Ferritin-Conjugated PROTAC Strategy for ERCC1/XPF Degradation and Platinum Sensitization in Resistant Tumors.

Cisplatin resistance remains a major clinical challenge in cancer therapy, often driven by the upregulation of DNA repair pathways. Here, we present a dual-functional nanotherapeutic system (HFn-NERiP-Pt(IV)) combining a glutathione-responsive PROTAC (NERiP) with a ferritin nanocarrier for targeted ERCC1/XPF degradation and enhanced platinum delivery. NERiP selectively degrades ERCC1/XPF upon release in reductive tumor environments, suppressing nucleotide excision repair and enhancing platinum cytotoxicity.

An electroneutral fluorescent probe for visualization of lipid droplets polarity heterogeneity and NAFLD detection.

Lipid droplets (LDs), omnipresent organelles in nearly all eukaryotic cells, have garnered significant attention in cell biology. Alterations in LD polarity not only signify cellular carcinogenesis but also correlate closely with the severity of nonalcoholic fatty liver disease (NAFLD). Despite their importance, the lack of suitable detection tools has limited research and clinical applications in this area.

LncRNA PCED1B-AS1 facilitates cervical cancer progression via targeting miR-361-3p.

In recent years, the incidence of cervical cancer has been on the rise, making it imperative to search for targeted therapeutic tumor-associated biomarkers. PCED1B-AS1 regulates gene expression and affects cell proliferation and differentiation in tumors. However, its function and potential mechanisms in cervical cancer remain unclear.

Cascade Catalytic Nanozymes: Design, Classification, and Biomedical Applications.

Enzyme catalysis plays a fundamental role in biological systems, particularly in multienzyme cascade reactions that achieve efficient and precise transformation of complex substrates through synergistic cooperation. These cascades exemplify the high-level division of labor and ordered regulation intrinsic to natural catalytic networks. Inspired by such biological systems, nanozymes, which are artificial catalytic materials that combine the physicochemical properties of nanomaterials with enzyme-like activities, have emerged as a promising platform for constructing multistep catalytic processes.

Fisetin Attenuates Mutant SOD1 Aggregation in Amyotrophic Lateral Sclerosis via Nrf2-Mediated Autophagy Activation.

Dysregulated autophagy and copper/zinc superoxide dismutase (SOD1) protein aggregation play a crucial role in amyotrophic lateral sclerosis (ALS). Here, we used stably transfected NSC34 motor neuron-like cells: (1) SOD1 mutants (G93A), (2) wild-type SOD1 (WT) controls, and (3) empty vector (EV) controls to observe the effects of fisetin. Pharmacological autophagy inhibition (Bafilomycin A1, 40 nM) and nuclear factor erythroid 2-related factor 2 (Nrf2) gene silencing (siRNA transfection) were employed to dissect molecular pathways.

Synergistic therapy for pancreatic cancer by deactivating cancer-associated fibroblasts and driving T-cell migration into tumor microenvironment using nanochaperone delivery system.

The success of immunotherapy in pancreatic ductal adenocarcinoma (PDAC) is greatly limited by the scarcity of cytotoxic T lymphocytes (CTLs) in tumor microenvironment, which is mainly due to the physical barrier formed by a dense extracellular matrix (ECM). Here we reported a potent strategy to rectify the CTLs infiltration in PDAC by synergistically deactivating cancer-associated fibroblasts (CAFs) and driving T-Cell migration into tumor microenvironment. This combination therapy is achieved by co-delivery of vitamin D receptor ligand (calcipotriol, Cal) and chemokine (CXCL9) using nanochaperone (nChap) delivery platform.

Separation and Differential Characterization of Gut Microbial Extracellular Vesicles in Salt-Sensitive Rats under High-Salt Diet Conditions.

High salt intake is a major risk factor for hypertension, and its underlying mechanism may be closely linked to extracellular vesicles (EVs) secreted by gut microbiota. These EVs, produced by gut microbiota, carry various bioactive components that may play a crucial role in the development of hypertension induced by a high-salt diet (HSD). To investigate this mechanism, we developed an efficient extraction method based on density gradient centrifugation to isolate EVs from the gut microbiota of salt-sensitive rats fed an HSD.

Cardiac arrhythmias in patients with focal and generalised epilepsy undergoing ambulatory electroencephalographic and electrocardiographic monitoring.

Background: Epilepsy may be associated with cardiac arrhythmias. The specific incidence and types of cardiac arrhythmias in different forms of epilepsy is not clearly defined.

Methods: We evaluated patients aged 16 years or older referred for continuous home-based ambulatory video-electroencephalographic(EEG)-electrocardiographic(ECG) monitoring (AVEEM) across 24 sites in Australia between 2020 and 2023.

Ta-doped NbO with enhanced performance for lithium-ion batteries.

Micrometer-sized niobium pentoxides (NbO), with inherent safety and capability for fast lithium insertion/deinsertion, have been regarded as promising anodes for high-volumetric-energy-density lithium-ion batteries (LIBs). However, they suffer from structural instability and capacity fading in practical applications. To address these issues, we adopt a Ta doping strategy to change the chemical composition of NbO.

Genome-Wide Identification of 109 NAC Genes and Dynamic Expression Profiles Under Cold Stress in .

(), a tropical tree valued for its medicinal, nutritional, and industrial applications, exhibits severe sensitivity to low-temperature stress in subtropical regions, particularly during seedling establishment. To address this challenge, this study systematically identified 109 NAC genes in and characterized their functional roles in cold adaptation via multi-omics analyses. All NAC proteins were hydrophilic.

Precision therapies for genetic epilepsies in 2025: Promises and pitfalls.

By targeting the underlying etiology, precision therapies offer an exciting paradigm shift to improve the stagnant outcomes of drug-resistant epilepsies, including developmental and epileptic encephalopathies. Unlike conventional antiseizure medications (ASMs) which only treat the symptoms (seizures) but have no effect on the underlying disease, precision therapies have the potential to suppress not only the seizures but also disabling comorbidities, including cognitive and behavioral abnormalities, which share the same causative mechanisms. Monogenic epilepsies are an attractive target for precision therapies because of their well-defined molecular mechanisms which can be tested in vitro and can be counteracted by specific drugs.

COMM domain containing 4 inhibits hephaestin and ferroportin to enhance neuronal ferroptosis by disturbing the Cu-Fe balance in amyotrophic lateral sclerosis.

Dysregulation of copper and iron homeostasis contributes to the progression of amyotrophic lateral sclerosis (ALS), but the role and mechanism of COMM domain containing 4 (COMMD4) in ALS remains unclear. In this research, we showed that the expression of COMMD4 was upregulated in ALS cells and animal models. The increased COMMD4 induced neuronal ferroptosis by disrupting the Cu-Fe balance.

Development and validation of an early prediction model for cardiac death risk in patients with light chain amyloidosis: a multicenter study.

Background: Cardiac involvement is the primary driver of death in systemic light chain (AL) amyloidosis. However, the early prediction of cardiac death risk in AL amyloidosis remains insufficient.

Objectives: We aimed to develop a novel prediction model and prognostic scoring system that enables early identification of these high-risk individuals.

The vertices number determined SERS activity of polyhedra and the application in oral cancer detection based on deep learning.

Due to the inherent specificity and high sensitivity, biomedical detections based on Surface-Enhanced Raman Scattering (SERS) technology have garnered increasing attention. In the SERS detection process, fabricating a highly sensitive SERS substrate is the most critical. Although various methods, such as self-assembly and nanocavities, are used to enhance the local electric field intensity and thus improve SERS activity, the foundation still lies in the preparation of individual noble metal nanoparticles with high SERS activity.

Multiple pathways through which the gut microbiota regulates neuronal mitochondria constitute another possible direction for depression.

As a significant mental health disorder worldwide, the treatment of depression has long faced the challenges of a low treatment rate, significant drug side effects and a high relapse rate. Recent studies have revealed that the gut microbiota and neuronal mitochondrial dysfunction play central roles in the pathogenesis of depression: the gut microbiota influences the course of depression through multiple pathways, including immune regulation, HPA axis modulation and neurotransmitter metabolism. Mitochondrial function serves as a key hub that mediates mood disorders through mechanisms such as defective energy metabolism, impaired neuroplasticity and amplified neuroinflammation.

Expression and immunological role of FUNDC2 in pan-cancer.

FUNDC2 is a novel mitochondrial protein and is highly involved in various cancers. However, expression pattern and possible role and mechanism of FUNDC2 in pan-cancer remain to be investigated. TIMER 2.

Distribution of Intranasally Administered rIL-10 Along the Olfactory Nerve and Perivascular Space After Intracerebral Hemorrhage.

Rationale: The utilization of anti-inflammatory therapy for treating brain diseases holds promise; however, research on intranasal administration of drug compounds remains limited. Quantitative data, particularly pharmacokinetics, are scant, and direct evidence of the distribution of intranasally administered recombinant interleukin 10 (rIL-10) within the brain is lacking.

Methods: Employing fluorescent labeling, in vivo imaging, and confocal microscopy, we meticulously monitored the distribution and delivery pathways of intranasally administered rIL-10 in the brain.

Activity and Safety Optimization of Mesoricin: A Dual-Domain Antifungal Peptide from sp.

infections pose a significant global health threat. This study introduces mesoricin, a novel dual-domain antimicrobial peptide (AMP) scaffold derived from sp. identified using an quantitative antifungal activity index (AFI).

Inhibition of Salt-Inducible Kinase 2 Protects Motor Neurons From Degeneration in ALS by Activating Autophagic Flux and Enhancing mTORC1 Activity.

Objectives: Autophagic impairment has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Salt-inducible kinase 2 (SIK2), a member of the AMP-activated protein kinase (AMPK) family widely expressed in the central nervous system, plays critical roles in neuronal survival, neurogenesis, and the regulation of autophagy. This study aims to investigate the effects and underlying mechanisms of SIK2 in the pathogenesis of ALS.

Exploration of deep operator networks for predicting the piezoionic effect.

The piezoionic effect holds significant promise for revolutionizing biomedical electronics and ionic skins. However, modeling this multiphysics phenomenon remains challenging due to its high complexity and computational limitations. To address this problem, this study pioneers the application of deep operator networks to effectively model the time-dependent piezoionic effect.

Challenges of face identification with varied mask coverage in the post COVID-19 era.

Introduction: Recent studies have shown that wearing masks can influence face recognition abilities. During the COVID-19 pandemic, people became increasingly familiar with seeing masked faces, leading to a reduced familiarity with fully uncovered faces. With Taiwan now transitioning to a post-COVID-19 phase and the removal of mask mandates, this study investigates how varying levels of mask coverage affect face identification accuracy and response times.

Integrated transcriptomics and metabolomics elucidate how arbuscular mycorrhizal fungi alleviate drought stress in Juglans sigillata.

Walnut (Juglans sigillata), an economically significant ecotype of the Juglans genus in the Juglandaceae family, is cultivated mainly in southwest China, a region prone to seasonal drought. Drought significantly reduced both the yield and quality of walnuts in this area. Arbuscular mycorrhizal fungi (AMF) are symbiotic fungi that colonize plant roots and play crucial roles in enhancing plant drought resistance.

High Proton Conductivity Enhancement Obtained by a Covalent Postsynthesis Modification Approach for Two Metal-Organic Frameworks.

This study demonstrates an effective strategy to enhance proton conductivity by synthesizing 2 three-dimensional metal-organic frameworks (MOFs), [Zn(DTD22)] (MOF 1) and [Cd(DTD22)] (MOF 2), (DTD22 = 4,4″-diamino-[1,1':4',1″-terphenyl]-2,2″-dicarboxylic acid). The DTD22 ligand used formed a continuous hydrogen-bonding network in the structure, constructing excellent hydrophilic channels. MOF 1 and MOF 2 were further postsynthesized and modified (PSM) by Schiff base reaction, and 4-chloro-3-formylbenzenesulfonic acid ligands containing -SOH and -Cl were successfully introduced into the framework to form PSM-MOF 1 and PSM-MOF 2.

Tetramethylpyrazine Nitrone in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: Tetramethylpyrazine nitrone has exhibited promising results in improving motor dysfunction in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

Objective: To evaluate the safety and efficacy of orally administered tetramethylpyrazine nitrone in patients with ALS.

Design, Setting, And Participants: This phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial was conducted from December 24, 2020, through July 14, 2023, in 11 centers in China, with a 180-day follow-up.

Does the interval between the first unprovoked seizure and EEG influence the diagnostic yield?

Objective: There is no consensus on the optimum time for an EEG after the first seizure. We sought to investigate whether the timing of an EEG after a first unprovoked seizure influences its diagnostic yield.

Methods: A retrospective analysis was conducted at a tertiary hospital in Australia.