A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain.

Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration.

A spatial long-read approach at near-single-cell resolution reveals developmental regulation of splicing and polyadenylation sites in distinct cortical layers and cell types.

Genome-wide spatial long-read approaches often lack single-cell resolution and yield limited read lengths. Here, we introduce spatial ISOform sequencing (Spl-ISO-Seq), which reveals exons and polyadenylation sites with near-single-cell resolution. Spl-ISO-Seq selects long cDNAs and doubles to triples read lengths compared to standard preparations.

Overlap between transitional care management after hospital discharge and alternative payment models.

Care coordination is integral during posthospital transitions. The Centers for Medicare & Medicaid Services (CMS) has sought to promote post-hospitalization care coordination through population-based alternative payment models (APMs) and transitional care management (TCM) services. Both can be associated with benefits, but data are lacking about their overlap.

A Novel Anti-BoNT/A Neutralizing Antibody Possessed Overlapped Epitope with SV2 and Had Prolonged Half-Life In Vivo.

The C-terminus of the BoNT/A heavy chain (BoNT/AHC) mediates binding to its receptor, SV2, a critical step for toxicity. Antibody inhibition of this interaction enhances neuronal survival. We previously identified a functional anti-BoNT/AHC nanobody, HM.

LDLR H3K27ac in PBMCs: An Early Warning Biomarker for Hypercholesterolemia Susceptibility in Male Newborns Treated with Prenatal Dexamethasone.

Dexamethasone, widely used as an exogenous glucocorticoid in clinical and animal practice, has recently been recognized as an environmental contaminant of concern. Existing evidence documents its ability to induce persistent dyslipidemia in adult offspring. In this study, plasma cholesterol levels in male rats exposed to dexamethasone prenatally (PDE) were increased.

Red blood cell count and its inverse association with diabetic retinopathy: Exploratory development of a risk assessment model in a retrospective cohort.

Objective: The purpose of this exploratory study was to investigate the association between red blood cell count (RBC) and diabetic retinopathy (DR) and to develop a preliminary risk assessment framework.

Methods: A total of 413 individuals diagnosed with type 2 diabetes mellitus (T2DM) at Suqian First Hospital's Endocrinology Department were included in this study. These participants were divided into training and validation groups in a 7:3 ratio, consisting of 289 and 124 patients respectively.

Screening Obstructive Sleep Apnea in Chinese Adults: Optimizing STOP-Bang and NoSAS Cutoff Values.

BACKGROUND This retrospective study of 3129 individuals aimed to screen obstructive sleep apnea (OSA) with the modified STOP-Bang questionnaire (SBQ) and Neck, Obesity, Snoring, Age, Sex (NoSAS) scores, establish more appropriate cutoff values for these 2 questionnaires in Chinese patients, and investigate whether adding minimum oxygen saturation (LSpO2) as an item could improve the ability of these questionnaires. MATERIAL AND METHODS We collected polysomnography data, demographic data, anthropometric measurements, and the SBQ and NoSAS scores from 3129 participants. The ability of the SBQ and NoSAS score with different cutoff values to detect OSA was assessed.

Evaluation of representativeness and sustainability of PCOS rat models induced by letrozole with or without high-fat diet.

This article aimed to evaluate the representativeness and sustainability of a rat model of polycystic ovary syndrome (PCOS) induced by letrozole (LE) with or without a high-fat diet (HFD). Sexually mature SD rats were randomly divided into a sham group (receiving 1% carboxymethyl cellulose sodium + standard chow, n = 9), a letrozole group (receiving LE + standard chow, n = 15), and a letrozole combined with HFD group (receiving LE + HFD, n = 15). After 21 days, model tests were performed based on body weight, estrous cycle, hormone levels, and ovarian histological changes, and successful modeling rats in LE and LE + HFD groups were further divided into two subgroups: an induction continuation group and an induction termination group (n = 6 in each group), respectively, which were treated for an additional 5 weeks.

Associations of accelerometer-measured weekend sleep catch-up and loss with risk of type 2 diabetes: a prospective cohort study.

Aims: To investigate the relationship between weekend sleep catch-up and loss and risk of type 2 diabetes (T2D).

Methods: This study included 80,414 adults aged 43-79 years from the UK Biobank. Weekend sleep catch-up and loss were derived from wrist-worn accelerometer data.

Unexpected richness and distinct patterns of () species diversity in Chongqing, a notable "Furnace City": unveiling rich diversity in hot regions.

species, commonly known as true morels and being cold-preferring fungi, are esteemed for their distinctive flavor as well as significant economic and prominent research value. Chongqing, located in southwestern China and renowned as the "Furnace City" due to its distinctive climate and extremely high summer temperatures, spans an area of 82,400 square kilometers with complex geographical topography, yet has lacked a comprehensive survey of true morels () so far. From 2017 to 2024, we conducted extensive field surveys across 13 districts and counties within Chongqing, resulting in the collection of over 1,000 wild morel samples.

Single-cell multimodal analysis reveals the dynamic immunopathogenesis of HBV-ACLF progression.

Background: Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome involving dysfunction of multiple immune cell types.

Objective: This study aimed to comprehensively depict the dynamic trajectory of immune responses throughout the disease course of HBV-related ACLF (HBV-ACLF).

Design: Single-cell RNA sequencing and single-cell proteomics were performed on the peripheral blood mononuclear cells of 45 samples from 17 patients who were hospitalised (progressive/stable/recovering course of HBV-ACLF, 6/5/6) and 15 control subjects (liver cirrhosis, chronic hepatitis B and healthy controls, 5/5/5).

Structural basis of peptide recognition and modulation for neuropeptide FF receptors.

Neuropeptide FF receptors 1 and 2 (NPFFR1 and NPFFR2) are RF-amide peptide receptors that couple to G proteins and regulate pain, opioid tolerance, and metabolism. Despite their physiological significance, their ligand selectivity and activation mechanisms remain unclear. Using cryoelectron microscopy, we resolved four NPFFR1 and NPFFR2 structures bound to NPFF or NPVF, revealing conserved C-terminal RF-amide interactions within the orthosteric pocket and N-terminal variations driving subtype specificity.

Declining Bowel Surgery Rates and Predictors for Surgery of Crohn's Disease: A Prospective Inception Cohort in Eastern China.

Objective: To investigate the rate of Crohn's disease (CD)-related bowel surgery within an inception cohort in Eastern China in the era of evolving diagnostic and therapeutic expertise.

Methods: A single-center, prospective cohort study was conducted from July 2019 to June 2022 in China. Patients with newly diagnosed CD were followed annually.

Isorhamnetin protects melanocytes against CD8+ T cell-mediated apoptosis and reduces inflammation in vitiligo-afflicted mouse.

Background: Vernonia anthelmintica (L.) Willd., containing isorhamnetin (ISO) as an active compound, is a conventional treatment for vitiligo within the Xinjiang region.

Progressive mitochondrial dysfunction impairs visual signal transduction and induces retinal degeneration in .

Mitochondrial dysfunction is closely associated with the pathogenesis of retinitis pigmentosa (RP), often through the generation of reactive oxygen species (ROS), which disrupts visual signal transduction. However, in certain instances, mitochondrial dysfunction does not correlate with an increase in ROS, and the precise mechanisms by which mitochondrial dysfunction contributes to RP remain poorly understood. In this study, we demonstrate that mitochondrial dysfunction can also impair visual signal transduction through ROS-independent mechanisms.

The safety and feasibility of the "pan-gate theory" in laparoscopic liver resection through laennec's approach combined with "regional hepatic inflow occlusion" for hepatocellular carcinoma.

Background: The "pan-gate theory", an innovative extension of the "gate theory," optimizes Laennec's approach in laparoscopic liver resection (LLR) by increasing adaptability to anatomical variations and facilitating rapid isolation of the target hepatic pedicle for precise regional inflow occlusion. This study evaluated the safety and feasibility of the "pan-gate theory" in LLR for hepatocellular carcinoma (HCC), with a focus on technical advantages and postoperative outcomes.

Methods: This was a single-arm retrospective study of 48 HCC patients who underwent LLR via the pan-gate Theory (June 2022-September 2023).

Serum tyrosine increases all-cause mortality in an older population.

Purpose: Amino acids play crucial roles in metabolic and cardiovascular diseases, especially branched-chain and aromatic amino acids, but their association with mortality remains understudied and inconclusive. This study explored the potential correlation between serum amino acids levels (including leucine(Leu), isoleucine(Ile), valine(Val), phenylalanine(Phe), and tyrosine (Tyr) and all-cause or cardiovascular deaths in an older population.

Methods: This study involved 1,238 older people selected from the Huai'an Diabetes Prevention Program aged ≥ 60 years.

Value of Novel Quantitative Acoustic Parameters Based on Mel Frequency Cepstral Coefficients in Pediatric Vocal Cord Nodules and Laryngopharyngitis.

Unlabelled: Pediatric vocal cord nodules and laryngopharyngitis are common childhood voice disorders. Previous studies have shown that novel acoustic indices developed based on Mel frequency cepstral coefficients (MFCCs) demonstrate promising value in assessing hoarseness in adults. We therefore explored the value of these new acoustic parameters in the detection of vowel sounds in pediatric patients with vocal cord nodules and laryngopharyngitis.

Genome-Wide 5-Methylcytosine and 5-Hydroxymethylcytosine Signatures Analysis of Plasma Cell-Free DNA in Schizophrenia.

Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder that affects ∼1% of people globally. Despite extensive research, there remains a lack of biomarkers for SCZ diagnosis and disease pathogenesis delineation. Cell-free DNA (cfDNA), which carries the genetic and epigenetic signatures of origin tissue cells, may provide a noninvasive method for biomarker discovery.

Performance of the China-CLIF framework in acute-on-chronic liver failure: a multicohort study across all aetiologies.

Background: Acute-on-chronic liver failure (ACLF) of various aetiologies is a complex syndrome with high short-term mortality and significant global burden.

Objective: To explore easily applicable diagnostic criteria and an accurate prognostic score for ACLF.

Design: Clinical data from 5288 patients (after exclusions from 7388 screened) with acute deterioration of chronic liver disease across various aetiologies were used to evaluate the performance of European Chronic Liver Failure (CLIF) and Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria.

Metastatic mediastinal malignant tumors of gastrointestinal origin with occult primary lesions: a case report.

Cancer of unknown primary origin (CUP), accounting for 3-5% of malignancies, poses significant diagnostic challenges because of the absence of identifiable primary lesions. While common occult primary tumors involve the lung or pancreas, gastrointestinal (GI)-originated mediastinal metastases are exceedingly rare. A 54-year-old male presented with chest tightness and dyspnea.

Combined single-cell profiling of chromatin-transcriptome and splicing across brain cell types, regions and disease state.

Measuring splicing and chromatin accessibility simultaneously in frozen tissues remains challenging. Here we combined single-cell isoform RNA sequencing and assay for transposase accessible chromatin (ScISOr-ATAC) to interrogate the correlation between these modalities in single cells in human and rhesus macaque frozen cortical tissue samples. Applying a previous definition of four 'cell states' in which the transcriptome and chromatin accessibility are coupled or decoupled for each gene, we demonstrate that splicing patterns in one cell state can differ from those of another state within the same cell type.

Towards a clinical pathway to food for special medical purpose in China: current progress based on a cross-sectional survey.

Background And Objectives: To investigate the current status of clinical pathway implementation for food for special medical purpose (FSMP) in China and provide a scientific basis for constructing a standardized pathway.

Methods And Study Design: An E-questionnaire was distributed to 27 clinical nutrition quality control centers in tertiary medical institutions in China from September to October 2023 via random stratified sampling.

Results: Ninety-eight valid questionnaires were ultimately recovered.

Spatial isoform sequencing at sub-micrometer single-cell resolution reveals novel patterns of spatial isoform variability in brain cell types.

Spatial long-read technologies are becoming more common but lack nanometer- and therefore often single-cell resolution. This leaves the question unanswered whether spatially variable isoforms represent spatial variability within one cell type or differences in cell-type abundance between different regions. Here, we develop Spl-ISO-Seq2 with 220nm spot size and 500nm resolution, and the accompanying software packages Spl-IsoQuant-2 and Spl-IsoFind and apply it to the adult mouse brain.

Metformin promotes osteogenic differentiation of human periodontal ligament stem cells via KLF2-mediated activation of miR-181a-5p under lipopolysaccharide stimulation.

Periodontal ligament stem cells (PDLSCs) constitute a promising source for successful periodontal regeneration. This study aims to explore roles of metformin, krüppel-like factor 2 (KLF2), and miR-181a-5p in mediating osteogenic differentiation of human PDLSCs (hPDLSCs) following lipopolysaccharide (LPS) stimulation. The osteogenic differentiation potential of hPDLSCs isolated from human premolar root samples were examined by alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin red S staining, and Western blotting of osteogenic markers.