Ginsenoside Rd Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Inflammation and Apoptosis through PI3K/Akt Signaling Pathway.

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.

Continuous enrichment and trace analysis of tetracyclines in bovine milk using dual-functionalized aqueous biphasic system combined with high-performance liquid chromatography.

Two PPG1000 based temperature-sensitive magnetic ionic liquid were synthesized and characterized. The temperature-sensitive magnetic ionic liquid aqueous biphasic system combined with HPLC was applied for the continuous enrichment and trace analysis of tetracycline antibiotics (TC) in bovine milk for the first time. High enrichment factors were achieved and the detection was highly sensitive. The trace analysis of TC was rapid, free of organic solvent, recyclable and magnetically assisted for phase separation. Under optimum conditions, wide linear ranges of 0.25-300 ng/mL for all TC, high enrichment factors of 217.7-231.4, good precisions with relative standard deviation in the range of 0.74-3.97%, very low limits of detection of 0.031-0.067 ng/mL, limits of quantification of 0.103-0.223 ng/mL, and good recoveries of 94.28-99.76% were acquired for the proposed analytical method. Real milk analysis was satisfactory. This developed analytical method is showing great potential for trace analysis of targeted analytes in foods and drinks.

A mobile APP-based, customizable automated device for self-administered olfactory testing and an implementation of smell identification test.

Olfactory tests are used for the evaluation of ability to detect and identify common odors in humans psychophysically. Olfactory tests are currently administered by professionals with a set of given odorants. Manual administration of such tests can be labor and cost intensive and data collected as such are confounded with experimental variables, which adds personnel costs and introduces potential errors and data variability. For large-scale and longitudinal studies, manually recorded data must be collected and compiled from multiple sites. It is difficult to standardize the way data are collected and recorded. There is a need for a computerized smell test system for psychophysical and clinical applications. A mobile digital olfactory testing system (DOTS) was developed, consisting of an odor delivery system (DOTS-ODD) and a mobile application program (DOTS-APP) connected wirelessly. The University of Pennsylvania Smell Identification Test was implemented in DOTS and compared to its commercial product on a cohort of 80 normosmic subjects and a clinical cohort of 12 Parkinson's disease patients. A test-retest was conducted on 29 subjects of the normal cohort. The smell identification scores obtained from the DOTS and standard UPSIT commercial test are highly correlated (r = 0.714, P < 0.001), and test-retest reliability coefficient was 0.807 (r = 0.807, P < 0.001). The DOTS is customizable and mobile compatible, which allows for the implementation of standardized olfactory tests and the customization of investigators' experimental paradigms. The DOTS-APP on mobile devices offers capabilities for a broad range of on-site, online, or remote clinical and scientific chemosensory applications.

How National Culture Influences the Speed of COVID-19 Spread: Three Cross-Cultural Studies.

The COVID-19 pandemic has affected 222 countries and territories around the globe. Notably, the speed of COVID-19 spread varies significantly across countries. This cross-cultural research proposes and empirically examines how national culture influences the speed of COVID-19 spread in three studies. Study 1 examines the effects of Hofstede's national cultural dimensions on the speed of COVID-19 spread in 60 countries. Drawing on the GLOBE study (House et al., 2004), Study 2 investigates how GLOBE cultural dimensions relate to the speed of the pandemic's spread in 55 countries. Study 3 examines the effect of cultural tightness in 31 countries. We find that five national cultural dimensions - power distance, uncertainty avoidance, humane orientation, in-group collectivism, and cultural tightness - are significantly related to the speed of COVID-19 spread in the initial stages, but not in the later stages, of the pandemic. Study 1 shows that the coronavirus spreads faster in countries with small power distance and strong uncertainty avoidance. Study 2 supports these findings and further reveals that countries with low humane orientation and high in-group collectivism report a faster spread of the disease. Lastly, Study 3 shows that COVID-19 spreads slower in countries with high cultural tightness.

Analysis of World-Scale Mitochondrial DNA Reveals the Origin and Migration Route of East Asia Goats.

Despite much attention on the history of goat evolution, information on origin, demographic history, and expansion route remains controversial. To address these questions, we collected 4,189 published goat DNA sequences including 1,228 sequences from 57 breeds in China and 2,961 sequences including 193 goat breeds from 71 other countries and carried out an integrated analysis. We found goat breeds from South China had the highest genetic diversity of lineage B, and subclades B2 only were found in Southwest China, suggesting that lineage B (particularly, subclade B2) probably originated from Southwest China and its surrounding areas. In addition, in this study, we found that lineage A from South China also presented higher genetic diversity and earlier expansion time (10, 606 years ago), even earlier than breeds from the Middle East. Hence, we speculated that South China and surrounding areas were the origin of lineage B and also the transportation hub for lineage A spreading to North China and Southwest Asia. Furthermore, according to the analysis of correlation between genetic differentiation value λ1 and λ2 and geographical distance, we further confirmed two phases of migration in goat breeds of North China. These results will contribute to a better understanding of the origin and migration history of domestic goat.

Prognostic Significance of Uric Acid in Patients with Obstructive and Nonobstructive Coronary Artery Disease Undergoing D-SPECT.

PURPOSE: The association of serum uric acid (SUA) levels with cardiovascular outcomes in patients with coronary artery disease (CAD) has been extensively studied and yielded conflicting results. We aimed to investigate whether the severity of coronary stenosis and ischemia influences the prognostic impact of SUA levels in patients with CAD undergoing D-SPECT. PATIENTS AND METHODS: This study consecutively included patients who were admitted for CAD in Shanghai Tenth People's Hospital between June 2014 and August 2018, had complete SUA data and underwent both coronary angiography and D-SPECT within 3 months. Hyperuricemia was defined as an SUA level of >7 mg/dL in men and >6 mg/dL in women. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, unplanned coronary revascularization, nonfatal myocardial infarction, ischemic stroke, heart failure, and angina-related hospitalization. RESULTS: A total of 695 patients were included, of whom 432 (62.2%) presented with obstructive CAD and 117 (16.8%) had hyperuricemia. During a median follow-up of 26 months, the incidence rates of MACE in patients with hyperuricemia and normouricemia were 15.2% and 21.1%, respectively. After a multivariable adjustment, hyperuricemia was significantly associated with an increased risk of MACE (HR: 1.39, 95% CI: 1.03-1.87, p = 0.033) when compared with normouricemia. When repeating the primary analysis in patients with and without obstructive CAD, we showed that hyperuricemia was independently associated with an 80% increased risk of MACE among patients with nonobstructive CAD (HR: 1.80, 95% CI: 1.04-3.11, p = 0.035), while such a significant association was not found among those with obstructive CAD (HR: 1.18, 95% CI: 0.82-1.72, p = 0.373). Moreover, we uncovered a U-shaped and linear trajectory of SUA levels with MACE in the obstructive and nonobstructive CAD, respectively. The sex-specific analysis showed that the adverse impact of hyperuricemia was only pronounced in males (HR: 1.73, 95% CI: 1.18-2.53, p = 0.005) but not in females (HR: 0.98, 95% CI: 0.57-1.66, p = 0.933). CONCLUSION: Hyperuricemia is significantly associated with increased risk of MACE in the nonobstructive CAD rather than in the obstructive CAD.

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.