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Introduction: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. Methods and results: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both in vitro and in vivo, and importantly, spermatogenesis in vivo. Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis. Discussion: In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI. [ABSTRACT FROM AUTHOR]

Oligoasthenoteratozoospermia is a human infertility syndrome caused by defects in spermatogenesis, spermiogenesis, and sperm maturation, and its etiology remains unclear. Kelch-like 10 (KLHL10) is a component of ubiquitin ligase E3 10 (KLHL10) and plays an important role in male fertility. Deletion or mutation of the Klhl10 gene in Drosophila or mice results in defects in spermatogenesis or sperm maturation. However, the molecular mechanisms by which KLHL10 functions remain elusive. In this study, we identified a missense mutation (c.1528AG, p.I510V) in exon 5 of KLHL10, which is associated with oligoasthenoteratozoospermia in humans. To investigate the effects of this mutation on KLHL10 function and spermatogenesis and/or spermiogenesis, we generated mutant mice duplicating the amino acid conversion using the clustered regularly interspaced palindromic repeat/caspase 9 (CRISPR/Cas9) system and designated them Klhl10I510V mice. However, the Klhl10I510V mice did not exhibit any defects in testis development, spermatogenesis, or sperm motility at ten-weeks-of-age, suggesting that this mutation does not disrupt the KLHL10 function, and may not be the cause of male infertility in the affected individual with oligoasthenoteratozoospermia. [ABSTRACT FROM AUTHOR]

Ensemble forecasting is a method to faithfully describe initial and model uncertainties in a weather forecasting system. Initial uncertainties are much more important than model uncertainties in the short-range numerical prediction. Currently, initial uncertainties are described by the ensemble transform Kalman filter (ETKF) initial perturbation method in Global and Regional Assimilation and Prediction Enhanced System-Regional Ensemble Prediction System (GRAPES-REPS). However, an initial perturbation distribution similar to the analysis error cannot be yielded in the ETKF method of the GRAPES-REPS. To improve the method, we introduce a regional rescaling factor into the ETKF method (we call it ETKF_R). We also compare the results between the ETKF and ETKF_R methods and further demonstrate how rescaling can affect the initial perturbation characteristics as well as the ensemble forecast skills. The characteristics of the initial ensemble perturbation improve after applying the ETKF_R method. For example, the initial perturbation structures become more reasonable, the perturbations are better able to explain the forecast errors at short lead times, and the lower kinetic energy spectrum as well as perturbation energy at the initial forecast times can lead to a higher growth rate of themselves. Additionally, the ensemble forecast verification results suggest that the ETKF_R method has a better spread-skill relationship, a faster ensemble spread growth rate, and a more reasonable rank histogram distribution than ETKF. Furthermore, the rescaling has only a minor impact on the assessment of the sharpness of probabilistic forecasts. The above results all suggest that ETKF_R can be effectively applied to the operational GRAPES-REPS. [ABSTRACT FROM AUTHOR]

In this paper, we present a reciprocity on finite abelian groups involving zero-sum sequences. Let G and H be finite abelian groups with (| G|, | H|) = 1. For any positive integer m, let sansM (G,m) denote the set of all zero-sum sequences over G of length m. We have the reciprocity | sansM (G, | H|)| = | sansM (H, | G|)|. Moreover, we provide a combinatorial interpretation of the above reciprocity using ideas from rational Catalan combinatorics. We also present and explain some other symmetric relationships on finite abelian groups with methods from invariant theory. Among others, we partially answer a question proposed by Panyushev in a generalized version. [ABSTRACT FROM AUTHOR]

Beijing, as a representative megacity in China, is experiencing some of the most severe air pollution in the world, and its fast urbanization has led to a substantial urban and peri-urban disparities in both health status and air quality. Uncertainties remain regarding the possible causal links between individual air pollutants and health outcomes, with spatial comparative investigations of these links lacking, particularly in developing megacities. In light of this challenge, Effects of AIR pollution on cardiopuLmonary disEaSe in urban and peri-urban reSidents in Beijing (AIRLESS) was initiated with the aim of addressing the complex issue of multipollutant exposures on cardiopulmonary outcomes. The two panel studies deployed included urban and peri-urban elderly Beijing residents recruited from two established cohorts. The project was strengthened further through the measurement of an extensive range of ambient and indoor pollutants during two intensive monitoring campaigns undertaken simultaneously with the collection of health data from the panel participants. This paper presents the novel elements and methodology deployed in the AIRLESS project that addressed gaps in current understanding: namely (1) contrast of the exposure to air pollution in peri-urban and urban areas in a developing megacity, (2) a nested case (hypertensive) - control (healthy) study design to identify potential susceptible population, (3) the detailed assessments of personal exposure to air pollution in diverse indoor and outdoor environments using miniaturised portable platforms; (4) detailed assessment of the chemical composition of particulate matter; and (5) a rich collection of biological markers to understand the underlying mechanisms of health responses to air pollution. [ABSTRACT FROM AUTHOR]

The inaccurate quantification of personal exposure to air pollution introduces error and bias in health estimations, severely limiting causal inference in epidemiological research worldwide. Rapid advancements in affordable, miniaturised air pollution sensor technologies offer the potential to address this limitation by capturing the high variability of personal exposure during daily life in large-scale studies with unprecedented spatial and temporal resolution. However, concerns remain regarding the suitability of novel sensing technologies for scientific and policy purposes. In this paper we characterise the performance of a portable personal air quality monitor (PAM) that integrates multiple miniaturised sensors for nitrogen oxides (NOx), carbon monoxide (CO), ozone (O3) and particulate matter (PM) measurements along with temperature, relative humidity, acceleration, noise and GPS sensors. Overall, the air pollution sensors showed excellent agreement with standard instrumentation in outdoor, indoor and commuting microenvironments across seasons and different geographical settings. An important outcome of this study is that the error of the PAM is significantly smaller than the error introduced when estimating personal exposure based on sparsely distributed outdoor fixed monitoring stations. Hence, novel sensing technologies as the ones demonstrated here can revolutionise health studies by providing highly resolved reliable exposure metrics at large scale to investigate the underlying mechanisms of the effects of air pollution on health. [ABSTRACT FROM AUTHOR]

Objective Engaging in physical activity (PA) plays an important role in promoting physical and mental health, but the PA data for Chinese preschool children are lacking. This study aims to objectively assess the PA levels of preschool children in Shanghai, China and to evaluate their PA levels relative to age-specific recommendations. Design, setting and participants A cross-sectional study was conducted among preschool children in Shanghai, city of China. There were a total of 303 preschool children (boys, 174; girls, 129) recruited from eight kindergarten classes in the Yangpu and Baoshan Districts of Shanghai. Main outcome measures Daily PA was assessed using ActiGraph GT3X+ accelerometers for seven consecutive days. Children were required to have data from at least 2 weekdays and 1 weekend day, with a minimum daily wear time of 480 min to be included in the analysis. Results Preschool children in Shanghai accumulated, on average, 70.9 min of moderate-to-vigorous PA (MVPA) and 168.0 min of total PA (TPA) per day (d). Boys engaged in more MVPA and TPA than girls (72.8 min/day vs 68.3 min/day and 171.9 min/day vs 162.9 min/day, respectively). Overall, 72.9% of the participants met the age-specific recommendations of MVPA, while 35.3% met TPA recommendations. Conclusions Findings of this study warn of the insufficiency of PA in Shanghai preschool children, suggesting there is substantial room to improve their PA. Trial registration number ChiCTR-OOC-15007439; Results. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin complex 1 (mTORC1) signaling is active in inflammation, but its involvement in septic acute kidney injury (AKI) has not been shown. mTORC1 activation (p-S6) in renal fibroblasts was increased in a mouse AKI model induced by 1.5 mg/kg lipopolysaccharide (LPS). Deletion of tuberous sclerosis complex 1 (TSC1), an mTORC1 negative regulator, in fibroblasts (Fibro-TSC1-/-) inhibited the elevation of serum creatinine and blood urea nitrogen in AKI compared with that in TSC1fl/fl control mice. Endothelin-1 (EDN1) and phospho-Jun-amino-terminal kinase (p-JNK) were up-regulated in Fibro-TSC1-/- renal fibroblasts after LPS challenge. Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl/fl and Fibro-TSC1-/- mice after LPS injection. Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs). SP600125, a Jun-amino-terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p-S6) level. The results indicate that mTORC1-JNK-dependent up-regulation of ECE1 elevated EDN1 in TSC1-knockout renal fibroblasts and contributed to improvement of renal function in Fibro-TSC1-/- mice with LPS-induced AKI. Renal fibroblast mTORC1 plays an important role in septic AKI. [ABSTRACT FROM AUTHOR]

Purpose. This study examined the associations of physical activity levels between parents and their pre-school children based on gender and weekday/weekend. Method. A total of 247 parent-preschool child triads from Shanghai, China were analyzed. The children had a mean age of 57.5 ± 5.2 months. Both sedentary behavior and physical activity were measured in all participants using an ActiGraph GT3X+ accelerometer over seven consecutive days from Monday through the following Sunday. A multivariate regression model was derived to identify significant relationships between parental and child physical activity according to gender and weekday/weekend. Results. There was a significant correlation between mothers' and girls' moderateto- vigorous physical activity (MVPA) and total physical activity (TPA) on weekdays. Fathers' MPVA levels correlated significantly with those of boys and girls, with paternal influence appearing to be stronger than maternal influence. However, there was not a significant correlation between fathers' and children's TPA. TPA levels of both mothers and fathers correlated with those of girls, but not with those of boys. Parental sedentary levels on the weekend correlated significantly with girls' levels, but not with boys' levels. Children's physical activity levels on weekends were influenced more by fathers' activity levels than by mothers', while the opposite was observed on weekdays. Conclusion. Sedentary behavior and physical activity levels of parents can strongly influence those of their preschool children, with maternal influence stronger during the weekdays and paternal influence stronger on the weekends. Parents' activity levels influence girls' levels more strongly than they influence boys' levels. [ABSTRACT FROM AUTHOR]

Based on the operational regional ensemble prediction system (REPS) in China Meteorological Administration (CMA), this paper carried out comparison of two initial condition perturbation methods: an ensemble transform Kalman filter (ETKF) and a dynamical downscaling of global ensemble perturbations. One month consecutive tests are implemented to evaluate the performance of both methods in the operational REPS environment. The perturbation characteristics are analyzed and ensemble forecast verifications are conducted; furthermore, a TC case is investigated. The main conclusions are as follows: the ETKF perturbations contain more power at small scales while the ones derived from downscaling contain more power at large scales, and the relative difference of the two types of perturbations on scales become smaller with forecast lead time. The growth of downscaling perturbations is more remarkable, and the downscaling perturbations have larger magnitude than ETKF perturbations at all forecast lead times. However, the ETKF perturbation variance can represent the forecast error variance better than downscaling. Ensemble forecast verification shows slightly higher skill of downscaling ensemble over ETKF ensemble. A TC case study indicates that the overall performance of the two systems are quite similar despite the slightly smaller error of DOWN ensemble than ETKF ensemble at long range forecast lead times. [ABSTRACT FROM AUTHOR]