Therapeutic effects of ginsenosides on osteoporosis for novel drug applications.

Osteoporosis (OP) is a metabolic bone disease with a high incidence rate worldwide. Its main features are decreased bone mass, increased bone fragility and deterioration of bone microstructure. It is caused by an imbalance between bone formation and bone resorption. Ginsenoside is a safe and effective traditional Chinese medicine (TCM) usually extracted from ginseng plants, having various therapeutic effects, of which the effect against osteoporosis has been extensively studied. We searched a total of 44 relevant articles with using keywords including osteoporosis, ginsenosides, bone mesenchymal cells, osteoblasts, osteoclasts and bone remodeling, all of which investigated the cellular mechanisms of different types of ginsenosides affecting the activity of bone remodeling by mesenchymal stem cells, osteoblasts and osteoclasts to counteract osteoporosis. This review describes the different types of ginsenosides used to treat osteoporosis from different perspectives, providing a solid theoretical basis for future clinical applications.

The clinical use of remote parameter testing during cardiac implantable electronic devices implantation procedures: a single center, randomized, open-label, non-inferiority trial.

Background: A novel non-contact system for remote parameter testing and reprogramming offers an alternative method for assessing device parameters during cardiac implantable electronic devices (CIEDs) implantation without the need for physical contact with the manufacturer's clinical service technician. The safety and feasibility of using this system in CIEDs implantation procedures remains to be determined. Objective: Evaluate the safety and feasibility of remote parameter testing in CIEDs implantation procedures. Methods: A single center, randomized, open-label, non-inferiority trial (ChiCTR2200057587) was conducted to compare the two approaches for interrogating CIEDs during implantation procedures: routine interrogation performed by on-site technicians or remote interrogation performed by technicians using the 5G-Cloud Technology Platform. Patients aged ≥18 years and elected to receive CIEDs were eligible for inclusion. The primary endpoint was the completion rate of the parameter test. Safety and efficiency were evaluated in all randomly assigned participants. Results: A total of 480 patients were finally enrolled and were randomly assigned to routine group (n = 240) or remote group (n = 240). The primary endpoint was achieved by 100% in both groups (P = 0.0060 for noninferiority). The parameters of sensing, threshold, and impedance regarding the right atrium, right ventricle, and left ventricle had no statistical significance between the two groups (P > 0.05). Procedure time, parameter testing time, and both duration and dose of x-ray irradiation were not significantly different between the two groups (P > 0.05). Shut-open door frequency was significantly higher in the routine group than the remote group [6.00 (4.00, 8.00) vs. 0, P < 0.0001]. Notably, no clinical or technical complications were observed in the remote group. Conclusions: Remote parameter testing is safe and feasible across various devices implantation procedures. The utilization of remote parameter testing and reprogramming could represent an innovative approach to improve healthcare accessibility and unlock the full potential of secondary centers in managing CIEDs. The Registration Identification: ChiCTR2200057587.

Diagnosis of malignant body fluids via cancer-universal methylation in cell-free DNA.

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).

The association of cigarette smoking with DNA methylation and gene expression in human tissue samples.

Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). We identified 6,350 smoking-associated CpGs in lung tissue (n = 212) and 2,735 in colon tissue (n = 210), most not reported previously. For all 7 other tissue types (sample sizes 38-153), no clear associations were observed (false discovery rate 0.05), but some tissues showed enrichment for smoking-associated CpGs reported previously. For 1,646 loci (in lung) and 22 (in colon), smoking was associated with both DNAm and local gene expression. For loci detected in both lung and colon (e.g., AHRR, CYP1B1, CYP1A1), top CpGs often differed between tissues, but similar clusters of hyper- or hypomethylated CpGs were observed, with hypomethylation at regulatory elements corresponding to increased expression. For lung tissue, 17 hallmark gene sets were enriched for smoking-associated CpGs, including xenobiotic- and cancer-related gene sets. At least four smoking-associated regions in lung were impacted by lung methylation quantitative trait loci (QTLs) that co-localize with genome-wide association study (GWAS) signals for lung function (FEV1/FVC), suggesting epigenetic alterations can mediate the effects of smoking on lung health. Our multi-tissue approach has identified smoking-associated regions in disease-relevant tissues, including effects that are shared across tissue types.

Risks and Clinical Predictors of Hepatocellular Carcinoma in Chinese Populations: A Real-World Study of 10,359 Patients in Six Medical Centers.

Purpose: Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China. Patients and Methods: A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up. Results: Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis. Conclusion: The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.

The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men.

BACKGROUND: American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity. METHODS: To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays. RESULTS: Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis. CONCLUSIONS: These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue. IMPACT: Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions.

Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.

Angong Niuhuang Wan inhibit ferroptosis on ischemic and hemorrhagic stroke by activating PPARγ/AKT/GPX4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Angong Niuhuang Wan (AGNHW) is a prescription from traditional Chinese medicine (TCM) that has been used for centuries to treat ischemic stroke (IS) and hemorrhagic stroke (HS). According to a recent study, targeting ferroptosis might be effective in the management of IS and HS. However, the ferroptosis-related effects and mechanisms of AGNHW have not yet been reported. AIM OF THE STUDY: This research examines the anti-ferroptosis mechanisms of AGNHW in the treatment of IS and HS. MATERIALS AND METHODS: A system pharmacological approach including in vivo experiment, UHPLC-Q-Orbitrap HRMS, network pharmacology, molecular docking, microscale thermophoresis, and in vitro experiment was utilized to study the anti-ferroptosis mechanisms of AGNHW against IS and HS. RESULTS: In vivo experiments indicated that AGNHW enhanced nerve function, decreased cerebral infarct volume, ameliorated histological brain injuries, improved the structural integrity of the blood-brain barrier, ameliorated the mitochondrial dysfunction and morphology disruption, and inhibits ROS, LPO and Fe2+ accumulations in IS and HS rats. Using UHPLC-Q-Orbitrap HRMS, the key ingredients of AGNHW-containing serum were identified as bilirubin, berberine, baicalin, and wogonoside. According to the network pharmacology analyses, AGNHW could inhibit ferroptosis by modulating the PPAR and PI3K/AKT signaling pathways. The core targets are PPARγ, AKT, and GPX4. Molecular docking and microscale thermophoresis experiments further revealed that the key ingredients have strong interactions with ferroptosis-regulating core proteins. Moreover, in vitro experiment results showed that AGNHW alleviated ferroptosis injury induced by erastin in PC12 cells, increased cell viability, reduced the LPO and Fe2+ levels, and up-regulated mRNA expressions of PPARγ, AKT, and GPX4. AGNHW also up-regulated protein expressions of PPARγ, p-AKT/AKT, and GPX4 in IS and HS rats. CONCLUSIONS: AGNHW attenuated ferroptosis in treating IS and HS by targeting the PPARγ/AKT/GPX4 pathway. This work reveals AGNHW's anti-ferroptosis mechanism against IS and HS, but it also develops an integrated approach to demonstrate the common characteristics of drugs in treating different diseases.

Three-dimensional eco-friendly bacterial nanocellulose (BNC) scaffold for regenerative dentistry: Characterization, cytocompatibility and differentiation potential.

OBJECTIVE: Regenerative dentistry (RD) is an innovative strategy for treating necrotic teeth and regenerating damaged dental tissue. Biocompatible materials are pivotal for the advancement of RD, and the rising interest in environmental sustainability drives exploration of sustainable materials for dentistry. Bacterial nanocellulose (BNC) has emerged as a promising eco-friendly option and this study aims to assess BNC's suitability as scaffolds for regenerative dentistry applications. METHODS: Different in vitro methods have been utilized to characterize the properties of BNC scaffolds in regenerative dentistry, such as scanning electron microscopy (SEM) to analyse surface property and porosity, as well as examining their absorption behaviour using phosphate-buffered saline and bovine serum. Dental pulp stem cell (DPSCs) attachment, viability, and proliferation were evaluated using SEM, live and dead, and tetrazolium reduction assays. The odontogenic potential of the scaffold was evaluated using Alizarin Red staining and qPCR (14 and 21 days). RESULTS: Scanning electron microscopy (SEM) images and ethanol displacement method demonstrated the porous architecture of the BNC scaffold with an average porosity of 70.02 ± 4.74% and 50.26 ± 1.43% respectively. The scaffold absorbed 2846.54 ± 258.95 of BSA and 1648.63 ± 50.37% PBS after immersion in solution for 1 h, following pseudo first and second order kinetics. The biocompatibility assay indicated that cell density increased with time and that the scaffold was appropriate for cell adhesion and migration. Moreover, the BNC led to significantly higher mineralization and odontogenic expression compared to the control (BNC in conditioned media). SIGNIFICANCE: BNC showed fast adsorption of bovine serum, allowed DPSC attachment, migration, and odontogenic differentiation. This suggests its suitability as a biocompatible scaffold for triggering in situ mineralized tissue regeneration for regenerative dental applications.

Overall quality changes and deterioration mechanism of fragrant rapeseed oils during 6-Month storage.

The strong-fragrant rapeseed oil (SFRO) is a popular rapeseed oil in China with a low refining degree only degumming with hot water, which remarkably affects its storage stability. The present study compared the overall changes of physical/chemical/nutrient quality of FROs at various temperatures, light wavelengths and headspace volumes. Results showed that red light (680 nm) had a most significant adverse effect on the overall quality of SFRO with the higher correlation coefficients to PV and TOTOX of 0.71 and 0.70, and lower correlation coefficients to chlorophyll and tocopherol of -0.95 and -0.53, respectively. Further studies revealed that red light accelerated the oxidation of fragrant rapeseed oils by degrading chlorophyll to initiate the photo-oxidation process and synthesize high amount of secondary oxidation products including aliphatic and aromatic oxidized compounds from linolenic acid. These findings provided a reference to control the deterioration of FROs by preventing the transmittance of red light.

Selection of yeast strains in naturally fermented cured meat as promising starter cultures for fermented cured beef, a traditional fermented meat product of northern China.

BACKGROUND: Fermented meat products are meat products with a unique flavor, color, and texture as well as an extended shelf life under natural or artificially controlled conditions. Microorganisms or enzymes are used to ferment the raw meat so that it undergoes a series of biochemical and physical changes. Common fermentation strains are lactic acid bacteria, yeasts, staphylococci, molds, and so forth. Studies on the inhibitory effect of yeast fermentation strain on N-nitrosamines in fermented meat products have not been reported. Two excellent yeast starters were identified to solve the problem of nitrosamines in fermented meat products. RESULTS: Meyerozyma guilliermondii and Debaryomyces hansenii led to weak acid production, strong resistance to NaCl and NaNO2 , and high tolerance to low acidic conditions. The inoculated fermented beef exhibited decreased lightness, moisture content, water activity, pH, protein content, nitrite content, and N-nitrosamine content in comparison with the control group fermented bacon. M. guilliermondii had a better effect, reducing pH from 5.69 to 5.41, protein content from 254.24 to 221.92 g·kg-1 , nitrite content from 28.61 to 25.33 mg·kg-1 and N-nitrosamine by 18.97%, and giving the fermented beef the desired meat color, mouthfeel, odor, taste, and tissue quality. CONCLUSION: In this study, two strains of yeast fermenters that can degrade N-nitrosamine precursors were identified, which to some extent solves the problem of the high risk of generating nitrosamines such as N-nitrosodiethylamine (NDEA) by processing fermented meat products with nitrites as precursors. These two strains are likely to be used as starter cultures for fermented meat products. © 2023 Society of Chemical Industry.

Coriaceumins A-D, the First Nitrogen-Containing Crenulide Diterpenoids from the Brown Alga Dictyota coriacea Collected in the East China Sea.

A phytochemical investigation of an East China Sea collection of the brown alga Dictyota coriacea has led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A-D (1-4), two rare nitrogenous xenicane diterpenoids, dictyolactams C (5) and D (6), and one known crenulide diterpenoid, hydroxycrenulide (7). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations. Coriaceumins A-D (1-4) represent the first examples of nitrogen-containing crenulide diterpenoids. In a bioassay, compounds 2, 3, 5, and 7 were found to exhibit different levels of inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) with IC50 values ranging from 7.3 to 19 µM. In addition, the primary structure-activity relationships of all the isolates were summarized.

Returning personal genetic information on susceptibility to arsenic toxicity to research participants in Bangladesh.

BACKGROUND: There is growing consensus that researchers should offer to return genetic results to participants, but returning results in lower-resource countries has received little attention. In this study, we return results on genetic susceptibility to arsenic toxicity to participants in a Bangladeshi cohort exposed to arsenic through naturally-contaminated drinking water. We examine the impact on behavioral changes related to exposure reduction. METHODS: We enrolled participants from the Health Effects of Arsenic Longitudinal Study who had (1) high arsenic (≥150 µg/g creatinine) in a recent urine sample and (2) existing data on genetic variants impacting arsenic metabolism efficiency (AS3MT and FTCD). We used genetic data to recruit three study groups, each with n = 103: (1) efficient metabolizers (low-risk), (2) inefficient metabolizers (high-risk), and (3) a randomly-selected control group (NCT05072132). At baseline, all participants received information on the effects of arsenic and how to reduce exposure by switching to a low arsenic well. The two intervention groups also received their arsenic metabolism efficiency status (based on their genetic results). Changes in behavior and arsenic exposure were assessed using questionnaires and urine arsenic measures after six months. RESULTS: Clear decreases in urine arsenic after six months were observed for all three groups. The inefficient group self-reported higher levels of attempted switching to lower arsenic wells than the other groups; however, there was no detectable difference in urine arsenic reduction among the three groups. Participants showed strong interest in receiving genetic results and found them useful. The inefficient group experienced higher levels of anxiety than the other groups. Among the efficient group, that receiving genetic results did not appear to hinder behavioral change. CONCLUSION: Returning genetic results increased self-reported exposure-reducing behaviors but did not have a detectable impact on reducing urine arsenic over and above a one-on-one educational intervention.

The distribution of intestinal flora after hematopoietic stem cell transplantation in children.

BACKGROUND: This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD). METHODS: A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri-transplant including pre-transplant, Day +3, and Day +30. RESULTS: By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p = .029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0-I° aGVHD and II-III° aGVHD indicates that children with II-III° aGVHD had more Bilophila before transplantation than children with 0-I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed. CONCLUSIONS: This study has synthetically shown the distribution of intestinal flora after allo-HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease.

Development of an autoantibody panel for early detection of lung cancer in the Chinese population.

Introduction: Tumor-associated autoantibodies have been revealed as promising biomarkers for the early detection of lung cancer. This study was designed to develop an autoantibody panel for early detection of lung cancer in the Chinese population. Methods: Recruited prospectively in three clinical centers, the subjects (n = 991) who had a definite diagnosis during follow-up were included in the development of the autoantibody panel. The levels of 14 autoantibody candidates in plasma were detected. Results: A panel of nine autoantibody markers (named as CN9), namely, P53, SOX2, SSX1, HuD, NY-ESO-1, CAGE, MAGE-A4, P62, and CK20, was preferably selected from 14 candidates. The overall specificity, sensitivity, and AUC were 90.5%, 40.8%, and 0.64, respectively. The CN9 panel demonstrated a reasonable detection rate in lung cancer patients at all stages, histological types, sizes of lesions, and risk levels. Its estimated overall accuracy is 85.5% and 90%, with PPV at 0.32 and 0.04, and NPV at 0.93 and 0.99 in the scenario of pulmonary nodules' characterizing and lung cancer screening, respectively. Two risk models were developed within the subgroups of malignant and benign pulmonary nodules in this study. By adding the CN9 result to the Mayo model indicators, it achieved a sensitivity of 41.3% and an AUC of 0.74 at a specificity of 91.3%. By adding the CN9 result to the Brock model indicators, it achieved a sensitivity of 47.7% and an AUC of 0.78 at a specificity of 91.3%. Both were improved compared with either the standalone Mayo or Brock model. Discussion: This multi-center prospective study indicates a panel of nine autoantibody markers that can help in the detection of lung cancer and the classification of pulmonary nodules in the Chinese population.

Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a disease with high mortality and morbidity. Regulator of G protein signaling protein 6 (RGS6), identified as a tumor suppressor gene, has received increasing attention owing to its close relationship with oxidative stress and inflammation. However, the association between ARDS and RGS6 has not been reported. METHODS: Congruously regulated G protein-coupled receptor (GPCR)-related genes and differentially expressed genes (DEGs) in an acute lung injury (ALI) model were identified, and functional enrichment analysis was conducted. In an in vivo study, the effects of RGS6 knockout were studied in a mouse model of ALI induced by lipopolysaccharide (LPS). HE staining, ELISA, and immunohistochemistry were used to evaluate pathological changes and the degree of inflammation. In vitro, qRT‒PCR, immunofluorescence staining, and western blotting were used to determine the dynamic changes in RGS6 expression in cells. The RGS6 overexpression plasmid was constructed for transfection. qRT‒PCR was used to assess proinflammatory factors transcription. Western blotting and flow cytometry were used to evaluate apoptosis and reactive oxygen species (ROS) production. Organoid culture was used to assess the stemness and self-renewal capacity of alveolar epithelial type II cells (AEC2s). RESULTS: A total of 110 congruously regulated genes (61 congruously upregulated and 49 congruously downregulated genes) were identified among GPCR-related genes and DEGs in the ALI model. RGS6 was downregulated in vivo and in vitro in the ALI model. RGS6 was expressed in the cytoplasm and accumulated in the nucleus after LPS stimulation. Compared with the control group, we found higher mortality, more pronounced body weight changes, more serious pulmonary edema and pathological damage, and more neutrophil infiltration in the RGS6 knockout group upon LPS stimulation in vivo. Moreover, AEC2s loss was significantly increased upon RGS6 knockout. Organoid culture assays showed slower alveolar organoid formation, fewer alveolar organoids, and impaired development of new structures after passaging upon RGS6 knockout. In addition, RGS6 overexpression decreased ROS production as well as proinflammatory factor transcription in macrophages and decreased apoptosis in epithelial cells. CONCLUSIONS: RGS6 plays a protective role in ALI not only in early inflammatory responses but also in endogenous lung stem cell regeneration.

Effect of calcium ion concentration on the ORR performance of Pd/C catalysts.

Noble metal electrocatalysts prepared by microbial methods have attracted extensive attention because of their environmental protection and easy preparation. However, the preparation of electrocatalysts by microbial methods has problems such as large nanoparticles size and low loading rate. In this study, the porous gel co-embedded with Shewanella and alginate is prepared as the adsorption matrix to further enhance its mass transfer and adsorption efficiency. The effect of calcium ion concentration on catalyst performance is explored by optimizing the CaCl2 concentration to expose more adsorption sites. The results show that when the Ca2+ concentration is 0.025 mmol L-1, the prepared catalyst has the smallest size and the highest Pd loading, and exhibits the best electrochemical activity and stability. This provides a new idea for the preparation of electrocatalysts by microbial methods.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes.

BACKGROUND: The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. AIM: To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. METHODS: We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. RESULTS: There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (ß = 1.953, P = 0.005). CONCLUSION: High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction.

We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.