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Air pollution containing particulate matter (PM) less than 2.5 μm (PM2.5) plays an essential role in regulating hepatic disease. However, its molecular mechanism is not yet clear, lacking effective therapeutic strategies. In this study, we attempted to investigate the effects and mechanisms of PM2.5 exposure on hepatic injury by the in vitro and in vivo experiments. At first, we found that PM2.5 incubation led to a significant reduction of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), along with markedly reduced expression of different anti-oxidants. Notably, suppressor of IKKε (SIKE), known as a negative regulator of the interferon pathway, was decreased in PM2.5-incubated cells, accompanied with increased activation of TANK-binding kinase 1 (TBK1) and nuclear factor-κB (NF-κB). The in vitro studies showed that Nrf2 positively regulated SIKE expression under the conditions with or without PM2.5. After PM2.5 treatment, Nrf2 knockdown further accelerated SIEK decrease and TBK1/NF-κB activation, and opposite results were observed in cells with Nrf2 over-expression. Subsequently, the gene loss- and gain-function analysis demonstrated that SIKE deficiency further aggravated inflammation and TBK1/NF-κB activation caused by PM2.5, which could be abrogated by SIKE over-expression. Importantly, SIKE-alleviated inflammation was mainly dependent on TBK1 activation. The in vivo studies confirmed that SIKE- and Nrf2-knockout mice showed significantly accelerated hepatic injury after long-term PM2.5 exposure through reducing inflammatory response and oxidative stress. Juglanin (Jug), mainly isolated from Polygonum aviculare, exhibits anti-inflammatory and anti-oxidant effects. We found that Jug could increase Nrf2 activation, and then up-regulated SIKE in cells and liver tissues, mitigating PM2.5-induced liver injury. Together, all these data demonstrated that Nrf2 might positively meditate SIKE to inhibit inflammatory and oxidative damage, ameliorating PM2.5-induced liver injury. Jug could be considered as an effective therapeutic strategy against this disease by improving Nrf2/SIKE signaling pathway., Graphical abstract Image 1, Highlights • PM2.5 incubation inhibits Nrf2 and SIKE activation in vitro. • Nrf2 positively regulates SIKE expression in PM2.5-incubated cells. • SIKE-regulated inflammatory response requires TBK1 blockage in PM2.5-treated cells. • Juglanin treatment suppresses inflammation in PM2.5-incubated cells through increasing SIKE expression.

Glycerol kinase (Gyk), consisting of 4 isoforms, plays a critical role in metabolism by converting glycerol to glycerol 3-phosphate in an ATP-dependent reaction. Only Gyk isoform b is present in whole cells, but its function in the nucleus remains elusive. Previous studies have shown that nuclear orphan receptor subfamily 4 group A member (NR4A)-1 is an important regulator of hepatic glucose homeostasis and lipid metabolism in adipose tissue. We aimed to elucidate the functional interaction between nuclear Gyk and NR4A1 during hepatic gluconeogenesis in the unfed state and diabetes. We identified nuclear Gyk as a novel corepressor of NR4A1 in the liver; moreover, this recruitment was dependent on the C-terminal ligand-binding domain instead of the N-terminal activation function 1 domain, which interacts with other NR4A1 coregulators. NR4A1 transcriptional activity was inhibited by Gyk via protein-protein interaction but not enzymatic activity. Moreover, Gyk overexpression suppressed NR4A1 ability to regulate the expression of target genes involved in hepatic gluconeogenesis in vitro and in vivo as well as blood glucose regulation, which was observed in both unfed and diabetic mice. These results highlight the moonlighting function of nuclear Gyk, which was found to act as a coregulator of NR4A1, participating in the regulation of hepatic glucose homeostasis in the unfed state and diabetes.-Miao, L., Yang, Y., Liu, Y., Lai, L., Wang, L., Zhan, Y., Yin, R., Yu, M., Li, C., Yang, X., Ge, C. Glycerol kinase interacts with nuclear receptor NR4A1 and regulates glucose metabolism in the liver.

Background: The pandemic of 2019 novel coronavirus (COVID-19) poses a challenge to health promotion in the days of lockdown We aimed to evaluate the characteri

Bacterial flagellin is a pathogen-associated molecular pattern recognized by surface-localized Toll-like receptor 5 (TLR5) and cytosolic NOD-like receptor protein 4 (NLRC4). CBLB502, derived from Salmonella flagellin, exhibits high radioprotective efficacy in mice and primates by regulating TLR5 and the nuclear factor kappa B (NF-κB) signaling pathway. In this study, we examined the effects of CBLB502 and mutations in its NLRC4- and TLR5-binding domains on radioprotective efficacy and the immune inflammatory response. The results showed that CBLB502 mutation with I213A in the TLR5-binding domain significantly reduced NF-κB activity and radioprotective activity, whereas CBLB502 mutation with L292A in NLRC4-binding domain did not. Additionally, CBLB502 with both mutations greatly reduced NF-κB activity and eliminated radioprotection in mice. In contrast, NLRC4-binding domain mutation reduced the secretion of inflammatory interleukin-1β and interleukin-18. CBLB502 exerts its radioprotective effects through both the TLR5 and NLRC4 pathways. Additionally, deletion in the NLRC4-binding domain did not reduce radioprotective activity but reduced the inflammatory response.

By taking the lived body as local, unstable, diverse, and open to urban and global incorporations, this book highlights contemporary Chinese and global reductions of diverse conditions into generalized objects, especially in the Chinese state's well-intended social welfare effort of "building socialist new villages" which in the mean time shows clearly how judgments come to be disguised as facts (Cf. Pigg 1992). The political economic roots and social determinants of "dirty villages," the strategies of inhabiting "villages with empty centers," and the local and national projects of cultural production all reveal much about class and power in China today. Unlike other close ethnographies of small places in China, this reading of local culture is considered in the context of the national and global practices that maintain a deeply divisive rural-urban divide in everyday hygienic practices. This book argues that substantive ethnographic attention to the specificities of village life in the contemporary Henan context can destabilize China's chronic rural-urban divide and contribute to an effective rural welfare intervention to improve the hygienic conditions of village life at present.

This study aimed to test the hypothesis that different neurotransmitters and hormones are presented at exercise fatigue in hot temperatures with differing relative humidities (RH).Eight trained male athletes performed a graded maximum oxygen consumption (VO2max) test in five different environmental conditions, namely, 21°C/20% RH (Normal), 33°C/20% RH (Hot 20%), 33°C/40% RH (Hot 40%), 33°C/60% RH (Hot 60%), and 33°C/80% RH (Hot 80%). Blood samples were taken pre- and post-exercise and analyzed for noradrenaline (NA), adrenaline (ADR), dopamine (DA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and prolactin (PRL). Weight and oral and skin temperatures were recorded pre- and post-exercise. Heart rate was continuously monitored throughout the exercise.Hot 20%, Hot 40%, and Hot 80% had lower VO2max levels compared with Normal (P0.05). The data pooled from all five conditions indicated that the NA (P0.0001), PRL (P0.0001), 5-HT (P=0.002), 5-HIAA (P=0.029), and DA (P=0.016) levels were affected by exercise. Accordingly, NA level was significantly associated with performance time. However, ADR did not show any significant effect between pre- and post-exercise (P=0.187).The maximal aerobic capacity was impaired in high temperature and most humidity conditions. NA was strongly associated with exercise time, which suggested that exercise duration and intensity had an important influence on NA neurotransmitter level irrespective of the environmental conditions.

This article describes emergent Chinese regimes of knowledge about “minority nationality medicines.” We adopt Weberian terms of rational and charismatic authority to better understand ethnic healing as it is developing among minorities in southwestern China. In the course of uneven development among diverse ethnic groups over recent decades, modern information regimes and institutional models have started to transform the many forms of healing and heritage that can be found “on the ground” in minority areas. We delineate a shifting border between official (or rational) and wild (or charismatic) forms of medicine, and argue that every healing situation results from a dynamic and sometimes destructive relation between these forms of authority. We draw from research conducted among seven minority nationalities scattered in five provinces in China's south and southwest. After an overview of relevant scholarly work that circulates nationally, we discuss views and practices of three healers belonging to Zhuang, Tujia, and Yao groups, respectively. Ultimately we suggest that all healing, including that taking place in biomedical clinics, relies on some contact with “the wild,” and forges a relationship between rationality and charisma.

Excess high-fat diet (HFD) intake predisposes the occurrence of obesity-associated heart injury, but the mechanism is elusive. Fisetin (FIS), as a natural flavonoid, has potential activities to alleviate obesity-induced metabolic syndrome. However, the underlying molecular mechanisms of FIS against HFD-induced cardiac injury remain unclear. The present study was to explore the protective effects of FIS on cardiac dysfunction in HFD-fed mice. We found that FIS alleviated HFD-triggered metabolic disorder by reducing body weight, fasting blood glucose and insulin levels, and insulin resistance. Moreover, FIS supplements significantly alleviated dyslipidemia in both mouse hearts and cardiomyocytes stimulated by metabolic stress. FIS treatment abolished HFD-induced inflammatory response in heart tissues through suppressing TNF receptor-1/TNF receptor-associated factor-2 (Tnfr-1/Traf-2) signaling. Furthermore, FIS induced a strong reduction in the expression of fibrosis-related genes, contributing to the inhibition of fibrosis by inactivating transforming growth factor (Tgf)-β1/Smads/Erk1/2 signaling. Collectively, these results demonstrated that FIS could be a promising therapeutic strategy for the treatment of obesity-associated cardiac injury.

Astrocytes activation related NF-κB signaling and oxidative stress were treated as key target associated with PM2.5 threating nerve injury. Unfortunately, the underlying molecular mechanisms of interaction between NF-κB signaling, glial cells activation in neuroinflammation are still not absolutely explained. Fisetin, a natural flavonoid was found to be promote health, partly due to its ability in antioxidant and anti-inflammation. In this regard, we constructed fisetin nanoparticles (FN) to investigate the anti-inflammatory effect in PM2.5-induced mice. Accordingly, qPCR and western blot analysis indicated that astrocytes activation related NF-κB signaling and oxidative stress contributed to PM2.5-induced neuroinflammation, which were significantly suppressed by increasing concentration of FN treatment. Also, FN may directly enhance anti-oxidative stress and anti-inflammatory way to perform inhibitory effects on NF-κB related glial cells activation. Overall, here we identified a new mechanism of action of FN as potential anti-inflammatory product against PM2.5-induced neuroinflammation via regulation of astrocytes activation related NF-κB.

This article shows how a newly “salvaged” and “sorted” minority nationality medicine is being rendered as information, while attending to the dynamic emergence of new knowledge. After providing som...

This collection of mostly ethnographic studies of rural China, with some contributions from the rather different discourse world of Chinese anthropology, seeks to bring into visibility the heterogeneity of life in the countryside. They argue that rural China must first and foremost be understood as socially and culturally heterogeneous. On the other hand, there is much resonance in the details among all these articles, reminding us that ethnography in contemporary China can accumulate to give us an anthropology or sociology of the state as it is seen from the point of view of its relatively denigrated or subaltern peripheries, that is, rural China. Many dilemmas and challenges facing the people described in these articles are held in common, and together they allow us to see a broad vision of contemporary China beyond the cities and the dominant mass media. Being rather ethnographic/descriptive, the articles gathered here show that good and attentive description, under some conditions, can also be critique.

Background Children are prone to get infections, especially in the respiratory system and the gut mainly because their immune system is immature. T cells significantly contribute to the prevention of infections, and different helper T cell (Th) subsets play different anti-pathogen roles. Interleukin (IL)-22 producing by T-helper 22 cells (Th22) play an important role in host defense against Gram-negative bacterial organisms in gut and lung. T-helper 17 cells (Th17) protect against extracelluar bacteria and fungi especially at the epithelial surface. However, there is no report comparing IL-22 producing T cells and Th17 cells in healthy young children to adults. Methods Flow cytometry (FCM) was used to observe whether Th22 subset existed in the peripheral blood of healthy young children. Meanwhile, we determined the frequencies of Th subsets including Th17, Th1 and Th2, cytotoxic T (Tc)1 subset, CD4+ and CD8+ memory T cells in the peripheral blood of both young children and adults. Results In the present study, we demonstrated that Th22 subset existed in peripheral blood of children, with IL-22 mainly secreted by CD4 + CD45RO+ memory T cells. Moreover, we observed that IL-22 + CD4 + T cells and Th subsets including Th17, Th1, and Th2 frequencies of young children (1–6 years old) were significantly lower than adults. While the Th1 frequency from Group A (1–3 years old) was markedly lower than that from Group B (4–6 years old). No significant differences of Th17 or IL-22 + CD4 + T cells frequencies were observed between these two groups. In addition, Tc1 subset frequencies were also remarkably lower in young children than in adults. Furthermore, lower frequencies of CD45RO+ memory CD4+ and CD8+ T cells in young children than in adults, and significant correlation between CD45RO+ memory CD4 + T cells and IL-22 + CD4 + T cells, Th1, Th17 were observed. Conclusions Th22 subset exists in the peripheral blood of young children. Compared with adults, there are lower frequencies of IL-22 + CD4 + T cells, as well as Th1, Th17, Th2 and Tc1 subsets in the peripheral blood of young children.

If one task of modern nation-states is to produce a commons or a known universe, a one-world world that is visible to all, what spaces are left for the uncommons? Drawing on a 2014 visit to a village, once a county town, just barely within the borders of China, we follow James Scott in asking not only how a state sees but what a state might be able to see, as well. To understand the uncanny (in)visibility of this place, we invoke Chinese yin-yang theory to reflect on the ways that human space transforms through time, partly hidden by yin shade and partly revealed in yang glare. The uncommons is not, in other words, an exterior to the one-world world; rather, it is a possible world that can make itself partly known in a mottled and ever-changing light and shade.

Previous studies suggest that the maximum oxygen uptake (VO2max) and the Wingate anaerobic test performances are decreased in hot environments, but it is unknown whether humidity changes in a hot environment further affect the results of the VO2max and Wingate anaerobic test. Nine male athletes performed VO2max and Wingate anaerobic tests under three environmental conditions: (1) 21 °C/20% relative humidity (R.H.) (control); (2) 33 °C/20% R.H. (hot–dry); and (3) 33 °C/80% R.H. (hot–wet). The participants' weight, oral temperature, and skin temperature were recorded pre-exercise and postexercise. The heart rate was monitored continuously throughout the exercise. Compared to the control condition, the hot–dry and the hot–wet conditions had lower VO2max values (control at 3779.0 ± 234.3 mL/min vs. hot–dry at 3528.2 ± 467.4 mL/min and hot–wet at 3595.9 ± 274.6 mL/min; p