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We systematically reviewed the evidence on the association between maternal folic acid supplementation and the risk of offspring's autism spectrum disorders (ASD). A total of 10 studies with 23 sub-studies (9795 ASD cases) were included. Folic acid supplementation during early pregnancy was associated with a lower risk of offspring's ASD [OR 0.57, 95% CI 0.41-0.78]. The consumption of a daily amount of at least 400 [mu]g folic acid from dietary sources and supplements, was associated with a reduced risk of offspring ASD [OR 0.55, 95% CI 0.36-0.83]. Critical effective maternal folic acid supplementation strategies, such as intake timing and intake dosage, may aid the reduction in the risk of offspring ASD. This meta-analysis provided new insights for the prevention of offspring's ASD.

The literature from inception to 2020 on the prevalence of epilepsy in autistic individuals was systematically reviewed and further explored by subgroup analyses and meta-regression models. This systematic review is registered with PROSPERO (CRD42020179725). A total of 66 studies from 53 articles were included. The updated pooled prevalence of epilepsy in autistic individuals was 10% (95% CI: 6-14). The respective prevalence estimate of epilepsy was 19% (95% CI: 6-35) in the clinical sample-based cross-sectional study, 7% (95% CI: 3-11) in the cohort study, and 9% (95% CI: 5-15) in the population-based cross-sectional study. The pooled prevalence of epilepsy was 7% (95% CI: 4-11) in autistic children and 19% (95% CI: 14-24) in autistic adults. Compared to the school-aged group, the adolescence group (OR: 1.15, 95% CI: 1.06-1.25) and the pre-school group (OR: 1.06, 95% CI: 0.94-1.19) were positively associated with the prevalence of epilepsy. The moderators of age, human development index of the country, gender, and intellectual function accounted for most of the heterogeneity. The prevalence estimates were associated with age, female gender, intellectual disability rate, and the human development index of countries. About 1/10 autistic individuals co-occurred with epilepsy, which was common in the clinical setting, adolescents, adults, females, or patients with intellectual disability, and less common in the country with high human development index.

Antibiotics are commonly used to prevent and control aquaculture diseases. However, long-term overuse of antibiotics not only leaves residues but also leads to changes in the nitrogen cycle in water, which threatens the survival of aquaculture organisms. The current results showed that sulfamethoxazole had no significant effect on the nitrogen cycle process in the actual aquaculture concentration. The inhibitory effect of 1.05 mg/L norfloxacin on ammonia-oxidizing bacteria was significantly greater than that on ammonia-oxidizing archaea, and the gene abundance of AOB amoA on the 14th day increased by 2.48 times compared with the 7th day. Under the influence of 3.9 mg/L oxytetracycline, the gene abundance of AOB amoA decreased significantly, while the number of AOA amoA genes increased, suggesting that there may be functional redundancy between AOA and AOB. At the genus level in the norfloxacin group, the relative abundance of Sva0485 increased by 14.0% on the 7th day compared with the control group but decreased 12.77% in the addition group. The relative abundance of Firmicutes, another dominant species in the oxytetracycline group, was 25.9%. This study shows that the addition of antibiotics may have a negative effect on the nitrogen-cycling microorganisms in aquaculture water.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system. Relapse and incomplete recovery from relapse are common in NMOSD. Most patients with NMOSD have IgG to aquaporin-4 (AQP4-IgG). New biological agents for AQP4-IgG-seropositive NMOSD, such as satralizumab, have become available for maintenance therapy. Satralizumab is an anti-interleukin-6 receptor monoclonal antibody. To date, few studies have evaluated satralizumab as an add-on treatment in pediatric NMOSD patients. Here, we report an 11-year-old girl with NMOSD who frequently relapsed under long-term treatment, including oral prednisone, rituximab, mycophenolate mofetil (MMF), and maintenance intravenous immunoglobulin treatment even with B-cell depletion. For the poor treatment response and to improve the efficacy of relapse prevention further, the patient received satralizumab treatment as an add-on therapy to MMF plus oral prednisone, with a dose of 120 mg administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks after that. After initiating satralizumab, the patient remained relapse-free for 14 months at the last follow-up. Satralizumab might be effective and safe as an add-on treatment in refractory pediatric AQP4-IgG-seropositive NMOSD under B-cell depletion.

Objective In an effort to prevent transfusion-transmitted hepatitis B infection, universal HBsAg screening, HBsAg+ MP nucleic acid test(NAT) for HBV and HBsAg + individual(ID) NAT were analyzed for cost-effectiveness. Methods On the basis of screening data and the documented parameter, the number of window period infections, chronic infections and occult infections was constructed, and cost-benefit analysis was conducted. Results Of 132 208 donations, the yield rate of ID NAT for HBsAg-/DNA+ (0.11%) was significantly higher than HBsAg+ MP NAT(0.058%). Furthermore, the predicted preventing transfusion transmitted HBV cases by ID NAT is 1.25 times as that by MP-6 NAT, so did the benefits. The cost-benefit of the three screening models were 1∶63.6、1∶28.6 and 1∶53.4. Conclusion Universal HBsAg in combination with ID HBV NAT screening was the most effective among all screening strategy. It is necessary to applied HBsAg and ID HBV NAT screening for the safety of blood transfusion.

Abstract With the control parameters of the wall thickness of the ball table and the thickness of the pressure plate of the ball table, four universal wrapped assembled joint models were designed for the research of stress performance via static loading test. The failure mode of the joint, the axial force–displacement curve of the web member, the equivalent stress distribution of the ball table and the pressure plate of the ball table were analyzed, and the ABQAUS finite element software was used for the analysis of parameter expansion of the specimen. The research results show that the failure modes of universally wrapped assembled joints can be divided into the buckling failure of the ball table and the strength failure of the material. The wall thickness of the ball table is the key parameter affecting the failure mode of the joints, and the thickness of the pressure plate of the ball table is the crucial parameter influencing the ultimate bearing capacity of the joints. The maximum equivalent stress of the pressure plate and the ball table at compression zone for all the joints is occurred at the side squeezed by the bolt ball, and the growth rate of the equivalent stress for the ball table at compression zone is more uniform than that at tension zone. According to the finite element analysis results, when the wall thickness of the ball table is greater than 7 mm, the thickness of the pressure plate of the ball table is greater than 16 mm, the growth rate of the ultimate bearing capacity of the joint is significantly decreased, therefore, it is recommended to use the wall thickness of 7 mm and the pressure plate thickness of 16 mm in the actual design of the project.

Abstract Long-chain polyunsaturated fatty acids (LC-PUFA), including eicosapentaenoic acid and docosahexaenoic acid, are the essential fatty acids for organs to maintain various biological functions and processes. The threadfin fish Eleutheronema, with its rich nutritional value especially the high fatty acid contents, has become one of the promising aquaculture species in China and the potential food source of fatty acids for human consumption. However, the molecular basis underlying the biosynthesis of fatty acids in Eleutheronema species is still unknown. The elongation of the very long-chain fatty acids (Elovl) gene family in fish plays several critical roles in LC-PUFA synthesis. Therefore, in the present study, we performed genome-wide identification of the Elovl gene family to study their evolutionary relationships and expression profiles in two threadfin fish species Eleutheronema tetradactylum and Eleutheronema rhadinum, the first representatives from the family Eleutheronema. Phylogenetic analysis revealed that the Elovl genes in Eleutheronema were classified into six subfamilies (elovl1a/1b, elovl4a/4b, elovl5, elovl6/6 l, elovl7a, elovl8b). Phylogenetic, gene structure, motif, and conserved domain analysis indicated that the Elovl genes were highly conserved within the same subfamily in Eleutheronema. In addition, the Elovl genes were distributed in 7/26 chromosomes, while the duplicated gene pair, elovl4a and elovl4b, showed collinear relationships. The predicted secondary structure patterns and the 3D models revealed the highly similar functions and evolutionary conserved structure of Elovl proteins in Eleutheronema. The selection pressure analysis revealed that Elovl genes underwent strong purifying selection during evolution, suggesting that their functions might be evolutionarily conserved in Eleutheronema. Additionally, the expression patterns of Elovl genes in different tissues and species were distinct, indicating the possible functional divergence during evolution in the Eleutheronema genus. Collectively, we provided the first comprehensive genomic information on Elovl genes in threadfin fish Eleutheronema. This study enhanced the understanding of the underlying mechanisms of fatty acids biosynthesis in Eleutheronema, and provided new insights on breeding new varieties of fatty acids-enriched fish with potential benefits to farmers and the health of consumers.

Objectives The operative microscope (OM) has revolutionized the field of modern spine surgery, however, it remains limited by several drawbacks. Recently, the exoscope (EX) system has been designed to assistant spine surgery. It provides a three‐dimensional (3D) high‐definition (HD) operative experience and becomes an alternative to the OM. The aim of the study was to evaluate the clinical outcomes, advantages and limitations of EX‐assisted minimally invasive transforaminal lumbar interbody fusion (EMIS‐TLIF) and OM‐assisted MIS‐TLIF (OMIS‐TLIF). Methods The clinical outcomes were assessed in 47 patients with lumbar degenerative diseases (LDD) who underwent MIS‐TLIF assisted with the OM or EX between January 2019 and September 2020. A total of 22 were treated with EMIS‐TLIF, and 25 received OMIS‐TLIF. Perioperative parameters (including sex, age, number of fusion levels and body mass index), perioperative parameters (operation time, intraoperative blood loss, postoperative drainage, postoperative hospitalization stay, and duration of follow‐up), visual analogue scale (VAS) of back pain, VAS of leg pain, Oswestry disability index (ODI) scores and clinical outcomes were assessed and compared. Image quality, handling of equipment, ergonomics, 3D glasses and educational usefulness were scored according to a questionnaire. Results Operation time in the OMIS‐TLIF group (121.92 ± 16.92 min) was significantly increased compared with that in the EMIS‐TLIF group (111.00 ± 19.87 min) (P

Abstract Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Context Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis.Objective This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism.Materials and methods Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting.Results Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis.Conclusions These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.

Accurate detection of antigen p24 for HIV−1 early diagnosis remains challenging. Here the authors present a click chemistry amplified nanopore (CAN) assay that allows p24 quantification at ultralow concentration range in clinical samples.

Abstract Background Autism spectrum disorder (ASD) is often accompanied by intellectual disability (ID). Despite extensive studies, however, the genetic basis for this comorbidity is still not clear. In this study, we tried to develop an analyzing pipeline for de novo mutations and possible pathways related to ID phenotype in ASD. Whole-exome sequencing (WES) was performed to screen de novo mutations and candidate genes in 79 ASD children together with their parents (trios). The de novo altering genes and relative pathways which were associated with ID phenotype were analyzed. The connection nodes (genes) of above pathways were selected, and the diagnostic value of these selected genes for ID phenotype in the study population was also evaluated. Results We identified 89 de novo mutant genes, of which 34 genes were previously reported to be associated with ASD, including double hits in the EGF repeats of NOTCH1 gene (p.V999M and p.S1027L). Interestingly, of these 34 genes, 22 may directly affect intelligence quotient (IQ). Further analyses revealed that these IQ-related genes were enriched in protein synthesis, energy metabolism, and amino acid metabolism, and at least 9 genes (CACNA1A, ALG9, PALM2, MGAT4A, PCK2, PLEKHA1, PSME3, ADI1, and TLE3) were involved in all these three pathways. Seven patients who harbored these gene mutations showed a high prevalence of a low IQ score (

Abstract Background Metabolic disturbance has been reported in patients with epilepsy. Still, the evidence about the causal role of metabolites in facilitating or preventing epilepsy is lacking. Systematically investigating the causality between blood metabolites and epilepsy would help provide novel targets for epilepsy screening and prevention. Methods We conducted two-sample Mendelian randomization (MR) analysis. Data for 486 human blood metabolites came from a genome-wide association study (GWAS) comprising 7824 participants. GWAS data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium for primary analysis and the FinnGen consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results 482 out of 486 metabolites were included for MR analysis following rigorous genetic variants selection. After IVW and sensitivity analysis filtration, six metabolites with causal effects on epilepsy were identified from the ILAE consortium. Only four metabolites remained significant associations with epilepsy when combined with the FinnGen consortium [uridine: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.48–3.71, P = 0.0003; 2-hydroxystearate: OR = 1.61, 95% CI = 1.19–2.18, P = 0.002; decanoylcarnitine: OR = 0.82, 95% CI = 0.72–0.94, P = 0.004; myo-inositol: OR = 0.77, 95% CI = 0.62–0.96, P = 0.02]. Conclusion The evidence that the four metabolites mentioned above are associated with epilepsy in a causal way provides a novel insight into the underlying mechanisms of epilepsy by integrating genomics with metabolism, and has an implication for epilepsy screening and prevention.

BackgroundTo explore the relationship between autistic clinical profiles and age at first concern and diagnosis among children with autism spectrum disorder. The clinical profiles included the severity of autism, cognition, adaptability, language development, and regression.MethodsThe multivariate linear regression model was used to examine the association of diagnostic age and first-concern age with autistic clinical profiles and with further stratification analysis.ResultsA total of 801 autistic children were included. Language delay and regression were associated with earlier diagnostic age (language delay: crudeβ: −0.80, 95%CI%: −0.92–−0.68; regression: crudeβ: −0.21, 95%CI%: −0.43–−0.00) and the age of first concern of autistic children (language delay: crudeβ: −0.55, 95%CI%: −0.65–−0.45; regression: crudeβ: −0.17, 95%CI%: −0.34–−0.00). After stratification by sex, language delay tended to be more associated with the earlier diagnostic age among boys (crudeβ: −0.85, 95%CI%: −0.98–−0.72) than among girls (crudeβ: −0.46, 95%CI%: −0.77–−0.16). After stratification by maternal education level or family income level, language delay was most associated with the earlier diagnostic age in autistic children from families with higher socioeconomic levels.ConclusionLanguage delay, rather than other symptoms, promoted an earlier diagnostic age. Among male autistic children or children from families with higher socioeconomic levels, language delay was most significantly associated with an earlier age of diagnosis. Cognitive delay, or adaptive delay, was associated with a later age at diagnosis and presented only in autistic children from families with lower socioeconomic levels. There may be sex or socioeconomic inequality in the diagnostic age for autistic children. More publicity and public education about the diversity of autistic symptoms are urgently needed in the future, especially for low-socioeconomic families.

Organic and inorganic substances coexist in the livers of marine mammals and may correlate with one another; however, their coexistence mechanisms and relevant key features remain largely unknown. In this study, temporal variations (2011–2021) in the concentrations of nine trace elements and 19 per- and polyfluoroalkyl substances (PFASs) in the livers of Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) were investigated. Interannual Cd in dolphins increased significantly whereas Pb concentrations decreased over the past decade (p

ObjectiveTo study the clinical features of children diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in southern China.MethodsClinical data of children diagnosed with MOGAD from April 2014 to September 2021 were analyzed.ResultsA total of 93 children (M/F=45/48; median onset age=6.0 y) with MOGAD were involved. Seizures or limb paralysis was the most common onset or course symptom, respectively. The most common lesion locations in brain MRI, orbital MRI, and spinal cord MRI were basal ganglia and subcortical white matter, the orbital segment of the optic nerve, and the cervical segment, respectively. ADEM (58.10%) was the most common clinical phenotype. The relapse rate was 24.7%. Compared with the patients without relapse, relapsed patients had a longer interval from onset to diagnosis (median: 19 days VS 20 days) and higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer positively persistent (median: 3 months VS 24 months). All patients received IVMP plus IVIG at the acute phase, and 96.8% of patients achieved remission after one to three courses of treatment. MMF, monthly IVIG, and maintaining a low dose of oral prednisone were used alone or in combination as maintenance immunotherapy for relapsed patients and effectively reduced relapse. It transpired 41.9% of patients had neurological sequelae, with movement disorder being the most common. Compared with patients without sequelae, patients with sequelae had higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer persistence (median: 3 months VS 6 months) and higher disease relapse rate (14.8% VS 38.5%).ConclusionsResults showed the following about pediatric MOGAD in southern China: the median onset age was 6.0 years, with no obvious sex distribution difference; seizure or limb paralysis, respectively, are the most common onset or course symptom; the lesions of basal ganglia, subcortical white matter, the orbital segment of the optic nerve, and cervical segment were commonly involved in the CNS MRI; ADEM was the most common clinical phenotype; most had a good response to immunotherapy; although the relapse rate was relatively high, MMF, monthly IVIG and a low dose of oral prednisone might effectively reduce relapse; neurological sequelae were common, and possibly associated with MOG antibody status and disease relapse.

The electronic structures of Ge nanowires under the [110] direction stress are calculated via effective-mass k · p theory, and the results manifest eight equivalent L -valleys will be split into fourfold degenerate L _1 -valleys and L _2 -valleys. With increasing stress, the electron levels at the L _1 -valleys and L _2 -valleys can be pushed close to and away from those at the Γ-valley, respectively, which causes the appearance of a rising inflection point in the Γ-valley filling ratio and gain peak intensity at around 2.5 GPa stress. Moreover, we prove the positive net peak gain with small diameters is apt to be obtained considering the free-carrier absorption loss.

With the rapid development of Internet social media,using recommendation algorithms to effectively model and filter massive amounts of information has become the key to predict user behavior preferences,hot spot tendency,network security si-tuation and other issues.At the same time,with the development of deep learning,graph neural network model has achieved good results in solving the dense graph structure data in recommendation system.Collaborative filtering algorithm,as the most widely used recommendation algorithm,uses user-item group interaction data to predict users' future preferences and item ratings.However,existing recommendation algorithms still face the problems of data sparseness and cold start,and lack of a good quantification of uncertainty.This paper proposes an inductive matrix completion prediction fusion algorithm based on probabilistic meta-learning(MetaIMC),which re-characterizes meta-learning from the perspective of Bayesian inference,builds a robust GNN-meta-learning model,and makes full use of data priors to build solutions for learning new tasks from sparse data.Firstly,MetaIMC can effectively use variational Bayesian inference to obtain the prior distribution,alleviate the uncertainty and ambiguity in the meta-model task training,and further improve the generalization ability of the model.Secondly,MetaIMC can implement new user reco-mmendations and solve the cold start problem without any user side information.Finally,in the two scenarios of traditional matrix completion and user cold start,the performance of the model is evaluated by using three public datasets of Flixster,Douban and Yahoo_music,which verifies the effectiveness of MetaIMC on traditional matrix completion task,and achieves the best performance on the cold start problem.

Anemia is a common complication of chronic kidney disease (CKD), and its prevalence rises as the disease progresses. Intravenous or subcutaneous erythropoiesis-stimulating agents (ESAs) are advised to treat CKD-associated anemia, since shortage of erythropoietin (EPO) and iron are the main cause of anemia. However, ESA resistance and safety have spurred a lot of interest in the development of alternate anemia therapies. Roxadustat, an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that increases erythropoiesis and may modulate iron metabolism, was recently licensed in China, Chile, South Korea, Japan and the European Union for the treatment of CKD-related anemia. Despite this, clinical trials have shown a number of adverse effects, including cardiovascular disease, hyperkalemia, and infections. In addition, of concern is roxadustat's possible effects on other organs and systems. In this review, based on clinical evidence, we discuss the potentially detrimental effects of roxadustat to the known biology on systems other than kidney, and the need for long-term follow-up in order for roxadustat to be approved in more countries in the future.

The occurrence of cyanobacterial blooms in summer are frequently accompanied by the succession of phytoplankton communities in freshwater. However, little is known regarding the roles of viruses in the succession, such as in huge reservoirs. Here, we investigated the viral infection characteristics of phytoplankton and bacterioplankton during the summer bloom succession in Xiangxi Bay of Three Gorges Reservoir, China. The results indicated that three distinct bloom stages and two successions were observed. From cyanobacteria and diatom codominance to cyanobacteria dominance, the first succession involved different phyla and led to a Microcystis bloom. From Microcystis dominance to Microcystis and Anabaena codominance, the second succession was different Cyanophyta genera and resulted in the persistence of cyanobacterial bloom. The structural equation model (SEM) showed that the virus had positive influence on the phytoplankton community. Through the Spearman’s correlation and redundancy analysis (RDA), we speculated that both the increase of viral lysis in the eukaryotic community and the increase of lysogeny in cyanobacteria may contributed to the first succession and Microcystis blooms. In addition, the nutrients supplied by the lysis of bacterioplankton might benefit the second succession of different cyanobacterial genera and sustain the dominance of cyanobacteria. Based on hierarchical partitioning method, the viral variables still have a marked effect on the dynamics of phytoplankton community, although the environmental attributes were the major factors. Our findings suggested that viruses played multiple potential roles in summer bloom succession and may help the blooms success of cyanobacteria in Xiangxi Bay. Under the background of increasingly serious cyanobacterial blooms worldwide, our study may have great ecological and environmental significance for understanding the population succession in phytoplankton and controlling the cyanobacterial blooms.