Causal relationship between Brugada syndrome and electrocardiogram traits: A bidirectional Mendelian randomization study.

Introduction: Observational studies have suggested associations between Brugada syndrome (BrS) and electrocardiograms traits. Nonetheless, the causal relationships remains uncertain in observational studies. This study aims to investigate the causal relationships between BrS phenotypic risk and electrocardiogram traits using Mendelian randomization (MR) analysis and colocalization analysis.

Event recognition method based on feature synthesizing for a zero-shot intelligent distributed optical fiber sensor.

Phase-sensitive optical time domain reflectometer (Φ-OTDR) is an emergent distributed optical sensing system with the advantages of high localization accuracy and high sensitivity. It has been widely used for intrusion identification, pipeline monitoring, under-ground tunnel monitoring, etc. Deep learning-based classification methods work well for Φ-OTDR event recognition tasks with sufficient samples.

Plasma acylcarnitine in elderly Taiwanese: as biomarkers of possible sarcopenia and sarcopenia.

Background: Sarcopenia is defined as the disease of muscle loss and dysfunction. The prevalence of sarcopenia is strongly age-dependent. It could bring about disability, hospitalization, and mortality.

HCH6-1, an antagonist of formyl peptide receptor-1, exerts anti-neuroinflammatory and neuroprotective effects in cellular and animal models of Parkinson's disease.

Microglial activation-induced neuroinflammation contributes to onset and progression of sporadic and hereditary Parkinson's disease (PD). Activated microglia secrete pro-inflammatory and neurotoxic IL-1β, IL-6 and TNF-α, which subsequently promote neurodegeneration. Formyl peptide receptor-1 (FPR1) of CNS microglia functions as pattern recognition receptor and is activated by N-formylated peptides, leading to microglial activation, induction of inflammatory responses and resulting neurotoxicity.

Coupling of N-Doped Mesoporous Carbon and N-Ti C in 2D Sandwiched Heterostructure for Enhanced Oxygen Electroreduction.

2D heterostructures provide a competitive platform to tailor electrical property through control of layer structure and constituents. However, despite the diverse integration of 2D materials and their application flexibility, tailoring synergistic interlayer interactions between 2D materials that form electronically coupled heterostructures remains a grand challenge. Here, the rational design and optimized synthesis of electronically coupled N-doped mesoporous defective carbon and nitrogen modified titanium carbide (Ti C ) in a 2D sandwiched heterostructure, is reported.

PLA2G6 mutations cause motor dysfunction phenotypes of young-onset dystonia-parkinsonism type 14 and can be relieved by DHA treatment in animal models.

Parkinson's disease (PD), the most common neurodegenerative motor disorder, is currently incurable. Although many studies have provided insights on the substantial influence of genetic factors on the occurrence and development of PD, the molecular mechanism underlying the disease is largely unclear. Previous studies have shown that point mutations in the phospholipase A2 group VI gene (PLA2G6) correlate with young-onset dystonia-parkinsonism type 14 (PARK14).

EGF promotes transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3.

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of β-catenin, a Wnt signaling effector. We investigated how expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser, which promoted its nuclear translocation.

A Pt(IV)-based mononitro-naphthalimide conjugate with minimized side-effects targeting DNA damage response via a dual-DNA-damage approach to overcome cisplatin resistance.

Platinum(Pt)(II) drugs and new Pt(IV) agents behave the dysregulation of apoptosis as the result of DNA damage repair and thus, are less effective in the treatment of resistant tumors. Herein, mononitro-naphthalimide Pt(IV) complex 10b with minimized side-effects was reported targeting DNA damage response via a dual-DNA-damage approach to overcome cisplatin resistance. 10b displayed remarkably evaluated antitumor (70.

A Polyamine-Based Dinitro-Naphthalimide Conjugate as Substrates for Polyamine Transporters Preferentially Accumulates in Cancer Cells and Minimizes Side Effects and .

Naphthalimides, such as amonafide and mitonafide in clinical trials, have been developed as antitumor agents for orthotopic tumor. However, the serious side effects in cancer patients limit their applications. Herein, a new class of polyamine-based naphthalimide conjugates , , and with and without the alkylation of the distant nitrogen in the polyamine chain were synthesized and the mechanism was determined.

Bromocoumarinplatin, targeting simultaneously mitochondria and nuclei with p53 apoptosis pathway to overcome cisplatin resistance.

Mitochondria as one of potential anticancer target, alternatively damaging mtDNA other than nDNA is a potential method for platinum-based anticancer drugs to overcome cisplatin resistance. We herein report that bromocoumarinplatin 1, a coumarin-Pt(IV) prodrug, targeted simultaneously mitochondria and nuclei with the contents of Pt in nDNA and mtDNA were 25.75% and 65.

Polyamine-Based Pt(IV) Prodrugs as Substrates for Polyamine Transporters Preferentially Accumulate in Cancer Metastases as DNA and Polyamine Metabolism Dual-Targeted Antimetastatic Agents.

Diverse platinum drug candidates have been designed to improve inhibitory potency and overcome resistance for orthotopic tumors. However, the antimetastatic properties have rarely been reported. We herein report that homospermidineplatin (), a polyamine-Pt(IV) prodrug, can potently inhibit tumor growth and reverse cisplatin resistance as expected, and more importantly, displays remarkably elevated antimetastatic activity (65.

Pparα deficiency inhibits the proliferation of neuronal and glial precursors in the zebrafish central nervous system.

Background: Many molecules and signaling pathways involved in neural development play a role in neurodegenerative diseases and brain tumor progression. Peroxisome proliferator-activated receptor (PPAR) proteins regulate the differentiation of tissues and the progression of many diseases. However, the role of these proteins in neural development is unclear.

Protected and De-protected Platinum(IV) Glycoconjugates With GLUT1 and OCT2-Mediated Selective Cancer Targeting: Demonstrated Enhanced Transporter-Mediated Cytotoxic Properties and .

Physiological characteristics of human malignancies are increased glycolysis and overexpression of glucose transporters (GLUTs). Flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers based on the Warburg effect. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, protected, and de-protected glucose, mannose, galactose, rhamnose, maltose, and lactose-conjugated platinum(IV) complexes were designed and synthesized.

C9orf72 is essential for neurodevelopment and motility mediated by Cyclin G1.

Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the function of C9orf72 in neural development and the pathogenic mechanism underlying neurodegeneration are unknown. We found that disrupting C9orf72 expression by using C9orf72 constructs that lack the complete DENN domain result in reduced GTPase activity in zebrafish embryos, demonstrating the indispensability of the complete DENN domain.