AAVR Expression is Essential for AAV Vector Transduction in Sensory Hair Cells.

Adeno-associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV-mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults.

Protocatechuic Acid improves Alzheimer's disease by regulating the cholinergic synaptic signaling pathway.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by memory decline and cognitive impairments. The clinical treatments for AD have numerous adverse effects, hence the exploration of natural products for AD therapy is of significant importance. Protocatechuic acid (PA), a natural phenolic acid, has been shown to possess various pharmacological activities, including anti-inflammatory, antioxidant, and antitumor effects.

Anchoring Sn Nanoparticles in Necklace-Like B,N,F-Doped Carbon Fibers Enables Anode-Less 5V-Class Li-Metal Batteries.

Li metal batteries (LMBs), particularly with a limited Li metal anode and a 5V-class cathode, offer significantly higher energy density compared to the state-of-the-art Li-ion batteries. However, the limited Li anode poses severe challenges to cycling stability due to low efficiency and large volume expansion issues associated with Li. Herein, we design a lightweight and functionalized host composed of Sn nanoparticles embedded into necklace-like B,N,F-doped carbon macroporous fibers (Sn@B/N/F-CMFs) toward anode-less 5V-class LMBs.

MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of Borrelia burgdorferi.

Borrelia (or Borreliella) burgdorferi, the causative agent of Lyme disease, is a motile and invasive zoonotic pathogen adept at navigating between its arthropod vector and mammalian host. While motility and chemotaxis are well known to be essential for its enzootic cycle, the role of each methyl-accepting chemotaxis proteins (MCPs) in the infectious cycle of B. burgdorferi remains unclear.

UF-5000 urinary erythrocyte parameters versus urinary aberrant erythrocytes and acanthocytes for diagnosing IgA glomerular hematuria.

This study evaluated the diagnostic value of the automated UF-5000 parameters and compared it with that of aberrant erythrocytes and acanthocytes classified by microscopy for identifying IgA glomerular hematuria to propose a predictive model for clinical use. It also compared correlations between erythrocyte parameters and malformed erythrocytes. Urine samples from 53 biopsy-proven IgA hematuria cases and 143 non-IGA nephropathic hematuria cases as controls were analyzed.

PKM2 controls cochlear development through lactate-dependent transcriptional regulation.

Understanding the role of metabolic processes during inner ear development is essential for identifying targets for hair cell (HC) regeneration, as metabolic choices play a crucial role in cell proliferation and differentiation. Among the metabolic processes, growing evidence shows that glucose metabolism is closely related to organ development. However, the role of glucose metabolism in mammalian inner ear development and HC regeneration remains unclear.

Halogenated Cholesterol Alters the Phase Behavior of Ternary Lipid Membranes.

Eukaryotic plasma membranes exhibit nanoscale lateral lipid heterogeneity, a feature that is thought to be central to their function. Studying these heterogeneities is challenging since few biophysical methods are capable of detecting domains at submicron length scales. We recently showed that cryogenic electron microscopy (cryo-EM) can directly image nanoscale liquid-liquid phase separation in extruded liposomes due to its ability to resolve the intrinsic thickness and electron density differences of ordered and disordered phases.

Intelligent Analgesia Management System in Postoperative Pain Management: A Retrospective Analysis.

Purpose: This study aimed to explore the effect of an intelligent analgesia management system on postoperative pain management and the working mode of acute pain service.

Design: This is a retrospective cohort study.

Methods: A total of 584 patients who underwent laparoscopic abdominal surgery under general anesthesia and voluntarily received intravenous patient-controlled analgesia (PCA) between January 2018 and April 2020 at our hospital were selected.

Gemcitabine-Loaded Microbeads for Transarterial Chemoembolization of Rabbit Renal Tumor Monitored by F-FDG Positron Emission Tomography/X-Ray Computed Tomography Imaging.

Background/objectives: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (F-FDG PET/CT).

Methods: DEBs were prepared by polyvinyl alcohol-based macromer crosslinked with -acryl tyrosine and ,'-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs.

DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles.

Background: Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against the virus.

Methods: In this study, we investigated the role of pyroptosis in the pathogenic mechanism of dengue fever by examining the level of pyroptosis in DENV-1-infected macrophages and further screened differentially expressed microRNAs by high-throughput sequencing to predict microRNAs that could affect the pyroptosis of the macrophage.

Effects of Different Stocking Densities on Snail Foot Muscle Nutritional Quality and Metabolic Function.

Snail is not only useful for bioremediation, purifying aquaculture environments, but it is also a commercially valuable and nutritionally rich aquatic product. To analyze the effect of various stocking densities on the muscle nutritional quality and metabolic functions of . The transcriptome and metabolome were analyzed and set up three different density groups-low (LD, 234.

Curative immunotherapy-based strategies for non-metastatic non-small cell lung cancer.

The emergence of immunotherapy has ushered in a new era in the management of non-small cell lung cancer (NSCLC). Various immune check point inhibitors have demonstrated significant benefit in the management of locally advanced NSCLC that are treated with either surgery or concurrent chemoradiation. We provide a comprehensive and up-to-date review of data from key studies, discuss the challenging clinical issue regarding the timing and duration of immunotherapy in patients undergoing surgery, and highlight the unmet needs and future directions of immunotherapy in NSCLC.

CD24-Fc resolves inflammation and rescues CD8 T cells with polyfunctionality in humanized mice infected with HIV-1 under cART.

Unlabelled: The persistence of HIV-1 reservoirs during combination anti-retroviral therapy (cART) leads to chronic immune activation and systemic inflammation in people with HIV (PWH), associating with a suboptimal immune reconstitution as well as an increased risk of non-AIDS events. This highlights the needs to develop novel therapy for HIV-1 related diseases in PWH. In this study, we assessed the therapeutic effect of CD24-Fc, a fusion protein with anti-inflammatory properties that interacts with danger-associated molecular patterns (DAMPs) and siglec-10, in chronic HIV-1 infection model using humanized mice undergoing suppressive cART.

Multiplexed mosaic tumor models reveal natural phenotypic variations in drug response within and between populations.

Many agents that show promise in preclinical cancer models lack efficacy in patients due to patient heterogeneity that is not captured in traditional assays. To address this problem, we have developed GENEVA, a platform that measures the molecular and phenotypic consequences of drug perturbations within diverse populations of cancer cells at single-cell resolution, both and . Here, we apply GENEVA to study the KRAS G12C inhibitors, recapitulating known properties of these drugs and uncovering a previously unknown role for mitochondrial activation in cell death induced by KRAS inhibition.

Connexin 43 and Pannexin 1 hemichannels as endogenous regulators of innate immunity in sepsis.

Sepsis is a life-threatening organ dysfunction resulting from a dysregulated host response to infections that is initiated by the body's innate immune system. Nearly a decade ago, we discovered that bacterial lipopolysaccharide (LPS) and serum amyloid A (SAA) upregulated Connexin 43 (Cx43) and Pannexin 1 (Panx1) hemichannels in macrophages. When overexpressed, these hemichannels contribute to sepsis pathogenesis by promoting ATP efflux, which intensifies the double-stranded RNA-activated protein kinase R (PKR)-dependent inflammasome activation, pyroptosis, and the release of pathogenic damage-associated molecular pattern (DAMP) molecules, such as HMGB1.

Beyond the desert sands: decoding the relationship between camels, gut microbiota, and antibiotic resistance through metagenomics.

Background: Camels, known as the enduring "ships of the desert," host a complex gut microbiota that plays a crucial role in their survival in extreme environments. However, amidst the fascinating discoveries about the camel gut microbiota, concerns about antibiotic resistance have emerged as a significant global challenge affecting both human and animal populations. Indeed, the continued use of antibiotics in veterinary medicine has led to the widespread emergence of antibiotic-resistant bacteria, which has worsened through gene transfer.

Anti-gene oligonucleotide clamps invade dsDNA and downregulate expression.

Anti-gene oligonucleotides belong to a group of therapeutic compounds, which, in contrast to antisense oligonucleotides, bind to DNA. Clamp anti-gene oligonucleotides bind through a double-stranded invasion mechanism. With two arms connected by a linker, they hybridize to one of the DNA strands forming Watson-Crick and Hoogsteen hydrogen bonds.

Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer.

Background: Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with the liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying the interaction between SCLC and liver microenvironment, fostering metastasis, remain unclear.

Methods: SCLC patient tissue array, bioinformatics analysis were performed to demonstrate the role of periostin (POSTN) in SCLC progression, metastasis, and prognosis.

NPC1 controls TGFBR1 stability in a cholesterol transport-independent manner and promotes hepatocellular carcinoma progression.

Niemann-Pick disease type C protein 1 (NPC1), classically associated with cholesterol transport and viral entry, has an emerging role in cancer biology. Here, we demonstrate that knockout of Npc1 in hepatocytes attenuates hepatocellular carcinoma (HCC) progression in both DEN (diethylnitrosamine)-CCl induced and MYC-driven HCC mouse models. Mechanistically, NPC1 significantly promotes HCC progression by modulating the TGF-β pathway, independent of its traditional role in cholesterol transport.

Unusual Temperature-Dependent Photoluminescence Due to Competing Excited-State Energy Transfer in Rare Earth Double Perovskites.

Lead-free halide double perovskites (DPs) have become a research hotspot in the field of photoelectrons due to their unique optical properties and flexible compositional tuning. However, the luminescence of DPs exhibits thermal quenching at high temperatures, which severely affects their further application. Herein, we synthesized the rare earth Dy and transition metal Mn codoped CsNaYCl rare earth DPs and characterized the optical properties using temperature-dependent photoluminescence spectra and time-resolved photoluminescence decay profiles at different temperatures.

[Pathological diagnosis of solid pancreatic lesions with endoscopic ultrasound-guided fine needle aspiration: a series study of 311 cases].

To investigate the combined application of cytology, cell block histology and immunohistochemistry to improve the diagnostic accuracy of solid pancreatic lesions in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples. The pathological data of EUS-FNA in 311 cases of solid pancreatic lesions submitted to the Second Hospital of Hebei Medical University, Shijiazhuang, China from May 2019 to September 2023 were retrospectively analyzed. The cases included pancreatic ductal adenocarcinoma (PDAC, 172 cases), solid pseudopapillary neoplasm (SPN, 12 cases), neuroendocrine tumors (PNET, 14 cases) and chronic pancreatitis (113 cases).

Efficacy and Safety of PARP Inhibitors in Prostate Cancer: An Umbrella Review of Systematic Reviews and Meta-analyses.

Prostate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients.

An Antibacterial Hemostasis Sponge of Gelatin/ε-Poly-L-Lysine Composite.

Massive bleeding and bacterial infection of wounds may be life-threatening or even lead to death. Nowadays, gelatin-based hemostatic sponges have been widely used, but gelatin is not antibacterial and has poor structural stability. In this study, we mixed an antibacterial polypeptide, ε-poly-L-lysine (EPL), into gelatin.

Purification, microstructure, functional properties and antioxidant activity of peptides from Chinese pond turtle hydrolysate.

Chinese pond turtle muscle peptide's molecular features, purification, structural characteristics, and antioxidant activity were investigated. The Flavourzyme hydrolysate demonstrated greater relative crystallinity (37.53%) than other hydrolysates using X-ray diffraction.

Disparities in Utilization of Immune Checkpoint Inhibitor Therapy Among Older Patients With Advanced Non-Small Cell Lung Cancer: A SEER-Medicare Analysis.

Purpose: In the United States, there are disparities in access to care for patients with non-small cell lung cancer (NSCLC) on the basis of socioeconomic and racial/ethnic factors. This study investigates the association between race/ethnicity and the utilization of immune checkpoint inhibitor (ICI) therapy among older patients with advanced NSCLC (aNSCLC).

Methods: This retrospective study used data from the SEER-Medicare-linked database.