Coxsackievirus B3 induces viral myocarditis by upregulating toll-like receptor 4 expression.

In the present study, we investigated the potential pathogenesis of coxsackievirus B3 (CVB3)-induced viral myocarditis and the promising protective effect of silencing RNA (small interfering RNA, siRNA). One hundred and twenty mice were included in the study, and 30 mice were intraperitoneally inoculated with CVB3 to establish an acute viral myocarditis model. The survival rate was observed for the CVB3-infected mouse model (MOD), and myocardial injury was examined by HE (hematoxylin and eosin) staining assay. Real-time PCR (RT-PCR) and Western blot assay were selected to detect the toll-like receptor 4 (TLR4) expression in myocardial tissues. The TLR4 gene was silenced for the MOD mice, and the effects of this treatment were observed. The results indicate that the expression of TLR4 mRNA and the protein significantly and persistently increased during the progression of CVB3-induced myocarditis. The activities of cardiac enzymes including CK, LDH, AST, and CK-MB were also enhanced in CVB3-induced myocardial tissues. Interestingly, when the TLR4 gene was silenced, the CVB3-induced TLR4 production was significantly decreased and the severity of myocarditis was significantly lessened. In conclusion, CVB3 may induce viral myocarditis by upregulating toll-like receptor 4 expression. The viral myocarditis can be ameliorated by silencing the TLR4 gene in the CVB3 viral myocarditis model, which may be a feasible therapeutic method for treatment of viral myocarditis.

Evaluating the water quality characteristics and tracing the pollutant sources in the Yellow River Basin, China.

Evaluating water quality characteristics (WQC) and tracing pollutant sources (PS) have gradually attracted worldwide attention. This study was conducted to develop an integrated method framework for evaluating WQC, tracing PS, and improving understanding of their relationship to efficiently managing the water environment. The single-factor index, comprehensive water quality index (CWQI), and hazard quotient and hazard index (HQ and HI) were used to evaluate the characteristics of single pollutant concentration, comprehensive concentration, and human health risk, respectively. These evaluation methods combined with relevant standards selected data from the original sampling data. These selected data were used for tracing PS by principal component analysis and Pearson correlation methods. 3384 sampling data were collected in the Yellow River Basin in 2021, and the WQC assessment and pollutant traceability were carried out by using the above-integrated method framework. The results showed that TN(total nitrogen) was the primary pollutant with an average concentration of 4.54 mg/L, followed by CODcr(dichromate oxidizability), NH4+-N(ammonia nitrogen), and TP(total phosphorous). The CWQI values ranged from 1.26 to 110.03, with an average of 7.74, indicating the pollution level of trace elements was excellent. The HQ and HI max values of As(arsenic) and Cr6+(hexavalent chromium) elements were over 1, meaning the elements have negatively affected local human health. Furthermore, the anthropogenic input was the primary pollutant source for TN. The anthropogenic input and agricultural source pollution emission could be considered for CODcr, NH4+-N, TP, and BOD5(five-day biological oxygen demand). The anthropogenic input and the weathering and leaching of loess could be considered for As elements. For Cr6+, F(fluorine), Anionic, and Petroleum, the anthropogenic activities were the primary pollutant sources, including the metal mining and production and the coal mining and processing industry. Our results could provide effective information to support adaptive management measures to improve water environment conditions and protect human health.

The driving effect of technological innovation on green development: dynamic efficiency spatial variation.

In order to further explore the internal transmission mechanism between technological innovation and green development in manufacturing industry under the background of obvious development characteristics in the new era, this paper constructed an integrated methodology system to evaluate the internal impact mechanism of technological innovation value chain efficiency on green development efficiency based on spatial perspective. First, the Network Slack-based model and Global Malmquist-Luenberger model are constructed to reveal the internal development law of technological innovation and green development of manufacturing industry. Secondly, the spatial Dubin model is employed to analyze the impact of current development characteristics and technological innovation on green development. The results show that innovation value chain efficiency is higher than technological innovation efficiency, and economic transformation efficiency is lower than that of technological innovation value chain. During the study period, the efficiency of technological innovation value chain in the four economic regions present fluctuant growth trend, and the eastern region has the highest value. The green development efficiency in the east, central, west, and northeast regions of manufacturing industry is higher than 1, and it shows an obvious spatial agglomeration effect. Besides, the efficiency of technological innovation, information and communication technology, urbanization, and the advanced industrial structure are all conducive to the improvement of green development in manufacturing industry. This paper studies the influence mechanism of technological innovation value chain efficiency on green development based on spatial perspective and puts forward relevant countermeasures and suggestions to effectively promote green development of manufacturing industry, providing relevant theoretical research for green and high-quality development.

Exploring a multisource-data framework for assessing ecological environment conditions in the Yellow River Basin, China.

Ecological environment conditions (EEC) assessment plays an important role in watershed management. However, due to insufficient field data, EEC assessment in large-scale watersheds faces challenges. Our study was conducted to develop an effective EEC assessment method framework that was capable of reducing the use of field data. Three indicators were developed from multisource data, including landscape ecological risk index (LERI), road network density (RND), and industry density (ID). The knowledge-based raster mapping approach integrated the three indicators into an overall score of the EEC. Then model validation was conducted with principal components of water quality from field sampling data by Pearson correlation analysis methods. Finally, we applied and demonstrated the constructed method framework in the EEC assessment of the YRB.The results showed that bad EEC (0.5326 < Overall score ≤ 0.7679) areas were mainly distributed in the northern part of the YRB, showing a circular distribution pattern. The areas with bad EEC were 15.84 million km2, accounting for 19.87 % of the YRB. The area of the highest LERI (0.157 < LERI≤0.246), the highest RND (4.4435 < RND ≤ 8.5574), and the highest ID (0.1403 < ID≤0.2597) finally converted to bad EEC was 7.22 million km2, 0.78 million km2, and 0.91 million km2, respectively. The results indicated that the ecological risk factors were the primary challenges for improving EEC, followed by industrial agglomeration and road network factors. The primary factors affecting EEC varied between the provinces in the YRB, suggesting that provinces take the management strategies and measures should be adaptive. The correlation coefficients between EEC and the principal components of water quality characteristics were between 0.022 and 0.241, P < 0.05. These findings validated that our method framework could distinguish the spatial variation of EEC in detail and further provide effective support for watershed management.

Energy conservation potential analysis of Chinese manufacturing industry: the case of Jiangsu province.

Improving energy conservation efficiency is one of the prerequisites for China's manufacturing industry to transform and upgrade. Jiangsu province which presents the maximum economic volume in manufacturing and its economic status in eastern China is comparable to Shanghai. Research on the sustainable development capacity of Jiangsu's manufacturing industry gives important guidance for upgrading the manufacturing industry all over China. The core of China's manufacturing transition to a manufacturing power is to enhance its independent innovation capabilities to improve energy efficiency and its position in the global value chain. Therefore, it is important to study the impact of technological factor on energy conservation potential and the transformation and upgrading of manufacturing. In this paper, multivariate regression research method combined with risk analysis is developed to explore the influence of the research and development factor on energy conservation while introducing macroeconomic variables. Additionally, energy conservation of manufacturing in Jiangsu province in 2020 and 2025 based on historical data from 1985 to 2015 is predicted. Compared with the business-as-usual scenario, the advanced scenario could reduce by 44.07 Mtce and 87.60 Mtce in 2020 and 2025, respectively. Thus, the results indicate that there is much room for improvement in terms of the energy efficiency for Jiangsu province.

Serum miR-92a is Elevated in Children and Adults with Obstructive Sleep Apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a highly prevalent condition that is associated with several comorbidities including cardiovascular disease (CVD). Recent studies have revealed mixed results as to whether standard OSA therapy reverses CVD in adult patients. Thus, many advocate for earlier recognition of OSA induced CVD, as early as childhood, to prompt treatment antecedent to the onset of irreversible CVD. Here we investigated if the serum level of miR-92a, a known biomarker for CVD, can be used to identify patients with OSA in both children and adults. METHODS: Consecutive snoring patients undergoing polysomnography were recruited for determination of circulating miR-92a, in addition to inflammatory and metabolic profiles. We assessed whether circulating miR-92a was associated with OSA severity. RESULTS: Using two separate cohorts of adults (n=57) and children (n=13), we report a significant increase in the serum level of miR-92a in patients with severe OSA (p=0.021) and further demonstrate a significant correlation (Spearman rank correlation 0.308, p=0.010) with serum miR-92a levels and the apnea hypopnea index (AHI), a primary measure of OSA severity. Stepwise regression analysis revealed that serum miR-92a levels were independently associated with AHI (ß=0.332, p=0.003), age (ß=0.394, p=0.002) and LDL cholesterol levels (ß=0.368, p=0.004). CONCLUSION: Our study is the first to establish that miR-92a is a useful biomarker for OSA severity in both children and adults. Given the canonical role of miR-92a on endothelial dysfunction, miR-92a may be useful to identify early onset CVD in OSA patients or stratify patient CVD risk to identify those that may benefit from earlier OSA treatment.

Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP-triggered apoptosis via the inhibition of the IRE-α pathway.

Clinically, diabetes mellitus is closely associated with and induces certain cardiovascular diseases. The aim of this study was to investigate endoplasmic reticulum (ER) stress-associated apoptosis of diabetic cardiomyopathy (DCM), and explore the protective mechanism of liraglutide. The DCM model was established with a high-fat diet and streptozotocin (STZ). Cardiac function was detected by echocardiogram examination and hematoxylin-eosin staining. ER stress unfolded protein response (UPR) hallmarks [inositol-requiring enzyme-α (IRE-α), p-Perk and ATF6] and transcription factors were detected with western blotting. Apoptosis inducers CHOP, c-Jun amino terminal kinase (JNK) and casapse-12 were also examined with western blotting. The results indicated that liraglutide is capable of improving cardiac function in DCM rats (P<0.05). IRE-α expression was significantly increased in the DCM group compared with the control group (P<0.05), and liraglutide is capable of decreasing IRE-α expression. X-box transcription factor-1 (XBP-1) was significantly spliced in the model group, and downregulated in the liraglutide-treated group. CHOP protein was upregulated in the DCM group, but inactivated by liraglutide treatment. In conclusion, liraglutide is capable of protecting DCM and blocking CHOP-mediated ER stress by inhibiting the IRE-α UPR pathway.

Immunocytochemical and immunohistochemical application of monoclonal antibodies against peroxisomal biogenesis factor 14.

PEX14 is an integral membrane protein essential for protein docking onto the peroxisomes and is a bi-functional protein capable of acting as a transcriptional co-repressor and a polypeptide transport modulator. Further studies showed that PEX14 is the sole peroxin that has a unique dual function in peroxisome formation and selective degradation. Its RNA transcripts are ubiquitously expressed; there is, however, no data on the expression profiles of PEX14 at the protein level due to a lack of MAbs suitable for immunohistochemical staining, thus hindering studies on its functions. In the present study, we generated one MAb that could be used in immunocytochemistry and immunohistochemistry and investigated PEX14 expression in normal and malignant human tissues. In contrast to the ubiquitous expression of its RNA transcripts, there is no PEX14 protein expression in normal human tissue, including liver, spleen, lung, rectum, brain, prostate, breast, ovary, and stomach. Protein expression of PEX14 was dramatically upregulated in some malignancies. Presented here are the first data on the expression profiles of PEX14 at the protein level, which will further our understanding of its functions.

Activation of Th17/Th1 and Th1, but not Th17, is associated with the acute cardiac event in patients with acute coronary syndrome.

OBJECTIVE: Th1 activation and regulatory T (Treg) cell suppression have been observed in acute coronary syndrome (ACS), including unstable angina (UA) and acute myocardial infarction (AMI). However, the role of Th17 cell or IL-17A remains controversial in ACS patients, and little is known about the role of recently discovered Th17/Th1 cells, a subset of Th17 cells, in coronary artery disease (CAD). The purpose of this study is to investigate functional changes of Th17/Th1, Th17, Th1, Th2 and Treg cells in ACS patients. METHODS: The contents of Th17/Th1, Th17, Th1, Th2 and Treg cells, related gene expression, and plasma cytokines from CAD and control patients with normal coronary arteries (NCA) were measured by flow cytometry, real-time quantitative PCR and ELISA. RESULTS: Th17/Th1 and Th1 cell contents and related gene expression (T-bet, IFN-γ, STAT4, RORγt, STAT3 and IL-17) were significantly increased in ACS patients, whereas plasma IFN-γ only increased in CAD patients. In contrast, Treg cell population, Foxp3 levels, and plasma TGF-ß1 were decreased in ACS patients compared with stable angina (SA) and NCA patients. CONCLUSION: The study showed activation of Th17/Th1 and Th1 cell in ACS patients, which may provide insight into the mechanisms underlying culprit plaque relevant T-cell activation in ACS patients.

[Changes of Foxp3(+); regulatory T cells in patients with acute coronary syndrome].

AIM: To investigate the changes of Foxp3(+); (including CD4(+);Foxp3(+); and CD4(+);CD25(+);Foxp3(+);) regulatory T cells (Tregs) in patients with acute coronary syndrome (ACS). METHODS: Forty-four ACS patients, twenty patients with stable angina (SA) and twenty-four control patients were enrolled. The percentages of the peripheral Tregs, Foxp3 mRNA and plasma level of TGF-ß1 were measured by flow cytometry, real-time quantitative PCR and ELISA. RESULTS: The percentages of CD4(+);CD25(+);Foxp3(+); Tregs and CD4(+);Foxp3(+); Tregs, Foxp3 mRNA and plasma level of TGF-ß1 significantly decreased in the ACS group as compared with those in the SA group and the controls (P<0.05), while there was no significant difference in the percentage of CD4(+);CD25(+); Tregs among all three groups. CONCLUSION: There are less Foxp3(+);Tregs, perhaps with impaired function, in ACS patients, which might contribute to plaque destabilization.