Self-Oxygenating PROTAC Microneedle for Spatiotemporally-Confined Protein Degradation and Enhanced Glioblastoma Therapy.

Glioblastoma (GBM) is the most aggressive subtype of primary brain tumors, which marginally respond to standard chemotherapy due to the blood-brain barrier (BBB) and the low tumor specificity of the therapeutics. Herein, a double-layered microneedle (MN) patch is rationally engineered by integrating acid and light dual-activatable PROteolysis TArgeting Chimera (PROTAC) nanoparticles and self-oxygenating BSA-MnO (BM) nanoparticles for GBM treatment. The MN is administrated at the tumor site to locally deliver the PROTAC prodrug and BM nanoparticles.

Fungal evasion of immunity involves blocking the cathepsin-mediated cleavage maturation of the danger-sensing protease.

Entomopathogenic fungi play a critical role in regulating insect populations, and representative species from the and genera have been developed as eco-friendly biocontrol agents for managing agricultural insect pests. Relative to the advances in understanding antifungal immune responses in , knowledge of how fungi evade insect immune defenses remains limited. In this study, we report the identification and characterization of a virulence-required effector Fkp1 in .

From intercropping to monocropping: The effects of Pseudomonas strain to facilitate nutrient efficiency in peanut and soil.

As an oilseed crop, the yield and quality of peanuts are severely constrained by nutrient deficiencies, particularly in calcareous soils in northern China. Maize-peanut intercropping is an effective strategy to enhance mineral nutrient efficiency in peanuts via plant-microbe interaction, but the underlying mechanisms remain elusive. Here, we conducted experiments using a Pseudomonas strain (Pse.

Catechin promotes the germination of Pistacia chinensis seeds via GA biosynthesis.

Background And Aims: Chinese pistachio (Pistacia chinensis), an important horticultural plant species, holds great ornamental value with beautiful leaves and fruits. Seedling propagation of this tree species is restricted by its erratic seed germination; however, the germination mechanism is ambiguous. The aim of this study was to determine the germination mechanism from a novel perspective based on the multi-omics data.

PROTAC Prodrug-Integrated Nanosensitizer for Potentiating Radiation Therapy of Cancer.

Radiation therapy (RT) is one of the primary options for clinical cancer therapy, in particular advanced head and neck squamous cell carcinoma (HNSCC). Herein, the crucial role of bromodomain-containing protein 4 (BRD4)-RAD51 associated protein 1 (RAD51AP1) axis in sensitizing RT of HNSCC is revealed. A versatile nanosensitizer (RPB7H) is thus innovatively engineered by integrating a PROteolysis TArgeting Chimeras (PROTAC) prodrug (BPA771) and hafnium dioxide (HfO) nanoparticles to downregulate BRD4-RAD51AP1 pathway and sensitize HNSCC tumor to RT.

Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for β-glucans.

The tactics used by animal pathogens to combat host immunity are largely unclear. Here, we report the depiction of the virulence-required effector Tge1 deployed by the entomopathogen Metarhizium robertsii to suppress Drosophila antifungal immunity. Tge1 can target both GNBP3 and GNBP-like 3 (GL3), and the latter can bind to β-glucans like GNBP3, whereas the glucan binding by both receptors can be attenuated by Tge1.

Immune modulation of gut microbiota and its metabolites in chronic hepatitis B.

The gut microbiota is a diverse ecosystem consisting of 100 trillion microbiomes. The interaction between the host's gut and distal organs profoundly impacts various functions such as metabolism, immunity, neurology, and nutrition within the human body. The liver, as the primary immune organ, plays a crucial role in maintaining immune homeostasis by receiving a significant influx of gut-derived components and toxins.

Lyophilization process optimization and molecular dynamics simulation of mRNA-LNPs for SARS-CoV-2 vaccine.

Some studies have shown that lyophilization significantly improves the stability of mRNA-LNPs and enables long-term storage at 2-8 °C. However, there is little research on the lyophilization process of mRNA-lipid nanoparticles (LNPs). Most previous studies have used empirical lyophilization with only a single lyoprotectant, resulting in low lyophilization efficiency, often requiring 40-100 h.

Efficacy, safety, and tolerability of antimicrobial agents for complicated intra-abdominal infection: a systematic review and network meta-analysis.

Background: Which antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted.

Methods: We systematically searched four major electronic databases from their inception through October 2022.

Preparation, Characterization and ex vivo Skin Permeability Evaluation of Type I Collagen-Loaded Liposomes.

Purpose: In the present study, we prepared collagen liposomes with the addition of polyol, which is expected to not only increase the solubility of collagen but also improve skin penetration.

Methods: Collagen liposomes were prepared by the film dispersion method, and their characteristics, integrity and biosafety were evaluated by Fourier transform infrared spectroscopy (FTIR), UV-VIS spectroscopy, polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscope (TEM). The transdermal absorption of collagen and collagen liposomes were tested by an ex vivo horizontal Valia-Chien diffusion cell system.

The relationship between serum albumin and prostate-specific antigen: A analysis of the National Health and Nutrition Examination Survey, 2003-2010.

Background: Previous studies have shown that serum albumin is associated with prostate cancer (PCa), but not with prostate-specific antigen (PSA) levels in populations without PCa history. Therefore, we analyzed secondary data provided by the National Health and Nutrition Examination Survey (NHANES) (2003-2010).

Methods: In total, 5,469 participants were selected from the NHANES database (2003-2010).

Cost-effectiveness analysis of ceftazidime-avibactam as definitive treatment for treatment of carbapenem-resistant bloodstream infection.

Background: Ceftazidime-avibactam (CAZ-AVI) is a novel antibiotic that has been confirmed in the United States and China for use in patients with carbapenem-resistant (CRKP) bloodstream infection (BSI). However, the cost-effectiveness of CAZ-AVI is unknown in China. This study aimed to evaluate the cost-effectiveness of CAZ-AVI compared to polymyxin B (PMB) monotherapy or PMB-based therapy for the treatment of CRKP BSI from the Chinese healthcare perspective.

Safety and Efficacy of Paxlovid Against Omicron Variants of Coronavirus Disease 2019 in Elderly Patients.

Introduction: Elderly patients are the most affected and vulnerable to COVID-19 and effective therapeutic interventions are urgently required. We clarified the safety and efficacy of Paxlovid in the treatment of elderly patients with coronavirus disease 2019 (COVID-19).

Methods: Patients aged over 60 years and with mild to moderate COVID-19 were admitted to the Zhongshan Hospital MinHang MeiLong Branch, Fudan University and received either Paxlovid treatment or only conventional therapy, between April 1 and May 31, 2022.

An integrative pan-cancer analysis revealing the difference in small ring finger family of SCF E3 ubiquitin ligases.

Background: The SCF (Skp1-cullin-F-box proteins) complex is the largest family of E3 ubiquitin ligases that mediate multiple specific substrate proteins degradation. Two ring-finger family members RBX1/ROC1 and RBX2/RNF7/SAG are small molecular proteins necessary for ubiquitin ligation activity of the multimeric SCF complex. Accumulating evidence indicated the involvement of RBX proteins in the pathogenesis and development of cancers, but no research using pan-cancer analysis for evaluating their difference has been directed previously.

An inflammatory response-related gene signature associated with immune status and prognosis of acute myeloid leukemia.

Objective: To determine the prognostic significance of inflammatory response-associated genes in acute myeloid leukemia (AML).

Methods: Transcriptomic profiles and related clinical information of AML patients were acquired from a public database. To establish a multi-gene prognosis signature, we performed least absolute shrinkage and selection operator Cox analysis for the TCGA cohort and evaluated the ICGC cohort for verification.

Immune Landscape and Classification in Lung Adenocarcinoma Based on a Novel Cell Cycle Checkpoints Related Signature for Predicting Prognosis and Therapeutic Response.

Lung adenocarcinoma (LUAD) is one of the most common malignancies with the highest mortality globally, and it has a poor prognosis. Cell cycle checkpoints play a central role in the entire system of monitoring cell cycle processes, by regulating the signalling pathway of the cell cycle. Cell cycle checkpoints related genes (CCCRGs) have potential utility in predicting survival, and response to immunotherapies and chemotherapies.

Gene Region Association Analysis of Longitudinal Quantitative Traits Based on a Function-On-Function Regression Model.

In the process of growth and development in life, gene expressions that control quantitative traits will turn on or off with time. Studies of longitudinal traits are of great significance in revealing the genetic mechanism of biological development. With the development of ultra-high-density sequencing technology, the associated analysis has tremendous challenges to statistical methods.

Cationic liposomes co-deliver chemotherapeutics and siRNA for the treatment of breast cancer.

In order to improve the targeting efficiency and reduce anti-breast cancer therapeutic side effects, paclitaxel (PTX), crizotinib (CRI), and Bcl-xL siRNA were co-loaded in cationic liposomes (CTL), which exhibited a substantial enhanced permeability and retention effect (EPR effect) in breast cancer. CTL containing crizotinib and paclitaxel (CRI-PTX-CTL) had particle sizes of (138.63 ± 1.

Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation.

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins.

Co-delivery of F7 and crizotinib by thermosensitive liposome for breast cancer treatment.

In order to enhance the targeting efficiency and reduce the side effects and drug resistance, crizotinib (Cri) and F7 were co-loaded in a thermosensitive liposome (TSL) (F7-Cri-TSL), which showed enhanced permeability and retention in breast cancer model, as well as local controlled release by external hyperthermia. Cri is an inhibitor for cell proliferation and a promoter of apoptosis, by inhibiting the phosphorylation of intracellular ALK and c-Met, but its drug resistance limits its application. F7 is a novel drug candidate with significant resistance to cyclin-dependent kinase, but its use was restricted by its high toxicity.

Inductive Production of the Iron-Chelating 2-Pyridones Benefits the Producing Fungus To Compete for Diverse Niches.

Diverse 2-pyridone alkaloids have been identified with an array of biological and pharmaceutical activities, including the development of drugs. However, the biosynthetic regulation and chemical ecology of 2-pyridones remain largely elusive. Here, we report the inductive activation of the silent polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) () gene cluster for the biosynthesis of the tenellin-type 2-pyridones in the insect-pathogenic fungus Beauveria bassiana when cocultured with its natural competitor fungus Metarhizium robertsii.