Platelet-derived extracellular vesicle drug delivery system loaded with kaempferol for treating corneal neovascularization.

Platelet-derived extracellular vesicles (PEVs) have drawn attention due to their multifunctionality, ease of procurement, and abundant supply from clinical-grade platelet concentrates. PEVs can be readily endocytosed due to their lipid bilayer membrane and nanoscale structure, enhancing the bioavailability and efficacy of their therapeutic effects. PEVs also contain various trophic factors that enhance their effectiveness as therapeutic agents.

The NF1 tumor suppressor regulates PD-L1 and immune evasion in melanoma.

Hotspot BRAF, hotspot NRAS, and NF1 loss-of-function mutations are found in approximately 50%, 25%, and 15% of cutaneous melanomas, respectively. Compared to mutant BRAF and NRAS, the role of NF1 loss in melanoma remains understudied. NF1 has a RAS GTPase-activating protein (GAP) function; however, studies also support NF1 RAS-independent tumor-suppressor functions.

Enabling Low-Temperature Zinc-Bromine Microbatteries with an Additive-Free Electrolyte Design.

Aqueous zinc-bromine microbatteries (Zn-Br MBs) are promising energy storage devices for miniaturized electronic applications. However, their performance in low-temperature environments remains a challenge due to poor compatibility between antifreeze agents and complexing agents. In this work, we propose an additive-free electrolyte design to address this incompatibility from the source.

Comparative Analysis of Surgery Using Combined Iliac Lumbar and Posterior Closed Screws for Pelvic Stability Maintenance.

BACKGROUND Pelvic fractures are prevalent complex fractures in traumatic orthopedics that tend to lead to an unstable posterior pelvic ring. This study aimed to analyze and compare the clinical efficacy of combined iliolumbar screws and posterior closure screws in the treatment of pelvic instability. MATERIAL AND METHODS Thirteen (study group) and 22 (control group) patients were treated with combined iliac lumbar screws and posterior closed screws, respectively.

Posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program.

Purpose: This study investigated whether Fibrosis-4 (FIB-4) score and its change can serve as predictors of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) infection receiving direct-acting antivirals (DAAs).

Methods: This study identified 9679 patients who completed DAA treatment and achieved sustained virologic response (SVR) from the Taiwan Nationwide Real-World HCV Registry Program, and their risk of HCC was analyzed.

Results: Multivariable Cox regression analyses identified diabetes mellitus (DM), alpha-fetoprotein (AFP) level, and FIB-4 score as independent predictors of HCC in both Model 1 (baseline) and Model 2 (SVR).

A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia.

Background: Progressive symmetric erythrokeratodermia (PSEK) is a group of hereditary cornification disorders characterized by symmetrical, progressive erythroderma and hyperkeratosis over the body. Loss-of-function variants in SLURP1, encoding secreted Ly-6/uPAR-related protein 1, is known to cause Mal de Meleda, an autosomal recessive palmoplantar keratoderma.

Objective: To identify the genetic basis and the pathogenesis of a sporadic patient with PSEK.

Characterization of the dual ITK/JAK3 small molecule covalent inhibitor ATI-2138.

Aclaris Therapeutics Inc (ATI)-2138 is a novel investigational covalent inhibitor of interleukin-2-inducible T cell kinase (ITK), resting lymphocyte kinase, and Janus kinase 3 (JAK3) in development for the treatment of autoimmune and inflammatory diseases. In this study, we evaluated the inhibitory effects of ATI-2138 on ITK and JAK3 signaling in cells and preclinical animal models and assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of ATI-2138 in healthy human participants. ATI-2138 potently, selectively, and irreversibly inhibited ITK, resting lymphocyte kinase, and JAK3 kinases with similar potency observed against ITK and JAK3 in biochemical and immune cell signaling assays.

Decoding the corneal immune microenvironment in healthy and diabetic mice during corneal wound healing.

Diabetic keratopathy (DK) is an underdiagnosed ocular complication of diabetes mellitus. The changes of ocular immune microenvironment contribute to the pathogenesis of DK, while precise mechanisms remain inadequately understood. Here, we employed single-cell RNA sequencing (scRNA-seq) to elucidate the transcriptional alterations of immune cells from diabetic and healthy control mouse corneas during homeostasis and wound healing.

Inhaled Alone versus Inhaled Plus Intravenous Polymyxin B for the Treatment of Pneumonia Due to Carbapenem-Resistant Gram-Negative Bacteria: A Prospective Randomized Controlled Trial.

Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are associated with considerable morbidity and mortality. Polymyxin B (PMB) is a first-line agent for CR-GNB-associated pneumonia, but limited data exist on the clinical use of inhaled (IH) PMB. A single-center, prospective randomized controlled trial was conducted in China to compare IH PMB alone with IH plus intravenous (IV) PMB between February 2022 and February 2024.

An antioxidant composite film based on loquat seed starch incorporating resveratrol-loaded core-shell nanoparticles.

A Novel bioactive food packaging film was prepared from non-grain sourced loquat seed starch (LSS) incorporated with resveratrol-loaded nanoparticles (NRs) based on a zein/pectin core-shell system, where the NRs were prepared using the anti-solvent method. The chemical constitution of the LSS was analyzed. The film was characterized by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM).

Blood-oxygenation-level-dependent (BOLD) MRI responses to CO and O inhalation in brain gliomas.

Purpose: Cerebrovascular abnormalities are intricately involved in gliomas. While static cerebrovascular properties such as cerebral blood flow, volume, and permeability have been extensively studied, dynamic vascular parameters have not been fully understood. This study aimed to characterize the vascular responses to CO and O inhalation in brain gliomas.

Loop diuretics mitigate juvenile immobilization treatment-induced hippocampal dysfunction.

Juvenile traumatic experiences can lead to adult cognitive impairments, including learning deficits and increased anxiety risk. Dysfunction of the hippocampus is crucial in stress-induced behavioral disorders, and recent evidence suggests that disrupted chloride homeostasis through the chloride transporter NKCC1 may alter GABAergic signaling and contribute to neuropathology. This study investigates the role of NKCC1 in long-term hippocampal dysfunction induced by juvenile immobilization (J_IMO).

Tenghuang Jiangu tablet in knee osteoarthritis therapy: a prospective multicenter registry study in China.

Ethnopharmacological Relevance: Chinese patent medicine Tenghuang Jiangu tablet (THJGT) is frequently used to treat knee osteoarthritis (KOA).

Aim: This prospective multicenter registry study investigated the effectiveness and safety of THJGT in treating KOA.

Materials And Methods: Patients with KOA aged 50-75 years were preferentially treated with THJGT, other nonsurgical conventional treatments (CTs), or both.

NRIR promotes immune escape in hepatocellular cancer by regulating IFNγ-induced PD-L1 expression.

Introduction: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with insensitive treatment and poor prognosis; in recent years, breakthroughs in IFN signaling pathway and PDL1/PD1 signaling pathway in HCC immunotherapy research.

Objectives: This study aimed to investigate the molecular mechanisms controlling the immune response and immune evasion.

Methods: NRIR was identified as a differential gene affecting the IFN signaling pathway and PDL1/PD1 signaling pathway in HCC by bioinformatics, and the function of NRIR was investigated in the HCC cell model and the xenograft mouse model.

Lactylation and regulated cell death.

Lactylation, a newly identified post-translational modification, entails the attachment of lactate to lysine residues within proteins, profoundly modulating diverse cellular mechanisms underlying regulated cell death (RCD). This modification encompasses two primary categories: histone lactylation and non-histone lactylation. Histone lactylation assumes a pivotal regulatory function in the RCD process, primarily by modulating the transcriptional landscape of genes implicated in cell death.

Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response.

Vitamin C (vitC) is essential for health and shows promise in treating diseases like cancer, yet its mechanisms remain elusive. Here, we report that vitC directly modifies lysine residues to form "vitcyl-lysine"-a process termed vitcylation. Vitcylation occurs in a dose-, pH-, and sequence-dependent manner in both cell-free systems and living cells.

The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities.

Necroptosis, a distinctive form of programmed cell death differs mechanistically from apoptosis pyroptosis, and autophagy, is characterized by the activation of receptor-interacting protein kinases (RIPK1/RIPK3) and their downstream effector, mixed lineage kinase domain-like protein (MLKL). This programmed cell death pathway serves as a crucial mediator of inflammatory responses and has been implicated in the pathogenesis of diverse pathological conditions. Recent evidence has implicated dysregulated necroptosis in the pathogenesis of severe pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), recurrent spontaneous abortion (RSA), and gestational diabetes mellitus (GDM).

Enhancement of wound healing by a bilayer hydrogel and nanofiber scaffold infused with Calophyllum inophyllum oil and Platostoma palustre aqueous extract.

Natural wound dressings have attracted substantial interest among researchers due to their biocompatible, bioactive, and eco-friendly properties. This paper focuses on introducing the bio-engineered bilayer design, fabrication, and characterizations of a Calophyllum inophyllum seed oil (CIO) - loaded scaffold within a polyvinyl alcohol/sodium alginate (PVA/SA) matrix, fortified with Hsiantsao aqueous extract. The scaffold - consisting of a semi-hydrophobic hydrogel and a hydrophilic nanofiber - was successfully synthesized using polymerization and centrifugal electrospinning techniques.

A new era for applications of multi-principal element alloys in the biomedical field.

In today's context of an aging population and the gradual decline of human physiological functions, we are increasingly confronted with health issues such as fractures and arthritis. The demand for implants has risen correspondingly, while traditional alloys have become insufficient to meet the developmental needs of this era. The emergence of multi-principal element alloys (or high-entropy alloys) in 2004 has attracted significant attention, leading to extensive research due to their remarkable four core effects.

Impact of urinary tract infection requiring hospital admission on short-term, mid-term and long-term renal outcomes in adult CKD patients - A potentially modifiable factor for CKD progression.

Background: Urinary tract infection (UTI) or acute pyelonephritis can lead to renal scarring and impact the subsequent renal function progression. The aims of this study were to investigate the changes in renal function related to UTI requiring hospital admission (UTI/HA) and the association between UTI/HA and long-term renal outcomes in patients with chronic kidney disease (CKD).

Methods: This was a multicenter, retrospective observational study.

Ferrihydrite sulfidation transformation and coupled As(V) and Cd(II) mobilization under anoxic conditions.

Ferrihydrite sulfidation is an important process influencing the environmental behavior of co-existent arsenate (As(V)) and cadmium (Cd(II)) pollutants in mining-impacted environments. However, the mineral evolution of ferrihydrite and the coupled mobilization behavior of co-existent As(V) and Cd(II) remain unclear. In this study, we have investigated As(V)-Cd(II)-bearing ferrihydrite conversion behavior induced by environmentally relevant concentrations of S(-II) (1 and 5 mM).

Stability and transformation behavior of hydrometallurgical hazardous arsenic-calcium residue in sulfidic anoxic environments.

Arsenic-calcium residue (ACR) is a hazardous solid waste generated by the metallurgical industry, posing a significant environmental risk. However, the stability and transformation behavior of ACR in sulfidic conditions remains unclear. Herein, we have investigated the stability and speciation evolution of arsenic (As), sulfur (S), and trace metals during the exposure of ACR to diverse S(-II) concentrations under anoxic conditions at pH of 6 and 11.

Comparative transcriptomic analysis reveals the reactive oxygen species metabolism involving in melatonin-alleviated chilling injury in postharvest banana fruit.

Banana fruit is susceptible to chilling injury (CI) during cold storage, which causes quality deterioration and commodity value decline. Here, the effects of melatonin on CI alleviation and reactive oxygen species (ROS) metabolism in postharvest banana were studied. The results displayed that 500 μmol L melatonin treatment effectively inhibited CI development in cold-stored banana during the 96 h of storage.

Effects of dexmedetomidine and propofol on the key endotypes of OSA: A randomized, single-blind, placebo-controlled, crossover trial.

Background: Drug-induced sleep has been shown to facilitate the diagnosis of obstructive sleep apnea (OSA). However, the effects of commonly used sedatives, such as dexmedetomidine and propofol, on the endotypic traits of OSA remained unclear.

Objective: We aim to investigate the impact of dexmedetomidine and propofol on OSA endotypic traits.