SARS-CoV-2 NSP6 reduces autophagosome size and affects viral replication via sigma-1 receptor.

Unlabelled: Autophagy is a cellular self-defense mechanism by which cells can kill invading pathogenic microorganisms and increase the presentation of components of pathogens as antigens. Contrarily, pathogens can utilize autophagy to enhance their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP6 can interact with ATPase proton pump component to inhibit lysosomal acidification, which was implicated in the autophagy process.

Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity.

Innate immunity serves as the primary defense against viral and microbial infections in humans. The precise influence of cellular metabolites, especially fatty acids, on antiviral innate immunity remains largely elusive. Here, through screening a metabolite library, palmitic acid (PA) has been identified as a key modulator of antiviral infections in human cells.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP.

Genome-Wide Identification and Expression Analysis of Genes in Reveals Their Potential Roles in Abiotic Stress Tolerance.

The bile acid sodium symporter (BASS) family plays an important role in transporting substances and coordinating plants' salt tolerance. However, the function of in has not yet been elucidated. In this study, eight genes distributed on five chromosomes were identified that belonged to four subfamilies.

Identification of neutralizing antibodies against monkeypox virus using high-throughput sequencing of A35H3LB cells from patients with convalescent monkeypox.

The global monkeypox virus (MPXV) outbreak in 2022 emphasizes the urgent need for effective and accessible new-generation vaccines and neutralizing antibodies. Herein, we identified MPXV-neutralizing antibodies using high-throughput single-cell RNA and V(D)J sequencing of antigen-sorted B cells from patients with convalescent monkeypox. IgG1-expressing B cells were obtained from 34 paired heavy- and light-chain B cell receptor sequences.

Atypical inflammatory kinase IKBKE phosphorylates and inactivates FoxA1 to promote liver tumorigenesis.

Physiologically, FoxA1 plays a key role in liver differentiation and development, and pathologically exhibits an oncogenic role in prostate and breast cancers. However, its role and upstream regulation in liver tumorigenesis remain unclear. Here, we demonstrate that FoxA1 acts as a tumor suppressor in liver cancer.

GLUL stabilizes N-Cadherin by antagonizing -Catenin to inhibit the progresses of gastric cancer.

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients.

High-fat diet promotes liver tumorigenesis via palmitoylation and activation of AKT.

Objective: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC.

Design: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT.

Genome-Wide Identification and Expression Analysis of Genes in Reveal Their Potential Roles in Abiotic Stress.

The () gene family plays a pivotal role in plant growth, induction of phytohormones, and the abiotic stress response. However, the gene family in has yet to be investigated. In this study, we identified 62 genes in the genome, which were classified into six subfamilies and distributed across 10 chromosomes.

AMPK phosphorylates and stabilises copper transporter 1 to synergise metformin and copper chelator for breast cancer therapy.

Background: Predominant roles of copper and its transporter, copper transporter 1 (CTR1), in tumorigenesis have been explored recently; however, the upstream regulation of CTR1 and combinational intervention of copper chelators in malignancies remain largely unclear.

Methods: CRISPR/Cas9-based kinome screening was used to identify the CTR1 upstream kinases. Immunofluorescence assays were utilised to detect CTR1 localisation.

AKT Blocks SIK1-Mediated Repression of STAT3 to Promote Breast Tumorigenesis.

Unlabelled: The PI3K-AKT signaling pathway is frequently dysregulated in cancer, and it is hyperactivated in approximately 50% of breast cancers. Although inhibitors directly targeting the PI3K-AKT axis have been developed, clinical efficacy has been limited to only a subset of patients. Identification of mechanisms underlying AKT-driven tumorigenesis could lead to alternative approaches to block pathway signaling and suppress breast tumor growth.

AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation.

The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth in response to amino acid and glucose levels. However, how mTORC1 senses glucose availability to regulate various downstream signalling pathways remains largely elusive. Here we report that AMP-activated protein kinase (AMPK)-mediated phosphorylation of WDR24, a core component of the GATOR2 complex, has a role in the glucose-sensing capability of mTORC1.

Revealing the Mechanisms for Linalool Antifungal Activity against and Its Efficient Control of Fusarium Wilt in Tomato Plants.

sp. () is a destructive soil-borne phytopathogenic fungus that causes Fusarium crown and root rot (FCRR) of tomato, leading to considerable field yield losses. In this study, we explored the antifungal capability of linalool, a natural plant volatile organic component, against and its role in controlling FCRR symptoms in tomatoes.

[Eukaryotic expression of human Y-box binding protein 1 (YB-1) promotes the proliferation and migration of human HepG2 cells].

Objective To establish the eukaryotic expression vector of Y-box-binding protein 1 (YB-1) with FLAG-tagged and transfect it into hepatocellular carcinoma HepG2 cells to identify the effects of YB-1 on the proliferation and migration. Methods Human YB-1 gene was amplified from the human ovary library by PCR. YB-1 fraction was double enzyme digested and connected with pcDNA3.

Interaction between BEND5 and RBPJ suppresses breast cancer growth and metastasis via inhibiting Notch signaling.

High frequent metastasis is the major cause of breast cancer (BC) mortality among women. However, the molecular mechanisms underlying BC metastasis remain largely unknown. Here, we identified six hub BC metastasis driver genes (BEND5, HSD11B1, NEDD9, SAA2, SH2D2A and TNFSF4) through bioinformatics analysis, among which BEND5 is the most significant gene.

MG53 Inhibits Necroptosis Through Ubiquitination-Dependent RIPK1 Degradation for Cardiac Protection Following Ischemia/Reperfusion Injury.

Rationale: While reactive oxygen species (ROS) has been recognized as one of the main causes of cardiac injury following myocardial infarction, the clinical application of antioxidants has shown limited effects on protecting hearts against ischemia-reperfusion (I/R) injury. Thus, the precise role of ROS following cardiac injury remains to be fully elucidated.

Objective: We investigated the role of mitsugumin 53 (MG53) in regulating necroptosis following I/R injury to the hearts and the involvement of ROS in MG53-mediated cardioprotection.

Network Structure Engineering of Organosilica Membranes for Enhanced CO Capture Performance.

The membrane separation process for targeted CO capture application has attracted much attention due to the significant advantages of saving energy and reducing consumption. High-performance separation membranes are a key factor in the membrane separation system. In the present study, we conducted a detailed examination of the effect of calcination temperatures on the network structures of organosilica membranes.

S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions.

Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT.

USP18 reduces paclitaxol sensitivity of triple-negative breast cancer via autophagy.

Paclitaxol is a first-line treatment for triple-negative breast cancer (TNBC). The molecular mechanisms underlying paclitaxol resistance in TNBC remain largely unclear. In this study, differential expressed genes (DEGs) between TNBC cells and paclitaxol-resistant (taxol-R) TNBC cells were screened by bioinformatics analysis.

IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis.

IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis.

SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions.

Background: 3-phosphoinositide-dependent protein kinase-1 (PDK1) acts as a master kinase of protein kinase A, G, and C family (AGC) kinase to predominantly govern cell survival, proliferation, and metabolic homeostasis. Although the regulations to PDK1 downstream substrates such as protein kinase B (AKT) and ribosomal protein S6 kinase beta (S6K) have been well established, the upstream regulators of PDK1, especially its degrader, has not been defined yet.

Method: A clustered regularly interspaced short palindromic repeats (CRISPR)-based E3 ligase screening approach was employed to identify the E3 ubiquitin ligase for degrading PDK1.

RHOV promotes lung adenocarcinoma cell growth and metastasis through JNK/c-Jun pathway.

Lung adenocarcinoma (LUAD) is a common type of lung cancer with high frequent metastasis and a high death rate. However, genes responsible for LUAD metastasis are still largely unknown. Here, we identify an important role of ras homolog family member V (RHOV) in LUAD metastasis using a combination of bioinformatic analysis and functional experiments.

Copper Promotes Tumorigenesis by Activating the PDK1-AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner.

Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3-phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis.