Natural compounds modulating mitophagy: Implications for cancer therapy.

Cancer is considered as the second leading cause of mortality, and cancer incidence is still growing rapidly worldwide, which poses an increasing global health burden. Although chemotherapy is the most widely used treatment for cancer, its effectiveness is limited by drug resistance and severe side effects. Mitophagy is the principal mechanism that degrades damaged mitochondria via the autophagy/lysosome pathway to maintain mitochondrial homeostasis.

Longitudinal Changes of Cognition and Frailty With All-Cause and Cause-Specific Mortality in Chinese Older Adults: An 11-Year Cohort Study.

Background And Objectives: Physical function deterioration is always accompanied by a cognitive decline in older adults. However, evidence is lacking for the long-term simultaneous changing patterns of cognition and physical frailty and their associations with mortality among older adults.

Research Design And Methods: This study included 8,231 adults aged ≥65 with a baseline and at least one follow-up assessment of both cognition and physical frailty from the 2007-2018 Chinese Longitudinal Healthy Longevity Survey.

The Relationship Between Physical Activity and All-Cause Mortality Among Older Adults - China, 1998-2018.

What Is Already Known About This Topic?: Previous research indicates that non-occupational physical activity can reduce mortality risk. Nevertheless, the relationship between occupational physical activity and health improvements has not been consistently established.

What Is Added By This Report?: The study found that regular exercise and leisure activities reduced the risk of all-cause mortality.

Cross-layer modeling and analysis of TCP communications over turbulent FSO links.

This paper addresses the accurate characterization of the performance of transmission control protocol (TCP) for end-to-end transport services over free-space optical (FSO) links. Unlike previous works on this topic, we introduce a second-order Markovian assumption for the variation of the TCP congestion window to capture the memory from turbulence channels and further propose a Markov chain model that maps two consecutive congestion windows along time into the state space to interpret TCP operations. The analytical expression of steady-state probability distribution vector of the proposed model in general cases where relay routers exist behind the TCP connection is derived, based on which the throughput efficiency of TCP is formulated.

Tetrandrine slows the radiographic progression of progressive massive fibrosis in pneumoconiosis: a retrospective cohort study.

Objective: This study aims to explore the clinical effect of Tetrandrine (Tet) on progressive massive fibrosis (PMF) of pneumoconiosis.

Methods: This retrospective study collected 344 pneumoconiosis patients with PMF, and 127 were eligible for the final analysis, including 57 patients in the Tet group and 70 patients in the control group. The progress of imaging and lung function were compared between the two groups.

Applications of transcriptomics in support of drug development for osteoarthritis.

Objective: Understanding the heterogeneity and pathophysiology of osteoarthritis (OA) is critical to support the development of tailored disease-modifying treatments. To this aim, transcriptomics tools are highly relevant to delineate dysregulated molecular pathways and identify new therapeutic targets.

Methods: We review the methodology and outcomes of transcriptomics studies conducted in OA, based on a comprehensive literature search of the PubMed and Google Scholar databases using the terms "osteoarthritis", "OA", "knee OA", "hip OA", "genes", "RNA-seq", "microarray", "transcriptomic" and "PCR" as key words.

Regulation effect of koumine on T-helper cell polarization in rheumatoid arthritis.

Koumine, an alkaloid, exerts therapeutic effects against rheumatoid arthritis (RA), and thus may have a potential application in novel treatment strategies against this disease. Herein, we investigated the regulatory effect of koumine on Th cell polarization using a "pyramid" structure model to elucidate the mechanism underlying its therapeutic effect on RA. The third layer of the model comprises the cytokine secretion layer, in which the effects of koumine on the balance of Th-related cytokines were investigated in mice with collagen-induced arthritis (CIA).

Association of blood lead exposure with frailty and its components among the Chinese oldest old.

Lead (Pb) is a widespread environmental contaminant, associated with a higher risk of functional impairment that can lead to frailty in older adults. However, few studies focused on the association of Pb exposure with frailty among the oldest old (aged ≥ 80 years). In this study, we aimed to assess the associations of Pb with frailty and its components in the oldest old.

APT1-Mediated Depalmitoylation Regulates Hippocampal Synaptic Plasticity.

Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity.

mTORC1 Signaling Pathway Mediates Chronic Stress-Induced Synapse Loss in the Hippocampus.

The mechanistic target of rapamycin complex 1 (mTORC1) signaling has served as a promising target for therapeutic intervention of major depressive disorder (MDD), but the mTORC1 signaling underlying MDD has not been well elucidated. In the present study, we investigated whether mTORC1 signaling pathway mediates synapse loss induced by chronic stress in the hippocampus. Chronic restraint stress-induced depression-like behaviors were tested by behavior tests (sucrose preference test, forced swim test and tail suspension test).

Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/β-Catenin Pathway in Human Hepatocellular Carcinoma.

() Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated.

Investigation of the Possible Allostery of Koumine Extracted From Benth. And Analgesic Mechanism Associated With Neurosteroids.

Translocator protein 18 kDa (TSPO) is an evolutionarily conserved 5-transmembrane domain protein, and has been considered as an important therapeutic target for the treatment of pain. We have recently reported the and pharmacological characterization of koumine as a TSPO positive allosteric modulator (PAM), more precisely ago-PAM. However, the probe dependence in the allostery of koumine is an important question to resolve, and the possible analgesic mechanism of koumine remains to be clarified.

Identification of Koumine as a Translocator Protein 18 kDa Positive Allosteric Modulator for the Treatment of Inflammatory and Neuropathic Pain.

Koumine is an alkaloid that displays notable activity against inflammatory and neuropathic pain, but its therapeutic target and molecular mechanism still need further study. Translocator protein 18 kDa (TSPO) is a vital therapeutic target for pain treatment, and recent research implies that there may be allostery in TSPO. Our previous competitive binding assay hint that koumine may function as a TSPO positive allosteric modulator (PAM).

Transcriptomic and proteomic analysis of putative digestive proteases in the salivary gland and gut of Empoasca (Matsumurasca) onukii Matsuda.

Background: Infestation by tea green leafhoppers (Empoasca (Matsumurasca) onukii) can cause a series of biochemical changes in tea leaves. As a typical cell-rupture feeder, E. onukii secretes proteases while using its stylet to probe the tender shoots of tea plants (Camellia sinensis).

Koumine Suppresses IL-1β Secretion and Attenuates Inflammation Associated With Blocking ROS/NF-κB/NLRP3 Axis in Macrophages.

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation.

Common homozygosity for predicted loss-of-function variants reveals both redundant and advantageous effects of dispensable human genes.

Humans homozygous or hemizygous for variants predicted to cause a loss of function (LoF) of the corresponding protein do not necessarily present with overt clinical phenotypes. We report here 190 autosomal genes with 207 predicted LoF variants, for which the frequency of homozygous individuals exceeds 1% in at least one human population from five major ancestry groups. No such genes were identified on the X and Y chromosomes.

NCBoost classifies pathogenic non-coding variants in Mendelian diseases through supervised learning on purifying selection signals in humans.

State-of-the-art methods assessing pathogenic non-coding variants have mostly been characterized on common disease-associated polymorphisms, yet with modest accuracy and strong positional biases. In this study, we curated 737 high-confidence pathogenic non-coding variants associated with monogenic Mendelian diseases. In addition to interspecies conservation, a comprehensive set of recent and ongoing purifying selection signals in humans is explored, accounting for lineage-specific regulatory elements.

NF-κB and Poly (ADP-ribose) Polymerase 1 Form a Positive Feedback Loop that Regulates DNA Repair in Acute Myeloid Leukemia Cells.

NF-κB mediates acquired resistance in acute myeloid leukemia (AML) cells treated with DNA-damaging agents. Because DNA repair is the major molecular shift that alters sensitivity to DNA-damaging agents, we explored whether activation of the NF-κB pathway promotes AML cell survival by regulating DNA repair after chemotherapy. Our results showed that RELA, an important subunit of NF-κB, regulated DNA repair by binding to the promoter region of the gene and affecting gene transcription.

Polarization coherent optical communications with adaptive polarization control over atmospheric turbulence.

In wireless optical communication systems, the coherent detection scheme suffers severe performance degradation due to the phase fluctuation and polarization offset. To deal with such challenges, we propose a polarization coherent optical communication scheme with adaptive polarization control (PCPC), where the transmitted continuous-wave light is split into two paths-the binary phase shift keying modulated signal light and the reference light-which are orthogonally polarized and combined before being sent to free space. In the receiving site, the interference between the two lights can effectively suppress the atmospheric turbulence-induced phase fluctuation.

Fabrication and characterization of chitosan/OGP coated porous poly(ε-caprolactone) scaffold for bone tissue engineering.

As one of the stimulators on bone formation, osteogenic growth peptide (OGP) improves both proliferation and differentiation of the bone cells in vitro and in vivo. The aim of this work was the preparation of three dimensional porous poly(ε-caprolactone) (PCL) scaffold with high porosity, well interpore connectivity, and then its surface was modified by using chitosan (CS)/OGP coating for application in bone regeneration. In present study, the properties of porous PCL and CS/OGP coated PCL scaffold, including the microstructure, water absorption, porosity, hydrophilicity, mechanical properties, and biocompatibility in vitro were investigated.

Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations.

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers.

Leflunomide treatment in corticosteroid-dependent myasthenia gravis: an open-label pilot study.

Leflunomide is an effective drug used in the treatment of rheumatoid arthritis. Here we report the findings of an open-label pilot study, which found that leflunomide is also an effective treatment for myasthenia gravis (MG). This study recruited 15 corticosteroid-dependent MG patients.