The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation.

C-type lectin receptors (CLRs) are essential to execute host defense against fungal infection. Nevertheless, a comprehensive understanding of the molecular underpinnings of CLR signaling remains a work in progress. Here, we searched for yet-to-be-identified tyrosine-phosphorylated proteins in Dectin-1 signaling and linked the stress-response protein valosin containing protein (VCP)/p97 to Dectin-1 signaling.

Stealth strategies of Candida albicans to evade host immunity.

During opportunistic pathogenic episodes, Candida albicans employs classical strategies such as the yeast-to-hyphae transition and immunogenic masking. In this issue of Cell Host & Microbe, Luo et al. unveil that the effector protein Cmi1 can be translocated into host cells and targets TBK1, thereby negatively regulating the host's antifungal immune responses.

ATP-elicited Cation Fluxes Promote Volume-regulated Anion Channel LRRC8/VRAC Transport cGAMP for Antitumor Immunity.

The cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells' cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-β response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear.

The secretory effector Sce1 licenses fungal virulence by masking the immunogenic β-1,3-glucan and promoting apoptosis of the host cells.

deploys a variety of mechanisms such as morphological switch and elicitor release to promote virulence. However, the intricate interactions between the fungus and the host remain poorly understood, and a comprehensive inventory of fungal virulence factors has yet to be established. In this study, we identified a secretory effector protein Sce1, whose induction and secretion are associated with vagina-simulative conditions and chlamydospore formation.

Simulating the land use change effects on non-point source pollution in the Duliujian River Basin.

The uncertainty in the generation and formation of non-point source pollution makes it challenging to monitor and control this type of pollution. The SWAT model is frequently used to simulate non-point source pollution in watersheds and is mainly applied to natural watersheds that are less affected by human activities. This study focuses on the Duliujian River Basin (Xiqing section), which is characterized by a dense population and rapid urbanization.

Drug Repurposing of ACT001 to Discover Novel Promising Sulfide Prodrugs with Improved Safety and Potent Activity for Neutrophil-Mediated Antifungal Immunotherapy.

Neutrophil-mediated immunotherapy is a promising strategy for treating infection due to its potential in dealing with drug-resistant events. Our previous study found that ACT001 exhibited good antifungal immunotherapeutic activity by inhibiting PD-L1 expression in neutrophils, but its strong cytotoxicity and high BBB permeability hindered its antifungal application. To address these deficiencies, a series of novel sulfide derivatives were designed and synthesized based on a slow-release prodrug strategy.

Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis.

Introduction: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear.

Methods: We enrolled ABPA patients, asthma patients and healthy controls.

Northern Shanghai Study II: systematic assessment and management of early organ damage and its role in preventing and reducing cardiovascular risk-protocol of a prospective study.

Introduction: Cardiovascular diseases are the leading cause of death and disease burden in China. However, there is a lack of prospective cohort studies suitable for evaluating early organ damage and its role in preventing and reducing cardiovascular risk among Chinese residents. This study intends to establish the first database based on the phenotypes of all early structural and functional damage of cardiovascular organs in Chinese population.

The therapeutic effect of wine-processed Corni Fructus on chronic renal failure in rats through the interference with the LPS/IL-1-mediated inhibition of RXR function.

Ethnopharmacological Relevance: Corni Fructus, derived from the fruit of Cornus officinalis Sieb. et Zucc, is a widely utilized traditional Chinese medicine (TCM) with established efficacy in the treatment of diverse chronic kidney diseases. Crude Corni Fructus (CCF) and wine-processed Corni Fructus (WCF) are the main processed forms of Corni Fructus.

The bioavailability enhancement and insight into the action mechanism of poorly soluble natural compounds from co-crystals preparation: Oridonin as an example.

Background: Natural bioactive molecules are important sources for the development of new drugs. However, most of them were limited in clinical applications due to their low aqueous solubility and bioavailability. Oridonin (ORI) is a powerful anticancer compound with above characteristics.

C-type lectin receptor 2d forms homodimers and heterodimers with TLR2 to negatively regulate IRF5-mediated antifungal immunity.

Dimerization of C-type lectin receptors (CLRs) or Toll-like receptors (TLRs) can alter their ligand binding ability, thereby modulating immune responses. However, the possibilities and roles of dimerization between CLRs and TLRs remain unclear. Here we show that C-type lectin receptor-2d (CLEC2D) forms homodimers, as well as heterodimers with TLR2.

STING negatively regulates antifungal immunity.

During viral infections, stimulator of interferon genes (STING) exerts a positive protective immune response. Chen et al. now shed light on the distinct role of STING in fungal infections.

Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis.

Background: Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.

Integrated metabolomics, network pharmacology, and molecular docking to reveal the mechanisms of Isodon excisoides against drug-induced liver injury.

Isodon excisoides (Y.Z.Sun ex C.

Study on mechanism of hepatoprotective effect of Chrysanthemum morifolium Ramat. based on metabolomics with network analysis and network pharmacology.

Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear.

An Efficient Federated Learning Framework for Machinery Fault Diagnosis With Improved Model Aggregation and Local Model Training.

Due to device operating environment limitations and data privacy protection, it is frequently difficult to obtain sufficient high-quality labeled data from devices, resulting in an insufficient generalization ability of fault diagnosis model. Therefore, a high-performance federated learning framework is proposed in this work, which makes improvements in the procedure of model aggregation and local model training. In the model aggregation of central server, an optimization aggregation strategy in which forgetting Kalman filter (FKF) is combined with cubic exponential smoothing (CES) is proposed to improve the efficiency of federated learning.

An integrated strategy to explore the wine-processed mechanism of Corni Fructus on chronic renal failure based on metabolomics, network analysis and bioinformatics approaches.

Objectives: Corni Fructus is one of the most famous traditional Chinese medicines (TCMs) for the treatment of various chronic kidney diseases. Wine-processed Corni Fructus (WCF) is the main processed form of Crude Corni Fructus (CCF). In this study, potential mechanisms of action of CCF and WCF on chronic renal failure (CRF) model were developed to explore wine-processed mechanism of Corni Fructus.

Screening and Capability Assessment of Tyrosinase Inhibitors in Isodon excisoides by Ultrafiltration Coupled with UHPLC-Q-TOF-MS and Molecular Docking Technology.

Tyrosinase inhibitors can alleviate the harm to the liver caused by tyrosinase. How to effectively screen out natural tyrosinase inhibitors becomes a focus. In this study, Isodon excisoides was first extracted with the ultrasound optimized by response surface methodology.

PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow.

Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 on neutrophil-mediated antifungal immunity remains wholly unknown. Here, we show that the expression of PD-L1 on murine and human neutrophils was upregulated upon the engagement of C-type lectin receptor Dectin-1 with its ligand β-glucans, exposed on fungal pathogen Candida albicans yeast.

Novel insight into the mechanism underlying synergistic cytotoxicity from two components in 5-Fluorouracil-phenylalanine co-crystal based on cell metabolomics.

Co-crystallization of active pharmaceutical ingredients (API) with co-formers can induce synergistic effects on cytotoxicity; however, the underlying mechanism is unclear. Here, cell metabolomics was used to gain insight into the mechanisms of synergistic effect from API and co-former in co-crystal. The 5-Fluorouracil-phenylalanine co-crystal system was selected as the model owing to the apparent difference of cytotoxicity occurring between co-crystal and physical mixture of two components (PM).

Inhibition of myeloid-derived suppressor cell arginase-1 production enhances T-cell-based immunotherapy against Cryptococcus neoformans infection.

Cryptococcosis is a potentially lethal disease that is primarily caused by the fungus Cryptococcus neoformans, treatment options for cryptococcosis are limited. Here, we show glucuronoxylomannan, the major polysaccharide component of C. neoformans, induces the recruitment of neutrophilic myeloid-derived suppressor cells in mice and patients with cryptococcosis.