medline via PubMed, Embase, Cochrane Libraries, and Web of Science) and three Chinese databases (CNKI, Wanfang, and VIP Libraries) up to July 31, 2023. The search was conducted in both English and Chinese for original research articles employing randomized-controlled-trial (RCT) designs to study PET's effects on individuals diagnosed with ASD according to DSM or other established criteria. Co-primary outcomes focused on the overall severity of autism, while secondary outcomes included measures of stereotyped behaviors, social deficits, social skills, and executive functioning. Data from the included studies were synthesized and analyzed using RevMan 5.4. This systematic review is registered with PROSPERO (CRD42023443951). RESULTS: A total of 28 RCTs comprising 1081 participants were analyzed. Of these, only three studies met high-quality standards. Compared to control groups, PET showed improvement in at least one core symptom of autism, including Motor Performance (SMD=1.72, 95%CI[1.01, 2.44], I2=90%), Restricted Repetitive Behaviors (SMD=-0.81, 95%CI[-1.00, -0.62], I2=0%), Social Dysfunction (SMD=-0.76, 95%CI[-1.06, -0.46], I2=47%). CONCLUSIONS: PET may offer benefits in reducing the overall severity and associated symptoms in individuals with ASD. However, given the high overall risk of bias in the included studies, these findings should be interpreted with caution.

Viscoelasticity in 3D Cell Culture and Regenerative Medicine: Measurement Techniques and Biological Relevance.

The field of mechanobiology is gaining prominence due to recent findings that show cells sense and respond to the mechanical properties of their environment through a process called mechanotransduction. The mechanical properties of cells, cell organelles, and the extracellular matrix are understood to be viscoelastic. Various technologies have been researched and developed for measuring the viscoelasticity of biological materials, which may provide insight into both the cellular mechanisms and the biological functions of mechanotransduction. Here, we explain the concept of viscoelasticity and introduce the major techniques that have been used to measure the viscoelasticity of various soft materials in different length- and timescale frames. The topology of the material undergoing testing, the geometry of the probe, the magnitude of the exerted stress, and the resulting deformation should be carefully considered to choose a proper technique for each application. Lastly, we discuss several applications of viscoelasticity in 3D cell culture and tissue models for regenerative medicine, including organoids, organ-on-a-chip systems, engineered tissue constructs, and tunable viscoelastic hydrogels for 3D bioprinting and cell-based therapies.

'Implicit rationing of nursing care processes'-Decision-making in ICU nurses' experiences: A qualitative study.

BACKGROUND: Implicit rationing of nursing care is defined as the withholding of necessary nursing measures for patients because of a lack of nursing resources. However, no studies have explored the experience of decision-making about implicit rationing of nursing care in an intensive care unit (ICU). AIM: To explore the process of ICU nurses' decisions and judgement based on the conceptual framework of implicit rationing of nursing care. STUDY DESIGN: A qualitative study was undertaken between June 2020 and September 2020. The data collection methods were participative observation and interview. Eighteen ICU nurses participated in interviews. A thematic analysis was performed for the data analysis. RESULTS: The following five themes emerged: assessment of the condition and nature of nursing and time taken; strategies for setting personal priorities; plan implementation under mitigation strategy; existing nursing in reality; evaluation of the implementation of implicit rationing care. Nurses choose different strategies during plan implementation. CONCLUSIONS: In the absence of explicit guidelines on rationing nursing care, nurses often rely on intuitive and situational decision-making processes for setting priorities. Given the vulnerability of ICU patients and the absence of family caregivers, nurses bear a heightened ethical responsibility to provide care. Establishing a positive nursing culture is essential. It is both reasonable and effective to organize work by accurately quantifying workload, improving staffing levels and optimizing scheduling methods. These themes align with the decision-making process outlined in the conceptual framework and offer fresh perspectives. RELEVANCE TO CLINICAL PRACTICE: Nurses have a greater responsibility to provide care in an ethical manner and to increase awareness of the importance of holistic nursing care for the patient, that is to raise awareness of the importance of care that is often missed. Nurses actively adopt strategies to reduce implicit rationing of nursing care, including teamwork, organized nursing, working overtime and ignoring quality. The findings highlight the importance of creating a positive nursing culture that encourages nurses to adopt positive strategies.

Removal of tetracycline in the water by a kind of S/N co-doped tea residue biochar.

Tetracycline (TC) is widely present in the environment, and adsorption technology is a potential remediation method. S/N co-doped tea residue biochar (SNBC) was successfully prepared by hydrothermal carbonization method using tea residue as raw material. S was doped by Na2S2O3·5H2O, and N was doped by N in tea residue. The adsorption efficiency of SNBC could reach 94.16% when the concentration of TC was 100 mg L-1. The adsorption effect of SNBC on TC was 9.38 times more than that of unmodified biochar. Tea biochar had good adsorption effect at pH 4-9. The maximum adsorption capacity of 271 mg g-1 was calculated by the Langmuir isotherm model. The adsorption mechanism involved many mechanisms such as pore filling, π-π interaction and hydrogen bonding. The adsorbent prepared in this study could be used as an effective adsorbent in the treatment of TC wastewater.

Characterizing Excretory-Secretory Products Proteome Across Larval Development Stages in Ascaris suum.

Introduction: Ascaris lumbricoides and Ascaris suum are parasitic nematodes that primarily infest the small intestines of humans and pigs, respectively. Ascariasis poses a significant threat to human health and swine health. Understanding Ascaris larval development is crucial for developing novel therapeutic interventions that will prevent ascariasis in both humans and pigs. This study aimed to characterize the excretory-secretory (ES) proteome of different Ascaris suum larval stages (L3-egg, L3-lung, L3-trachea) to identify potential targets for intervention to prevent Ascaris -induced global morbidity. Methods: Stage-specific larvae were isolated, cultured in vitro and ES-product was collected. Third-stage Ascaris larvae (L3) were isolated from embryonated eggs (L3-egg), isolated from the lungs of Balb/c mice infected with Ascaris suum eggs at day 8 post infection (L3-lungs) and isolated from the trachea of Balb/c mice infected with Ascaris suum eggs at day 12 post infection (L3-trachea). ES products were obtained by culturing larvae. Proteomic analysis was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatic tools including MaxQuant, Perseus, and Andromeda, following a detailed protocol available on GitHub. The analysis encompassed peptide identification, scoring, and quantification against an organism-specific database, with subsequent quality control, correlation assessment, and differential abundance determination using the Amica algorithm. Results: A total of 58 unique proteins were identified in the ES products. Fourteen proteins were common across all stages, while others were stage-specific. Principal component analysis revealed distinct protein profiles for each stage, suggesting qualitatively different proteomes. Gene ontology analysis indicated stage-specific GO enrichment of specific protein classes, such as nuclear proteins in L3-egg ES products and metabolic enzymes in L3-lung and L3-trachea ES products. Discussion: This study revealed stage-specific differences in the composition of Ascaris ES products. Further investigation into the functional roles of these proteins and their interactions with host cells is crucial for developing novel therapeutic and diagnostic strategies against ascariasis.

Progress of SGLT2 inhibitors in the treatment of common immune-related nephropathies.

The immune system can lead to a variety of renal diseases through direct or indirect mechanisms. In immune-mediated nephropathy, though standardized treatment, there are still a small number of patients with further decline in renal function, which may even progress to renal failure; sodium-glucose cotransporter protein 2 (SLC5A2,SGLT2) inhibitors not only can significantly reduce blood glucose, but also have an additional protective effect on the kidneys and the heart; this review concludes the potential mechanism of the renal protective effect of SGLT2i and the new advances in the recent years in common immune-mediated nephropathies, which can provide new theoretical references to optimize the therapeutic strategy of common immune-mediated nephropathies.

Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.

Discovery of a first-in-class protein degrader for the c-ros oncogene 1 (ROS1).

The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.

From electricity to vitality: the emerging use of piezoelectric materials in tissue regeneration.

The unique ability of piezoelectric materials to generate electricity spontaneously has attracted widespread interest in the medical field. In addition to the ability to convert mechanical stress into electrical energy, piezoelectric materials offer the advantages of high sensitivity, stability, accuracy and low power consumption. Because of these characteristics, they are widely applied in devices such as sensors, controllers and actuators. However, piezoelectric materials also show great potential for the medical manufacturing of artificial organs and for tissue regeneration and repair applications. For example, the use of piezoelectric materials in cochlear implants, cardiac pacemakers and other equipment may help to restore body function. Moreover, recent studies have shown that electrical signals play key roles in promoting tissue regeneration. In this context, the application of electrical signals generated by piezoelectric materials in processes such as bone healing, nerve regeneration and skin repair has become a prospective strategy. By mimicking the natural bioelectrical environment, piezoelectric materials can stimulate cell proliferation, differentiation and connection, thereby accelerating the process of self-repair in the body. However, many challenges remain to be overcome before these concepts can be applied in clinical practice, including material selection, biocompatibility and equipment design. On the basis of the principle of electrical signal regulation, this article reviews the definition, mechanism of action, classification, preparation and current biomedical applications of piezoelectric materials and discusses opportunities and challenges for their future clinical translation.

Origin of the Improved Photoelectrochemical and Photocatalytic Activity in a ZnO-TiO2 Nanohybrid Revealed by Experimental and Density Functional Theory Studies.

Heterojunctions of metal oxides have attracted a great deal of attention as photo (electro) catalysts owing to their excellent photoactivity. While multiple fundamental studies have been dedicated to heteroaggregation, self-assembly of oppositely charged particles to obtain heterojunctions for energy applications has been underexplored. Herein, we report the synthesis of ZnO-TiO2 heterojunctions using the electrostatic self-assembly approach. The synthesized ZnO-TiO2 heterojunctions were characterized by using multiple experimental techniques. Density functional theory calculations were conducted to establish the heterojunction formation mechanism and electronic properties. The ZnO-TiO2 nanohybrid was tested for the photodegradation of rhodamine B dye and water splitting applications. The photocatalytic performance of the ZnO-TiO2 nanohybrid is 3.5 times higher than that of bare ZnO. In addition, the heterostructure exhibited an excellent photocurrent density of 2.4 mA cm-2 at a low onset potential during photoelectrochemical oxygen evolution. The performance improvements are attributed to the formation of the type II heterojunction between ZnO and TiO2, which suppresses carrier recombination and enhances carrier transport, boosting the catalytic activity.

Rosa roxburghii Fruit Extracts Upregulate Telomerase Activity and Ameliorate Cell Replicative Senescence.

Anti-aging functional foods benefit the elderly. Telomeres are chromosomal ends that maintain genome stability extended by telomerase catalytic subunit TERT. Due to the end-replication problem, telomeres shorten after each cell cycle without telomerase in most human cells, and eventually the cell enters the senescence stage. Natural products can attenuate the aging process by increasing telomerase activity, such as TA-65. However, TA-65 is expensive. Other Chinese natural products may achieve comparable effects. Here, we found that Rosa roxburghii fruit extracts effectively increase TERT expression and telomerase activity in cultured human mesenchymal stem cells. Both R. roxburghii fruit extracts obtained by freeze-drying and spray-drying increased the activity of telomerase. R. roxburghii fruit extracts were able to reduce reactive oxygen species levels, enhance superoxide dismutase activity, and reduce DNA damage caused by oxidative stress or radiation. R. roxburghii fruit extracts promoted cell proliferation, improved senescent cell morphology, delayed replicative cellular senescence, attenuated cell cycle suppressors, and alleviated the senescence-associated secretory phenotype. Transcriptome and metabolic profiling revealed that R. roxburghii fruit extracts promote DNA replication and telomere maintenance pathways and decrease triglyceride levels. Overall, we provide a theoretical basis for the application of R. roxburghii fruit as an anti-aging product.

The protective effect and bioactive compounds of Astragalus membranaceus against neurodegenerative disorders via alleviating oxidative stress in Drosophila.

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.

Single-Cell Imaging of mRNA by Target RNA-Initiated RCA.

We present a powerful method for direct mRNA detection based on ligation-based recognition and in situ amplification, capable of single-cell imaging mRNA at single-nucleotide and single-molecule resolution. Attributed to the use of Splint R ligase that can ligate padlock probe with RNA as target template, this method can efficiently detect mRNA in the absence of reverse transcription. This method enables spatial localization and correlation analysis of gene expression in single cells, which helps us to elucidate gene function and regulatory mechanisms.

Epidemic Characteristics and Meteorological Risk Factors of Hemorrhagic Fever With Renal Syndrome in 151 Cities in China From 2015 to 2021: Retrospective Analysis.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) continues to pose a significant public health threat to the population in China. Previous epidemiological evidence indicates that HFRS is climate sensitive and influenced by meteorological factors. However, past studies either focused on too-narrow geographical regions or investigated time periods that were too early. There is an urgent need for a comprehensive analysis to interpret the epidemiological patterns of meteorological factors affecting the incidence of HFRS across diverse climate zones. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics of HFRS and explore the linkage between monthly HFRS cases and meteorological factors at different climate levels in China. METHODS: The reported HFRS cases and meteorological data were collected from 151 cities in China during the period from 2015 to 2021. We conducted a 3-stage analysis, adopting a distributed lag nonlinear model and a generalized additive model to estimate the interactions and marginal effects of meteorological factors on HFRS. RESULTS: This study included a total of 63,180 cases of HFRS; the epidemic trends showed seasonal fluctuations, with patterns varying across different climate zones. Temperature had the greatest impact on the incidence of HFRS, with the maximum hysteresis effects being at 1 month (-19 ºC; relative risk [RR] 1.64, 95% CI 1.24-2.15) in the midtemperate zone, 0 months (28 ºC; RR 3.15, 95% CI 2.13-4.65) in the warm-temperate zone, and 0 months (4 ºC; RR 1.72, 95% CI 1.31-2.25) in the subtropical zone. Interactions were discovered between the average temperature, relative humidity, and precipitation in different temperature zones. Moreover, the influence of precipitation and relative humidity on the incidence of HFRS had different characteristics under different temperature layers. The hysteresis effect of meteorological factors did not end after an epidemic season, but gradually weakened in the following 1 or 2 seasons. CONCLUSIONS: Weather variability, especially low temperature, plays an important role in epidemics of HFRS in China. A long hysteresis effect indicates the necessity of continuous intervention following an HFRS epidemic. This finding can help public health departments guide the prevention and control of HFRS and develop strategies to cope with the impacts of climate change in specific regions.

In-situ direct seawater electrolysis using floating platform in ocean with uncontrollable wave motion.

Direct hydrogen production from inexhaustible seawater using abundant offshore wind power offers a promising pathway for achieving a sustainable energy industry and fuel economy. Various direct seawater electrolysis methods have been demonstrated to be effective at the laboratory scale. However, larger-scale in situ demonstrations that are completely free of corrosion and side reactions in fluctuating oceans are lacking. Here, fluctuating conditions of the ocean were considered for the first time, and seawater electrolysis in wave motion environment was achieved. We present the successful scaling of a floating seawater electrolysis system that employed wind power in Xinghua Bay and the integration of a 1.2 Nm3 h-1-scale pilot system. Stable electrolysis operation was achieved for over 240 h with an electrolytic energy consumption of 5 kWh Nm-3 H2 and a high purity (>99.9%) of hydrogen under fluctuating ocean conditions (0~0.9 m wave height, 0~15 m s-1 wind speed), which is comparable to that during onshore water electrolysis. The concentration of impurity ions in the electrolyte was low and stable over a long period of time under complex and changing scenarios. We identified the technological challenges and performances of the key system components and examined the future outlook for this emerging technology.

Cross-cultural adaptation and validation of the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) for Chinese community-dwelling residents: A cross-sectional Study.

OBJECTIVE: To cross-culturally adapt the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) and verify the reliability and validity of its cognitive activity domain. METHODS: According to Beaton's guidelines, the ANU-ADRI was were translated into Chinese. The psychometric properties of ANU-ADRI its cognitive activity was conducted among community-dwelling residents (n = 442) in Changchun, Harbin and Hegang from December 2021 to July 2023. RESULTS: The Chinese version of the ANU-ADRI had good content validity and face validity. Exploratory factor analysis of cognitive activity revealed a 3-factor structure, with a cumulative variance contribution rate of 64.124 %. Confirmatory factor analysis revealed a good model fit (x2/df = 1.664, RMSEA = 0.055, RMR = 0.090, GFI = 0.942, CFI = 0.919, IFI = 0.921, TLI = 0.902, and NFI = 0.824). The internal consistency (Cronbach's α = 0.807) and test-retest reliability (ICC = 0.787) were considered satisfactory. CONCLUSION: The ANU-ADRI showed acceptable reliability and validity for assessing risk factors for Alzheimer's disease among middle-aged and elderly community-dwelling residents.

A non-antibiotic antimicrobial drug, a biological bacteriostatic agent, is useful for treating aerobic vaginitis, bacterial vaginosis, and vulvovaginal candidiasis.

Background: Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are widely used to treat vaginitis, recurrent vaginitis occurs in some patients. Resistance to these agents is the major cause of recurrent vaginitis. Therefore, there is an urgent need to develop novel drugs. Methods: We investigated the efficacy of a new biological bacteriostatic agent (BBA), composed of lysozyme, phytoalexin, chitosan oligosaccharide, sinensetin, 18ß/20α-glycyrrhizin, and betaine, against vaginitis using in vitro and in vivo studies. First, we evaluated the antibacterial effects of BBA against 13 microbial strains commonly present in aerobic vaginitis, bacterial vaginosis, vulvovaginal candidiasis, and healthy vaginas. Second, we assessed the safety of various doses of BBA administered orally for 4 weeks in female mice. Third, we examined the in vivo anti-proliferative and anti-inflammatory effects of BBA in Candida albicans-, Candida glabrata-, and Gardnerella-induced vaginitis models. Finally, we evaluated the anti-vaginitis effect of a BBA gel prepared with 0.5% (w/v) ammonium acryloyldimethyltaurate/Vp copolymer. Results: BBA effectively suppressed the growth of the main causative pathogens of vaginitis in vitro. BBA, either undiluted or diluted two-fold, inhibited all microorganisms cultured for 8 h. No obvious organ damage was detected when BBA was administered to mice. Both BBA alone and 70% BBA in a gel formulation effectively inhibited the proliferation of C. albicans, C. glabrata, and Gardnerella in vaginal lavage samples and alleviated tissue inflammation in mice with vaginitis. The 70% BBA gel performed better than BBA alone at treating vaginitis in mice infected with Gardnerella vaginalis. Conclusion: BBA alone and a 70% BBA gel inhibited the growth of pathogens and effectively alleviated inflammation caused by C. albicans, C. glabrata, and G. vaginalis.

Modulation of Ras signaling pathway by exosome miRNAs in T-2 toxin-induced chondrocyte injury.

This study aims to investigate the impact of T-2 toxin on the regulation of downstream target genes and signaling pathways through exosome-released miRNA in the development of cartilage damage in Kashin-Beck disease (KBD). Serum samples from KBD patients and supernatant from C28/I2 cells treated with T-2 toxin were collected for the purpose of comparing the differential expression of exosomal miRNA using absolute quantitative miRNA-seq. Target genes of differential exosomal miRNAs were identified using Targetscan and Miranda databases, followed by GO and KEGG enrichment analyses. Validation of key indicators of chondrocyte injury in KBD was conducted using Real-time quantitative PCR (RT-qPCR) and Immunohistochemical staining (IHC). A total of 20 exosomal miRNAs related to KBD were identified in serum, and 13 in chondrocytes (C28/I2). The identified exosomal miRNAs targeted 48,459 and 60,612 genes, primarily enriched in cell organelles and membranes, cell differentiation, and cytoskeleton in the serum, and the cytoplasm and nucleus, metal ion binding in chondrocyte (C28/I2). The results of the KEGG enrichment analysis indicated that the Ras signaling pathway may play a crucial role in the pathogenesis of KBD. Specifically, the upregulation of hsa-miR-181a-5p and hsa-miR-21-3p, along with the downregulation of hsa-miR-152-3p and hsa-miR-186-5p, were observed. Additionally, T-2 toxin intervention led to a significant downregulation of RALA, REL, and MAPK10 expression. Furthermore, the protein levels of RALA, REL, and MAPK10 were notably decreased in the superficial and middle layers of cartilage tissues from KBD. The induction of differential expression of chondrocyte exosomal miRNAs by T-2 toxin results in the collective regulation of target genes RALA, REL, and MAPK10, ultimately mediating the Ras signaling pathway and causing a disruption in chondrocyte extracellular matrix metabolism, leading to chondrocyte injury.