ROS-responsive resiquimod prodrug nanoparticles for macrophage reprogramming and enhanced immune checkpoint inhibitor therapy in bladder cancer.

Bladder cancer remains a formidable challenge, especially for patients who fail to respond adequately to immune checkpoint inhibitors (ICIs). The suboptimal efficacy of current treatments underscores an urgent need for more effective immunomodulatory strategies. Here, we propose a ROS-responsive resiquimod (R848) prodrug (R-P) that improves drug delivery and reshapes the immunosuppressive tumor microenvironment.

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).

The Impact of miR-455-5p Modulation on Enhancing Tendon-Bone Interface Healing and Macrophage Polarization Following Anterior Cruciate Ligament Reconstruction.

MicroRNAs (miRNAs) have emerged as key regulators in physiological and pathological processes, including tendon-bone healing after anterior cruciate ligament reconstruction (ACLR). This study identifies the upregulation of miR-455-5p in tendon-bone interface tissues during early postoperative periods. Using a mouse ACLR model, we explored the impact of miR-455-5p inhibition on macrophage polarization and tendon-bone healing.

Anti-inflammatory and hepatoprotective effects of galactose-rich heteropolysaccharides from Laoshan green tea and its physicochemical properties.

The extraction conditions of Laoshan green tea extracts were optimised by response surface method. , the MDA, NO, TNF-α, and IL-6 levels were significantly inhibited and SOD level was increased after Laoshan green tea polysaccharides (GTPS) administration in RAW264.7 cells induced by LPS.

Neutralizing antibody levels as a key factor in determining the immunogenic efficacy of the novel PEDV alpha coronavirus vaccine.

Porcine epidemic diarrhea virus (PEDV) causes significant global agricultural losses. Despite commercial inactivated and live attenuated vaccines, persistent outbreaks underscore the need for more effective solutions. Here, we isolated a novel Chinese PEDV variant, PEDV ShXXY2-2023, with amino acid substitutions in key neutralizing epitopes (N-terminal domain, receptor-binding domain, and CO-26K equivalent epitope) compared to vaccine strains.

Cascade Catalytic Nanozymes Induce Tumor Ca Overload and Ferroptosis by Reducing Energy Supply and Amplifying Oxidative Stress.

Nanozyme-mediated nanocatalytic therapy, by mimicking the activity of redox enzymes, generates highly toxic reactive oxygen species (ROS) within tumor cells, thereby opening a pathway for tumor-specific therapy. However, achieving satisfactory therapeutic outcomes with nanozymes remains challenging due to the inherent complexity of the tumor microenvironment (TME). In this context, we designed a two-dimensional layered double hydroxide (LDH) nanozyme loaded with Au nanoparticles, while incorporating bioactive Ca and Fe ions (denoted as MgCaFe-LDH@Au NSs) to target the specific needs of the TME.

Single-Cell and Spatial Transcriptomics Explore Purine Metabolism-Related Prognostic Risk Model and Tumor Immune Microenvironment Modulation in Ovarian Cancer.

Ovarian cancer (OC) ranks as the second leading cause of gynecological cancer-related deaths in women globally. Single-cell and spatial transcriptomics could precisely describe the heterogeneity of OC that affect the clinical treatment. Single-cell sequencing and spatial transcriptomics information were from different public datasets.

Thermosensitive Resiquimod-Loaded Lipid Nanoparticles Promote the Polarization of Tumor-Associated Macrophages to Enhance Bladder Cancer Immunotherapy.

Bladder cancer is a common malignant tumor of the urinary system and is associated with high morbidity, recurrence, and mortality rates. Immunotherapy with immune checkpoint inhibitors has shown great therapeutic outcomes and safety in bladder cancer. Immune checkpoint inhibitors have also been approved as first- and second-line drugs for the treatment of locally advanced or metastatic bladder cancer.

CRISPR mutant rapid identification in : RNA-Seq functional profiling and breeding technology application.

Introduction: Traditional rapeseed breeding is inefficient and imprecise. CRISPR genome editing offers a precise alternative for trait improvement. Here, we edited the gene in elite rapeseed cultivar ZS11 to study its role in floral organ abcission and enable rapid trait transfer to elite lines.

Fluroxypyr Inhibits Maize Growth by Disturbing the Diversity of the Endophytic Bacterial Communities in Maize Roots.

Fluroxypyr (4-amino-3,5-dichloro-6-fluoro-2-pyridyloxyacetic acid) is a widely used herbicide sprayed on crops worldwide. The effects of fluroxypyr on maize growth and the soil microbial community structure have not been reported. In this study, the impacts of fluroxypyr on maize growth and the bacterial community structure in endophytes and rhizospheric/non-rhizospheric soils were evaluated.

TCF19/CDKN2A Regulates Glycolysis and Macrophage M2 Polarization for Osteosarcoma Progression.

Osteosarcoma (OS) is the most common malignant tumor of the bone. This paper aimed to explore the mechanism of macrophage polarization and glycolysis in OS. Gene expression microarray GSE42572 for OS was downloaded from the GEO database and validated in TCGA-SARC.

Antimicrobial Peptides: Classification, Mechanism, and Application in Plant Disease Resistance.

Antimicrobial peptides (AMPs) are a class of alkaline, small molecules found widely in nature. This article surveys the classifications of AMPs, delving into their modes of action and their role in controlling significant plant diseases caused by bacteria, viruses, and fungi. It also explores the prospects and challenges in this field, aiming to provide insights for enhancing crop disease resistance, ensuring food security, deepening the understanding of pathogen mechanisms, and protecting ecological balance.

Evaluating passive immunity in piglets from sows vaccinated with a PEDV S protein subunit vaccine.

Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus that causes severe diarrhea and high mortality in neonatal piglets. Current control measures, such as inactivated and live-attenuated vaccines, have limitations in providing complete protection. In this study, we evaluate the immunogenicity and protective efficacy of a PEDV S protein subunit vaccine compared to a traditional inactivated vaccine.

Responsive boronate ester lipid nanoparticles for enhanced delivery of veliparib and platinum (IV) prodrug in chemotherapy.

The chemotherapeutic effectiveness of breast cancer treatment is currently unsatisfactory due to inadequate drug delivery, suboptimal drug release, and drug inactivation. Herein, we present an innovative boronate ester lipid nanoformulation to improve the delivery of a platinum (IV) prodrug (Pt-C12) and veliparib (Veli), aiming to increase their therapeutic efficacy through a synergistic effect. We identify the optimal ratio of Pt-C12 to Veli for achieving synergy in vitro, followed by the encapsulation of Pt-C12 and Veli in lipid nanoparticles (NPs) incorporating responsive boronate ester lipids (LPC-PPE) to produce responsive lipid NPs (LPV NPs).

Genomic characterization and tissue tropism variations of two porcine delta coronavirus strains isolated in China.

The porcine delta coronavirus (PDCoV) is a member of the Delta coronavirus genus, which can lead to diarrhea, vomiting, and mortality in piglets. First detected in Hong Kong in 2012, PDCoV has since spread globally. In January 2024, two strains, CHN-ANHZ-2024 and CHN-JSSQ-2024, were isolated from diarrheal piglets in Anhui and Jiangsu provinces.

A General "Two-Lock" Strategy to Enhance Drug Loading and Lysosomal Escape in Intelligent Boronate Ester Polymer Nanoparticles for Improved Chemotherapy.

Boronate ester can be used to prepare intelligent polymer nanoparticles (NPs). However, the traditional boronate ester polymer NPs made of boronic acid and diols using a "single-lock" strategy (B-O NPs) exhibit low drug loading capacity (DLC) and insufficient lysosomal escape ability, resulting in limited antitumor efficacy. We develop a "two-lock" strategy that combines dodecanamine and boronic acid using boron-nitrogen (B ← N) coordination to enhance the formation of a boronate ester polymer.

Senolytic cocktail dasatinib and quercetin attenuates chronic high altitude hypoxia associated bone loss in mice.

Chronic high-altitude hypoxia (CHH) induces irreversible abnormalities in various organisms. Emerging evidence indicates that CHH markedly suppresses bone mass and bone strength. Targeting senescent cells and the consequent senescence-associated secretory phenotype (SASP) with senolytics is a recently developed novel therapy for multiple age-related diseases.

Multi-stage anoxic/oxic sequencing batch reactor realizes shortcut nitrogen removal for anaerobically co-digested liquor of municipal sludge and urban organic wastes.

Nitrogen removal from the combined anaerobic digestion dehydration liquor (CADDL) of municipal sludge and urban organic wastes is challenging due to high ammonium concentrations, low C/N ratio, and poor biodegradability. This study proposes a multi-stage anoxic/oxic (A/O) sequencing batch reactor with step feeding to realize partial nitrification and denitrification for shortcut nitrogen removal from the CADDL. We investigated the effects of external carbon source (acetate), dissolved oxygen (DO), A/O duration ratio, and A/O stage number on biological nitrogen removal.

Mechanism of the KIAA1429/KLF1/PD-L1 Axis in Regulating Immune Escape in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC), accounting for approximately 80% of lung cancer cases, remains the leading cause of cancer-related mortality. Immune evasion is a critical challenge in NSCLC, contributing to poor treatment outcomes. This study investigates the role of KIAA1429 in immune evasion, aiming to identify novel therapeutic targets and provide a theoretical basis for NSCLC treatment.

Electrostatic Assembly of Gold Nanoclusters in Reverse Emulsion Enabling Nanoassemblies with Tunable Structure and Size for Enhanced NIR-II Fluorescence Imaging.

The precise control of the assembly structure and size of gold nanoclusters (AuNCs) can potentially amplify their near-infrared II (NIR-II) fluorescence imaging and targeting properties. However, the conventional electrostatic assembly of AuNCs and charged molecules faces challenges in balancing the inherent electrostatic repulsions among charged units and regulating the diffusion of assembly units. These difficulties limit precise control over assembly size and structure, along with limited options for coassembled molecules, thereby restricting imaging properties and targeting capability.

The Marine-Origin Exopolysaccharide-Producing Bacteria HZ Inhibits Pb Uptake in Pakchoi ( L.) and Affects Rhizosphere Microbial Communities.

Exopolysaccharides (EPSs) produced by microorganisms play an important role in biotolerance and reducing heavy metal (HM) contamination by limiting the migration of HMs into plants. However, research on the application of EPS-producing marine bacteria for soil heavy metal remediation remains limited, particularly regarding their mechanisms of HM immobilization in soil and impact on plant growth. In this study, the EPS-producing marine bacterium HZ was investigated for its ability to immobilize Pb and produce EPSs in soil filtrate.

The gene regulates flowering time and leaf angle in .

The flowering time and plant architecture of were significantly associated with yield. In this study, we found that the /() gene regulated the flowering time and plant architecture of . However, the precise regulatory mechanism remains unclear.

Joint and interactive associations of body mass index and genetic factors with cardiovascular disease: a prospective study in UK Biobank.

Background: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF).

Associations of ambient air pollution and lifestyle with the risk of NAFLD: a population-based cohort study.

Background: Both ambient air pollution and lifestyle factors contribute to the incidence of non-alcoholic fatty liver disease (NAFLD), but previous studies usually focused on single-factor associations. We aimed to assess the joint associations of ambient air pollution and lifestyle with the NAFLD risk and investigate whether lifestyle modifies the association of air pollution with NAFLD risk.

Methods: A total of 417,025 participants from the UK Biobank were included in this study.

Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank.

Background: The association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes.

Methods: A total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses.