A 3M K-means algorithm for fast and practicably identifying COVID-19 close contacts

Given that the risk of the COVID-19 epidemic still exists and the flow of patients is difficult to monitor, identifying the people who have had close contact with the confirmed cases is important in anti-epidemic tasks whether in areas where the epidemic is developing rapidly or in areas where the epidemic has been phase-controlled. This article discusses how to locate people who have been in close contact with confirmed cases quickly and determine the risk of infection. From the perspective of the government, this work proposes a multi-snapshot multi-stage minority K-means (3M K-means) algorithm. This algorithm reduces the amount of data and considerably improves the speed of clustering by quickly ignoring the excluded risk classes and points in the process in the early stages, whereas traditional algorithms involve with O(N2) computational complexity which needs several days, impracticably for the COVID-19 urgent situations. The 3M algorithm greatly cuts down the computational time, thereof making the rapid warning of close contacts practicable. The methods are simple, yet efficient and practicable for the COVID-19 urgent situations The use of this algorithm can help control the COVID-19 epidemic, achieve significant cost savings, and provide the psychological guarantee of people for work resumption

Stage II Pancreatic Adenocarcinoma after Endovascular Repair of Abdominal Aortic Aneurysm: A Case Report and Literature Review

Backgrounds: Concomitant abdominal aortic aneurysms (AAA) and gastrointestinal malignancies are uncommon. Endovascular repair (EVAR) is widely used to treat AAA. However, no consensus exists on the optimal strategy for treating AAA when associated with pancreatic adenocarcinoma. In addition, only few reports of pancreaticoduodenectomy (PD) after EVAR exist. Presentation of case: A pancreatic tumor was detected during follow-up after EVAR for AAA in an 83-year-old female patient. The diagnosis was high-grade intraepithelial neoplasia. Modified pylorus-preserving pancreaticoduodenectomy was safely performed. The patient recovered moderately and was discharged two weeks after surgery. The pathological diagnosis was middle-grade pancreatic ductal adenocarcinoma. The patient survived for 24 months with no recurrence or cardiovascular complications. Conclusions: Conducting periodic follow-ups after AAA surgery is helpful for the early discovery of gastrointestinal tumors. EVAR surgery is safe and feasible and thus recommended for AAA patients with pancreatic cancer, although it may increase the risk of cancer. The stage of malignancy and post-EVAR medical history can be valuable in evaluating the benefits of pancreatic surgery for such cases

Phenylalanine Residues in the Active Site of CYP2E1 Participate in Determining the Binding Orientation and Metabolism-Dependent Genotoxicity of Aromatic Compounds

The composition of amino acids forming the active site of a CYP enzyme is impactful in its substrate selectivity. For CYP2E1, the role of PHE residues in the formation of effective binding orientations for its aromatic substrates remains unclear. In this study, molecular docking and molecular dynamics analysis were performed to reflect the interactions between PHEs in the active site of human CYP2E1 and various aromatic compounds known as its substrates. The results indicated that the orientation of 1-methylpyrene (1-MP) in the active site was highly determined by the presence of PHEs, PHE478 contributing to the binding free energy most significantly. Moreover, by building a random forest model the relationship between each of 19 molecular descriptors of polychlorinated biphenyl (PCB) compounds (from molecular docking, quantum mechanics, and physicochemical properties) and their human CYP2E1-dependent mutagenicityas established mostly in our lab, was investigated. The presence of PHEs did not appear to significantly modify the electronic or structural feature of each bound ligand (PCB), instead, the flexibility of the conformation of PHEs contributed substantially to the effective binding energy and orientation. It is supposed that PHE residues adjust their own conformation to permit a suitablly shaped cavity for holding the ligand and forming its orientation as favorable for a biochemical reaction. This study has provided some insights into the role of PHEs in guiding the interactive adaptation of the active site of human CYP2E1 for the binding and metabolism of aromatic substrates

Associations of Homocysteine, Folate, and Vitamin B12 with Osteoarthritis: A Mendelian Randomization Study

Homocysteine, inversely related to folate and vitamin B12, is an independent risk factor for several age-related disorders. However, little is known about the association of homocysteine and related vitamins with osteoarthritis (OA). This study aimed to elucidate the potential causal effects of homocysteine, folate, and vitamin B12 on site- and gender-specific OA by applying the two-sample Mendelian randomization (MR) approach. Genetically predicted homocysteine showed adverse effects on overall OA (95% confidence interval (CI): 1.044–1.155), knee OA (95% CI: 1.000–1.167), hip OA (95% CI: 1.057–1.297), and spine OA (95% CI: 1.017–1.216). Genetically predicted folate showed protective effects on overall OA (95% CI: 0.783–0.961) and spine OA (95% CI: 0.609–0.954). Folate (95% CI: 0.887–1.004) and vitamin B12 (95% CI: 0.886–1.009) showed a protective trend against knee OA. The patterns of associations were site and gender specific. In conclusion, homocysteine had adverse effects on OA, especially on OA at weight-bearing joints and in females. Folate and vitamin B12 had protective effects on OA. Homocysteine-lowering interventions may be a potential option in the treatment and prevention of OA

Preventative effect of TSPO ligands on mixed antibody-mediated rejection through a Mitochondria-mediated metabolic disorder

Abstract Background Immune-mediated rejection was the major cause of graft dysfunction. Although the advances in immunosuppressive agents have markedly reduced the incidence of T-cell-mediated rejection after transplantation. However, the incidence of antibody-mediated rejection (AMR) remains high. Donor-specific antibodies (DSAs) were considered the major mediators of allograft loss. Previously, we showed that treatment with 18-kDa translocator protein (TSPO) ligands inhibited the differentiation and effector functions of T cells and reduced the rejection observed after allogeneic skin transplantation in mice. This study we further investigate the effect of TSPO ligands on B cells and DSAs production in the recipients of mixed-AMR model. Methods In vitro, we explored the effect of treatment with TSPO ligands on the activation, proliferation, and antibody production of B cells. Further, we established a heart-transplantation mixed-AMR model in rats. This model was treated with the TSPO ligands, FGIN1-27 or Ro5-4864, to investigate the role of ligands in preventing transplant rejection and DSAs production in vivo. As TSPO was the mitochondrial membrane transporters, we then investigated the TSPO ligands effect on mitochondrial-related metabolic ability of B cells as well as expression of downstream proteins. Results In vitro studies, treatment with TSPO ligands inhibited the differentiation of B cells into CD138+CD27+ plasma cells; reduced antibodies, IgG and IgM, secretion of B cells; and suppressed the B cell activation and proliferation. In the mixed-AMR rat model, treatment with FGIN1-27 or Ro5-4864 attenuated DSA-mediated cardiac-allograft injury, prolonged graft survival, and reduced the numbers of B cells, including IgG+ secreting B cells, T cells and macrophages infiltrating in grafts. For the further mechanism exploration, treatment with TSPO ligands inhibited the metabolic ability of B cells by downregulating expression of pyruvate dehydrogenase kinase 1 and proteins in complexes I, II, and IV of the electron transport chain. Conclusions We clarified the mechanism of action of TSPO ligands on B-cell functions and provided new ideas and drug targets for the clinical treatment of postoperative AMR

MicroRNA-30a regulates cell proliferation and tumor growth of colorectal cancer by targeting CD73

Abstract Background MicroRNAs are non-coding RNAs which regulate a variety of cellular functions in the development of tumors. Among the numerous microRNAs, microRNA-30a (miR-30a) is thought to play an important role in the processes of various human tumors. In this study, we aimed to explore the role of miR-30a in the process of colorectal cancer (CRC). Methods The quantitative real-time PCR and western blot analysis were used to detect the expressions of miR-30a and CD73 in CRC cell lines and clinical tissues. The luciferase reporter assay was conducted to validate the association between miR-30a and CD73. The CCK-8, terminal deoxynucleotidyl transferase dUTP -biotin nick end labeling (TUNEL) assays and cell cycle flow cytometry were carried out to verify the biological functions of miR-30a in vitro. The nude mouse tumorigenicity experiment was used to clarify the biological role of miR-30a in vivo. Results The expression of miR-30a was significantly reduced in tumor cells and tissues of CRC. The proliferation ability of CRC cells was suppressed and the apoptosis of cells was promoted when miR-30a is over-regulated, however, the biological effects would be inverse since the miR-30a is down-regulated. CD73 is thought to be a target binding gene of miR-30a because miR-30a can bind directly to the 3′-UTR of CD73 mRNA, subsequently reducing its expression. The proliferation suppression of the CRC cells mediated by miR-30a could be rescued after up-regulating the expression of CD73. Conclusions MiR-30a plays an important role on regulating the cell proliferation and apoptosis, thus affecting the growth of the tumor in CRC. And it may participate in the disease process of CRC by regulating the expression of CD73