Beyond the Amyloid Core: Modulation of Aggregate Conformational Diversity by Mutations in the Noncore Regions.

Emerging evidence underscores the regulatory roles of nonamyloidogenic regions in controlling the aggregation dynamics and cytotoxicity of amyloidal proteins, but the mechanism remains unclear. Herein we investigated how flanking sequences modulate the conformational heterogeneity in the p53 238-262 amyloid segment using scanning tunneling microscopy (STM). By comparing the wild-type (wt) and three pathogenic mutations (R248W, R248Q, R249S) in the noncore regions, we reveal that flanking alterations remodel β-sheet aggregates and induce conformational plasticity in β-strand ensembles through the generation of novel conformational substates and selective elimination of existing conformational substates.

A prospective study of transorbital ultrasound multimodal imaging in the detection and evaluation of increased intracranial pressure.

Background: To develop and validate a multimodal transorbital ultrasound model for noninvasive detection of increased intracranial pressure (IICP) by integrating anatomical and hemodynamic parameters.

Methods: In this prospective diagnostic study, 136 neurology patients scheduled for lumbar puncture underwent pre-procedural ultrasound measurement of optic nerve sheath diameter (ONSD), ONSD-to-eyeball transverse diameter ratio (ONSD/ETD), and central retinal artery hemodynamics (peak systolic velocity [PSV], resistance index [RI]). Patients were classified as IICP (CSF pressure > 200 mmH₂O) or normal ICP (NICP) groups.

Intervention of Astragalus Membranaceus Extract in rats of spinal cord injury: a systematic review and meta-analysis.

Objective: Spinal cord injury (SCI) causes motor, sensory and autonomic dysfunction below the level of injury and its incidence is increasing every year. Astragalus Membranaceus Extract (AME) has received attention in spinal cord injury in recent years, but its specific effects in spinal cord injury are unclear.

Methods: Databases of PubMed, Embase, WOS, Cochrane Library, FMRS, Clinical trial, CNKI, VIP, and WangFang were searched from their establishment to December 1, 2024 using the following terms: "Astragalus propinquus," "Huang qi," " Bunge," "Spinal cord injuries," "spinal cord diseases," "spinal cord trauma.

Amorphous MnO nanoflower with high laccase-like activity for colorimetric detection of pheochromocytoma biomarker.

Manganese dioxide (MnO), a classical catalyst, plays a pivotal role in modern chemistry and industrial production. However, its laccase-like activity has been underexplored, and particularly the intriguing relationship between its diverse structures and laccase-like properties remains an unresolved question. In this study, five types of MnO, including crystalline α-MnO, β-MnO, γ-MnO, δ-MnO and amorphous MnO nanoflower (NF), were successfully synthesized.

Submolecular Resolution of β‑Sheet Plasticity: Decoding Mutations and PTMs in Protein Aggregation Disorders.

The functional diversity of proteins often arises from the remodeling of conformational ensembles, particularly through mutations and post-translational modifications (PTMs). However, experimentally characterizing such ensembles remains challenging due to their heterogeneous and transient nature. Here, we report the determination of the conformational substates of β-sheets and the effect associated with mutations and PTMs in human islet amyloid polypeptide (hIAPP) via scanning tunneling microscopy (STM).

Caregiver insights on challenges and needs in fecal incontinence products: a mixed methods study.

Aims: This study explores the real-world use and challenges of fecal incontinence (FI) collection products-both absorbent items (pads, diapers) and dedicated fecal-collection devices with adhesive fixators-among long-term, bed-bound hospital patients, while also considering broader public-health implications. It seeks to identify barriers to optimal product use and to offer recommendations for improving incontinence management outcomes.

Background: Effective FI management is essential to patient wellbeing and to preventing healthcare-associated infections (HAIs).

Submolecular Resolution Imaging of Amyloid Aggregation: An STM Approach to Decipher Missense Mutation Effects in α-Synuclein.

Intrinsically disordered regions (IDRs) are critical regulators of cellular function, and their aberrant phase transitions into amyloid fibrils underlie the pathogenesis of amyloidosis. Missense mutations modulate IDR aggregation, but mechanisms remain unclear. Here, we investigate the impact of Parkinson's disease-associated mutations (A53V and T72M) on the aggregation dynamics of α-synuclein (α-Syn), a prototype protein containing IDRs, using scanning tunneling microscopy (STM).

Assessing the effectiveness of test-trace-isolate interventions using a multi-layered temporal network.

In the early stage of an infectious disease outbreak, public health strategies tend to gravitate towards non-pharmaceutical interventions (NPIs) given the time required to develop targeted treatments and vaccines. One of the most common NPIs is Test-Trace-Isolate (TTI). One of the factors determining the effectiveness of TTI is the ability to identify contacts of infected individuals.

Arginine-Rich Peptides Regulate the Pathogenic Galectin-10 Crystallization and Mitigate Crystallopathy-Associated Inflammation.

Protein self-assembly into a crystal in vivo triggers acute or chronic organ injury that can lead to intractable diseases lacking specific treatment options. In this study, we report the discovery of ionic arginine-rich peptides to disrupt the pathogenic galectin-10 (gal-10) crystallization, where the aberrant deposition of gal-10 crystals in airways causes the activation of IL-1β-dependent inflammation and the stimulation of epithelial cells to produce TNF-α. Gal-10 crystals show susceptibility to pH changes and charged residue substitutions at the protein packing interfaces, manifesting the role of charge-charge attractions across protein-protein interaction interfaces in governing gal-10 crystallization.

Safety and efficacy of oral administrated cepharanthine in non-hospitalized, asymptomatic or mild COVID-19 patients: a Double-blind, randomized, placebo-controlled trial : Author detials.

Cepharanthine (CEP) is a natural remedy that potently inhibits SARS-CoV-2 activity both in vitro and in vivo. To evaluate the efficacy and safety of CEP compared with placebo in adults with asymptomatic or mild coronavirus disease 2019 (COVID-19), we conducted a proof-of-concept, double-blind, randomized, placebo-controlled trial. Patients were randomized to receive 120 mg/day of CEP, 60 mg/day CEP or placebo for 5 days.

High selectivity, capacity and stability for electrochemical lithium extraction on boron-doped HMnO by tailoring lattice constant and intercalation energy.

A sustainable supply of lithium from salt-lake brines is necessary due to the surge in demand of the lithium-battery market. However, the presence of coexisting ions, particularly Na, poses a significant challenge due to the similarities in charge, electronic structure, and hydrated size. The electrochemical system with manganese (Mn)-based lithium-ion (Li) sieves electrodes is a promising method for Li recovery, but often suffers from geometric configuration distortion, which reduces their selectivity and capacity.

Phase change material composites based on 3D lignin-derived porous carbon prepared by in-situ activation for efficient solar-driven energy conversion and storage.

Utilization of three-dimensional biomass-derived porous carbons can effectively address issues of easy leakage, low thermal conductivity, and weak photothermal conversion of phase change materials (PCMs). This enables the production of high-performance composites for solar-induced energy collection, conversion, and storage. In this study, hierarchical lignin-derived porous carbon (HLPC), microporous lignin-derived porous carbon (MILPC) and mesoporous lignin-derived porous carbon (MELPC) were prepared through high-temperature in-situ activation using lignosulphonate (LS) as a carbon precursor and CaCO, KOH and ZnCO as activators.

2-Methylbenzimidazole-copper nanozyme with high laccase activity for colorimetric differentiation and detection of aminophenol isomers.

Laccase is well-known for its eco-friendly applications in environmental remediation and biotechnology, but its high cost and low stability have limited its practical use. Therefore, there is an urgent need to develop efficient laccase mimetics. In this study, a novel laccase-mimicking nanozyme (MBI-Cu) was successfully synthesized using 2-methylbenzimidazole (MBI) coordinated with Cu by mimicking the copper active site and electron transfer pathway of natural laccase.

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

Purpose: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation.

Materials And Methods: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively.

Stable peptide-assembled nanozyme mimicking dual antifungal actions.

Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly.

A nomogram for predicting neurogenic lower urinary tract dysfunction in patients with acute ischemic stroke: A retrospective study.

Aims: To investigate the risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS), and develop an internally validated predictive nomogram. The study aims to offer insights for preventing AIS-NLUTD.

Methods: We conducted a retrospective study on AIS patients in a Shenzhen Hospital from June 2021 to February 2023, categorizing them into non-NLUTD and NLUTD groups.

Discovery of TRPA1 Antagonist : Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease.

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium ion channel highly expressed in the primary sensory neurons, functioning as a polymodal sensor for exogenous and endogenous stimuli, and has been implicated in neuropathic pain and respiratory disease. Herein, we describe the optimization of potent, selective, and orally bioavailable TRPA1 small molecule antagonists with strong target engagement in rodent models. Several lead molecules in preclinical single- and short-term repeat-dose toxicity studies exhibited profound prolongation of coagulation parameters.

The Realities and Needs of Nursing Assistants Caring for Disabled Patients with Fecal Incontinence During Hospitalization: A Qualitative Study.

Objective: To explore the experience, role, and needs of medical nursing assistants during hospitalization in patients with incapacitated fecal incontinence.

Methods: Qualitative study using reflexive thematic analysis. Semi-structured interviews were conducted with 21 medical nursing assistants from three hospitals in Southern China.

Targeting the mammalian target of rapamycin pathway in neurological manifestations of Covid-19.

The diverse and severe nature of neurological manifestations associated with coronavirus disease 2019 (Covid-19) has garnered increasing attention. Exploring the potential to decrease neurological complications in Covid-19 patients involves targeting the mammalian target of rapamycin (mTOR) pathway as a therapeutic strategy. The mTOR pathway, widely recognised for its central role in essential cellular processes like synthesising proteins, facilitating autophagy, and modulating immune responses, has implications in various neurological disorders.

A Key-Points Based Anchor-Free Cervical Cell Detector.

Cervical cell detection is crucial to cervical cytology screening at early stage. Currently most cervical cell detection methods use anchor-based pipeline to achieve the localization and classification of cells, e.g.

Zoledronic acid and ibandronate-induced nephrotoxicity in 2D and 3D proximal tubule cells derived from human and rat.

Drug-induced proximal tubule (PT) injury remains a serious safety concern throughout drug development. Traditional in vitro 2-dimensional (2D) and preclinical in vivo models often fail to predict drug-related injuries presented in clinical trials. Various 3-dimensional (3D) microphysiological systems (MPSs) have been developed to mimic physiologically relevant properties, enabling them to be more predictive toward nephrotoxicity.

Reproducibility and usefulness of quantitative apparent diffusion coefficient measurements for predicting program death-ligand 1 expression in nasopharyngeal carcinoma.

Background: Accurate assessment of programmed death-ligand 1 (PD-L1) expression status in nasopharyngeal carcinoma (NPC) before immunotherapy is crucial. We aimed to explore the reproducibility and usefulness of the quantitative apparent diffusion coefficient (ADC) measurements for predicting PD-L1expression status in NPC.

Methods: We retrospectively recruited 134 NPC patients who underwent MRI scans and PD-L1 detection.