Effects of Geniposide on Cerebral Ischemia/Reperfusion-Induced Neuron Damage by Inhibiting Autophagy via cGAS-STING.

Aim Of The Study: This study aimed to investigate the protective effects of Geniposide (GEN) against cerebral ischemia-reperfusion injury by targeting the cGAS-STING pathway and modulating autophagy in neuronal cells.

Materials And Methods: In vivo middle cerebral artery occlusion/reperfusion (MCAO/R) model and an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model to mimic the pathology of cerebral ischemic stroke in humans. Behavioral tests, tissue staining to assess neurological deficits and tissue damage in mice.

Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity.

Precision application of targeted therapies is urgently needed to improve long-term clinical outcomes for children affected by inflammatory arthritis, known as juvenile idiopathic arthritis (JIA). Progress has been hampered by our limited understanding of the cellular basis of inflammation in the target tissue of the disease, the synovial membrane. Here, we analyzed biopsies from the inflamed joints of treatment-naïve children with JIA, early in the course of their disease, using single-cell RNA sequencing, multiplexed immunofluorescence, and spatial transcriptomics to establish a cellular atlas of the JIA synovium.

Critical Properties for Stabilizing Pd Nanoparticles in Graphene Oxide Framework-Supported Catalysts: Insights from Multifaceted Characterization.

Graphene oxide frameworks (GOFs) have great potential as supports for metal nanoparticle (NP) catalysts due to their advantageous properties, such as engineerable pores. Since GOFs are prepared by bridging GO sheets with linker molecules, their properties depend on the GO raw material, and thus, designing guidelines for GOs is important but has not been established yet. The most significant obstacle is the diversity of the physicochemical properties of GOs, making it difficult to determine which properties are linked to their performance as catalyst supports.

Distinct viral reservoirs and immune signatures in individuals on long-term antiretroviral therapy with perinatally acquired HIV-1.

Early initiation of antiretroviral therapy (ART) following HIV-1 infection restricts the size of the latent reservoir, following both horizontal and vertical infections. Here, we comprehensively profile the reservoirs and immunological milieus of nine young adults who acquired HIV-1 perinatally and remained on suppressive long-term ART (median: 20 years) since infancy (LeukoHIV cohort). Genome-intact reservoirs are markedly smaller compared to a cohort of adults on suppressive ART started in adulthood, with some LeukoHIV individuals characterized by an absence or near absence of intact proviruses in up to a billion peripheral blood mononuclear cells (PBMCs).

Spatial Transcriptomics Identifies Immune-Stromal Niches Associated with Cancer in Adult Dermatomyositis.

Adult-onset dermatomyositis (DM) is an autoimmune inflammatory myopathy with distinct cutaneous manifestations and a strong malignancy association. Through comparative analysis with cutaneous lupus erythematosus (CLE), our integrated spatial and single-cell transcriptomics analysis revealed unique immune and stromal niches associated with DM subtypes. Unexpectedly, we found an association between cancer-associated DM skin lesions and the presence of dispersed immune infiltrates enriched with macrophages, CD8+ T cells, plasma cells, and B cells with preserved vascular architecture.

Spatial patterning of fibroblast TGFβ signaling underlies treatment resistance in rheumatoid arthritis.

Treatment-refractory rheumatoid arthritis (RA) is a major unmet need, and the mechanisms driving treatment resistance are poorly understood. To identify molecular determinants of RA non-remission, we performed spatial transcriptomic profiling on pre- and post-treatment synovial tissue biopsies from treatment naïve patients who received conventional DMARDs or adalimumab for 6 months. In the baseline biopsies of non-remission patients, we identified significant expansion of fibrogenic fibroblasts marked by high expression of , a fibrosis-associated extracellular matrix protein.

Additive interaction between CYP2C19AA gene polymorphism and Lp(a) on the prognosis of stroke patients.

Objective: To investigate the influence of cytochrome P450 2C19 (CYP2C19) gene polymorphism and lipoprotein (a) (Lp(a)) levels, and their interaction, on the prognosis of stroke patients.

Methods: A total of 120 stroke patients admitted to Wuming Hospital of Guangxi Medical University from January 2022 to June 2024 were retrospectively selected as the observation group. Additionally, 118 healthy people with normal outpatient physical examination indices during the same period were selected as the control group, matched for age, gender, and body mass index (BMI).

Circular RNA hsa_circ_0000288 protects against epilepsy in mice by binding to and stabilizing caprin1 protein.

Current anti-epileptic drugs remain to be unsatisfactory, new therapeutic approaches are needed. Circular RNA is a promising class of therapeutic RNAs. Recent studies have shown the role of circRNA in the pathologic process of epilepsy.

Two novel SNPs rs1736952 and rs17354984 are highly associated with uveitis in ankylosing spondylitis.

Background: Noninfectious anterior uveitis shares genetic factors, including HLA-B27, with ankylosing spondylitis (AS). The aim of this study was to identify significant single nucleotide polymorphisms (SNPs) associated with noninfectious anterior uveitis in AS patients, which may help predict help predict the risk of developing this condition and provide deeper insights into its genetic basis.

Methods: A genome-wide association study (GWAS) was conducted using the genomic data of 468 AS patients, including 90 with noninfectious anterior uveitis and 378 without it, from the Taiwan Precision Medicine Initiative.

Profound reduction of HIV-1 reservoir cells over 3 decades of antiretroviral therapy started in early infancy.

HIV-1 reservoir cells persist indefinitely during suppressive antiretroviral therapy (ART) in individuals who acquire infection in adulthood, but little is known about the longitudinal evolution of viral reservoir cells during long-term ART started during early infancy. We studied 2 fraternal twins who acquired HIV-1 perinatally, started ART at week 10 after birth and remained on ART for 28 years. We observed that the frequency of genome-intact proviruses, determined by single-genome near-full-length proviral sequencing, declined by approximately 4,000- to 13,000-fold during this period, indicating enhanced decay rates of intact proviruses even after adjusting for dilution effects from somatic growth.

Structure-Driven Performance Enhancement in Palladium-Graphene Oxide Catalysts for Electrochemical Hydrogen Evolution.

Graphene oxide (GO) has recently gained significant attention in electrocatalysis as a promising electrode material owing to its unique physiochemical properties such as enhanced electron transfers due to a conjugated π-electron system, high surface area, and stable support for loading electroactive species, including metal nanoparticles. However, only a few studies have been directed toward the structural characteristics of GO, elaborating on the roles of oxygen-containing functional groups, the presence of defects, interlayer spacing between the layered structure, and nonuniformity in the carbon skeleton along with their influence on electrochemical performance. In this work, we aim to understand these properties in various GO materials derived from different graphitic sources.

Footprints of innate immune activity during HIV-1 reservoir cell evolution in early-treated infection.

Antiretroviral treatment (ART) initiation during the early stages of HIV-1 infection is associated with a higher probability of maintaining drug-free viral control during subsequent treatment interruptions, for reasons that remain unclear. Using samples from a randomized-controlled human clinical trial evaluating therapeutic HIV-1 vaccines, we here show that early ART commencement is frequently associated with accelerated and efficient selection of genome-intact HIV-1 proviruses in repressive chromatin locations during the first year after treatment initiation. This selection process was unaffected by vaccine-induced HIV-1-specific T cell responses.

Capn3b-deficient zebrafish model reveals a key role of autoimmune response in LGMDR1.

Mutations in calcium-dependent papain-like protease CALPAIN3 (CAPN3) cause Limb-Girdle Muscular Dystrophy Recessive Type 1 (LGMDR1), the most common limb-girdle muscular dystrophy in humans. In addition to progressive muscle weakness, persistent inflammatory infiltration is also a feature of LGMDR1. Despite the underlying mechanism remaining poorly understood, we consider that it may relate to the newly defined role of CAPN3/Capn3b in the nucleolus.

The preparation methods and types of cell sheets engineering.

Cell therapy has emerged as a viable approach for treating damaged organs or tissues, particularly with advancements in stem cell research and regenerative medicine. The innovative technique of cell sheet engineering offers the potential to create a cell-dense lamellar structure that preserves the extracellular matrix (ECM) secreted by cells, along with the cell-matrix and intercellular junctions formed during in vitro cultivation. In recent years, significant progress has been made in developing cell sheet engineering technology.

Research progress in stem cell therapy for Wilson disease.

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive disorder characterized by disorganized copper metabolism caused by mutations in the gene. Currently, the main treatment options for WD involve medications such as d-penicillamine, trientine hydrochloride, zinc acetate, and liver transplantation. However, there are challenges that encompass issues of poor compliance, adverse effects, and limited availability of liver sources that persist.

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).

Selection of epigenetically privileged HIV-1 proviruses during treatment with panobinostat and interferon-α2a.

CD4 T cells with latent HIV-1 infection persist despite treatment with antiretroviral agents and represent the main barrier to a cure of HIV-1 infection. Pharmacological disruption of viral latency may expose HIV-1-infected cells to host immune activity, but the clinical efficacy of latency-reversing agents for reducing HIV-1 persistence remains to be proven. Here, we show in a randomized-controlled human clinical trial that the histone deacetylase inhibitor panobinostat, when administered in combination with pegylated interferon-α2a, induces a structural transformation of the HIV-1 reservoir cell pool, characterized by a disproportionate overrepresentation of HIV-1 proviruses integrated in ZNF genes and in chromatin regions with reduced H3K27ac marks, the molecular target sites for panobinostat.

Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues.

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, and gene signatures associated with pathological features, and are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance of three commercial iST platforms on serial sections from tissue microarrays (TMAs) containing 23 tumor and normal tissue types for both relative technical and biological performance. On matched genes, we found that 10x Xenium shows higher transcript counts per gene without sacrificing specificity, but that all three platforms concord to orthogonal RNA-seq datasets and can perform spatially resolved cell typing, albeit with different false discovery rates, cell segmentation error frequencies, and with varying degrees of sub-clustering for downstream biological analyses.

IL-15-dependent immune crosstalk between natural killer cells and dendritic cells in HIV-1 elite controllers.

As the principal effector cell population of the innate immune system, natural killer (NK) cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory chromatin features, we demonstrate here that cytotoxic NK (cNK) cells from elite controllers (ECs) display elevated activating histone modifications at the interleukin 2 (IL-2)/IL-15 receptor β chain and the BCL2 gene loci. These histone changes translate into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincides with higher levels of IL-15 transcription by myeloid dendritic cells in ECs.

Persistence of intact HIV-1 proviruses in the brain during antiretroviral therapy.

HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia.

Hhex and Prox1a synergistically dictate the hepatoblast to hepatocyte differentiation in zebrafish.

The specification of endoderm cells to prospective hepatoblasts is the starting point for hepatogenesis. However, how a prospective hepatoblast gains the hepatic fate remains elusive. Previous studies have shown that loss-of-function of either hhex or prox1a alone causes a small liver phenotype but without abolishing the hepatocyte differentiation, suggesting that absence of either Hhex or Prox1a alone is not sufficient to block the hepatoblast differentiation.

The HIV-2 proviral landscape is dominated by defective proviruses.

Background: Compared with HIV-1 infection, HIV-2 infection is associated with a slower progression to AIDS. Understanding the persistence of HIV-2 infection might inform the mechanisms responsible for differences in the pathogenicity of HIV-2 versus HIV-1.

Methods: In this study, we analyzed the genetic composition of the proviral reservoir in archived blood samples collected from 13 untreated HIV-2-infected adults from Senegal.