The key to 2,6-dichloro-1,4-benzoquinone reproductive toxicity and green tea detoxification: Covalent binding and competitive binding.

Halobenzoquinones (HBQs) are ubiquitous disinfection by-products (DBPs) in chlorinated drinking water with various health risks including reproductive toxicity, while the potential mechanisms are still unclear. Although green tea exhibits common detoxifying properties, its ability to mitigate the toxicity of HBQs still needs to be further deepened and explored. This study attempted to investigate the possible mechanism of the most common HBQ, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ) induced reproductive toxicity and elucidate the protective effect of green tea using a series of liquid chromatography-tandem mass spectrometry (LC-MS) approaches.

Split G-Quadruplex Programmed Recyclable AIE-Biosensor for Label-Free Detection of miRNA in Acute Kidney Injury.

We herein rationally designed a target-recyclable AIE-biosensor based on a split G-quadruplex for label-free detection of miRNA in acute kidney injury. Initially, the PG was in an "OFF" state, and the two split segments (G4-a and G4-b) of G4 were tethered at the two terminals of P1 and far away from each other due to the rigid duplex structure formed by the partially complementary intermediate sequences of P2 and P1, bringing MG with quenched fluorescence. In the presence of target, the 5'-PO P2 was displaced from PG probe and competitively hybridized with target, which led to G4-a and G4-b tending to form an intact intermolecular G-quadruplex, providing sites for MG intercalation, thus generating an activated "ON" fluorescence signal due to the restriction of intermolecular motion.

A Programmable Handheld Extrusion-Based Bioprinting Platform for In Situ Skin Wounds Dressing: Balance Mobility and Customizability.

Bioprinting technology plays a crucial role for constructing tissue substitutes. However, the mismatched scaffold shapes and the poor treatment timeliness limit its clinical translational application. In situ printing technology that prints bioregenerants directly inside patient's body can meet the needs of specific tissue repair.

Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia.

The blood-brain barrier (BBB) is a critical interface that maintains the central nervous system homeostasis by controlling the exchange of substances between the blood and the brain. Disruption of the BBB plays a vital role in the development of neuroinflammation and neurological dysfunction in sepsis, but the mechanisms by which the BBB becomes disrupted during sepsis are not well understood. Here, we induced endotoxemia, a major type of sepsis, in mice by intraperitoneal injection of lipopolysaccharide (LPS).

Quantitative dynamics of intracellular NMN by genetically encoded biosensor.

Nicotinamide mononucleotide (NMN) is the direct precursor and a major booster of NAD with increasing applications in NAD- and aging-related pathologies. However, measuring live cell NMN dynamics was not possible, leaving key questions in NMN uptake and intracellular regulation unanswered. Here we developed genetically encoded bioluminescent and fluorescent sensors to quantify subcellular NMN in live cells by engineering specific NMN-responsive protein scaffolds fused to luciferase and fluorescent proteins.

Preparation of a thioxoimidazolidin-linked sialoside BSA conjugate for the inhibition of influenza virus.

A novel thioxoimidazolidin-linked sialoside bovine serum albumin (WM-BSA) conjugate was synthesized and evaluated as an inhibitor of influenza virus hemagglutinin (HA) and neuraminidase (NA). The multivalent conjugate was prepared by the attachment of thioxoimidazolidin-sialoside monomer (WM) to BSA via adipate linker. Surface plasmon resonance analysis revealed that WM-BSA exhibited potent binding to recombinant influenza HA and NA proteins, with dissociation constants in the submicromolar range.

Development and experimental validation of computational methods for human antibody affinity enhancement.

High affinity is crucial for the efficacy and specificity of antibody. Due to involving high-throughput screens, biological experiments for antibody affinity maturation are time-consuming and have a low success rate. Precise computational-assisted antibody design promises to accelerate this process, but there is still a lack of effective computational methods capable of pinpointing beneficial mutations within the complementarity-determining region (CDR) of antibodies.

Improving regulatory T cell-based therapy: insights into post-translational modification regulation.

Regulatory T (Treg) cells are pivotal for maintaining immune homeostasis and play essential roles in various diseases, such as autoimmune diseases, graft-versus-host disease (GVHD), tumors, and infectious diseases. Treg cells exert suppressive function via distinct mechanisms, including inhibitory cytokines, granzyme or perforin-mediated cytolysis, metabolic disruption, and suppression of dendritic cells. Forkhead Box P3 (FOXP3), the characteristic transcription factor, is essential for Treg cell function and plasticity.

Myelin oligodendrocyte glycoprotein-associated transverse myelitis after SARS-CoV-2 infection: A case report.

Background: Cases of myelin oligodendrocyte glycoprotein (MOG) antibody-related disease have a history of coronavirus disease 2019 infection or its vaccination before disease onset. Severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection has been considered to be a trigger of central nervous system autoimmune diseases.

Case Summary: Here we report a 20-year male with MOG-associated transverse myelitis after a SARS-CoV-2 infection.

An In Silico Design of a Vaccine against All Serotypes of the Dengue Virus Based on Virtual Screening of B-Cell and T-Cell Epitopes.

Dengue virus poses a significant global health challenge, particularly in tropical and subtropical regions. Despite the urgent demand for vaccines in the control of the disease, the two approved vaccines, Dengvaxia and TV003/TV005, there are current questions regarding their effectiveness due to an increased risk of antibody-dependent enhancement (ADE) and reduced protection. These challenges have underscored the need for further development of improved vaccines for Dengue Virus.

Isolation and Characterization of Novel O157:H7 Phage SPEC13 as a Therapeutic Agent for Infections In Vitro and In Vivo.

O157:H7 is a recognized food-borne pathogen causing severe food poisoning at low doses. Bacteriophages (phages) are FDA-approved for use in food and are suggested as natural preservatives against specific pathogens. A novel phage must be identified and studied to develop a new natural preservative or antimicrobial agent against O157:H7.

Central Role of the Actomyosin Ring in Coordinating Cytokinesis Steps in Budding Yeast.

Eukaryotic cells must accurately transfer their genetic material and cellular components to their daughter cells. Initially, cells duplicate their chromosomes and subsequently segregate them toward the poles. The actomyosin ring, a crucial molecular machinery normally located in the middle of the cells and underneath the plasma membrane, then physically divides the cytoplasm and all components into two daughter cells, each ready to start a new cell cycle.

Anti-TNFR2 Antibody-Conjugated PLGA Nanoparticles for Targeted Delivery of Adriamycin in Mouse Colon Cancer.

High levels of tumor necrosis factor receptor type II (TNFR2) are preferentially expressed by immunosuppressive CD4Foxp3 regulatory T cells (T), especially those present in the tumor microenvironment, as initially reported by us. There is compelling evidence that targeting TNFR2 markedly enhances antitumor immune responses. Furthermore, a broad spectrum of human cancers also expresses TNFR2, while its expression by normal tissue is very limited.

Glutathione-responsive biodegradable nanohybrid for cancer photoacoustic imaging and gas-assisted photothermal therapy.

Photothermal therapy (PTT), particularly in the near-infrared-II (NIR-II) range, has attracted widespread attention over the past years. However, the accompanied inflammatory responses can result in undesirable side effects and contribute to treatment ineffectiveness. Herein, we introduced a novel biodegradable nanoplatform (CuS/HMON-PEG) capable of PTT and hydrogen sulfide (HS) generation, aimed at modulating inflammation for improved cancer treatment outcomes.

Structure of tetrameric forms of the serotonin-gated 5-HT3 receptor ion channel.

Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography.

Nanotherapeutic Approaches of Interleukin-3 to Clear the α-Synuclein Pathology in Mouse Models of Parkinson's Disease.

Astrocyte-microglia crosstalk is vital for neuronal survival and clearing aggregate accumulation in neurodegenerative diseases. While interleukin-3 (IL-3) has been reported to exert both protective and detrimental effects in neurodegenerative diseases, however, its role in α-synuclein pathology remains unclear. In this study, it is found that astrocytic IL-3 and microglial IL-3R are positively responsive to α-synuclein pathology in the brains of transgenic A53T Parkinson's disease (PD) mice and in an adeno-associated virus (AAV)-human α-synuclein (AAV-hα-Syn)-injected PD mouse model.

Unravelling biosynthesis and biodegradation potentials of microbial dark matters in hypersaline lakes.

Biosynthesis and biodegradation of microorganisms critically underpin the development of biotechnology, new drugs and therapies, and environmental remediation. However, most uncultured microbial species along with their metabolic capacities in extreme environments, remain obscured. Here we unravel the metabolic potential of microbial dark matters (MDMs) in four deep-inland hypersaline lakes in Xinjiang, China.

Population Pharmacokinetic-Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats.

(1) Background: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic-pharmacodynamic (PK-PD) model of reserpine in rats, linking to its impact on monoamines (MAs).

Cooperative insulation of regulatory domains by CTCF-dependent physical insulation and promoter competition.

The specificity of gene expression during development requires the insulation of regulatory domains to avoid inappropriate enhancer-gene interactions. In vertebrates, this insulator function is mostly attributed to clusters of CTCF sites located at topologically associating domain (TAD) boundaries. However, TAD boundaries allow some physical crosstalk across regulatory domains, which is at odds with the specific and precise expression of developmental genes.

Targeting post-stroke neuroinflammation with Salvianolic acid A: molecular mechanisms and preclinical evidence.

Salvianolic acid A (SalA), a bioactive compound extracted from Salvia miltiorrhiza, has garnered considerable interest for its potential in ameliorating the post-stroke neuroinflammation. This review delineates the possible molecular underpinnings of anti-inflammatory and neuroprotective roles of SalA, offering a comprehensive analysis of its therapeutic efficacy in preclinical studies of ischemic stroke. We explore the intricate interplay between post-stroke neuroinflammation and the modulatory effects of SalA on pro-inflammatory cytokines, inflammatory signaling pathways, the peripheral immune cell infiltration through blood-brain barrier disruption, and endothelial cell function.

A novel tumor theranostic strategy based on metabolic glycoengineering and disulfidptosis.

Traditional metabolic glycoengineering involves participation of a monofunctional unnatural monosaccharide. To broaden the application boundary of this powerful technique, a bifunctional molecule, AcManNSSN, is designed and applied for a tumor theranostic strategy in this work. The results from both cell and animal experiments show good tumor detection and tumor inhibition effects.