Deciphering PDH1's role in mung bean domestication: a genomic perspective on pod dehiscence.

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.

SoyDNGP: a web-accessible deep learning framework for genomic prediction in soybean breeding.

Soybean is a globally significant crop, playing a vital role in human nutrition and agriculture. Its complex genetic structure and wide trait variation, however, pose challenges for breeders and researchers aiming to optimize its yield and quality. Addressing this biological complexity requires innovative and accurate tools for trait prediction. In response to this challenge, we have developed SoyDNGP, a deep learning-based model that offers significant advancements in the field of soybean trait prediction. Compared to existing methods, such as DeepGS and DNNGP, SoyDNGP boasts a distinct advantage due to its minimal increase in parameter volume and superior predictive accuracy. Through rigorous performance comparison, including prediction accuracy and model complexity, SoyDNGP represents improved performance to its counterparts. Furthermore, it effectively predicted complex traits with remarkable precision, demonstrating robust performance across different sample sizes and trait complexities. We also tested the versatility of SoyDNGP across multiple crop species, including cotton, maize, rice and tomato. Our results showed its consistent and comparable performance, emphasizing SoyDNGP's potential as a versatile tool for genomic prediction across a broad range of crops. To enhance its accessibility to users without extensive programming experience, we designed a user-friendly web server, available at http://xtlab.hzau.edu.cn/SoyDNGP. The server provides two features: 'Trait Lookup', offering users the ability to access pre-existing trait predictions for over 500 soybean accessions, and 'Trait Prediction', allowing for the upload of VCF files for trait estimation. By providing a high-performing, accessible tool for trait prediction, SoyDNGP opens up new possibilities in the quest for optimized soybean breeding.

Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis.

Diabetic nephropathy (DN) is one of the common microvascular complications in diabetic patients. Marrow mesenchymal stem cells (MSCs) have attracted attention in DN therapy but the underlying mechanism remains unclear. Here, we show that MSC administration alleviates high glucose (HG)-induced human kidney tubular epithelial cell (HK-2 cell) injury and ameliorates renal injury in DN mice. We identify that Smad2/3 is responsible for MSCs-regulated DN progression. The activity of Smad2/3 was predominantly upregulated in HG-induced HK-2 cell and DN mice and suppressed with MSC administration. Activation of Smad2/3 via transforming growth factor-ß1 (TGF-ß1) administration abrogates the protective effect of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Smad2/3 has been reported to interact with methyltransferase of N6-methyladenosine (m6A) complex and we found a methyltransferase, Wilms' tumor 1-associating protein (WTAP), is involved in MSCs-Smad2/3-regulated DN development. Moreover, WTAP overexpression abrogates the improvement of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Subsequently, α-enolase (ENO1) is the downstream target of WTAP-mediated m6A modification and contributes to the MSCs-mediated regulation. Collectively, these findings reveal a molecular mechanism in DN progression and indicate that Smad2/3/WTAP/ENO1 may present a target for MSCs-mediated DN therapy.

Characterization of a novel multi-resistant Pseudomonas juntendi strain from China with chromosomal blaVIM-2 and a megaplasmid coharboring blaIMP-1-like and blaOXA-1.

BACKGROUND: Pseudomonas juntendi is a newly identified opportunistic pathogen, of which we have limited understanding. P. juntendi strains are often multidrug resistant, which complicates clinical management of infection. METHODS: A strain of Pseudomonas juntendi (strain L4326) isolated from feces was characterized by MALDI-TOF-MS and Average Nucleotide Identity BLAST. This strain was further subject to whole-genome sequencing and Maximum Likelihood phylogenetic analysis. The strain was phenotypically characterized by antimicrobial susceptibility testing and conjugation assays. RESULTS: We have isolated the novel P. juntendi strain L4236, which was multidrug resistant, but retained sensitivity to amikacin. L4236 harbored a megaplasmid that encoded blaOXA-1 and a novel blaIMP-1 resistance gene variant. P. juntendi strain L4236 was phylogenetically related to P. juntendi strain SAMN30525517. CONCLUSION: A rare P. juntendi strain was isolated from human feces in southern China with a megaplasmid coharboring blaIMP-1-like and blaOXA-1. Antimicrobial selection pressures may have driven acquisition of drug-resistance gene mutations and carriage of the megaplasmid.

Prognostic biomarkers associated with immune checkpoint inhibitors in hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC), particularly advanced HCC, has been a serious challenge. Immune checkpoint inhibitors (ICIs) are landmark drugs in the field of cancer therapy in recent years, which have changed the landscape of cancer treatment. In the field of HCC treatment, this class of drugs has shown good therapeutic prospects. For example, atezolizumab in combination with bevacizumab has been approved as first-line treatment for advanced HCC due to significant efficacy. However, sensitivity to ICI therapy varies widely among HCC patients. Therefore, there is an urgent need to search for determinants of resistance/sensitivity to ICIs and to screen biomarkers that can predict the efficacy of ICIs. This manuscript reviews the research progress of prognostic biomarkers associated with ICIs in HCC in order to provide a scientific basis for the development of clinically individualised precision medication regimens.

Epidemiology of childhood enterovirus infections in Hangzhou, China, 2019-2023.

Human enteroviruses are highly prevalent world-wide. Up to more than 100 subtypes of enteroviruses can cause several diseases, including encephalitis, meningitis, myocarditis, hand-foot-mouth disease, conjunctivitis, respiratory diseases, and gastrointestinal diseases, thus posing a great threat to human health. This study aimed to investigate the epidemiological characteristics of enterovirus in children in Hangzhou, China before and after the COVID-19 outbreak. Systematic monitoring of enterovirus infections was performed by collecting samples from the children admitted to the inpatient wards and outpatient departments in the Children's Hospital, Zhejiang University School of Medicine, between January 2019 and May 2023. A commercial real-time RT PCR kit was utilized to detect enteroviruses. Among the 34,152 samples collected, 1162 samples, accounting for 3.4% of the samples, were tested positive for enteroviruses. The annual positive rates of the enteroviruses were 5.46%, 1.15%, 4.43%, 1.62%, and 1.96% in 2019, 2020, 2021, 2022, and May 2023, respectively. The positivity rate of the enteroviruses was highest among children aged 3-5 years and 5-7 years. Moreover, the monthly positivity rate of enterovirus infection ranged from 0.32% to 10.38%, with a peak in June and July. Serotypes, especially EV71 and CA16, causing severe symptoms such as HFMD, were decreasing, while the proportion of unidentified serotypes was on the rise. The incidence of enteroviruses in Hangzhou was higher in children aged 1-3 years and 7-18 years.

Lactate-mitochondrial crosstalk: A new direction in the treatment of sepsis-induced acute kidney injury.

Independent risk factors for sepsis-associated acute kidney injury (S-AKI) patients include elevated lactate levels, but the specific mechanism remains unclear. Recently, An et al. discovered that excessive acetylation and inactivation of PDHA1 lead to overproduction of lactate, resulting in mitochondrial fragmentation, ATP depletion, excessive mtROS production, and mitochondrial apoptosis, thereby exacerbating AKI in sepsis. Therefore, understanding the pathophysiological processes of mitochondrial function and lactate generation in SAKI is essential and can aid in the development of novel therapeutic strategies. This review elucidates the pathological mechanisms of mitochondrial autophagy and dynamics in AKI. We also discuss the sources of lactate in SAKI and some consequences of lactonization, which may provide new strategies for improving renal injury and delaying the progression of these diseases.

Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.

WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8 weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR = 0.22, 95% CI: 0.08-0.59, p < 0.01), less decreased creatinine clearance (RR = 0.96, 95% CI: 0.93-0.99, p < 0.01), but more tolerated injection sites adverse events (p < 0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p > 0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.

Global, regional, and national total burden related to hepatitis B in children and adolescents from 1990 to 2021.

BACKGROUND: Hepatitis B remains a significant global health concern with widespread communicability. Nevertheless, data on its burden and trends in children and adolescents were limited. We aim to evaluate the global, regional, and national trends of total burden related to hepatitis B in children and adolescents aged 0-19 years from 1990 to 2021. METHODS: The age-standardized incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated by the Global Burden of Disease (GBD) study from 1990 to 2021. These indicators were stratified by sex, age, socio-demographic index (SDI), and disease stage. We calculated the correlation between them and SDI. The temporal trends were examined using the annual average percentage change (AAPC) and joinpoint regression. RESULTS: The global age-standardized incidence of hepatitis B in children and adolescents decreased from 1385.20 per 100,000 population in 1990 to 418.68 per 100,000 population in 2021, with an AAPC of -3.76%. Similarly, age-standardized DALYs decreased from 70.78 per 100,000 population to 36.31 per 100,000 population, with an AAPC of -2.13%. The age-standardized prevalence (AAPC - 3.53%) and mortality (AAPC - 2.09%) of hepatitis B also decreased significantly. From 1990 to 2021, the age-standardized incidence and prevalence among males exhibited a higher trend compared to females, although both declined over time. These two indicators also decreased across all age subgroups, with consistently higher rates observed in the 15-19 age group compared to other age groups. The burden of hepatitis B demonstrated a notable reduction in countries with high-middle SDI, while it was highest in countries with low SDI. In 2021, Central sub-Saharan Africa and West sub-Saharan Africa reported the highest age-standardized incidence. For age-standardized DALYs, South Asia was the only region to experience an increase (AAPC 1.09%), while East Asia showed the largest decline (AAPC - 7.58%). Alcohol and drug use remained important risk factors for DALYs among people aged 15-19 years. Furthermore, the impact of drug use on disease burden was increasing, particularly in high-SDI countries. CONCLUSIONS: The global burden and trends of hepatitis B decreased significantly in children and adolescents, exhibiting regional and national variations. Management of alcohol and drug use remains a major challenge for people aged 15-19 years.

STM1863, a Member of the DUFs Protein Family, Is Involved in Environmental Adaptation, Biofilm Formation, and Virulence in Salmonella Typhimurium.

Salmonella Typhimurium (STM) is an important zoonotic Gram-negative pathogen that can cause infection in a variety of livestock and poultry. Meanwhile, as an important foodborne pathogen, the bacterium can survive in various stressful environments and transmits through the fecal-oral route, posing a serious threat to global food safety. To investigate the roles of STM1863, a member of the DUFs protein family, involved in STM environmental adaptation, biofilm formation, and virulence. We analyzed the molecular characteristics of the protein encoded by STM1863 gene and examined intra- and extracellular expression levels of STM1863 gene in mouse macrophages. Furthermore, we constructed STM1863 gene deletion and complementation strains and determined its environmental adaptation under stressful conditions such as acid, alkali, high salt, bile salt, and oxidation. And the capacity of biofilm formation and pathogenicity of those strains were analyzed and compared. In addition, the interaction between the promoter of STM1863 gene and RcsB protein was analyzed using DNA gel electrophoresis migration assay (electrophoretic mobility shift assay [EMSA]). The experiments revealed that acid adaptability and biofilm formation ability of STM1863 gene deletion strain were significantly weakened compared with the parental and complementary strains. Moreover, the adhesion and invasion ability of STM1863 deletion strain to mouse macrophages was significantly decreased, while the median lethal dose (LD50) increased by 2.148-fold compared with the parental strain. In addition, EMSA confirmed that RcsB protein could bind to the promoter sequence of STM1863 gene, suggesting that the expression of STM1863 gene might be modulated by RcsB. The present study demonstrated for the first time that STM1863, a member of the DUFs protein family, is involved in the modulation of environmental adaptation, biofilm formation, and virulence.

A 2PLM-RANK multidimensional forced-choice model and its fast estimation algorithm.

High-stakes non-cognitive tests frequently employ forced-choice (FC) scales to deter faking. To mitigate the issue of score ipsativity derived, many scoring models have been devised. Among them, the multi-unidimensional pairwise preference (MUPP) framework is a highly flexible and commonly used framework. However, the original MUPP model was developed for unfolding response process and can only handle paired comparisons. The present study proposes the 2PLM-RANK as a generalization of the MUPP model to accommodate dominance RANK format response. In addition, an improved stochastic EM (iStEM) algorithm is devised for more stable and efficient parameter estimation. Simulation results generally supported the efficiency and utility of the new algorithm in estimating the 2PLM-RANK when applied to both triplets and tetrads across various conditions. An empirical illustration with responses to a 24-dimensional personality test further supported the practicality of the proposed model. To further aid in the application of the new model, a user-friendly R package is also provided.

Complete-genome sequencing and comparative genomic characterization of blaNDM-5 carrying Citrobacter freundii isolates from a patient with multiple infections.

BACKGROUND: The emergence and wide spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a growing threat to global public health. However, clinically derived carbapenemase-producing Citrobacter causing multiple infections has rarely been investigated. Here we first report the isolation and comparative genomics of two blaNDM-5 carrying Citrobacter freundii (C. freundii) isolates from a patient with bloodstream and urinary tract infections. RESULTS: Antimicrobial susceptibility testing showed that both blaNDM-5 carrying C. freundii isolates were multidrug-resistant. Positive modified carbapenem inactivation method (mCIM) and EDTA-carbapenem inactivation method (eCIM) results suggested metallo-carbapenemase production. PCR and sequencing confirmed that both metallo-carbapenemase producers were blaNDM-5 positive. Genotyping and comparative genomics analyses revealed that both isolates exhibited a high level of genetic similarity. Plasmid analysis confirmed that the blaNDM-5 resistance gene is located on IncX3 plasmid with a length of 46,161 bp, and could successfully be transferred to the recipient Escherichia coli EC600 strain. A conserved structure sequence (ISAba125-IS5-blaNDM-5-trpF-IS26-umuD-ISKox3) was found in the upstream and downstream of the blaNDM-5 gene. CONCLUSIONS: The data presented in this study showed that the conjugative blaNDM-5 plasmid possesses a certain ability to horizontal transfer. The dissemination of NDM-5-producing C. freundii isolates should be of close concern in future clinical surveillance. To our knowledge, this is the first study to characterize C. freundii strains carrying the blaNDM-5 gene from one single patient with multiple infections.

The progress of research on immune checkpoint inhibitor resistance and reversal strategies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in humans, which is prone to recurrence and metastasis and has a poor prognosis. The occurrence and progression of HCC are closely related to immune elimination, immune homeostasis, and immune escape of the immune system. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has shown powerful anti-tumor capabilities in HCC patients. However, there are still some HCC patients who cannot benefit from ICIs treatment due to their innate or acquired drug resistance. Therefore, it is of great practical significance to explore the possible mechanisms of resistance to ICIs in HCC and to use them as a target to design strategies to reverse resistance, to overcome drug resistance in HCC and to improve the prognosis of patients. This article summarizes the possible primary (tumor microenvironment alteration, and signaling pathways, etc.) and acquired (immune checkpoint upregulation) resistance mechanisms in patients with HCC treated with ICIs, and based on this, discusses the status and effectiveness of combination drug strategy to reverse drug resistance, to provide a reference for subsequent related studies and decisions.

Association of glycemic variability with death and severe consciousness disturbance among critically ill patients with cerebrovascular disease: analysis of the MIMIC-IV database.

BACKGROUND: The association of glycemic variability with severe consciousness disturbance and in-hospital all-cause mortality in critically ill patients with cerebrovascular disease (CVD) remains unclear, This study aimed to investigate the association of glycemic variability with cognitive impairment and in-hospital death. METHOD: We extracted all blood glucose measurements of patients diagnosed with CVD from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Glycemic variability was defined as the coefficient of variation (CV), which was determined using the ratio of standard deviation and the mean blood glucose levels. Cox hazard regression models were applied to analyze the link between glycemic variability and outcomes. We also analyzed non-linear relationship between outcome indicators and glycemic variability using restricted cubic spline curves. RESULTS: The present study included 2967 patients diagnosed with cerebral infarction and 1842 patients diagnosed with non-traumatic cerebral hemorrhage. Log-transformed CV was significantly related to cognitive impairment and in-hospital mortality, as determined by Cox regression. Increasing log-transformed CV was approximately linearly with the risk of cognitive impairment and in-hospital mortality. CONCLUSION: High glycemic variability was found to be an independent risk factor for severe cognitive decline and in-hospital mortality in critically ill patients with CVD. Our study indicated that enhancing stability of glycemic variability may reduced adverse outcomes in patients with severe CVD.

Incidence and risk of hypertension associated with PARP inhibitors in cancer patients: a systematic review and meta-analysis.

OBJECTIVE: To analyze the incidence and risk of hypertension associated with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in cancer patients and provide reference for clinicians. METHODS: We used R software to conduct a meta-analysis of phase II/III randomized controlled trials (RCT) on PARP inhibitors for cancer treatment published in PubMed, Embase, Clinical Trials, Cochrane Library and Web of Science from inception to July 29th, 2022. RESULTS: We included 32 RCTs with 10,654 participants for this meta-analysis. For total PARP inhibitors, the incidence and risk ratio of all-grade hypertension were 12% and 1.22 (95% CI: 0.91-1.65, P = 0.19, I2 = 81%), and the incidence and risk ratio of grade 3-4 hypertension were 4% and 1.24 (95% CI: 0.74-2.08, P = 0.42, I2 = 68%). Compared with the control group, the niraparib group, olaparib 800 mg/day group, and olaparib plus cediranib group increased the risk of any grade and grade 3-4 hypertension, while the veliparib group and rucaparib group did not increase the risk of any grade and grade 3-4 hypertension, and olaparib 200 mg-600 mg/day group (exclude olaparib plus cediranib regime) reduced the risk of any grade and grade 3-4 hypertension. CONCLUSION: Olaparib 200-600 mg/day (excluding olaparib plus cediranib regimen) may be the most suitable PARP inhibitor for cancer patients with high risk of hypertension, followed by veliparib and rucaparib. Niraparib, olaparib 800 mg/day and olaparib combined with cediranib may increase the risk of developing hypertension in cancer patients, clinicians should strengthen the monitoring of blood pressure in cancer patients and give medication in severe cases.

Association of Aspirin with Dementia or Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: At present, the effect of aspirin in preventing dementia or mild cognitive impairment (MCI) is controversial. Clarifying their association is of interest for subsequent relevant clinical trials. METHODS: Four databases (PubMed, Embase, Web of Science, and the Cochrane Library) were searched from inception to May 12, 2023, for randomized controlled trials (RCTs) that explored the effects between aspirin and dementia or MCI. Two reviewers independently extracted and analyzed data using Stata software. Discrepancy was resolved by a third reviewer. The primary outcomes were dementia and MCI. The secondary outcomes were cognitive decline and changes in cognitive scores. RESULTS: Five RCTs with 46,804 participants at randomization were included. For the primary outcomes, low-certainty evidence showed that aspirin was not associated with dementia (odds ratio [OR] = 0.93, 95% confidence interval [CI]: [0.85, 1.03], p > 0.05, I2 = 0%) or MCI (OR = 1.00, 95% CI: [0.88, 1.14], p > 0.05, I2 = 3.3%). For the secondary outcomes, moderate-certainty evidence showed that aspirin was not associated with cognitive decline (OR = 1.02, 95% CI: [0.93, 1.11], p > 0.05, I2 = 0%) and a change in global cognitive score (standard mean difference [SMD] = -0.01, 95% CI: [-0.03, 0.02], p > 0.05, I2 = 0%). Low-certainty evidence showed that aspirin was not associated with a change in verbal learning memory score (SMD = -0.04, 95% CI: [-0.09, 0.01], p > 0.05; I2 = 72.5%). CONCLUSIONS: Low- and moderate-certainty evidence showed that aspirin was not associated with dementia, MCI, cognitive decline, or better cognitive scores. Future research may need to focus more on subtypes of dementia, mainly vascular dementia or other vascular neurocognitive diseases, and assess whether aspirin has long-term clinical benefits in a large sample of patients with dementia or MCI.

Single-cell RNA sequencing reveals the vascular smooth muscle cell phenotypic landscape in aortic aneurysm.

BACKGROUND AND OBJECTIVES: Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm. METHODS: Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package 'Seurat'. Cell annotation was determined by the R package 'singleR' and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cell‒cell junctions and cell-matrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package 'Monocle2'. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms. RESULTS: A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia. CONCLUSION: A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process. Video Abstract.

LACC1: A critical involvement in macrophage immunometabolism.

Laccase domain-containing 1 (LACC1) protein is an enzyme highly expressed in inflammatory macrophages, and studies have shown that it has a key role in diseases such as inflammatory bowel disease, arthritis, and microbial infections. Therefore, in this review, we focus on LACC1-mediated catalysis. In detail, LACC1 converts l-CITrulline (l-CIT) to l-ORNithine (l-ORN) and isocyanic acid in mice and humans and acts as a bridge between proinflammatory nitric oxide synthase (NOS2) and polyamine immunometabolism, thus exerting anti-inflammatory and antibacterial effects. Considering the actions of LACC1, targeting LACC1 may be a potent therapeutic avenue for inflammation-related diseases and microbial infection diseases.

Duyun compound green tea extracts regulate bile acid metabolism on mice induced by high-fat diet.

Duyun compound green tea (DCGT) is a healthy beverage with lipid-lowering effect commonly consumed by local people, but its mechanism is not very clear. We evaluated the effect of DCGT treatment on bile acids (BA) metabolism of mice with high-fat diet (HFD) - induced hyperlipidaemia by biochemical indexes and metabolomics and preliminarily determined the potential biomarkers and metabolic pathways of hyperlipidaemia mice treated with DCGT as well as investigated its lipid-lowering mechanism. The results showed that DCGT treatment could reduce HFD - induced gain in weight and improve dyslipidaemia. In addition, a total of ten types of BA were detected, of which seven changed BA metabolites were observed in HFD group mice. After DCGT treatment, glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic acid were significantly down-regulated, while hyodeoxycholic acid, deoxycholic acid and chenodeoxycholic acid were markedly up-regulated. These results demonstrated that DCGT treatment was able to make the BA metabolites in the liver of hyperlipidaemia mice normal and alleviate hyperlipidaemia by regulating the metabolites such as glycocholic acid, tauroursodeoxycholic acid and taurochenodeoxycholic, as well as the BA metabolic pathway and cholesterol metabolic pathway involved.

Fluoroquinolones increase susceptibility to aortic aneurysm and aortic dissection: Molecular mechanism and clinical evidence.

Aortic aneurysm (AA) and aortic dissection (AD) are prevalent severe cardiovascular diseases that result in catastrophic complications and unexpected deaths. Owing to the lack of clinically established and effective medications, the only treatment options are open surgical repair or endovascular therapy. Most researchers have focused on the development of innovative medications or therapeutic targets to slow the progression of AA/AD or lower the risk of malignant consequences. Recent studies have shown that the use of fluoroquinolones (FQs) may increase susceptibility to AA/AD to some extent, especially in patients with aortic dilatation and those at a high risk of AD. Therefore, it is crucial for doctors, particularly those in cardiovascular specialties, to recognize the dangers of FQs and adopt alternatives. In the present review, the main clinical observational studies on the correlation between FQs and AA/AD in recent years are summarized, with an emphasis on the relative physiopathological mechanism incorporating destruction of the extracellular matrix (ECM), phenotypic transformation of vascular smooth muscle cells, and local inflammation. Although additional data are required, it is anticipated that the rational use of FQs will become the standard of care for the treatment of aortic diseases.