Targeted degradation of hexokinase 2 by a novel engineered bispecific chimeric liposome-based Nano-PROTACs for enhancing tumor chemotherapy.

Aerobic glycolysis is critical for tumor development and metastasis. Regulating the activity of vital metabolic enzymes in the tumor glycolysis process, such as hexokinase 2 (HK-2), is expected for tumor treatment. However, conventional small molecule inhibitors only block the activity of proteases with consistently high doses via occupation-driven pattern, leading to off-target effects which limit their clinical application.

Tuning Anisotropic Swelling in a Liquid Crystalline Polyester-Polyethylene Glycol Hydrogel via Large Strain and Annealing.

The anisotropic swelling behavior of hydrogels can be controlled by the alignment of their molecular chains. In this work, we report a strategy to precisely control the anisotropic swelling direction of hydrogels by leveraging a rationally designed liquid crystalline polymer in combination with large strain and annealing. A liquid crystalline polyester-polyethylene glycol random block copolymer (LCP--PEG) is synthesized via one-pot polycondensation.

Effects of a Comprehensive Intervention Program of Static-Dynamic Balance Training Combined with Reminiscence Therapy on the Level of Healthy Aging Among Older Adults in a Rural Community: A Randomized Controlled Trial.

Purpose: Healthy aging levels are generally low among rural older adults, yet the effects of combined static-dynamic balance training and reminiscence therapy on this population remain underexplored. This study evaluated the efficacy of a combined static-dynamic balance training and reminiscence therapy (SDBT-RT) program in promoting healthy aging in rural communities, with emphasis on both immediate and sustained outcomes.

Patients And Methods: A randomized, assessor-blinded, controlled trial with two parallel groups included 64 adults >60 years from rural Huzhou, China, randomized to intervention (n=32) and control (n=32) groups.

Multi-omics analysis reveals synergistic effects of terpenoids and phenylpropanoid compounds on flavour formation in skin and pulp of 'Shine Muscat' grape.

Flavour is a key trait that determines table grape quality and marketability. However, specific volatile compounds remain inadequately characterised. In this study, we have performed a comprehensive analysis of the volatile compounds in Muscat 'Shine Muscat' and no-flavour 'Thompson Seedless' during three different stages using widely targeted metabolomics and transcriptomics.

Advanced Strategies in Phage Research: Innovations, Applications, and Challenges.

The escalating global threat of antimicrobial resistance (AMR) underscores the urgent need for innovative therapeutics. Bacteriophages (phages), natural bacterial predators, offer promising solutions, especially when harnessed through advances in artificial intelligence (AI). This review explores how AI-driven innovations are transforming phage biology, with an emphasis on three pivotal areas: (1) AI-enhanced structural prediction (e.

Tumor Microenvironment Specifically Regulated Nano Chemoamplifier for Chemosensitization and Activation of Anti-Tumor Immune Response by Coordinating Intracellular Magnesium Overload.

Chemotherapy is an established treatment modality for breast cancer; however, it is impaired by issues such as highly refractory chemoresistance and significant side effects. Magnesium ions (Mg), inorganic metal ions with anti-tumor bioactivity, sensitize cancer cells to chemotherapy by depressing P-glycoprotein (P-gp) expression. Moreover, Mg functions as an immunoadjuvant to potentiate anti-tumor immune responses, while excessive Mg can induce marked tumor cell apoptosis.

Somato-Cognitive Action Network in Focal Dystonia.

Background: The central pathology causing idiopathic focal dystonia remains unclear. The recently identified somato-cognitive action network (SCAN) has been implicated.

Objective: We tested whether the effector-agnostic SCAN may constitute a central pathology shared across dystonia subtypes, whereas the effector-specific regions in the primary sensorimotor cortex may show distinct functional changes specific to the dystonic body part.

Exploring the effects of capsule in microcirculatory dysfunction model rats through laser speckle contrast imaging and metabolomics.

Background: Microcirculatory dysfunction leads to a number of diseases and worsen prognosis. Blood-activating drugs like capsule may improve circulation, but its pharmacological effects in microcirculatory dysfunction remain unclear.

Objective: The purpose of this study is to determine the pharmacological effect of capsules in treating microcirculatory dysfunction.

Cross-species single-cell transcriptomic atlas of retinal photoreceptors reveals molecular signatures underlying color vision adaptation.

The retina exhibits conserved structural and functional features across species, yet the evolutionary mechanisms underlying color vision remain unclear. Here, we employ a single-cell prediction (scPred) model to construct a cross-species single-cell retinal atlas from 24 species. We identify conserved retinal cell types and expression patterns, with photoreceptor cells, especially rods, showing evolutionary shifts.

Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels.

Objectives: The clinical implications of positive anti-mitochondrial antibodies (AMAs) and/or primary biliary cholangitis (PBC)-specific anti-nuclear antibodies (ANAs) in patients with normal alkaline phosphatase (ALP) remain uncertain.

Methods: Patients at The Second Hospital of Nanjing with positive AMAs/PBC-ANAs and normal ALP levels from January 2016 to July 2024 were categorized into three groups based on autoantibody profiles: [AMA/AMA-M2][gp210/sp100], [AMA/AMA-M2][gp210/sp100], and [AMA/AMA-M2][gp210/sp100]. The study compared PBC diagnostic rates, clinical symptoms, laboratory results, and pathology across these groups.

Deep-ultraviolet plasmon resonances on hybrid Si nanostructures for photoluminescence enhancement.

Deep ultraviolet (DUV) nanophotonic technologies are of vital importance for applications in biomedical sensing, advanced lithography, light sources, and optoelectronic devices. Plasmonic nanostructures with DUV resonance properties can generate highly confined optical fields. They therefore have great potential in amplifying spectral signals from molecules with intense vibronic transitions in the DUV region and improving the sensitivity of solar-blind detection.

Association of aspirin use with mortality in critically ill patients with chronic obstructive pulmonary disease: A retrospective propensity score-matched cohort study.

Background: The impact of aspirin on mortality in patients with chronic obstructive pulmonary disease (COPD) remains unclear, particularly those who are critically ill.

Methods: This retrospective cohort study utilized data from the MIMIC-IV 3.1 database to investigate the correlation between aspirin use and 30-day mortality among critically ill adult patients diagnosed with COPD.

Reactive oxygen species and reactive nitrogen species are double-edged swords in Salmonella infection.

Salmonella contains a group of serovars, which are more than just enteropathogenic bacteria but dangerous pathogens causing systemic infection of human, livestock, and poultry. As an innate immune response, inflammation induces reactive oxygen species (ROS) and reactive nitrogen species (RNS) production from host cells in response to Salmonella infection. Generally, ROS and RNS are regarded as bactericidal substances for their ability to oxidize and modify the bacterial biomolecules including proteins, DNA, RNA, lipids, etc.

Emericellopsic acid, a helvolic acid derivative with a 6/5/7/5 tetracyclic skeleton from sponge-derived Emericellopsis maritima.

Emericellopsic acid (1), the first B/C ring-rearranged fusidane-type antibiotic possessing a 6/5/7/5-fused ring framework, together with seven known helvolic acid derivatives, was isolated from the sponge-associated fungus Emericellopsis maritima IMB18-123 cultivated with autoclaved Pseudomonas aeruginosa. The structure of 1 was determined by extensive spectroscopic data analysis combined with ECD calculation. Compound 1 exhibited moderate antimicrobial activities against Staphylococcus aureus and S.

Machine Learning-Assisted Discovery of Bimetallic Oxides for Highly Efficient Catalytic Ozonation.

Catalytic ozonation stands out as an effective process in the advanced treatment of industrial wastewater, where heterogeneous catalysts play a pivotal role. Here, by screening 1603 bimetallic oxides via machine learning (ML), a pioneering ZnCuO was dug out, validated by density-functional theory and experiments. Compared with the literature, ZnCuO significantly boosted the degradation rate constant for oxalic acid ( = 0.

and anti- activity of a scorpion peptide derivative.

Introduction: is an important opportunistic and foodborne disease-related bacterium, and the increasing antibiotic resistance of the pathogen leads to the urgent exploration of new and effective antibacterial agents. In this study, a scorpion peptide derivative HTP2 was designed.

Methods: The anti- activity was evaluated using a broth microdilution assay.

Deciphering the mechanism and substance basis of Dingxiang Shidi Decoction for the treatment of chemotherapy-induced nausea and vomiting by integrating mass spectrometry, network pharmacology and molecular docking.

BackgroundChemotherapy-induced nausea and vomiting (CINV) remains a prevalent and debilitating side effect of cancer treatment with limited therapeutic options. Dingxiang Shidi Decoction (DXSD), a classical Chinese herbal formula, has demonstrated clinical efficacy in CINV management. However, its active components and mechanism of action require systematic investigation.

Atomically Precise Au Clusters for 3D Visualization of Pathological Progression in Sepsis-Induced Multi-Organ Injury.

Sepsis has a high global incidence and mortality, requiring early identification and assessment of organ damage. We present a NIR-II 3D visualization strategy using atomically precise fluorescent Au clusters to detect sepsis-induced multi-organ injury. These clusters emit strong fluorescence at 1044 nm with extended photostability (up to 300 min).

Protein Tyrosine Kinase 2 Circular RNA Promotes Proliferation and Invasion of Bladder Cancer.

Background/aims: Bladder cancer is a type of malignant tumor that disrupts normal urinary function in patients, thereby significantly impacting their quality of life. This disease also imposes a heavy economic burden on both patients and public health agencies due to high medical costs. Current common therapies, such as surgical intervention, chemical treatment, and radiotherapy, are associated with serious adverse reactions and risks of metastasis recurrence.

Unexpected Generation of Singlet Oxygen at the Air-Water Interface of Aqueous Microdroplets.

Singlet oxygen (O) is a classical nonradical reactive oxygen species (ROS), which is of great significance in both natural and engineering environments. Here, we found that O can be generated spontaneously at the air-water interface of microdroplets under dark conditions. O isotope labeled O (O) and water (HO) were used to identify the source and formation pathway of O and previously reported ROS produced in microdroplets.

Wheat endosperm-specific transcription factor TaDOF6 enhances grain development by regulating expression and facilitating sugar and gibberellin transport.

Seed size is regulated by the coordinated growth of the seed coat, embryo, and endosperm, and is modulated by multiple factors. Plant hormones, sugars, and cell cycle-related processes play key roles in this regulation. In this study, we demonstrate that overexpressing the endosperm-specific DOF transcription factor gene significantly enhances the accumulation of sugars and gibberellin (GA) in grains during the grain-filling stage.

ICAM-1-mediated Src signaling pathway plays a pivotal role in encephalomyocarditis virus entry.

Encephalomyocarditis virus (EMCV), a potential zoonotic pathogen with a broad host range, has been reported to enter cells via caveolin-mediated endocytosis (CavME), a process initiated by caveolae detachment from the plasma membrane. However, the molecular mechanism underlying EMCV's cellular entry remains incompletely characterized. Here, we identified for the first time that the overexpression of Src kinase and Fyn kinase individually enhanced the replication and proliferation of EMCV.

Facile fabrication of net-like fluorescent microsphere/AuNP tags for a dual-modal colorimetric/fluorescence lateral flow assay.

Lateral flow assays (LFAs) offer a simple and rapid option for diagnosis, widely utilized for point-of-care or at-home testing. However, they often suffer from low sensitivity and high false positive owing to the single output signal. Herein, we developed a dual-mode colorimetry/fluorescence LFA via employing a novel net-like nanprobe as a reporter tag, which was obtained by coupling the fluorescent microspheres (FMs) with gold nanoparticles (AuNPs).

Anti-Pseudomonas aeruginosa Activity of the Scorpion-Derived Peptide GK8.

The increasing infection and antibiotic resistance of Pseudomonas aeruginosa has become a major threat to public health, making exploring new and effective antimicrobial agents particularly important. In this study, the scorpion-derived cationic peptide GK8 was designed, which showed effectiveness against P. aeruginosa including clinical resistance strains with low hemolytic activity.