Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.

Invasive fungal infections (IFIs) have become prominent global health threats, escalating the burden on public health systems. The increasing occurrence of invasive fungal infections is due primarily to the extensive application of chemotherapy, immunosuppressive therapies, and broad-spectrum antifungal agents. At present, therapeutic practices utilize multiple categories of antifungal agents, such as azoles, polyenes, echinocandins, and pyrimidine analogs.

EPHA5 regulates antifungal innate immunity by phosphorylating EPHB2 and Dectin-1.

Invasive fungal infections (IFIs) have emerged as a significant health threat and cause approximately 3.75 million deaths per year globally. Understanding the detailed mechanism of the immune response to eliminate invasive fungal pathogens may help to provide new insights for the development of antifungal methods and drugs.

Antifungal immunity: advances in PRR recognition, adaptive responses, and immune-based therapies.

As a common disease in human life, fungal infection poses a serious threat to human life and health. Moreover, owing to the rapid development of the immune escape mechanisms of fungi and the emergence of new drug-resistant fungi, existing therapeutic drugs are no longer able to meet the treatment needs of patients. In particular, the World Health Organization (WHO) published the first Fungal Priority Pathogens List (FPPL) in 2022, further emphasizing that we need to pay more attention to invasive fungal infections.

Simultaneous Blockade of CD209 and CD209L by Monoclonal Antibody Does Not Provide Sufficient Protection Against Multiple Viral Infections In Vivo.

Many virus species, including Ebola virus, Marburg virus, SARS-CoV-2, dengue virus (DENV) and Zika virus (ZIKV), exploit CD209 and CD209L as alternative or attachment receptors for viral cis- or trans-infection. Thus, CD209 and CD209L may be critical targets for the development of therapeutic monoclonal blocking antibody drugs to disrupt the infection process caused by multiple viruses. Here, we produced a human chimeric monoclonal blocking antibody that simultaneously blocks CD209 and CD209L, namely 7-H7-B1.

MYO1F positions cGAS on the plasma membrane to ensure full and functional signaling.

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) detects viral or endogenous DNA, activating the innate immune response to infections and autoimmune diseases. Upon binding to double-stranded DNA, cGAS synthesizes 2'3' cGMP-AMP, which triggers type I interferon production. Besides its presence in the cytosol and nucleus, cGAS is found at the plasma membrane, although its significance remains unclear.

Research on failure mechanism of landslide with retaining-wall-like locked segment and instability prediction by inverse velocity method.

The locked segment is critical for determining the stability of locked segment-type landslides. Research indicates that the volume expansion point marks the transition from the secondary creep stage to the tertiary creep stage in a landslide's evolution, and also separates the stable crack growth stage from the unstable crack growth stage in the locked segment. Identifying the volume expansion point is essential for early warning and predicting locked segment-type landslides.

Extracellular bioreduction is the main Cr(VI) detoxification strategy of Bacillus sp. HL1.

Bacterium with high Cr(VI) detoxification capability belonged to the genus Bacillus have been largely explored, yet their reduction strategies are still in debate. Cr(VI) removal performance and mechanism of Bacillus sp. HL1 isolated from tailings a site was comprehensively investigated in this study.

Effects of three plant growth-promoting bacterial symbiosis with ryegrass for remediation of Cd, Pb, and Zn soil in a mining area.

The quality of soil containing heavy metals (HMs) around nonferrous metal mining areas is often not favorable for plant growth. Three types of plant growth promoting rhizobacteria (PGPR)-assisted ryegrass were examined here to treat Cd, Pb, and Zn contaminated soil collected from a nonferrous metal smelting facility. The effects of PGPR-assisted plants on soil quality, plant growth, and the migration and transformation of HMs were evaluated.

T-cell activation Rho GTPase-activating protein maintains intestinal homeostasis by regulating intestinal T helper cells differentiation through the gut microbiota.

Common variants of the T-cell activation Rho GTPase-activating protein (TAGAP) are associated with the susceptibility to human inflammatory bowel diseases (IBDs); however, the underlying mechanisms are still unknown. Here, we show that TAGAP deficiency or TAGAP expression downregulation caused by TAGAP gene polymorphism leads to decreased production of antimicrobial peptides (AMPs), such as reg3g, which subsequently causes dysregulation of the gut microbiota, which includes and strains. These two strains can polarize T helper cell differentiation in the gut, and aggravate systemic disease associated with the dextran sodium sulfate-induced (DSS) disease's phenotype in mice.

BTNL2 promotes colitis-associated tumorigenesis in mice by regulating IL-22 production.

Interleukin 22 (IL-22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL-22 production in the intestinal system is still unclear. Here, we present evidence that butyrophilin-like protein 2 (BTNL2) is required for colorectal IL-22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL-22.

Tumor-Derived Small Extracellular Vesicles Involved in Breast Cancer Progression and Drug Resistance.

Breast cancer is one of the most serious and terrifying threats to the health of women. Recent studies have demonstrated that interaction among cancer cells themselves and those with other cells, including immune cells, in a tumor microenvironment potentially and intrinsically regulate and determine cancer progression and metastasis. Small extracellular vesicles (sEVs), a type of lipid-bilayer particles derived from cells, with a size of less than 200 nm, are recognized as one form of important mediators in cell-to-cell communication.

SIPA1 Regulates LINC01615 to Promote Metastasis in Triple-Negative Breast Cancer.

Long non-coding RNAs (lncRNAs) are reported to play an important regulatory effect in carcinogenesis and malignancy. We found by high-throughput sequencing that LINC01615 is upregulated in breast cancer patients and reduces patients' overall survival. In vivo and in vitro experiments, we clarified that overexpression of LINC01615 can promote breast cancer cell metastasis ability.

Stress-strain and acoustic emission characteristics of cement-based materials used to simulate soft rock with fractures.

Instability failure in rock mass engineering is closely related to expansion of joint fissures. In this study, uniaxial compression tests and acoustic emission (AE) measurements were carried out simultaneously on specimens of soft rock-like material with different fracture angles and connectivity values to better understand their influence on the deformation and failure of the material. The stress-strain curve and AE signal of fractured soft rock-like material are similar to those of intact soft rock-like; specifically, they exhibit a compaction, elastic deformation, stable fracture development, and unstable fracture development.

Extracellular Vesicles Derived from SIPA1 Breast Cancer Cells Enhance Macrophage Infiltration and Cancer Metastasis through Myosin-9.

Tumour cell metastasis can be genetically regulated by proteins contained in cancer cell-derived extracellular vesicles (EVs) released to the tumour microenvironment. Here, we found that the number of infiltrated macrophages was positively correlated with the expression of signal-induced proliferation-associated 1 (SIPA1) in invasive breast ductal carcinoma tissues and MDA-MB-231 xenograft tumours. EVs derived from MDA-MB-231 cells (231-EVs) significantly enhanced macrophage migration, compared with that from -knockdown MDA-MB-231 cells (231/si-EVs) both in vitro and in vivo.

SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of , which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis.

Microbial community profiles in soils adjacent to mining and smelting areas: Contrasting potentially toxic metals and co-occurrence patterns.

Mining and smelting activities have introduced severe potentially toxic metals (PTMs) contamination into surrounding soil settings. Influences of PTMs on microbial diversity have been widely studied. However, variations of microbial communities, network structures and community functions in different levels of PTMs contaminated soils adjacent to mining and smelting aera are still poorly investigated.

Exosomal Thrombospondin-1 Disrupts the Integrity of Endothelial Intercellular Junctions to Facilitate Breast Cancer Cell Metastasis.

Transendothelial migration of malignant cells plays an essential role in tumor progression and metastasis. The present study revealed that treating human umbilical vein endothelial cells (HUVECs) with exosomes derived from metastatic breast cancer cells increased the number of cancer cells migrating through the endothelial cell layer and impaired the tube formation of HUVECs. Furthermore, the expression of intercellular junction proteins, including vascular endothelial cadherin (VE-cadherin) and zona occluden-1 (ZO-1), was reduced significantly in HUVECs treated with carcinoma-derived exosomes.

PVP-templated highly luminescent copper nanoclusters for sensing trinitrophenol and living cell imaging.

Copper nanoclusters (CuNCs) exhibit susceptibility to oxidation in the subnanometer size range. In this work, a facile and green protocol is reported for the successful synthesis of water soluble CuNCs, with poly(vinylpyrrolidone) as a template and ascorbic acid as a mild reducing agent. The as-prepared CuNCs exhibit a green fluorescence and high quantum yield (QY = 44.

Soluble Hyperbranched Porous Organic Polymers.

Soluble porous organic polymers (SPOPs) are currently the subject of extensive investigation due to the enhanced processability compared to insoluble counterparts. Here, a new concept for the construction of SPOPs is presented, which combines the unique topological structure of hyperbranched polymers with rigid building blocks. By using this facile, one-step strategy, a class of novel SPOPs which possess surface areas up to 646 m g have been synthesized.

[Studies on nano-particle sols of hydroxyaptite and titanium dioxide for haemo-compatibility].

A biological evaluation is conducted for two types of nano-particle sols, hydroxyaptite(HAP) and titanium dioxide(TiO2). The results show that HAP sol significnatly prolongs the bleeding time and coagulation time of mice as well as the prothrombin time(PT) and partial thromboplastin time(PTT) of rats while TiO2 sol exhibits no such effects. Neither HAP sol nor TiO2 sol instigated in-vitro hemolysis of rabbit erythrocyte.