Purine metabolism in tumorigenesis and its clinical implications.

Metabolic reprogramming constitutes a hallmark of malignant neoplasms. Purine metabolism emerges as a pivotal regulator in cellular metabolic networks through multiple mechanisms, including dysregulation of de novo biosynthesis/salvage pathway coordination, adenosine-mediated immunosuppressive microenvironment formation, and collective contributions to tumorigenesis and malignant progression. During metastatic progression, purine metabolism reinforces tumor cell plasticity through mitochondrial energy regulation and modulation of cell cycle checkpoints (eg, G1/S transition).

Hot-Spot-Guided Generative Deep Learning for Drug-Like PPI Inhibitor Design.

Protein-protein interactions (PPIs) are essential therapeutic targets, yet their large and relatively flat interfaces hinder the development of small-molecule inhibitors. Traditional computational approaches rely heavily on existing chemical libraries or expert heuristics, restricting exploration of novel chemical space. To address these challenges, we present Hot2Mol, a generative deep learning framework for the de novo design of target-specific and drug-like PPI inhibitors.

ARCADE: Controllable Codon Design from Foundation Models via Activation Engineering.

Codon sequence design is crucial for generating mRNA sequences with desired functional properties for tasks such as creating novel mRNA vaccines or gene editing therapies. Yet existing methods lack flexibility and controllability to adapt to various design objectives. We propose a novel framework, ARCADE, that enables flexible control over generated codon sequences.

A Stability-Aware Dual-Head Network with Prototype-Based Consistency for Semi-Supervised Medical Image Segmentation.

Semi-supervised semantic segmentation for medical images has evolved through time. While it can leverage the unlabeled data to significantly improve the segmentation performance, it still suffers the problems of intra-class variance and the consequent class-domain distribution misalignment along with costly training. In this paper, a stability-aware dual-head architecture is proposed to synergize prototype-based and Fully Convolutional Network (FCN) methodologies.

Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation.

Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucleinopathies. However, the precise role of these PTM in pathology formation, neurodegeneration, and pathology spreading remains unclear. Here, we systematically investigated the role of post-fibrillization C-terminal aSyn truncations in regulating uptake, processing, seeding, and LB-like inclusion formation using a neuronal seeding model that recapitulates LB formation and neurodegeneration.

Fe(Ⅱ)-mediated detoxification mitigates low-dose rare earth elements-induced stress on anammox consortia for mining tailwater treatment.

Rare earth mining activities cause severe nitrogen pollution in watersheds, yet the residual hazardous rare earth elements (REEs) toxicity in tailings wastewater challenges biological nitrogen removal technology. This work demonstrated that introducing low-dose Fe(II) into partial denitrification/anammox (PD/A) system significantly alleviated REEs-induced stress on anammox consortia via detoxification and physical barrier reinforcement. The PD/A bioreactor with 15 mg/L Fe(II) (R1) was compared against a control without Fe(II) for real rare earth tailings wastewater treatment.

How long is long enough for traffic conflict observation: An investigation using extreme value theory approaches.

Determining the appropriate duration for traffic conflict observation remains a critical yet unresolved challenge in road safety analysis. Existing approaches lack a quantitative approach to determine adequate sample sizes for general conflict-based applications. This study addresses this gap by proposing an extreme value theory based framework to determine appropriate observation durations, based on the inherent stability of road entity safety for a specified period.

Antigen escape in CAR-T therapy: A tumor microenvironment perspective from hematological to solid tumors.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in hematologic malignancies, but antigen escape remains a major challenge, especially in solid tumors, where the tumor microenvironment (TME) exacerbates the problem. Mechanisms of antigen escape include antigen loss, epitope masking, lineage switching, and trogocytosis-mediated CAR dysfunction. The TME promotes immune evasion through physical barriers, immunosuppressive cells, and metabolic competition.

Decitabine suppresses tumor growth by activating mouse mammary tumor virus and interferon-β pathways.

Decitabine (DAC), a DNA methyltransferase inhibitor (DNMTi), is clinically effective in hematological malignancies such as myelodysplastic syndrome and acute myeloid leukemia, but its precise antineoplastic mechanisms remain incompletely understood. Beyond promoter demethylation, DAC is known to activate endogenous retroviruses (ERVs) and trigger type I interferon (IFN-I) responses, a phenomenon known as viral mimicry. The aim of this study was to investigate the roles of the mouse mammary tumor virus (MMTV) and interferon-β (IFN-β) in DAC-mediated tumor suppression.

Dendrobium officinale polysaccharide relieves hepatointestinal damage induced by chronic arsenic exposure in chickens by regulating gut microbiota.

Arsenic is a toxic substance that can enter the body through diet, and even skin contact. Dendrobium officinale polysaccharide (DOP) is one of the main active components of Dendrobium officinale, which has antioxidant and anti-inflammatory effects. To specify DOP's protective role against arsenic-induced hepatointestinal damage in chickens, this study explored the potential target and mechanism of DOP in intestinal barrier injury based on network pharmacological analysis.

Dietary hispidulin ameliorated chemically-induced colitis by inhibiting epithelial cell ferroptosis the ACAT2-GPX4 axis and remodeling the gut microbiota.

Hispidulin, a dietary flavonoid occurring naturally in brown algae, has attracted considerable interest owing to its functions in modulating inflammatory responses and neutralizing reactive oxygen species. This study examined the consequences of hispidulin in a chemically induced acute colitis model. RNA sequencing (RNA_seq), 16s rRNA_seq, and non-targeted metabolomics were conducted to determine the mechanisms underlying hispidulin-induced effects on colitis.

SHR-2005, an FcγR-Dependent CD40 Agonistic Antibody with Potent Antitumor Activities and Favorable Safety Profile.

Activation of CD40, a pivotal component of immune oncology, could facilitate the infiltration of immune cells into the tumor microenvironment. In this investigation, we characterized SHR-2005, a second-generation CD40 agonistic mAb, as a potential candidate for cancer immune therapy. Our results showed that SHR-2005 possessed high affinity in binding to both human and rhesus CD40 and could effectively compete with CD40L for CD40 binding.

Effects of protein supplementation on body composition, physiological adaptations, and performance during endurance training: a systematic review and meta-analysis.

Introduction: This study aimed to evaluate the long-term effects of endurance training combined with protein supplementation on body composition, physiological adaptations (aerobic/anaerobic capacity), and performance.

Methods: A systematic search was conducted in Web of Science, PubMed, and SPORTDiscus databases on April 16, 2025, using the keywords "endurance training" and "protein supplementation." Meta-analysis was conducted using a random-effects model, and the main effect size of each outcome was summarized using the standard mean difference (SMD), and moderators were explored using subgroup and regression analyses.

Multi-Step Screening-Guided Core-Shell RuO@TaO Nanorods Electrocatalyst for Acidic Oxygen Evolution Reaction.

In the acidic oxygen evolution reaction (OER), the exploration of highly efficient and stable electrocatalysts is essential for the environmentally friendly production of hydrogen. Although RuO exhibits high catalytic activity, its solubility and corrosion in acidic environments are of concern. In this study, high-melting-point metal oxides were multi-step rationally screened as protective layers for RuO to identify their roles in the acidic OER process.

Supragingival microbial profiles in caries-free and caries-active adolescents treated with fixed orthodontics.

Background: Dental caries occur primarily due to the formation of excessive dental plaque biofilm on teeth surfaces. This study aims to analyze the supragingival microbial profiles of permanent teeth in caries-free and caries-active adolescents with fixed orthodontic appliances and to identify bacterial biomarkers that may be indicative of caries activity in specific population.

Methods: Twelve-year-old adolescents treated with fixed orthodontic appliances were selected as the study population, with 5 caries-free and 5 caries-active subjects.

A TARGET database-driven nomogram for pediatric osteosarcoma prognosis.

Objective: To analyze risk factors for pediatric osteosarcoma and to construct and evaluate a risk prediction model for pediatric osteosarcoma.

Methods: We retrospectively analyzed data from patients diagnosed with osteosarcoma between 2000 and 2013 (n = 129) from the TARGET database. First, independent prognostic factors associated with osteosarcoma-specific death were identified through Cox proportional hazards modeling.

Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.

Neuropathic pain causes plasticity in the nervous system, which is often associated with altered protein synthesis. Proteins are the key executors of cellular functions, and their alteration is closely related to the occurrence of neuropathic pain. Protein synthesis is a finely regulated process involving the interaction of multiple biomolecules.

Targeting LINC02544/miR-497-5p/CAPRIN1 axis via exosome-based siRNA to overcome immunotherapy resistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, leading to poor clinical outcomes and resistance to targeted therapies. Immunotherapy has shown limited success due to the development of resistance mechanisms. This study aimed to investigate the role of long non-coding RNA LINC02544 in mediating immunotherapy resistance through regulation of the miR-497-5p/CAPRIN1 axis in TNBC.

ADP-ribose is a competitive inhibitor of methanol dehydrogenases from Bacillus methanolicus.

Methanol dehydrogenase (MDH), a representative of Type III alcohol dehydrogenases (ADHs), plays a pivotal role in methanol assimilation pathways, making it a key enzyme for the biosynthesis of chemicals and fuels from one-carbon feedstocks. An activator protein belonging to the Nudix hydrolase family, ACT, was found to increase the activity of MDH by 40-fold. Despite the widespread observation of this in vitro activation phenomenon in pairs of type III alcohol dehydrogenases and Nudix hydrolases, the mechanistic details have remained unresolved for decades.

Effects of oat flour on rice flour and fermented rice cake: Processing properties, quality attributes, and starch digestive characteristics.

The rising incidence of diet-related chronic and celiac diseases underlines the demand for high-quality, functional gluten-free products that improve health. This study systematically evaluated the impact of oat flour (OF) substitution at different levels on the mixed flour and the final FGCs (OF 0%, OF 10%, OF 20%, OF 30%, OF 40%), along with underlying mechanisms. OF substitution enhanced the system's water-binding capacity, the integrity of starch granules, and viscoelasticity, while inhibiting gelatinization and promoting short-term retrogradation, as evidenced by reduced pasting enthalpy and increased pasting temperature and setback value.

Triple-Enhanced Absorption Anisotropy in Arrayed Core-Shell Nanowire Design.

One-dimensional semiconductor nanowires (NWs) are natural polarization photodetectors, thanks to their optical absorption anisotropy and efficient electrical transport channels. However, ultrathin NWs beyond practical fabrication capabilities are often required to achieve the desired polarization sensitivity. Here, we demonstrate a configuration of planar arrayed core-shell NW architectures with substantially enhanced absorption dichroism for linearly polarized light.

Development of a prediction model for risk of breakthrough urinary tract infection in children with primary vesicoureteral reflux.

Background: Many factors influence the risk of breakthrough urinary tract infection (BTUTI) in children with primary vesicoureteral reflux (VUR). Distal ureteral diameter ratio (UDR) and VUR index (VURx) have been shown in studies as predictors of BTUTI. We aimed to establish a predictive model through selecting voiding cystourethrography (VCUG)-related parameters in combination with clinical parameters for BTUTI in children with primary VUR.

Strontium-incorporated hydroxyapatite nanocomposites promoting bone formation and angiogenesis by modulating M2 macrophage polarization in the bone microenvironment.

The treatment of osteoporosis is urgently needed in the clinic. Hydroxyapatite (HAP) has a bone-inducing ability on osteogenic differentiation. Especially, the presence of strontium component in HAP nanoparticles may improve the positive effect on bone regeneration and avoid undesirable bone resorption.

CodonMoE: DNA Language Models for mRNA Analyses.

Genomic language models (gLMs) face a fundamental efficiency challenge: either maintain separate specialized models for each biological modality (DNA and RNA) or develop large multi-modal architectures. Both approaches impose significant computational burdens - modality-specific models require redundant infrastructure despite inherent biological connections, while multi-modal architectures demand massive parameter counts and extensive cross-modality pretraining. To address this limitation, we introduce CodonMoE (Adaptive Mixture of Codon Reformative Experts), a lightweight adapter that transforms DNA language models into effective RNA analyzers without RNA-specific pretraining.

Sacral Neuromodulation for Post-Hysterectomy Hydroureteronephrosis in a Patient with Cervical Cancer: A Case Report.

BACKGROUND Uterine cervical cancer in its early stage is managed with a standard treatment protocol of radical hysterectomy with bilateral pelvic lymphadenectomy. Common complications after the surgery include hydronephrosis, partially leading to renal failure. Currently, there are few reports on upper urinary tract function impairment caused by delayed lower urinary tract dysfunction after radical hysterectomy.