Targeting SLITRK4 Restrains Proliferation and Liver Metastasis in Colorectal Cancer via Regulating PI3K/AKT/NFκB Pathway and Tumor-Associated Macrophage.

Liver metastasis is the major cause of death in colorectal cancer (CRC) due to the lack of effective treatment. To explore novel drivers of CRC liver metastasis, the transcriptomes of primary paracancerous, colorectal tumors and metastases from human patients are profiled. It is found that SLIT- and NTRK-like family member 4 (SLITRK4) is the top upregulated gene in liver metastases and is associated with worse overall survival of CRC patients.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression.

Scaffold Adhering to Peptide-Based Biomimetic Extracellular Matrix Composite Nanobioglass Promotes the Proliferation and Migration of Skin Fibroblasts Through the GSK-3β/β-Catenin Signaling Axis.

Introduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3β/β-catenin signaling axis and toxicological effects.

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination. Furthermore, Dok6 is highly expressed in peripheral neurons but not in Schwann cells, and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding, axon destruction, and hindered retrograde axonal transport.

Discovery of NLRP3 inhibitors using machine learning: Identification of a hit compound to treat NLRP3 activation-driven diseases.

NLRP3 is vital in developing many human diseases as one of the most critical inflammasomes. Developing related inhibitors has been instrumental in advancing the development of therapies for associated diseases. To date, there are no NLRP3 inhibitors on the market.

The role of Angiogenesis and remodeling (AR) associated signature for predicting prognosis and clinical outcome of immunotherapy in pan-cancer.

Background: Angiogenesis and remodeling (AR) is necessary for the growth and metastasis of cancers. Although AR related genes involved in this process are reported, the correlation between AR and clinical outcome, immune cell infiltration, and immunotherapy is still unknown in diverse cancers. This study aimed to investigate the role of AR in the tumor immune microenvironment (TIME) in pan-cancer, and explore its values in prognostic prediction and therapeutic responses.

Application of multimodal identification technology in the innovative management operation department.

Background: The optimization of surgical procedures and the management of surgical quality and safety have become the focus of attention of hospital managers. The application of multimodal identification technology in the innovative management mode of hospital operating department has made remarkable progress.

Methods: To investigate the effect of the upgraded multimodal identification technology on the innovative management of the operating department, 2,280 cases of laparoscopic surgery using traditional surgical management procedures from January to December 2019 before the management upgrade were set as the control group, and 2,350 laparoscopic surgeries with the upgraded multimodal identification management process from January to December 2020 were selected as the experimental group.

Relationship Between Gross Motor Skills and Inhibitory Control in Preschool Children: A Pilot Study.

Purpose: Gross motor skills (GMS) and inhibitory control (IC) which are both development in preschool stage is significant for preschooler to healthy growth. However, the evidence of relationship between them in preschoolers are still insufficient, most of studies only focus on youth. Thus, the aim of this research is to examine the association between GMS and IC in preschool children.

DTX-P7, a peptide-drug conjugate, is highly effective for non-small cell lung cancer.

Despite tremendous success of molecular targeted therapy together with immunotherapy, only a small subset of patients can benefit from them. Chemotherapy remains the mainstay treatment for most of tumors including non-small cell lung cancer (NSCLC); however, non-selective adverse effects on healthy tissues and secondary resistance are the main obstacles. Meanwhile, the quiescent or dormant cancer stem-like cells (CSLCs) are resistant to antimitotic chemoradiotherapy.

Relationship between Adverse Childhood Experiences and Mental Health in Chinese Adolescents: Differences among Girls and Boys.

The negative effects of adverse childhood experiences (ACEs) on individual mental health have been widely demonstrated, yet fewer studies have examined the impact of ACEs on depression and anxiety of Chinese adolescents and their sex differences. This cross-sectional study surveyed 12421 adolescents aged 10−17 in Hechi City, Guangxi Province, to measure their levels of ACEs, depression symptoms, and anxiety symptoms. The results found that: (1) Girls were more likely to experience ACEs than boys (37.

Discovery of novel ataxia telangiectasia mutated (ATM) kinase modulators: Computational simulation, biological evaluation and cancer combinational chemotherapy study.

Ataxia-telangiectasia mutated (ATM) kinase is a serine/threonine protein kinase and plays a key role in DNA double-strand breaks repair. Thus, ATM is considered a promising target for radiotherapy and chemotherapy sensitizing. Herein, we report the discovery of ATM agonist A22 and inhibitor A41 by computational methods and further biological evaluation.

Dietary glucose oxidase and/or catalase supplementation alleviates intestinal oxidative stress induced by diquat in weaned piglets.

This study investigated the effects of dietary exogenous glucose oxidase (GOD) and/or catalase (CAT) on the intestinal antioxidant capacity and barrier function in piglets under oxidative stress. Sixty pigs assigned randomly to five treatment groups-CON: basal diet; DIQ: basal diet; GOD: basal diet + 40-U GOD/kg diet; CAT: basal diet + 50-U CAT/kg diet; and GC: basal diet + 40-U GOD/kg diet + 50-U CAT/kg diet-were analyzed. On Day 14, the CON group was injected with saline, and the others were treated with diquat.

Microbial analysis and enrichment of anaerobic phenol and p-cresol degrading consortia with addition of AQDS.

Quinones and humus are ubiquitous in the biosphere and play an important role in the anaerobic biodegradation and biotransformation of organic acids, poisonous compounds as well as inorganic compounds. The impact of humic model compound, anthraquinone-2, 6-disulfonate (AQDS) on anaerobic phenol and p-cresol degradation were studied. Four methanogenic AQDS-free phenol and p-cresol enrichments and two phenol-AQDS enrichments were obtained using two sludges with potential biodegradability of phenol and cresol isomers as inoculum.

Effects of dietary supplementation of glucose oxidase, catalase, or both on reproductive performance, oxidative stress, fecal microflora and apoptosis in multiparous sows.

Objective: The objective of this experiment was to investigate the effect of dietary glucose oxidase (GOD), catalase (CAT), or both supplementation on reproductive performance, oxidative stress, and apoptosis in sows.

Methods: A total of 104 multiparous sows were randomly assigned to four groups (n = 26) with each group given a basal diet, basal diet plus GOD at 60 U/kg, basal diet plus CAT at 75 U/kg, and basal diet plus GOD at 60 U/kg and CAT at 75 U/kg. Sows were fed the experimental diets throughout gestation and lactation.

Exogenous HS Induces Hrd1 S-sulfhydration and Prevents CD36 Translocation via VAMP3 Ubiquitylation in Diabetic Hearts.

Hydrogen sulfide (HS) plays physiological roles in vascular tone regulation, cytoprotection, and ATP synthesis. HMG-CoA reductase degradation protein (Hrd1), an E3 ubiquitin ligase, is involved in protein trafficking. HS may play a role in controlling fatty acid uptake in diabetic cardiomyopathy (DCM) in a manner correlated with modulation of Hrd1 S-sulfhydration; however, this role remains to be elucidated.

Exogenous HS Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice.

Hydrogen sulfide (HS), an important gasotransmitter, regulates cardiovascular functions. Mitochondrial damage induced by the overproduction of reactive oxygen species (ROS) results in myocardial injury with a diabetic state. The purpose of this study was to investigate the effects of exogenous HS on mitophagy formation in diabetic cardiomyopathy.

Exogenous HS reduces the acetylation levels of mitochondrial respiratory enzymes via regulating the NAD-SIRT3 pathway in cardiac tissues of mice.

Hydrogen sulfide (HS), a gaseous molecule, is involved in modulating multiple physiological functions, such as antioxidant, antihypertension, and the production of polysulfide cysteine. HS may inhibit reactive oxygen species generation and ATP production through modulating respiratory chain enzyme activities; however, the mechanism of this effect remains unclear. In this study, mice, neonatal rat cardiomyocytes, and H9c2 cells treated with high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes.

Hydrogen sulfide regulates muscle RING finger-1 protein S-sulfhydration at Cys to prevent cardiac structural damage in diabetic cardiomyopathy.

Background And Purpose: Hydrogen sulfide (H S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger-1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H S alleviates cardiac muscle degradation through modifications of MuRF1 S-sulfhydration in db/db mice.

Exogenous HS switches cardiac energy substrate metabolism by regulating SIRT3 expression in db/db mice.

Unlabelled: Hydrogen sulfide (HS) is involved in diverse physiological functions, such as anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive oxygen species production. Sirtuin 3 (SIRT3) is a NAD -dependent deacetylase that regulates mitochondrial energy metabolism. The role of HS in energy metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3 expression; however, this role remains to be elucidated.

Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway.

Background/aim: Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H2S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H2S via autophagy during high glucose treatment.

MT2-MMP induces proteolysis and leads to EMT in carcinomas.

Epithelial-mesenchymal transition (EMT) is critical for carcinoma invasiveness and metastasis. To investigate the role of membrane-type-2 matrix metalloproteinase (MT2-MMP) in EMT, we generated lentiviral constructs of wild-type (WT) and an inactive Glu260Ala (E260A) mutant MT2-MMP and derived stably transfected HCT116 and A549 cell lines. WT-transfected cells appeared mesenchymal-like, whereas cells transfected with the E260A mutant were epithelial-like, as were cells treated with an MMP inhibitor (GM6001).

Antibacterial evaluation of flavonoid compounds against E. coli by microcalorimetry and chemometrics.

Fighting against multidrug-resistant bacteria requires reliable methods to evaluate the effect of antibacterial agents. As a universal, non-destructive, and highly sensitive tool, microcalorimetry has been used in many biological investigations to provide continuous real-time monitoring of the metabolic activity. This method, based on heat-flow output, was used to evaluate the influence of two flavonoid compounds (liquiritigenin and liquiritin) on Escherichia coli.