HDAC6 deacetylates TRIM56 to negatively regulate cGAS-STING-mediated type I interferon responses.

Histone deacetylase HDAC6 has been implicated in regulating antiviral innate immunity. However, its precise function in response to DNA virus infection remains elusive. Herein, we find that HDAC6 deficiency promotes the activation of cGAS-STING signaling and type I interferon (IFN) production, both in vitro and in vivo, resulting in a decrease in HSV-1 infection.

Effective Antitumor Synergistic Treatment with Fiber-Photothermal Therapy and Heat Shock Protein Inhibitors.

Effective treatment of malignant tumors remains a thorny issue in current medicine. As a new type of anticancer strategy, photothermal therapy (PTT) has attracted tremendous attention due to its favorable therapeutic effectiveness, high spatial-temporal controllability, and low occurrence of side effects. However, the efficacy of PTT is significantly reduced due to the limited penetration of light and heat-induced overexpression of heat shock protein (Hsp).

CaARP1/CaSGT1 Module Regulates Vegetative Growth and Defense Response of Pepper Plants against .

Pepper ( L.) suffers severe quality and yield loss from oomycete diseases caused by . CaSGT1 was previously determined to positively regulate the immune response of pepper plants against , but by which mechanism remains elusive.

KYNU Expression Promotes Cisplatin Resistance in Esophageal Cancer.

Chemotherapy resistance is a barrier to effective cancer prognoses. Cisplatin (CDDP) resistance is a major challenge for esophageal cancer (EC) therapy. A deeper understanding of the fundamental mechanisms of cisplatin resistance and improved targeting strategies are required in clinical settings.

JD-02, a novel Hsp90 inhibitor, induces ROS/SRC axis-dependent cytoprotective autophagy in colorectal cancer cells.

Heat shock protein 90 (Hsp90) is a tumor marker that accelerates cancer growth by disrupting protein homeostasis. However, concerns such as low clinical efficacy and drug resistance continue to be obstacles to the successful marketing of Hsp90 inhibitors. The cytoprotective function of autophagy has been identified as one of the mechanisms by which tumor cells gain resistance to chemotherapy.

Synthetic Biohybrids of Red Blood Cells and Cascaded-Enzymes@ Metal-Organic Frameworks for Hyperuricemia Treatment.

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H O .

Acute toxicological evaluation of AT-533 and AT-533 gel in Sprague-Dawley rats.

Background: AT-533 is a novel heat shock protein 90 inhibitor that exerting anti-inflammatory, antiviral, and antitumor efficacy. Furthermore, the gel made of AT-533 as raw material named AT-533 gel has the function of repairing keratitis and dermatitis caused by herpes virus infection. However, the acute safety evaluation of AT-533 and AT-533 gel has not been conducted.

Ralstonia solanacearum effector RipAK suppresses homodimerization of the host transcription factor ERF098 to enhance susceptibility and the sensitivity of pepper plants to dehydration.

Plants have evolved a sophisticated immune system to defend against invasion by pathogens. In response, pathogens deploy copious effectors to evade the immune responses. However, the molecular mechanisms used by pathogen effectors to suppress plant immunity remain unclear.

Identification of circRNA-miRNA-mRNA Network Regulated by Hsp90 in Human Melanoma A375 Cells.

Background: Melanoma is the deadliest form of skin cancer. Heat shock protein 90 (Hsp90) is highly expressed in human melanoma. Hsp90 inhibitors can suppress the growth of human melanoma A375 cells; however, the underlying mechanism remains unclear.

Reprogramming of rhythmic liver metabolism by intestinal clock.

Background & Aims: Temporal oscillations in intestinal nutrient processing and absorption are coordinated by the local clock, which leads to the hypothesis that the intestinal clock has major impacts on shaping peripheral rhythms via diurnal nutritional signals. Here, we investigate the role of the intestinal clock in controlling liver rhythmicity and metabolism.

Methods: Transcriptomic analysis, metabolomics, metabolic assays, histology, quantitative (q)PCR, and immunoblotting were performed with Bmal1-intestine-specific knockout (iKO), Rev-erba-iKO, and control mice.

PER2 integrates circadian disruption and pituitary tumorigenesis.

The role of circadian clock in pituitary tumorigenesis remains elusive. Here we investigate whether and how circadian clock modulates the development of pituitary adenomas. We found altered expression of pituitary clock genes in patients with pituitary adenomas.

Targeting EFNA1 suppresses tumor progression via the cMYC-modulated cell cycle and autophagy in esophageal squamous cell carcinoma.

Purpose: Esophageal squamous cell carcinoma (ESCC) remains one of the most common causes of cancer death due to the lack of effective therapeutic options. New targets and the targeted drugs are required to be identified and developed.

Methods: Highly expressed genes in ESCA were identified using the edgeR package from public datasets.

Dual-Stage Irradiation of Size-Switchable Albumin Nanocluster for Cascaded Tumor Enhanced Penetration and Photothermal Therapy.

The triple-negative breast cancer (TNBC) microenvironment makes a feature of aberrant vasculature, high interstitial pressure, and compact extracellular matrix, which combine to reduce the delivery and penetration of therapeutic agents, bringing about incomplete elimination of cancer cells. Herein, employing the tumor penetration strategy of size-shrinkage combined with ligand modification, we constructed a photothermal nanocluster for cascaded deep penetration in tumor parenchyma and efficient eradication of TNBC cells. In our approach, the photothermal agent indocyanine green (ICG) is laded in human serum albumin (HSA), which is cross-linked by a thermally labile azo linker (VA057) and then further modified with a tumor homing/penetrating tLyP-1 peptide (HP), resulting in a TNBC-targeting photothermal-responsive size-switchable albumin nanocluster (ICG@HSA-Azo-HP).

N-Methyltransferase Acts as a Positive Regulator of Immunity against Bacterial Pathogens in Pepper.

Proteins with conserved SET domain play a critical role in plant immunity. However, the means of organization and functions of these proteins are unclear, particularly in non-model plants such as pepper ( L.).

E4BP4 Coordinates Circadian Control of Cognition in Delirium.

Improved understanding of the etiologies of delirium, a common and severe neuropsychiatric syndrome, would facilitate the disease prevention and treatment. Here, the authors invesitgate the role of circadian rhythms in the pathogenesis of delirium. They observe perturbance of circadian rhythms in mouse models of delirium and disrupted clock gene expression in patients with delirium.

The CaPti1-CaERF3 module positively regulates resistance of Capsicum annuum to bacterial wilt disease by coupling enhanced immunity and dehydration tolerance.

Bacterial wilt, a severe disease involving vascular system blockade, is caused by Ralstonia solanacearum. Although both plant immunity and dehydration tolerance might contribute to disease resistance, whether and how they are related remains unclear. Herein, we showed that immunity against R.

Efficacy comparison of oxcarbazepine and levetiracetam monotherapy among patients with newly diagnosed focal epilepsy in China: A multicenter, open-label, randomized study.

Aims: This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China.

Methods: Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited.

Herpes Simplex Virus 1 Induces Microglia Gasdermin D-Dependent Pyroptosis Through Activating the NLR Family Pyrin Domain Containing 3 Inflammasome.

Herpes simplex virus type 1 (HSV-1) is a highly prevalent virus in humans and causes severe forms of inflammation, such as herpes simplex encephalitis (HSE). Pyroptosis is a new inflammatory cell death triggered by inflammasome and cysteine-requiring aspartate protease-1 (caspase-1) activation. Nonetheless, HSV-1 induces encephalitis, and cell death mechanisms are not understood.

Hsp90 Inhibitors Prevent HSV-1 Replication by Directly Targeting UL42-Hsp90 Complex.

Herpes simplex virus type I (HSV-1) is a member of the Alphaherpesvirinae family, which could initiate labial herpes caused by the reactivation of HSV-1 primary infection, and secondary infection even causes herpes encephalitis. The study presented here demonstrates that Hsp90 inhibitors (AT-533 and 17-AAG) directly targeted the HSV-1 UL42-Hsp90 complex, and Hsp90 interacted with HSV-1 UL42 in silicon and experiment. Interestingly, Hsp90 inhibitors also reduced virus titers of ACV-resistant clinical HSV-1 strains (153 and blue strain), revealing that HSV-1 UL42 would be a new target against ACV-resistant HSV-1 strains.

Methyltransferase like 7B is a potential therapeutic target for reversing EGFR-TKIs resistance in lung adenocarcinoma.

Background: Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance.

Methods: METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance.

Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization.

Herpes simplex virus 1 (HSV-1) is a common neurotropic virus, the herpes simplex encephalitis (HSE) caused by which is considered to be the most common sporadic but fatal encephalitis. Traditional antiviral drugs against HSV-1 are limited to nucleoside analogs targeting viral factors. Inhibition of heat shock protein 90 (Hsp90) has potent anti-HSV-1 activities numerous mechanisms, but the effects of Hsp90 inhibitors on HSV-1 infection in neuronal cells, especially in the phase of virus entry, are still unknown.

Prognostic Value of C-Reactive Protein, Glasgow Prognostic Score, and C-Reactive Protein-to-Albumin Ratio in Colorectal Cancer.

Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC. Overall, 307 stage I-III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019.

Deficiency of intestinal Bmal1 prevents obesity induced by high-fat feeding.

The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1 mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1 mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers.

Novel nanomedicines to overcome cancer multidrug resistance.

Chemotherapy remains a powerful tool to eliminate malignant cells. However, the efficacy of chemotherapy is compromised by the frequent emergence of intrinsic and acquired multidrug resistance (MDR). These chemoresistance modalities are based on a multiplicity of molecular mechanisms of drug resistance, including : 1) Impaired drug uptake into cancer cells; 2) Increased expression of ATP-binding cassette efflux transporters; 3) Loss of function of pro-apoptotic factors; 4) Enhanced DNA repair capacity; 5) Qualitative or quantitative alterations of specific cellular targets; 6) Alterations that allow cancer cells to tolerate adverse or stressful conditions; 7) Increased biotransformation or metabolism of anticancer drugs to less active or completely inactive metabolites; and 8) Intracellular and intercellular drug sequestration in well-defined organelles away from the cellular target.

A Novel and Efficient High-Yield Method for Preparing Bacterial Ghosts.

Bacterial ghosts (BGs) are empty cell envelopes possessing native extracellular structures without a cytoplasm and genetic materials. BGs are proposed to have significant prospects in biomedical research as vaccines or delivery carriers. The applications of BGs are often limited by inefficient bacterial lysis and a low yield.