With metabolic syndrome (MS) in obese Zucker rats (OZR), the ability of in situ skeletal muscle to resist fatigue is compromised well before muscle function; implicating microvascular or perfusion‐based impairments as playing a causal role. However, our results suggest that bulk flow to muscle is not sufficiently constrained to explain the poor performance, and indices such as dilator/constrictor reactivity, vessel wall mechanics and capillary density are not strong predictors of functional outcomes. We have determined that altered RBC distribution at arteriolar bifurcations (γ) is increasingly heterogeneous in OZR muscle, iterating to produce a wide heterogeneity of pre‐capillary flow distribution vs. controls. This increased spatial heterogeneity of perfusion at bifurcations is not compensated for via temporal switching, rather it is exacerbated owing to blunted temporal activity. The combined effect of these behaviors is that microvascular hematocrit becomes increasingly heterogeneous and fixed, compromising perfusion:demand matching and muscle performance. The magnitude of the deviation of γ from 0.5, and its temporal stability are the strongest predictors of muscle performance to date. Grant Funding Source : Supported by National Institutes of Health and American Heart Association
It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions. NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .
An outbreak of trichinosis occurred in the city of Zhengzhou, central China, between December 1995 and February 1996, affecting 85 of the administrative units into which the city is split. Of 297 subjects from eight of the affected units, 54% were seropositive for Trichinella and 41% had symptoms consistent with acute trichinosis. Of the 490 subjects who had eaten at one particular dumpling restaurant 1-5 weeks before the outbreak and who were traced, 291 (59%) were seropositive and 212 (43%) had been or were ill. MOst of the infections were in manual workers, cadres and merchants aged 20-49 years. Most of those who had been infected failed to develop gastro-intestinal symptoms or a cutaneous rash. Eyelid oedema was only seen in the early stages of the infection, the main clinical manifestations being fever of long duration of tiredness. Surprisingly, six cases had no marked symptoms after repeated infection. Eosinophilia (eosinophils > 7% of leucocytes) was noted in 71 (55%) of the 130 cases in which blood cells were counted. When 212 sera were tested for antibodies to Trichinella, seropositivities were found to increase from 89.1% (IFAT) of 87.7% (microprecipitation test) at presentation to 100% (both tests) 1 week after treatment with albendazole. All those treated were cured. The outbreak was one of the most extensive, single-source outbreaks ever recorded in China, probably with > 600 infections and > 300 clinical cases. The entire episode was attributed to the ingestion of undercooked pork dumplings at one restaurant.
ABSTRACT The emergence of novel variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to pose an ongoing challenge for global public health services, highlighting the urgent need for effective therapeutic interventions. Neutralizing monoclonal antibodies (mAbs) are a major therapeutic strategy for the treatment of COVID-19 and other viral diseases. In this study, we employed hybridoma technology to generate mAbs that target the BA.5 receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Through a comprehensive screening process, we identified four mAbs capable of effectively neutralizing BA.5, XBB.1.16, and related variant infections in vitro , among which ORB10 was found to neutralize BA.5 variants with a plaque reduction neutralization test (PRNT 50 ) of 8.7 ng/mL. Additionally, competitive binding assays, sequencing of heavy and light chain variable regions, and binding kinetics characterization provided insights into the epitopes and binding affinities of the identified mAbs. Moreover, in vivo experiments in the K18-hACE2 mouse model demonstrated the protective efficacy of ORB10 against both BA.5 and XBB.1.16 variants. Finally, cryo-electron microscopy structural analysis of the ORB10–RBD complex identified key residues involved in the antibody–antigen interactions, providing insights into the molecular mechanisms of neutralization and immune escape of SARS-CoV-2 Omicron variants from mAbs. IMPORTANCE The ongoing evolution of SARS-CoV-2 has led to the emergence of variants capable of evading immune responses elicited by natural infection and vaccination, especially the highly transmissible and immune-evasive Omicron variants. This study generated and characterized a panel of monoclonal antibodies (mAbs) specifically targeting the RBD of the Omicron BA.5 variant, of which the ORB10 showed efficacy against Omicron BA.5 and XBB.1.16 variants both in vitro and in vivo . Cryo-EM structural analysis further elucidated the binding epitope interactions and neutralization mechanism between ORB10 and the BA.5 RBD protein. This study enhances our understanding of antibody-mediated neutralization of SARS-CoV-2 and provides valuable insights into the development of effective therapeutic strategies to combat ongoing SARS-CoV-2 variant infections.
Small strain stiffness characteristics are critical to predict the deformation caused by the interaction between soil and structures, especially masonry foundations and settlement-sensitive structures. Among them, the importance of Poisson’s ratio has not attracted enough attention in the study of small strain stiffness of unsaturated soils in the past. For fine-grained soils with significant volume change, the compression characteristics of soils under different saturations are different, which means that Poisson’s ratio is a function of saturation or matric suction. Using the relative humidity control method, the variation law of Poisson’s ratio with saturation was obtained through indoor elastic wave velocity and volume change test. The results show that when the sample is saturated, the value of Poisson’s ratio ν is between 0.49 and 0.5, and the soil is in an approximate incompressible state. With the decrease of saturation, the ν decreases linearly with the saturation. The ν of the silt decreases rapidly when the saturation is between 96 and 85%, and then fluctuates around 0.37 without obvious change. Compared with sand and silt, the saturation has a more significant effect on the Poisson’s ratio of clay.
Abstract Background： Anoectochilus roxburghii , a traditional Chinese herbal medicine, has been widely used for treating numerous metabolic diseases. Anoectochilus roxburghii polysaccharide (ARPs) is an important constituent of Anoectochilus roxburghii . This study tried to investigate whether ARPs could improve cognitive dysfunction in diet-induced obesity. Methods: C57BL/6J male mice were randomly divided into the normal chow diet group (CD), the high-fat diet group (HFD) and HFD supplemented with ARPs (HARPs). Morris water maze test and Y maze test were used to evaluate spatial learning and memory. Serum TNF-α and LPS concentrations were detected by ELISA. Genes involved in Neurotrophic factors, inflammation and Intestinal permeability were detected by RT-PCR. Immunohistochemistry was used to detect TNF-α and ZO-1 proteins. BDNF in hippocampus was detected by immunofluorescence staining. 16S rDNA sequencing was used to detect intestinal microbial diversity. Results: Dietary supplement of ARPs ameliorates cognitive dysfunction induced by HFD. Compared with HFD mice, body weight, plasma glucose, total cholesterol and triglyceride levels in HARPs group were decreased significantly. Moreover, the cognitive function and memory of HFD mice were decreased, while ARPs abolished these effects. In addition, Tau protein levels were decreased and BDNF increased significantly in hippocampus from HARPs mice. Furthermore, compared with HFD group, IL-6 and TNF-α levels in hippocampus and colon from HARPs mice were decreased. Moreover, ARPs increased the tight junction protein levels and intestinal microbiota diversity significantly. Conclusions: Diet supplemented with ARPs prevented mice from HFD-induced cognitive dysfunction, indicated that ARPs has a good effect on obesity-related neuropathy. Mechanically, these effects at least in part attribute to the “gut-brain” axis regulation, and which can provide reference for the development of ARPs as functional foods in the future.
To understand the prevalence and control of several common chronic disease in Beijing adults.16,658 adult residents were randomly selected with stratified multi-stage cluster sampling method. Each participant was invited to receive a set of standardized questionnaire, physical examinations and laboratory tests.Data showed that the prevalence, awareness, treatment and the rate of control on hypertension among the adults in Beijing were 29.1%, 49.3%, 42.3% and 10.6% respectively. The counterparts of diabetes mellitus were 8.8%, 56.7%, 50.0% and 15.0%. The four corresponding figures for dyslipidemia were 33.2%, 31.1%, 13.0% and 4.3%, respectively. 22.9% of the Beijing adults had metabolic syndrome including 8.1 per thousand suffering from myocardial infarction and 18.4 per thousand from stroke. Except for diabetes, all the chronic diseases had higher prevalence rate in rural area than in urban area, according to the findings under our study. Postmenopausal women were more susceptible to chronic disease than men.The prevalence rate of chronic disease in Beijing was still high. The prevalence rate in rural area had exceeded the level in urban area. Adjustment and attention should be made according to the prevalence features and weakness existed in present chronic disease control strategy.
Abstract Background: Studies on osteoporosis awareness among general population in China are still limited. We examined the level of osteoporosis awareness among residents in China, determined the risk factors associated with lower level of osteoporosis awareness, and assessed the sources of their knowledge about osteoporosis. Methods: We conducted a cross-sectional study among 368 general residents aged 30 years or older from 19 provinces during January-March 2018 in China. All participants were identified and interviewed face-to-face by medical students in Jilin University using a structured questionnaire. Osteoporosis awareness scores (percent of correct answer) was determined across several domains, including definition, diagnosis, risk factors, and prevention of osteoporosis. We used multiple linear regression models to test the relationship between risk factors and overall awareness scores. Results: The mean age of participants was 52.9 ± 10.2 years, and 53% of them were male. Osteoporosis awareness score for definition was 77.7%, diagnosis 49.6%, risk factors 49.2%, treatment 60.5%, and prevention 69.9%. The overall awareness score was 67.8%. Lower family income and education level were significantly associated with lower overall awareness score (all p <0.05). Television or radio health program was reported to be their main source of knowledge about osteoporosis. Conclusion: The awareness level for osteoporosis is moderate; lower family income and education level were risk factors for lower awareness. Television or radio health program had the greatest contribution to osteoporosis awareness.
Abstract Background Studies on osteoporosis awareness among the general population in China are still limited. We examined the level of osteoporosis awareness among residents in China, determined the risk factors associated with a lower level of osteoporosis awareness, and assessed the sources of their knowledge about osteoporosis. Methods We conducted a cross-sectional study among 368 general residents aged 30 years or older from 19 provinces during January–March 2018 in China. All participants were identified and interviewed face-to-face by medical students in Jilin University using a structured questionnaire. Osteoporosis awareness scores (percent of the correct answer) were determined across several domains, including definition, diagnosis, risk factors, and prevention of osteoporosis. We used multiple linear regression models to test the relationship between risk factors and overall awareness scores. Results The mean age of included participants was 52.9 ± 10.2 years, and 53% of them were male. Osteoporosis awareness score for definition was 77.7%, diagnosis 49.6%, risk factors 49.2%, treatment 60.5%, and prevention 69.9%. The overall awareness score was 67.8%. Lower family income and education level were significantly associated with lower overall awareness score (all p < 0.05). Television or radio health program was reported to be their main source of knowledge about osteoporosis. Conclusion The awareness level for osteoporosis in our study is moderate; lower family income and education level were risk factors for lower awareness. Television or radio health programs had the greatest contribution to osteoporosis awareness.
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