NOTCH3 Mutation Causes Glymphatic Impairment and Promotes Brain Senescence in CADASIL.

Aims: The aim of this study is to investigate the role of glymphatic function of cerebral autosomal dominant arteriopathy, subcortical infarcts, and leukoencephalopathy (CADASIL), the most common monogenic small vessel disease caused by NOTCH3 mutation, and to explore potential therapeutic strategies to improve glymphatic function.

Methods: We assessed glymphatic influx and efflux function in CADASIL mouse models (Notch3) and correlated these findings with brain atrophy in CADASIL patients. We also investigated the underlying mechanisms of glymphatic impairment, focusing the expression of AQP4 in astrocytic endfeet.

Metagenomic and Transcriptomic Analysis Reveals Crosstalk Between Intratumor Mycobiome and Hosts in Early-Stage Nonsmoking Lung Adenocarcinoma Patients.

Background: The mycobiome in the tumor microenvironment of non-smokers with early-stage lung adenocarcinoma (ES-LUAD) has been minimally investigated.

Methods: In this study, we conducted ultra-deep metagenomic and transcriptomic sequencing on 128 samples collected from 46 nonsmoking ES-LUAD patients and 41 healthy controls (HC), aiming to characterize the tumor-resident mycobiome and its interactions with the host.

Results: The results revealed that ES-LUAD patients exhibited fungal dysbiosis characterized by reduced species diversity and significant imbalances in specific fungal abundances.

Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition.

Breast cancer utilizes diverse immunosuppressive mechanisms to evade immune surveillance, thereby impairing immunotherapeutic effects. In this work, a chimeric peptide functionalized immunostimulant (designated as aGlyR) is fabricated to boost photodynamic immunotherapy through PD-L1 deglycosylation and CD47 inhibition. The photosensitizer protoporphyrin IX (PpIX) is conjugated to a PD-L1 deglycosylation peptide via a hydrophilic PEG linker, yielding the chimeric peptide Fmoc-K(PpIX)-PEG-GFTATPPAPDSPQEP.

Sprouting sympathetic fibres release CXCL16 and norepinephrine to synergistically mediate sensory neuronal hyperexcitability in a rodent model of neuropathic pain.

Background: Chronic neuropathic pain generally has a poor response to treatment with conventional drugs. Sympathectomy can alleviate neuropathic pain in some patients, suggesting that abnormal sympathetic-somatosensory signaling interactions might underlie some forms of neuropathic pain. The molecular mechanisms underlying sympathetic-somatosensory interactions in neuropathic pain remain obscure.

B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells.

Background: Chordoma is a slow-growing, primary malignant bone tumor that arises from notochordal tissue in the midline of the axial skeleton. Surgical excision with negative margins is the mainstay of treatment, but high local recurrence rates are reported even with negative margins. High-dose radiation therapy (RT), such as with proton or carbon ions, has been used as an alternative to surgery, but late local failure remains a problem.

SQSTM1/P62 Mediates the Effects of CPNE3 on the Epithelialmesenchymal Transition and Migratory Inhibition of Lung Adenocarcinoma Cells.

Introduction: Copine-3 (CPNE3) is a conservative calcium-dependent phospholipid-binding protein belonging to the copines protein family. CPNE3 has been implicated in the development and progression of several diseases, including cancer.

Method: Herein, we investigated the molecular mechanisms through which CPNE3 regulates the migration of lung adenocarcinoma (LUAD) cells in vitro.

Multifidus fat infiltration negatively influences the postoperative outcomes in lumbar disc herniation following transforaminal approach percutaneous endoscopic lumbar discectomy.

Purpose: This study aims to investigate the influence of multifidus muscle fat infiltration on clinical outcomes in lumbar disc herniation (LDH) undergoing percutaneous endoscopic lumbar discectomy (PELD).

Methods: A retrospective analysis was conducted on 224 patients who underwent lateral PELD, with complete one-year follow-up data. Patients were divided into two groups based on preoperative MRI evaluation of L4 multifidus muscle fat infiltration: a mild group (< 25%) and a severe group (≥ 25%).

Complete genome sequence of Pseudomonas aeruginosa YK01, a sequence type 16 isolated from a patient with keratitis.

Objectives: Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is frequently associated with multidrug resistance and global epidemic outbreaks, contributing significantly to morbidity and mortality in hospitalized patients. However, P. aeruginosa belonging to the sequence type (ST) 16 was rarely reported.

Versatile poly (deep eutectic solvents) electroactive chitosan eutectogel for infected wound healing and monitoring administration.

The treatment and monitoring of infected skin wounds present significant clinical challenges. Herein, a multifunctional poly(deep eutectic solvent) (PDES) electroactive hydrogel is developed by optimizing the components and the ratio of hydrogen donors and acceptors, achieving well wound hemostasis, wound healing, and monitoring administration performace. The PDES hydrogel dressing exhibits mechanical properties, including high toughness, fatigue resistance (over 9000 compression cycles), and superior skin adhesion (over 70 kPa).

Analysis of promotion and obstacles in long-term care grading services for home-based older adults with disabilities in China.

Long-term care (LTC) grading services refers to professional assessors using specific tools to systematically evaluate people with long-term care needs,develop and implement graded service standards that align with the care needs of individuals based on their varying levels of disability.It has been nearly a decade since China initiated home-based long-term care for the disabled elderly; however, challenges remain, such as the lack of detailed graded service standards and inadequate allocation of medical and nursing resources. This study aimed to gain insights into factors about influencing the current system by understanding the perspectives of those directly involved in providing care and to promote LTC services for older adults with disabilities in China.

The lysosome-related characteristics affects the prognosis and tumor microenvironment of lung adenocarcinoma.

Background: The lysosome plays a vitally crucial role in tumor development and is a major participant in the cell death process, involving aberrant functional and structural changes. However, there are few studies on lysosome-associated genes (LAGs) in lung adenocarcinoma (LUAD).

Methods: Bulk RNA-seq of LUAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).

GSH/pH-responsive copper-based cascade nanocomplexes inducing immunogenic cell death through cuproptosis/ferroptosis/necroptosis in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) remains a formidable challenge due to high recurrence rates and limited efficacy of conventional treatments. Immunotherapy holds potential, but its effectiveness is often restricted by low patient responsiveness. This study presents a novel therapeutic strategy using GSH/pH-responsive copper-based cascade nanocomplexes to induce immunogenic cell death (ICD) in OSCC.

FOLR1 Regulates the Malignant Progression of Glioblastoma through the SRC/ERK1/2 Axis.

Background: GBM is an aggressive brain tumor with limited treatment options. Prior research has indicated FOLR1 as a pivotal gene involved in cancer pathogenesis.

Aim: This study aimed to explore the involvement of folate receptor alpha (FOLR1) in glioblastoma (GBM) and evaluate its potential as a therapeutic target.

Association between platelet-to-lymphocyte ratio and immune checkpoint inhibitor-induced thyroid dysfunction.

Purpose: To investigate the relationship between platelet-to-lymphocyte ratio (PLR) or neutrophil-to-lymphocyte ratio (NLR) and Immune checkpoint inhibitor (ICI)-induced thyroid dysfunction.

Methods: This was a single-center retrospective observational study of patients with solid tumors receiving ICI therapy. Clinical characteristics of patients were assessed at baseline and during ICI therapy.

Prognostic value of nighttime blood pressure in patients with chronic kidney disease.

The optimal blood pressure (BP) in patients with chronic kidney disease (CKD) remains uncertain. Therefore, this cohort study aimed to investigate the prognostic value of ambulatory blood pressure (ABP) in patients with CKD and to determine the optimal range for ABP. In total, 1051 hospitalized patients with CKD were enrolled.

Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization.

Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen.

Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma.

Purpose: Cancer-associated fibroblasts (CAFs) are the primary stromal component of the tumor microenvironment in hepatocellular carcinoma (HCC), affecting tumor progression and post-resection recurrence. Fibroblast activation protein (FAP) is a key biomarker of CAFs. However, there is limited evidence on using FAP as a target in near-infrared (NIR) fluorescence imaging for HCC.

Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation.

Purpose: Immunometabolism is pivotal in rheumatoid arthritis (RA) pathogenesis, yet the intricacies of its pathological regulatory mechanisms remain poorly understood. This study explores the complex immunometabolic landscape of RA to identify potential therapeutic targets.

Patients And Methods: We integrated genome-wide association study (GWAS) data involving 1,400 plasma metabolites, 731 immune cell traits, and RA outcomes from over 58,000 participants.

Dehydrocorydaline maintains the vascular smooth muscle cell contractile phenotype by upregulating Spta1.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a crucial role in the initiation and progression of atherosclerosis. Dehydrocorydaline (DHC), a major active component of the traditional Chinese herbal medicine Rhizoma Corydalis, exhibits diverse pharmacological effects. However, its impact on VSMCs remains largely unknown.

Sacubitril/valsartan attenuates inflammation and myocardial fibrosis in Takotsubo-like cardiomyopathy.

Background: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

Aim: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

Bidirectional Mendelian Randomization Analysis of the Association Between Mitochondrial Proteins and Neurodegenerative Diseases.

Background: Neurodegenerative diseases involve progressive neuronal dysfunction and cognitive decline, posing substantial global challenges. Although the precise causes remain unclear, several studies highlight the role of protein metabolism abnormalities in disease development. This study investigates the causal links between variations in mitochondrial protein genes and neurodegenerative diseases, aiming to elucidate their potential contributions to disease progression and identify novel therapeutic strategies.

Differentiating Tangerine Peels from Other through GC-MS, UPLC-Q-Exactive Orbitrap-MS, and HPLC-PDA.

The nonvolatile and volatile compounds in the peels of 13 cultivars (4 mandarins, 5 tangerines, and 4 hybrids) and 5 (sweet oranges) cultivars were analyzed. Initially, 66 volatile compounds were detected using gas chromatography-mass spectrometry (GC-MS). Tangerines were distinguished from other citrus cultivars (mandarins, sweet oranges, hybrids) by having higher volatile oil extraction rates and higher relative contents of o-Cymene, α-Terpinene, d-α-Pinene, Terpinolene, γ-Terpinene, l-β-Pinene, and 3-Thujene.

IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility.

IgA antibodies are critical components of the mucosal immune barrier, providing essential first-line defense against viral infections. In this study, we investigated the impact of antibody class switching on neutralization efficacy by engineering recombinant antibodies of different isotypes (IgA1, IgG1) with identical variable regions from SARS-CoV-2 convalescent patients. A potent, broad-spectrum neutralizing monoclonal antibody CAV-C65 exhibited a ten-fold increase in neutralization potency upon switching from IgG1 to IgA1 monomer.

D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes.

Background: Diabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.

Methods: Here, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro.