Achievement of Guideline-Recommended Targets for Secondary Prevention of Cardiovascular Disease in 38 Low-Income and Middle-Income Countries.

BACKGROUND: This study aimed to estimate the prevalence of achieving the secondary prevention targets recommended in the World Health Organization (WHO) guidelines for cardiovascular disease (CVD) in 38 low-income and middle-income countries (LMICs). METHODS: We pooled nationally representative cross-sectional surveys from 38 LMICs between 2013 and 2020. Treatment, metabolic and lifestyle targets were assessed for individuals with a self-reported history of CVD according to WHO's recommendations. Associations between the prevalence of guideline adherence and sociodemographic characteristics were assessed using multivariate Poisson regression models. RESULTS: The pooled sample included 126 106 participants, of whom 9821 (6.8% [95% CI 6.4-7.2]) reported a history of CVD. Overall, the prevalence of achieving treatment targets in patients with CVD was 22.7% (95% CI, 21.0-24.5%) for antihypertensive drugs, 19.6% (17.9-21.4%) for aspirin, and 13.6% (12.0-15.44%) for statins. The prevalence of achieving metabolic targets was 54.9% (52.5-57.3%) for BMI, 39.9% (37.7-42.2%) for blood pressure, 46.1% (43.6-48.6%) for total cholesterol, and 84.9% (83.1-86.5%) for fasting blood glucose. The prevalence of achieving lifestyle targets was 83.2% (81.5-84.7%) for not smoking, 83.1% (81.2-84.9%) for not drinking, 65.5% (63.1-67.7%) for sufficient physical activity and 16.2% (14.5-18.0%) for healthy diet. Only 6.1% (5.1-7.4%) achieved three treatment targets, 16.0% (14.3-17.9%) achieved four metabolic targets, and 6.9% (5.8-8.0%) achieved four lifestyle targets. Upper-middle income countries were better than low-income countries at achieving the treatment, non-drinking and dietary targets. Being younger and female were associated with poorer achievement of metabolic targets. CONCLUSION: In LMICs, achieving the targets recommended in the guideline for treatment, metabolism and healthy lifestyles for patients with CVD is notably low. This highlights an urgent need for effective, systematic secondary prevention strategies to improve CVD management.

IL-4 attenuates myocardial infarction injury by promoting M2 macrophage polarization.

IL-4, an immunoregulatory cytokine, plays a role in various cellular pathways and is known to regulate M2 macrophage polarization. Numerous studies have suggested that promoting the polarization of macrophages toward the M2 phenotype is beneficial for myocardial infarction (MI) recovery. However, whether IL-4 can achieve therapeutic effects in MI by regulating M2 macrophage polarization remains unclear. In this study, the authors observed that IL-4 increased the proportion of M2 macrophages in the ischemic myocardium compared to the PBS group. Additionally, IL-4 reduced the infiltration of inflammatory cells and the expression of proinflammatory-related proteins, while enhancing the expression of genes associated with tissue repair. Furthermore, IL-4 facilitated the recovery of cardiac function and reduced fibrosis in the post-MI phase. Importantly, when macrophages were depleted, the therapeutic benefits of IL-4 mentioned above were attenuated. These findings provide evidence for the effectiveness of IL-4 in treating MI through the regulation of M2 macrophage polarization, thereby encouraging further development of this therapeutic approach.

NIR-II emissive anionic copper nanoclusters with intrinsic photoredox activity in single-electron transfer.

Ultrasmall copper nanoclusters have recently emerged as promising photocatalysts for organic synthesis, owing to their exceptional light absorption ability and large surface areas for efficient interactions with substrates. Despite significant advances in cluster-based visible-light photocatalysis, the types of organic transformations that copper nanoclusters can catalyze remain limited to date. Herein, we report a structurally well-defined anionic Cu40 nanocluster that emits in the second near-infrared region (NIR-II, 1000-1700 nm) after photoexcitation and can conduct single-electron transfer with fluoroalkyl iodides without the need for external ligand activation. This photoredox-active copper nanocluster efficiently catalyzes the three-component radical couplings of alkenes, fluoroalkyl iodides, and trimethylsilyl cyanide under blue-LED irradiation at room temperature. A variety of fluorine-containing electrophiles and a cyanide nucleophile can be added onto an array of alkenes, including styrenes and aliphatic olefins. Our current work demonstrates the viability of using readily accessible metal nanoclusters to establish photocatalytic systems with a high degree of practicality and reaction complexity.

Plants interfere with non-self recognition of a phytopathogenic fungus via proline accumulation to facilitate mycovirus transmission.

Non-self recognition is a fundamental aspect of life, serving as a crucial mechanism for mitigating proliferation of molecular parasites within fungal populations. However, studies investigating the potential interference of plants with fungal non-self recognition mechanisms are limited. Here, we demonstrate a pronounced increase in the efficiency of horizontal mycovirus transmission between vegetatively incompatible Sclerotinia sclerotiorum strains in planta as compared to in vitro. This increased efficiency is associated with elevated proline concentration in plants following S. sclerotiorum infection. This surge in proline levels attenuates the non-self recognition reaction among fungi by inhibition of cell death, thereby facilitating mycovirus transmission. Furthermore, our field experiments reveal that the combined deployment of hypovirulent S. sclerotiorum strains harboring hypovirulence-associated mycoviruses (HAVs) together with exogenous proline confers substantial protection to oilseed rape plants against virulent S. sclerotiorum. This unprecedented discovery illuminates a novel pathway by which plants can counteract S. sclerotiorum infection, leveraging the weakening of fungal non-self recognition and promotion of HAVs spread. These promising insights provide an avenue to explore for developing innovative biological control strategies aimed at mitigating fungal diseases in plants by enhancing the efficacy of horizontal HAV transmission.

Functional regulation of microglia by vitamin B12 alleviates ischemic stroke-induced neuroinflammation in mice.

Ischemic stroke is the second leading cause of death and disability worldwide, and efforts to prevent stroke, mitigate secondary neurological damage, and promote neurological recovery remain paramount. Recent findings highlight the critical importance of microbiome-related metabolites, including vitamin B12 (VB12), in alleviating toxic stroke-associated neuroinflammation. Here, we showed that VB12 tonically programmed genes supporting microglial cell division and activation and critically controlled cellular fatty acid metabolism in homeostasis. Intriguingly, VB12 promoted mitochondrial transcriptional and metabolic activities and significantly restricted stroke-associated gene alterations in microglia. Furthermore, VB12 differentially altered the functions of microglial subsets during the acute phase of ischemic stroke, resulting in reduced brain damage and improved neurological function. Pharmacological depletion of microglia before ischemic stroke abolished VB12-mediated neurological improvement. Thus, our preclinical studies highlight the relevance of VB12 in the functional programming of microglia to alleviate neuroinflammation, minimize ischemic injury, and improve host neurological recovery after ischemic stroke.

Recent insights into breast milk microRNA: their role as functional regulators.

Breast milk (BM) is a primary biofluid that plays a crucial role in infant development and the regulation of the immune system. As a class of rich biomolecules in BM, microRNAs (miRNAs) are regarded as active factors contributing to infant growth and development. Surprisingly, these molecules exhibit resilience in harsh conditions, providing an opportunity for infants to absorb them. In addition, many studies have shown that miRNAs in breast milk, when absorbed into the gastrointestinal system, can act as a class of functional regulators to effectively regulate gene expression. Understanding the absorption pattern of BM miRNA may facilitate the creation of formula with a more optimal miRNA balance and pave the way for novel drug delivery techniques. In this review, we initially present evidence of BM miRNA absorption. Subsequently, we compile studies that integrate both in vivo and in vitro findings to illustrate the bioavailability and biodistribution of BM miRNAs post-absorption. In addition, we evaluate the strengths and weaknesses of previous studies and discuss potential variables contributing to discrepancies in their outcomes. This literature review indicates that miRNAs can be absorbed and act as regulatory agents.

Improving the Rechargeable Li-CO2 Battery Performances by Tailoring Oxygen Defects on Li-Ni-Co-Mn Multi-Metal Oxide Catalysts Recycled from Spent Ternary Lithium-Ion Batteries.

Rechargeable Li-CO2 batteries are considered as a promising carbon-neutral energy storage technology owing to their ultra-high energy density and efficient CO2 capture capability. However, the sluggish CO2 reduction/evolution kinetics impedes their practical application, which leads to huge overpotentials and poor cyclability. Multi-element transit metal oxides (TMOs) are demonstrated as effective cathodic catalysts for Li-CO2 batteries. But there are no reports on the integration of defect engineering on multi-element TMOs. Herein, the oxygen vacancy-bearing Li-Ni-Co-Mn multi-oxide (Re-NCM-H3) catalyst with the α-NaFeO2-type structure is first fabricated by annealing the NiCoMn precursor that derived from spent ternary LiNi0.8Co0.1Mn0.1O2 cathode, in H2 at 300 °C. As demonstrated by experimental results and theory calculations, the introduction of moderate oxygen vacancy has optimized electronic state near the Fermi level (Ef), eventually improving CO2 adsorption and charge transfer. Therefore, the Li-CO2 batteries with Re-NCM-H3 catalyst deliver a high capacity (11808.9 mAh g-1), a lower overpotential (1.54 V), as well as excellent stability over 216 cycles at 100 mA g-1 and 165 cycles at 400 mA g-1. This study not only opens up a sustainable application of spent ternary cathode, but also validates the potential of multi-element TMO catalysts with oxygen defects for high-efficiency Li-CO2 batteries.

RNA-dependent RNA polymerases regulate ascospore discharge through the exonic-sRNA-mediated RNAi pathway.

Ascospores, forcibly released into the air from perithecia, are the primary inoculum for Fusarium head blight. In Fusarium graminearum, the biological functions of four RNA-dependent RNA polymerases (RdRPs) (Fgrdrp1-4) have been reported, but their regulatory mechanisms are poorly understood and the function of Fgrdrp5 is still unknown. In this study, we found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays an important role in ascospore discharge, and they all participate in the generation of turgor pressure in a polyol-dependent manner. Moreover, these three genes all affect the maturation of ascospores. Deep sequencing and co-analysis of small RNA and mRNA certified that Fgrdrp1, Fgrdrp2, and Fgrdrp5 partly share their functions in the biogenesis and accumulation of exonic small interference RNA (ex-siRNA), and these three RdRPs negatively regulate the expression levels of ex-siRNA corresponding genes, including certain genes associated with ascospore development or discharge. Furthermore, the differentially expressed genes of deletion mutants, those involved in lipid and sugar metabolism or transport as well as sexual development-related transcription factors, may also contribute to the defects in ascospore maturation or ascospore discharge. In conclusion, our study suggested that the components of the dicer-dependent ex-siRNA-mediated RNA interference pathway include at least Fgrdrp1, Fgrdrp2, and Fgrdrp5. IMPORTANCE: We found that in addition to Fgrdrp1 and Fgrdrp2, Fgrdrp5 also plays important roles in ascospore maturation and ascospore discharge of Fusarium graminearum. These three RNA-dependent RNA polymerases participate in the biogenesis and accumulation of exonic small interference RNA and then regulate ascospore discharge.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese: a randomized, double-blind, placebo-controlled, multiple-dose phase 1b study.

BACKGROUND: TG103, a glucagon-like peptide-1 analog, is being investigated as an option for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of TG103 injection in participants who are overweight or obese without diabetes. METHODS: In this randomized, double-blind, placebo-controlled, multiple-dose phase 1b study, participants aged 18-75 years with a body-mass index (BMI) ≥ 26.0 kg/m2 and body weight ≥ 60 kg were enrolled from three centers in China. The study included three cohorts, and in each cohort, eligible participants were randomly assigned (3:1) to one of three once-weekly subcutaneous TG103 groups (15.0, 22.5 and 30.0 mg) or matched placebo, without lifestyle interventions. In each cohort, the doses of TG103 were escalated in 1-week intervals to the desired dose over 1 to 4 weeks. Then participants were treated at the target dose until week 12 and then followed up for 2 weeks. The primary endpoint was safety and tolerability assessed by the incidence and severity of adverse events (AEs) from baseline to the end of the follow-up period. Secondary endpoints included pharmacokinetic and pharmacodynamic profiles of TG103 and the occurrence of anti-drug antibodies to TG103. RESULTS: A total of 147 participants were screened, and 48 participants were randomly assigned to TG103 (15.0, 22.5 and 30.0 mg groups, n = 12 per group) or placebo (n = 12). The mean (standard deviation, SD) age of the participants was 33.9 (10.0) years; the mean bodyweight was 81.65 (10.50) kg, and the mean BMI was 29.8 (2.5) kg/m2. A total of 466 AEs occurred in 45 of the 48 participants, with 35 (97.2%) in the TG103 group and 10 (83.3%) in the pooled placebo group. Most AEs were grade 1 or 2 in severity, and there were no serious adverse events (SAEs), AEs leading to death, or AEs leading to discontinuation of treatment. The steady-state exposure of TG103 increased with increasing dose and was proportional to Cmax,ss, AUCss, AUC0-t and AUC0-inf. The mean values of Cmax,ss ranged from 951 to 1690 ng/mL, AUC0-t ranged from 150 to 321 µg*h/mL, and AUC0-inf ranged from 159 to 340 µg*h/mL. TG103 had a half-life of 110-116 h, with a median Tmax of 36-48 h. After treatment for 12 weeks, the mean (SD) values of weight loss from baseline in the TG103 15.0 mg, 22.5 mg and 30.0 mg groups were 5.65 (3.30) kg, 5.35 (3.39) kg and 5.13 (2.56) kg, respectively, and that in the placebo group was 1.37 (2.13) kg. The least square mean percent weight loss from baseline to D85 in all the TG103 groups was more than 5% with p < 0.05 for all comparisons with placebo. CONCLUSIONS: In this trial, all three doses of once-weekly TG103 were well tolerated with an acceptable safety profile. TG103 demonstrated preliminary 12-week body weight loss without lifestyle interventions, thus showing great potential for the treatment of overweight and obesity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04855292. Registered on April 22, 2021.

The relationship between landscape pattern and plant species diversity in east Dongting lake wetland based on different Eco-environment.

Exploring the impact factors associated with biodiversity and the relationship between them has always been a concerned issue in recent years. However, the previous research mostly focus on theoretical layer. Accordingly, the relationship between landscape pattern and biodiversity is to be analyzed in this research. The landscape pattern determines the function and ecological process of the landscape, and affects the species flow, information flow and energy flow in the landscape. Land use patterns has inevitably left an impact on the landscape pattern. Landscape pattern determines the function and ecological process of landscape and thus plays a significant role in biodiversity. East Dongting Lake National Nature Reserve is taken as the research object of the paper, and the remote sensing image data of three different time periods are collected, including 2000, 2010 and 2020. With an interpretation of the vegetation landscape pattern changes inside the protected area to collect and analyze the vegetation coverage. By comparing landscape patterns and the dynamic changes of land use in different periods of time, the correlation between landscape pattern characteristics and regional biodiversity is to be analyzed. Research shows: (1) From 2000 to 2020, the vegetation coverage of East Dongting Lake increased, but the landscape shape, scale, diversity and uniformity index decreased to varying degrees. (2) At the class level of landscape type, the relationship between landscape index and biodiversity is different. A complex relationship between farmland landscape and biodiversity. There is a significant positive correlation between the index of grassland landscape type and the index of regional biodiversity. (3) The correlation analysis results at the landscape level show that the landscape characteristic index is positively correlated with the regional biodiversity index. The grassland landscape in the area is the main habitat of biological species. At the same time, as the main grain producing area, the impact of farmland landscape cannot be ignored. This study has certain theoretical guiding significance for the protection and management of biodiversity in the region in terms of maintaining landscape pattern in particular the grassland landscape area and increasing vegetation coverage in the process of land use.

Functional fractions of Astragalus polysaccharides as a potential prebiotic to alleviate ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that is significantly influenced by an imbalance in the gut microbiota. Astragalus membranaceus, particularly its polysaccharide components, has shown therapeutic potential for the treatment of UC, although the specific active constituents and their mechanistic pathways remain to be fully elucidated. In this study, we investigated two molecular weight fractions of Astragalus polysaccharides (APS), APS1 (Mw < 10 kDa) and APS2 (10 kDa < Mw < 50 kDa), isolated by ultrafiltration, focusing on their prebiotic effects, effects on UC, and the underlying mechanism. Our results showed that both APS1 and APS2 exhibit prebiotic properties, with APS1 significantly outperforming APS2 in ameliorating UC symptoms. APS1 significantly attenuated weight loss and UC manifestations, reduced colonic pathology, and improved intestinal mucosal barrier integrity. In addition, APS1 significantly reduced the levels of inflammatory cytokines in the serum and colonic tissue, and downregulated colonic chemokines. Furthermore, APS1 ameliorated dextran sulfate sodium salt (DSS)-induced intestinal dysbiosis by promoting the growth of beneficial microbes and inhibiting the proliferation of potential pathogens, leading to a significant increase in short-chain fatty acids. In conclusion, this study highlights the potential of APS1 as a novel prebiotic for the prevention and treatment of UC.

A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity, and Inflammation.

BACKGROUND & AIMS: Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel disease are also associated with higher risk of hyperoxaluria and nephrolithiasis. However, the potential role of PAT1 deficiency in gut-barrier integrity and susceptibility to colitis is currently elusive. METHODS: Age-matched PKO and wild-type littermates were administered 3.5% dextran sulfate sodium in drinking water for 6 days. Ileum and colon of control and treated mice were harvested. Messenger RNA and protein expression of tight junction proteins were determined by reverse transcription polymerase chain reaction and western blotting. Severity of inflammation was assessed by measuring diarrheal phenotype, cytokine expression, and H&E staining. Gut microbiome and associated metabolome were analyzed by 16S ribosomal RNA sequencing and mass spectrometry, respectively. RESULTS: PKO mice exhibited significantly higher loss of body weight, gut permeability, colonic inflammation, and diarrhea in response to dextran sulfate sodium treatment. In addition, PKO mice showed microbial dysbiosis and significantly reduced levels of butyrate and butyrate-producing microbes compared with controls. Co-housing wild-type and PKO mice for 4 weeks resulted in PKO-like signatures on the expression of tight junction proteins in the colons of wild-type mice. CONCLUSIONS: Our data demonstrate that loss of PAT1 disrupts gut microbiome and related metabolites, decreases gut-barrier integrity, and increases host susceptibility to intestinal inflammation. These findings, thus, highlight a novel role of the oxalate transporter PAT1 in promoting gut-barrier integrity, and its deficiency appears to contribute to the pathogenesis of inflammatory bowel diseases.

An effector SsCVNH promotes the virulence of Sclerotinia sclerotiorum through targeting class III peroxidase AtPRX71.

Many plant pathogens secrete effector proteins into the host plant to suppress host immunity and facilitate pathogen colonization. The necrotrophic pathogen Sclerotinia sclerotiorum causes severe plant diseases and results in enormous economic losses, in which secreted proteins play a crucial role. SsCVNH was previously reported as a secreted protein, and its expression is significantly upregulated at 3 h after inoculation on the host plant. Here, we further demonstrated that deletion of SsCVNH leads to attenuated virulence. Heterologous expression of SsCVNH in Arabidopsis enhanced pathogen infection, inhibited the host PAMP-triggered immunity (PTI) response and increased plant susceptibility to S. sclerotiorum. SsCVNH interacted with class III peroxidase AtPRX71, a positive regulator of innate immunity against plant pathogens. SsCVNH could also interact with other class III peroxidases, thus reducing peroxidase activity and suppressing plant immunity. Our results reveal a new infection strategy employed by S. sclerotiorum in which the fungus suppresses the function of class III peroxidases, the major component of PTI to promote its own infection.

Knowledge, concerns, and vaccine acceptance related to Mpox (Monkeypox) among university students in North and Northeast China: An online cross-sectional study.

The growing number of Mpox cases in China has posed a challenge to public health. The prevalence of men who have sex with men behaviors among students has been consistently increasing each year in China, accompanied by a high frequency of unprotected anal sex. As crowded places, schools are highly likely to cause an Mpox outbreak among students through long-term close contact. Understanding university students' perceptions about Mpox and willingness to vaccinate play a vital role in implementing preventive measures in schools. This study aimed to assess knowledge, concerns, and vaccine acceptance toward Mpox among university students in North and Northeast China. A cross-sectional study was conducted among 3831 university students from seven universities in North and Northeast China between September 10 and September 25, 2023. This study found a relative insufficiency in Mpox knowledge among university students (71.60%), with less than half expressing concern about the Mpox outbreak (39.57%), and the majority exhibiting a positive attitude to vaccination (76.30%). Multivariate regression analysis revealed that a good knowledge level was associated with age, study discipline, education level, and a high level of concern about Mpox. Male, elderly, or highly educated participants had a low level of concern about Mpox. Participants with a high level of knowledge toward Mpox were more likely to have the vaccination willingness. This study might help governments and schools to understand students' Mpox perceptions and vaccination intentions, enabling them to implement effective measures in addressing the issue of inadequate understanding regarding Mpox among university students.

Particulate polycyclic aromatic hydrocarbons and metals, DNA methylation and DNA methyltransferase among middle-school students in China.

The main components of particulate matter (PM) had been reported to change DNA methylation levels. However, the mixed effect of PM and its constituents on DNA methylation and the underlying mechanism in children has not been well characterized. To investigate the association between single or mixture exposures and global DNA methylation or DNA methyltransferases (DNMTs), 273 children were recruited (110 in low-exposed area and 163 in high-exposed area) in China. Serum benzo[a]pyridin-7,8-dihydroglycol-9, 10-epoxide (BPDE)-albumin adduct and urinary metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, and DNMT3A were measured. The linear regression, quantile-based g-computation (QGC), and mediation analyses were performed to investigate the effects of individual and mixture exposure. We found that significantly lower levels of % 5mC (P < 0.001) and the mRNA expression of DNMT3A in high-PM exposed group (P = 0.031). After adjustment for age, gender, BMI z-score, detecting status of urinary cotinine, serum folate, and white blood cells, urinary arsenic (As) was negatively correlated with the % 5mC. One IQR increase in urinary As (19.97 µmol/mol creatinine) was associated with a 11.06 % decrease in % 5mC (P = 0.026). Serum BPDE-albumin adduct and urinary cadmium (Cd) were negatively correlated with the levels of DNMT1 and DNMT3A (P < 0.05). Mixture exposure was negatively associated with expression of DNMT3A in QGC analysis (ß: -0.19, P < 0.001). Mixture exposure was significantly associated with decreased % 5mC in the children with non-detected cotinine or normal serum folate (P < 0.05), which the most contributors were PAHs and As. The mediated effect of hypomethylation through DNMT1 or DNMT3A pathway was not observed. Our findings indicated that individual and mixture exposure PAHs and metal components had negative associations with global DNA methylation and decreased DNMT3A expression significantly in school-age individuals.

ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels.

BACKGROUND: Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive. METHODS: We analyzed colony-forming, self-renewal, and vessel-forming potential of ABCG2 (ATP binding cassette subfamily G member 2)-expressing ECs in human umbilical vessels. To study the contribution of Abcg2-expressing ECs to vessel development and regeneration, we developed Abcg2CreErt2;ROSA TdTomato mice and performed lineage tracing during mouse development and during tissue regeneration after myocardial infarction injury. RNA sequencing and chromatin methylation chromatin immunoprecipitation followed by sequencing were conducted to study the gene regulation in Abcg2-expressing ECs. RESULTS: In human and mouse vessels, ECs with higher ABCG2 expression (ABCECs) possess higher clonal proliferative potential and in vivo vessel-forming potential compared with mature ECs. These cells could clonally contribute to vessel formation in primary and secondary recipients after transplantation. These features of ABCECs meet the criteria of CRECs. Results from lineage tracing experiments confirm that Abcg2-expressing CRECs (AbcCRECs) contribute to arteries, veins, and capillaries in cardiac tissue development and vascular tissue regeneration after myocardial infarction. Transcriptome and epigenetic analyses reveal that a gene expression signature involved in angiogenesis and vessel development is enriched in AbcCRECs. In addition, various angiogenic genes, such as Notch2 and Hey2, are bivalently modified by trimethylation at the 4th and 27th lysine residue of histone H3 (H3K4me3 and H3K27me3) in AbcCRECs. CONCLUSIONS: These results are the first to establish that a single prospective marker identifies CRECs in mice and human individuals, which holds promise to provide new cell therapies for repair of damaged vessels in patients with endothelial dysfunction.

Developing excellent plantar pressure sensors for monitoring human motions by using highly compressible and resilient PMMA conductive iongels.

Based on real-time detection of plantar pressure, gait recognition could provide important health information for rehabilitation administration, fatigue prevention, and sports training assessment. So far, such researches are extremely limited due to lacking of reliable, stable and comfortable plantar pressure sensors. Herein, a strategy for preparing high compression strength and resilience conductive iongels has been proposed by implanting physically entangled polymer chains with covalently cross-linked networks. The resulting iongels have excellent mechanical properties including nice compliance (young's modulus < 300 kPa), high compression strength (>10 MPa at a strain of 90 %), and good resilience (self-recovery within seconds). And capacitive pressure sensor composed by them possesses excellent sensitivity, good linear response even under very small stress (∼kPa), and long-term durability (cycles > 100,000) under high-stress conditions (133 kPa). Then, capacitive pressure sensor arrays have been prepared for high-precision detection of plantar pressure spatial distribution, which also exhibit excellent sensing performances and long-term stability. Further, an extremely sensitive and fast response plantar pressure monitoring system has been designed for monitoring plantar pressure of foot at different postures including upright, forward and backward. The system achieves real-time tracking and monitoring of changes of plantar pressure during different static and dynamic posture processes. And the characteristics of plantar pressure information can be digitally and photography displayed. Finally, we propose an intelligent framework for real-time detection of plantar pressure by combining electronic insoles with data analysis system, which presents excellent applications in sport trainings and safety precautions.

Elucidation of genes enhancing natural product biosynthesis through co-evolution analysis.

Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis. Among the 597 genes that co-evolved with polyketide BGCs, 11 genes in the 'coenzyme' category have been examined, including a gene cluster encoding for the cofactor pyrroloquinoline quinone. When the pqq gene cluster was engineered into 11 Streptomyces strains, it enhanced production of 16,385 metabolites, including 36 known natural products with up to 40-fold improvement and several activated silent gene clusters. This study provides an innovative engineering strategy for improving polyketide production and finding previously unidentified BGCs.

Correlation of BARD1 gene polymorphisms with risk of neuroblastoma: a meta-analysis.

BRCA1-associated RING domain protein 1 (BARD1) gene polymorphisms may be associated with neuroblastoma (NB) susceptibility. However, the results remain controversial. Relevant studies were identified by searching PubMed, Web of Science, Embase, China National Knowledge Infrastructure databases up to March 5, 2023. The strength of the association between BARD1 polymorphisms and susceptibility of NB was assessed by calculating odds ratios (ORs) and 95% confidence intervals (95% CIs) through the fixed- or random-effects model. Eight articles involving 12 studies were finally included. We found that rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T variant increase the risk of NB in allelic, dominant, recessive, homozygous and heterozygous genetic models, while rs7585356 G > A variant appeared protective against NB. When stratified by ethnicity, subgroup analysis indicated that the above association remained significant in Caucasian populations in all genetic models, except for rs7585356G > A polymorphism in Asians. In Asian populations, we found the similar results in the allelic and dominant model of rs6435862 T > G, rs3768716 A > G, rs17487792 C > T and rs7587476 C > T as in Caucasians, while there lacked a significant association in the other three model. In addition, rs7585356 G > A was not associated with an increased risk of NB in the Asian population. After Bonferroni correction, significant associations for rs7585356 G > A disappeared in both Asian and Caucasian populations, with no significant association found for rs7587476 in the allelic and dominant models among Asians. BARD1 polymorphisms might be significantly associated with NB susceptibility. It is crucial that these finding should be further confirmed through extensive and well-planned studies.