External supply risk of agricultural products trade along the Belt and Road under the background of COVID-19.

Agricultural product trade along the Belt and Road (B&R) is an important part of the international food security system, the vulnerabilities of which have been highlighted by the recent COVID-19 pandemic. Based on the complex network analysis, this study analyzes the characteristics of agricultural products trade network along the B&R. It also combines the effects of COVID-19 with the import trade volume of agricultural products in countries along the B&R to build a risk supply model of agricultural products. The results show that: (1) In 2021, the spatial correlation structure of agricultural products trade along the B&R became increasingly sparse, and the network connectivity and density also decreased. (2) The network showed obvious scale-free distribution characteristics and obvious heterogeneity. Five communities emerged under the influence of the core node countries, but the formation of community in 2021 had obvious geopolitical characteristics. (3) Under the influence of the COVID-19 epidemic, the number of countries with medium-risk and high-risk level along the route facing external dependence risk (REDI), import concentration risk (RHHI) and COVID-19 epidemic risk (RRICI) increased in 2021, and the number of countries with extremely low-risk level decreased. (4) The dominant risk type of external supply of agricultural products along the route changed from compound risk type in 2019 to epidemic risk in 2021. Hence, the results can be expected to prevent external risk impact from reducing excessive concentration of agricultural products trade and excessive dependence on the external market.

Recent advances in PLGA micro/nanoparticle delivery systems as novel therapeutic approach for drug-resistant tuberculosis.

Tuberculosis is a severe infectious disease caused by Mycobacterium tuberculosis and is a significant public health concern globally. The World Health Organization (WHO) recommends a combination regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (ETB), to treat tuberculosis. However, these drugs have low plasma concentrations after oral administration and require multiple high doses, which may lead to the occurrence and development of drug-resistant tuberculosis. Micro/Nanotechnology drug delivery systems have considerable potential in treating drug-resistant tuberculosis, allowing the sustained release of the drug and delivery of the drug to a specific target. These system properties could improve drug bioavailability, reduce the dose and frequency of administration, and solve the problem of non-adherence to the prescribed therapy. This study systematically reviewed the recent advances in PLGA micro/nanoparticle delivery systems as a novel therapeutic approach for drug-resistant tuberculosis.

Cancer-Secreted Exosomal MiR-620 Inhibits ESCC Aerobic Glycolysis via FOXM1/HER2 Pathway and Promotes Metastasis.

Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide. MicroRNAs (MiRNAs) have been reported to regulate cell functions through exosomes. Through the Gene Expression Omnibus (GEO) database, miR-620 was selected as a serum miRNA highly expressed in ESCC, but its detailed role in ESCC has not been explored. Tumor-secreted miRNAs have been reported to promote cancer metastasis through reprogramming the aerobic glycolysis of lung fibroblasts. Therefore, we intended to verify whether exosomal miR-620 secreted in ESCC cells may regulate the aerobic glycolysis of lung fibroblasts. Methods: The effect of miR-620 on the aerobic glycolysis of ESCC cells was firstly verified through bioinformatics prediction and mechanism assays. Exosomes secreted from ESCC cells was detected, and the influence of exosomal miR-620 in regulating the aerobic glycolysis of lung fibroblasts was then verified both in vitro and in vivo. Results: MiR-620 inhibited ESCC malignancy and suppressed the aerobic glycolysis of ESCC cells via targeting Forkhead box M1 (FOXM1) and human epidermal growth factor receptor 2 (HER2). Moreover, exosomal miR-620 was highly secreted in ESCC and could regulate HFL1 aerobic glycolysis via FOXM1/HER2 signaling. Furthermore, exosomal miR-620 could promote ESCC metastasis by reprogramming the aerobic glycolysis of lung fibroblasts (HFL1). Conclusion: Exosomal miR-620 secreted by ESCC cells inhibited the aerobic glycolysis via FOXM1/HER2 axis and promoted cancer metastasis.

The Evolutionary Characteristics of Apple Production Layout in China from 1978 to 2016 / As características evolutivas do layout de produção da maçã na China de 1978 a 2016

ABSTRACT: Based on the apple acreage and output data of 23 provinces in China, the LMDI decomposition method and the barycenter analysis model were used to systematically analyze the spatiotemporal characteristics of apple production in China from 1978 to 2016. The results showed that the apple acreage and output continued to increase, and the apple production layout has moved to south-westward; Shaanxi, Shandong, Henan, Shanxi, Gansu, Hebei, Liaoning, and Xinjiang were the main contributors to the apple output increase in China; yield contributed more to apple output increase, the increase of yield was a significant contributing factor to the apple output growth in 17 provinces, whereas the expansion of apple acreage was a significant contributing factor in the other 6 provinces; the barycenter of apple acreage and output respectively moved to the southwest by 506.63 kilometers and 574.12 kilometers, and the barycenter of apple production gradually shifted to the Loess Plateau. To stabilize the effective supply of apple and maintain industrial security, the policymakers should attach importance to the fundamental role of technological progress in the development of the apple industry, and bring into play the technological progress, economic, social, and environmental effects of apple industry agglomeration by optimizing the apple production layout and strengthening policy guidance and regulatory measures.

RESUMO: Com base nos dados de área cultivada e produção de maçã de 23 províncias na China, o método de decomposição do LMDI e o modelo de análise de barcenter foram utilizados para analisar sistematicamente as características espaço-temporais da produção de maçã na China entre 1978 e 2016. Os resultados mostraram que a área cultivada de maçã e a produção continuou a aumentar, e o layout da produção da maçã mudou para o Sudoeste; Shaanxi, Shandong, Henan, Shanxi, Gansu, Hebei, Liaoning e Xinjiang foram os principais contribuintes para o aumento da produção de maçãs na China; o rendimento contribuiu mais para o aumento da produção de maçã, o aumento do rendimento foi fator de contribuição significativo para o crescimento da produção de maçã em 17 províncias, enquanto a expansão da área cultivada de maçã foi fator de contribuição significativo nas outras 6 províncias; o baricentro da área cultivada e a produção de maçãs se deslocaram para o Sudoeste em 506,63 quilômetros e 574,12 quilômetros respectivamente. O baricentro da produção de maçãs mudou gradualmente para o platô de Loess. Para estabilizar o fornecimento efetivo de maçã e manter a segurança industrial, os formuladores de políticas devem atribuir importância ao papel fundamental do progresso tecnológico no desenvolvimento da indústria da maçã e colocar em jogo o progresso tecnológico, os efeitos econômicos, sociais e ambientais da indústria da maçã aglomeração, otimizando o layout da produção da maçã e fortalecendo a orientação política e as medidas regulatórias.

[Astragalus injection mediates autophagy and myocardial remodeling in rats with ischemic cardiomyopathy through calumenin].

OBJECTIVE: To study the effects of astragalus injection on myocardial remodeling, calumenin and autophagy in rats with ischemic cardiomyopathy. METHODS: Thirty-six male SD rats were divided into normal control group, ischemic cardiomyopathy group and astragalus injection group, 12 in each group. Electrocardiogram (ECG) and echocardiography were performed before operation in three groups. Rats in ischemic cardiomyopathy group and astragalus injection group underwent thoracotomy and ligation of coronary artery for 20 minutes, then thoracic cavity was closed after reperfusion. In the astragalus injection group,10 g/kg body weight of Astragalus injection was injected once a week, four times in total. Four weeks after operation, rats in three groups were executed by echocardiography and their hearts were collected for Hematoxylin-Eosin (HE) staining and Van Gieson (VG) staining to observe myocardial pathological changes. Calumenin, LC3-I, LC3-II expressions and LC3-I/LC3-II ratio were detected by Western blot. RESULTS: Compared with ischemic cardiomyopathy group, the echocardiography and myocardial pathology of rats in astragalus injection group changed obviously, and the expressions of calumenin, LC3-I, LC3-II and LC3-I/LC3-II ratio changed significantly (P＜0.01). CONCLUSION: Astragalus injection has apparent inhibitory effect on ventricular remodeling and autophagy of myocardial cells in rats with ischemic cardiomyopathy, which may be mediated by calumenin.

An empirical study on spatial-temporal dynamics and influencing factors of apple production in China.

In the context of supply-side structural reform, revealing the characteristics of spatial-temporal dynamics and influencing factors of China's apple production layout is of great significance to ensure apple supply and demand balance and timely adjustment of industrial policies and regional layout strategies. Based on national and provincial apple production data from 1978 to 2016, this study used the apple production concentration index to analyse the evolution characteristics of regional apple production patterns in China. A theoretical analysis framework was established and a spatial econometric model was used to quantitatively explore the influencing factors of China's apple production layout. The results showed that, first, since the reform and opening-up policy, a general trend of fluctuating growth was found for apple production in China. The centre of apple production layout moved in the southwest direction, with the shift from the Bohai Bay region to the Loess Plateau region. Second, apple production had a significant spatial correlation, while the degree of spatial agglomeration gradually decreased. Third, these changes were significantly influenced by apple comparative income, infrastructure, policies, and climatic conditions. Therefore, it is necessary to continue optimizing and adjusting the apple spatial layout to enhance the technological progress and economic effect of the apple industry and to ensure the stability and balance of regional supply and demand.

Trapidil determines the fate of RHF rats through inhibition of ER stress.

Pulmonary arterial hypertension is a fatal disease, especially when it causes right heart failure (RHF). However, it is difficult to treat. It has been reported that trapidil (Tra) can improve the redox balance and cardiac conditions. In this study, we investigated the effect of Tra on RHF induced by monocrotaline (MCT) in rats. Male Wistar rats were treated with MCT or Tra. Treatment lasted 28 days, then rats were euthanized after echocardiography and catheterization. Subsequently, lungs and right ventricular myocardia were evaluated by hematoxylin and eosin, Masson, and TUNEL staining. Protein expression was detected by western blotting. We found remarkably expanded right ventricle end-diastolic volume, decreased partial pressure of oxygen (PaO2), increased partial pressure of carbon dioxide (PaCO2), right ventricular systolic pressure, mean pulmonary arterial pressure, lung/body weight, and liver/body weight in the RHF rat group, as well as increases in the apoptosis rate and the expression of endoplasmic reticulum stress (ERS)-related proteins. However, these changes were significantly inhibited by Tra. Our data suggested that inhibition of ERS is essential for improving RHF, and that therapeutic intervention of Tra in RHF rats works by reducing ERS.

Astragalus Root dry extract restores connexin43 expression by targeting miR-1 in viral myocarditis.

BACKGROUND: Viral myocarditis is defined as viral infection of myocardial tissue leading to impaired heart function and heart failure. Accumulating evidences have shown that arrhythmia is one of important complicating diseases of viral myocarditis causing increased mortality and morbidity. There are no effective treatment for the viral infection and complicating arrhythmia. PURPOSE: This study investigated the effect and mechanism of Astragalus Root dry extract (ARDE) on arrhythmia induced by CVB3 in mice. METHODS: The mice and HL-1 cells were treated with CVB3 and ARDE. Reciprocal regulation of Cx43 and miR-1 were observed in the CVB3 infected mouse myocardium and culture HL-1 cells. RESULTS: CVB3 IP injection increased immune cell infiltration in mouse left ventricle and caused irregular arrhythmia. ARDE treatment prevented the increase of immune cell infiltration and arrhythmia. Overexpression of miR-1 significantly inhibited both endogenous Cx43 expression and Cx43 3'UTR luciferase activity in HL-1 cells. Mutation of census binding site of +1586-1593 bp not +465-472 bp in Cx43 3'UTR luciferase resulted in abolishment of miR-1 inhibitory effects in HL-1 cells. Loss-of- function of miR-1 restored CVB3-induced Cx43 expression reduction in cultured HL-1 cells. The presence of ARDE attenuated the augmented miR-1 induced by CVB3 infection in vivo and in vitro. CONCLUSION: This study identified that CVB3 infection reduced Cx43 expression by elevating miR-1 level in mouse viral myocarditis. For the first time, ARDE was shown to prevent arrhythmia, and rescue CVB3-induced endogenous Cx43 expression by regulating miR-1 level.

[Effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and expression of connexin in cardiomyopathy rats induced by adriamycin].

OBJECTIVES: To investigate the effect of Astragalus injection on cardiomyocyte apoptosis, endoplasmic reticulum stress and connexin protein in cardiomyopathy rats induced by adriamycin. METHODS: Thirty-six male Wister rats were randomly divided into control group (n=12), adriamycin(ADR) group (n=12) and Astragalus group (n=12). The normal saline (10 ml/kg body weight) was injected intraperitoneally in control group rats, ADR (2 mg/kg body weight) was injected intraperitoneally in ADR group rats, ADR (10 ml/kg body weight) and Astragalus injection (10 ml/kg body weight) were injected intraperitoneally in rats of astragalus group, one time a week, totle 3 times. By the end of the 7th week, the left ventricular end-diastolic diameter(LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were measured by echocardiography. Then the rats in the three groups were sacrificed and the left ventricle section was stained by HE, Masson, uranyl acetate/lead citrate respectively, the cardiomyopathy and ultrastructural changes were observed under light microscope and transmission electron microscope. The apoptosis of rat cardiomyocyte were analyzed by TUNEL. The expression of connexin Cx43 and p-Cx43 was detected by immunohistochemistry. The expression of glucose-regulated protein 78 (Grp78),activating transcription factor 4 (ATF-4) and C/EBP homologous protein (CHOP) were detected by real time PCR. RESULTS: Compared with control group, LVEDD, LVESD increased and LVEF decreased, myocardial fibers were disordered and edematous, infiltrated by lymphocytes, the mitochondria were destroyed and vacuolized, and the number of cardiomyocyte apoptosis was increased(P<0.01) in ADR group. The expression of Grp78, ATF-4, CHOP and p-Cx43 were increased, and the expression of Cx43 was decreased in ADR group. However, compared with ADR group, LVEDD, LVESD decreased and LVEF increased, the cardiomyopathy and ultrastructural changes were significantly improved, the number of cardiomyocyte apoptosis was significantly decreased (P<0. 01); the expression of Grp78, ATF-4, CHOP and p-Cx43 decreased (P<0.01); the expression of Cx43 increased in Astragalus group (P<0.01). CONCLUSIONS: Astragalus injection may effectively improve the myocardial damage induced by adriamycin, its mechanism may be related to the inhibition of endoplasmic reticulum stress (ERS) and the decrease of phosphorylation of CX43 in cardiomyopathy rats induced by adriamycin.

MiRNA Signaling in Viral Myocarditis Novel and Unique Pathological Features.

BACKGROUND: Micro-RNAs (miRNAs) are small non-coding RNAs that modulate many target genes. Viral myocarditis is common cardiomyopathy, however, there is an absence of effective therapeutic strategies for viral myocarditis (VMC). The purpose of this research was to characterize changes in miRNAs expression in VMC mice. METHODS: Atrial myocytes were infected coxsackievirus B3 and miRNAs microarray was performed. miRNAs target predicted and the bioinformatics analysis was carried out by gene ontology (GO) and KEGG pathway analysis. To validate the results, Difference miRNAs were identified in heart of mice by real-time polymerase chain reaction (PCR). RESULTS: We identified 94 miRNAs that were differentially expressed (27 were up-regulated and 67 were down-regulated by at least 2.0-fold). Real time PCR analysis has confirmed that the expression levels of 7 miRNAs up-regulated, 18 miRNAs down-regulated. They were mainly involved in protein binding, small GTPase mediated signal transduction, protein phosphorylation by GO. Pathway analysis showed that a significant enrichment in several pathways related to cAMP signaling pathway, AMPK signaling pathway, RAS signaling pathway, Rap1 signaling pathway, ErbB signaling pathway, Oxytocin signaling pathway. CONCLUSIONS: Our results provide a better understanding of the mechanisms of viral myocarditis pathophysiology.

MiR-378 modulates energy imbalance and apoptosis of mitochondria induced by doxorubicin.

Doxorubicin (DOX) is an effective anticancer drug, however its clinical application is limited due to its cardiotoxicity. Therefore, understanding the mechanisms of cardiotoxicity induced by DOX is essential. We found that the level of miR-378 was decreased in the hearts of DOX-treated rats. Increasing the expression of miR-378 resulted in a decrease of lactate dehydrogenase (LDH) upon DOX treatment in vitro by targeting lactate dehydrogenase A (LDHA). Furthermore, bioinformatics analysis indicated that cyclophilin A (PPIA), a regulator of apoptosis, is also a direct target gene of miR-378. We confirmed this by Western blot. Our results also showed that the overexpression of miR-378 inhibited the hyperactivation of ER stress signaling induced by DOX. In addition, MiR-378 overexpression was found to protect cardiomyocytes from DOX-induced energy imbalance and apoptosis of mitochondria. These results may allow for a therapeutic approach that overcomes the cardiotoxicity of DOX-based treatments for cancer.

Calumenin DNA methylation and gene expression in viral myocarditis.

The main death reason is inflammatory response of myocardial tissue caused a sharp decline in myocardial contractility and heart failure. At present, viral myocarditis with heart failure is lack of effective and specific treatment. Basic and clinical studies have shown that intervention apoptosis is an effective way to prevent and cure heart failure. The mechanism of apoptosis is complex, endoplasmic reticulum (ER) stress is a new apoptotic signal transduction pathway was been found. In this study, the apoptosis could be increased in mice with CVB3 treatment. The ER stress related proteins GRP78, ATF4, CHOP were up-regulated in VMC. The mechanism of VMC regulated ERS induced apoptosis was identified. Calumenin protein could relieve ERS induced apoptosis in viral myocarditis in vivo. The DNA methylation of calumenin was analyzed in CON and VMC, however, we found VMC down-regulate the expression of calumenin unrelated with DNA methylation of calumenin.