Combination of single-nucleus and bulk RNA-seq reveals the molecular mechanism of thalamus haemorrhage-induced central poststroke pain

Central poststroke pain (CPSP) induced by thalamic haemorrhage (TH) can be continuous or intermittent and is accompanied by paresthesia, which seriously affects patient quality of life. Advanced insights into CPSP mechanisms and therapeutic strategies require a deeper understanding of the molecular processes of the thalamus. Here, using single-nucleus RNA sequencing (snRNA-seq), we sequenced the transcriptomes of 32332 brain cells, which revealed a total of four major cell types within the four thalamic samples from mice. Compared with the control group, the experimental group possessed the higher sensitivity to mechanical, thermal, and cold stimuli, and increased microglia numbers and decreased neuron numbers. We analysed a collection of differentially expressed genes and neuronal marker genes obtained from bulk RNA sequencing (bulk RNA-seq) data and found that Apoe, Abca1, and Hexb were key genes verified by immunofluorescence (IF). Immune infiltration analysis found that these key genes were closely related to macrophages, T cells, related chemokines, immune stimulators and receptors. Gene Ontology (GO) enrichment analysis also showed that the key genes were enriched in biological processes such as protein export from nucleus and protein sumoylation. In summary, using large-scale snRNA-seq, we have defined the transcriptional and cellular diversity in the brain after TH. Our identification of discrete cell types and differentially expressed genes within the thalamus can facilitate the development of new CPSP therapeutics

Coastal upwelling and redox variations in the northwestern Tarim Basin (northwest China) during the Middle-Late Ordovician: implication for paleo-depositional conditions of the organic matter enrichment in the Saergan Formation

The black shales of the Saergan Formation, which represent one of the main hydrocarbon source rocks in the Tarim Basin, witnessed a time span of organic matter enrichment by profound changes in the Earth System. A multi-proxy geochemistry study was carried out on the samples of the Saergan Formation to reconstruct the depositional environment and to explore the mechanism of organic matter enrichment of the unit at the Yingshanbeipo section, Keping area, northwest Tarim. Elemental and TOC data are suggestive of an upwelling setting, with a less pronounced oxygen minimum zone (OMZ) compared to the highly productive Peru and Namibian margins. Ferruginous anoxic bottom water conditions prevailed during most time of the deposition, with suboxic conditions dominating the basal and the top parts of the studied unit. As a whole, primary productivity seems to be the dominating factor that controlled the micronutrients and OM accumulations in the Saergan Formation whereas the role of benthic redox conditions may have been subordinate. The variations in primary productivity and bottom water redox conditions were resulted by the multiple, interacting environmental factors including nutrient supply regulated by oceanic circulation and climate changes, and relative sea-level fluctuations

The use of multiple datasets to identify autophagy-related molecular mechanisms in intracerebral hemorrhage

Background: Intracerebral hemorrhage (ICH) is a stroke syndrome with high mortality and disability rates, but autophagy’s mechanism in ICH is still unclear. We identified key autophagy genes in ICH by bioinformatics methods and explored their mechanisms.Methods: We downloaded ICH patient chip data from the Gene Expression Omnibus (GEO) database. Based on the GENE database, differentially expressed genes (DEGs) for autophagy were identified. We identified key genes through protein–protein interaction (PPI) network analysis and analyzed their associated pathways in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Gene-motif rankings, miRWalk and ENCORI databases were used to analyze the key gene transcription factor (TF) regulatory network and ceRNA network. Finally, relevant target pathways were obtained by gene set enrichment analysis (GSEA).Results: Eleven autophagy-related DEGs in ICH were obtained, and IL-1B, STAT3, NLRP3 and NOD2 were identified as key genes with clinical predictive value by PPI and receiver operating characteristic (ROC) curve analysis. The candidate gene expression level was significantly correlated with the immune infiltration level, and most of the key genes were positively correlated with the immune cell infiltration level. The key genes are mainly related to cytokine and receptor interactions, immune responses and other pathways. The ceRNA network predicted 8,654 interaction pairs (24 miRNAs and 2,952 lncRNAs).Conclusion: We used multiple bioinformatics datasets to identify IL-1B, STAT3, NLRP3 and NOD2 as key genes that contribute to the development of ICH

Systemic Risk in Global Volatility Spillover Networks: Evidence from Option-implied Volatility Indices

With option-implied volatility indices, we provide a new tool for event studies in a network setting and document systemic risk in the spillover networks across global financial markets. Network linkages are sufficiently asymmetric because the US stock and bond markets play as dominant volatility suppliers to other countries and markets. Shocks from the US generate systemic risk through intensifying volatility spillovers across countries and asset classes. The findings offer new evidence that asymmetric network linkages can lead to sizable aggregate fluctuations and thus potential systemic risk

The stock-bond correlation and macroeconomic conditions: One and a half centuries of evidence

Using monthly stock and bond return data in the past 150 years (1855-2001) for both the US and the UK, this study documents time-varying stock-bond correlation over macroeconomic conditions (the business cycle, the inflation environment and monetary policy stance). There are different patterns of time variation in stock-bond correlations over the business cycle between US and UK, which implies that bonds may be a better hedge against stock market risk and offer more diversification benefits to stock investors in the US than in the UK. Further, there is a general pattern across both the US and the UK during the post-1923 subperiod and during the whole sample period: higher stock-bond correlations tend to follow higher short rates and (to a lesser extent) higher inflation rates.Stock-bond correlation Business cycle Asymmetry Smooth transition GARCH

Mechanisation of sugarcane production in China: Experience with Sugarcane Machinery on Guang Qian State Farm

Sugarcane is an important industrial crop in South China, mainly grown in Guangdong, Guangxi, Yuennan and Fujian Provinces. State farms are important cane producers. They produce about one-tenth of the nation’s total cane. These sugar companies are integrated enterprises including farm and milling activities but, due to declining sugar prices, they are not particularly profitable. Under the “Responsibility system” which is now used on state farms, a large number of small canegrowers are allocated land (average area 1.6 hectares) on which to grow cane which they harvest and transport to a collection area for transport to the mill. Because of their small area and low work efficiency, these canegrowers’ average incomes are very low. Besides the economic problems flowing from lower sugar prices, the state farms are also suffering from labour shortages and many temporary workers have to be employed. The managers of some of the state farm companies believe that the solution to their problems lies in mechanization of canegrowing and harvesting operations. A large investment in Austrlian sugarcane machinery was made by the Guang Qian Sugar Farm in Zhangjiang, Guandong Province, south China in 1997. This paper reports some experiences with the machinery in actual farm production and addresses some of the economic considerations involved in the mechanisation of sugarcane production in China

Conditional Coskewness in Stock and Bond Markets: Time-Series Evidence

In the context of a three-moment intertemporal capital asset pricing model specification, we characterize conditional coskewness between stock and bond excess returns using a bivariate regime-switching model. We find that both conditional U.S. stock coskewness (the relation between stock return and bond volatility) and bond coskewness (the relation between bond return and stock volatility) command statistically and economically significant negative ex ante risk premiums. The impacts of stock and bond coskewness on the conditional stock and bond premiums are quite robust to various model specifications and various sample periods, and also hold in another major developed country (the United Kingdom). The findings also carry important implications for portfolio management.regime switching, conditional coskewness, intertemporal asset pricing, stock and bond comovements

What Makes Safe-haven Currencies? Evidence from Conditional Co-skewness

We examine the currency co-skewness with the global stock market (i.e., covariance between currency returns and global equity volatility) and investigate its role in safe-haven currencies, which are a hedge for a portfolio of risky assets in times of financial stress. Three safe-haven currencies (USD, SWF, and JPY) have positive co-skewness, providing a hedge against global stock volatility. Moreover, currency co-skewnesses are significantly priced with the expected negative risk premium. Lower excess returns and interest rates on these safe-haven currencies can be partially attributed to their desirable hedging property of positive co-skewness, which differs from time-varying beta, volatility, and skewness