Trimethylamine N-oxide induces cardiac diastolic dysfunction by down-regulating Piezo1 in mice with heart failure with preserved ejection fraction.

Aims: The present study aimed to investigate the direct link between trimethylamine N-oxide (TMAO) and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF).

Materials And Methods: Diastolic dysfunction is the main manifestation of HFpEF, so the "two-hit" mouse HFpEF model are used. After treated with high-fat diet (HFD) and N-nitro-l-arginine methyl ester (L-NAME) for 8 weeks, the cardiac function, myocardial fibrosis, oxidative stress levels, and molecular alterations were assessed.

ESOD: Efficient Small Object Detection on High-Resolution Images.

Enlarging input images is a straightforward and effective approach to promote small object detection. However, simple image enlargement is significantly expensive on both computations and GPU memory. In fact, small objects are usually sparsely distributed and locally clustered.

Recessive genetic contribution to congenital heart disease in 5,424 probands.

Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the recessive contribution to the broad range of CHD phenotypes has been limited. We analyzed whole exome sequences of 5,424 CHD probands.

PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (ventriculomegaly) is a defining feature of congenital hydrocephalus (CH) and an under-recognized concomitant of autism. Here, we show that de novo mutations in the autism risk gene PTEN are among the most frequent monogenic causes of CH and primary ventriculomegaly. Mouse Pten-mutant ventriculomegaly results from aqueductal stenosis due to hyperproliferation of periventricular Nkx2.

Injectable polyplex-loaded glycol chitosan thermogel for efficient and safe inner ear gene delivery.

Gene therapy has emerged as a promising approach for treating inner ear disorders, such as hearing loss and balance impairments, which require precise and efficient delivery mechanisms. This study introduces a dual-component delivery system combining RH-PAMAM G2 dendrimer-based polyplexes with hexanoyl glycol chitosan (HGC) thermogel to enhance gene delivery to the inner ear. The RH-PAMAM G2 dendrimers, modified with histidine and arginine, demonstrated high DNA binding affinity, low cytotoxicity, and effective cellular uptake, facilitating stable plasmid DNA (pDNA) transfection in HEI-OC1 auditory cells.

Association between blood eosinophil levels and prognosis in critically ill patients with different heart failure phenotypes.

Heart failure (HF) is associated with poor prognosis. While various immune markers have been linked to HF outcomes, the relationship between eosinophils (EOS) and prognosis across different HF phenotypes remains unclear and controversial. In this study, we analyzed 2,677 HF patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database, categorizing them into reduced ejection fraction (≤ 50%) and preserved ejection fraction (> 50%) groups.

De Novo MET-amplified NSCLC treated with savolitinib achieved remarkable tumor regression: a case report and review of literature.

Primary MET amplification is an infrequent tumorigenic driver gene alteration identified in pulmonary neoplasms. Data on the effectiveness of MET-tyrosine kinase inhibitor (TKI) therapy in de novo MET amplification are relatively scarce, and there remains a dearth of empirical evidence supporting the use of precision therapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with primary MET amplification. We present a case of advanced lung adenocarcinoma in an elderly patient with primary MET amplification.

Hydrogen sulfide attenuates sepsis-induced cardiac dysfunction in infant rats by inhibiting the expression of cold-inducible RNA-binding protein.

Sepsis-induced cardiac dysfunction is one of the most common complications of sepsis. It is also a major cause of death in pediatric intensive care units. The underlying mechanism of sepsis-induced cardiac dysfunction remains elusive.

Intratympanic administration of dexamethasone attenuates radiation induced damage to middle ear mucosa.

Radiotherapy (RTx) is a highly effective treatment for head and neck cancer that can cause concurrent damage to surrounding healthy tissues. In cases of nasopharyngeal carcinoma (NPC), the auditory apparatus is inevitably exposed to radiation fields and sustains considerable damage, resulting in dysfunction. To date, little research has been conducted on the changes induced by RTx in the middle ear and the underlying mechanisms involved.

Non small cell lung cancer with SMARCA4 deficiency harboring rare EGFR mutations exhibited significant tumor response when treated with afatinib: a case report.

SMARCA4-deficient non small cell lung cancer (SMARCA4-dNSCLC) has recently garnered increasing attention due to its high malignancy and poor prognosis. The literature suggests that in non small cell lung cancer (NSCLC), the loss of SMARCA4 frequently co-occurs with mutations in KRAS, KEAP1, and STK11 rather than in EGFR, ALK, and ROS1. Herein, we present the first documented case of SMARCA4-dNSCLC accompanied with rare mutations of EGFR exon 20 S768I and exon 18 G719X.

De novo variants disrupt an LDB1-regulated transcriptional network in congenital ventriculomegaly.

Congenital hydrocephalus (CH), characterized by cerebral ventriculomegaly (CV), is among the most common and least understood pediatric neurosurgical disorders. We have identified in the largest-assembled CV cohort (>2,697 parent-proband trios) an exome-wide significant enrichment of protein-altering de novo variants (DNVs) in LDB1 (p = 1.11 x 10-15).

PCSK9 promotes vascular neointimal hyperplasia through non-lipid regulation of vascular smooth muscle cell proliferation, migration, and autophagy.

We aim to explore the impact of Proprotein convertase subtilisin-kexin type 9 (PCSK9) and its inhibitor evolocumab on neointimal hyperplasia. Wild type and PCSK9 knockout (PCSK9) mice were subjected to ligation of the common carotid artery, with or without subcutaneous injection of evolocumab. Mouse aortic vascular smooth muscle (MOVAS) cells were pretreated with evolocumab or under siRNA-mediated suppression of PCSK9, and then exposed to platelet-derived growth factor type BB(PDGF-BB), a major promoter of MOVAS transformation to a proliferative phenotype.

Circulating microRNA-409-5p and USP7 are associated with left ventricular remodeling in patients with acute myocardial infarction.

Background: Our previous study demonstrated that microRNA-409-5p (miR-409-5p) and its target ubiquitin-specific protease 7 (USP7) were involved in hypoxia-induced cardiomyocyte injury and ischemic left ventricular remodeling (LVR) in rats. This study aimed to probe into the relationship between plasma miR-409-5p and USP7 levels and LVR and dysfunction in patients with acute myocardial infarction (AMI).

Methods: Sixty patients with acute myocardial infarction (AMI) and 60 cases with chronic coronary syndrome (CCS) were enrolled.

On Matrix Representation of Extension Field GF() and Its Application in Vector Linear Network Coding.

For a finite field GF(pL) with prime and L>1, one of the standard representations is L×L matrices over GF() so that the arithmetic of GF(pL) can be realized by the arithmetic among these matrices over GF(). Based on the matrix representation of GF(pL), a conventional linear network coding scheme over GF(pL) can be transformed to an -dimensional vector LNC scheme over GF(). Recently, a few real implementations of coding schemes over GF(2L), such as the Reed-Solomon (RS) codes in the ISA-L library and the Cauchy-RS codes in the Longhair library, are built upon the classical result to achieve matrix representation, which focuses more on the structure of every individual matrix but does not shed light on the inherent correlation among matrices which corresponds to different elements.

Hydrogen sulfide ameliorated endothelial dysfunction in hyperhomocysteinemia rats: Mechanism of IRE1α/JNK pathway-mediated autophagy.

Previous studies showed that hyperhomocysteinemia (HHcy) induced endothelial dysfunction by endoplasmic reticulum (ER) stress induction and autophagy stimulation. This study aimed to determine the effect of hydrogen sulfide (HS) in homocysteine (Hcy)-induced endothelial dysfunction and observe the possible mechanism involved. Male Wistar rats (160-180g) were used and randomly divided into four groups: Control group, HHcy group, HHcy+Sodium hydrosulfide (NaHS) group and NaHS group.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis.

Aim: Sepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms.

Methods: Patients with sepsis and healthy controls were included.

Biomimetic Channels Design in Metal-Organic Framework Enabling Highly Lithium-Ion Conduction for Lithium-Metal Batteries.

Solid-state electrolytes (SSEs) based on metal-organic frameworks (MOFs) are an ideal material for constructing high-performance lithium metal batteries (LMBs). However, the low ion conductivity and poor interface contact (especially at low temperatures) still seriously hinder its further application. Herein, inspired by the Na/K conduction in biology systems, a series (NH, OH, NH-(CH)-SOH)-modified MIL-53-X as SSEs is reported.

HS alleviated sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway.

To investigate the protective mechanisms of hydrogen sulfide (HS) in sepsis-induced acute kidney injury (SAKI), we conducted an in vivo study using a SAKI mouse model induced by intraperitoneal lipopolysaccharide (LPS) injection. Following 6 h of LPS injection, levels of tumor necrosis factor-alpha (TNF-α) and blood urea nitrogen (Bun) were significantly elevated in mouse plasma. In the kidneys of SAKI mice, expression of HS-generating enzymes cysteinyl-tRNA synthetase (CARS), cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) was markedly downregulated, while glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R-like endoplasmic reticulum kinase/protein kinase R-like endoplasmic reticulum kinase (p-PERK/PERK), and B-cell lymphoma-2 recombinant protein X/B-cell lymphoma-2 (Bax/Bcl2) expression was significantly upregulated.

BPI-28592 as a novel second generation inhibitor for NTRK fusion tumors.

Aberrant activation of tropomyosin receptor kinases (TRKs) is a well-defined oncogenic driver for neurotrophic tropomyosin receptor kinase (NTRK)-fusion cancers, and acquired resistant mutations have emerged with clinical use of the first-generation TRK inhibitors. Here we present BPI-28592, a novel second-generation TRK inhibitor with efficacy against TRK fusion-positive cancers, including those with resistant mutations. Docking simulations indicated no steric hindrance between BPI-28592 and TRK mutants, suggesting its potential to overcome drug resistance.

Systemic immune inflammation index is associated with in-stent neoatherosclerosis and plaque vulnerability: An optical coherence tomography study.

Background: In-stent neoatherosclerosis (ISNA) is identified as the primary cause of in-stent restenosis (ISR). The systemic immune inflammation index (SII), shows promise for predicting post-percutaneous coronary intervention (PCI) adverse cardiovascular events and is associated with coronary stenosis severity; however, its specific relationship with ISNA remains unclear. This study aimed to investigate the association between the SII and ISNA after drug-eluting stent (DES) implantation.

An Evaluation Model for Node Influence Based on Heuristic Spatiotemporal Features.

The accurate assessment of node influence is of vital significance for enhancing system stability. Given the structural redundancy problem triggered by the network topology deviation when an empirical network is copied, as well as the dynamic characteristics of the empirical network itself, it is difficult for traditional static assessment methods to effectively capture the dynamic evolution of node influence. Therefore, we propose a heuristic-based spatiotemporal feature node influence assessment model (HEIST).

TCFormer: Visual Recognition via Token Clustering Transformer.

Transformers are widely used in computer vision areas and have achieved remarkable success. Most state-of-the-art approaches split images into regular grids and represent each grid region with a vision token. However, fixed token distribution disregards the semantic meaning of different image regions, resulting in sub-optimal performance.

Potential clinical applications of advanced genomic analysis in cerebral palsy.

Cerebral palsy (CP) has historically been attributed to acquired insults, but emerging research suggests that genetic variations are also important causes of CP. While microarray and whole-exome sequencing based studies have been the primary methods for establishing new CP-gene relationships and providing a genetic etiology for individual patients, the cause of their condition remains unknown for many patients with CP. Recent advancements in genomic technologies offer additional opportunities to uncover variations in human genomes, transcriptomes, and epigenomes that have previously escaped detection.

Pathogenic variants in autism gene cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics.

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of () in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly.

Toward Enhancing Low Temperature Performances of Lithium-Ion Transport for Metal-Organic Framework-Based Solid-State Electrolyte: Nanostructure Engineering or Crystal Morphology Controlling.

Metal-organic frameworks (MOFs) have emerged as attractive candidates for Li conducting electrolytes due to their regular channels and controllable morphology, making their presence prominent in the field of solid-state lithium batteries. However, most MOF-based electrolytes are researched at or near room temperature, which poses a challenge to their practical applications at low temperatures. Herein, a thin layer flower-shaped 2D Cu-MOF (CuBDC-10)-based solid-state electrolytes (SSEs) for lithium-ion batteries (LIBs) are developed for facilitating Li transport at lower temperatures, which achieve an ion conductivity of 10 S cm at -30 °C.