Vanilloid agonist-mediated activation of TRPV1 channels requires coordinated movement of the S1-S4 bundle rather than a quiescent state.

Transient receptor potential vanilloid1 (TRPV1) channel plays an important role in a wide range of physiological and pathological processes, and a comprehensive understanding of TRPV1 gating will create opportunities for therapeutic intervention. Recent incredible advances in cryo-electron microscopy (cryo-EM) have yielded high-resolution structures of all TRPV subtypes (TRPV1-6) and all of them share highly conserved six transmembrane (TM) domains (S1-S6). As revealed by the open structures of TRPV1 in the presence of a bound vanilloid agonist (capsaicin or resiniferatoxin), TM helicesS1 to S4 form a bundle that remains quiescent during channel activation, highlighting differences in the gating mechanism of TRPV1 and voltage-gated ion channels.

Investigating the predictive value of vascular endothelial growth factor in the evaluation of treatment efficacy and prognosis for patients with non-surgical esophageal squamous cell carcinoma.

In this study, we aim to investigate the predictive value of serum vascular endothelial growth factor (VEGF) in evaluating treatment efficacy and long-term prognosis for patients with non-surgical esophageal squamous cell carcinoma (ESCC). The patients diagnosed with ESCC by histopathology who didn't receive surgical treatment were retrospectively analyzed. Through follow-up and prognostic analysis, we explored the value of serum VEGF changes before, during, and after radiotherapy for predicting treatment efficacy, and identified important indicators to construct the predictive model.

Aroclor 1254 induced inhibitory effects on osteoblast differentiation in murine MC3T3-E1 cells through oxidative stress.

This study aimed to evaluate the osteotoxicity of polychlorinated biphenyls in murine osteoblastic MC3T3-E1 cells, and to explore the underlying mechanism focused on oxidative stress. The cells were exposed to Aroclor 1254 at concentrations of 2.5-20 µmol/L, and then cell viability, oxidative stress, intracellular calcium concentration, osteocalcin content, and calcium nodules formation were measured.

Boosting the photocatalytic performance of CuO for hydrogen generation by Au nanostructures and rGO nanosheets.

As a narrow band-gap semiconductor, cuprous oxide (CuO) has a relatively high conduction band that can exhibit high driving force for the photocatalytic generation of hydrogen under visible light. Besides, its adjustable morphologies and abundant source also make it possible to be employed as a theoretically optimal photocatalyst. However, the low charge migration and poor stability commonly limit its practical application, and various strategies have been explored in previous studies.

Yin-chen Wu-ling powder alleviate cholestatic liver disease: Network pharmacological analysis and experimental validation.

Background: Yin-chen Wu-ling Powder (YWP) has potential therapeutic effects on cholestatic liver disease (CLD), however, its active compounds and conceivable mechanism are as yet indistinct.

Methods: The network pharmacology and gene function annotation examined the multiple active ingredients, potential targets, and possible mechanisms of YWP in CLD treatment. Then the molecular docking reassured the reliability of the core compounds including the key genes and farnesoid X receptor (FXR).

Nobiletin suppresses cholangiocarcinoma proliferation via inhibiting GSK3β.

Cholangiocarcinoma (CCA) is a type of hepatobiliary cancer characterized by uncontrolled cell proliferation, with a poor prognosis and high mortality. Nobiletin (NBT) is a promising anti-tumor compound derived from the peels of oranges and other citrus plants, citrus plant. But the effect of NBT on CCA remains unknown.

A deep learning-based diagnostic pattern for ultrasound breast imaging: can it reduce unnecessary biopsy?

Background: Early studies have demonstrated the potential of deep learning in bringing revolutionary changes in medical analysis. However, it is unknown which deep learning based diagnostic pattern is more effective for differentiating malignant and benign breast lesions (BLs) and can assist radiologists to reduce unnecessary biopsies.

Methods: A total of 506 malignant BLs and 557 benign BLs were enrolled in this study after excluding incomplete ultrasound images.

Expression of STING Is Increased in Monocyte-Derived Macrophages and Contributes to Liver Inflammation in Hepatic Ischemia-Reperfusion Injury.

Ischemia/reperfusion (I/R) injury, aggravated by innate immune cell-mediated inflammatory response, is a major problem in liver transplantation. Stimulator of interferon gene (STING) is a crucial regulatory signaling molecule in the DNA-sensing pathway, and its activation can produce strong innate immunity. However, the STING-mediated innate immune pathway in hepatic I/R injury has not been fully elucidated.

Antibiotics enhancing drug-induced liver injury assessed for causality using Roussel Uclaf Causality Assessment Method: Emerging role of gut microbiota dysbiosis.

Drug-induced liver injury (DILI) is a disease that remains difficult to predict and prevent from a clinical perspective, as its occurrence is hard to fully explain by the traditional mechanisms. In recent years, the risk of the DILI for microbiota dysbiosis has been recognized as a multifactorial process. Amoxicillin-clavulanate is the most commonly implicated drug in DILI worldwide with high causality gradings based on the use of RUCAM in different populations.

PARK7 deficiency inhibits fatty acid β-oxidation via PTEN to delay liver regeneration after hepatectomy.

Transient regeneration-associated steatosis (TRAS) is a process of temporary hepatic lipid accumulation and is essential for liver regeneration by providing energy generated from fatty acid β-oxidation, but the regulatory mechanism underlying TRAS remains unknown. Parkinsonism-associated deglycase (Park7)/Dj1 is an important regulator involved in various liver diseases. In nonalcoholic fatty liver diseased mice, induced by a high-fat diet, Park7 deficiency improves hepatic steatosis, but its role in liver regeneration remains unknown METHODS: Park7 knockout (Park7 ), hepatocyte-specific Park7 knockout (Park7 ) and hepatocyte-specific Park7-Pten double knockout mice were subjected to 2/3 partial hepatectomy (PHx) RESULTS: Increased PARK7 expression was observed in the regenerating liver of mice at 36 and 48 h after PHx.

Interleukin-22 protects from endotoxemia by inducing suppressive F4/80Ly6GLy6C cells population.

Background: Excessive inflammatory response is the primary cause of early death in patients with endotoxemia. Interleukin 22 (IL-22) has been shown to play critical roles in the modulation of infectious diseases, but its function in regulating immune responses during endotoxemia remains unclear.

Methods: Lipopolysaccharide (LPS) was used to induce endotoxemia mouse model with or without a recombinant fusion protein containing human IL-22 (F-652).

Dynamic recognition of naloxone, morphine and endomorphin1 in the same pocket of µ-opioid receptors.

Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid abuse. The mechanism by which the MOR distinguishes between the two is unclear. Molecular dynamics (MD) simulations on a 1-μs time scale and metadynamics-enhanced conformational sampling are used here to determine the different interactions of these two ligands with MOR: morphine adjusted its pose by continuously flipping deeper into the pocket, whereas naloxone failed to penetrate deeper because its allyl group conflicts with several residues of MOR.

An Immunity-Related Gene Model Predicts Prognosis in Cholangiocarcinoma.

The prognosis of patients with cholangiocarcinoma (CCA) is closely related to both immune cell infiltration and mRNA expression. Therefore, we aimed at conducting multi-immune-related gene analyses to improve the prediction of CCA recurrence. Immune-related genes were selected from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the Immunology Database and Analysis Portal (ImmPort).

A gene signature is critical for intrahepatic cholangiocarcinoma stem cell self-renewal and chemotherapeutic response.

Background: Improved understanding of the stemness regulation mechanism in intrahepatic cholangiocarcinoma (ICC) could identify targets and guidance for adjuvant transarterial chemoembolization (TACE).

Methods: TCGA database was excavated to identify the ICC stemness-associated genes. The pro-stemness effect of target genes was further analyzed by sphere formation assay, qRT-PCR, western blot, flow cytometric analysis, IHC, CCK8 assay and metabolomic analysis.

A Novel Ferroptosis-Related Gene Signature to Predict Prognosis of Esophageal Carcinoma.

Objective: This study aimed to develop a novel ferroptosis-related gene-based prognostic signature for esophageal carcinoma (ESCA).

Methods: The TCGA-ESCA gene expression profiles and corresponding clinical data were downloaded from the TCGA database. Ferroptosis-related genes were identified from the literature and public databases, which were intersected with the differentially expressed genes between ESCA and normal samples.

Jiu-Wei-Yong-An Formula suppresses JAK1/STAT3 and MAPK signaling alleviates atopic dermatitis-like skin lesions.

Ethnopharmacological Relevance: Jiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear.

Quantitative proteomics of HFD-induced fatty liver uncovers novel transcription factors of lipid metabolism.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease, which progression is tightly regulated by transcription factors (TFs), nuclear receptors, and cellular enzymes. In this study, a label-free quantitative proteomic approach was used to determine the effect of the high-fat diet on the proteomics profile of liver tissue and to identify novel NAFLD related TFs. Mice were fed with HFD for 16 weeks to establish a NAFLD mouse model.

KIF26B in the Prognosis and Immune Biomarking of Various Cancers: A Pan-Cancer Study.

KIF26B has been identified as an oncogene in several tumors; however, its utility as a prognostic indicator for various cancers has not yet been comprehensively evaluated. Here, we first examined how KIF26B intervenes in thirty-three cancers within the TCGA database, including potential immunological functions, and how it affects the prognosis. Based on the open databases TCGA, TIMER2, GEPIA2, GTEx, CPTAC, and HPA, we found that, when compared with normal tissues, KIF26B is overexpressed in 22 tumor tissues.

Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death.

Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury.

SARS-CoV-2 variant B.1.1.7 caused HLA-A2 CD8 T cell epitope mutations for impaired cellular immune response.

Here, we evaluated the immune properties of the HLA-A2 restricted CD8 T cell epitopes containing mutations from B.1.1.

Immobilized Titanium (IV) Ion Affinity Chromatography Contributes to Efficient Proteomics Analysis of Cellular Nucleic Acid-Binding Proteins.

Cellular nucleic acid-binding proteins (NABPs), namely, DNA-binding proteins (DBPs) and RNA-binding proteins (RBPs), play important roles in many biological processes. However, extracting NABPs with high efficiency in living cells is challenging, which greatly limited their proteomics analysis and comprehensive characterization. Here, we discovered that titanium (IV) ion-immobilized metal affinity chromatography (Ti-IMAC) material could enrich DNA and RNA with high efficiency (96.

Comparison of [ Ga]Ga-FAPI-04 and [F]-FDG for the detection of primary and metastatic lesions in patients with gastric cancer: a bicentric retrospective study.

Introduction: The low sensitivity of [F]-fluorodeoxyglucose ([F]-FDG) for the diagnosis of gastric cancer limits its application. In this study, we aimed to investigate the potential advantage of [ Ga]Ga-FAPI-04 over [F]-FDG in the evaluation of gastric cancer.

Methods: This was a bicentric retrospective analysis of a prospective parent study (clinical trial: HS-KY-2020-826 (Huashan Hospital) and DF-2020-102 (Shanghai East Hospital)).

Myeloid DJ-1 deficiency protects acetaminophen-induced acute liver injury through decreasing inflammatory response.

Background: DJ-1 (also known as PARK7), a noted protein implicated in modulating ROS production and immune response, has been observed to play critical roles in the pathogenesis of many forms of liver disease through multiple mechanisms. However, its role and specific mechanism in acetaminophen (APAP) -induced liver injury have not been explored.

Results: In this present study, by employing an acute liver injury induced by APAP overdose mouse model, we demonstrated that DJ-1 knockout (DJ-1) mice showed reduced liver injury and lower mortality.

Methyl Diet Enhanced Sepsis-Induced Mortality Through Altering Gut Microbiota.

Introduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.

Aldolase A Enhances Intrahepatic Cholangiocarcinoma Proliferation and Invasion through Promoting Glycolysis.

Energy metabolism reprogramming has been implicated in tumorigenesis and development. Key metabolism enzyme Aldolase A (ALDOA) has been shown to be highly expressed and involved in various kinds of cancers including hepatocellular carcinoma. In this study, we found that ALDOA was highly expressed in clinical intrahepatic cholangiocarcinoma (ICC) tissues, and its high expression was negatively correlated with overall survival (OS) and recurrence-free survival (RFS) in ICC patients.