Identification of cuproptosis-related molecular subtypes and a novel predictive model of COVID-19 based on machine learning

BackgroundTo explicate the pathogenic mechanisms of cuproptosis, a newly observed copper induced cell death pattern, in Coronavirus disease 2019 (COVID-19).MethodsCuproptosis-related subtypes were distinguished in COVID-19 patients and associations between subtypes and immune microenvironment were probed. Three machine algorithms, including LASSO, random forest, and support vector machine, were employed to identify differentially expressed genes between subtypes, which were subsequently used for constructing cuproptosis-related risk score model in the GSE157103 cohort to predict the occurrence of COVID-19. The predictive values of the cuproptosis-related risk score were verified in the GSE163151 cohort, GSE152418 cohort and GSE171110 cohort. A nomogram was created to facilitate the clinical use of this risk score, and its validity was validated through a calibration plot. Finally, the model genes were validated using lung proteomics data from COVID-19 cases and single-cell data.ResultsPatients with COVID-19 had higher significantly cuproptosis level in blood leukocytes compared to patients without COVID-19. Two cuproptosis clusters were identified by unsupervised clustering approach and cuproptosis cluster A characterized by T cell receptor signaling pathway had a better prognosis than cuproptosis cluster B. We constructed a cuproptosis-related risk score, based on PDHA1, PDHB, MTF1 and CDKN2A, and a nomogram was created, which both showed excellent predictive values for COVID-19. And the results of proteomics showed that the expression levels of PDHA1 and PDHB were significantly increased in COVID-19 patient samples.ConclusionOur study constructed and validated an cuproptosis-associated risk model and the risk score can be used as a powerful biomarker for predicting the existence of SARS-CoV-2 infection

The impact of family function on post-traumatic reactions of Chinese adolescents infected with COVID-19: a latent profile study

BackgroundSince the end of 2019, Corona Virus Disease 2019, also known as COVID-19, has broken out in various countries. However, the change of China's COVID-19 prevention and control policy and the sharp increase in the number of infected people are making the teenagers have post-traumatic reactions. Negative post-traumatic reactions include: post-traumatic stress disorder (PTSD), depression, anxiety. Positive post-traumatic reaction mainly refers to post-traumatic growth (PTG). The purpose of this study is to explore the post-traumatic reaction, which refers to PTSD, depression, anxiety and the co-occurrence pattern of growth after trauma and to further explore the influence of family function on different categories of Post-traumatic Reactions.MethodsLatent profile analysis (LPA) was used to explore the co-occurrence of PTSD, depression, anxiety, and PTG. Multiple logistics regression was used to analyze the influence of family function on different categories of post-traumatic response.ResultsThere were three categories of post-traumatic reactions in adolescents infected with COVID-19 adolescents infected with COVID-19, namely: growth class, struggling class, and pain class. Multivariate Logistic regression showed that the growth class and struggling class were affected by problem solving and behavior control in family function, while the growth class and pain class were affected by problem solving, roles, behavior control, and general functioning. Multiple logistic regression showed that the growth class and struggling class were affected by problem solving and roles.ConclusionsThe findings of this study provide evidence for the identification of high-risk individuals and the provision of effective interventions in clinical practice, as well as the influence of family functioning on the different categories of PTSD among adolescents infected with COVID-19

The Effects of ATIR Blocker on the Severity of COVID-19 in Hypertensive Inpatients and Virulence of SARS-CoV-2 in Hypertensive hACE2 Transgenic Mice.

Angiotensin-converting enzyme 2 (ACE2) is required for the cellular entry of the severe acute respiratory syndrome coronavirus 2. ACE2, via the Ang-(1-7)-Mas-R axis, is part of the antihypertensive and cardioprotective effects of the renin-angiotensin system. We studied hospitalized COVID-19 patients with hypertension and hypertensive human(h) ACE2 transgenic mice to determine the outcome of COVID-19 with or without AT1 receptor (AT1R) blocker treatment. The severity of the illness and the levels of serum cardiac biomarkers (CK, CK-BM, cTnI), as well as the inflammation markers (IL-1, IL-6, CRP), were lesser in hypertensive COVID-19 patients treated with AT1R blockers than those treated with other antihypertensive drugs. Hypertensive hACE2 transgenic mice, pretreated with AT1R blocker, had increased ACE2 expression and SARS-CoV-2 in the kidney and heart, 1 day post-infection. We conclude that those hypertensive patients treated with AT1R blocker may be at higher risk for SARS-CoV-2 infection. However, AT1R blockers had no effect on the severity of the illness but instead may have protected COVID-19 patients from heart injury, via the ACE2-angiotensin1-7-Mas receptor axis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12265-021-10147-3

Integrins promote axonal regeneration after injury of the nervous system.

Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling. Integrin biology is more complex in the central nervous system. Integrins receptors are transported into growing axons during development, but selective polarised transport of integrins limits the regenerative response in adult neurons. Manipulation of integrins and related molecules to control their activation state and localisation within axons is a promising route towards stimulating effective regeneration in the central nervous system

Image_1_Identification of cuproptosis-related molecular subtypes and a novel predictive model of COVID-19 based on machine learning.pdf

BackgroundTo explicate the pathogenic mechanisms of cuproptosis, a newly observed copper induced cell death pattern, in Coronavirus disease 2019 (COVID-19).MethodsCuproptosis-related subtypes were distinguished in COVID-19 patients and associations between subtypes and immune microenvironment were probed. Three machine algorithms, including LASSO, random forest, and support vector machine, were employed to identify differentially expressed genes between subtypes, which were subsequently used for constructing cuproptosis-related risk score model in the GSE157103 cohort to predict the occurrence of COVID-19. The predictive values of the cuproptosis-related risk score were verified in the GSE163151 cohort, GSE152418 cohort and GSE171110 cohort. A nomogram was created to facilitate the clinical use of this risk score, and its validity was validated through a calibration plot. Finally, the model genes were validated using lung proteomics data from COVID-19 cases and single-cell data.ResultsPatients with COVID-19 had higher significantly cuproptosis level in blood leukocytes compared to patients without COVID-19. Two cuproptosis clusters were identified by unsupervised clustering approach and cuproptosis cluster A characterized by T cell receptor signaling pathway had a better prognosis than cuproptosis cluster B. We constructed a cuproptosis-related risk score, based on PDHA1, PDHB, MTF1 and CDKN2A, and a nomogram was created, which both showed excellent predictive values for COVID-19. And the results of proteomics showed that the expression levels of PDHA1 and PDHB were significantly increased in COVID-19 patient samples.ConclusionOur study constructed and validated an cuproptosis-associated risk model and the risk score can be used as a powerful biomarker for predicting the existence of SARS-CoV-2 infection.</p

A meta-analysis of early oral refeeding and quickly increased diet for patients with mild acute pancreatitis

Background/Aim: The objective of the study is to clarify whether early oral refeeding (EORF) and quickly increasing diet (QID) are of benefit to patients with mild acute pancreatitis compared with a traditional oral refeeding strategy. Materials and Methods: Studies were searched in PubMed, Cochrane library, ScienceDirect, SpringerLink, China Biology Medicine disc and Embase. A meta-analysis was then performed, using relapse of abdominal pain, nausea/vomiting, and length of hospital stay (LOHS) as the evaluation indices. Results: Eight trials met the inclusion criteria. For the oral refeeding time group, EORF could significantly decrease the LOHS (mean deviation [MD] −1.97; 95% confidence interval (CI) −3.32 to −0.62;P = 0.004), and there was no significant difference for relapse of abdominal pain (relative risk [RR] 1.17; 95% CI 0.69–2.00;P = 0.56) or nausea/vomiting (RR 1.30; 95% CI 0.19–8.82;P = 0.79) when compared with conventional oral refeeding. For the oral refeeding material group, there was no significant difference for relapse of abdominal pain (RR 0.86; 95% CI 0.53–1.40;P = 0.54), nausea/vomiting (risk difference −0.01; 95% CI −0.19–0.18;P = 0.94), or LOHS (MD −0.88; 95% CI −2.24–0.48;P = 0.20) between the QID and stepwise increasing diet groups. Conclusion: Pure EORF or QID caused no damage to patients with mild acute pancreatitis, and EORF could significantly decrease the LOHS

The wurtzite-rocksalt phase transition for a BexMgyZn1-x-yO alloy: Be content vs Mg content

The Be-and Mg-content-dependent phase transition of BexMgyZn1 x O-y alloy is investigated by theoretically calculations and experiments. For a given content of Be, the maximum content of Mg at which the wurtzite structure still remains in BexMgyZn1 x O-y alloy is intensively studied. We find that as the content of Be increases, the maximum content of Mg in wurtzite BexMgyZn(1 x) O-y alloy increases accordingly. Moreover, the Be-and Mg-content-dependent band gap of the alloy at each wurtzite-rocksalt transition point is evaluated, which is expressed as an empirical law. In addition, the mechanism underlying the tunable band gap of the alloy in wurtzite BexMgyZn1 x O-y alloy is revealed. (C) 2014 Elsevier B.V. All rights reserved