Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome.

The Core-Shell Microneedle with Probiotic Extracellular Vesicles for Infected Wound Healing and Microbial Homeostasis Restoration.

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management.

Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila.

Gut Akkermansia muciniphila (Akk) has been implicated in impacting immunotherapy or oncogenesis. This study aims to dissect the Akk-associated tumor immune ecosystem (TIME) by single-cell profiling coupled with T cell receptor (TCR) sequencing. We adopted mouse cancer models under anti-PD-1 immunotherapy, combined with oral administration of three forms of Akk, including live Akk, pasteurized Akk (Akk-past), or its membrane protein Amuc_1100 (Amuc).

Erratum: β-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.

[This corrects the article on p. 370 in vol. 11, PMID: 33575077.

Lysine Deacetylation Is a Key Function of the Lysyl Oxidase Family of Proteins in Cancer.

Mammalian members of the lysyl oxidase (LOX) family of proteins carry a copper-dependent monoamine oxidase domain exclusively within the C-terminal region, which catalyzes ε-amine oxidation of lysine residues of various proteins. However, recent studies have demonstrated that in LOX-like (LOXL) 2-4 the C-terminal canonical catalytic domain and N-terminal scavenger receptor cysteine-rich (SRCR) repeats domain exhibit lysine deacetylation and deacetylimination catalytic activities. Moreover, the N-terminal SRCR repeats domain is more catalytically active than the C-terminal oxidase domain.

COVID-19 vaccination is associated with enhanced efficacy of anti-PD-(L)1 immunotherapy in advanced NSCLC patients: a real-world study.

Background: Coronavirus disease 2019 (COVID-19) vaccine has played a major role in ending the pandemic. However, little is known about the influence of COVID-19 vaccine on the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC).

Objectives: The goal of this study is to explore whether COVID-19 vaccine impacts the efficacy of immune checkpoint inhibitors (ICIs) in NSCLC patients.

Virgin coconut oil attenuates lipopolysaccharide-induced depression-like behaviors: Integrating network pharmacology analysis and molecular mechanism evaluation.

Depression is a mental disease that seriously affects the quality of life. Its pathophysiology is complex and includes neuroinflammation and apoptosis. Virgin coconut oil (VCO) is a natural food that has been found to have remarkable anti-inflammatory and antiapoptotic properties.

Circulating eosinophils associated with responsiveness to COVID-19 vaccine and the disease severity in patients with SARS-CoV-2 omicron variant infection.

Objective: This study aimed to investigate the longitudinal circulating eosinophil (EOS) data impacted by the COVID-19 vaccine, the predictive role of circulating EOS in the disease severity, and its association with T cell immunity in patients with SARS-CoV-2 Omicron BA.2 variant infection in Shanghai, China.

Methods: We collected a cohort of 1,157 patients infected with SARS-CoV-2 Omicron/BA.

Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice.

Although gut microbiota has been linked to cancer, little is known about the crosstalk between gut- and intratumoral-microbiomes. The goal of this study was to determine whether gut Akkermansia muciniphila (Akk) is involved in the regulation of intratumoral microbiome and metabolic contexture, leading to an anticancer effect on lung cancer. We evaluated the effects of gut endogenous or gavaged exogenous Akk on the tumorigenesis using the Lewis lung cancer mouse model.

Acetylation licenses Th1 cell polarization to constrain Listeria monocytogenes infection.

T helper 1 (Th1) immunity is typically viewed as a critical adaptation by vertebrates against intracellular pathogens. Identifying novel targets to enhance Th1 cell differentiation and function is increasingly important for anti-infection immunity. Here, through small-molecule screening focusing on epigenetic modifiers during the in vitro Th1 cell differentiation process, we identified that the selective histone deacetylase 6 (HDAC6) inhibitors ricolinostat and nexturastat A (Nex A) promoted Th1 cell differentiation.

YAP signaling in horizontal basal cells promotes the regeneration of olfactory epithelium after injury.

The horizontal basal cells (HBCs) of olfactory epithelium (OE) serve as reservoirs for stem cells during OE regeneration, through proliferation and differentiation, which is important in recovery of olfactory function. However, the molecular mechanism of regulation of HBC proliferation and differentiation after injury remains unclear. Here, we found that yes-associated protein (YAP) was upregulated and activated in HBCs after OE injury.

Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis.

Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway.

Biomimetic microcavity interfaces for a label-free capture of pathogens in the fluid bloodstream by vortical crossflow filtration.

Bacterial sepsis is a lethal disease triggered by microbial pathogens. The blood pathogen load is a major contributor to both disease severity and mortality in patients with sepsis blood. Therefore, it is crucial to reduce the load of pathogens, in particular the drug-resistant pathogens.

Microglia-Specific Expression of and Leads to Poor Prognosis in Glioblastoma Patients.

Glioblastoma multiforme (GBM) is one of the deadliest cancers in brain. There have been few treatment advances for GBM despite increasing scientific understanding of this disease. β-hexosaminidase (Hex) is an important enzyme system in human body, encoded by two genes, and , are closely related to central nervous system (CNS) diseases such as Sandhoff disease (SD) and Tay-Sachs disease (TSD).

YAP prevents premature senescence of astrocytes and cognitive decline of Alzheimer's disease through regulating CDK6 signaling.

Senescent astrocytes accumulate with aging and contribute to brain dysfunction and diseases such as Alzheimer's disease (AD), however, the mechanisms underlying the senescence of astrocytes during aging remain unclear. In the present study, we found that Yes-associated Protein (YAP) was downregulated and inactivated in hippocampal astrocytes of aging mice and AD model mice, as well as in D-galactose and paraquat-induced senescent astrocytes, in a Hippo pathway-dependent manner. Conditional knockout of YAP in astrocytes significantly promoted premature senescence of astrocytes, including reduction of cell proliferation, hypertrophic morphology, increase in senescence-associated β-galactosidase activity, and upregulation of several senescence-associated genes such as p16, p53 and NF-κB, and downregulation of Lamin B1.

Astrocytic YAP protects the optic nerve and retina in an experimental autoimmune encephalomyelitis model through TGF-β signaling.

Optic neuritis is one of main symptoms in multiple sclerosis (MS) that causes visual disability. Astrocytes are pivotal regulators of neuroinflammation in MS, and astrocytic yes-associated protein (YAP) plays a critical role in neuroinflammation. Meanwhile, YAP signaling is involved in visual impairment, including glaucoma, retinal choroidal atrophy and retinal detachment.

SARM1 promotes neuroinflammation and inhibits neural regeneration after spinal cord injury through NF-κB signaling.

Axonal degeneration is a common pathological feature in many acute and chronic neurological diseases such as spinal cord injury (SCI). SARM1 (sterile alpha and TIR motif-containing 1), the fifth TLR (Toll-like receptor) adaptor, has diverse functions in the immune and nervous systems, and recently has been identified as a key mediator of Wallerian degeneration (WD). However, the detailed functions of SARM1 after SCI still remain unclear.

Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering.

The applications of hydrogels in biomedical field has been since multiple decades. Discoveries in biology and chemistry render this platform endowed with much engineering potentials and growing continuously. Novel approaches in constructing these materials have led to the production of complex hybrid hydrogels systems that can incorporate both natural and synthetic polymers and other functional moieties for mediated cell response, tunable release kinetic profiles, thus they are used and research for diverse biomedical applications.

β-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.

Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of β-elemene in glioma senescence remains unknown.

Changes in cognitive function and related brain regions in chronic benzene poisoning: a case report.

To discuss the changes in cognitive function and related brain regions in patients with chronic benzene poisoning. Few studies have explored the damage to cognitive function that occurs in benzene toxic encephalopathy. It is important to identify early in the course of disease whether cognitive dysfunction is caused by benzene poisoning so that disease prognosis and appropriate treatment can be determined.

Exosomal hsa-miR-129-2 and hsa-miR-889 from a 6-microRNA Signature Might be a Potential Biomarker for Predicting the Prognosis of Papillary Thyroid Carcinoma.

Background: Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time.

Objective: This study aimed to build a risk score (RS) system for PTC patients.

Methods: PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database.

The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant diseases because of its non-symptomatic tumorigenesis. We previous found heat shock factor 1 (HSF1) was critical for PDAC progression and the aim of this study was to clarified the mechanisms on early activation of HSF1 and its role in the pancreatic cancer tumorigenesis.

Methods: The expression and location of HSF1 on human or mice pancreatic tissues were examined by immunohistochemically staining.

D-galactose induces senescence of glioblastoma cells through YAP-CDK6 pathway.

Treatment of glioblastoma using radiotherapy and chemotherapy has various outcomes, key among them being cellular senescence. However, the molecular mechanisms of this process remain unclear. In the present study, we tested the ability of D-galactose (D-gal), a reducing sugar, to induce senescence in glioblastoma cells.

A Novel Putative Role of TNK1 in Atherosclerotic Inflammation Implicating the Tyk2/STAT1 Pathway.

Objective: Atherosclerosis is a chronic inflammatory disease which is responsible for many clinical manifestations. The present study was to investigate the anti-inflammatory functions and mechanisms of TNK1 in atherosclerosis.

Methods: The ApoE(-/-) mice and human carotid endarterectomy (CEA) atherosclerotic plaques were used to investigate the differential expression of TNK1.