10P3Me: A GPC3-Targeted Peptide PET Probe for Subcutaneous and Orthotopic HCC Imaging.

Hepatocellular carcinoma (HCC) remains a growing global health threat, necessitating the development of precise molecular probes for its prevention, early diagnosis, and treatment. Glypican-3 (GPC3) is highly expressed in various HCC subtypes and exhibits minimal expression in normal liver tissue, making it a promising biomarker for early-stage HCC diagnosis. Herein, we report a novel cyclic peptide molecular probe, 10P3Me, exhibiting high binding affinity for GPC3, with a of 93.

Single-cell omics reveal the mechanisms of traditional Chinese medicines.

Background: Traditional Chinese medicines (TCMs) have a long-standing history and diverse applications. However, their complex multi-component compositions and intricate mechanisms of action pose significant challenges for modern scientific investigation. Addressing these complexities requires advanced techniques capable of dissecting cellular and molecular interactions with high resolution.

Molecular characterization of endosomal self RNA Rmrp-engaged TLR3 dimerization to prime innate activation.

The pre-dimerization of endosome-localized RNA sensor Toll-like receptor 3 (TLR3) is required for its innate recognition, yet how TLR3 pre-dimers are formed and precisely primed for innate activation remains unclear. Here, we demonstrate that endosome-localized self RNA Rmrp directly binds to TLR3 and induces TLR3 dimerization in the early endosome but does not interact with endosome-localized TLR7, TLR8, TLR9 or cytoplasmic RNA sensor RIG-I under homeostatic conditions. Cryo-EM structure of Rmrp-TLR3 complex reveals a novel lapped conformation of TLR3 dimer engaged by Rmrp, which is distinct from the activation mechanism by dsRNA and the specific structural feature at the 3'-end of Rmrp is critical for its functional interaction with TLR3.

Initiation of tocilizumab within 24 hours in acute necrotizing encephalopathy is related to a good outcome: a systematic review.

Objective: To evaluate the clinical efficacy of tocilizumab, a interleukin-6 (IL-6) receptor blocker, for the treatment of acute necrotizing encephalopathy (ANE).

Methods: PubMed, Cochrane Library, Embase, and Web of Science were searched for systematic review based on PRISMA guidelines. ANE patients treated with and without tocilizumab were included.

3D-CT Study of Buccal Fat Pad Volume in Patients with Prominent Zygoma.

Objective: To compare the symmetry of bilateral buccal fat pad(BFP) volumes in patients with prominent zygomatic bones before surgery.

Methods: Fifty cosmetic female patients were selected and scanned using computed tomography. Based on the symmetry of the patients' zygomatic bones prior to surgery, they were divided into the Sym group and the Asym group.

Effect of depression on risks of Alzheimer's disease and vascular dementia: A real-world longitudinal study.

Objectives: To evaluate the relationship between depression and the risk of dementia.

Design: A real-world longitudinal study.

Setting: This comprehensive study involved elderly adults in Yichang, China, who were dementia-free at baseline from 2016 to 2023.

Small extracellular vesicles orchestrated pathological communications between breast cancer cells and cardiomyocytes as a novel mechanism exacerbating anthracycline cardiotoxicity by fueling ferroptosis.

Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) via orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs).

UCP2 is identified as a therapeutic target for abdominal aortic aneurysm by comprehensive bioinformatic analysis and experimental validation.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition that currently lacks effective pharmacological treatment. The disease is strongly associated with chronic inflammation, where immune cells like macrophages play a crucial role. Efferocytosis, the process by which apoptotic cells are cleared, is involved in regulating inflammation.

Deciphering pancreatobiliary intraductal oncocytic papillary neoplasms: integrative analysis of histomorphologic patterns, immunophenotypic markers, and emerging molecular biomarkers.

Purpose: We reviewed recent advancements in the characterization of intraductal oncocytic papillary neoplasm (IOPN) of the pancreas, with a specific focus on developments in immunohistochemical markers, molecular pathology, and pathogenic mechanisms over the past ten years (2015-2024). Through comprehensive analysis of current literature, we aimed to elucidate the evolving understanding of IOPN's biological behavior and diagnostic features, while identifying potential areas for future research in this distinctive pancreatic neoplasm.

Methods: English-language articles on IOPN were searched from Pubmed from the first report of IOPN of the pancreas in 2015 to 2024.

Deep learning-assisted system improves practical effect in cervical cytopathology diagnosis: A comparative study of reading modes.

Deep learning (DL) has significantly improved the diagnostic accuracy and efficiency of cytopathologists. However, current DL-assisted reading modes have yet to be fully evaluated, and there is limited evidence regarding cytopathologists' preferences and experiences. This study employs a randomized, controlled, four-way crossover design to assess the effectiveness of four different reading modes in cervical cytopathology readings.

A multifunctional L-arginine-linked melanin Nanozyme for Theranostic applications in liver fibrosis: Non-invasive dual-modal imaging and reactive oxygen species scavenging for Pyroptosis suppression.

Liver fibrosis, a pivotal pathological stage in the progression of chronic liver diseases to cirrhosis and hepatocellular carcinoma is characterized by liver sinusoidal endothelial cell (LSEC) capillarization, oxidative stress imbalance, and cell pyroptosis. Current clinical interventions show limited efficacy in reversing fibrosis, highlighting the urgent need for novel therapeutic strategies. In this study, we developed an L-arginine-loaded melanin-like nanozyme (L-Arg@MeNPs) that targets liver fibrosis through a triple-action mechanism: (1) sustained nitric oxiderelease from L-Arg restores LSEC fenestration, improving sinusoidal permeability; (2) the MeNPs exhibit catalase/superoxide dismutase-mimicking activity to scavenge reactive oxygen species, thereby blocking the NOD-like receptor pyrin domain-containing 3/caspase-1-mediated pyroptosis pathway; and (3) intrinsic photoacoustic/magnetic resonance dual-modal imaging enables real-time therapeutic monitoring.

An HIV fusion-inhibitory lipopeptide provides robust post-exposure prophylaxis and prevents viral reservoir seeding in macaques.

LP-98 is a lipopeptide HIV fusion inhibitor showing strong treatment and pre-exposure prophylaxis efficacies in non-human primates. In this study, we further characterized its pharmacokinetics, long-lasting antiviral activity, and post-exposure prophylaxis (PEP) efficacy using 62 macaques. In cynomolgus macaques, LP-98 achieved high concentrations (C) with a half-life (T) of ∼31 h, and sustained an effective therapeutic concentration for two weeks post-injection.

Protocol for using treeLFA to infer multimorbidity patterns in the form of disease topics from diagnosis data in biobanks.

Research on multimorbidity patterns promotes our understanding of the common pathological mechanisms that underlie co-occurring diseases. Here, we present a protocol to infer multimorbidity clusters in the form of disease topics from large-scale diagnosis data using treeLFA, a topic model based on the Bayesian binary non-negative matrix factorization. We describe steps for installing software, preparing input data, and training the model.

Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.

Background: Depression is a common mental illness with a high relapse rate, which has a serious negative impact on national economic development and happiness. At present, the pathogenesis of depression is still unclear, and there are inevitable limitations in first-line clinical treatment. Therefore, it is very important to clarify the pathological mechanism of depression for the development of safe and effective antidepressants.

Rapid Diagnosis and Subtyping of Hermansky-Pudlak Syndrome With Flow Cytometry Analysis.

The diagnostic approaches for Hermansky-Pudlak Syndrome (HPS) include genetic sequencing, immunoblotting, electron microscopy (EM), and flow cytometry with mepacrine staining. However, these methods are often impractical for routine clinical use due to high cost, technical complexity, and limited availability. In this study, we evaluated dense granules (DGs) function in HPS mouse models using flow cytometry with mepacrine and FluoZin-3 staining.

Single-Cell Transcriptome Profiling Reveals Dynamic Cell Populations and Immune Infiltration in Moyamoya Disease.

Background: The cellular composition and molecular mechanisms of the pathological arteries in Moyamoya disease (MMD) remain poorly understood. To improve our understanding of pathogenesis in MMD, we aimed to comprehensively map the cellular composition and molecular alterations within the pathological arteries of patients with MMD.

Methods: Superficial temporal artery samples were collected from patients with MMD (n=2) and healthy controls (n=3), yielding a total of 26 371 cells that were used for single-cell RNA sequencing.

Machine learning for the prediction of blood transfusion risk during or after mitral valve surgery: a multicenter retrospective cohort study.

This study aimed to identify the optimal prediction method and key preoperative variables for red blood cell (RBC) transfusion risk in patients undergoing mitral valve surgery. We conducted a retrospective study involving 1477 patients from eight large tertiary hospitals in China who underwent mitral valve surgery with cardiopulmonary bypass. From thirty collected preoperative variables, the Max-Relevance and Min-Redundancy (mRMR) method was used for feature selection, and various machine learning models were evaluated.

Reverse Wenckebach Phenomenon After Surgical Repair of Bicuspid Aortic Valve: Long-Term Follow-Up.

Background: The Wenckebach phenomenon of atrioventricular conduction is deemed a physiological response of the atrioventricular node to a high atrial rate. However, the reverse Wenckebach phenomenon is under-recognized.

Case Summary: We report an instance of reverse Wenckebach phenomenon developing into complete heart block in a 33-year-old man who experienced syncope after surgical repair of prolapsed bicuspid aortic valves.

A novel extracellular mannan from Bacillus velezensis ameliorates metabolic-associated fatty liver disease by modulating gut microbiota in mice model.

Metabolic associated fatty liver disease (MAFLD) is a globally recognized chronic metabolic disorder characterized by lipid metabolism abnormalities. Accumulating evidence indicates that exopolysaccharides (EPS) could modulate the gut microbiota structure and function to prevent and treat MAFLD. Herein, a novel EPS designated BVP1 was isolated from Bacillus velezensis CGMCC 24752.

Remimazolam besylate versus propofol as sedative agents in cardiac surgery: A randomized noninferiority clinical trial.

Background: Remimazolam besylate, despite being widely used in various clinical settings, lacks evidence in cardiac anesthesia. This trial compared its efficacy with propofol in elective cardiac surgery.

Methods: A total of 320 adult patients undergoing elective cardiac surgery via cardiopulmonary bypass between December 2024 and March 2025 were randomized 1:1 to either propofol (1 mg/kg for induction and 1-1.