Rapid industrialization and urbanization in developing countries has led to an increase in air pollution, along a similar trajectory to that previously experienced by the developed nations. In China, ...particulate pollution is a serious environmental problem that is influencing air quality, regional and global climates, and human health. In response to the extremely severe and persistent haze pollution experienced by about 800 million people during the first quarter of 2013 (refs 4, 5), the Chinese State Council announced its aim to reduce concentrations of PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 micrometres) by up to 25 per cent relative to 2012 levels by 2017 (ref. 6). Such efforts however require elucidation of the factors governing the abundance and composition of PM2.5, which remain poorly constrained in China. Here we combine a comprehensive set of novel and state-of-the-art offline analytical approaches and statistical techniques to investigate the chemical nature and sources of particulate matter at urban locations in Beijing, Shanghai, Guangzhou and Xi'an during January 2013. We find that the severe haze pollution event was driven to a large extent by secondary aerosol formation, which contributed 30-77 per cent and 44-71 per cent (average for all four cities) of PM2.5 and of organic aerosol, respectively. On average, the contribution of secondary organic aerosol (SOA) and secondary inorganic aerosol (SIA) are found to be of similar importance (SOA/SIA ratios range from 0.6 to 1.4). Our results suggest that, in addition to mitigating primary particulate emissions, reducing the emissions of secondary aerosol precursors from, for example, fossil fuel combustion and biomass burning is likely to be important for controlling China's PM2.5 levels and for reducing the environmental, economic and health impacts resulting from particulate pollution.
Metformin, the world's most prescribed anti-diabetic drug, is also effective in preventing type 2 diabetes in people at high risk
. More than 60% of this effect is attributable to the ability of ...metformin to lower body weight in a sustained manner
. The molecular mechanisms by which metformin lowers body weight are unknown. Here we show-in two independent randomized controlled clinical trials-that metformin increases circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15), which has been shown to reduce food intake and lower body weight through a brain-stem-restricted receptor. In wild-type mice, oral metformin increased circulating GDF15, with GDF15 expression increasing predominantly in the distal intestine and the kidney. Metformin prevented weight gain in response to a high-fat diet in wild-type mice but not in mice lacking GDF15 or its receptor GDNF family receptor α-like (GFRAL). In obese mice on a high-fat diet, the effects of metformin to reduce body weight were reversed by a GFRAL-antagonist antibody. Metformin had effects on both energy intake and energy expenditure that were dependent on GDF15, but retained its ability to lower circulating glucose levels in the absence of GDF15 activity. In summary, metformin elevates circulating levels of GDF15, which is necessary to obtain its beneficial effects on energy balance and body weight, major contributors to its action as a chemopreventive agent.
Deep learning describes a class of machine learning algorithms that are capable of combining raw inputs into layers of intermediate features. These algorithms have recently shown impressive results ...across a variety of domains. Biology and medicine are data-rich disciplines, but the data are complex and often ill-understood. Hence, deep learning techniques may be particularly well suited to solve problems of these fields. We examine applications of deep learning to a variety of biomedical problems—patient classification, fundamental biological processes and treatment of patients—and discuss whether deep learning will be able to transform these tasks or if the biomedical sphere poses unique challenges. Following from an extensive literature review, we find that deep learning has yet to revolutionize biomedicine or definitively resolve any of the most pressing challenges in the field, but promising advances have been made on the prior state of the art. Even though improvements over previous baselines have been modest in general, the recent progress indicates that deep learning methods will provide valuable means for speeding up or aiding human investigation. Though progress has been made linking a specific neural network's prediction to input features, understanding how users should interpret these models to make testable hypotheses about the system under study remains an open challenge. Furthermore, the limited amount of labelled data for training presents problems in some domains, as do legal and privacy constraints on work with sensitive health records. Nonetheless, we foresee deep learning enabling changes at both bench and bedside with the potential to transform several areas of biology and medicine.
Although a single bout of postmeal exercise can lower postprandial glucose (PPG), its optimal timing remains unclear.
This study aimed to investigate the effect of exercise timing using an ...individualized approach on PPG in overweight or obese young men.
Twenty men age: 23.0 ± 4.3 y; BMI (kg/m2): 27.4 ± 2.8 each completed three 240-min trials in a randomized order separated by 6–14 d: 1) sitting (SIT), 2) walking initiated at each participant's PPG-peak time (PPGP) (iP), and 3) walking initiated 20 min before the PPGP (20iP). For each participant, PPGP was predetermined using continuous glucose monitoring. Walking was performed at 50% maximal oxygen consumption for 30 min. Venous blood was collected at 15- and 30-min intervals for 0–120 min and 120–240 min, respectively. The primary outcome was plasma PPG. Generalized estimating equations were used for comparison between trials.
Compared with SIT, the 4-h incremental AUCs (iAUCs) for plasma PPG (−0.6 mmol · L−1 · h; P = 0.047) and insulin (−28.7%, P < 0.001) were reduced in 20iP only, and C-peptide concentrations were lower after iP (−14.9%, P = 0.001) and 20iP (−28.7%, P < 0.001). Plasma insulin (−11.1%, P = 0.006) and C-peptide (−8.3%, P = 0.012) were lower due to the 20iP compared with iP treatment. Finally, PPG reductions due to iP and 20iP occurred only in men with a BMI > 27.5 kg/m2 (iP, −11.2%; 20iP, −14.7%; P = 0.047) and higher glucose iAUC values during SIT (iP, −25.5%; 20iP, −25.7%; P < 0.001).
Walking initiated 20 min before PPGP lowered PPG and plasma insulin and C-peptide concentrations in young men with overweight or obesity, in particular in those with high BMI or glucose iAUC values during SIT; it also lowered plasma insulin and C-peptide concentrations more effectively than did exercise initiated at PPGP. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR1900023175.
Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause ...illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 H1N1pdm and seasonal A/H1N1, A/H3N2, and B viruses). The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology) correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response). Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.
Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, ...yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.
Seasonal influenza viruses are typically restricted to the human upper respiratory tract whereas influenza viruses with greater pathogenic potential often also target extra-pulmonary organs. Infants, ...pregnant women, and breastfeeding mothers are highly susceptible to severe respiratory disease following influenza virus infection but the mechanisms of disease severity in the mother-infant dyad are poorly understood. Here we investigated 2009 H1N1 influenza virus infection and transmission in breastfeeding mothers and infants utilizing our developed infant-mother ferret influenza model. Infants acquired severe disease and mortality following infection. Transmission of the virus from infants to mother ferrets led to infection in the lungs and mother mortality. Live virus was also found in mammary gland tissue and expressed milk of the mothers which eventually led to milk cessation. Histopathology showed destruction of acini glandular architecture with the absence of milk. The virus was localized in mammary epithelial cells of positive glands. To understand the molecular mechanisms of mammary gland infection, we performed global transcript analysis which showed downregulation of milk production genes such as Prolactin and increased breast involution pathways indicated by a STAT5 to STAT3 signaling shift. Genes associated with cancer development were also significantly increased including JUN, FOS and M2 macrophage markers. Immune responses within the mammary gland were characterized by decreased lymphocyte-associated genes CD3e, IL2Ra, CD4 with IL1β upregulation. Direct inoculation of H1N1 into the mammary gland led to infant respiratory infection and infant mortality suggesting the influenza virus was able to replicate in mammary tissue and transmission is possible through breastfeeding. In vitro infection studies with human breast cells showed susceptibility to H1N1 virus infection. Together, we have shown that the host-pathogen interactions of influenza virus infection in the mother-infant dyad initiate immunological and oncogenic signaling cascades within the mammary gland. These findings suggest the mammary gland may have a greater role in infection and immunity than previously thought.
The physical activity-environment relationship has been infrequently investigated in Chinese children. Reliable and valid environmental measures specific to the age group and the local context are ...crucial for better understanding this relationship. The purposes of this study were to adapt the Neighborhood Environment Walkability Scale for youth (NEWS-Y) for Chinese children (termed NEWS-CC), and to examine the reliability and factorial validity of the NEWS-CC.
The development of the NEWS-CC involved the translation of the NEWS-Y to Chinese and the addition of nine new items capturing Hong Kong specific environmental attributes which were generated in our previous study. A total of 953 Hong Kong children aged 9-14 years volunteered to complete the NEWS-CC twice with 7-14 days apart. Confirmatory factor analysis (CFA) was performed to examine the factorial validity of the NEWS-CC. Test-retest reliability of subscales and individual items in the NEWS-CC was examined by intraclass correlation coefficients (ICCs).
The CFA identified a 7-factor measurement model for the NEWS-CC which fitted the data well, with an additional "pollution" factor not included in the original NEWS-Y. The final NEWS-CC consisted of 67 items in 10 subscales. The test-retest reliability of subscales (range of ICC = 0.47-0.86) and individual items (range of ICC = 0.41-0.79) in the final NEWS-CC was moderate to good.
The results of this study support the psychometric properties of the NEWS-CC. The NEWS-CC can be used to assess physical activity-related neighborhood environment among children in Hong Kong, as well as cities that share similar urban forms with Hong Kong.
Summary
Sleep and daytime movement behaviours occur co‐dependently with each other within a finite 24 h day. Sleep parameters other than sleep duration, such as social jetlag and chronotype, have ...been linked to health problems and unhealthy behaviours among children and adolescents. Given the increasing number of studies examining sleep timing/chronotype and weight‐related behaviours, including physical activity and sedentary behaviour, in the past decade, this systematic review and meta‐analysis collated and evaluated the evidence on the relationships of social jetlag and chronotype with physical activity and sedentary behaviour among children and adolescents aged 3–17 years. Seven databases were searched on 16 March 2022, and 52 studies were identified as eligible for inclusion, 47 of which were suitable for the meta‐analysis. A positive association was found between social jetlag and screen media use (r = 0.14, 95% CI: 0.04–0.24; I2 = 96%; p = 0.008). The morning chronotype was associated with a higher level of physical activity and a lower level of sedentary behaviour than the evening chronotype. No relationship was found between social jetlag and physical activity. The magnitude of heterogeneity among the included studies was high. Further experimental studies are urgently required to understand how circadian preference or misalignment affects activity behaviours. Interventions to promote an active lifestyle in young populations should consider their circadian preference, especially among individuals with the evening chronotype.
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