Search

Thermogenic adipocytes have been extensively investigated because of their energy-dissipating property and therapeutic potential for obesity and diabetes. Besides serving as fuel sources, accumulating evidence suggests that intermediate metabolites play critical roles in multiple biological processes. However, their role in adipocyte differentiation and thermogenesis remains unexplored. Here, we report that human and mouse obesity is associated with marked downregulation of glutamine synthetase (Glul) expression and activity in thermogenic adipose tissues. Glul is robustly upregulated during brown adipocyte (BAC) differentiation and in brown adipose tissue (BAT) upon cold exposure and Cl316,243 stimulation. Further genetic, pharmacologic, or metabolic manipulations of Glul and glutamine levels reveal that glutamine cells autonomously stimulate BAC differentiation and function and BAT remodeling and improve systemic energy homeostasis in mice. Mechanistically, glutamine promotes transcriptional induction of adipogenic and thermogenic gene programs through histone modification–mediated chromatin remodeling. Among all the glutamine-regulated writer and eraser genes responsible for histone methylation and acetylation, only Prdm9, a histone lysine methyltransferase, is robustly induced during BAC differentiation. Importantly, Prdm9 inactivation by shRNA knockdown or a selective inhibitor attenuates glutamine-triggered adipogenic and thermogenic induction. Furthermore, Prdm9 gene transcription is regulated by glutamine through the recruitment of C/EBPb to its enhancer region. This work reveals glutamine as a novel activator of thermogenic adipocyte differentiation and uncovers an unexpected role of C/EBPb-Prdm9–mediated H3K4me3 and transcriptional reprogramming in adipocyte differentiation and thermogenesis. Article Highlights: Glutamine is a pivotal player in multiple biological processes and disease progression, but its role in thermogenic adipocyte differentiation and function remains unclear. Through genetic, pharmacologic, or metabolic manipulations of glutamine synthetase (Glul) and glutamine levels, the role and mechanism of the Glul-glutamine pathway in adipocyte thermogenesis and systemic homeostasis was investigated. Glul-mediated glutamine production was found to be critical for brown adipocyte differentiation and uncovered an unexpected role of C/EBPb-Prdm9–mediated histone methylation and transcriptional reprogramming in this process. This work highlights the therapeutic and translational potential of targeting the Glul-glutamine-Prdm9 pathway to treat obesity and associated metabolic diseases. [ABSTRACT FROM AUTHOR]

Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway. Interorgan communications play key roles in the regulation of whole-body energy metabolism. Here, the authors report the myokine Musclin as a negative regulator of beige adipose thermogenesis and systemic energy homeostasis through Tfr1/PKA signalling mediated muscle fat crosstalk. [ABSTRACT FROM AUTHOR]

Purpose: With the rapid development of paid online social question and answer (Q&A) communities, monetary social functions have been introduced and have potential benefits for both platforms and users. However, these functions' impact on knowledge contribution remains uncertain. This study proposes a conceptual model based on the stimulus–organism–response framework, according to which monetary and non-monetary social functions can help nurture short-term and long-term relationships among community users, and thereafter improves social identity and knowledge-sharing intentions. Design/methodology/approach: This study selects Zhihu, a famous online social Q&A community in China, and conducts an online survey to collect data from its frequent users. A sample of 286 valid questionnaires was collected to test our research model by using a structural equation modeling method. In addition, a bootstrapping approach is used to test the mediation effect. Findings: Results indicate that monetary social functions help nurture short-term and long-term relationships among community users. However, non-monetary social functions only affect short-term relationships directly. Short-term and long-term relationships both have a positive relationship with social identity and thereafter improve users' knowledge-sharing intentions. Originality/value: This study focuses on users' knowledge-sharing intentions in Q&A communities from the perspective of social. Specifically, we separated social functions in Q&A platforms into monetary and non-monetary ones and explored their impact on the development of short-term and long-term relationships. Results demonstrate the importance of monetary social functions and explain how monetary and non-monetary social functions affect users' knowledge-sharing intentions in different approaches. [ABSTRACT FROM AUTHOR]

Background: Clonorchis sinensis granulin (CsGRN), a component of the excretory/secretory products of this species, is a multifunctional growth factor that can promote the metastasis of cholangiocarcinoma cells. However, the effect of CsGRN on human intrahepatic biliary epithelial cells (HIBECs) is unclear. Here, we investigated the effect of CsGRN on the malignant transformation of HIBECs and its possible underlying mechanism. Methods: The malignant transformation phenotypes of HIBECs after CsGRN treatment were estimated by EdU-488 incorporation assay, colony formation assay, wound-healing assay, Transwell assay and western blot. The biliary damage of CsGRN-treated mice was detected by western blot, immunohistochemical staining and hematoxylin and eosin staining. The phenotypes of the macrophages [human monocytic leukemia cell line (THP-1)] were analyzed by flow cytometry, immunofluorescence and immunohistochemistry, both in vitro and in vivo. A co-culture system was developed to explore the interaction between THP-1 and HIBECs in CsGRN-containing medium. Enzyme-linked immunosorbent assay and western blot were used to detected the activation of interleukin 6 (IL-6), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. An inhibitor of the MEK/ERK pathway, PD98059, was used to determine whether this pathway is involved in CsGRN-mediated cell interactions as well as in STAT3 phosphorylation and malignant transformation of HIBECs. Results: Excessive hyperplasia and abnormal proliferation of HIBECs, enhanced secretion of hepatic pro-inflammatory cytokines and chemokines, as well as biliary damage, were observed in vitro and in vivo after treatment with CsGRN. The expression of the markers of M2 macrophages significantly increased in CsGRN-treated THP-1 cells and biliary duct tissues compared with the controls. Moreover, following treatment with CsGRN, the HIBECs underwent malignant transformation in the THP-1-HIBECs co-culture group. In addition, high expression of IL-6 was observed in the CsGRN-treated co-culture media, which activated the phosphorylation of STAT3, JAK2, MEK and ERK. However, treatment with an inhibitor of the MEK/ERK pathway, PD98059, decreased expression of p-STAT3 in CsGRN-treated HIBECs and further repressed the malignant transformation of HIBECs. Conclusions: Our results demonstrated that, by inducing the M2-type polarization of macrophages and activating the IL-6/JAK2/STAT3 and MEK/ERK pathways in HIBECs, CsGRN promoted the malignant transformation of the latter. [ABSTRACT FROM AUTHOR]

The toxic effects of four cationic porphyrins on various human cells were studied in vitro. It was found that, under dark conditions, porphyrins are almost nontoxic, while, under the action of light, the toxic effect was observed starting from nanomolar concentrations. At a concentration of 100 nM, porphyrins caused inhibition of metabolism in the MTT test in normal and cancer cells. Furthermore, low concentrations of porphyrins inhibited colony formation. The toxic effect was nonlinear; with increasing concentrations of various porphyrins, up to about 1 μM, the effect reached a plateau. In addition to the MTT test, this was repeated in experiments examining cell permeability to trypan blue, as well as survival after 24 h. The first visible manifestation of the toxic action of porphyrins is blebbing and swelling of cells. Against the background of this process, permeability to porphyrins and trypan blue appears. Subsequently, most cells (even mitotic cells) freeze in this swollen state for a long time (24 and even 48 h), remaining attached. Cellular morphology is mostly preserved. Thus, it is clear that the cells undergo mainly necrotic death. The hypothesis proposed is that the concentration dependence of membrane damage indicates a limited number of porphyrin targets on the membrane. These targets may be any ion channels, which should be considered in photodynamic therapy. [ABSTRACT FROM AUTHOR]

Objective: To analyze the trends in disease burden of diabetes-related chronic kidney disease (CKD) by year, age, gender and types of diabetes in China from 1990 to 2019. Methods: Data on prevalence, deaths and disability-adjusted life years (DALYs) for diabetes-related CKD were extracted from the Global Burden of Disease (GBD) 2019 study. Analyses were performed by year, age, gender and types of diabetes. Results: In China, the numbers of deaths and DALYs of diabetes-related CKD continuously increased but the age-standardized rates (per 100,000 population) decreased over 30 years, in which the numbers of deaths and DALYs attributable to type 1 diabetes mellitus (T1DM)-related CKD barely changed and the age-standardized rates decreased over the years; and the number of deaths and DALYs attributable to type 2 diabetes mellitus (T2DM)-related CKD continuously increased, but the age-standardized rates also decreased. In 2019, 76.03 (58.24-95.61) thousand deaths and 2.13 (1.65–2.67) million DALYs were attributable to diabetes-related CKD, of which, T2DM accounted for 83.32% and 77.0% respectively, and T1DM accounted for the rest. Increasing gender disparity was seen, with males being more heavily impacted. The burden of diabetes-related CKD varied among different age groups, with the numbers of deaths and DALYs attributable to T1DM-related CKD peaking between 45 and 54 years of age and T2DM-related CKD peaking between 75 and 79 years of age; and the crude rates of deaths and DALYs attributable to T1DM-related CKD peaking between 70 and 79 years of age and 40 to 54 years of age, respectively, and T2DM-related CKD peaking over 90 years of age. Among neighboring and G20 countries, the burden of diabetes-related CKD in China was relatively controlled reflected by the ranking of adjusted death and DALYs rates. Conclusions: The burden of diabetes-related CKD in China worsens and shows gender disparities and different age distribution. Greater efforts are needed to improve the health outcomes of these patients, especially among males. [ABSTRACT FROM AUTHOR]

Background: Low bone mineral density (LBMD), including osteoporosis and low bone mass, has becoming a serious public health concern. We aimed to estimate the disease burden of LBMD and its related fractures in 204 countries and territories over the past 30 years. Methods: We collected detailed information and performed a secondary analysis for LBMD and its related fractures from the Global Burden of Disease Study 2019. Numbers and age-standardized rates related to LBMD of disability-adjusted life-years (DALYs) and deaths in 204 countries and territories were compared by age, gender, socio-demographic index (SDI), and location. Results: Global deaths and DALYs number attributable to LBMD increased from 207 367 and 8 588 936 in 1990 to 437 884 and 16 647 466 in 2019, with a raise of 111.16% and 93.82%, respectively. DALYs and deaths number of LBMD-related fractures increased 121.07% and 148.65% from 4 436 789 and 121248 in 1990 to 9 808 464 and 301 482 in 2019. In 2019, the five countries with the highest disease burden of DALYs number in LBMD-related fractures were India (2 510 288), China (1 839 375), United States of America (819 445), Japan (323 094), and Germany (297 944), accounting for 25.59%, 18.75%, 8.35%, 3.29%, and 3.04%. There was a quadratic correlation between socio-demographic index (SDI) and burden of LBMD-related fractures: DALYs rate was 179.985-420.435SDI+417.936SDI2(R2 = 0.188, p<0.001); Deaths rate was 7.879-13.416SDI+8.839 SDI2(R2 = 0.101, p<0.001). Conclusions: The global burden of DALYs and deaths associated with LBMD and its related fractures has increased significantly since 1990. There were differences in disease burden between regions and countries. These estimations could be useful in priority setting, policy-making, and resource allocation in osteoporosis prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Dietary risks have raised attention worldwide during recent decades. The present burden‐of‐disease study aimed to evaluate the global dietary risks for non‐communicable diseases (NCDs) from 1990 to 2019 and quantify their impact on mortality and disability‐adjusted life‐years (DALYs). Data from the 2019 Global Burden of Disease Study on deaths and DALYs from NCDs attributable to worldwide dietary risks were obtained and underwent deep analysis by year, age, gender, location, leading risks and leading causes, and their associations were examined. The socio‐demographic index (SDI) was used as an indicator of national socio‐economic status, as well as the relationships between age‐standardised rates of deaths or DALYs and socio‐economic status. Results: In 2019, 7.9 million deaths and 187.7 million DALYs were attributable to dietary risk factors. High intake of sodium and low intake of whole grains and fruits were leading dietary risks for deaths and DALYs worldwide. However, both indices showed a decreasing trend by year, an increase by age and a higher disease burden in males. The main distribution of dietary‐related NCDs was located in highly populated countries. A negative association between the SDI and disease burden and a positive association between the SDI and male preponderance were found. Conclusions: Dietary risk factors for NCDs increased significantly and varied across regions during 1990–2019. Therefore, greater efforts are needed to raise public awareness of interventions and improve dietary practices aiming to reduce the disease burden caused by suboptimal dietary intake, especially in developing countries and among males. [ABSTRACT FROM AUTHOR]

Purpose: To assess the trend patterns and gender disparity in global burden of vision loss due to diabetic retinopathy (DR) by year, age, region and socioeconomic status using prevalence and years lived with disability (YLDs) from Global Burden of Disease (GBD) study 2017. Methods: Prevalence and YLDs data of vision loss attributable to DR were extracted from GBD Study 2017 in 195 countries and territories. Socio‐demographic Index (SDI) in 2017 was cited as indicators of socioeconomic status. Kruskal–Wallis test, Dunn's multiple comparisons and Pearson linear correlation were adopted to evaluate the gender disparity and association with socioeconomic levels. Results: Globally, total age‐standardized prevalence and YLDs rates of vision loss due to DR peaked around 2005, with prevalence rate of 58.98 [95% uncertainty interval (UI) 50.95–68.56] and YLDs rate of 5.00 (95% UI 3.51–6.84) per 100 000 population, respectively. The burden were expected to increase to 65.74 (95% UI 60.14–70.86) and 5.68 (95% UI 4.07–7.22) by 2050. The burden would increase according to our projection based on current epidemiological situation. However, gender disparity has existed since 1990 and been enlarging in recent years, with female being more heavily impacted. This pattern remained with ageing among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age‐standardized prevalence rates was positively related to SDI (r = 0.1661, p = 0.0203). Diabetes has become a more important risk over the past 3 decades among the leading causes of vision loss. Conclusions: The DR‐related vision loss burden tended to increase under ageing population according to our projection with significant gender disparity. Public awareness of DR and gender sensitive health policy should be emphasized. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The increasing burden of noncommunicable diseases (NCDs) attributable to high body mass index (BMI) represents both a threat and an opportunity for intervention. Estimates of the global latest trend of high BMI-related NCDs and its association with socioeconomic status can facilitate strategic intervention and inform further research. Methods: This global burden of disease study extracted global, regional, and national data on death and disability-adjusted life years (DALYs) attributable to high BMI-related NCDs from the GBD Study 2017. Secondary analyses were performed by year, age, sex, and specific causes of death and DALYs. The 2017 Socio-demographic Index (SDI) was used as an indicator of national socioeconomic status. The association between age-standardized death or DALYs rate and socioeconomic status were analyzed. Results: Worldwide, 4.7 million deaths and 147.7 million DALYs of NCDs were related to high BMI in 2017, with a projection to 5.5 million deaths and 176.9 million DALYs in 2025. Globally, high BMI-related burden showed an increasing trend with males being more heavily impacted overall. The trend and magnitude of high BMI-related disease burden varied substantially in different geographical and socioeconomic regions. Specifically, the low-middle, middle, and high-middle SDI countries were associated with a higher burden. The leading three causes of DALYs attributable to high BMI in 2017 were ischemic heart diseases, stroke, and diabetes mellitus. Conclusions: High BMI-related burden of NCDs is worsening, particularly in developing countries. Our findings may enhance public awareness of interventions to reduce the diseases burden caused by high BMI. [ABSTRACT FROM AUTHOR]

Simple Summary: Pomacea canaliculata is one of the 100 worst invasive alien species in the world, causing significant effects and harm to native species, ecological environment, human health, and social economy. In this study, we used species distribution modeling (SDM) methods to predict the potential distribution of P. canaliculata in China and found that with climate change, there would be a trend of expanding and moving northward in the future. Pomacea canaliculata is one of the 100 worst invasive alien species in the world, which has significant effects and harm to native species, ecological environment, human health, and social economy. Climate change is one of the major causes of species range shifts. With recent climate change, the distribution of P. canaliculata has shifted northward. Understanding the potential distribution under current and future climate conditions will aid in the management of the risk of its invasion and spread. Here, we used species distribution modeling (SDM) methods to predict the potential distribution of P. canaliculata in China, and the jackknife test was used to assess the importance of environmental variables for modeling. Our study found that precipitation of the warmest quarter and maximum temperature in the coldest months played important roles in the distribution of P. canaliculata. With global warming, there will be a trend of expansion and northward movement in the future. This study could provide recommendations for the management and prevention of snail invasion and expansion. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a leading cause of mortality and reduced life expectancy. We aim to estimate the burden of diabetes by type, year, regions, and socioeconomic status in 195 countries and territories over the past 28 years, which provide information to achieve the goal of World Health Organization Global Action Plan for the Prevention and Control of Noncommunicable Diseases in 2025. Data were obtained from the Global Burden of Disease Study 2017. Overall, the global burden of diabetes had increased significantly since 1990. Both the trend and magnitude of diabetes related diseases burden varied substantially across regions and countries. In 2017, global incidence, prevalence, death, and disability-adjusted life-years (DALYs) associated with diabetes were 22.9 million, 476.0 million, 1.37 million, and 67.9 million, with a projection to 26.6 million, 570.9 million, 1.59 million, and 79.3 million in 2025, respectively. The trend of global type 2 diabetes burden was similar to that of total diabetes (including type 1 diabetes and type 2 diabetes), while global age-standardized rate of mortality and DALYs for type 1 diabetes declined. Globally, metabolic risks (high BMI) and behavioral factors (inappropriate diet, smoking, and low physical activity) contributed the most attributable death and DALYs of diabetes. These estimations could be useful in policy-making, priority setting, and resource allocation in diabetes prevention and treatment. [ABSTRACT FROM AUTHOR]

Online social networks are an important part of people’s life and also become the platform where spammers use suspicious accounts to spread malicious URLs. In order to detect suspicious accounts in online social networks, researchers make a lot of efforts. Most existing works mainly utilize machine learning based on features. However, once the spammers disguise the key features, the detection method will soon fail. Besides, such methods are unable to cope with the variable and unknown features. The works based on graph mainly use the location and social relationship of spammers, and they need to build a huge social graph, which leads to much computing cost. Thus, it is necessary to propose a lightweight algorithm which is hard to be evaded. In this article, we propose a lightweight algorithm GroupFound, which focuses on the structure of the local graph. As the bi-followers come from different social communities, we divide all accounts into different groups and compute the average number of accounts for these groups. We evaluate GroupFound on Sina Weibo dataset and find an appropriate threshold to identify suspicious accounts. Experimental results have demonstrated that our algorithm can accomplish a high detection rate of 86 . 27 % at a low false positive rate of 8 . 54 % . [ABSTRACT FROM AUTHOR]