Causal Associations Between the Gut Microbiota and Hypertension-Related Traits Through Mendelian Randomization: A Cross-Sectional Cohort Study.

Previous studies have suggested a link between the gut microbiome and hypertension-related traits like blood pressure. However, these reports are often limited by weak causal evidence. This study investigates the potential causal association between gut microbiota and hypertension-related traits using Mendelian randomization with summary data from genome-wide association studies. The inverse-variance weighted method revealed that the Clostridium innocuum group (Odds ratio [OR]: 1.0047, 95% confidence interval [CI]: 1.0004-1.0090, p = 0.0336), Eubacterium fissicatena group (OR: 1.0047, 95% CI: 1.0005-1.0088, p = 0.0266), Lachnospiraceae FCS020 group (OR: 1.0063, 95% CI: 1.0004-1.0122, p = 0.0361), and Olsenella (OR: 1.0044, 95% CI: 1.0001-1.0088, p = 0.0430) were associated with an increased risk of hypertension. Conversely, Flavonifractor (OR: 0.9901, 95% CI: 0.9821-0.9982, p = 0.0166), Parabacteroides (OR: 0.9874, 95% CI: 0.9776-0.9972, p = 0.0121), and Senegalimassilia (OR: 0.9907, 95% CI: 0.9842-0.9974, p = 0.0063) were associated with a decreased risk of hypertension. External validation with the Guangdong Gut Microbiome Project confirmed a negative correlation between Parabacteroides and hypertension, potentially through metabolic pathways. These findings provide further evidence supporting the hypothesis that microbes and their metabolites play a role in blood pressure regulation.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Light-sensitive PEG hydrogel with antibacterial performance for pacemaker pocket infection prevention.

Prevention of cardiovascular implantable electronic devices (CIED) infection is crucial for successful outcomes. In this study, we report an adhesive and antibacterial hydrogel coating for CIED infection treatment, by immobilizing polyethylene glycol (PEG) and 2'-O-hydroxypropyl trimethyl ammonium chloride chitosan (HAC) on Ti surface. Initial alkali and APTES treatment caused the formation of -NH2 to enhance the adhesion of the hydrogel coating to Ti implants, followed by immobilizing a photo-cross-linkable PEG/2'-O-HTACCS hydrogel on Ti/OH/NH2 surface. Surface characterization of Ti/OH/NH2 sample and adhesion testing of hydrogel on Ti/OH/NH2 surface confirm successful immobilization of hydrogel onto the Ti/OH/NH2 surface. In vitro and in vivo antimicrobial results exhibited that the photo-cross-linkable PEG/HAC composite hydrogel has excellent antimicrobial capabilities against both Grampositive (S. aureus and S. epidermidis) and Gram-negative (P. aeruginosa and E. coli) bacteria. The outcome of this study demonstrates the photo-cross linked PEG/HAC coating hydrogels can be easily formed on the Ti implants, and has great potential in preventing CIED pocket infection.

Temporal colonization and metabolic regulation of the gut microbiome in neonatal oxen at single nucleotide resolution.

The colonization of microbes in the gut is key to establishing a healthy host-microbiome symbiosis for newborns. We longitudinally profiled the gut microbiome in a model consisting of 36 neonatal oxen from birth up to 2 months postpartum and carried out microbial transplantation to reshape their gut microbiome. Genomic reconstruction of deeply sequenced fecal samples resulted in a total of 3931 metagenomic-assembled genomes from 472 representative species, of which 184 were identified as new species when compared with existing databases of oxen. Single nucleotide level metagenomic profiling shows a rapid influx of microbes after birth, followed by dynamic shifts during the first few weeks of life. Microbial transplantation was found to reshape the genetic makeup of 33 metagenomic-assembled genomes (FDR < 0.05), mainly from Prevotella and Bacteroides species. We further linked over 20 million microbial single nucleotide variations to 736 plasma metabolites, which enabled us to characterize 24 study-wide significant associations (P < 4.4 × 10-9) that identify the potential microbial genetic regulation of host immune and neuro-related metabolites, including glutathione and L-dopa. Our integration analyses further revealed that microbial genetic variations may influence the health status and growth performance by modulating metabolites via structural regulation of their encoded proteins. For instance, we found that the albumin levels and total antioxidant capacity were correlated with L-dopa, which was determined by single nucleotide variations via structural regulations of metabolic enzymes. The current results indicate that temporal colonization and transplantation-driven strain replacement are crucial for newborn gut development, offering insights for enhancing newborn health and growth.

Early microbial intervention reshapes phenotypes of newborn Bos taurus through metabolic regulations.

BACKGROUND: The rumen of neonatal calves has limited functionality, and establishing intestinal microbiota may play a crucial role in their health and performance. Thus, we aim to explore the temporal colonization of the gut microbiome and the benefits of early microbial transplantation (MT) in newborn calves. RESULTS: We followed 36 newborn calves for 2 months and found that the composition and ecological interactions of their gut microbiomes likely reached maturity 1 month after birth. Temporal changes in the gut microbiome of newborn calves are widely associated with changes in their physiological statuses, such as growth and fiber digestion. Importantly, we observed that MT reshapes the gut microbiome of newborns by altering the abundance and interaction of Bacteroides species, as well as amino acid pathways, such as arginine biosynthesis. Two-year follow-up of those calves further showed that MT improves their later milk production. Notably, MT improves fiber digestion and antioxidant capacity of newborns while reducing diarrhea. MT also contributes to significant changes in the metabolomic landscape, and with putative causal mediation analysis, we suggest that altered gut microbial composition in newborns may influence physiological status through microbial-derived metabolites. CONCLUSIONS: Our study provides a metagenomic and metabolomic atlas of the temporal development of the gut microbiome in newborn calves. MT can alter the gut microbiome of newborns, leading to improved physiological status and later milk production. The data may help develop strategies to manipulate the gut microbiota during early life, which may be relevant to the health and production of newborn calves.

Efficacy and association of hyperbaric oxygen therapy combined with butylphthalide and oxiracetam with serum levels of inflammatory markers in vascular cognitive impairment after acute ischemic stroke.

Objectives: This study evaluated the efficacy of hyperbaric oxygen therapy (HBOT) combined with butylphthalide (NBP) and oxiracetam (OXR) for vascular cognitive impairment after acute ischemic stroke and investigated the association between such combination therapy and the serum levels of inflammatory markers. Methods: This was a prospective study which included eighty patients with post-AIS cognitive impairment (PAISCI) treated in Dongguan City People's Hospital from January 2020 to January 2022. They were randomized into study group and control group. The control group was provided with conventional therapy consisting of NBP for intravenous transfusion and oral OXR, while the study group received combination therapy of HBOT, NBP, and OXR. A comparison was drawn between the two groups regarding clinical outcomes, levels of recovery of cognitive and neurological function and intelligence, changes in inflammatory markers, and incidence of adverse drug reactions (ADRs). Results: The response rate of the study group was significantly higher than that of the control group (p=0.04). The cognitive function scores of the study group were significantly better than those of the control group at the end of treatment (p<0.05). The post-treatment levels of inflammatory markers were significantly reduced in the study group when compared with the control group (p<0.05). At two weeks after treatment, the ADR rate of study group was significantly lower than the control group (p=0.03). Conclusions: The combination therapy of HBOT, NBP, and OXR demonstrates robust efficacy in patients with PAISCI. It is deemed to be a safe and effective treatment regimen.

Remnant cholesterol is associated with cardiovascular mortality.

Background: Genetic, observational, and clinical intervention studies indicate that circulating levels of remnant cholesterol (RC) are associated with cardiovascular diseases. However, the predictive value of RC for cardiovascular mortality in the general population remains unclear. Methods: Our study population comprised 19,650 adults in the United States from the National Health and Nutrition Examination Survey (NHANES) (1999-2014). RC was calculated from non-high-density lipoprotein cholesterol (non-HDL-C) minus low-density lipoprotein cholesterol (LDL-C) determined by the Sampson formula. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of RC with cardiovascular mortality. Results: The mean age of the study cohort was 46.4 ± 19.2 years, and 48.7% of participants were male. During a median follow-up of 93 months, 382 (1.9%) cardiovascular deaths occurred. In a fully adjusted Cox regression model, log RC was significantly associated with cardiovascular mortality [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.17-6.81]. The restricted cubic spline curve indicated that log RC had a linear association with cardiovascular mortality (p for non-linearity = 0.899). People with higher LDL-C (≥130 mg/dL), higher RC [≥25.7/23.7 mg/dL in males/females corresponding to the LDL-C clinical cutoff point (130 mg/dL)] and abnormal HDL-C (<40/50 mg/dL in males/females) levels had a higher risk of cardiovascular mortality (HR 2.18; 95% CI 1.13-4.21 in males and HR 2.19; 95% CI 1.24-3.88 in females) than the reference group (lower LDL-C, lower RC and normal HDL-C levels). Conclusions: Elevated RC levels were associated with cardiovascular mortality independent of traditional risk factors.

Lowering serum homocysteine in H-type hypertensive patients with atrial fibrillation after radiofrequency catheter ablation to prevent atrial fibrillation recurrence.

Background: Prior investigation revealed that elevated serum total homocysteine (tHcy) are strongly correlated with atrial fibrillation (AF) recurrence. Herein, the goal of this study was to elucidate whether folic acid (FA) treatment reduced AF recurrence following radiofrequency catheter ablation (RFCA). Methods: To conduct this retrospective research, we included consecutive H-type hypertensive AF patients, who were treated with first RFCA, between January 2010 and January 2022. We assessed the AF recurrence risk between patients who were taking 10 mg enalapril and 0.8 mg FA in a single-pill combination (enalapril-FA) daily and those who were taking a pill of 10 mg enalapril only. Outcomes were compared using the propensity-score matched analysis. Cox regression model was employed for the evaluation of AF recurrence events. Results: Out of 2,714 patients, 645 patients receiving enalapril and 282 patients receiving enalapril-FA were included for analysis. Following propensity score matching, 239 patients remained in each group. These patients were followed-up for a median of 379 (137-596) days, and revealed that the enalapril-FA patients had drastically reduced AF recurrence, compared to the enalapril patients [adjusted hazard ratio (HR), 0.68; 95% confidence interval (CI), 0.48-0.97; P = 0.029]. Apart from this, no interactions were detected in the subgroup analysis. Conclusion: In H-type hypertensive AF patients who were treated with first RFCA, FA supplementation was correlated with a reduced AF recurrence risk.

High-quality Arabidopsis thaliana Genome Assembly with Nanopore and HiFi Long Reads.

Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains a significant number of missing segments. Here, we reported a high-quality and almost complete Col-0 genome assembly with two gaps (named Col-XJTU) by combining the Oxford Nanopore Technologies ultra-long reads, Pacific Biosciences high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality (QV) scores > 60 (ranging from 62 to 68), which are higher than those of the TAIR10.1 reference (ranging from 45 to 52). We completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 was completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2. We also investigated the structure and epigenetics of centromeres. Four clusters of CEN180 monomers were detected, and the centromere-specific histone H3-like protein (CENH3) exhibited a strong preference for CEN180 Cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as the genetic and epigenetic features in plants.

Decoding microbial genomes to understand their functional roles in human complex diseases.

Complex diseases such as cardiovascular disease (CVD), obesity, inflammatory bowel disease (IBD), kidney disease, type 2 diabetes (T2D), and cancer have become a major burden to public health and affect more than 20% of the population worldwide. The etiology of complex diseases is not yet clear, but they are traditionally thought to be caused by genetics and environmental factors (e.g., dietary habits), and by their interactions. Besides this, increasing pieces of evidence now highlight that the intestinal microbiota may contribute substantially to the health and disease of the human host via their metabolic molecules. Therefore, decoding the microbial genomes has been an important strategy to shed light on their functional potential. In this review, we summarize the roles of the gut microbiome in complex diseases from its functional perspective. We further introduce artificial tools in decoding microbial genomes to profile their functionalities. Finally, state-of-the-art techniques have been highlighted which may contribute to a mechanistic understanding of the gut microbiome in human complex diseases and promote the development of the gut microbiome-based personalized medicine.

Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.

BACKGROUND Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although it is not life-threatening, the accompanying rapid and irregular ventricular rate can lead to hemodynamic deterioration and obvious symptoms, especially the risk of cerebrovascular embolism. Our study aimed to identify novel and promising genes that could explain the underlying mechanism of AF development. MATERIAL AND METHODS Expression profiles GSE41177, GSE79768, and GSE14975 were acquired from the Gene Expression Omnibus Database. R software was used for identifying differentially expressed genes (DEGs), and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. A protein-protein interaction network was constructed in Cytoscape software. Next, a least absolute shrinkage and selection operator (LASSO) model was constructed and receiver-operating characteristic curve analysis was conducted to assess the specificity and sensitivity of the key genes. RESULTS We obtained 204 DEGs from the datasets. The DEGs were mostly involved in immune response and cell communication. The primary pathways of the DEGs were related to the course or maintenance of autoimmune and chronic inflammatory diseases. The top 20 hub genes (high scores in cytoHubba) were selected in the PPI network. Finally, we identified 6 key genes (FCGR3B, CLEC10A, FPR2, IGSF6, S100A9, and S100A12) via the LASSO model. CONCLUSIONS We present 6 target genes that are potentially involved in the molecular mechanisms of AF development. In addition, these genes are likely to serve as potential therapeutic targets.

Cell Membrane-Coated Electrospun Fibers Enhance Keratinocyte Growth through Cell-Type Specific Interactions.

Although cell membrane-coated fiber scaffolds can be useful for regenerative medicine by presenting both cell surface antigens and topographical cues, it remains unknown whether changes in cellular behavior on cell membrane-coated scaffolds are due to specific cell-cell interactions. In this work, the effects of scaffold fiber diameters and surface charges on the cell membrane coating efficiency were explored. Furthermore, fibroblast membrane-coated scaffolds improved the growth of human keratinocytes as compared to red blood cell membrane-coated and plain scaffolds. These results suggest the biofunctionality of cell membrane-coated scaffolds and the specific cell-cell interactions that are preserved to modulate cellular response.

Hyaluronic acid-based antibacterial hydrogels constructed by a hybrid crosslinking strategy for pacemaker pocket infection prevention.

In this study, we developed an injectable antibacterial hydrogel based on hyaluronic acid (HA) and chlorhexidine (CHX) for cardiovascular implantable electronic device (CIED) infection treatment. To balance stability and moldability, the HA scaffold was pre-crosslinked by 1,4-butanediol diglycidyl ether (BDDE) and then ground to form an HA microgel (CHA). Then, the antibacterial agent CHX was further crosslinked in the CHA microgel through electrostatic interactions between CHA and CHX to obtain hybrid crosslinked hydrogels (CHA/CHX). These hydrogels exhibited shear-thinning/self-recovery behavior, allowing easy injection into the CIED pocket and good matching with the pocket shape without extra space requirements, which represents an improvement on previously reported methods. In vitro and in vivo antibacterial tests showed that the CHA/CHX hydrogels had both good biocompatibility and very effective antibacterial action. The above results indicated that the CHA/CHX hydrogels would be an excellent candidate for CIED pocket infection treatment.

Chromosome-Scale Genome Assembly of Fusarium oxysporum Strain Fo47, a Fungal Endophyte and Biocontrol Agent.

Here, we report a chromosome-level genome assembly of Fusarium oxysporum Fo47 (12 pseudomolecules; contig N50: 4.52 Mb), generated using a combination of PacBio long-read, Illumina paired end, and high-throughput chromosome conformation capture sequencing data. Although F. oxysporum causes vascular wilt to over 100 plant species, the strain Fo47 is classified as an endophyte and is widely used as a biocontrol agent for plant disease control. The Fo47 genome carries a single accessory chromosome of 4.23 Mb, compared with the reference genome of F. oxysporum f. sp. lycopersici Fol4287. The high-quality assembly and annotation of the Fo47 genome will be a valuable resource for studying the mechanisms underlying the endophytic interactions between F. oxysporum and plants as well as for deciphering the genome evolution of the F. oxysporum species complex.

FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways.

High fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α-smooth muscle actin (α-SMA), and collagen-1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α-SMA, collagen-1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N-acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.

Retracted Article: Knockdown of TUG1 aggravates hypoxia-induced myocardial cell injury via regulation of miR-144-3p/Notch1.

Myocardial infarction is a common cause of mortality in cardiovascular diseases. Long noncoding RNA taurine-upregulated gene 1 (TUG1) has been reported to play an important role in the regulation of myocardial injury; however, the mechanism via which TUG1 participates in myocardial infarction is unknown. In this study, hypoxia-treated cardiomyoblast H9c2 cells were used as a model of myocardial infarction. Cell transfection was conducted using Lipofectamine 2000 for 48 h. Hypoxia-induced injury was investigated by cell viability and apoptosis using the trypan blue exclusion method, flow cytometry and Western blot. The expressions of TUG1, microRNA-144-3p (miR-144-3p) and the Notch1 pathway were investigated by a quantitative real-time polymerase chain reaction and Western blot. The association between miR-144-3p and TUG1 or Notch1 was analyzed by bioinformatics analysis and luciferase reporter assay. Our results showed that hypoxia-induced H9c2 cell injury led to the inhibition of cell viability and promotion of apoptosis. Moreover, hypoxia could cause the up-regulation of TUG1 and Notch1 expression and down-regulation of miR-144-3p. The knockdown of TUG1 or overexpression of miR-144-3p aggravated the hypoxia-induced viability suppression and apoptosis production in the H9c2 cells. Moreover, miR-144-3p was indicated to be bound to TUG1, and its abrogation reversed the silencing of TUG1-mediated promotion of hypoxia-induced injury. In addition, Notch1 was a target of miR-144-3p, and its restoration attenuated the miR-144-3p-mediated promotion of hypoxia-induced injury. Moreover, TUG1 interference alleviated the hypoxia-induced activation of the Notch1/Hes-1 pathway via the regulation of miR-144-3p. In conclusion, the interference of TUG1 contributed to hypoxia-induced injury via the regulation of the miR-144-3p/Notch1/Hes-1 pathway; this indicated a novel mechanism for understanding the pathogenesis of myocardial infarction.