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Abstract In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1+/UCHL1+ EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer’s disease (AD), and Parkinson’s disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1+/UCHL1+ EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1+/UCHL1+, NMDAR2A+, and NFL+ EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1+/UCHL1+ EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A+ and NFL+ EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration.

BackgroundTuberous sclerosis is a multi-system disorder caused by mutations in either TSC1 or TSC2. The majority of affected patients (85%–90%) have heterozygous variants, and a smaller number (around 5%) have mosaic variants. Despite using various techniques, some patients still have “no mutation identified” (NMI).MethodsWe hypothesized that the causal variants of patients with NMI may be structural variants or deep intronic variants. To investigate this, we sequenced the DNA of 26 tuberous sclerosis patients with NMI using targeted long-read sequencing.ResultsWe identified likely pathogenic/pathogenic variants in 13 of the cases, of which 6 were large deletions, four were InDels, two were deep intronic variants, one had retrotransposon insertion in either TSC1 or TSC2, and one was complex rearrangement. Furthermore, there was a de novo Alu element insertion with a high suspicion of pathogenicity that was classified as a variant of unknown significance.ConclusionOur findings expand the current knowledge of known pathogenic variants related to tuberous sclerosis, particularly uncovering mosaic complex structural variations and retrotransposon insertions that have not been previously reported in tuberous sclerosis. Our findings suggest a higher prevalence of mosaicism among tuberous sclerosis patients than previously recognized. Our results indicate that long-read sequencing is a valuable approach for tuberous sclerosis cases with no mutation identified (NMI).

Abstract The Maritime Continent (MC), a critical region for inter‐basin climate interaction, harbors the world's highest marine biodiversity. Ocean warming in the MC, although with notable impacts on regional climate and marine ecosystems, remains poorly constrained by observations. By applying a volume‐correction algorithm to existing gridded observational data sets, this study provides an estimate for the ocean heat content (OHC) change of the MC. The results suggest a substantial OHC increase of 2.65 ± 0.46 Zettajoules during 1990–2015 (1.08 ± 0.17 W m−2) and limited changes before and after. This increase primarily arose from the enhanced Pacific Walker circulation, which drove a convergence of upper‐layer warm water toward the MC. A potential heat storage “hotspot” with enhanced warming below 500 m emerges within the Sulu Sea, which is supported by analysis of profile data collected in boreal winter but not in other seasons.

Introduction: Intelligent power distribution systems are vital in the modern power industry, tasked with managing power distribution efficiently. These systems, however, encounter challenges in anomaly detection, hampered by the complexity of data and limitations in model generalization.Methods: This study developed a Transformer-GAN model that combines Transformer architectures with GAN technology, efficiently processing complex data and enhancing anomaly detection. This model’s self-attention and generative capabilities allow for superior adaptability and robustness against dynamic data patterns and unknown anomalies.Results: The Transformer-GAN model demonstrated remarkable efficacy across multiple datasets, significantly outperforming traditional anomaly detection methods. Key highlights include achieving up to 95.18% accuracy and notably high recall and F1 scores across diverse power distribution scenarios. Its exceptional performance is further underscored by achieving the highest AUC of 96.64%, evidencing its superior ability to discern between normal and anomalous patterns, thereby reinforcing the model’s advantage in enhancing the security and stability of smart power systems.Discussion: The success of the Transformer-GAN model not only boosts the stability and security of smart power distribution systems but also finds potential applications in industrial automation and the Internet of Things. This research signifies a pivotal step in integrating artificial intelligence into the power sector, promising to advance the reliability and intelligent evolution of future power systems.

In recent years, extensive research has been conducted on bismuth tungstate (Bi2WO6) in the field of photocatalysis owing to its unique crystal structure and favorable bandgap. This study offers a comprehensive review of the research on Bi2WO6-based photocatalysts from 2007 to 2022 using bibliometric analysis. The analysis utilized the Web of Science Core Collection Database and encompassed a dataset of 2064 publications. The bibliometric analysis and science mapping were carried out using the bibliometix R-package and CiteSpace software. This analysis examined and discussed the network of relationships among countries, journals, organizations, authors, and keywords pertaining to the topic and subtopics under investigation. The findings demonstrate that China has played a significant role in this research area and has formed close collaborations with other countries. The identification of highly-cited emerging terms suggests that enhancing the photocatalytic performance of Bi2WO6-based nanomaterials is a primary research focus. Moreover, there has been increasing interest in exploring the synergistic effects of photocatalysis and adsorption as a means to improve catalytic efficiency. This study provides valuable insights for researchers seeking a deeper understanding of Bi2WO6-based photocatalysts.

Abstract Background Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. Methods Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. Results Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. Conclusions Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Abstract Background Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied. Methods Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel’s test and Baron and Kenny’s causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach. Results In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (β=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (β=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (β=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction. Conclusion The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.

Abstract Background White-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous mutation in POGZ (Pogo Transposable Element Derived with ZNF Domain). This syndrome is characterized by delayed psychomotor development apparent in infancy and abnormal facial features. To date, 80 cases have been reported in the literature; however, the phenotypic characterizations remain incomplete. Case presentation We herein describe a 2-year-old girl harboring a novel frameshift de novo POGZ variant: c.2746del (p.Thr916ProfsTer12). This patient presented with multisystem abnormalities affecting the digestive tract and neurological functioning, as well as congenital heart disease, which involved an atrial septal defect (18 × 23 × 22 mm) with pulmonary arterial hypertension (42 mmHg). The relationship between congenital heart disease and White-Sutton syndrome as described in both the GeneReview and OMIM databases (#616,364) remains unclear. A review of the current literature revealed 18 cases of White-Sutton syndrome with POGZ variants and congenital heart disease, and we summarize their clinical features in this study. Conclusions Our findings based on the present case and those in the literature indicate a relationship between POGZ mutation and congenital heart disease.

Abstract The implementation of air pollution reduction measures has significantly reduced the concentration of atmospheric fine particles (PM2.5) in Beijing, among which the “coal-to-gas” conversion measures may play a crucial role. However, the effect of this conversion measure on brown carbon (BrC) is not well known. Here, the chemical composition of BrC in humic-like fraction (HULIS-BrC) and water-insoluble fraction (WI-BrC) were characterized for ambient PM2.5 samples collected in Beijing before and after the “coal-to-gas” conversion measure. After the conversion measure, the number of HULIS-BrC compounds increased by ~14%, while the number of WI-BrC compounds decreased by ~8%. The intensity of over 90% of HULIS-BrC compounds also increased after the conversion measure, and correspondingly the O/C ratios of CHO and CHON compounds in HULIS-BrC fraction generally increased with the increase of intensity ratios after/before the conversion measure, indicating that there were more water-soluble highly oxygenated BrC compounds after “coal-to-gas” conversion measure. On the contrary, the intensity of more than 80% of WI-BrC compounds decreased after the conversion measure, and the O/C ratios of CHO and CHON compounds in WI-BrC fraction generally decreased with the decrease of intensity ratios after/before the conversion measure, indicating that after the “coal-to-gas” conversion measure the water-insoluble low oxygenated BrC compounds decreased. This work sheds light on the differences in the chemical composition of BrC between before and after the “coal-to-gas” conversion measure and suggests that future studies on the residential coal combustion BrC and secondary BrC deserve further exploration.

Abstract Background We aimed to explore the association between WeChat usage and depression in the Chinese middle-aged and elderly and the role of social participation. Methods Data were obtained from China Health and Retirement Longitudinal Study (CHARLS) of 2018. The dependent variable was depressive symptoms, measured with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). We used the propensity score matching (PSM) to match the WeChat users with the non-WeChat users. Correlations between WeChat usage and depressive symptoms were verified by using logistic regression and linear regression, and the mediating role of social participation was verified by using stepwise regression and KHB method. Results Four thousand five hundred forty-five samples were ultimately matched for analysis in this study. After including all control variables, results of logistic regression showed that WeChat usage was significantly associated with a lower prevalence of depression (aOR:0.701,95% CI: 0.605–0.812). And the results of linear regression showed that WeChat usage was associated with lower levels of depression which was significant (p

Accurate three-dimensional (3D) cloud structure measurements are critical for assessing the influence of clouds on the Earth’s atmospheric system. This study extended the MODIS (Moderate-Resolution Imaging Spectroradiometer) cloud vertical profile (64 × 64 scene, about 70 km in width × 15 km in height) retrieval technique based on conditional generative adversarial networks (CGAN) to construct seamless 3D cloud fields for the MODIS granules. Firstly, the accuracy and spatial continuity of the retrievals (of 7180 samples from the validation set) were statistically evaluated. Then, according to the characteristics of the retrieval error, a spatially overlapping-scene ensemble generation method and a bidirectional ensemble binning probability fusion (CGAN-BEBPF) technique were developed, which improved the CGAN retrieval accuracy and support to construct seamless 3D clouds for the MODIS granules. The CGAN-BEBPF technique involved three steps: cloud masking, intensity scaling, and optimal value selection. It ensured adequate coverage of the low reflectivity areas while preserving the high-reflectivity cloud cores. The technique was applied to retrieve the 3D cloud fields of Typhoon Chaba and a multi-cell convective system and the results were compared with ground-based radar measurements. The cloud structures of the CGAN-BEBPF results were highly consistent with the ground-based radar observations. The CGAN-EBEPF technique retrieved weak ice clouds at the top levels that were missed by ground-based radars and filled the gaps of the ground-based radars in the lower levels. The CGAN-BEBPF was automated to retrieve 3D cloud radar reflectivity along the MODIS track over the seas to the east and south of mainland China, providing valuable cloud information to support maritime and near-shore typhoons and convection prediction for the cloud-sensitive applications in the regions.

Abstract Staggered-peak production (SP)—a measure to halt industrial production in the heating season—has been implemented in North China Plain to alleviate air pollution. We compared the variations of PM1 composition in Beijing during the SP period in the 2016 heating season (SPhs) with those in the normal production (NP) periods during the 2015 heating season (NPhs) and 2016 non-heating season (NPnhs) to investigate the effectiveness of SP. The PM1 mass concentration decreased from 70.0 ± 54.4 μg m−3 in NPhs to 53.0 ± 56.4 μg m−3 in SPhs, with prominent reductions in primary emissions. However, the fraction of nitrate during SPhs (20.2%) was roughly twice that during NPhs (12.7%) despite a large decrease of NOx, suggesting an efficient transformation of NOx to nitrate during the SP period. This is consistent with the increase of oxygenated organic aerosol (OOA), which almost doubled from NPhs (22.5%) to SPhs (43.0%) in the total organic aerosol (OA) fraction, highlighting efficient secondary formation during SP. The PM1 loading was similar between SPhs (53.0 ± 56.4 μg m−3) and NPnhs (50.7 ± 49.4 μg m−3), indicating a smaller difference in PM pollution between heating and non-heating seasons after the implementation of the SP measure. In addition, a machine learning technique was used to decouple the impact of meteorology on air pollutants. The deweathered results were comparable with the observed results, indicating that meteorological conditions did not have a large impact on the comparison results. Our study indicates that the SP policy is effective in reducing primary emissions but promotes the formation of secondary species.

Ta-10W alloy has great potential in the aerospace and nuclear industries due to its good formability, high melting point and excellent high-temperature strength. The purpose of this study was to experimentally research the tribological behaviors of Ta-10W at elevated temperatures and the effects of temperatures on the friction coefficient and the wear rate of Ta-10W in sliding wear. It was found that the main wear mechanism of the material at 100°C was abrasive wear, as well as adhesive wear and slight oxidative wear occurred at 200°C and 300°C. The friction coefficients increased as the temperature rose, which was attributed to the increase in metal viscosity at elevated temperatures. The wear rate gradually decreased with the temperature rising, such that there was a conversion from severe wear to light wear. At 200°C and 300°C, a large amount of stable oxide film covered the scar surface, resulting in decreased wear rate.

Abstract Background Neutralizing antibodies are approved drugs to treat coronavirus disease-2019 (COVID-19) patients, yet mutations in severe acute respiratory syndrome coronavirus (SARS-CoV-2) variants may reduce the antibody neutralizing activity. New monoclonal antibodies (mAbs) and antibody remolding strategies are recalled in the battle with COVID-19 epidemic. Results We identified multiple mAbs from antibody phage display library made from COVID-19 patients and further characterized the R3P1-E4 clone, which effectively suppressed SARS-CoV-2 infection and rescued the lethal phenotype in mice infected with SARS-CoV-2. Crystal structural analysis not only explained why R3P1-E4 had selectively reduced binding and neutralizing activity to SARS-CoV-2 variants carrying K417 mutations, but also allowed us to engineer mutant antibodies with improved neutralizing activity against these variants. Thus, we screened out R3P1-E4 mAb which inhibits SARS-CoV-2 and related mutations in vitro and in vivo. Antibody engineering improved neutralizing activity of R3P1-E4 against K417 mutations. Conclusion Our studies have outlined a strategy to identify and engineer neutralizing antibodies against SARS-CoV-2 variants.

Abstract This paper presents a non‐intrusive method for identifying the load state of a distribution network. The method focuses on continuously varying loads. By considering the load on‐off state switching points and the continuous features at on state, a deep convolutional method considering non‐local spatiotemporal features is proposed. The addition of an attention component to the convolutional network enhances the non‐local feature extraction capability of the convolutional network. Ultimately, the effectiveness of the method is demonstrated in an experimental setting. In addition, this paper demonstrates that the proposed method can effectively integrate switching point features as well as persistent features through neural network visualization techniques.

ObjectiveDespite numerous guidelines, the overall outcome of infantile spasms is poor, with only a small number of patients being able to attend school. The purpose of this study was to investigate long-term outcomes. Patients had poor access to the recommended first-line anti-seizure medications (ASMs), such as hormones (corticotropin or prednisolone/prednisone) and vigabatrin, and their alternative treatment was other ASMs and a ketogenic diet.MethodsPatients suffering from infantile spasms who had at least 2 years of medical records in the electronic medical record system between January 2014 and August 2022 were included in this study. Patient information was retrospectively reviewed. All patients had received ketogenic diet therapy (mainly classical ketogenic diet therapy). The ketogenic diet therapy was combined with ASMs not used as first-line therapies. The primary endpoint outcome measure was the number of patients with seizure freedom. The secondary measures included the duration of ketogenic diet therapy, choice of ASMs, and patient development at the last visit.ResultsA total of 177 patients with infantile spasms were included, and 152 (86%) of them had seizure freedom. The median duration from the first to the last hospital visit was 53.27 months, and the number of visits was 47.00. The median age at the initial hospital visit was 8.00 months, and the median age at initiation of the ketogenic diet was 17.73 months. At the last visit, the proportions of patients with neurodevelopmental delay, developmental epileptic encephalopathy, drug-resistant epilepsy, and generalized seizures increased significantly. The frequently used ASMs were topiramate, valproic acid, levetiracetam, nitrazepam, and vitamin B6 injection, while the recommended first-line drugs corticotropin and vigabatrin were rarely selected. The study duration of 9.5 years was divided into three periods but the prescription of ASMs did not change significantly between these periods.ConclusionsAlthough the seizure freedom rate was high with ketogenic diet therapy combined with non-standard ASMs, the patients had a significant neurodevelopmental delay at the last visit, which was, however, similar to that of standard treatment. To improve the outcomes of infantile spasms, multicenter clinical trials of the ketogenic diet as a first-line treatment in combination with non-standard ASMs are needed.

Summary: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the global coronavirus disease 2019 (COVID-19) pandemic, contains a unique, four amino acid (aa) “PRRA” insertion in the spike (S) protein that creates a transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and enhances viral infectivity. More research into immunogenic epitopes and protective antibodies against this SARS-CoV-2 furin cleavage site is needed. Methods: Combining computational and experimental methods, we identified and characterized an immunogenic epitope overlapping the furin cleavage site that detects antibodies in COVID-19 patients and elicits strong antibody responses in immunized mice. We also identified a high-affinity monoclonal antibody from COVID-19 patient peripheral blood mononuclear cells; the antibody directly binds the furin cleavage site and protects against SARS-CoV-2 infection in a mouse model. Findings: The presence of “PRRA” amino acids in the S protein of SARS-CoV-2 not only creates a furin cleavage site but also generates an immunogenic epitope that elicits an antibody response in COVID-19 patients. An antibody against this epitope protected against SARS-CoV-2 infection in mice. Interpretation: The immunogenic epitope and protective antibody we have identified may augment our strategy in handling COVID-19 epidemic. Funding: The National Natural Science Foundation of China (82102371, 91542201, 81925025, 82073181, and 81802870), the Chinese Academy of Medical Sciences Initiative for Innovative Medicine (2021-I2M-1-047 and 2022-I2M-2-004), the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2020-PT310-006, 2019XK310002, and 2018TX31001), the National Key Research and Development Project of China (2020YFC0841700), US National Institute of Health (NIH) funds grant AI158154, University of California Los Angeles (UCLA) AI and Charity Treks, and UCLA DGSOM BSCRC COVID-19 Award Program. H.Y. is supported by Natural Science Foundation of Jiangsu Province (BK20211554 and BE2022728).

Abstract Background Descending necrotizing mediastinitis (DNM) is one of the most virulent forms of mediastinitis. The main causes of high mortality in DNM are believed to stem from difficulty and delay in the diagnosis. Fast and accurate identification of pathogens is important for the treatment of these patients. Metagenomics next-generation sequencing (mNGS) is a powerful tool to identify all kinds of pathogens, especially for rare and complex infections. Case presentation A 64-year-old male patient was admitted to the intensive care unit (ICU) with unconsciousness, dyspnea, and swelling in the mandible and neck. Computed tomography (CT) scan results combined with clinical laboratory examination indicated DNM. Vancomycin and imipenem were used, and vacuum sealing drainage was applied for debridement and drainage of the infected area. The positive mNGS results of drainage fluid confirmed the presence of mixed infection caused by Streptococcus anginosus , Prevotella oris, and several other anaerobes. The antibiotics were adjusted to piperacillin/tazobactam and tinidazole according to the mNGS results and antimicrobial susceptibility testing of cultured pathogens. After 11 days of antibiotic therapy, the infection symptoms of the neck and mediastinum improved, and the patient was transferred out of the ICU on the 26th day after negative result of drainage fluid culture. Conclusion This case suggested that mNGS is a promising technology for precise and fast pathogens identification with high sensitivity, which may guide the diagnosis of infectious diseases in the future trend.

In recent years, the use of magnetic biochar in wastewater treatment has shown significant effects and attracted scholars’ attention. However, due to the relatively short research time and the lack of systematic summaries, it is difficult to provide a more in-depth analysis. This study utilizes RStudio and CiteSpace software to comprehensively analyze the research trends and progress of magnetic biochar in wastewater treatment. The analysis of bibliometrics is performed on 551 relevant papers retrieved from the Web of Science, spanning the period between 2011 and 2022. The most influential countries, institutions, journals, disciplinary distribution, and top 10 authors and papers in this field have been identified. The latest dataset has been used for keyword clustering and burst analysis. The results indicated that: (1) Bin Gao is the most influential author in this field, and high-level journals such as Bioresource Technology are more inclined to publish articles in the field of magnetic biochar. (2) Research in this field has predominantly focused on the removal of heavy metals and organic compounds. Keyword burst analysis shows a shift in research direction towards the removal of complex organic pollutants recently. (3) For the future development of magnetic biochar, an environment-friendly approach, economic viability, and joint technology are the directions that need more exploration. Finally, this paper provides a summary of the various adsorption mechanisms of magnetic biochar and several common modification methods, aiming to assist scholars in their research endeavors.

Tuberous sclerosis, also known as tuberous sclerosis complex (TSC), is an autosomal dominant defect characterized by hamartomas in multiple organ systems. Inactivating variants cause this defect in either the TSC1 gene or the TSC2 gene, leading to hamartin or tuberin protein dysfunction, thus resulting in TSC. The diagnostic criteria for TSC suggest that it can be diagnosed by identifying a heterozygous pathogenic variant of TSC1 or TSC2, even in the absence of clinical signs. In a 4-year-old girl, we identified a splicing variant (NM_000548.4: c.2967-1G>T) that she inherited from her father. Neither the girl (patient) nor her father showed typical features of TSC. This variant is located in a NAGNAG acceptor, which can produce mRNA isoforms that differ by a three-nucleotide indel. Reverse transcription polymerase chain reaction analysis of the patient and both parents’ blood RNA samples suggested two different splicing patterns, and these two splicing patterns differed in the presence or absence of the first codon of exon 27, thus providing two splicing products designated as isoforms A and B, respectively. Furthermore, the proportions of these two patterns varied between the patient and either parent. A minigene assay further confirmed that the c.2967-1G>T variant led to the absence of isoform A (including the first codon of exon 27). The finding of our study demonstrates this variant, c.2967-1G>T, disrupts the balance of an alternative splice event which involves the use of two tandem alternatives acceptors and is not associated with typical symptoms of tuberous sclerosis. Our finding is of importance for genetic counseling and suggests that we need to be vigilant to avoid misdiagnosis when we encounter such a site.

ObjectiveTuberous sclerosis complex (TSC) is a rare disease with a high risk of epilepsy and cognitive impairment in children. Ketogenic diet (KD) therapy has been consistently reported to be beneficial to TSC patients. In this study, we aimed to investigate the efficacy and safety of KD in the treatment of drug-resistant epilepsy and cognitive impairment in children with TSC.MethodsIn this multicenter study, 53 children (33 males and 20 females) with drug-resistant epilepsy or cognitive impairment caused by TSC were retrospectively recruited from 10 hospitals from January 1, 2010, to December 31, 2020. Intention-to-treat analysis was used to evaluate seizure reduction and cognition improvement as outcomes after KD therapy.ResultsOf the 53 TSC patients included, 51 failed to be seizure-free with an average of 5.0 (range, 4–6) different anti-seizure medications (ASMs), before KD therapy. Although the other two patients achieved seizure freedom before KD, they still showed psychomotor development delay and electroencephalogram (EEG) abnormalities. At 1, 3, 6, and 12 months after the KD therapy, 51 (100%), 46 (90.2%), 35 (68.6%), and 16 patients (31.4%) remained on the diet therapy, respectively. At these time points, there were 26 (51.0%), 24 (47.1%), 22 (43.1%) and 13 patients (25.5%) having ≥50% reductions in seizure, including 11 (21.6%), 12 (23.5%), 9 (17.6%) and 3 patients (5.9%) achieving seizure freedom. In addition, of 51 patients with psychomotor retardation, 36 (36 of 51, 70.6%) showed cognitive and behavioral improvements. During the KD therapy, no serious side effects occurred in any patient. The most common side effects were gastrointestinal disturbance (20 of 53, 37.7%) and hyperlipidemia (6 of 53, 11.3%). The side effects were gradually relieved after adjustment of the ketogenic ratio and symptomatic treatment.ConclusionKD is an effective and safe treatment for TSC-related drug-resistant epilepsy and cognitive impairment in children. KD can reduce seizure frequency and may potentially improve cognition and behavior.

Progressive myoclonic epilepsy (PME) is a group of rare diseases characterized by progressive myoclonus, cognitive impairment, ataxia, and other neurologic deficits. PME has high genetic heterogeneity, and more than 40 genes are reportedly associated with this disorder. SEMA6B encodes a member of the semaphorin family and was first reported to cause PME in 2020. Herein, we present a rare case of PME due to a novel SEMA6B gene mutation in a 6-year-old boy born to healthy non-consanguineous Chinese parents. His developmental milestones were delayed, and he developed recurrent atonic seizures and myoclonic seizures without fever at 3 years and 11 months of age. He experienced recurrent myoclonic seizures, non-convulsive status epilepticus (NCSE), atonic seizures, and atypical absence seizures during the last 2 years. At different time points since onset, valproic acid, levetiracetam, piracetam, and clobazam were used to control the intractable seizures. Notably, NCSE was controlled by a combination of piracetam with clobazam and valproic acid instead of intravenous infusion of midazolam and phenobarbital. Due to the limited number of cases reported to date, the clinical description of our case provides a better understanding of the genotype–phenotype correlations associated with PME and indicate that piracetam may be effective against NCSE in patients with SEMA6B-related PME.

In the recent 3 years, subjects with Pumilio1-associated developmental disability, ataxia, and seizure syndrome have been identified as harboring Pumilio homolog 1 (PUM1) mutations. However, the characteristics of the seizure phenotype remain to be elucidated. We herein described a 3-year-old female proband who was diagnosed with developmental and epileptic encephalopathy presenting with some features suggestive of a Dravet-like syndrome. For genetic analyses, trio-based whole-exome sequencing and array comparative genomic hybridization were performed. Consequently, a de novo heterozygous missense variant was identified in exon 22 of the PUM1 gene: NM_001020658: c.3439C > T (p.Arg1147Trp). Upon thoroughly reviewing the existing literature, nine cases of PUM1 mutation-related epilepsy were identified, and their clinical features were summarized. A relationship between PUM1 mutation and clinical manifestations characteristic of a Dravet-like syndrome was proposed. To our knowledge, this is the first report of a patient with PUM1 mutation presenting with a Dravet-like syndrome.

ObjectiveThe aim of this study was to analyze the phenotypic spectrum, treatment, and prognosis of 72 Chinese children with SCN2A variants.MethodsThe SCN2A variants were detected by next-generation sequencing. All patients were followed up at a pediatric neurology clinic in our hospital or by telephone.ResultsIn 72 patients with SCN2A variants, the seizure onset age ranged from the first day of life to 2 years and 6 months. The epilepsy phenotypes included febrile seizures (plus) (n = 2), benign (familial) infantile epilepsy (n = 9), benign familial neonatal-infantile epilepsy (n = 3), benign neonatal epilepsy (n = 1), West syndrome (n = 16), Ohtahara syndrome (n = 15), epilepsy of infancy with migrating focal seizures (n = 2), Dravet syndrome (n = 1), early infantile epileptic encephalopathy (n = 15), and unclassifiable developmental and epileptic encephalopathy (n = 8). Approximately 79.2% (57/72) patients had varying degrees of developmental delay. All patients had abnormal MRI findings with developmental delay. 91.7% (55/60) patients with de novo SCN2A variants had development delay, while only 16.7% (2/12) patients with inherited SCN2A variants had abnormal development. 83.9% (26/31) SCN2A variants that were located in transmembrane regions of the protein were detected in patients with development delay. Approximately 69.2% (9/13) SCN2A variants detected in patients with normal development were located in the non-transmembrane regions. Approximately 54.2% (39/72) patients were seizure-free at a median age of 8 months. Oxcarbazepine has been used by 38 patients, and seizure-free was observed in 11 of them (11/38, 28.9%), while 6 patients had seizure worsening by oxcarbazepine. All 3 patients used oxcarbazepine and with seizure onset age > 1 year presented seizure exacerbation after taking oxcarbazepine. Valproate has been used by 53 patients, seizure-free was observed in 22.6% (12/53) of them.ConclusionThe phenotypic spectrum of SCN2A-related epilepsy was broad, ranging from benign epilepsy in neonate and infancy to severe epileptic encephalopathy. Oxcarbazepine and valproate were the most effective drugs in epilepsy patients with SCN2A variants. Sodium channel blockers often worsen seizures in patients with seizure onset beyond 1 year of age. Abnormal brain MRI findings and de novo variations were often related to poor prognosis. Most SCN2A variants located in transmembrane regions were related to patients with developmental delay.

Retrieving cloud vertical structures with satellite remote-sensing measurements is highly desirable and technically challenging. In this paper, the conditional adversarial neural network (CGAN) for retrieving the equivalent cloud radar reflectivity at 94 GHz of the Cloud Profile Radar (CPR) onboard CloudSat is extended and evaluated comprehensively for different cloud types and geographical regions. The CGAN-based retrieval model was extended with additional data samples and improved with a new normalization adjustment. The model was trained with the labeled datasets of the moderate-resolution imaging spectroradiometer (MODIS) cloud top pressure, cloud water path, cloud optical thickness, and effective particle radius data, and the CloudSat/CPR reflectivity from 2010 to 2017 over the global oceans. The test dataset, containing 24,427 cloud samples, was statistically analyzed to assess the performance of the model for eight cloud types and three latitude zones with multiple verification metrics. The results show that the CGAN model possesses good reliability for retrieving clouds with reflectivity > −25 dBZ. The model performed the best for deep convective systems, followed by nimbostratus, altostratus, and cumulus, but presented a very limited ability for stratus, cirrus, and altocumulus. The model performs better in the low and middle latitudes than in the high latitudes. This work demonstrated that the CGAN model can be used to retrieve vertical structures of deep convective clouds and nimbostratus with great confidence in the mid- and lower latitude region, laying the ground for retrieving reliable 3D cloud structures of the deep convective systems including convective storms and hurricanes from MODIS cloud products and used for predicting these storms.

Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype–phenotype correlations.Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children’s Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied.Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed.Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype–phenotype correlation.Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).

Sea fog is a particular kind of atmospheric aerosol that often poses hidden risks to ship navigation, ocean exploration, human productivity, and life. In light of the aforementioned issues, this research conducted a thorough investigation of the polarization transmission properties in a sea fog environment. We studied the physical characteristics of sea fog and established a polarized radiative transfer model based on RT3/PolRadtran (polarized radiative transfer) in a sea fog environment based on the theory of Mie scattering. The effects of wavelength, polarization state, sea fog concentration, and salt content on the polarization degree were simulated by using the polarization transport model. An indoor sea fog simulation device was designed and built. The simulation test results were compared with the experimental test results from many aspects, and the existing errors were analyzed so that they could be mutually verified for the overall trend. According to the modeling results, distinct polarization states of light exhibit evident depolarization as the sea fog concentration rises. Overall, circularly polarized light has superior polarization-maintaining properties compared to linearly polarized light under the same contrast settings. The penetrating impact of incoming light in the visible range improves with increasing wavelength, and the amount of salt in sea fog has some bearing on the degree of polarization.

SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.

Abstract Pyroptosis, a type of programmed cell death that along with inflammation, is mainly regulated by two main pathways, cysteinyl aspartate specific proteinase (caspase)-1-induced canonical inflammatory pathway and caspase-11-induced non-canonical inflammatory pathway. The non-canonical inflammatory pathway-induced pyroptosis is a unique immune response in response to gram-negative (G−) bacteria. It is induced by lipopolysaccharide (LPS) on the surface of G− bacteria. This activates caspase-11 which, in turn, activates a series of downstream proteins eventually forming protein pores on the cell membrane and inducing cell sacrificial processes. Caspase-11 belongs to the caspase family and is an homologous protein of caspase-1. It has the ability to specifically hydrolyze proteins, but it is still unclear how it regulates cell death caused by non-canonical inflammatory pathways. The present study describes a pathway that enables LPS to directly enter the cell and activate caspase-11, and the key role caspase-11 plays in the activation of pyroptosis and inflammation.

Null pointer exceptions are common software faults, but they are dangerous and can cause a program to crash if they occur. In addition, it is hard to find them by simply running test cases. When a null pointer exception occurs, the stack trace stored by the Java runtime environment can help us to locate the cause of the exception. In this paper, firstly, we propose an automatically null pointer exception localization approach guided by stack trace, from the null pointer dereference to the null value assignment point. Secondly, an empirical study is designed to evaluate the effectiveness of the tool on eight open source projects. The experimental results show that the tool is effective in locating the null pointer exception.

Characteristics and sources of volatile organic compounds (VOCs) were investigated with highly time-resolved measurements by a proton-transfer-reaction time-of-flight mass spectrometer (PTR-ToF-MS) at an urban site in Beijing in winter 2017. During the measurement period, high mixing ratios of VOCs (48.9 ppbv) and trace gases were observed, with alternating episodes of strong haze pollution and clean air. Ten VOC families showed clear dependence on the VOC concentration. Aromatics increased the most during haze, with significantly elevated benzene concentration at high VOC concentration, while CxHyO3 and CxHy increased the least. The positive matrix factorization (PMF) receptor model was applied to the VOC mass spectra, yielding four major VOC factors: traffic emissions (21.0%), solid fuel combustion (SFC, 24.4%), and two oxygenated VOC (OVOC) factors (32.3% and 22.3%). Traffic and solid fuel combustion were dominant during the periods of high total VOC concentration, while the OVOC1 fraction was reduced. Comparisons with organic aerosol (OA) sources showed increased oxygenated organic aerosol (OOA) concentration during high VOC concentration periods, indicating the importance of OVOCs to secondary organic aerosol formation. Furthermore, trajectory analysis showed that most of the clean days were associated with northerly winds with high ratios of OVOC1. In contrast, the haze periods were not only due to high primary emissions under stagnant conditions, but also influenced by air masses from a more regional scale.

The study of the characteristics and variations of cloud condensation nuclei (CCN) plays an important role in understanding the effects of aerosol–cloud interactions. This paper selected observation data in a city region of Shijiazhuang in North China from 2005 to 2007, along with the corresponding MERRA-2 and ERA5 data, to analyze the characteristics of CCN, sort the factors affecting the diurnal variation of CCN number concentration (NCCN) according to their importance, and build the relationship between NCCN and supersaturation (SS) in the heavily polluted region. The results show that there was a bimodal distribution of a daily time series for NCCN in Shijiazhuang, China. By calculating the correlation between CCN and pollutants observed in winter 2007, we identified that the dominant factor for peaks of NCCN is SO2 in the morning but NO2 in the evening. We also ranked the factors affecting the diurnal variation of NCCN by using observation and reanalysis data and found that the concentration of pollutants is the greatest impact factor in summer, but the atmospheric stability is the greatest factor in winter. Finally, we determined the relationship between NCCN and SS according to the Twomey formula (NCCN=cSSk) and found there was a reasonable value range (i.e., 0.5~0.7) for the parameter k in East and North China. Specifically, it is more reasonable for k to be 0.5 in summer and 0.7 in winter.

Zoom lens with stationary external entrance pupil and internal stop is a type of special optical system that can be used in cascaded optics to meet the requirements of long focal length or variable magnification. We proposed a 4× zoom lens to improve the pupil walking limitation observed in the conventional design. Varifocal- and pupil-stable differential equations are presented and a paraxial design of the lens with two moving parts was developed. Moreover, the zoom lens, which functions in the visible waveband 500 nm~750 nm, is designed using seven types of common optical glasses, has a constant f-number of 10 and focal range of 100 mm~400 mm, and achieves pupil walking in the range −3.9 mm to +4.3 mm. The results demonstrate that the design had good image quality and tolerance characteristics. Owing to the limited pupil walking and zoom capability, the scheme is of considerable interest for application in electrical optical systems.

To mitigate air pollution in China, a legislative ‘Air Pollution Prevention and Control Action Plan’ has been implemented by the Chinese government since 2013. There is, however, a lack of investigations for long-term trends in the composition, sources and evolution processes of PM1 (particulate matter with diameter less than 1 μm) after the implementation. To evaluate the effectiveness of these control measures, we present a year-long real-time measurement of the chemical composition of PM1 at an urban site in Beijing from November 2014 to November 2015, and the results are compared with previous studies from 2008 to 2013 to gain insights into the variations of the chemical composition and sources of PM1 in Beijing. Large seasonal differences were observed in the mass concentrations of PM1 species and general declining trend was observed in the last seven years. Specifically, the annual averages of mass concentrations in 2014–2015 decrease by 16–43% (PM1), 23–43% (organic aerosol, OA), 38–68% (sulfate), 26–51% (nitrate), 18–33% (ammonium) and 27–38% (chloride) compared to those from 2008 to 2013. During winter and summer, the seasonal mass concentrations of sulfate and nitrate show more significant declines especially in summer 2008 (79% and 81%) and summer 2011 (76% and 77%). The nitrate-to-sulfate ratio is higher in 2014–2015 (1.5 ± 0.6) than that in 2013 (1.0 ± 0.3), largely due to significant reduction in SO2 emissions, suggesting that nitrate is becoming more important than sulfate in particulate pollution in Beijing. OA is the dominant PM1 fraction (>45%) in all seasons and the mass concentrations/contributions of both primary and secondary OA show different seasonality. As for the more oxidized oxygenated OA (MO-OOA) and less oxidized oxygenated OA (LO-OOA), the contributions of MO-OOA are much higher than those of LO-OOA (27–62% vs. 6–26%) in both high-pollution and low-pollution days. Aqueous-phase processes are found to facilitate the formation of MO-OOA while photochemical oxidation formation is a major contributor of LO-OOA in winter, and photochemical oxidation plays a major role in the formation of MO-OOA in summer and fall. The current study provides a comprehensive seasonal comparison of chemical composition and formation of PM1 in Beijing and a pacesetter in tackling PM pollution for other equally polluted megacities, after implementation of more stringent control measures after 2013.

A 56-day feeding trial was implemented to evaluate the effects of promoted biofloc on the water quality, growth performance, digestive enzymes activity, immune-related genes and antioxidant status of golden crucian carp in negligible exchange culture tanks. Four handred fifty healthy golden crucian carp juveniles (5.03 ± 0.22 g) were randomly assigned among 15 tanks. Five C:N ratios in triplicate tanks were tried: C/N = 5.48:1 with a commercial diet (Control), C/N = 10:1, C/N = 15:1, C/N = 20:1 and C/N = 25:1. Anhydrous glucose (99.97 %) was added to the commercial diet to maintain elevated carbon ratio in the three treatments. Uninterrupted 24 -h aeration was supplied during the test by using an air-stone connected to an air pump to develop the biofloc in the water column. The results demonstrated that BFT significantly reduced ammonia nitrogen (TAN), nitrite (NO2−-N), total phosphorus (TP) concentration and water transparency (Secchi depth) in C/N 15–25 than control (p < 0.05), wheras the chemical oxygen demand (COD) and nitrate nitrogen (NO3−-N) concentration gradually increased over time. Apart from, weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) were considerately elevated in C/N 20 and C/N 25 than control (p < 0.05).This was coincidental with the higher activities for protease, lipase and amylase in liver. Significant increases in lysozyme (LSZ), acid phosphatase (ACP) and alkaline phosphatase (AKP) activities of golden crucian carp were found in the C/N 20 group than control (p < 0.05), and regulating the expression of immune-related genes including IL-1β, TNF-α and HSP70 after a 56-day feeding trial. Comparing the antioxidant capacity of golden crucian carp from the five experimental groups, the activity of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT) activity and glutathione peroxidase (GSH-PX) activity of juveniles in the C/N 20 and C/N 25 groups were significant higher (p < 0.05), and the content of malondialdehyde (MDA) was much lower (p < 0.05) than in the control under this experiment condition. Overall, this findings suggest that BFT not only can enhance golden crucian carp growth performance, elevate digestive enzymes activity, and strengthen antioxidant status but also upgrade immune response. Keywords: C/N, Water quality, Digestion, Immune response, Antioxidant status

The observations of meteorological wind speed may be biased due to the influence of various distractions. Therefore, the original measured data should be corrected in a targeted manner. Wind tunnel tests (WTT) and computational fluid dynamics (CFD) numerical simulation methods are used to study the local wind environment characteristics of observation sites in Noi Ling Ding Island (NLDI) and Ping An International Financial Center (PAFC) in the Shenzhen area. The interference effects of NLDI and the building components and instruments in the hollow-layer atop PAFC on their corresponding anemometer measurement results were analyzed, and a quantitative description was provided with the wind speed influence coefficient (CVI), which is the wind speed ratio in disturbed and undisturbed cases. Results show that the CVI of WTT at the NLDI site is slightly higher than that of CFD, and the wind speed in the wind-sensitive direction is accelerated by 12% due to the influence of NLDI. The large pillars at the corner of PAFC have a considerable occlusion effect on the wind speed under the wind direction of 45°. An acceleration effect with CVI of 1.163 is found in the dominant wind direction when instruments are absent atop the hollow-layer, whereas a sheltering effect is observed with the CVI of 0.593 when instruments are present. These results are used to correct the recorded wind speed at the NLDI and PAFC sites during Super Typhoon Manghut with No. 201822, and then converted into the 10 min mean wind pressure value at 10 m height under the standard landform. The reference wind pressure values obtained are 0.526 and 0.505 kPa. The analogous conversion values achieve the purpose of mutual verification, and the effectiveness and reliability of the methodologies are presented.

This study investigates how L1 Chinese scholars in hard science disciplines use metadiscourse in their English academic writing, by comparing the deployment of metadiscoursal resources written by L1 Chinese and L1 English scholars. Hyland’s (2005) interpersonal model of metadiscourse was adopted for the analysis. We found that L1 Chinese scholars used less metadiscoursal resources than L1 English scholars on the whole. In the two dimensions of interaction, L1 Chinese scholars made more use of interactive devices, while L1 English scholars used more interactional items. This reflects that L1 Chinese scholars made greater efforts to guide the readers through their papers, and L1 English scholars are more concerned with creating author identity and engaging their readers. The t-tests confirmed that L1 Chinese scholars used significantly more code glosses in interactive metadiscourse and less self-mentions in interactional metadiscourse. An in-depth analysis reveals two functions of code glosses and five functions of self-mentions in RA abstracts.

A field experiment of nocturnal mountain wind and corresponding particulate matter (PM) evolution under weak synoptic forcing at five sites within urban Beijing was conducted using a moving Doppler wind lidar and a fixed tower. Clear wind shear and zero-horizontal-wind zones at 40–320 m above the ground with a delay of 1.5 h were found at two sites between 20 km from north to south urban Beijing. The wind speed and height of the low-level jet at the north urban Beijing site were greater than those at the east urban Beijing site. The average horizontal distribution of low-level PM at 240 m was similar to the ground-level PM at night. The PM2.5 (aerodynamic diameter ≤2.5 μm) accumulation center showed no abrupt changes with a shift in wind direction until the northerly wind jet arrived.

Background. Diabetes is a progressive metabolic disease characterized by hyperglycemia. Functional impairment of islet β cells can occur to varying degrees. This impairment can initially be compensated for by proliferation and metabolic changes of β cells. Cell division control protein 42 (Cdc42) and the microRNA (miRNA) miR-29 have important roles in β-cell proliferation and glucose-stimulated insulin secretion (GSIS), which we further explored using the mouse insulinoma cell line MIN6. Methods. Upregulation and downregulation of miR-29a and Cdc42 were accomplished using transient transfection. miR-29a and Cdc42 expression was detected by real-time PCR and western blotting. MIN6 proliferation was detected using a cell counting kit assay. GSIS under high-glucose (20.0 mM) or basal-glucose (5.0 mM) stimulation was detected by enzyme-linked immunosorbent assay. The miR-29a binding site in the Cdc42 mRNA 3′-untranslated region (UTR) was determined using bioinformatics and luciferase reporter assays. Results. miR-29a overexpression inhibited proliferation (P

This study was aimed to isolate sinapine-degrading bacteria from the intestinal tract of laying hens and to identify the predominant bacteria. Thirty-week old healthy laying hens were killed, and the chyme in the digestive tract was inoculated into modified Czapek medium containing sinapin and cultivated at 37 °C for 10 days. The optical density (OD) values of the bacterial solutions at different cultivating times were detected by a spectrophotometric method. The predominant strains were identified by 16S rRNA gene analysis. We extracted the extracellular products of the predominant strains to determine the total protein using the Coomassie brilliant blue method, and to determine the activities of some extracellular enzymes using the agar plate diffusion method. Nine strains were isolated from the lower intestinal tract of laying hens. Among the 9 strains, 5 were from the ileum, 2 were from the ceca and 2 were from the jejunum. We could not isolate any strains from the upper intestinal tract, such as the stomach and duodenum. Eight of those 9 isolated strains were gram negative and one was gram positive. Strains YD-1 and YD-2 were better than other strains in their abilities to degrade sinapine. Strains YD-1 and YD-2 were identified as Escherichia coli and Klebsiella spp., respectively, by the 16S rRNA sequence analysis. The total protein level of the extracellular products was 1.213 g/L for YD-1 and 1.990 g/L for YD-2. Both extracellular products of YD-1 and YD-2 had the activities of protease, amylase and urease. This study confirmed that the primary site of sinapine degradation is in the lower intestinal tract of laying hens. The sinapine-degrading strains are mainly gram negative. Strains YD-1 and YD-2 are predominant in degrading sinapine and they belong to E. coli and Klebsiella spp., respectively. Both extracellular products of YD-1 and YD-2 contain protease, amylase and urease. Strain YD-2 is better than strain YD-1 in its ability to degrade sinapine.

With the advent of the Internet of things (IoT), intelligent transportation has evolved over time to improve traffic safety and efficiency as well as to reduce congestion and environmental pollution. However, there are some challenging issues to be addressed so that it can be implemented to its full potential. The major challenge in intelligent transportation is that vehicles and pedestrians, as the main types of edge nodes in IoT infrastructure, are on the constant move. Hence, the topology of the large scale network is changing rapidly over time and the service chain may need reestablishment frequently. Existing Virtual Network Function (VNF) chain placement methods are mostly good at static network topology and any evolvement of the network requires global computation, which leads to the inefficiency in computing and the waste of resources. Mapping the network topology to a graph, we propose a novel VNF placement method called BVCP (Border VNF Chain Placement) to address this problem by elaborately dividing the graph into multiple subgraphs and fully exploiting border hypervisors. Experimental results show that BVCP outperforms the state-of-the-art method in VNF chain placement, which is highly efficient in large scale IoT of intelligent transportation.

Tropical cyclones and meiyu-baiu fronts, as the two main synoptic systems over East Asia, bring heavy rain during summers, but their long-term and vertical raindrop size distribution (RSD) features over the midlatitude Japan Islands are limited. Radar-based quantitative precipitation estimation (QPE) techniques require RSD observations. In this study, five-year observations from Tokyo with a ground-based impact Joss-Waldvogel disdrometer (JWD) and a vertically pointing micro rain radar (MRR) with a vertical range of 0.2−6.0 km were used to study the vertical structures of RSD and QPE parameters. The results showed that the convective rain associated with tropical cyclones had a maritime nature, while the rain associated with the meiyu-baiu front had a continental nature. The rain associated with tropical cyclones had a relatively higher concentration of raindrops and a larger average raindrop diameter than the rain associated with the meiyu-baiu front. The Z−R (radar reflectivity-rain rate) relationships (Z = ARb) based on the JWD data for tropical cyclones, the meiyu-baiu front and total summer rainfall in Tokyo were Z = 189 R1.38, Z = 214 R1.35 and Z = 212 R1.33, respectively. When the Z−R relationships obtained in this study were used to replace the operational relationship of Z = 300 R1.4, the standard deviation of the rain rate was reduced from 5.50 mm/h (2.34 mm/h) to 2.34 mm/h (1.32 mm/h) for typhoon (meiyu-baiu front) rainfall, although the change for total summer rainfall was small. In addition, with increasing height below 4 km, the value of A and b decreased.

Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this background, new ways to treat cancer will be important for development of improved cancer control strategies. Cdc42 is a member of the Rho GTPase family and plays an important role in cell-to-cell adhesion, formation of cytoskeletal structures, and cell cycle regulation. It thus influences cellular proliferation, transformation, and homeostasis, as well as the cellular migration and invasion processes underlying tumor formation. Cdc42 acts as a collection point for signal transduction and regulates multiple signaling pathways. Moreover, recent studies show that in most human cancers Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis. Regarding possible new treatments for cancer, miRNA and small molecules targeting Cdc42 and related pathways have been recently found to be effective on cancer. In this review, we analyze the newly recognized regulation mechanisms for Cdc42 and Cdc42-related signal pathways, and particularly new treatments using small molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may slow down the metastasis process, improve cancer therapy and lead to novel strategies for development of antineoplastic drugs.

Fingerprint positioning can take advantage of existing WLAN to achieve indoor locations, which has been widely studied. We analyzed the corresponding positions distribution of similar fingerprints, and then found that the fuzzy similarity between fingerprints is the root cause of the larger errors existing. According to clusters distribution feature of corresponding positions of the similar fingerprints, we proposed a K -Means+ clustering algorithm to achieve fine-grained fingerprint positioning. Due to the K -Means+ algorithm failing to locate the positions of outliers, we also designed a linear sequence matching algorithm to improve the outliers positioning, and reduce the impact of fuzzy similarity. Experimental results illustrate that our algorithm can get a maximum positioning error less than 5 m, which outperforms other algorithms. Meanwhile, all the positioning errors over 4 m in our algorithm are less than 2%. The positioning accuracy has been improved significantly.

Objective: To report clinical, virological, and epidemiological features of the first death caused by a H5N6 avian influenza virus in Yunnan Province, China. Method: The case was described in clinical expression, chest radiography, blood test and treatment. Real-time RT-PCR was used to detect H5N6 virus RNA in clinical and environment samples. Epidemiological investigation was performed including case exposure history determinant, close contacts follow up, and environment sample collection. Results: The patient initially developed sore throat and coughs on 27 January 2015. The disease progressed to severe pneumonia, multiple organ dysfunction syndrome, and acute respiratory distress syndrome. And the patient died on 6 February. A highly pathogenic avian influenza A H5N6 virus was isolated from the tracheal aspirate specimen of the patient. The viral genome analyses revealed that the H5 hemmagglutinin gene belongs to 2.3.4.4 clade. Epidemiological investigation showed that the patient had exposure to wild bird. All close contacts of the patient did not present the same disease in seven consecutive days. A high H5 positive rate was detected in environmental samples from local live poultry markets. Conclusion: The findings suggest that studies on the source of the virus, transmission models, serologic investigations, vaccines, and enhancing surveillance in both humans and birds are necessary.

Severe retinal ischemia causes persistent visual impairments in eye diseases. Retinal pigment epithelium (RPE) cells are located near the choroidal capillaries, and are easily affected by ischemic or hypoxia. Ginsenoside Rg-1 has shown significant neuroprotective effects. This study was performed to test the cytoprotective effect of ginsenoside Rg-1 in RPE cells against hypoxia and cobalt chloride (CoCl2) assaults, and to understand the underlying mechanisms. We found that Rg-1 pre-administration significantly inhibited CoCl2- and hypoxia-induced RPE cell death and apoptosis. Reactive oxygen specisis (ROS)-dependent p38 and c-Jun NH(2)-terminal kinases (JNK) MAPK activation was required for CoCl2-induced RPE cell death, and Rg-1 pre-treatment significantly inhibited ROS production and following p38/JNK activation. Further, CoCl2 suppressed pro-survival mTOR complex 1 (mTORC1) activation in RPE cells through activating of AMP-activated protein kinase (AMPK), while Rg-1 restored mTORC1 activity through inhibiting AMPK activation. CoCl2-induced AMPK activation was also dependent on ROS production, and anti-oxidant N-acetylcysteine (NAC) prevented AMPK activation and RPE cell death by CoCl2. Our results indicated that Rg-1 could be further investigated as a novel cell-protective agent for retinal ischemia.