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Dongfeng Gu and colleagues report a genome-wide association study for coronary artery disease in Han Chinese individuals. They identify four loci newly associated with coronary artery disease. We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases and 5,019 controls followed by replication studies in 15,460 cases and 11,472 controls, all of Chinese Han ancestry. We identify four new loci for coronary artery disease that reached the threshold of genome-wide significance ( P < 5 × 10 −8 ). These loci mapped in or near TTC32 - WDR35 , GUCY1A3 , C6orf10-BTNL2 and ATP2B1 . We also replicated four loci previously identified in European populations (in or near PHACTR1 , TCF21 , CDKN2A-CDKN2B and C12orf51 ). These findings provide new insights into pathways contributing to the susceptibility for coronary artery disease in the Chinese Han population.

After the chaos of the ten-year Cultural Revolution, the People's Republic of China embarked on a course of economic recovery and transformation. By opening the previously government controlled economy to free-market mechanisms, the leaders of the Chinese government promised a speedy economic growth, and a significant improvement in the material living conditions of its people. The purpose of this study was to assess the impact of the economic transformation on the lives of Chinese academic women. A group of forty-eight women faculty members and researchers from seventeen academic institutions in Shanghai were selected as subjects. The method used for data collection was in-depth personal interviews. The study focused on the following questions: What are the changes taking place in the professional and personal lives of academic women during the economic transformation? What are the attitudes of academic women toward such changes and how are they coping with the changes? Are young women academicians more receptive to the changes? Are women academicians with experience abroad more receptive to the changes? The study found that Chinese women academicians are generally in support of the decision made by the government to steer away from a past of political turmoil and to focus on the economic development of the nation. However, they are worried that the fast-paced, unbalanced economic development which China has experienced, so far, is breeding social unrest. From the perspective of their individual lives, the women academicians acknowledged that the economic transformation has brought dramatic changes. The newly established financial responsibility system has not only generated competition and pressure at work, but linked academic activities to business enterprise. At the same time, a commercialized market with high inflation is actually weakening the financial position of Chinese academic households. Faced with the challenges, the academic women in this study expressed passivity. Exceptions were young women academicians looking for career alternatives, and women academicians with experience abroad exploring career development opportunities at the international level.

Rhei Radix et Rhizoma, also known as rhubarb or Da Huang , has been widely used as a spice and as traditional herbal medicine for centuries, and is currently marketed in China as the principal herbs in various prescriptions, such as Da-Huang-Zhe-Chong pills and Da-Huang-Qing-Wei pills. Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the efficacious therapeutic potential of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties. This comprehensive review aims to provide an updated summary of recent developments on these pharmacological efficacies and molecular mechanisms of emodin, with a focus on the underlying molecular targets and signaling networks. We also reviewed recent attempts to improve the pharmacokinetic properties and biological activities of emodin by structural modification and novel material-based targeted delivery. In conclusion, emodin still has great potential to become promising therapeutic options to immune and inflammation abnormality, organ fibrosis, common malignancy, pathogenic bacteria or virus infections, and endocrine disease or disorder. Scientifically addressing concerns regarding the poor bioavailability and vague molecular targets would significantly contribute to the widespread acceptance of rhubarb not only as a dietary supplement in food flavorings and colorings but also as a health-promoting TCM in the coming years.

CO 2 hydrogenation to chemicals and fuels is a significant approach for achieving carbon neutrality. It is essential to rationally design the chemical structure and catalytic active sites towards the development of efficient catalysts. Here we show a Ce-CuZn catalyst with enriched Cu/Zn-O V -Ce active sites fabricated through the atomic-level substitution of Cu and Zn into Ce-MOF precursor. The Ce-CuZn catalyst exhibits a high methanol selectivity of 71.1% and a space-time yield of methanol up to 400.3 g·kg cat −1 ·h −1 with excellent stability for 170 h at 260 °C, comparable to that of the state-of-the-art CuZnAl catalysts. Controlled experiments and DFT calculations confirm that the incorporation of Cu and Zn into CeO 2 with abundant oxygen vacancies can facilitate H 2 dissociation energetically and thus improve CO 2 hydrogenation over the Ce-CuZn catalyst via formate intermediates. This work offers an atomic-level design strategy for constructing efficient multi-metal catalysts for methanol synthesis through precise control of active sites. Carbon dioxide hydrogenation is an important industrial reaction. Here, the authors design a CeCuZn catalyst through a metal organic framework template for CO 2 hydrogenation to methanol with excellent methanol yield and stability.

SignificanceDifferences in immune functioning stem from multiple factors, including sex and aging. However, the specific roles of these variables in immunity remain elusive. We profiled immunocytes from young and old males and females at single-cell resolution and constructed a precise atlas of blood-circulating immunocytes. T cell– and B cell–activated signals were higher in young females than males, while aging increased the sex-related differences in immunocytes, cellular composition, and inflammatory signaling. Additionally, males showed a higher accumulation of inflammatory factors during aging, whereas cell–cell communication analysis revealed different trends in gene expression between females and males with aging. These findings might aid in the understanding of the mechanisms underlying sex-based differences in immunity and disease susceptibility across the lifespan. Sex and aging influence the human immune system, resulting in disparate responses to infection, autoimmunity, and cancer. However, the impact of sex and aging on the immune system is not yet fully elucidated. Using small conditional RNA sequencing, we found that females had a lower percentage of natural killer (NK) cells and a higher percentage of plasma cells in peripheral blood compared with males. Bioinformatics revealed that young females exhibited an overrepresentation of pathways that relate to T and B cell activation. Moreover, cell–cell communication analysis revealed evidence of increased activity of the BAFF/APRIL systems in females. Notably, aging increased the percentage of monocytes and reduced the percentage of naïve T cells in the blood and the number of differentially expressed genes between the sexes. Aged males expressed higher levels of inflammatory genes. Collectively, the results suggest that females have more plasma cells in the circulation and a stronger BAFF/APRIL system, which is consistent with a stronger adaptive immune response. In contrast, males have a higher percentage of NK cells in blood and a higher expression of certain proinflammatory genes. Overall, this work expands our knowledge of sex differences in the immune system in humans.

Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas. The incidence of CP is increasing worldwide but the effective therapies are lacking. Hence, it is necessary to identify economical and effective agents for the treatment of CP patients. Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy. Clinical studies show that VD deficiency is prevalent in CP patients. However, the correlation between VD level and the risk of CP remains controversial. VD and its analogues have been demonstrated to inhibit pancreatic fibrosis by suppressing the activation of pancreatic stellate cells and the production of extracellular matrix. Limited clinical trials have shown that the supplement of VD can improve VD deficiency in patients with CP, suggesting a potential therapeutic value of VD in CP. However, the mechanisms by which VD and its analogues inhibit pancreatic fibrosis have not been fully elucidated. We are reviewing the current literature concerning the risk factors for developing CP, prevalence of VD deficiency in CP, mechanisms of VD action in PSC-mediated fibrogenesis during the development of CP and potential therapeutic applications of VD and its analogues in the treatment of CP.

Despite encouraging progresses in the development of novel therapies, cancer remains the dominant cause of disease-related mortality and has become a leading economic and healthcare burden worldwide. Scutellariae radix (SR, Huangqin in Chinese) is a common herb used in traditional Chinese medicine, with a long history in treating a series of symptoms resulting from cancer, like dysregulated immune response and metabolic abnormalities. As major bioactive ingredients extracted from SR, flavonoids, including baicalein, wogonin, along with their glycosides (baicalin and wogonoside), represent promising pharmacological and anti-tumor activities and deserve extensive research attention. Emerging evidence has made great strides in elucidating the multi-targeting therapeutic mechanisms and key signaling pathways underlying the efficacious potential of flavonoids derived from SR in the field of cancer treatment. In this current review, we aim to summarize the pharmacological actions of flavonoids against various cancers in vivo and in vitro. Moreover, we also make a brief summarization of the endeavor in developing a drug delivery system or structural modification to enhance the bioavailability and biological activities of flavonoid monomers. Taken together, flavonoid components in SR have great potential to be developed as adjuvant or even primary therapies for the clinical management of cancers and have a promising prospect.

Poor sleep has become an important public health issue. With loss of sleep durations, poor sleep has been linked to the increased risks for diseases. Here we employed mass cytometry and single-cell RNA sequencing to obtain a comprehensive human immune cells landscape in the context of poor sleep, which was analyzed in the context of subset composition, gene signatures, enriched pathways, transcriptional regulatory networks, and intercellular interactions. Participants subjected to staying up had increased T and plasma cell frequency, along with upregulated autoimmune-related markers and pathways in CD4+ T and B cells. Additionally, staying up reduced the differentiation and immune activity of cytotoxic cells, indicative of a predisposition to infection and tumor development. Finally, staying up influenced myeloid subsets distribution and induced inflammation development and cellular senescence. These findings could potentially give high-dimensional and advanced insights for understanding the cellular and molecular mechanisms of pathologic conditions related to poor sleep.Liu et al. use mass cytometry and single-cell RNA sequencing of healthy human blood samples to obtain a comprehensive human immune cell landscape when sleep duration is reduced. Their findings could provide highdimensional insight into the cellular and molecular mechanisms of pathologic conditions affect by poor sleep.

Chronic inflammation in response to persistent exogenous stimuli or damage results in liver fibrosis, which subsequently progresses into malignant liver diseases with high morbidity and mortality. Ferulic acid (FA) is a phenolic acid widely isolated from abundant plants and exhibits multiple biological activities including anti-oxidant, anti-inflammation and enhancement of immune responses. Adenosine monophosphate-activated protein kinase (AMPK) functions as a critical energy sensor and is regulated through the phosphorylation of liver kinases like LKB1 or dephosphorylation by protein tyrosine phosphatases (PTPs). However, the role of FA in carbon tetrachloride (CCl 4 )-induced chronic inflammation and liver fibrosis and AMPK activation has not been elucidated. Here we reported that FA ameliorated CCl 4 -induced inflammation and fibrotic liver damage in mice as indicated by reduced levels of serum liver function enzyme activities and decreased expression of genes and proteins associated with fibrogenesis. Additionally, FA inhibited hepatic oxidative stress, macrophage activation and HSC activation via AMPK phosphorylation in different liver cells. Mechanically, without the participation of LKB1, FA-induced anti-inflammatory and anti-fibrotic effects were abrogated by a specific AMPK inhibitor, compound C. Combining with the results of molecular docking, surface plasmon resonance and co-immunoprecipitation assays, we further demonstrated that FA directly bound to and inhibited PTP1B, an enzyme responsible for dephosphorylating key protein kinases, and eventually leading to the phosphorylation of AMPK. In summary, our results indicated that FA alleviated oxidative stress, hepatic inflammation and fibrotic response in livers through PTP1B-AMPK signaling pathways. Taken together, we provide novel insights into the potential of FA as a natural product-derived therapeutic agent for the treatment of fibrotic liver injury.

Nonalcoholic fatty liver disease (NAFLD) is a growing health concern worldwide. Administration of probiotics and prebiotics has been proposed as a convenient and effective treatment. Our study aims to evaluate the therapeutic benefits of N1115 (N1115) and fructooligosaccharides (FOS) by examining the histopathogenesis and underlying molecular events of NAFLD. An NAFLD mouse model was established by feeding C57BL/6 mice with a high-fat diet (HFD). N1115, FOS and synbiotics were administered for 16 weeks. N1115, FOS and synbiotics alleviated HFD-induced hepatic steato-sis and release of tumor necrosis factor-α, and slowed the progression of cirrhosis. Compared to the HFD group, these dietary supplements reduced serum total triglyceride and cholesterol, and appeared to decrease the fasting blood glucose and insulin. Intraperitoneal glucose tolerance tests, homeostatic model assessment of insulin resistance and real-time PCR showed that the regimens could overcome insulin resistance. These findings were associated with the transcriptional repression of inflammatory factors such as lipopolysaccharides, Toll-like receptor 4 and nuclear factor-κB. Lastly, N1115, FOS, and synbiotics improved the intestinal barrier functions and histologic integrity. This was accompanied by the restoration of the p38 MAPK pathway and in-creased expression of the tight junction components occludin-1 and claudin-1. N1115, FOS and synbiotics are effective in the prevention and treatment of NAFLD. Our data support the translation of these agents into clinical evaluation in human subjects with NAFLD and/or associated risk factors.