Multiomics integration-based molecular characterizations of COVID-19

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly became a global health challenge, leading to unprecedented social and economic consequences. The mechanisms behind the pathogenesis of SARS-CoV-2 are both unique and complex. Omics-scale studies are emerging rapidly and offer a tremendous potential to unravel the puzzle of SARS-CoV-2 pathobiology, as well as moving forward with diagnostics, potential drug targets, risk stratification, therapeutic responses, vaccine development and therapeutic innovation. This review summarizes various aspects of understanding multiomics integration-based molecular characterizations of COVID-19, which to date include the integration of transcriptomics, proteomics, genomics, lipidomics, immunomics and metabolomics to explore virus targets and developing suitable therapeutic solutions through systems biology tools. Furthermore, this review also covers an abridgment of omics investigations related to disease pathogenesis and virulence, the role of host genetic variation and a broad array of immune and inflammatory phenotypes contributing to understanding COVID-19 traits. Insights into this review, which combines existing strategies and multiomics integration profiling, may help further advance our knowledge of COVID-19.Peer reviewe

MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway.

The Hippo pathway plays a central role in tissue homoeostasis, and its dysregulation contributes to tumorigenesis. Core components of the Hippo pathway include a kinase cascade of MST1/2 and LATS1/2 and the transcription co-activators YAP/TAZ. In response to stimulation, LATS1/2 phosphorylate and inhibit YAP/TAZ, the main effectors of the Hippo pathway. Accumulating evidence suggests that MST1/2 are not required for the regulation of YAP/TAZ. Here we show that deletion of LATS1/2 but not MST1/2 abolishes YAP/TAZ phosphorylation. We have identified MAP4K family members--Drosophila Happyhour homologues MAP4K1/2/3 and Misshapen homologues MAP4K4/6/7-as direct LATS1/2-activating kinases. Combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses phosphorylation of LATS1/2 and YAP/TAZ in response to a wide range of signals. Our results demonstrate that MAP4Ks act in parallel to and are partially redundant with MST1/2 in the regulation of LATS1/2 and YAP/TAZ, and establish MAP4Ks as components of the expanded Hippo pathway

Effects and Mechanisms of Transcutaneous Electroacupuncture on Chemotherapy-Induced Nausea and Vomiting

Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA) at Neiguan (PC6) and Jianshi (PC5) on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n=34) and TEA group (n=38). TEA was performed at PC 6 and PC 5 (1 h, bid) in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1) In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P<0.01) and reduced the nausea score (P<0.05), compared with sham-TEA. (2) TEA significantly reduced serum levels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated via mechanisms involving serotonin and dopamine

Y-STR Haplotypic Polymorphisms for the Hakka Population in West China and Its Phylogenic Comparison with Other Chinese Populations

The Hakkas, undergone a series of great migrations, are usually identified with people who speak the Hakka language or share at least same Hakka ancestry. As the largest Hakka dialect island in West China, the Dongshan region was closely linked with the great migration wave of Hakka. However, the paternal genetic profiles of Dongshan Hakka have never been revealed. In the present study, 41 Y-chromosomal short tandem repeat (Y-STR) loci included in the SureID® PathFinder Plus Kit were analyzed in 353 unrelated male individuals (171 Hakka and 182 Han) of Sichuan Province, China. By analyzing 166 different haplotypes among Dongshan Hakkas and 176 different haplotypes among Sichuan Han males, haplotype diversity (HD) of the Hakka population was calculated as 0.9997 with a discrimination capacity (DC) of 0.9708. HD and DC were 0.9996 and 0.9670 for the Sichuan Han population, respectively. Most of the Y-STR loci were highly informative in both populations except DYS645. The genetic relationships were evaluated by comparing the Hakka population with 11 other groups that are relevant to the migration routes of Hakkas. The results of the MDS plot and phylogenetic tree indicate that the Dongshan Hakka population was closely related to Han nationalities from Anhui, Jiangxi, and Fujian Provinces

Theory of d+idd + id Second-Order Topological Superconductors

Topological superconductors are a class of unconventional superconducting materials featuring sub-gap zero-energy Majorana bound modes that hold promise as a building block for topological quantum computing. In this work, we study the realization of second-order topology that defines anomalous gapless boundary modes in a two-orbital superconductor with spin-orbital couplings. We reveal a time-reversal symmetry-breaking second-order topological superconducting phase with $d+id$-wave orbital-dependent paring without the need for the external magnetic field. Remarkably, this orbital-active $d$-wave paring gives rise to anomalous zero-energy Majorana corner modes, which is in contrast to conventional chiral $d$-wave pairing, accommodating one-dimensional Majorana edge modes. Our work not only reveals a unique mechanism of time-reversal symmetry breaking second-order topological superconductors but also bridges the gap between second-order topology and orbital-dependent pairings.Comment: 5+ pages, 5 figure

Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

<p>Abstract</p> <p>Background</p> <p>Synuclein gamma (SNCG), initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA) levels.</p> <p>Methods</p> <p>SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS.</p> <p>Results</p> <p>SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS) and overall survival (OS) (<it>P </it>< 0.0001). Multivariate analysis revealed that both tissue SNCG and serum CEA were independent prognostic factors of DFS (<it>P </it>= 0.001, <0.0001, respectively) for 170 patients with colon adenocarcinomas. Importantly, SNCG remained a prognostic determinant of DFS and OS (<it>P </it>= 0.001, 0.002) for 97 patients with normal preoperative serum CEA level.</p> <p>Conclusions</p> <p>Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.</p

NADPH oxidase mediates oxidative stress and ventricular remodeling through SIRT3/FOXO3a pathway in diabetic mice

Oxidative stress and mitochondrial dysfunction are important mechanisms of ventricular remodeling, predisposed to the development of diabetic cardiomyopathy (DCM) in type 2 diabetes mellitus. In this study, we have successfully established a model of type 2 diabetes using a high-fat diet (HFD) in combination with streptozotocin (STZ). The mice were divided into three groups of six at random: control, diabetes, and diabetes with apocynin and the H9c2 cell line was used as an in vitro model for investigation. We examined the molecular mechanisms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation on mitochondrial dysfunction and ventricular remodeling in the diabetic mouse model. Hyperglycemia-induced oxidative stress led to a reduced expression of sirtuin 3 (SIRT3), thereby promoting forkhead box class O 3a (FOXO3a) acetylation in ventricular tissue and H9c2 cells. Reactive oxygen species (ROS) overproduction promoted ventricular structural modeling and conduction defects. These alterations were mitigated by inhibiting NADPH oxidase with the pharmaceutical drug apocynin (APO). Apocynin improved SIRT3 and Mn-SOD expression in H9c2 cells transfected with SIRT3 siRNA. In our diabetic mouse model, apocynin improved myocardial mitochondrial function and ROS overproduction through the recovery of the SIRT3/FOXO3a pathway, thereby reducing ventricular remodeling and the incidence of DCM