PurposeSocial determinants of health (SDoH) and dietary Inflammatory Index (DII) are pivotal factors in population health. However, whether DII mediates the impact of SDoH on blood pressure and obesity remains insufficiently characterized. This study aimed to quantify the associations among SDoH burden, blood pressure, obesity, and DII, and to further explore the mediating role of DII.MethodsData from 22,870 participants in NHANES 2009-2018 were analyzed. Weighted multivariable linear regression (LR) and restricted cubic spline (RCS) models were used to estimate beta coefficients and characterize dose-response relations. Subgroup analyses and stratified RCS were conducted to assess heterogeneity. Mediation analyses were then performed to systematically evaluate the mediating effect of DII on these associations.ResultsAfter all covariates were adjusted, each one-unit increase in the SDoH score was associated with significant increases in SBP (beta = 0.59, 95% CI: 0.39-0.80), DBP (beta = 0.18, 95% CI: 0.03-0.33), PP (beta = 0.42, 95% CI: 0.21-0.62), ABSI (beta = 0.20, 95% CI: 0.15-0.26), BMI (beta = 0.12, 95% CI: 0.01-0.22), and DII (beta = 0.15, 95% CI: 0.13-0.17). RCS analyses demonstrated nonlinear relationships with these indices. Mediation analyses indicated that DII mediated the effects of adverse SDoH on SBP, PP, hypertension, ABSI, and BMI, with mediation proportions of 5.92%, 9.89%, 11.52%, 10.93%, and 20.00%, respectively.ConclusionsAdverse SDoH were positively associated with blood pressure and obesity, with DII acting as an important mediator. These findings underscore the importance of jointly considering SDoH and dietary inflammation in the development of prevention and intervention strategies for hypertension and obesity.

Over the past decade, colchicine has re-emerged as a promising therapeutic candidate for atherosclerotic cardiovascular disease. Here we review evidence from large randomized controlled trials together with advances in mechanistic research that have clarified how colchicine modulates vascular inflammation and plaque stability. Canonically, colchicine disrupts microtubule dynamics and suppresses NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation. Beyond these actions, it limits oxidative stress, modulates cytoskeletal cross-talk, attenuates cholesterol crystal formation and reprograms inflammatory and metabolic proteomic networks. Colchicine influences multiple vascular and immune cell types, including neutrophils, monocytes, macrophages, endothelial cells, smooth muscle cells and platelets, collectively reducing vascular inflammation and promoting plaque stability. Notably, while colchicine has demonstrated benefit in coronary artery disease, several recent trials in cerebrovascular disease have reported neutral outcomes, suggesting disease-specific inflammatory mechanisms and therapeutic responsiveness. Integrating mechanistic insights with clinical evidence will be critical to optimize colchicine use and advance precision anti-inflammatory strategies in atherosclerotic cardiovascular disease.

Despite effective secondary prevention for coronary heart diseases, recurrent events remain high. Elevated high-sensitivity C-reactive protein (hsCRP) indicates increased inflammation risk. This study aimed to investigate the trained immunity of circulating monocytes in unstable angina (UA) patients with elevated hsCRP. We analyzed CD14+ monocytes from UA patients, comparing high-risk (hsCRP ≥3 mg/L) and low-risk (hsCRP <1 mg/L) groups. We assessed cytokine production and conducted metabolic, transcriptional, and epigenetic profiling. Patients with elevated hsCRP exhibited enhanced proinflammatory responses, glycolytic activity, and altered immune profiles, indicating sustained monocyte trained immunity, which contributes to residual inflammation risk in cardiovascular disease.

Background/Objectives: Previous studies have shown varying efficacy of high-fiber diets containing different ingredients in abdominal aortic aneurysms (AAAs). This study aimed to identify which high-fiber diet protects against AAA in mice and elucidate the underlying mechanisms. Methods: This study compared inulin, cellulose, and chow diets in terms of their impact on aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and macrophage differentiation. It also examined gut microbiota composition, focusing on Akkermansia, and evaluated intestinal barrier function and systemic inflammatory response. Results: The inulin diet, but not the cellulose diet, compared with the chow diet, reduced aneurysm enlargement, elastin degradation, matrix metalloproteinase 2 and 9 expressions, CD3+ T cell and CD68+ macrophage infiltration, and skewed macrophage towards M2 differentiation. The inulin diet enriched Akkermansia in both the small and large intestine. The inulin diet also enhanced the intestinal barrier by augmenting goblet cells, upregulating the gene related to the epithelial barrier and antibacterial peptides in the small intestine, and reducing circulating lipopolysaccharide and interleukin-1β levels. The inulin diet lowered the proportion of Ly6Chi monocytes and C-C chemokine receptor 2 expression on these cells in the bone marrow, reducing aneurysm infiltration. Administering Akkermansia to AAA mice decreased intestinal permeability and mitigated AAA. Conclusions: A diet rich in fermentable fiber inulin, as opposed to cellulose, alleviates AAA in mice. This beneficial effect is attributed to the enhanced presence of Akkermansia bacteria and improvement of the intestinal barrier.

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.

In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. Here, we developed scNanoATAC-seq2, a single-cell assay for transposase-accessible chromatin using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and two-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in noncanonical imprinting, imprinted X chromosome inactivation, and low-mappability genomic regions, such as repetitive elements and paralogs. Our data provide insights into chromatin dynamics during mammalian preimplantation development and lineage differentiation.

Plaque rupture in atherosclerosis (AS) is a major cause of acute cardiovascular events. Macrophage-induced inflammatory responses and accumulation of excess reactive oxygen species (ROS) primarily induce unstable plaques. Therefore, targeting ROS clearance and functional modulation of macrophages are clinically crucial for improving plaque stability and inhibiting AS progression. Here, we constructed a bionic nano-delivery platform, PBP@siR@PM, using platelet membranes (PM) coated with black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. Meanwhile, PM-coated BPNSs (PBP@siR@PM) were used to deliver small interfering RNA silencing Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) into macrophages. Furthermore, macrophage efferocytosis was restored by inhibiting CaMKIIγ and increasing the expression of MerTK, a cytosolic receptor, thus promoting the clearance of apoptotic cells from plaques. This study demonstrated that intraplaque macrophage-targeted therapy using the bionic nano-delivery platform PBP@siR@PM effectively removed excess ROS from macrophages, promoted efferocytosis, cleared apoptotic cells in plaques, improved plaque stability, and largely inhibited AS progression in ApoE-/- mice after high fat diet. In summary, this study proposes a therapeutic strategy for AS and highlights the outstanding therapeutic potential of biomimetic nanomaterials in this type of chronic inflammatory disease. STATEMENT OF SIGNIFICANCE: Rupture of atherosclerotic unstable plaques is a major cause of acute cardiovascular events. Macrophage-induced chronic inflammation and oxidative stress due to overloaded ROS are major contributors to plaque rupture. In this study, we focused on the improvement of macrophage efferocytosis within the plaque for the effective treatment of atherosclerosis. A bionic nano-delivery platform was constructed using platelet membranes (PM) coated black phosphorus nanosheets (BPNSs) to target macrophages in atherosclerotic plaques. In conclusion, intraplaque macrophage-targeted therapy based on the bionic nano-delivery platform PBP@siR@PM effectively scavenges overloaded ROS in macrophages, promotes efferocytosis, removes apoptotic cells from plaques, and improves plaque stability, which significantly inhibits the progression of atherosclerosis in ApoE-/- mice after a high-fat diet.

BackgroundPrevious studies have established a genetic link between gut microbiota and hypertension, but whether blood cell count plays a mediating role in this remains unknown. This study aims to explore genetic associations and causal factors involving the gut microbiome, peripheral blood cell count, and blood pressure.MethodsWe utilized summary statistics derived from genome-wide association studies to conduct a two-sample mediation Mendelian randomization analysis (https://gwas.mrcieu.ac.uk/). We applied inverse variance weighted (IVW) estimation method as the primary method, along with MR Egger, Weighted median, Simple mode and Weighted mode as complementary methods. To ensure the robustness of the results, several sensitivity analyses were conducted.ResultsGenetic variants significantly associated with the microbiome, blood pressure, or peripheral blood cell counts were selected as instrumental variables. Fourteen microbial taxa were found to have suggestive associations with diastolic blood pressure (DBP), while fifteen microbial taxa showed suggestive associations with systolic blood pressure (SBP). Meanwhile, red blood cell count, lymphocyte count, and platelet count were identified to mediate the influence of the gut microbiome on blood pressure. Specifically, red cell count was identified to mediate the effects of the phylum Cyanobacteria on DBP (mediated proportion: 8.262 %). Lymphocyte count was found mediate the effects of the genus Subdoligranulum (mediated proportion: 2.642 %) and genus Collinsella (mediated proportion: 2.749 %) on SBP. Additionally, platelet count was found to mediate the relationship between the genus Eubacterium ventriosum group and SBP, explaining 3.421 % of the mediated proportion.ConclusionsOur findings highlighted that gut microbiota may have causal influence on the blood pressure by modulating blood cell counts, which sheds new light on the pathogenesis and potential clinical interventions through the intricate axis of gut microbiome, blood cell counts, and blood pressure.

Although the link between ischemia-reperfusion injury (IRI) and T cell-mediated rejection (TCMR) in kidney transplantation (KT) is well known, the mechanism remains unclear. We investigated essential genes and biological processes involved in interactions between IRI and TCMR. METHODS:Renal IRI and TCMR datasets were obtained from the Gene Expression Omnibus database. IRI and TCMR co-expression networks were built using weighted gene co-expression network analysis, and essential modules were identified to acquire shared genes and conduct functional enrichment analysis. Shared genes were used for TCMR consensus clustering, differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was conducted. Three machine learning algorithms screened for hub genes, which underwent miRNA prediction and transcription factor analysis. Hub gene expression was verified, and survival analysis was performed using Kaplan-Meier curves. RESULTS:IRI and TCMR shared 84 genes. Functional enrichment analysis revealed that inflammation played a significant role. Based on shared genes, TCMR was divided into two clusters. GSEA revealed that graft rejection-related pathways varied between the two clusters. TCMR hub genes, guanylate-binding protein 1 (GBP1) and CD69, showed increased expression. Decreased survival rates were found in patients who had undergone KT and had high GBP1 and CD69 levels. CONCLUSIONS:The study demonstrates that renal IRI has a potential role in renal TCMR and the pathogenic pathways are potentially inflammation-related.

The improvement of the myocardial microenvironment largely determines the prognosis of myocardial infarction (MI). After MI, early removal of excessive reactive oxygen species (ROS) in the microenvironment can alleviate oxidative stress injury and promote M2 phenotype polarization of macrophages, which is important for advocating myocardial repair. In this study, we combined traditional natural hydrogel materials chitosan (CS) and gelatin (Gel) to encapsulate polydopamine-modified black phosphorus nanosheets (BP@PDA). We designed an injectable composite gel (CS–Gel–BP@PDA) with a time-released ability to achieve in situ sustained-release BP@PDA in the area of MI. Utilizing the inflammation inhibition ability of CS-Gel itself and the high reactive activity of BP@PDA with ROS, continuous improvement of infarct microenvironment and myocardial repair were achieved. The studies in vivo revealed that, compared with the saline group, CS-Gel-BP@PDA group had alleviated myocardial fibrosis and infarct size and importantly improved cardiac function. Immunofluorescence results showed that the ROS level and inflammatory response in the microenvironment of the CS–Gel–BP@PDA group were decreased. In conclusion, our study demonstrated the time-released ability, antioxidative stress activity and macrophage polarization modulation of the novel composite hydrogel CS-Gel-BP@PDA, which provides inspiration for novel therapeutic modalities for MI.

Atherosclerosis-induced coronary artery disease is a major cause of cardiovascular mortality. Clinically, conservative treatment strategies for atherosclerosis still focus on lifestyle interventions and the use of lipid-lowering and anticoagulant medications. Despite achieving some therapeutic effects, these approaches are limited by low bioavailability, long intervention periods, and significant side effects. With the advancement of nanotechnology, nanomaterials have demonstrated extraordinary potential in the biomedical field. Their excellent biocompatibility, surface modifiability, and high targeting capability not only enable efficient diagnosis of plaque progression but also allow precise drug delivery within atherosclerotic plaques, significantly enhancing drug bioavailability and reducing systemic side effects. Here, we systematically review the current research progress of nanomaterials in the field of atherosclerosis to summarize not only the types of nanomaterials but also their applications in both the diagnosis and treatment of atherosclerosis. Notably, in the context of plaque therapy, we provide a comprehensive overview of current nanomaterial applications based on their targeted therapeutic systems for different cell types within plaques. Additionally, we address the persistent challenge of clinical translation of nanomaterials by summarizing current issues and providing directions for innovation and improvement in nanomaterial design. Overall, we believe that this review systematically summarizes the applications and challenges of biomedical nanomaterials in atherosclerosis diagnosis and therapy, thereby offering insights and references for the development of therapeutic materials for atherosclerosis.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, which can cause heart failure and lead to death. In this study, we performed high-resolution single-cell RNA-sequencing of 2115 individual cardiomyocytes obtained from HCM patients and normal controls. Signature up- and down-regulated genes in HCM were identified by integrative analysis across 37 patients and 41 controls from our data and published human single-cell and single-nucleus RNA-seq datasets, which were further classified into gene modules by single-cell co-expression analysis. Using our high-resolution dataset, we also investigated the heterogeneity among individual cardiomyocytes and revealed five distinct clusters within HCM cardiomyocytes. Interestingly, we showed that some extracellular matrix (ECM) genes were up-regulated in the HCM cardiomyocytes, suggesting that they play a role in cardiac remodelling. Taken together, our study comprehensively profiled the transcriptomic programs of HCM cardiomyocytes and provided insights into molecular mechanisms underlying the pathogenesis of HCM.

Narrowband photodetectors (NPDs) with the capability of detecting light within a selective wavelength range are in high demand for numerous emerging applications such as imaging systems, machine vision, and optical communication. Halide perovskite materials have been developed for eliminating the current complex filtering systems in NPDs due to their beneficial properties, while currently NPDs using perovskite materials are limited by hardly fully eliminated short wavelength response, low charge collection efficiency (CCE), complex fabrication process, and so forth. Herein, a series of perovskite single-crystalline heterojunctions (PSCHs) with a structure of Bi-MAPbX3/MAPbY3 are fabricated by liquid phase epitaxy for filter-free narrowband detection. By varying the halide component in the PSCH, the PSCH-based NPDs can realize continuously tunable spectral response range from blue to NIR regions and ultra-narrow full width at half-maximum (FWHM) of <20 nm. Specifically, the PSCH-based NPD with a high CCE under a large electric filed shows a high spectra rejection ratio of >1000, a fast response speed with rise/fall time of ∼160/∼225 μs, and long-term stability more than 3 months in ambient air. This work provides a simple strategy for designing low-cost and high-performance filter-free NPDs with a tunable spectral response.

Narrowband photodetectors have broad application prospects in many fields where only a range of specific wavelengths of light needs to be detected. However, the current narrowband detectors have some disadvantages, such as the integration is difficult, the full width at half-maximum is not narrow enough, and the spectral rejection ratio is not ideal (≤20). Here, we present a self-filtering photodetector based on MAPbX3 single crystals with a very narrow spectral response and a full width of 15 nm at half maximum. It also shows a high responsivity (∼100 mA/W) and a high spectral rejection ratio (∼300). What is more, the response spectrum can be tuned within a certain range (from 440 to 560 nm) by varying the halide composition and thus its bandgap. This provides a new design paradigm for self-filtering narrowband photodetectors.

The incidence of Alzheimer’s disease (AD) is constantly increasing as the older population grows, and no effective treatment is currently available. In this study, we focused on the identification of AD molecular subtypes to facilitate the development of effective drugs. AD sequencing data collected from the Gene Expression Omnibus (GEO) database were subjected to cluster sample analysis. Each sample module was then identified as a specific AD molecular subtype, and the biological processes and pathways were verified. The main long non-coding RNAs and transcription factors regulating each “typing pathway” and their potential mechanisms were determined using the RNAInter and TRRUST databases. Based on the marker genes of each “typing module,” a classifier was developed for molecular typing of AD. According to the pathways involved, five sample clustering modules were identified (mitogen-activated protein kinase, synaptic, autophagy, forkhead box class O, and cell senescence), which may be regulated through multiple pathways. The classifier showed good classification performance, which may be useful for developing novel AD drugs and predicting their indications.

Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

BACKGROUND Aberrant DNA hypermethylation of CpG islands (CGIs) occurs frequently and is genome-wide in human gastric cancer (GC). A DNA methylation approach in plasma cell-free DNA (cfDNA) is attractive for the noninvasive detection of GC. Here, we performed genome-scale cfDNA methylation analysis in patients with GC. METHODS We used MCTA-Seq, a genome-scale DNA methylation analysis method, on the plasma samples of patients with GC (n = 89) and control participants (n = 82), as well as 28 pairs of GC and adjacent noncancerous tissues. The capacity of the method for detecting GC and discriminating GC from colorectal cancer (CRC) and hepatocellular carcinoma (HCC) was assessed. RESULTS We identified 153 cfDNA methylation biomarkers, including DOCK10, CABIN1, and KCNQ5, for detecting GC in blood. A panel of these biomarkers gave a sensitivity of 44%, 59%, 78%, and 100% for stage I, II, III, and IV tumors, respectively, at a specificity of 92%. CpG island methylation phenotype (CIMP) tumors and NON-CIMP tumors could be distinguished and detected effectively. We also identified several hundreds of cfDNA biomarkers differentially methylated between GC, CRC, and HCC, and showed that MCTA-Seq can discriminate early-stage GC, CRC, and HCC in blood by using a high specificity (approximately 100%) algorithm. CONCLUSIONS Our comprehensive analyses provided valuable data on cfDNA methylation biomarkers of GC and showed the promise of cfDNA methylation for the blood-based noninvasive detection of GC.

More and more patients suffered from Coronavirus disease 2019 (COVID-19) have got recovery gradually due to suitable intervention. Increasing data mainly studies the clinical characteristics of recovered COVID-19 patients, and their molecular changes especially proteome changes also play the same important role in understanding of biological characteristics of recovered COVID-19 patients as clinical characteristics do. In our study, we reported the whole lung-ground glass-CT value-average of mild/severe recovered patients 3 months after discharge without underlying diseases was significantly lower than that of healthy subjects. Then we isolated the extracellular vesicles (EVs) of plasma from 19 healthy subjects and 67 recovered COVID-19 patients. Mass Spectrometry was used to catalogue the proteins of these EVs compared to a defined group of controls. Identified 174 proteins were differentially expressed in the EVs of COVID-19 patients compared with healthy subjects, which involved in lipid metabolic process, response to cellular, and response to stress oxygen-containing compound. Besides, we identified several protein of plasma EVs in recovered patients associated with coagulation activity, inflammatory reaction, immune response, and low organ function. In addition, proteins correlating with clinical index such as alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were also detected. Moreover, we also identified many unique or characteristic associations found in the recovered COVID-19 patients, which especially involved the kidney, serum electrolyte levels, and inflammation functions. This finding suggests that monitoring the situation of recovered patients might be useful, especially the indexes of coagulation, inflammation, immunity, and organ function, which can prevent bleeding, reinfection and organ dysfunction.