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Calcium ions (Ca2+) play crucial roles in sperm motility and fertilization. The copine (CPNE) family comprises several Ca2+-dependent phospholipid-binding proteins. Of these, CPNE1 is extensively expressed in mammalian tissues; however, its precise role in testicular development and spermatogenesis is yet to be fully characterized. In this study, we used proteomics to analyze testicular biopsies and found that levels of CPNE1 were significantly reduced in patients with non-obstructive azoospermia (defective spermatogenesis) compared to those in patients with obstructive azoospermia (physiological spermatogenesis). In mice, CPNE1 is expressed at various stages of germ cell development and is associated with the Golgi apparatus. Ultimately, CPNE1 is expressed in the flagella of mature sperms. To further examine the role of CPNE1, we developed a Cpne1 knockout mouse model. Analysis showed that the loss of Cpne1 did not impair testicular development, spermatogenesis, or sperm morphology and motility in physiological conditions. When treated with gadolinium (III) chloride or 2-aminoethoxydiphenyl borate, known inhibitors of store-operated Ca2+ entry, Ca2+ signals and sperm motility were significantly compromised in wild-type mice; however, both mechanisms were conserved in KO mice. These results suggested that CPNE1 is dispensable for testicular development, spermatogenesis or sperm motility in physiological conditions. In addition, CPNE1 may represent a target of Ca2+ channel inhibitors and may therefore be implicated in the regulation of Ca2+ signaling and sperm motility.

Convection-allowing ensemble prediction (CAEP) is an important approach to improve the capability of strong convective weather prediction, and how to construct reasonable initial disturbance is one of the key issues of CAEP. In this paper, the experiments of the per⁃ turbed-observation (PO) method in the CAEP system in the Inner Mongolia region were carried out and evaluated by comparing them with the downscaling (DOWN) method. The performance of the PO method in the CAEP system was then analyzed, which will provide a technical ref⁃ erence for the construction of the CAEP system in Inner Mongolia. The results are as follows. (1) The initial perturbation constructed by the PO method can effectively include the observations in the Inner Mongolia region, which can reduce the uncertainty of the background field and the perturbation has sufficient growth capacity. (2) Compared with the DOWN method, the PO method can significantly reduce the short-term forecast error of CAEP. The root mean square error (RMSE) of upper-level elements is reduced by 4% ~43%, and the RMSE of ground surface elements is reduced by 3% ~9%, suggesting a slightly decreased ensemble spread. The continuous ranked probability score (CRPS) of upper-level elements can be reduced by up to 53% and the CRPS of ground surface elements is reduced by an average of 6%, which generally indicates an improvement in the quality of convective scale ensemble forecasts. (3) The PO method can also improve the capability of short-term precipitation forecasts. The TS score for precipitation levels of 0.1 mm, 4 mm, and 13 mm increased by 0.015, 0.003, and 0.0015, re⁃ spectively. Furthermore, the case study shows that the PO method is more accurate in predicting the precipitation areas and intensity levels.

Abstract Serological tests for Epstein–Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV‐positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL‐5) and large, buoyant low density lipoprotein particles (LDL‐1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR‐based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811‐0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL‐5 and LDL‐1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

Background: Environmental temperature is negatively associated with blood pressure (BP), and hypertension may exacerbate this association. The aim of this study is to investigate whether hypertensive individuals are more susceptible to acute BP increases following temperature decrease than non-hypertensive individuals. Methods: The study panel consisted of 126 hypertensive and 125 non-hypertensive (n = 251) elderly participants who completed 940 clinical visits during the winter of 2016 and summer of 2017 in Beijing, China. Personal-level environmental temperature (PET) was continuously monitored for each participant with a portable sensor platform. We associated systolic BP (SBP) and diastolic BP (DBP) with the average PET over 24 h before clinical visits using linear mixed-effects models and explored hourly lag patterns for the associations using distributed lag models. Results: We found that per 1 °C decrease in PET, hypertensive individuals showed an average (95 % confidence interval) increase of 0.96 (0.72, 1.19) and 0.28 (0.13, 0.42) mmHg for SBP and DBP, respectively; and non-hypertensive participants showed significantly smaller increases of 0.28 (0.03, 0.53) mmHg SBP and 0.14 (-0.01, 0.30) mmHg DBP. A lag pattern analysis showed that for hypertensive individuals, the increases in SBP and DBP were greatest following lag 1 h PET decrease and gradually attenuated up to lag 10 h exposure. No significant BP change was observed in non-hypertensive individuals associated with lag 1–24 h PET exposure. The enhanced increase in PET-associated BP in hypertensive participants (i.e., susceptibility) was more significant in winter than in summer. Conclusions: We found that a decrease in environmental temperature was associated with acute BP increases and these associations diminished over time, disappearing after approximately 10 hours. This implies that any intervention measures to prevent BP increases due to temperature drop should be implemented as soon as possible. Such timely interventions are particularly needed for hypertensive individuals especially during the cold season due to their increased susceptibility.

IntroductionMales 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 resultsHerein, 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.DiscussionIn 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.

Spatially resolved proteomics is an emerging approach for mapping proteome heterogeneity. Here, the authors report a method based on the combination of hydrogel-based tissue transformation with mass spectrometry-based proteomics, that enables proteome profiling with a lateral resolution of 160 µm.

BackgroundPrevious studies focused on the impact of cardiovascular diseases (CVD) risk factors in breast cancer patients with chemotherapy (CT) or radiotherapy (RT). This study aimed to identify the impact of tumor characteristics on CVD death in these patients.MethodsData of female breast cancer patients with CT or RT between 2004 and 2016 were included. The risk factors of CVD death were identified using Cox regression analyses. A nomogram was constructed to evaluate the predicted value of tumor characteristics, and then validated by the concordance indexes (C-index) and calibration curves.ResultA total of 28,539 patients were included with an average follow-up of 6.1 years. Tumor size > 45 mm (adjusted HR = 1.431, 95% CI = 1.116–1.836, P = 0.005), regional (adjusted HR = 1.278, 95% CI = 1.048–1.560, P = 0.015) and distant stage (adjusted HR = 2.240, 95% CI = 1.444–3.474, P

Abstract Spectrally diverse fluorescent proteins (FPs) provide straightforward means for multiplexed imaging of biological systems. Among FPs fitting standard color channels, blue FPs (BFPs) are characterized by lower brightness compared to other spectral counterparts. Furthermore, available BFPs were not systematically characterized for imaging in cultured mammalian cells and common model organisms. Here we introduce a pair of new BFPs, named Electra1 and Electra2, developed through hierarchical screening in bacterial and mammalian cells using a novel dual-expression vector. We performed systematic benchmarking of Electras against state-of-art BFPs in cultured mammalian cells and demonstrated their utility as fluorescent tags for structural proteins. The Electras variants were validated for multicolor neuroimaging in Caenorhabditis elegans, zebrafish larvae, and mice in comparison with one of the best in the class BFP mTagBFP2 using one-photon and two-photon microscopy. The developed BFPs are suitable for multicolor imaging of cultured cells and model organisms in vivo. We believe that the described dual-expression vector has a great potential to be adopted by protein engineers for directed molecular evolution of FPs.

In order to solve the problem of fast path planning and effective obstacle avoidance for autonomous underwater vehicles (AUVs) in two-dimensional underwater environment, a path planning algorithm based on deep Q-network and Quantum particle swarm optimization (DQN-QPSO) was proposed. Five actions are defined first: normal, exploration, particle explode, random mutation, and fine-tuning operation. After that, the five actions are selected by DQN decision thinking, and the position information of particles is dynamically updated in each iteration according to the selected actions. Finally, considering the complexity of underwater environment, the fitness function is designed, and the route length, deflection angle, and the influence of ocean current are considered comprehensively, so that the algorithm can find the solution path with the shortest energy consumption in underwater environment. Experimental results show that DQN-QPSO algorithm is an effective algorithm, and its performance is better than traditional methods.

ObjectiveTo evaluate the feasibility and safety of superficial temporal artery (STA)–middle cerebral artery (MCA) anastomosis in combination with encephalo-myo-synangiosis (EMS) in Chinese adult patients with moyamoya disease (MMD).MethodsA total of 65 patients with MMD who underwent combined STA–MCA bypass + EMS surgical revascularisation were included in this study. Each patient had a follow-up visit 6 months after discharge. Early bypass function was evaluated via computed tomography angiography and digital subtraction angiography, which were performed preoperatively and at 6 months after surgery. The perfusion parameters of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT) and time to peak (TTP) were obtained and analysed. The clinical status of each patient was evaluated using a modified Rankin scale (mRS) preoperatively and at 1 week and 6 months after surgery.ResultsAmong the 65 enrolled patients, postoperative complications were observed in 5 (7.69%) patients, with 2 cases of dysphasia, 2 cases of new cerebral infarction and 1 case of seizure. Six months after surgery, 66 out of 68 hemispheres were found to have a functioning extra-intracranial bypass, and the patency rate was 97.06%. In terms of CBF perfusion, both the CBF and CBV increased significantly, while the MTT and TTP decreased after surgery. The mRS scores measured 1 week and 6 months after surgery were much lower than those measured preoperatively.ConclusionA direct STA–MCA bypass procedure in combination with indirect EMS bypass is feasible and safe for Chinese adult patients with MMD.

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.1528A→G, 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.

Engineered light, oxygen, and voltage (LOV)-based proteins are able to fluoresce without oxygen requirement due to the autocatalytic incorporation of exogenous flavin as a chromophore thus allowing for live cell imaging under hypoxic and anaerobic conditions. They were also discovered to have high sensitivity to transition metal ions and physiological flavin derivatives. These properties make flavin-binding fluorescent proteins (FPs) a perspective platform for biosensor development. However, brightness of currently available flavin-binding FPs is limited compared to GFP-like FPs creating a need for their further enhancement and optimization. In this study, we applied a directed molecular evolution approach to develop a pair of flavin-binding FPs, named miniGFP1 and miniGFP2. The miniGFP proteins are characterized by cyan-green fluorescence with excitation/emission maxima at 450/499 nm and a molecular size of ∼13 kDa. We carried out systematic benchmarking of miniGFPs in Escherichia coli and cultured mammalian cells against spectrally similar FPs including GFP-like FP, bilirubin-binding FP, and bright flavin-binding FPs. The miniGFPs proteins exhibited improved photochemical properties compared to other flavin-binding FPs enabling long-term live cell imaging. We demonstrated the utility of miniGFPs for live cell imaging in bacterial culture under anaerobic conditions and in CHO cells under hypoxia. The miniGFPs’ fluorescence was highly sensitive to Cu(II) ions in solution with Kd values of 67 and 68 nM for miniGFP1 and miniGFP2, respectively. We also observed fluorescence quenching of miniGFPs by the reduced form of Cu(I) suggesting its potential application as an optical indicator for Cu(I) and Cu(II). In addition, miniGFPs showed the ability to selectively bind exogenous flavin mononucleotide demonstrating a potential for utilization as a selective fluorescent flavin indicator. Altogether, miniGFPs can serve as a multisensing platform for fluorescence biosensor development for in vitro and in-cell applications.

Abstract Background The objectives of this study were to screen out cut-off age value and age-related differentially expressed genes (DEGs) in clear cell renal cell carcinoma (CCRCC) from Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. Methods We selected 45,974 CCRCC patients from SEER and 530 RNA-seq data from TCGA database. The age cut-off value was defined using the X-tile program. Propensity score matching (PSM) was used to balance the differences between young and old groups. Hazard ratio (HR) was applied to evaluate prognostic risk of age in different subgroups. Age-related DEGs were identified via RNA-seq data. Survival analysis was used to assess the relationship between DEGs and prognosis. Results In this study, we divided the patients into young (n = 14,276) and old (n = 31,698) subgroups according to cut-off value (age = 53). Age > 53 years was indicated as independent risk factor for overall survival (OS) and cancer specific survival (CSS) of CCRCC before and after PSM. The prognosis of old group was worse than that in young group. Eleven gene were differential expression between the younger and older groups in CCRCC. The expression levels of PLA2G2A and SIX2 were related to prognosis of the elderly. Conclusion Fifty-three years old was cut-off value in CCRCC. The prognosis of the elderly was worse than young people. It remind clinicians that more attention and better treatment should be given to CCRCC patients who are over 53 years old. PLA2G2A and SIX2 were age-related differential genes which might play an important role in the poor prognosis of elderly CCRCC patients.

In this study, based on the retrieval data from the Fengyun geostationary meteorological satellite and the Tropical Rainfall Measuring Mission satellite, a large-scale precipitation case in eastern China is selected to address the systematic deviations of deterministic forecasts for clouds and precipitation. A multi-physical ensemble transform Kalman filter (ETKF) is constructed in this research based on the Weather Research and Forecast model version 3.6, and its forecasting ability in terms of cloud-top height and temperature, hydrometeors, and precipitation is evaluated by quantitatively comparing three microphysical parameterization schemes (Lin, Morrison, and CAM5.1 schemes) and their corresponding multi-physical ensemble mean. The results show that the Lin, Morrison, and CAM5.1 schemes all underestimate the range of cloud systems and have different advantages and disadvantages in forecasting different elements, while the forecasting improvement of the multi-physical ensemble mean is limited. However, the multi-physical ETKF can effectively improve the forecast accuracy of the cloud system range. In addition, the multi-physical ETKF has the advantages of different physical parameterization schemes, which can dramatically improve the forecast accuracy of cloud hydrometeors, reduce precipitation forecast errors, and improve threat scores.

In this study, three model perturbation schemes, the stochastically perturbed parameter scheme (SPP), stochastically perturbed physics tendency (SPPT), and multi-physics process parameterization (MP), were used to represent the model errors in the regional ensemble prediction systems (REPS). To study the effects of different model perturbation schemes on heavy rainfall forecasting, three sensitive experiments using three different combinations (EXP1: MP, EXP2: SPPT + SPP, and EXP3: MP + SPPT + SPP) of the model perturbation schemes were set up based on the Weather Research and Forecasting (WRF)-V4.2 model for a heavy rainfall case that occurred in Henan, China during 20–22 July 2021. The results show that the model perturbation schemes can provide forecast uncertainties for this heavy rainfall case. The stochastic physical perturbation method could improve the heavy rainfall forecast skill by approximately 5%, and EXP3 had better performance than EXP1 or EXP2. The spread-to-root mean square error ratios (spread/RMSE) of EXP3 were closer to 1 compared with those of the EXP1 and EXP2; particularly for the meridional wind above 10 m, the spread/RMSE was 0.94 for EXP3 and approximately 0.85 for EXP1 and EXP2. EXP3 exhibited better performance in Brier score verification. EXP3 had a 5% lower Brier score than EXP1 and EXP2, when the rainfall threshold was 25 mm. The growth of the initial ensemble variances of different model perturbation schemes were explored, and the results show that the perturbation energy of EXP3 developed faster, with a magnitude of 27.22 J/kg, whereas those of EXP1 and EXP2 were only 19.18 J/kg and 20.81 J/kg, respectively. The weak initial perturbation associated with the wind shear north of the heavy rainfall location can be easily developed by EXP3.

BackgroundCardiovascular death (CVD) in breast cancer patients without chemotherapy (CT) or (and) radiotherapy (RT) has not been studied yet. This study evaluates the correlation between breast cancer and CVD risk independent of chemotherapy or (and) radiotherapy.MethodsData of female breast cancer patients without receiving CT or RT were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database (2004–2015). Data were divided into two cohorts: tumor resection cohort and no resection cohort. The CVD risk in patients was expressed as standardized mortality ratios (SMRs). A 1:1 propensity score matching (PSM) was applied to balance inter-group bias, and competing risk regressions were utilized to evaluate the impact of tumor resection on CVD.ResultsThe CVD risk was significantly higher (SMR = 2.196, 95% CI: 2.148–2.245, P

Background: The use of proxy exposure estimates for PM2.5 and NO2 in air pollution studies instead of personal exposures, introduces measurement error, which can produce biased epidemiological effect estimates. Most studies consider total personal exposure as the gold standard. However, when studying the effects of ambient air pollution, personal exposure from outdoor sources is the exposure of interest. Objectives: We assessed the magnitude and variability of exposure measurement error by conducting a systematic review of the differences between personal exposures from outdoor sources and the corresponding measurements for ambient concentrations in order to increase understanding of the measurement error structures of the pollutants. Data sources and eligibility criteria: We reviewed the literature (ISI Web of Science, Medline, 2000–2016) for English language studies (in any age group in any location (NO2) or Europe and North America (PM2.5)) that reported repeated measurements over time both for personal and ambient PM2.5 or NO2 concentrations. Only a few studies reported personal exposure from outdoor sources. We also collected data for infiltration factors and time-activity patterns of the individuals in order to estimate personal exposures from outdoor sources in every study. Study appraisal and synthesis methods: Studies using modelled rather than monitored exposures were excluded. Type of personal exposure monitor was assessed. Random effects meta-analysis was conducted to quantify exposure error as the mean difference between “true” and proxy measures. Results: Thirty-two papers for PM2.5 and 24 for NO2 were identified. Outdoor sources were found to contribute 44% (range: 33–55%) of total personal exposure to PM2.5 and 74% (range: 57–88%) to NO2. Overall estimates of personal exposure (24-hour averages) from outdoor sources were 9.3 μg/m3 and 12.0 ppb for PM2.5 and NO2 respectively, while the corresponding difference between these exposures and the ambient concentrations (i.e. the measurement error) was 5.72 μg/m3 and 7.17 ppb. Our findings indicated also higher error variability for NO2 than PM2.5. Large heterogeneity was observed which was not explained sufficiently by geographical location or age group of the study sample. Limitations, conclusions and implications of key findings: Relying only on information available in published studies led to some limitations: the contribution of outdoor sources to total personal exposure for NO2 had to be inferred, individual variation in exposure misclassification was unavailable and instrument error could not be addressed. The larger magnitude and variability of errors for NO2 compared with PM2.5 has implications for biases in the health effect estimates of multi-pollutant epidemiological models. Results suggest that further research is needed regarding personal exposure studies and measurement error bias in epidemiological models.

Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

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’ moderate-to-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.

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.

Background/Aims: An increasing body of evidence demonstrates that L-carnitine plays a pivotal role in lipid metabolism of hemodialysis (HD) patients. However, there are still some reservations about its benefits. Therefore, we performed a meta-analysis to assess the effects of L-carnitine supplementation on lipid profile in HD patients. Methods: Literature search was performed to identify the relevant randomized controlled trials that investigated the effects of L-carnitine on the lipid profile of subjects. Two independent authors used an Excel file to extract data and assess trials quality. The primary effect measure was the difference in means of the final lipid measurements between the intervention and control groups. The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Results: Twelve studies with a total of 391 patients met the inclusion criteria. The use of L-carnitine was not associated with a reduction in the total cholesterol (SMD, -0.11; 95% CI, -0.31 to 0.09), HDL-cholesterol (SMD, 0.01; 95% CI, -0.36 to 0.39), VLDL-cholesterol (SMD, 0.54; 95% CI, -0.06 to 1.14), and the serum triglycerides (SMD, -0.12; 95% CI, -0.36 to 0.12). However, L-carnitine can significantly decrease the LDL-cholesterol (SMD, -0.29; 95% CI, -0.53 to -0.06) in HD patients. In a subgroup meta-analysis, a significant LDL-cholesterol-lowering effect of L-carnitine supplementation was observed in intravenous application group, and patients with longer interventional duration and renal diseases. Conclusion: The limited evidence suggests that there was no effect of L-carnitine on serum total cholesterol, HDL-cholesterol, VLDL-cholesterol and serum triglycerides. By contrast, this meta-analysis suggests a promising effect of L-carnitine on LDL-cholesterol. Further large-scale, well-designed randomized controlled trials are urgently needed

To improve the skills of the regional ensemble forecast system (REFS), a modified ensemble transform Kalman filter (ETKF) initial perturbation strategy was developed. First, sensitivity tests were conducted to investigate the influence of the perturbation scale on the ensemble spread growth and forecast skill. In addition, the scale characteristic of the forecast error was analyzed based on the results of these tests, and a new initial condition perturbation method was developed through scale-selection of the ETKF perturbations, namely, ETKF-SS (scale-selective ETKF). The performances of the ETKF-SS scheme and the original ETKF (hereinafter referred to as ETKF) scheme were tested and compared. The results showed that the large-scale perturbations were much easier to grow than the original ETKF perturbations. In addition, scale analysis of the forecast error showed that the large-scale errors showed significant growth at the upper levels, while the small and meso-scale errors grew fast at the lower levels. The comparison results of the ETKF-SS and the ETKF showed that the ETKF-SS perturbations had more obvious growth than the ETKF perturbations, and the ETKF-SS perturbations in the short-term forecast lead times were more precise than the ETKF perturbations. The ensemble forecast verification results showed that the ETKF-SS ensemble had a larger spread and smaller root mean square error than the ETKF at short forecast lead times, while the probabilistic scores of the ETKF-SS also outperformed those of the ETKF method. In addition, the ETKF-SS ensemble can provide a better precipitation forecast than the ETKF.

The regional ensemble prediction system (REPS) of North China is currently under development at the Institute of Urban Meteorology, China Meteorological Administration, with initial condition perturbations provided by global ensemble dynamical downscaling. To improve the performance of the REPS, a comparison of two initial condition perturbation methods is conducted in this paper: (i) Breeding, which was specifically designed for the REPS, and (ii) Dynamical downscaling. Consecutive tests were implemented to evaluate the performances of both methods in the operational REPS environment. The perturbation characteristics were analyzed, and ensemble forecast verifications were conducted. Furthermore, a heavy precipitation case was investigated. The main conclusions are as follows: the Breeding perturbations were more powerful at small scales, while the downscaling perturbations were more powerful at large scales; the difference between the two perturbation types gradually decreased with the forecast lead time. The downscaling perturbation growth was more remarkable than that of the Breeding perturbations at short forecast lead times, while the perturbation magnitudes of both schemes were similar for long-range forecasts. However, the Breeding perturbations contained more abundant small-scale components than downscaling for the short-range forecasts. The ensemble forecast verification indicated a slightly better downscaling ensemble performance than that of the Breeding ensemble. A precipitation case study indicated that the Breeding ensemble performance was better than that of downscaling, particularly in terms of location and strength of the precipitation forecast.