Pan-omics-based characterization and prediction of highly multidrug-adapted strains from an outbreak fungal species complex.

Strains from the species complex (CGSC) have caused the Pacific Northwest cryptococcosis outbreak, the largest cluster of life-threatening fungal infections in otherwise healthy human hosts known to date. In this study, we utilized a pan-phenome-based method to assess the fitness outcomes of CGSC strains under 31 stress conditions, providing a comprehensive overview of 2,821 phenotype-strain associations within this pathogenic clade. Phenotypic clustering analysis revealed a strong correlation between distinct types of stress phenotypes in a subset of CGSC strains, suggesting that shared determinants coordinate their adaptations to various stresses.

SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression.

The role of the gut microbiota in tumor, immunity, and immunotherapy.

In recent years, with the deepening understanding of the gut microbiota, it has been recognized to play a significant role in the development and progression of diseases. Particularly in gastrointestinal tumors, the gut microbiota influences tumor growth by dysbiosis, release of bacterial toxins, and modulation of host signaling pathways and immune status. Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment efficacy by enhancing immune cell responses.

Fungicide-tolerant persister formation during cryptococcal pulmonary infection.

Bacterial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to bactericides, have been studied extensively because of their clinical importance. In comparison, much less is known about the determinants underlying fungicide-tolerant fungal persister formation in vivo. Here, we report that during mouse lung infection, Cryptococcus neoformans forms persisters that are highly tolerant to amphotericin B (AmB), the standard of care for treating cryptococcosis.

Ferroptosis, autophagy, tumor and immunity.

Ferroptosis was first proposed in 2012, a new form of cell death. Autophagy plays a crucial role in cell clearance and maintaining homeostasis. Autophagy is involved in the initial step of ferroptosis under the action of histone elements such as NCOA4, RAB7A, and BECN1.

Confronting antifungal resistance, tolerance, and persistence: Advances in drug target discovery and delivery systems.

Human pathogenic fungi pose a serious threat to human health and safety. Unfortunately, the limited number of antifungal options is exacerbated by the continuous emergence of drug-resistant variants, leading to frequent drug treatment failures. Recent studies have also highlighted the clinical importance of other modes of fungal survival of antifungal treatment, including drug tolerance and persistence, pointing to the complexity of the fungal response to antifungal drugs.

A forkhead transcription factor contributes to the regulatory differences of pathogenicity in closely related fungal pathogens.

and its sister species are important human fungal pathogens. Despite their phylogenetically close relationship, these two pathogens are greatly different in their clinical characteristics. However, the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.

In Situ Blue-Light-Induced Photocurable and Weavable Hydrogel Filament.

A self-lubricating hydrogel filament was achieved by establishing an in situ photocuring system and using camphorquinone/diphenyl iodonium hexafluorophosphate (CQ/DPI) as the blue-light photoinitiators, acrylamide (AM) and ,-dimethylacrylamide (DMAA) as the monomers, polyethylene glycol diacrylate (PEGDA) as the cross-linker, and lecithin as the lipid lubricant. The blue-light photopolymerization efficiency and the photorheological properties of the hydrogel precursor were investigated by photodifferential scanning calorimetry and a photorheological system. With the increase of DMAA, the photopolymerization efficiency of the precursor improved, while the elasticity of poly(DMAA/AM) decreased accordingly.

Harpagide alleviate neuronal apoptosis and blood-brain barrier leakage by inhibiting TLR4/MyD88/NF-κB signaling pathway in Angiotensin II-induced microglial activation in vitro.

Angiotensin II, the effector peptide of the renin-angiotensin system, is not only a pivotal peptide implicated in the regulation of blood pressure but also a key mediator of the inflammatory processes that play an important role in the pathology of hypertension-related cSVD. Harpagide is the major bioactive constituent of Scrophulariae Radix widely used in traditional Chinese medicine for numerous diseases including hypertension. The present study aimed to investigate the effect of harpagide on Ang II-induced neuroinflammation and the potential mechanism.

Silencing long non‑coding RNA NEAT1 suppresses the tumorigenesis of infantile hemangioma by competitively binding miR‑33a‑5p to stimulate HIF1α/NF‑κB pathway.

Infantile hemangioma (IH) is one of the most common vascular tumors that occurs during childhood, but its pathogenesis is currently not completely understood. Even though lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays vital roles in tumorigenesis of malignant tumors, its roles in IH remain unclear. Therefore, we evaluate the function of lncRNA NEAT1 in IH.

Effects of high mobility group protein box 1 and toll like receptor 4 pathway on warts caused by human papillomavirus.

Accumulative evidence has demonstrated that inflammation has an important role in human papillomavirus (HPV) oncogenicity. However, the effects of high mobility group protein box 1 (HMGB1)-toll like receptor 4 (TLR4) signaling pathway associated inflammation on epidermal warts caused by HPV remain unclear. The present study investigated the HMGB1, TLR4 and nuclear factor-κB p65 expression in condyloma acuminatum (CA) and verruca vulgaris (VV).

Expression and significance of HMGB1, TLR4 and NF-κB p65 in human epidermal tumors.

Background: High mobility group protein box 1 (HMGB1) is a DNA binding protein located in nucleus. It is released into extracellular fluid where it acts as a novel proinflammatory cytokine which interacts with Toll like receptor 4 (TLR4) to activate nuclear factor-κB (NF-κB). This sequence of events is involved in tumor growth and progression.

[Predicting value of dynamic alteration of blood neutrophil/lymphocyte ratio on recurrence-free survival in patients with advanced colon cancer after operation and chemotherapy].

Objective: To evaluate whether neutrophil-lymphocyte ratio(NLR) predicts risk of recurrence in patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy.

Methods: A total of 149 patients with advanced colon cancer undergoing curative resection followed by adjuvant chemotherapy(FOLFOX6 protocol) were included. NLR was calculated preoperatively and before chemotherapy.