Notes

Priming COVID-19 salience raises bias and also discriminatory intention towards The natives along with Hispanics.
When deaths were unrelated to methamphetamine, the median concentrations of methamphetamine and amphetamine were 130 and 44 ng/mL, respectively. The highest median methamphetamine concentration was found in urine (5281 ng/mL), followed by stomach contents (878 ng/mL), bile (762 ng/mL), vitreous humor (3 ng/mL), and blood (208 ng/mL). Almost 40% of the studied cases involved violence, 61% were accidental, 21% were suicides, 17% were homicides, and 2% were natural deaths. Methamphetamine is highly addictive. Increases in deaths have been seen in various countries. More awareness, education and treatment programs are required to reduce the likelihood of addiction, crimes, suicide, and other fatalities resulting from methamphetamine abuse.We present a case of fatal poisoning from accidental ingestion of Gelsemium elegans (G. elegans), a rarely toxic plant. A 41-year-old man was found dead, at his home, 6 h after drinking homemade herbal liqueur during lunch. Autopsy and routine toxicological analyses identified neither significant pathological findings nor routine poisons. However, a local botanist revealed that the homemade herbal liqueur contained G. elegans, a poisonous plant specific to Asia. To ascertain whether the decedent had ingested G. elegans, we performed liquid chromatography-mass spectrometry (LC-MS) and found two alkaloids (gelsemine and koumine) in his blood, gastric contents, as well as the suspected herbal liqueur. The cause of death was therefore confirmed to be G. elegans poisoning. Case reports of fatal poisoning due to ingestion of G. elegans are quite rare in English. Therefore, the present case broadens the scope on the possibility of death due to ingestion of G. elegans for forensic pathologists and toxicologists.NOD-like receptor protein 3 (NLRP3) inflammasome is tightly related to the pathogenesis of cerebral ischemia/reperfusion (I/R) injury, and oridonin (Ori) has shown the potential to alleviate ischemia/reperfusion injury with underlying mechanisms. Our study aims to figure out whether Ori protects against the cerebral ischemia/reperfusion injury by the NLRP3 inflammasome signaling. In this study, a temporary middle cerebral artery occlusion (MCAO) and reperfusion surgery was conducted on male C57BL/6 mice to mimic cerebral I/R injury in vivo. Cellular model of cerebral I/R in vitro was achieved by oxygen-glucose deprivation and reintroduction (OGD/R) in BV2 microglia cells. We found that Ori treatment significantly relieved the neurological deficits, neuronal injury and microglia activation in I/R mice according to morphological and histological analyses. Meanwhile, the inactivation of NLRP3 inflammasome was determined in Ori-treated mice with significantly down-regulated expressions of inflammasome-related genes. Western-blot analysis further demonstrated the negative effect of Ori on NF-κB signaling with diminished phosphorylation and degradation of IκBα as well as suppressed translocation of p65. Furthermore, we indicated that Ori suppressed the activation of NLRP3 inflammasome in OGD/R induced BV2 microglia cells by inhibiting NF-κB signaling. In summary, our findings make Ori a potential candidate for therapy of cerebral I/R injury in the future.Umbilical cord-derived mesenchymal stem cells (UC-MSCs) constitute a class of cells with significant self-renewal and multilineage differentiation properties and have great potential for therapeutic applications and the genetic conservation of endangered animals. In this study, we successfully isolated and cultured UC-MSCs from the blood vessels of giant panda umbilical cord (UC). The cells were arranged in a vortex or cluster pattern and exhibited a normal karyotype, showing the morphological characteristics of fibroblasts. In addition, we found that basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) promoted cell proliferation, whereas stem cell factor (SCF) did not promote cell proliferation. Cultured UC-MSCs were negative for CD34 (hematopoietic stem cell marker) and CD31 (endothelial cell marker), but positive for MSC markers (CD44, CD49f, CD105, and CD73) and stem cell markers (KLF4, SOX2, and THY1). Similar to other MSCs, giant panda UC-MSCs have multiple differentiation ability and can differentiate into adipocytes, osteoblasts and chondrocytes. Giant panda UC-MSCs are new resources for basic research as cell models following their differentiation into different cell types and for future clinical treatments of giant panda diseases.Tendon injuries are the leading cause of chronic debilitation to patients. Tendon stem/progenitor cells (TSPCs) are potential seed cells for tendon tissue engineering and regeneration, but TSPCs are prone to lose their distinct phenotype in vitro and specific differentiation into the tenocyte lineage is challenging. Utilizing small molecules in an ex vivo culture system may be a promising solution and can significantly improve the therapeutic applications of these cells. Here, by using an image-based, high-throughput screening platform on small molecule libraries, this study established an effective stepwise culture strategy for TSPCs application. The study formulated a cocktail of small molecules which effected proliferation, tenogenesis initiation and maturation phases, and significantly upregulated expression of various tendon-related genes and proteins in TSPCs, which were demonstrated by high-throughput PCR, ScxGFP reporter assay and immunocytochemistry. Furthermore, by combining small molecule-based culture system with 3D printing technology, we embedded living, chemical-empowered TSPCs within a biocompatible hydrogel to engineer tendon grafts, and verified their enhanced ability in promoting functional tendon repair and regeneration both in vivo and in situ. The stepwise culture system for TSPCs and construction of engineered tendon grafts can not only serve as a platform for further studies of underlying molecular mechanisms of tenogenic differentiation, but also provide a new strategy for tissue engineering and development of novel therapeutics for clinical applications.Citrullination is a post-translational modification (PTM) that converts peptidyl-arginine into peptidyl-citrulline; citrullination is catalyzed by the protein arginine deiminases (PADs). This PTM is associated with several physiological processes, including the epigenetic regulation of gene expression, neutrophil extracellular trap formation, and DNA-damage induced apoptosis. Notably, aberrant protein citrullination is relevant to several autoimmune and neurodegenerative diseases and certain forms of cancer. As such, the PADs are promising therapeutic targets. In this review, we discuss recent advances in the development of PAD inhibitors and activity-based probes, the development and use of citrulline-specific probes in chemoproteomic applications, and methods to site-specifically incorporate citrulline into proteins.The SARS-CoV-2 Variant of Concern 202012/01 (VOC-202012/01) emerged in southeast England and rapidly spread worldwide. This variant is believed to be more transmissible, with all attention being given to its spike mutations. However, VOC-202012/01 has also a mutation (Q27stop) that truncates the ORF8, a likely immune evasion protein. Removal of ORF8 changes the clinical outset of the disease, which may affect the virus transmissibility. Here I provide a detailed analysis of all reported ORF8-deficient lineages found in the background of relevant spike mutations, identified among 231,433 SARS-CoV-2 genomes. I found 19 ORF8 nonsense mutations, most of them occurring in the 5' half of the gene. The ORF8-deficient lineages were rare, representing 0.67% of sequenced genomes. Nevertheless, I identified two clusters of related sequences that emerged recently and spread in different countries. The widespread D614G spike mutation was found in most ORF-deficient lineages. Although less frequent, HV69-70del and L5F spike mutations occurred in the background of six different ORF8 nonsense mutations. I also confirmed that VOC-202012/01 is the ORF8-deficient variant with more spike mutations reported to date, although other variants could have up to six spike mutations, some of putative biological relevance. Overall, these results suggest that monitoring ORF8-deficient lineages is important for the progression of the COVID-19 pandemic, particularly when associated with relevant spike mutations.Studying thermal stability of proteins not only provides insight into protein structure but also is instrumental in identifying previously unknown interaction partners. We develop a machine learning strategy that combines orthogonal partial least squares regression and stability screening of Silver Bullets Bio library to identify biologically active molecules that enhance protein stability. This strategy proves effective in extracting the stability-enhancing molecules for SMYD5, a histone lysine methyltransferase that regulates chromosome integrity. Protamine, a histone substitute in chromatin condensation during spermatogenesis, is identified as the most influential molecule to enhance SMYD5 thermal stability. We find that the C-terminal poly-glutamic acid tract (poly-E) and a 30-residue insertion in MYND domain (M-insertion), which are unique to SMYD5, regulate the structural stability. However, protamine plays a dominant role in SMYD5 stability, and in the presence of protamine, the poly-E tract or M-insertion loses its ability to affect the stability. The stability-enhancing effect of protamine is SMYD5 specific, and for SMYD2, a closely related homolog, protamine exhibits opposite, destabilizing effects. We find that both SMYD5 and SMYD2 interact with protamine, where SMYD5 interaction is independent of the poly-E tract and M-insertion. Protamine not only helps provide insight into the structure-stability relationships of SMYD5, but also suggests a potential functional link of SMYD5 to spermatogenesis. SMYD5 is a ubiquitously expressed gene with the highest expression in testis, especially in the seminiferous ducts that contain germ cells. Thus, our study opens up avenues that could help delineate major mechanisms underlying chromatin dynamics during spermatogenesis.Atherosclerosis is a progressive inflammatory disease characterized by the accumulation of lipids in the arterial wall. Inflammation plays a key role in the pathogenesis of atherosclerosis and some previous studies have shown the role of adipokines during the inflammatory process of atherosclerosis. check details Therefore, the present study aimed to evaluate the impacts of adiponectin and CTRP15 on inflammatory cytokines secretions from THP1 and primary macrophages.
THP1 monocytes were differentiated to macrophages and primary monocytes were then isolated from patients with coronary artery disease and controls who were differentiated to macrophages. Macrophages were treated with LPS, LPS+adiponectin, and LPS+CTRP15.

Adiponectin and CTRP15 have reduced IL-6 and TNF-α secretions from LPS-induced THP1 macrophages, and the CTRP15 indicated a more potent anti-inflammatory property compared to adiponectin. In addition, adiponectin reduced cytokines' expressions and secretions in primary macrophages of both patient and control groups.
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