Truncating Mutations in BBS10 and BBS12 Impair Proteostasis and Ciliary Architecture in Bardet-Biedl Syndrome.

Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive ciliopathy characterized by genetic heterogeneity. Despite significant progress in understanding the BBSome-coding genes associated with ciliopathies, the pathogenesis linked to mutations in chaperonin-coding genes (BBS6, BBS10, and BBS12) remains poorly defined. This study aims to confirm the genetic diagnosis of BBS and elucidate the pathological mechanisms in causative genes of BBS10 and BBS12.

Potential role of gut bacteria in the development of hepatocellular carcinoma.

Liver cancer is the fourth most deadly cancer, and early detection and timely treatment apparently play a crucial role in it. Intestinal bacteria affect the development of liver cancer through various pathways. In this study, the gut bacteria of liver cancer patients are analysed in detail by using metagenomic sequencing technology, and some of the bacterial species and metabolic pathways that may affect the development of liver cancer have been identified.

Multimodal imaging of dark without pressure in high myopia reveals evidence that photoreceptor microscopic lesions may be reversible.

Dark without pressure (DWP) is the more darkly pigmented area of the retina in the fundus, typically exhibits relatively distinct boundaries, and varies in shape, size, and distribution across different individuals. Previous studies have concluded that DWP alone has no impact visual acuity, visual field, or other visual functions. This study aims to reveal the multimodal imaging manifestations of DWP in high myopia and to explore its impact on retinal function.

Acetylation profiling by Iseq-Kac reveals insights into HSC aging and lineage decision.

Profiling post-translational modifications face challenges with low-input samples. We developed Iseq-Kac (internal standard-assisted enrichment-free approach for high-throughput quantitative analysis of lysine acetylation) to profile the acetylome in as few as 10-10 cells. By using a hyperacetylated internal standard, Iseq-Kac can be used in mass spectrometry (MS) to enhance MS1 signals and facilitate MS2 fragmentation of acetylated peptides.

Genetic Diversity, Antimicrobial Resistance, and Virulence Profiles of Isolates from Nantong, China (2020-2023).

poses significant public health and food safety risks due to its environmental resilience and pathogenicity. In this study, we utilized whole-genome sequencing to characterize 15 strains isolated from Nantong, China (2020-2023), recovered from food and clinical samples. Antimicrobial susceptibility testing revealed that the Nantong isolates exhibited high resistance rates to ciprofloxacin (93.

Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an exceptionally rare inflammatory disorder affecting choroid and retinal pigment epithelial (RPE) cells. Although recent studies suggest an immune-driven nature, the underlying etiology of APMPPE remains elusive. In this study, we conducted a comprehensive investigation on the peripheral blood mononuclear cells (PBMCs) profile of an APMPPE patient using single-cell RNA sequencing.

AAV2-PDE6B restores retinal structure and function in the retinal degeneration 10 mouse model of retinitis pigmentosa by promoting phototransduction and inhibiting apoptosis.

JOURNAL/nrgr/04.03/01300535-202508000-00030/figure1/v/2024-09-30T120553Z/r/image-tiff Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death. However, there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.

Preservation of Mitochondrial Function by SkQ1 in Skin Fibroblasts Derived from Patients with Leber's Hereditary Optic Neuropathy Is Associated with the PINK1/PRKN-Mediated Mitophagy.

Increased or altered mitochondrial ROS production in the retinal ganglion cells is regarded as the chief culprit of the disease-causing Leber's hereditary optic neuropathy (LHON). SkQ1 is a rechargeable mitochondria-targeted antioxidant with high specificity and efficiency. SkQ1 has already been used to treat LHON patients, and a phase 2a randomized clinical trial of SkQ1 has demonstrated improvements in eyesight.

Proteomics identifies multiple retinitis pigmentosa associated proteins involved in retinal degeneration in a mouse model bearing a Pde6b mutation.

Retinitis pigmentosa (RP) is a progressive and degenerative retinal disease resulting in severe vision loss. RP have been extensively studied for pathogenetic mechanisms and treatments. Yet there is little information about alterations of RP associated proteins in phosphodiesterase 6 beta (Pde6b) mutated model.

Mechanisms underlying morphological and functional changes of cilia in fibroblasts derived from patients bearing ARL3 and ARL3 mutations.

ARL3 is essential for cilia development, and mutations in ARL3 are closely associated with ciliopathies. In a previous study, we observed distinct phenotypes of retinal dystrophy in patients with heterozygous ARL3 and compound heterozygous ARL3 mutations, indicating that different mutation types may exert diverse effects on their functions. Here, we generated transformed immortal fibroblast cells from patients carrying heterozygous ARL3 and compound heterozygous ARL3 mutations, and systematically evaluated their cilia morphology and function, which were further validated in ARPE-19 cells.

Antibiotic Resistance and Epidemiology of from Clinical Samples in Nantong, China, 2018-2021.

Purpose: The objective of this study was to investigate the prevalence and molecular characteristics of isolates from fecal samples of patients in Nantong, China.

Methods: From 2018 to 2021, a total of 106 clinical cases and samples of infection were collected. The virulence genes, serotypes and antibiotic resistance of these isolates were analyzed.

Proteomic Profiling Reveals Increased Glycolysis, Decreased Oxidoreductase Activity and Fatty Acid Degradation in Skin Derived Fibroblasts from LHON Patients Bearing m.G11778A.

LHON is a common blinding inherited optic neuropathy caused by mutations in mitochondrial genes. In this study, by using skin fibroblasts derived from LHON patients with the most common m.G11778A mutation and healthy objects, we performed proteomic analysis to document changes in molecular proteins, signaling pathways and cellular activities.

A novel mutation located in the intermembrane space domain of AFG3L2 causes dominant optic atrophy through decreasing the stability of the encoded protein.

Dominant optic atrophy (DOA) is the most common hereditary optic neuropathy. Although DOA is caused by mutations in several genes, there are still many cases that have not been diagnosed or misdiagnosed. Herein, we present a large family of 11 patients with DOA.

Multi-mtDNA Variants May Be a Factor Contributing to Mitochondrial Function Variety in the Skin-Derived Fibroblasts of Leber's Hereditary Optic Neuropathy Patients.

Heterogeneity is a major feature of Leber's hereditary optic neuropathy (LHON) and has a significant impact on the manifestation and diagnosis of the disease. This study explored whether multiple variations in mitochondrial genes were associated with the heterogeneity, mainly phenotypic heterogeneity. Ophthalmic examinations were conducted in two probands with LHON with G11778A and multiple mitochondrial DNA gene (mtDNA) variants.

Retinal Proteomic Alterations and Combined Transcriptomic-Proteomic Analysis in the Early Stages of Progression of a Mouse Model of X-Linked Retinoschisis.

X-linked retinoschisis (XLRS) is among the most commonly inherited degenerative retinopathies. XLRS is caused by functional impairment of RS1. However, the molecular mechanisms underlying RS1 malfunction remain largely uncharacterized.

Longitudinal Photoreceptor Phenotype Observation and Therapeutic Evaluation of a Carbonic Anhydrase Inhibitor in a X-Linked Retinoschisis Mouse Model.

Purpose: To study the long-term photoreceptor changes and to evaluate the effects of topical application of a carbonic anhydrase inhibitor (CAI) in a mouse model of X-linked retinoschisis (XLRS).

Methods: Conventional electroretinograms (ERGs) and dark-adapted 10-Hz flicker ERGs were recorded in control and mice generated with CRISPR/Cas9. ON-pathway blocker 2-amino-4-phosphobutyric acid (APB) was injected intravitreally.

Identification of Age-associated Proteins and Functional Alterations in Human Retinal Pigment Epithelium.

Retinal pigment epithelium (RPE) has essential functions, such as nourishing and supporting the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE during aging remain poorly understood. Here, we isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10-67 years old).

Combined use of extracorporeal membrane oxygenation with interventional surgery for acute pancreatitis with pulmonary embolism: A case report.

Background: Acute pancreatitis (AP) is an acute inflammatory process of the pancreas characterized by self-digestion of pancreatic tissue, which can trigger a systemic inflammatory response. Venous thrombosis, resulting from a hypercoagulable state, is a vascular complication of AP. AP complicated by pulmonary embolism (PE) is very rare, and the combined use of extracorporeal membrane oxygenation (ECMO) with a vascular interventional procedure for AP complicated by PE is even rarer.

Glycyrrhetinic acid restricts mitochondrial energy metabolism by targeting SHMT2.

Glycyrrhetinic acid (GA) is a natural product of licorice with mitochondria targeting properties and shows broad anticancer activities, but its targets and underlying mechanisms remain elusive. Here, we identified the mitochondrial enzyme serine hydroxymethyltransferase 2 (SHMT2) as a target of GA by using chemical proteomics. Binding to and inhibiting the activity of SHMT2 by GA were validated and .