Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress.

The PINK1/Parkin pathway targets damaged mitochondria for degradation via mitophagy. Genetic evidence implicates impaired mitophagy in Parkinson's disease, making its pharmacological enhancement a promising therapeutic strategy. Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458.

Electrochemically Modified Interface Promoting the Oxygen-Electrocatalytic Kinetics in Near-Neutral Zinc-Air Batteries.

The development of near-neutral zinc-air batteries (ZABs) has been hindered by the sluggish oxygen reaction kinetics, severely limiting energy efficiency and power output. While recent advances in catalyst design have improved the intrinsic activity of electrocatalysts, their overall impact on battery performance remains limited. Here, an electrochemical modification strategy is presented that simultaneously enhances the surface properties of both the gas diffusion layer (GDL) and the bifunctional catalyst.

sp. nov. and sp. nov., isolated from traditional Chinese pickle.

Two novel bacteria (designated N501-2 and N40-8-2) belonging to the genera and were isolated from traditional Chinese pickle ('Suan cai') and identified. Strain N501-2 was phylogenetically related to the type strains of , , and , having 98.7-99.

Targeting CTP synthetase 1 to restore interferon induction and impede nucleotide synthesis in SARS-CoV-2 infection.

Despite the global impact caused by the most recent SARS-CoV-2 pandemic, our knowledge of the molecular underpinnings of its highly infectious nature remains incomplete. We report here that SARS-CoV-2 exploits cellular CTP synthetase 1 (CTPS1) to promote CTP synthesis and suppress interferon (IFN) induction. In addition to catalyzing CTP synthesis, CTPS1 also deamidates interferon regulatory factor 3 (IRF3) to dampen interferon induction.

The Influence of Interlocking Effects in Conjugated Polymers Synthesized by Aldol Polycondensation on Field-Effect Transistor Properties and Morphology.

The environmental and economic drawbacks of traditional palladium-catalyzed coupling reactions in the synthesis of conjugated polymers have prompted the exploration of green alternatives. This study presents the synthesis and characterization of a series of ladder-type conjugated polymers via aldol and Knoevenagel condensation reactions, which use simple acid or base catalysts and produce only water as a byproduct. We explore the interlocking effect of the backbone and study its role in enhancing the backbone planarity, charge transport, and morphology.

In-Depth Comparison of Reagent-Based Digestion Methods and Two Commercially Available Kits for Bottom-Up Proteomics.

Proteomic analysis plays an essential role in biology with several methodologies available for sample preparation and analysis. This study evaluates and compares various cell lysis and protein digestion protocols for bottom-up proteomics using HeLa S3 cells. We assessed two physical disruption methods to homogenize cells-sonication and BeatBox-alongside four digestion protocols.

Inhibition of IP3 (Inositol 1,4,5-Trisphosphate) Receptors Retards SARS-CoV-2-Induced Endothelial von Willebrand Factor Secretion and Thrombosis.

Patients with coronavirus disease 2019 (COVID-19) are at high risk of developing a hypercoagulable state and thrombosis. The von Willebrand factor (vWF) produced by endothelial cells (ECs) is a critical thrombosis regulator. We previously found that cytoskeleton-associated protein 4 (CKAP4) is a novel receptor for the spike protein of severe acute respiratory syndrome coronavirus-2 and is involved in COVID-19-associated coagulopathy.

Enterococcus hailinensis sp. nov., Isolated from Traditional Chinese Pickle.

Two enterococcal isolates, designated as strains N48-2 and N48-9.1, were isolated from traditional Chinese pickle ('Suan cai') and characterized using a polyphasic approach. Phylogenies based on 16S rRNA gene sequences and whole genome sequences indicated that strains N48-2 and N48-9.

Reducing Cofilin dosage makes embryos resilient to heat stress.

In addition to regulating the actin cytoskeleton, Cofilin also senses and responds to environmental stress. Cofilin can promote cell survival or death depending on context. Yet, many aspects of Cofilin's role in survival need clarification.

Nuclear Control of Mitochondrial Homeostasis and Venetoclax Efficacy in AML via COX4I1.

Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression.

Discovery and biological evaluation of potent 2-trifluoromethyl acrylamide warhead-containing inhibitors of protein disulfide isomerase.

Protein disulfide isomerase (PDI) regulates multiple protein functions by catalyzing the oxidation, reduction, and isomerization of disulfide bonds. The enzyme is considered a potential target for treating thrombosis. We previously developed a potent PDI inhibitor, CPD, which contains the propiolamide as a warhead targeting cysteine residue in PDI.

Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.

Human p97/VCP is a vital AAA ATPase (ATPase associated with diverse cellular activity) that plays critical roles in protein homeostasis by regulating autophagy, endosomal trafficking, and the ubiquitin-proteasome system. Global proteomics analysis of p97/VCP inhibition with CB-5083 has been performed in HCT116 colon cells. Here, we examined the impact of CB-5083 treatment in another cancer model, the HL-60 acute myeloid leukemia cell line, employing subcellular fractionation combined with label-free proteomics to analyze changes in protein levels across cytoplasmic, nuclear, and insoluble membrane protein compartments.

sp. nov., isolated from the gut of honeybee ().

Two novel bifidobacteria (designated F806-1 and F814-1.1) isolated from the gut of honeybee () were characterized in the present study. 16S rRNA gene sequence analysis indicated that strains F806-1 and F814-1.

Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.

As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD synthesis.

Fluoranthene imide dimers with strong isomeric effects on the charge transport properties.

To date, the development of high-performance n-type organic semiconductors has remained challenging due to the scarcity of highly electron-deficient π-conjugated structural units and the difficulty of controlling intermolecular packing in the thin-film state. In addition, there have been few reports on the use of dimer design to tune the optoelectronic properties of materials. Herein, we report new cyano-substituted fluoranthene imide-based dimers (F16 and F17) for small-molecule n-type organic semiconductors.

Lapidilactobacillus salsurivasis sp. nov., Secundilactobacillus muriivasis sp. nov., and Streptococcus parasalivarius sp. nov., isolated from Traditional Chinese Pickle.

Four Gram-stain-positive bacterial strains (designated 475-2, 46-6B, 778-2 and A810-3), isolated from traditional Chinese pickle, were characterized using a polyphasic taxonomic approach. Strain 475-2 was most closely related to the type strain of Lapidilactobacillus achengensis, having 99.9% 16S rRNA gene sequence similarity, 94.

Role of a holo-insertase complex in the biogenesis of biophysically diverse ER membrane proteins.

Mammalian membrane proteins perform essential physiologic functions that rely on their accurate insertion and folding at the endoplasmic reticulum (ER). Using forward and arrayed genetic screens, we systematically studied the biogenesis of a panel of membrane proteins, including several G-protein-coupled receptors (GPCRs). We observed a central role for the insertase, the ER membrane protein complex (EMC), and developed a dual-guide approach to identify genetic modifiers of the EMC.

MiR-204/-211 double knockout exacerbates rheumatoid arthritis progression by promoting splenic inflammation.

Objective: Collagen-induced arthritis (CIA) model was induced in C57BL/6 wild-type (wt) and C57BL/6 miR-204/-211 double-knockout (dKO) mice to investigate the role of miR-204/-211 in suppressing splenic inflammation in rheumatoid arthritis (RA).

Methods: Differences of miR-204/-211 and structure-specific recognition protein 1 (SSRP1) in the spleen of DBA/1J wt and CIA mice were detected via PCR and immunohistochemistry. CIA was induced in both C57BL/6 wt and C57BL/6 miR-204/-211 dKO mice, and the onset of CIA and disease severity were statistically analyzed.

Single-tissue proteomics in reveals proteins resident in intestinal lysosome-related organelles.

The nematode intestine is the primary site for nutrient uptake and storage as well as the synthesis of biomolecules; lysosome-related organelles known as gut granules are important for many of these functions. Aspects of intestine biology are not well understood, including the export of the nutrients it imports and the molecules it synthesizes, as well as the complete functions and protein content of the gut granules. Here, we report a mass spectrometry (MS)-based proteomic analysis of the intestine of the and of its gut granules.

Increasing Proteome Coverage Through a Reduction in Analyte Complexity in Single-Cell Equivalent Samples.

The advancement of sophisticated instrumentation in mass spectrometry has catalyzed an in-depth exploration of complex proteomes. This exploration necessitates a nuanced balance in experimental design, particularly between quantitative precision and the enumeration of analytes detected. In bottom-up proteomics, a key challenge is that oversampling of abundant proteins can adversely affect the identification of a diverse array of unique proteins.

Integrating predictive coding and a user-centric interface for enhanced auditing and quality in cancer registry data.

Data curation for a hospital-based cancer registry heavily relies on the labor-intensive manual abstraction process by cancer registrars to identify cancer-related information from free-text electronic health records. To streamline this process, a natural language processing system incorporating a hybrid of deep learning-based and rule-based approaches for identifying lung cancer registry-related concepts, along with a symbolic expert system that generates registry coding based on weighted rules, was developed. The system is integrated with the hospital information system at a medical center to provide cancer registrars with a patient journey visualization platform.

Impact of left ventricular ejection fraction and aortic valve gradient on mortality following transcatheter aortic valve intervention.

Background: Data regarding the impact of reduced left ventricular ejection fraction (LVEF) and/or reduced mean aortic valve gradient (AVG) on outcomes following transcatheter aortic valve intervention (TAVI) have been conflicting. We sought to assess the relationship between LVEF, AVG, and 1-year mortality in patients undergoing TAVI.

Methods: We prospectively evaluated 298 consecutive adults undergoing TAVI from 2015 to 2018 at an academic tertiary medical center.

sp. nov., isolated from traditional Chinese pickle.

Three Gram-stain-positive bacterial strains (designated 231-9, 142-6 and 463-4) were isolated from traditional Chinese pickle, and were characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strains 231-9, 142-6 and 463-4 were phylogenetically related to the type strains of , , , and , having 98.6-99.

Hijacking of nucleotide biosynthesis and deamidation-mediated glycolysis by an oncogenic herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and multiple types of B cell malignancies. Emerging evidence demonstrates that KSHV reprograms host-cell central carbon metabolic pathways, which contributes to viral persistence and tumorigenesis. However, the mechanisms underlying KSHV-mediated metabolic reprogramming remain poorly understood.