RACK1 is required for normal B cell development and signaling but not RAG1 degradation.

V(D)J recombination is constrained by timely degradation of the RAG1 and RAG2 proteins through distinct mechanisms. Previously, we showed that full-length RAG1 stability is regulated by viral protein R binding protein (VprBP) through its association with an amino-terminal region in RAG1, but the mechanism remains unclear. As an unbiased approach to uncover potential cofactors involved in the process, we compared protein interactomes between RAG1/RAG2 complexes formed when the amino-terminal third of RAG1 was present or absent.

Quantifying Hydrogen Populations in Liquid Mixtures Using H NMR Relaxometry.

The fractions of hydrogen populations in various liquid mixtures, including liquid drug products, were quantified using time-domain H NMR relaxometry. Different hydrogens in a liquid mixture have different H transverse relaxation rates (H), forming the basis for quantification. For drug products that contain two dominant ingredients (the solvent and the solute, with or without minor ingredients), H NMR relaxometry can quantify the two ingredients in the form of hydrogen population fractions within 1 min.

Metal-π Interaction-Enhanced Electrochemiluminescence via U-Shaped Schiff Base Luminophores for Ultrasensitive Clindamycin Detection.

The advancement of electrochemiluminescence (ECL) sensing has been increasingly restricted by the lack of rationally designed luminophores that simultaneously support efficient charge transfer, excited-state stability, and catalytic amplification. Herein, we report a Fe(II)-coordinated U-shaped Schiff base luminophore (Fe-PDLILUM) that achieves significantly enhanced ECL via synergistic metal-π interactions and topological rigidification. This luminophore is synthesized through imine-bridged conjugation between isoluminol and 1,10-phenanthroline-2,9-dicarboxaldehyde, forming an extended π-delocalized framework that promotes intramolecular charge transport and suppresses nonradiative decay.

Poly-Arginine Tails and Helical Segments of Natural Antimicrobial Peptides Display Concerted Action at Membranes for Enhanced Antimicrobial Effects.

Sequence motifs or patterns found in natural antimicrobial peptides (AMPs) have a great impact on their microbicidal activities. Here, through database inquiries and biological assays, we explore the enhanced antibacterial function associated with poly arginine (poly-R) motifs that typically occur as 3-5 concatenated R residues in many natural AMPs. Using a suite of biophysical techniques, we explore the structural consequences of a C-terminal poly-R motif at membranes and correlate our findings with the functional assays.

Biocompatible Mesoporous Materials for Bone Therapy.

As global population aging intensifies, bone-related diseases have become a significant public health challenge, necessitating the development of efficient and precise bone repair strategies. Biocompatible mesoporous materials (BMMs), characterized by their high specific surface area, tunable pore size, multidimensional functionalization potential, and excellent biocompatibility, have demonstrated revolutionary application prospects in treating bone-related diseases. This review systematically summarizes the latest research progress and application mechanisms of BMMs (e.

Synergistic effects of melatonin and chitosan in alleviating drought stress in saffron: (Crocus sativus) insights into plant growth and biochemical responses.

Saffron ( L.) is recognized as a strategic crop with high economic, nutritional, and cultural value in Iran; however, in recent years, its yield has significantly declined due to climate change, particularly drought stress. This study was conducted to evaluate the combined effects of drought stress at three field capacity (FC) levels (100%, 70%, and 40%), melatonin (100, 200, and 400 mg/L), and chitosan (100, 150, and 200 mg/L) on saffron performance over two years.

Age-dependent variations of amino acid metabolism in pigs and correlation with gut microbiota.

Background: Understanding the amino acid metabolic characteristics in the intestines and liver of pigs is critically important for nutritional interventions aimed at improving nitrogen utilization efficiency.

Objectives: This study explored age-dependent variations in amino acid metabolism within the liver and intestinal tissues of growing-finishing pigs.

Methods: Fifty boars (Duroc × Landrace × Large White, 36.

A Randomized, Open-Label, Single-Dose, Parallel-Group Bioequivalence Study of Ferric Carboxymaltose Injection Under Fasting Conditions in Chinese Adult Subjects With Iron Deficiency Anemia.

The objectives of this study were to compare the pharmacokinetics and safety profiles of the test (T) preparation (Ferric carboxymaltose injection, BrightGene Bio-Medical Technology Co. Ltd.) and reference (R) preparation (Ferinject, Vifor France) after intravenous injection in Chinese adult subjects with iron deficiency anemia (IDA) under fasting conditions.

Mapping Alzheimer's disease pathology using free water through integrated analysis of plasma biomarkers, microstructural DTI metrics, and macrostructural MRI measures.

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) and tau pathologies that drive neuroinflammation and neurodegeneration. Free water (FW), a diffusion tensor imaging (DTI) metric reflecting extracellular fluid changes, has emerged as a sensitive marker of neuroinflammation. This study examined the role of FW in AD and its associations with plasma biomarkers, brain structural measures, and cognitive decline.

Construction of Fused-Bridged Tricycles by Molecular Reorganization Involving Prins Cyclization/Dicycloexpansion.

The development of efficient methods for constructing structurally complex and diverse polycyclic carbon frameworks remains in high demand for the synthesis of pharmaceuticals and bioactive natural products. One such method lies in engineered one-step molecular reorganization through the cascade cyclization/cycloexpansion of rationally designed precursors with interconnected small-ring systems. Here, we have strategically designed and developed a synthetically valuable method to construct fused-bridged tricyclic systems through cascade Prins cyclization/dicycloexpansion of substrates with a cycloalkylidene (CAD) tethered to a cycloketones.

Engineering Energy Dissipation Pathway via Topological Design: Toward Tunable Macroscopic Mechanical Performances of Dynamic Polymer Networks.

The incorporation of multiple supramolecular interactions as sacrificial bonds for energy dissipation has emerged as a powerful strategy to enhance the mechanical properties of elastomeric materials. However, precise control over energy dissipation pathways remains challenging, primarily due to the difficulty in selectively activating specific interactions on demand. Herein, we present an orthogonal self-assembly strategy that integrates host-guest recognition and metal-coordination to tailor energy dissipation mechanisms.

Plasmon Resonance Energy Transfer for Molecular-Scale Tracking Receptor Dimerization and Apoptosis at the Single-Cell Level.

Plasmon resonance energy transfer (PRET) faces critical challenges in achieving precise molecular-scale distance control and non-perturbative operation within single live-cell environments, e.g., the inability to dynamically tune the donor-acceptor distance () at the single molecular dipole level.

Surface-Engineered Molybdenum Oxide with Cucurbit[6]uril for Enhanced Nitrogen Reduction Electrocatalysis.

Electrocatalytic nitrogen reduction (NRR) offers a sustainable pathway for ammonia (NH) production but is challenged by the low solubility of N in aqueous electrolytes, the high energy barrier of N activation, and the competing hydrogen evolution reaction (HER). Herein, cucurbit[6]uril (CB[6]) is immobilized onto the surface of molybdenum oxide (CB[6]@MoO). The CB[6]@MoO catalyst exhibits a high NH production rate of 27.

Universal NIR-II-Emitting Unimolecular Micelles with Tailorable Pharmacokinetic and Optical Properties for Adaptive Imaging.

π-Conjugated fluorophores show great potential for NIR-II bio-imaging owing to their superior brightness and photostability, yet their clinical translation has been hindered by suboptimal pharmacokinetics. To address this issue, a strategy is developed to tailor the in vivo behavior of π-conjugate fluorophores by breaking π-π stacking in polymer brush-engineered unimolecular micelles. This approach marks a significant shift from traditional methods of tuning micelles, which rely on varying the hydrophilic-to-hydrophobic ratios and are often ineffective for π-conjugated systems due to the dominance of π-π interactions.

Plasma tau biomarkers for biological staging of Alzheimer's disease.

A blood biomarker-based staging system for Alzheimer's disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides.

Evaluation of variability in applicator position and organs at risk dose in fractionated intracavitary brachytherapy for cervical cancer.

Background: Cervical cancer remains a major cause of mortality in low- and middle-income countries (LMICs). Intracavitary brachytherapy (ICBT) is critical for curative radiotherapy; however, inter-fractional variability in applicator positioning may compromise treatment reproducibility and organ-at-risk (OAR) sparing.

Objective: This study assessed inter-fractional applicator positional stability and its dosimetric impact on OARs during fractionated ICBT for cervical cancer.

rGO/Polypyrrole-modified bioelectrode reshapes microbial communities for enhanced energy-recovering denitrification in carbon-limited wastewater.

A denitrifying bio-electrochemical system (BES) with reduced graphene oxide/polypyrrole (rGO/PPy)-modified biocathodes was explored to achieve near-complete nitrate removal at low carbon-to-nitrogen (C/N) ratios (1, 3, and 5). Mechanistic investigations indicated that the rGO/PPy scaffold provided high surface area microbial anchoring sites and mediated efficient electron shuttling between the electrode and biofilm. The conductive 3D rGO/PPy network facilitated direct extracellular electron transfer, eliminating the need for organic carbon supplementation while achieving a maximum power density of 8.

Opportunities in proximity modulation: Bridging academia and industry.

In the past decade, exciting therapeutic strategies to harness the ubiquitin-proteasome system (UPS) for degradation of target proteins have emerged. Proximity-inducing modalities are at the center of these strategies and act by modulating protein-protein interactions. While we are still learning to harvest this approach, it holds tremendous promise for developing treatments for hitherto undruggable proteins.

Microflow LC-MS/MS reveals platform-specific post-translational modification signatures in recombinant adeno-associated virus capsids linked to enhanced potency and stability: A quality control framework for gene therapy.

Recombinant adeno-associated viruses (rAAVs) are pivotal gene therapy vectors due to their safety and stable transduction, yet comprehensive characterization of capsid post-translational modifications (PTMs)-critical for potency, immunogenicity, and manufacturing consistency-remains limited across production platforms. This study employs microflow LC-MS/MS coupled with electron-activated dissociation (EAD) to analyze PTMs in clinically relevant rAAV5 and rAAV9 serotypes produced via mammalian (HEK293) and insect (Sf9) cells, with parallel cellular-level evaluation of vector potency and infectivity, conducted under matched purity and capsid thermal stability conditions to isolate PTM-specific effects. Intact mass analysis revealed conserved N-terminal acetylation in VP1/VP3 across both platforms, while PTM profiling identified six distinct modification types, including deamidation, oxidation, and phosphorylation, with Sf9-derived vectors exhibiting 14 % more PTMs than HEK293-produced counterparts.

Targeted ROS Scavenging for Disease Therapies Using Nanomaterials.

Reactive oxygen species (ROS) are essential by-products of cellular metabolism and serve as key mediators in cell signaling and homeostasis. Excessive ROS production is associated with cellular damage and various diseases. Therefore, targeted ROS scavenging may enhance therapeutic efficacy and minimize side effects.

Synthesis of calcium oxide and antimicrobial activity enhancement of chitosan bio-composite films: An active packaging material.

The incorporation of antimicrobial agents into renewable polymers has significant potential to develop sustainable materials for active packaging, addressing perishable food waste and environmental issues. Calcium oxide (CaO) particles were synthesized as an alternative antimicrobial agent using a co-precipitation technique and calcination at 650 °C for 1 h. The effect of synthesis stirring times (60, 90, and 120 min) on antimicrobial activity was analyzed.

Injectable Antimicrobial Quaternary Chitosan Salt/Tannic Acid as a Delivery Platform for Enhanced Cranial Bone Regeneration via the Synergy of BMP-2 and VEGF.

Treating large, irregularly shaped bone defects continues to be a major challenge in clinical practice. In this work, an innovative injectable antimicrobial delivery platform is introduced. The therapeutic system leverages the combination of quaternary chitosan salt (QCS) and tannic acid (TA), synergistically supplemented with BMP-2 and VEGF, to enhance the regenerative efficacy.

Strontium/magnesium-doped coralline hydroxyapatite for bone regeneration.

The biocompatibility, osteoconductivity and porous structure of coral make it a popular material for bone regeneration. However, coral mismatches host bone degradation rates and lacks osteoinductivity. No prior research has investigated the physicochemical properties of strontium-doped coralline hydroxyapatite (Sr-CHA), magnesium-doped (Mg-CHA) and strontium- and magnesium-co-doped (Sr-Mg-CHA), especially their osteogenic mechanisms.

Cancer-induced nerve injury promotes resistance to anti-PD-1 therapy.

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer.