Emerging opportunities and challenges in small molecule development for non-HSP90 chaperones.

Heat shock proteins (HSPs) are pivotal regulators of proteostasis, with their dysregulation implicated in cancer, neurodegeneration, and infectious diseases. Significant progress has been made in targeting HSP90, particularly in oncology, where inhibitors have demonstrated considerable therapeutic potential and validated HSP90 as a promising drug target. However, other HSP families remain relatively underexplored as drug targets despite their critical biological roles.

ATP6V0A4 as a novel prognostic biomarker and potential therapeutic target in oral squamous cell carcinoma.

Background: Increasing evidence indicates that the dysregulation of ATP6V0A4 is linked to aggressive behaviors in various types of cancer. Nevertheless, the exact role and molecular mechanisms of ATP6V0A4 in oral squamous cell carcinoma (OSCC) are not yet fully understood.

Methods: This study initially integrated TCGA and GEO databases for cross-platform differential gene screening.

HPD-Kit: a comprehensive toolkit for pathogen detection and analysis.

Introduction: Unbiased metagenomic sequencing (mNGS) is crucial for infectious disease diagnosis and epidemiological surveillance. However, its analysis requires specialized bioinformatics skills, creating barriers for clinicians. We developed HPD-Kit (Henbio Pathogen Detection Toolkit) with an integrated pathogen database to simplify pathogen detection and analysis for both human and animal pathogens.

Ubiquitin-specific protease 21 aggravates enterovirus 71 (EV71) infection by restricting Lys48-linked ubiquitination of EV71-2A protease.

EV71-encoded 2A protease (2A) plays an important regulatory role in EV71 infection and replication. EV71-2A can help the viral immune escape by inhibiting host proteins, thereby disrupting the host antiviral immune response. However, the mechanism by which 2A proteins are regulated in host cells remains largely unknown.

Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment.

Biliary tract cancer (BTC) has greatly influenced patient survival for years. Nowadays, immunotherapy represents a promising breakthrough and proteomics is one of powerful technologies in biomarker research. We collected plasma and tissue samples from 37 patients with advanced BTC and 92 proteins were analyzed by proximity extension assay (PEA).

Targeting Viperin prevents coxsackievirus B3-induced acute heart failure.

Coxsackievirus B3 (CVB3)-induced acute heart failure (AHF) is a common cause of cardiogenic death in young- and middle-aged people. However, the key molecular events linking CVB3 to AHF remain largely unknown, resulting in a lack of targeted therapy strategies thus far. Here, we unexpectedly found that Viperin deficiency does not promote CVB3 infection but protects mice from CVB3-induced AHF.

AI One-Click Processing-Assisted Nanozyme-Based Fluorescence Capillary Imprinted Sensor Array for Microvolume Rapid Discrimination Antidepressants.

The increasing global demand for antidepressants (ADs) has led to their widespread presence in wastewater and aquatic environments, posing risks to ecosystems and human health. In this study, a nanozyme fluorescence capillary imprinted sensor array combined with fluorescence mode and artificial intelligence (AI) one-click processing fluorescence image mode was developed for the rapid visual discrimination and quantification of five ADs (imipramine, citalopram, clomipramine, amitriptyline, and sertraline). Benefiting from the differential recognition of molecularly imprinted polymers with the high sensitivity of nanozyme, two imprinted polymers on the surface of nanozymes were prepared as two sensing units by the sol-gel method.

Design and Synthesis of 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid Derivatives as PP5 Inhibitors To Reverse Temozolomide Resistance in Glioblastoma Multiforme.

The serine/threonine phosphatase family is important in tumor progression and survival. Due to the high conserved catalytic domain, designing selective inhibitors is challenging. Herein, we obtained compound with 38-fold enhanced PP5 selectivity (PP2A/5 IC = 33.

Do patients with cN0 oral squamous cell carcinoma benefit from elective neck dissection? A large-scale population-based study.

Background: The neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END.

Specific Recognition and Adsorption of Volatile Organic Compounds by Using MIL-125-Based Porous Fluorescence Probe Material.

The severity of the volatile organic compounds (VOCs) issue calls for effective detection and management of VOC materials. Metal-organic frameworks (MOFs) are organic-inorganic hybrid crystals with promising prospects in luminescent sensing for VOC detection and identification. However, MOFs have limitations, including weak response signals and poor sensitivity towards VOCs, limiting their application to specific types of VOC gases.

Ceftazidime reduces cellular Skp2 to promote type-I interferon activity.

Skp2 plays multiple roles in malignant tumours. Here, we revealed that Skp2 negatively regulates type-I interferon (IFN-I)-mediated antiviral activity. We first noticed that Skp2 can promote virus infection in cells.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB.

Silica nanocarrier-mediated intracellular delivery of rapamycin promotes autophagy-mediated M2 macrophage polarization to regulate bone regeneration.

Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy.

Human serum-derived exosomes modulate macrophage inflammation to promote VCAM1-mediated angiogenesis and bone regeneration.

During exogenous bone-graft-mediated bone defect repair, macrophage inflammation dictates angiogenesis and bone regeneration. Exosomes from different human cells have shown macrophage immunomodulation-mediated bone regeneration potential. However, the effect of human serum-derived exosomes (serum-Exo) on macrophage immunomodulation-mediated angiogenesis during bone defect repair has not been investigated yet.

Methotrexate and Triptolide regulate Notch signaling pathway by targeting the Nedd4-Numb axis.

Methotrexate (MTX) is used to treat rheumatoid arthritis, acute leukemia, and psoriasis. MTX can cause certain side effects, such as myelosuppression, while the exact mechanism of myelosuppression caused by MTX is unknown. Notch signaling pathway has been considered to be essential to regulate hematopoietic stem cell (HSC) regeneration and homeostasis, thus contributing to bone marrow hematopoiesis.

Protein Phosphatase 5-Recruiting Chimeras for Accelerating Apoptosis-Signal-Regulated Kinase 1 Dephosphorylation with Antiproliferative Activity.

A normal phosphorylation state is essential for the function of proteins. Biased regulation frequently results in morbidity, especially for the hyperphosphorylation of oncoproteins. The hyperphosphorylation of ASK1 at Thr838 leads to a persistently high activity state, which accelerates the course of gastric cancer.

Is it necessary to remove bone-impacted teeth? A retrospective study.

Background: In clinical practice, it is risky to extract bone-impacted teeth and they're prone to a variety of complications, such as pathological fracture, adjacent tooth fracture, maxillary sinus perforation, and so on, making it difficult for clinicians to decide whether to extract them.

Purpose: In order to illustrate our opinions on the possibility of extracting full third molars (M3), 360 examples of complete third molars were analyzed in this study.

Materials And Method: We investigated 2189 patients, and 261 of them provided CBCT images of 360 teeth.

A decade of approved first-in-class small molecule orphan drugs: Achievements, challenges and perspectives.

In the past decade (2011-2020), there was a growing interest in the discovery and development of orphan drugs for the treatment of rare diseases. However, rare diseases only account for a population of 0.65‰-1‰ which usually occur with previously unknown biological mechanisms and lack of specific therapeutics, thus to increase the demands for the first-in-class (FIC) drugs with new biological targets or mechanisms.

Menthone inhibits type-I interferon signaling by promoting Tyk2 ubiquitination to relieve local inflammation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. RA development is mediated by the abnormal activation of multiple signaling pathways. Recent studies have revealed that type-I interferon (IFN-I) signaling plays an essential role in the occurrence and development of RA.

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis.

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown.

E3 ubiquitin ligase MID1 ubiquitinates and degrades type-I interferon receptor 2.

Type I interferon (IFN-I) is a common biological molecule used for the treatment of viral diseases. However, the clinical antiviral efficacy of IFN-I needs to be greatly improved. In this study, IFN-I receptor 2 (IFNAR2) was revealed to undergo degradation at the protein level in cells treated with IFN-I for long periods of time.

Overexpression of angiogenic factors and matrix metalloproteinases in the saliva of oral squamous cell carcinoma patients: potential non-invasive diagnostic and therapeutic biomarkers.

Backgrounds: Salivary biomarkers hold huge potential for the non-invasive diagnosis of oral squamous cell carcinoma. Angiogenic factors and matrix-metalloproteinases (MMPs) are highly expressed in OSCC tissue, but their expression patterns in the saliva are unknown. This study aimed to analyze the levels of angiogenic factors and MMPs in tumor tissue and saliva of OSCC patients.

Chordin-Like 1 Regulates Epithelial-to-Mesenchymal Transition and Metastasis the MAPK Signaling Pathway in Oral Squamous Cell Carcinoma.

Background: Accumulating evidence suggests that dysregulation of Chordin-like 1 (CHRDL1) is associated with malignant biological behaviors in multiple cancers. However, the exact function and molecular mechanism of CHRDL1 in oral squamous cell carcinoma (OSCC) remain unclear.

Methods: The expression levels of CHRDL1 in OSCC tissues and CAL27 cells were determined by RT-qPCR.

The Emerging Role of the Serine Incorporator Protein Family in Regulating Viral Infection.

Serine incorporator (SERINC) proteins 1-5 (SERINC1-5) are involved in the progression of several diseases. SERINC2-4 are carrier proteins that incorporate the polar amino acid serine into membranes to facilitate the synthesis of phosphatidylserine and sphingolipids. SERINC genes are also differentially expressed in tumors.