Unveiling the overlooked microbial niches thriving on building exteriors.

Rapid urbanization in the Asia-Pacific region is expected to place two-thirds of its population in concrete-dominated urban landscapes by 2050. While diverse architectural facades define the unique appearance of these urban systems. There remains a significant gap in our understanding of the composition, assembly, and ecological potential of microbial communities on building exteriors. Here, we examined bacterial and protistan communities on building surfaces along an urbanization gradient (urban, suburban and rural regions), investigating their spatial patterns and the driving factors behind their presence. A total of 55 bacterial and protist phyla were identified. The bacterial community was predominantly composed of Proteobacteria (33.7% to 67.5%). The protistan community exhibited a prevalence of Opisthokonta and Archaeplastida (17.5% to 82.1% and 1.8% to 61.2%, respectively). The composition and functionality of bacterial communities exhibited spatial patterns correlated with urbanization. In urban buildings, factors such as facade type, light exposure, and building height had comparatively less impact on bacterial composition compared to suburban and rural areas. The highest bacterial diversity and lowest Weighted Average Community Identity (WACI) were observed on suburban buildings, followed by rural buildings. In contrast, protists did not show spatial distribution characteristics related to facade type, light exposure, building height and urbanization level. The distinct spatial patterns of protists were primarily shaped by community diffusion and the bottom-up regulation exerted by bacterial communities. Together, our findings suggest that building exteriors serve as attachment points for local microbial metacommunities, offering unique habitats where bacteria and protists exhibit independent adaptive strategies closely tied to the overall ecological potential of the community.

Unveiling unique alternative splicing responses to low temperature in Zoysia japonica through ZjRTD1.0, a high-quality reference transcript dataset.

Inadequate reference databases in RNA-seq analysis can hinder data utilization and interpretation. In this study, we have successfully constructed a high-quality reference transcript dataset, ZjRTD1.0, for Zoysia japonica, a widely-used turfgrass with exceptional tolerance to various abiotic stress, including low temperatures and salinity. This dataset comprises 113,089 transcripts from 57,143 genes. BUSCO analysis demonstrates exceptional completeness (92.4%) in ZjRTD1.0, with reduced proportions of fragmented (3.3%) and missing (4.3%) orthologs compared to prior datasets. ZjRTD1.0 enables more precise analyses, including transcript quantification and alternative splicing assessments using public datasets, which identified a substantial number of differentially expressed transcripts (DETs) and differential alternative splicing (DAS) events, leading to several novel findings on Z. japonica's responses to abiotic stresses. First, spliceosome gene expression influenced alternative splicing significantly under abiotic stress, with a greater impact observed during low-temperature stress. Then, a significant positive correlation was found between the number of differentially expressed genes (DEGs) encoding protein kinases and the frequency of DAS events, suggesting the role of protein phosphorylation in regulating alternative splicing. Additionally, our results suggest possible involvement of serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in generating inclusion/exclusion isoforms under low-temperature stress. Furthermore, our investigation revealed a significantly enhanced overlap between DEGs and differentially alternatively spliced genes (DASGs) in response to low-temperature stress, suggesting a unique co-regulatory mechanism governing transcription and splicing in the context of low-temperature response. In conclusion, we have proven that ZjRTD1.0 will serve as a reliable and useful resource for future transcriptomic analyses in Z. japonica.

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer.

Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A's implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.

Integration of hepatitis B virus into patients' sperm genome and its clinical risks.

BACKGROUND: Like the coronavirus disease 2019, the hepatitis B virus is also wreaking havoc worldwide, which has infected over 2 billion people globally. Using an experimental animal model, our previous research observed that the hepatitis B virus genes integrated into human spermatozoa can replicate and express after being transmitted to embryos. However, as of now, this phenomenon has not been confirmed in clinical data from patients. OBJECTIVES: To explore the integration of the hepatitis B virus into patients' sperm genome and its potential clinical risks. MATERIALS AND METHODS: Forty-eight patients with chronic hepatitis B virus infection were categorized into two groups: Test Group-1 comprised 23 patients without integration of hepatitis B virus DNA within the sperm genome. Test Group-2 comprised 25 patients with integration of hepatitis B virus DNA within the sperm genome. Forty-eight healthy male donors were included as control. The standard semen parameter analysis, real-time polymerase chain reaction, quantitative real-time polymerase chain reaction, sperm chromatin structure assay, fluorescence in situ hybridization, and immunofluorescence assays were utilized. RESULTS: The difference in the median copy number of hepatitis B virus DNA per mL of sera between Test Group-1 and Group-2 was not statistically significant. In Test Group-2, the integration rate of hepatitis B virus DNA was 0.109%, which showed a significant correlation with the median copy number of hepatitis B virus DNA in motile spermatozoa (1.18 × 103 /mL). Abnormal semen parameters were found in almost all these 25 patients. The integrated hepatitis B virus S, C, X, and P genes were detected to be introduced into sperm-derived embryos through fertilization and retained their function in replication, transcription, and translation. CONCLUSION: Our findings suggest that hepatitis B virus infection can lead to sperm quality deterioration and reduced fertilization capacity. Furthermore, viral integration causes instability in the sperm genome, increasing the potential risk of termination, miscarriage, and stillbirth. This study identified an unconventional mode of hepatitis B virus transmission through genes rather than virions. The presence of viral sequences in the embryonic genome poses a risk of liver inflammation and cancer.

Gait Recognition and Assistance Parameter Prediction Determination Based on Kinematic Information Measured by Inertial Measurement Units.

The gait recognition of exoskeletons includes motion recognition and gait phase recognition under various road conditions. The recognition of gait phase is a prerequisite for predicting exoskeleton assistance time. The estimation of real-time assistance time is crucial for the safety and accurate control of lower-limb exoskeletons. To solve the problem of predicting exoskeleton assistance time, this paper proposes a gait recognition model based on inertial measurement units that combines the real-time motion state recognition of support vector machines and phase recognition of long short-term memory networks. A recognition validation experiment was conducted on 30 subjects to determine the reliability of the gait recognition model. The results showed that the accuracy of motion state and gait phase were 99.98% and 98.26%, respectively. Based on the proposed SVM-LSTM gait model, exoskeleton assistance time was predicted. A test was conducted on 10 subjects, and the results showed that using assistive therapy based on exercise status and gait stage can significantly improve gait movement and reduce metabolic costs by an average of more than 10%.

Association between dietary inflammatory index and cognitive impairment among American elderly: a cross-sectional study.

Background: It has been shown that inflammation may be associated with cognitive impairment (CI). Diet modulates inflammation. However, there is currently a scarcity of epidemiological studies exploring the connection between the inflammatory potential of diet and CI. The objective was to investigate the correlation between the dietary inflammatory index (DII) and cognitive impairment in older adults in the United States. Methods: The present investigation utilized a cross-sectional dataset obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dietary intake data was used to calculate DII scores, which were then used to categorize participants into quartiles. Participants' cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Individuals who scored in the lowest quartile on any of these tests were classified as exhibiting low cognitive performance. The association between DII and cognitive impairment was investigated by multivariate logistic regression, smooth curve fitting, and subgroup analysis. Results: A total of 947 older adults were enrolled in the study. Following the adjustment of confounding variables, DII scores exhibited a significant and positive correlation with low cognitive performance, as measured by AFT (OR 1.15, 95% CI 1.02-1.28, p = 0.02) and the DSST (OR 1.38, 95% CI 1.13-1.68, p = 0.004). Compared with the lowest quartile of DII, the highest weighted odds ratio of cognitive impairment based on AFT was observed in the fourth quartile group (OR 1.89, 95% CI 1.05-3.38, p = 0.03). Similarly, a comparable pattern was evident in DSST (OR 4.30, 95% CI 1.85-9.98, p = 0.003). Additionally, the smooth curve fitting results showed a nonlinear relationship between DII and cognitive decline evaluated by DSST (p for nonlinearity = 0.016). No interaction effects between cognitive impairment and age or gender were observed in relation to all cognitive test scores. Conclusion: This research reveals a positive link between diet with higher inflammatory potential and cognitive decline among elderly individuals in America. However, additional studies on dietary interventions are necessary to explore the cause-and-effect relationship.

The Pharmacogenetic Variability Associated With the Pharmacokinetics and Pharmacodynamics of Rivaroxaban in Healthy Chinese Subjects: A National Multicenter Exploratory Study.

PURPOSE: This study aimed to explore the pharmacogenetic variability associated with the pharmacokinetics (PK) and pharmacodynamics (PD) of rivaroxaban in healthy Chinese subjects. METHODS: This was a multicenter study that included 304 healthy adults aged 18 to 45 years with unknown genotypes. All participants were administered a single dose of rivaroxaban at 10 mg, 15 mg, or 20 mg. PK and PD parameters were measured, and exome-wide association analysis was conducted. FINDINGS: Sixteen SNPs located on 11 genes influenced the AUC0-t. Among these, the 3 most influential genes were MiR516A2, PARP14, and MIR618. Thirty-six SNPs from 28 genes were associated with the PD of rivaroxaban. The 3 most influential genes were PKNOX2, BRD3, and APOL4 for anti-Xa activity, and GRIP2, PLCE1, and MLX for diluted prothrombin time (dPT). Among them, BRD3 played an important role in both the PK and PD of rivaroxaban. Anti-Xa activity (ng/mL) differed significantly among subjects with BRD3 rs467387: 145.1 ± 55.5 versus 139.9 ± 65.1 versus 164.0 ± 68.6 for GG, GA, and AA carriers, respectively (P = 0.0002). IMPLICATIONS: This study found that that the regulation of the BRD3 gene might affect the PK and PD of rivaroxaban, suggesting that it should be studied as a new pharmacologic target. The correlation between this gene locus and clinical outcomes has yet to be verified in patients undergoing clinical treatment.

New sesquiterpenoids with neuroprotective effects in vitro and in vivo from the Picrasma chinensis.

Three undescribed sesquiterpenes, designed as pichinenoid A-C (1-3), along with nine known ones (4-12) were isolated from the stems and leaves of Picrasma chinensis. The new isolates including their absolute configurations were elucidated based on extensive spectroscopic methods, single crystal X-ray diffraction, and electronic circular dichroism (ECD) experiments, as well as comparison with literature data. Structurally, compounds 1 and 2 are descending sesquiterpenes, while pichinenoid C (3) is a rare sesquiterpene bearing a 2-methylenebut-3-enoic acid moiety at the C-6 side chain. All the isolated compounds were tested for their neuroprotective effects against the H2O2-induced damage on human neuroblastoma SH-SY5Y cells, and most of them showed moderate neuroprotective activity. Especially, compounds 1, 3-5, and 7 showed a potent neuroprotective effect at 25 or 50 µM. Moreover, the neuroprotective effects of compounds 1 and 4 were tested on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Results of western blot and immunofluorescence indicated that compound 4 significantly counteract the toxicity of MPTP, and reversed the expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum (ST) of the mouse brain. Interestingly, western blot data suggested compound 4 also enhanced B-cell lymphoma-2 (Bcl-2) and heme oxygenase 1 (HO-1) expressions in the brain tissues from MPTP damaged mouse.

Chronic exposure to ambient air pollution and the risk of non-alcoholic fatty liver disease: A cross-sectional study in Taiwan and Hong Kong.

BACKGROUND: Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD. METHODS: We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO2) and ozone (O3) were estimated using a space-time regression model, and the concentrations of fine particulate matter (PM2.5) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis. RESULTS: We found positive relationships between PM2.5 and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m3) increases in PM2.5 exposure being associated with a 10% (95% confidence interval [CI]: 9%-11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%-9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%-9%) and 7% (95% CI: 6%-8%) with per SD (18.9 µg/m3) increasement in NO2 concentration, respectively. Additionally, for every SD (9.9 µg/m3) increasement in O3 concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%-13%) and 11% (95% CI: 9%-12%), respectively. CONCLUSION: Higher ambient PM2.5 and NO2 are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM2.5 and NO2 concentrations may be an effective way for preventing NAFLD. Further studies on O3 are warranted.

Involvement of DJ-1 in the pathogenesis of intervertebral disc degeneration via hexokinase 2-mediated mitophagy.

Intervertebral disc degeneration (IDD) is an important pathological basis for degenerative spinal diseases and is involved in mitophagy dysfunction. However, the molecular mechanisms underlying mitophagy regulation in IDD remain unclear. This study aimed to clarify the role of DJ-1 in regulating mitophagy during IDD pathogenesis. Here, we showed that the mitochondrial localization of DJ-1 in nucleus pulposus cells (NPCs) first increased and then decreased in response to oxidative stress. Subsequently, loss- and gain-of-function experiments revealed that overexpression of DJ-1 in NPCs inhibited oxidative stress-induced mitochondrial dysfunction and mitochondria-dependent apoptosis, whereas knockdown of DJ-1 had the opposite effect. Mechanistically, mitochondrial translocation of DJ-1 promoted the recruitment of hexokinase 2 (HK2) to damaged mitochondria by activating Akt and subsequently Parkin-dependent mitophagy to inhibit oxidative stress-induced apoptosis in NPCs. However, silencing Parkin, reducing mitochondrial recruitment of HK2, or inhibiting Akt activation suppressed DJ-1-mediated mitophagy. Furthermore, overexpression of DJ-1 ameliorated IDD in rats through HK2-mediated mitophagy. Taken together, these findings indicate that DJ-1 promotes HK2-mediated mitophagy under oxidative stress conditions to inhibit mitochondria-dependent apoptosis in NPCs and could be a therapeutic target for IDD.

Risk factors and a nomogram for predicting cognitive frailty in Chinese patients with lung cancer receiving drug therapy: A single-center cross-sectional study.

BACKGROUND: To identify independent factors of cognitive frailty (CF) and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy. METHODS: In this cross-sectional study, patients with lung cancer undergoing drug therapy from October 2022 to July 2023 were enrolled. The data collected includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis. RESULTS: A total of 372 patients were recruited, with a cognitive frailty prevalence of 56.2%. Age, education background, diabetes mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors. Then, a nomogram model was constructed and patients were classified into high- and low-risk groups with a cutoff value of 0.552. The internal validation results revealed good concordance, calibration and discrimination. The decision curve analysis presented prominent clinical utility. CONCLUSIONS: The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment.

C-type lectin-like receptor 2: roles and drug target.

C-type lectin-like receptor-2 (CLEC-2) is a member of the C-type lectin superfamily of cell surface receptors. The first confirmed endogenous and exogenous ligands of CLEC-2 are podoplanin and rhodocytin, respectively. CLEC-2 is expressed on the surface of platelets, which participates in platelet activation and aggregation by binding with its ligands. CLEC-2 and its ligands are involved in pathophysiological processes, such as atherosclerosis, cancer, inflammatory thrombus status, maintenance of vascular wall integrity, and cancer-related thrombosis. In the last 5 years, different anti- podoplanin antibody types have been developed for the treatment of cancers, such as glioblastoma and lung cancer. New tests and new diagnostics targeting CLEC-2 are also discussed. CLEC-2 mediates thrombosis in various pathological states, but CLEC-2-specific deletion does not affect normal hemostasis, which would provide a new therapeutic tool for many thromboembolic diseases. The CLEC-2-podoplanin interaction is a target for cancer treatment. CLEC-2 may be applied in clinical practice and play a therapeutic role.

Exposure to Neighborhood Greenness and Hypertension Incidence in Adults: A Longitudinal Cohort Study in Taiwan.

BACKGROUND: There are few studies on the health effects of long-term exposure to neighborhood greenness in a longitudinal setting, especially in Asian countries with high population densities. OBJECTIVES: This study investigates the association between long-term exposure to neighborhood greenness and hypertension among adults in Taiwan. METHODS: We selected 125,537 participants (≥18 years of age) without hypertension from Taiwan who had joined the standard medical examination program between 2001 and 2016. Neighborhood greenness was estimated using the normalized difference vegetation index (NDVI), derived from satellite images at a resolution of 250 m2. The 2-y average NDVI value within a 500-m circular buffer around participants' residences was calculated. A time-varying Cox regression model was used to investigate the association between neighborhood greenness and incident hypertension. Mediation analyses were performed to examine whether the association was explained by air pollution, leisure-time physical exercise, or body mass index (BMI). RESULTS: Compared with living in areas within the first quartile of neighborhood greenness, living in areas within the second, third, and fourth quartiles of neighborhood greenness was found to be associated with a lower risk of hypertension, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.95 (95% CI: 0.91, 1.00), 0.95 (95% CI: 0.90, 0.99), and 0.93 (95% CI: 0.88, 0.97), respectively. Each 0.1-unit increase in the NDVI was associated with a 24% lower risk of developing hypertension (HR=0.76; 95% CI: 0.66, 0.87), with this associations being stronger among males and those with higher education levels. This association was slightly mediated by BMI but not by air pollution or leisure-time physical exercise. DISCUSSION: Our findings suggest the protective effects of neighborhood greenness on hypertension development, especially in males and well-educated individuals. Our results reinforced the importance of neighborhood greenness for supporting health. https://doi.org/10.1289/EHP13071.

Trajectories of body mass index before the diagnosis of type 2 diabetes in a cohort of Taiwanese adults.

BACKGROUND: Although the prevalence of overweight/obesity is lower in Asian countries, the risk of type 2 diabetes (T2DM) is disproportionally higher. We identified and characterized the trajectory patterns of body mass index (BMI) before the onset of T2DM in a Taiwanese population. METHODS: Using the Taiwan MJ cohort study, we sampled the health examination data of 22,934 participants, including 7618 cases of T2DM and 15,316 controls. We used latent class trajectory analysis to identify distinct groups of pre-disease BMI trajectory. To compare the trajectories of cardiometabolic risk factors among different groups, we used linear mixed-effects models. RESULTS: These 22,934 participants included 13,074 men (57%) and 9860 women (43%) who were on average followed for 9.0 years. We identified three distinct pre-disease BMI trajectories in cases: "stable overweight" (n = 7016, 92.1%), "weight gain" (n = 333, 4.4%) and "obesity" (n = 269, 3.5%). The "stable overweight" group had a mean BMI of 24.6 kg/m2 at 15 years prior to diagnosis, had a 1.2 unit increase during follow-up, and had a mean BMI of 25.8 kg/m2 at the time of diagnosis. The "weight gain" group had the most increasing trends in blood pressure/low-density lipoprotein cholesterol over time. CONCLUSION: The BMI trajectory patterns among individuals who later developed diabetes in Taiwan seemed comparable to that of Western populations, but our population developed T2DM at a much lower BMI. Given that most cases belong to the "stable overweight" group, we also support using a population-based strategy for diabetes prevention instead of focusing on the high risk individuals.

Outdoor artificial light at night and incident cardiovascular disease in adults: A national cohort study across China.

Cardiovascular diseases (CVDs) become a major public health concern. Evidence concerning the effects of outdoor artificial light at night (ALAN) on CVD in adults is scarce. We aimed to investigate the extent to which outdoor ALAN could affect the risk of CVD over a exposure range. Data from the China Health and Retirement Longitudinal Study, a population-based longitudinal study, launched in 2011-2012 and follow up till 2018, covering 28 provinces, autonomous regions and municipalities across mainland China. This study included 14,097 adults aged ≥45 years. Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's baseline residence was obtained from satellite image data. CVD was defined from medical diagnosis. The population was divided into three groups based on outdoor ALAN exposure from low to high. Cox regression model was used to estimate the association between outdoor ALAN exposure and incident CVD with hazard ratios (HRs) and 95 % confidence intervals (CIs). The mean (SD) age of the cohort was 57.6 (9.1) years old and 49.3 % were males. Outdoor ALAN exposure of study participants ranged from 0.02 to 39.79 nW/cm2/sr. During 83,033 person-years of follow-up, 2190 (15.5 %) cases of CVD were identified. Both low (HR: 1.21; 95 % CI: 1.02-1.43) and high (HR: 1.23; 95 % CI: 1.04-1.46) levels of outdoor ALAN exposure group were associated with higher risk of CVD compared with intermediate levels of outdoor ALAN exposure group. Body mass index was a significant effect modifier in the association between outdoor ALAN and risk of CVD, with stronger effects among those who was overweight or obese. The findings of this study suggest that low and high outdoor ALAN exposure were associated with a higher risk for CVD. More attention should be given to the cardiovascular effects associated with outdoor ALAN exposure.

Correlation between symptoms and cognitive function changes in patients with primary insomnia and pathways in gut microbiota.

Background: Primary insomnia (PI) refers to syndromes of difficulty falling asleep, poor sleep quality, early awakening, and difficulty falling asleep after waking up. Although there have been numerous studies, the specific etiology and pathogenesis of PI are still misunderstanding. In recent years, the gut microbiota has been proved to be involved in the metabolism of many mental disorders. But the specific mechanisms of its involvement in PI have not been fully elucidated. This study aims to explore the relationship between the gut microbiota and the symptoms, cognitive function changes in PI. Methods: In this study, the gut microbiota of PI patients and healthy controls was profiled by performing stool 16s rRNA gene sequencing. The co-occurrence network was constructed by using Weight Gene Co-expression Network Analysis (WGCNA) algorithm. The correlation between gut microbiota associated pathways and traits in PI were predicted. Results: WGCNA results demonstrated several Operational Taxonomic Units (OTU) modules are correlated to symptoms. By using PICRUSt2 software, we predicted the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of microbiota in modules. For instance, sleep efficiency may be correlated with the presence of Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane and chlorobenzene degradation. Total sleep time may be correlated with the presence of Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation and Biosynthesis of unsaturated fatty acids. The severity of insomnia may be correlated with Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism and RNA polymerase. Change of name score in Montreal Cognitive Assessment (MoCA) may be correlated with Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Nitrotoluene degradation, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation in Gut Microbiota (GM). Conclusion: This study revealed the potential relationships between gut microbiota and PI. By using pathway prediction and enrichment analysis, we concluded many metabolic pathways may associated with some important traits of insomnia patients, including sleep efficiency, severe insomnia, total sleep time and change of name score in MoCA. The metabolic pathways include Insulin signaling pathway, Flavonoid biosynthesis, Ascorbate and aldarate metabolism, Nitrotoluene degradation, Biotin metabolism, RNA polymerase and Chlorocyclohexane, chlorobenzene degradation, Tyrosine metabolism, Propanoate metabolism, Carbon fixation pathways in prokaryotes, Carotenoid biosynthesis, Systemic lupus erythematosus, Biosynthesis of unsaturated fatty acids, Apoptosis, Steroid hormone biosynthesis, Geraniol degradation, Protein digestion and absorption and Bisphenol degradation.Our study demonstrated that PI patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and syndromes of PI.

Qihuang Zhuyu formula alleviates coronary microthrombosis by inhibiting PI3K/Akt/αIIbß3-mediated platelet activation.

BACKGROUND: Coronary microembolism (CME) is commonly seen in the peri-procedural period of Percutaneous Coronary Intervention (PCI), where local platelet activation and endothelial cell inflammation crosstalk may lead to micro thrombus erosion and rupture, with serious consequences. Qihuang Zhuyu Formula (QHZYF) is a Chinese herbal compound with high efficacy against coronary artery disease, but its antiplatelet mechanism is unclear. HYPOTHESIS/PURPOSE: This study aimed to elucidate the effects and mechanisms of QHZYF on sodium laurate-induced CME using network pharmacology and in vitro and in vivo experiments. METHODS: We employed high-performance liquid chromatography mass spectrometry to identify the main components of QHZYF. Network pharmacology analysis, molecular docking and surface plasmon resonance (SPR) were utilized to predict the primary active components, potential therapeutic targets, and intervention pathways mediating the effects of QHZYF on platelet activation. Next, we pretreated a sodium laurate-induced minimally invasive CME rat model with QHZYF. In vivo experiments were performed to examine cardiac function in rats, to locate coronary arteries on heart sections to observe internal microthrombi, to extract rat Platelet-rich plasma (PRP) for adhesion assays and CD62p and PAC-1 (ITGB3/ITGA2B) flow assays, and to measure platelet-associated protein expression in PRP. In vitro clot retraction and Co-culture of HUVECs with PRP were performed and the gene pathway was validated through flow cytometry and immunofluorescence. RESULTS: Combining UPLC-Q-TOF/MS technology and database mining, 78 compounds were finally screened as the putative and representative compounds of QHZYF, with 75 crossover genes associated with CME. QHZYF prevents CME mainly by regulating key pathways of the inflammation and platelets, including Lipid and atherosclerosis, Fluid shear stress, platelet activation, and PI3K-Akt signaling pathways. Five molecules including Calyson, Oroxin A, Protosappanin A,Kaempferol and Geniposide were screened and subjected to molecular docking and SPR validation in combination with Lipinski rules (Rule of 5, Ro5). In vivo experiments showed that QHZYF not only improved myocardial injury but also inhibited formation of coronary microthrombi. QHZYF inhibited platelet activation by downregulating expression of CD62p receptor and platelet membrane protein αIIbß3 and reduced the release of von Willebrand Factor (vWF), Ca2+ particles and inflammatory factor IL-6. Further analysis revealed that QHZYF inhibited the activation of integrin αIIbß3, via modulating the PI3K/Akt pathways. In in vitro experiments, QHZYF independently inhibited platelet clot retraction. Upon LPS induction, the activation of platelet membrane protein ITGB3 was inhibited via the PI3K/Akt pathway, revealing an important mechanism for attenuating coronary microthrombosis. We performed mechanistic validation using PI3K inhibitor LY294002 and Akt inhibitor MK-2206 to show that QHZYF inhibited platelet membrane protein activation and inflammation to improved coronary microvessel embolism by regulating PI3K/Akt/αIIbß3 pathways, mainly by inhibiting PI3K and Akt phosphorylation. CONCLUSION: QHZYF interferes with coronary microthrombosis through inhibition of platelet adhesion, activation and inflammatory crosstalk, thus has potential in clinical anti-platelet applications. Calyson, Oroxin A, Protosappanin A, Kaempferol and Geniposide may be the major active ingredient groups of QHZYF that alleviate coronary microthrombosis.

[Analysis of the causes of cage subsidence after oblique lateral lumbar interbody fusion].

OBJECTIVE: To observe the cage subsidence after oblique lateral interbody fusion (OLIF) for lumbar spondylosis, summarize the characteristics of the cage subsidence, analyze causes, and propose preventive measures. METHODS: The data of 144 patients of lumbar spine lesions admitted to our hospital from October 2015 to December 2018 were retrospectively analyzed. There were 43 males and 101 females, and the age ranged from 20 to 81 years old, with an average of (60.90±10.06) years old. Disease types:17 patients of lumbar intervertebral disc degenerative disease, 12 patients of giant lumbar disc herniation, 5 patients of discogenic low back pain, 33 patients of lumbar spinal stenosis, 26 patients of lumbar degenerative spondylolisthesis, 28 patients of lumbar spondylolisthesis with spondylolisthesis, 11 patients of adjacent vertebral disease after lumbar internal fixation, 7 patients of primary spondylitis in the inflammatory outcome stage, and 5 patients of lumbar degenerative scoliosis. Preoperative dual-energy X-ray bone mineral density examination showed 57 patients of osteopenia or osteoporosis, and 87 patients of normal bone density. The number of fusion segments:124 patients of single-segment, 11 patients of two-segment, 8 patients of three-segment, four-segment 1 patient. There were 40 patients treated by stand-alone OLIF, and 104 patients by OLIF combined with posterior pedicle screw. Observed the occurrence of fusion cage settlement after operation, conducted monofactor analysis on possible risk factors, and observed the influence of fusion cage settlement on clinical results. RESULTS: All operations were successfully completed, the median operation time was 99 min, and the median intraoperative blood loss was 106 ml. Intraoperative endplate injury occurred in 30 patients and vertebral fracture occurred in 5 patients. The mean follow-up was (14.57±7.14) months from 6 to 30 months. During the follow-up, except for the patients of primary lumbar interstitial inflammation and some patients of lumbar spondylolisthesis with spondylolisthesis, the others all had different degrees of cage subsidence. Cage subsidence classification:119 patients were normal subsidence, and 25 patients were abnormal subsidence (23 patients were gradeⅠ, and 2 patients were gradeⅡ). There was no loosening or rupture of the pedicle screw system. The height of the intervertebral space recovered from the preoperative average (9.48±1.84) mm to the postoperative average (12.65±2.03) mm, and the average (10.51±1.81) mm at the last follow-up. There were statistical differences between postoperative and preoperative, and between the last follow-up and postoperative. The interbody fusion rate was 94.4%. The low back pain VAS decreased from the preoperative average (6.55±2.2 9) to the last follow-up (1.40±0.82), and there was statistically significant different. The leg pain VAS decreased from the preoperative average (4.72±1.49) to the final follow-up (0.60±0.03), and the difference was statistically significant (t=9.13, P<0.000 1). The ODI index recovered from the preoperative average (38.50±6.98)% to the latest follow-up (11.30±3.27)%, and there was statistically significant different. The complication rate was 31.3%(45/144), and the reoperation rate was 9.72%(14/144). Among them, 8 patients were reoperated due to fusion cage subsidence or displacement, accounting for 57.14%(8/14) of reoperation. The fusion cage subsidence in this group had obvious characteristics. The monofactor analysis showed that the number of abnormal subsidence patients in the osteopenia or osteoporosis group, Stand-alone OLIF group, 2 or more segments fusion group, and endplate injury group was higher than that in the normal bone mass group, OLIF combined with pedicle screw fixation group, single segment fusion group, and no endplate injury group, and the comparison had statistical differences. CONCLUSION: Cage subsidence is a common phenomenon after OLIF surgery. Preoperative osteopenia or osteoporosis, Stand-alone OLIF, 2 or more segments of fusion and intraoperative endplate injury may be important factors for postoperative fusion cage subsidence. Although there is no significant correlation between the degree of cage subsidence and clinical symptoms, there is a risk of cage migration, and prevention needs to be strengthened to reduce serious complications caused by fusion of cage subsidence, including reoperation.

Baroreflex activation therapy for heart failure with reduced ejection fraction: A comprehensive systematic review and meta-analysis.

Background: In recent years, baroreflex activation therapy (BAT) has been utilized to treat heart failure with reduced ejection fraction (HFrEF). However, the supporting literature on its efficacy and safety is still limited. This investigation elucidates the effects of BAT in HFrEF patients to provide a reference for future clinical applications. Methods: This investigation follows Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. Relevant investigations on the use of BAT in HFrEF patients were searched and selected from 5 databases, including Web of Science, MEDLINE, PubMed, Embase, and Cochrane Library, from inception to December 2022. The methodological quality of eligible articles was assessed via the Cochrane risk of bias tool, and for meta-analysis, RevMan (5.3) was used. Results: Randomized controlled trials comprising 343 participants were selected for the meta-analysis, which revealed that in HFrEF patients, BAT enhanced the levels of LVEF (MD: 2.97, 95 % CI: 0.53 to 5.41), MLHFQ (MD: -14.81, 95 % CI: -19.57 to -10.06) and 6MWT (MD: 68.18, 95 % CI: 51.62 to 84.74), whereas reduced the levels of LVEDV (MD: -15.79, 95 % CI: -32.96 to 1.37) and DBP (MD: -2.43, 95 % CI: -4.18 to -0.68). Conclusion: It was concluded that BAT is an efficient treatment option for HFrEF patients. However, to validate this investigation, further randomized clinical trials with multiple centers and large sample sizes are needed.

An image-driven micromechanical approach to characterize multiscale remodeling in infarcted myocardium.

Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework to elucidate the fiber-level remodeling mechanisms that drive tissue-level adaptation for each subject. We found that a progressively diffused collagen fiber structure combined with similarly disorganized myofiber architecture in the healthy region leads to the loss of LVFW anisotropy post-MI, offering an important tissue-level hallmark for LV maladaptation. In contrast, our results suggest that reductions in collagen undulation are an adaptive mechanism competing against LVFW thinning. Additionally, we show that the inclusion of subject-specific geometry when modeling myocardial tissue is essential for accurate prediction of tissue kinematics. Our approach serves as an essential step toward identifying fiber-level remodeling indices that govern the transition of MI to systolic heart failure. These indices complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI. In addition, our approach offers an integrated methodology to advance the design of personalized interventions, such as hydrogel injection, to reinforce and suppress native adaptive and maladaptive mechanisms, respectively, to prevent the transition of MI to heart failure. STATEMENT OF SIGNIFICANCE: Biomechanical and architectural adaptation of the LVFW remains a central, yet overlooked, remodeling process post-MI. Our study indicates the biomechanical adaptation of the LVFW post-MI is highly individual and driven by altered fiber network architecture and collective changes in collagen fiber content, undulation, and stiffness. Our findings demonstrate the possibility of using cardiac strains to infer such fiber-level remodeling events through in-silico modeling, paving the way for in-vivo characterization of multiscale biomechanical indices in humans. Such indices will complement the traditional, organ-level measures of LV anatomy and function that often fall short of early prognostication of heart failure in MI.