Browning of Pig White Preadipocytes by Co-Overexpressing Pig PGC-1α and Mice UCP1

Background/Aims: Brown adipose tissue (BAT) is critical for mammals’ survival in the cold environment. BAT-dependent non-shivering thermogenesis is attributed to uncoupling protein 1 (UCP1)’s disengagement of oxidative phosphorylation from ATP synthesis and dissipates energy as heat. Thus individuals with a substantial amount of BAT are better equipped during cold stress and less likely to become obese. Recently, our laboratory has shown pig adipocytes have no UCP1 protein. The inability of newborn piglets to generate heat contributed to its high death rate. Repairing the genetic defect of UCP1 in pig adipocytes has implications in defending against cold for piglets and developing an alternative treatment for human obesity. Methods: Q-PCR, western blotting (WB) and oxygen consumption measurement were used to enable functional UCP1 protein in preadipocytes. Immunoprecipitation (IP), chromatin immunoprecipitation (CHIP), and dual-luciferase reporter assay system were used to clarify the thermogenesis mechanism of functional UCP1. Results: Only co-overexpressing mice UCP1 and pig PGC-1α increased not only the mitochondrial number but also the uncoupled respiration rate in the transfected pig adipocytes. The functional mice UCP1 increased the pig PGC-1α activity through the AMPK-SIRT1 pathway. The active form PGC-1α interacted with transcription factors Lhx8, Zic1, ERRα, and PPARα to regulate the expression of mitochondrial energy metabolism and adipocytes browning-related genes. Conclusion: Our data suggest a model in which pig PGC-1α and mice UCP1 work collaboratively to restore uncoupling respiration in pig preadipocytes. These results have great implications for piglet survival and developing an alternative treatment for human obesity in the future

Identification and Quantification, Metabolism and Pharmacokinetics, Pharmacological Activities, and Botanical Preparations of Protopine: A Review

Through pharmacological activity research, an increasing number of natural products and their derivatives are being recognized for their therapeutic value. In recent years, studies have been conducted on Corydalis yanhusuo W.T. Wang, a valuable medicinal herb listed in the Chinese Pharmacopoeia. Protopine, one of its components, has also become a research hotspot. To illustrate the identification, metabolism, and broad pharmacological activity of protopine and the botanical preparations containing it for further scientific studies and clinical applications, an in-depth and detailed review of protopine is required. We collected data on the identification and quantification, metabolism and pharmacokinetics, pharmacological activities, and botanical preparations of protopine from 1986 to 2021 from the PubMed database using “protopine” as a keyword. It has been shown that protopine as an active ingredient of many botanical preparations can be rapidly screened and quantified by a large number of methods (such as the LC-ESI-MS/MS and the TLC/GC-MS), and the possible metabolic pathways of protopine in vivo have been proposed. In addition, protopine possesses a wide range of pharmacological activities such as anti-inflammatory, anti-platelet aggregation, anti-cancer, analgesic, vasodilatory, anticholinesterase, anti-addictive, anticonvulsant, antipathogenic, antioxidant, hepatoprotective, neuroprotective, and cytotoxic and anti-proliferative activities. In this paper, the identification and quantification, metabolism and pharmacokinetics, pharmacological activities, and botanical preparations of protopine are reviewed in detail to lay a foundation for further scientific research and clinical applications of protopine

Hydrothermal Aging Mechanisms of All-Steel Radial Tire Composites

This work focused on the effects of the hydrothermal environment on the aging of all-steel radial tire (ASRT) composites. Composite specimens were conditioned by immersion in deionized water at 30, 60 and 90 °C. Its water absorption, thermal and mechanical properties (tensile strength, elasticity modulus, elongation at break and interfacial shear strength), morphological structure, as well as molecular cross-linking reaction were investigated before and after aging. Results indicated that there was no dynamic equilibrium of water absorption of ASRT composites after deviating from the Fickian model. The molecular cross-linking density of the rubber matrix showed an increase in the early stage of aging. Then, the mechanical properties suffered of a drop due to the degradation of the rubber matrix and the poor interface between the steel fiber and rubber matrix. Additionally, a systematic hygrothermal aging mechanism was proposed

MiR-501-3p Forms a Feedback Loop with FOS, MDFI, and MyoD to Regulate C2C12 Myogenesis

Skeletal muscle plays an essential role in maintaining body energy homeostasis and body flexibility. Loss of muscle mass leads to slower wound healing and recovery from illness, physical disability, poor quality of life, and higher health care costs. So, it is critical for us to understand the mechanism of skeletal muscle myogenic differentiation for maintaining optimal health throughout life. miR-501-3p is a novel muscle-specific miRNA, and its regulation mechanism on myoblast myogenic differentiation is still not clear. We demonstrated that FOS was a direct target gene of miR-501-3p, and MyoD regulated miR-501-3p host gene Clcn5 through bioinformatics prediction. Our previous laboratory experiment found that MDFI overexpression promoted C2C12 myogenic differentiation and MyoD expression. The database also showed there is an FOS binding site in the MDFI promoter region. Therefore, we hypothesize that miR-501-3p formed a feedback loop with FOS, MDFI, and MyoD to regulate myoblast differentiation. To validate our hypothesis, we demonstrated miR-501-3p function in the proliferation and differentiation period of C2C12 cells by transfecting cells with miR-501-3p mimic and inhibitor. Then, we confirmed there is a direct regulatory relationship between miR-501-3p and FOS, MyoD and miR-501-3p, FOS and MDFI through QPCR, dual-luciferase reporter system, and ChIP experiments. Our results not only expand our understanding of the muscle myogenic development mechanism in which miRNA and genes participate in controlling skeletal muscle development, but also provide treatment strategies for skeletal muscle or metabolic-related diseases in the future

Xingnaojing for Moderate-to-severe Acute ischemic Stroke (XMAS): study protocol for a randomized controlled trial

Abstract Background Xingnaojing injection (XNJ) is widely used for the treatment of stroke in China. However, there is currently a lack of high-quality evidence of its efficacy for acute ischemic stroke. The main objective of this study is to determine whether the addition of XNJ to standard care improves the 3-month functional outcome in patients with acute ischemic stroke (AIS). Methods/design The XMAS study is a multicenter, prospective, randomized controlled, open-label trial with a blinded endpoints design. A total of 720 patients will be randomly allocated to either the intervention or the control group in a 1:1 ratio. The intervention group receives XNJ combined with standard care, and the control group receives standard care alone. XNJ will be administered intravenously every 12 h for 10 days. The primary outcome is the proportion of patients who are independent at 3 months after stroke onset defined as a modified Rankin Scale score of 0 to 2. Secondary outcomes include early neurological deterioration at 48 h, the change in National Institutes of Health Stroke Scale score, patient-reported outcome, symptomatic intracranial hemorrhage at 10 days, the Barthel Index score, deaths from any cause and cardiovascular events at 3 months. Discussion The results of this trial will provide critical evidence for XNJ in the treatment of AIS as a complementary approach that can be initiated after reperfusion therapy or when the AIS is not eligible for thrombolytic treatment. Trial registration Clinical Trials.gov, ID: NCT02728180 . Registered on 28 March 2016

The complete mitochondrial genome of Pagetopsis macropterus (Notothenioidei: Channichthyidae) with phylogenetic consideration

In this study, the complete mitochondrial genome of Pagetopsis macropterus was obtained, which was 17,342 bp including 2 ribosomal RNAs, 13 protein-coding genes, 22 transfer RNAs, and one control region. Of the 37 genes, 28 were encoded on the heavy strand, while 9 were encoded on light strand. The overall nucleotide composition of mitogenome is 27.08% for A, 25.75% for T, 29.78% for C, 17.39% for G, respectively, in accordance with structural characteristics of AT rich. Further, the phylogenetic tree based on complete mtDNA sequences revealed that the P. macropterus was closest to some species of Channichthyidae. This study could provide some valuable information for the studies on evolution for low-temperature adaptability, stock evaluation, and population genetics of P. macropterus

HPCC: high precision congestion control

© 2019 Association for Computing Machinery. Congestion control (CC) is the key to achieving ultra-low latency, high bandwidth and network stability in high-speed networks. From years of experience operating large-scale and high-speed RDMA networks, we find the existing high-speed CC schemes have inherent limitations for reaching these goals. In this paper, we present HPCC (High Precision Congestion Control), a new high-speed CC mechanism which achieves the three goals simultaneously. HPCC leverages in-network telemetry (INT) to obtain precise link load information and controls traffic precisely. By addressing challenges such as delayed INT information during congestion and overreaction to INT information, HPCC can quickly converge to utilize free bandwidth while avoiding congestion, and can maintain near-zero in-network queues for ultra-low latency. HPCC is also fair and easy to deploy in hardware. We implement HPCC with commodity programmable NICs and switches. In our evaluation, compared to DCQCN and TIMELY, HPCC shortens flow completion times by up to 95%, causing little congestion even under large-scale incasts

Table_1_MGMT unmethylation and high levels of CD47 and TIGIT indicate a poor prognosis in adult diffuse gliomas.doc

IntroductionIn 2021, the World Health Organization published a new classification system for central nervous system tumors. This study reclassified the adult diffuse glioma (ADG) into astrocytoma, oligodendroglioma, and glioblastoma (GBM) according to the new tumor classification.MethodsThe association of TERT promoter (pTERT) mutation, MGMT methylation, and CD47/TIGIT expression with patient prognosis was investigated.ResultsImmunohistochemical analysis showed that the expression levels of CD47 and TIGIT in tumor tissues were significantly higher than those in normal brain tissues. CD47 levels were higher in GBM and grade 4 astrocytoma tissues. TIGIT expression was also higher in patients with GBM. The high expressions of CD47, TIGIT, and CD47/TIGIT were positively correlated with MGMT unmethylation but not pTERT mutation. Moreover, MGMT unmethylation was associated with poor overall survival in astrocytoma. High CD47, TIGIT, and CD47/TIGIT levels were associated with significantly reduced survival in ADG and GBM. GBM, MGMT unmethylation, and high CD47 expression were independent prognostic factors for overall survival in ADG.DiscussionCollectively, these results showed that the MGMT unmethylation and high levels of CD47 and TIGIT are associated with a poor prognosis in ADG. Patients with high CD47 and TIGIT expression may benefit from anti-CD47 and TIGIT immunotherapy.</p