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Background The influence of overall lifestyle behaviors on diabetic microvascular complications remains unknown. In addition, the potential mediating biomarkers underlying the association is unclear. This study aimed to examine the associations of the combined lifestyle factors with risks of total and individual microvascular complications among patients with type 2 diabetes (T2D) and to explore the potential mediation effects of metabolic biomarkers. Methods and findings This retrospective cohort study included 15,104 patients with T2D free of macro- and microvascular complications at baseline (2006 to 2010) from the UK Biobank. Healthy lifestyle behaviors included noncurrent smoking, recommended waist circumference, regular physical activity, healthy diet, and moderate alcohol drinking. Outcomes were ascertained using electronic health records. Over a median of 8.1 years of follow-up, 1,296 cases of the composite microvascular complications occurred, including 558 diabetic retinopathy, 625 diabetic kidney disease, and 315 diabetic neuropathy, with some patients having 2 or 3 microvascular complications simultaneously. After multivariable adjustment for sociodemographic characteristics, history of hypertension, glycemic control, and medication histories, the hazard ratios (95% confidence intervals (CIs)) for the participants adhering 4 to 5 low-risk lifestyle behaviors versus 0 to 1 were 0.65 (0.46, 0.91) for diabetic retinopathy, 0.43 (0.30, 0.61) for diabetic kidney disease, 0.46 (0.29, 0.74) for diabetic neuropathy, and 0.54 (0.43, 0.68) for the composite outcome (all Ps-trend [less than or equal to]0.01). Further, the population-attributable fraction (95% CIs) of diabetic microvascular complications for poor adherence to the overall healthy lifestyle ( Conclusions Adherence to overall healthy lifestyle behaviors was associated with a significantly lower risk of microvascular complications in patients with T2D, and the favorable associations were partially mediated through improving biomarkers of glycemic control, systemic inflammation, liver function, and lipid profile., Author(s): Tingting Geng 1, Kai Zhu 1, Qi Lu 1, Zhenzhen Wan 1, Xue Chen 1, Liegang Liu 1, An Pan 2,*, Gang Liu 1,* Introduction Diabetes is a global [...]

Taking 27 cities in the Yangtze River Delta as an example, the time section data from 2009 to 2019 are selected, and the location entropy index and the modified E-G index are introduced to measure the collaborative agglomeration level of intercity manufacturing industry in the Yangtze River Delta. The spatial weight matrix is constructed based on the highway mileage between cities. Using Moran's index and Local Moran's index, this article analyzes the spatial correlation of the collaborative agglomeration level of intercity manufacturing industry in the Yangtze River Delta. The results show that: Firstly, the overall agglomeration degree of manufacturing industry of cities in the Yangtze River Delta shows a fluctuating downward trend. The agglomeration degree of manufacturing industry in Jiangsu and Zhejiang Provinces has decreased, that of most cities in Anhui Province has increased steadily. Secondly, the collaborative agglomeration level of manufacturing industry between Shanghai, Nanjing, Hangzhou and other cities in Jiangsu and Zhejiang Provinces showed a downward trend, while the collaborative agglomeration level with Anhui cities increased steadily. The collaborative agglomeration level of manufacturing industry between Wuxi, Suzhou, Nanjing and cities with obvious advantages in manufacturing industry agglomeration degree shows an upward trend, while the collaborative agglomeration level with other cities has declined. The collaborative agglomeration level of intercity manufacturing industry in Hefei has generally improved, especially the collaborative agglomeration quality and depth of manufacturing industry between Hefei and other cities in Anhui Province have significantly improved. Thirdly, the regions with high collaborative agglomeration level of intercity manufacturing industry in the Yangtze River Delta are still mainly concentrated in Jiangsu and Zhejiang Provinces. Although there has been a trend of westward transfer in the past decade, the overall change range is small, and the spatial correlation of the collaborative agglomeration level of intercity manufacturing industry shows a weakening trend as a whole. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of physical exercise on sleep quality and the mediating effect of smartphone use behavior in college students. Methods: A cross-sectional study design was adopted. An online survey of 5,075 college students was conducted using the Physical Activity Rating Scale-3, the Pittsburgh Sleep Quality Index, and the Mobile Phone Addiction Tendency Scale. Results: The sleep quality of college students was poor, and the proportion of college students with good sleep quality was 23.567%. A significant correlation existed between sleep quality and physical exercise (r = −0.159, P < 0.001) and mobile phone addiction (r = 0.355, P < 0.001). Physical exercise can predict sleep quality in college students (β = −0.011, P < 0.001). Smartphone use plays a part in mediating the process by which physical exercise affects sleep quality. Conclusion: Chinese college students have poor sleep quality. Physical exercise and smartphone use behavior are important factors affecting the sleep quality of college students. Physical exercise can directly predict the sleep quality of college students and can predict the sleep quality of college students through the mediating effect of smartphone use behavior. [ABSTRACT FROM AUTHOR]

Over the past decade, therapeutic monoclonal antibodies (mAbs) have established their role as valuable agents in the treatment of various diseases ranging from cancers to infectious, cardiovascular and autoimmune diseases. Reactive groups of the amino acids within these proteins make them susceptible to many kinds of chemical modifications during manufacturing, storage and in vivo circulation. Among these reactions, the oxidation of methionine residues to their sulfoxide form is a commonly observed chemical modification in mAbs. When the oxidized methionine is in the complementarity-determining region (CDR), this modification can affect antigen binding and thus abrogate biological activity. For these reasons, it is essential to identify oxidation liabilities during the antibody discovery and development phases. Here, we present an in silico method, based on protein modeling and molecular dynamics simulations, to predict the oxidation-liable residues in the variable region of therapeutic antibodies. Previous studies have used the 2-shell water coordination number descriptor (WCN) to identify methionine residues susceptible to oxidation. Although the WCN descriptor successfully predicted oxidation liabilities when the residue was solvent exposed, the method was much less accurate for partially buried methionine residues. Consequently, we introduce a new descriptor, WCN-OH, that improves the accuracy of prediction of methionine oxidation susceptibility by extending the theoretical framework of the water coordination number to incorporate the effects of polar amino acids side chains in close proximity to the methionine of interest. [ABSTRACT FROM AUTHOR]

Car sharing has become a new mode of transport during the past two decades in the world. Its rapid growth in China has attracted a wide range of users and posed some problems. The main focus is on service efficiency and user satisfaction. To explore possible service enhancement and management intervention, this study aims at capturing the user characteristics according to different user types and scrutinizing their satisfaction with station-based one-way car sharing service. The study firstly illustrates descriptive statistics of user profile. This is followed by a study of user satisfaction influenced by user rates on staffs, the efficiency of rental process, vehicle situation, the use of credit card and their familiarity towards rental station. Furthermore, by clustering users according to the total travel time and distance during one rent, two different types of users are identified and defined as User Group A (UGA) and User Group B (UGB). To examine how fully do users utilize the shared cars, ANOVA was conducted implying family car ownership, total travel distance and main travel purpose have strong impact on total rental time for UGB, while for UGA, travel purpose and age have strong impact. Finally, ordinal logistic regression was introduced to find that for UGB, "shopping" is the main travel purpose with longer rental time, whereas for UGA, "out for business", "shopping", "visit friends" or "pick up others" are the main travel purposes with longer total travel time. Based on the findings, advices for operators on how to improve service quality and suggestions for government management strategy are discussed, respectively. [ABSTRACT FROM AUTHOR]

Sugarcane ratoon stunting disease (RSD) caused by Leifsonia xyli subsp. xyli (Lxx) is a common destructive disease that occurs around the world. Lxx is an obligate pathogen of sugarcane, and previous studies have reported some physiological responses of RSD-affected sugarcane. However, the molecular understanding of sugarcane response to Lxx infection remains unclear. In the present study, transcriptomes of healthy and Lxx-infected sugarcane stalks and leaves were studied to gain more insights into the gene activity in sugarcane in response to Lxx infection. RNA-Seq analysis of healthy and diseased plants transcriptomes identified 107,750 unigenes. Analysis of these unigenes showed a large number of differentially expressed genes (DEGs) occurring mostly in leaves of infected plants. Sugarcane responds to Lxx infection mainly via alteration of metabolic pathways such as photosynthesis, phytohormone biosynthesis, phytohormone action-mediated regulation, and plant-pathogen interactions. It was also found that cell wall defense pathways and protein phosphorylation/dephosphorylation pathways may play important roles in Lxx pathogeneis. In Lxx-infected plants, significant inhibition in photosynthetic processes through large number of differentially expressed genes involved in energy capture, energy metabolism and chloroplast structure. Also, Lxx infection caused down-regulation of gibberellin response through an increased activity of DELLA and down-regulation of GID1 proteins. This alteration in gibberellic acid response combined with the inhibition of photosynthetic processes may account for the majority of growth retardation occurring in RSD-affected plants. A number of genes associated with plant-pathogen interactions were also differentially expressed in Lxx-infected plants. These include those involved in secondary metabolite biosynthesis, protein phosphorylation/dephosphorylation, cell wall biosynthesis, and phagosomes, implicating an active defense response to Lxx infection. Considering the fact that RSD occurs worldwide and a significant cause of sugarcane productivity, a better understanding of Lxx resistance-related processes may help develop tools and technologies for producing RSD-resistant sugarcane varieties through conventional and/or molecular breeding. [ABSTRACT FROM AUTHOR]

Feeding strategies of sympatric squid species help to understand their role in marine ecosystems. Four loliginid squids, Uroteuthis duvaucelii, Uroteuthis edulis, Uroteuthis chinensis, and Loliolus uyii are the major cephalopod species in the coastal waters of the northern South China Sea, where they occur together. We investigated their feeding strategies in terms of foraging behavior and habitat use by comparing fatty acid profiles and spatial distributions. There were no significant differences in the proportions of saturated or polyunsaturated fatty acids among species. Similar findings were obtained for most individual fatty acids that made up of an average of more than 84% of total fatty acid content for each species. Substantial overlap and high similarity in the fatty acid composition were observed. However, there were no significant effects of individual size or sampling station on the fatty acid compositions. The spatial overlap analysis demonstrated that there was clear spatial segregation and habitat use among the species. Cumulatively, our results suggest that the four squids are opportunistic carnivores, unselectively foraging on similar prey items, while spatial segregation is likely a major mechanism leading to their coexistence in the northern South China Sea. [ABSTRACT FROM AUTHOR]

Osmopriming with PEG has potential to improve seed germination, seedling emergence, and establishment, especially under stress conditions. This research investigated germination performance, seedling establishment, and effects of osmopriming with PEG on physiology in sorghum seedlings and their association with post-priming stress tolerance under various soil moisture stress conditions. Results showed that seed priming increased the environmental range suitable for sorghum germination and has potential to provide more uniform and synchronous emergence. Physiologically, seed priming strengthened the antioxidant activities of APX, CAT, POD, and SOD, as well as compatible solutes including free amino acid, reducing sugar, proline, soluble sugar, and soluble protein contents. As a result, seed priming reduced lipid peroxidation and stabilized the cell membrane, resulting in increased stress tolerance under drought or excessive soil moisture environments. Overall, results suggested that seed priming with PEG was effective in improving seed germination and seedling establishment of sorghum under adverse soil moisture conditions. Osmopriming effectively strengthened the antioxidant system and increased osmotic adjustment, likely resulting in increased stress tolerance. [ABSTRACT FROM AUTHOR]

In this paper, an analogue of hirsutine (compound 1) has been synthesized and evaluated as an anti-hypertension agent, which exhibits extraordinary effects on the contractile response of thoracic aorta rings from male SD rats in vitro (IC50 = 1.129×10-9±0.5025) and the abilities of reducing the systolic blood pressure (SBP) and heart rate (HR) of SHR in vivo. The mechanism investigation reveals that the vasodilatation induced by compound 1 is mediated by both endothelium-dependent and -independent manners. The relaxation in endothelium-intact aortic rings induced by compound 1 can be inhibited by L-NAME (1×10-6 mol•L-1) and ODQ (1×10-6 mol•L-1). Moreover, compound 1 can also block Ca2+ influx through L-type Ca2+ channels and inhibit intracellular Ca2+ release while no effect on K+ channel has been observed. All these data demonstrated that the NO/cyclic GMP pathway can be involved in endothelium-dependent manner induced by compound 1. Meanwhile the mechanism on the vasodilatation of compound 1 probably also related to blockade of Ca2+ influx through L-type Ca2+ channels and inhibition of intracellular Ca2+ release may have no relationship with K+ channels. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT) cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs). Mechanistically, interleukin (IL)-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. Method: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. Results: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. Conclusion: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated. Author Summary: Systemic inflammation is characteristic of severe hand, foot, and mouth disease (HFMD). Steroids are considered immunomodulators and have been officially recommended to treat the severe HFMD patients with CNS complications in China. So far, it is uncertain whether steroid treatment has an immunomodulatory role in inflammation in HFMD patients and has a real beneficial effect on their prognosis. This study revealed that even relatively mild HFMD patients without CNS complications had elevated inflammation. Unexpectedly, the inflammatory cytokine levels in patients treated with methylprednisolone, one kind of steroid, were not significantly different from those in patients without the treatment. Rather, the treated patients tended to have elevated levels of IL-17A, whose expression levels were actually not significantly associated with the presence of HFMD. IL-17A is known to play a role in the pathogenesis of CNS-related inflammatory diseases. Altogether, our study does not support the presumption that steroids have beneficial effect on the prognosis of HFMD patients by inhibiting systemic inflammation. [ABSTRACT FROM AUTHOR]

CD4+ T cell-mediated immunity plays a central role in determining the immunopathogenesis of viral infections. However, the role of CD4+ T cells in EV71 infection, which causes hand, foot and mouth disease (HFMD), has yet to be elucidated. We applied a sophisticated method to identify promiscuous CD4+ T cell epitopes contained within the sequence of the EV71 polyprotein. Fifteen epitopes were identified, and three of them are dominant ones. The most dominant epitope is highly conserved among enterovirus species, including HFMD-related coxsackieviruses, HFMD-unrelated echoviruses and polioviruses. Furthermore, the CD4+ T cells specific to the epitope indeed cross-reacted with the homolog of poliovirus 3 Sabin. Our findings imply that CD4+ T cell responses to poliovirus following vaccination, or to other enteroviruses to which individuals may be exposed in early childhood, may have a modulating effect on subsequent CD4+ T cell response to EV71 infection or vaccine.

FILIA is a member of the recently identified oocyte/embryo expressed gene family in eutherian mammals, which is characterized by containing an N-terminal atypical KH domain. Here we report the structure of the N-terminal fragment of FILIA (FILIA-N), which represents the first reported three-dimensional structure of a KH domain in the oocyte/embryo expressed gene family of proteins. The structure of FILIA-N revealed a unique N-terminal extension beyond the canonical KH region, which plays important roles in interaction with RNA. By co-incubation with the lysates of mice ovaries, FILIA and FILIA-N could sequester specific RNA components, supporting the critical roles of FILIA in regulation of RNA transcripts during mouse oogenesis and early embryogenesis.