Search

Objective: Current evidence shows the master of physical education has attracted attention since its opening. The study aims to quantify recent trends in the public interest and related online search behavior for master of physical education, and “nowcast” future scenarios with respect to the master of physical education. Methods: Baidu Index, a database of search engines with massive information, was employed. By searching for the keyword master of physical education, and using content analysis to understand the data information related to master of physical education. It extracted the search trend data regarding Chinese interest in the master of physical education from November 21, 2016, to November 21, 2022. Finally, it compares the search trend of search interests in the master of physical education with related terms. Results: It found that the search trend of master of physical education was on the rise overall. Specifically, the peak value appeared in September 2019, the valley value appeared around the Spring Festival each year, and the search trend in other periods was stable. Conclusion: The raise in public interest in a master of physical education will likely result in an increase in the number of candidates who are going to attend the National Graduate Entrance Exam to pursue a master of physical education. In the coming months or more, the competition for the employment of sports professionals in China will become more intense. Affected by the COVID-19, more people are interested in health and physical exercise, and then pay attention to the Master of Physical Education. The Sports Law of the People's Republic of China has been revised recently, which has led to more people interested in the master of physical education.

IntroductionThe transcription factor WRKY is widespread in the plant kingdom and plays a crucial role in diverse abiotic stress responses in plant species. Tritipyrum, an octoploid derived from an intergeneric cross between Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is a valuable germplasm resource for introducing superior traits of Th. elongatum into T. aestivum. The recent release of the complete genome sequences of T. aestivum and Th. elongatum enabled us to investigate the organization and expression profiling of Tritipyrum WRKY genes across the entire genome.ResultsIn this study, 346 WRKY genes, from TtWRKY1 to TtWRKY346, were identified in Tritipyrum. The phylogenetic analysis grouped these genes into three subfamilies (I-III), and members of the same subfamilies shared a conserved motif composition. The 346 TtWRKY genes were dispersed unevenly across 28 chromosomes, with 218 duplicates. Analysis of synteny suggests that the WRKY gene family may have a common ancestor. Expression profiles derived from transcriptome data and qPCR demonstrated that 54 TtWRKY genes exhibited relatively high levels of expression across various salt stresses and recovery treatments. Tel1E01T143800 (TtWRKY256) is extremely sensitive to salt stress and is on the same evolutionary branch as the salt-tolerant A. thaliana genes AtWRKY25 and AtWRKY33. From 'Y1805', the novel AtWRKY25 was cloned. The Pearson correlation analysis identified 181 genes that were positively correlated (R>0.9) with the expression of TtWRKY256, and these genes were mainly enriched in metabolic processes, cellular processes, response to stimulus, biological regulation, and regulation of biological. Subcellular localization and qRT-PCR analysis revealed that TtWRKY256 was located in the nucleus and was highly expressed in roots, stems, and leaves under salt stress.DiscussionThe above results suggest that TtWRKY256 may be associated with salt stress tolerance in plants and may be a valuable alien gene for improving salt tolerance in wheat.

BackgroundOccupational noise is one of the most common and prevalent occupational hazards worldwide and may induce adverse auditory and/or non-auditory health effects. However, the relationship between occupational noise exposure and hypertension is controversial and has long been debated.MethodsBased on large sample cross-sectional data from all registered occupational health examination units from 2021 to 2022 (N = 101,605), this study aimed to analyze the prevalence of hearing loss and hypertension and to explore the influencing factors of hypertension of workers in Wuhan. Descriptive statistics, univariate analyses and multivariate analyses were used. Forest plot and nomograms were constructed for the visualization of predictive results. The ROC curve, AUC, C-index and calibration curves were used to assess the predictive accuracy and validity. DCA was performed to evaluate the net benefit that workers could receive.ResultsHigher rate of high-frequency hearing loss (25.3%), speech frequency hearing loss (8.8%), ECG abnormalities (31.9%) and hypertension (21.0%) were found in workers exposed to occupational noise in Wuhan. Occupational noise exposure (OR = 1.09, 95% CI: 1.01–1.18, p = 0.04), growth of age (OR: 1.07, 95% CI: 1.07–1.07, p < 0.001), overweight (OR: 1.82, 95% CI: 1.73–1.92, p < 0.001), obesity (OR: 3.62, 95% CI: 3.42–3.83, p < 0.001), hyperglycemia (OR: 1.84, 95% CI: 1.73–1.96, p < 0.001), hypercholesterolemia (OR = 1.34; 95% CI 1.22–1.48; p < 0.001), ECG abnormalities (OR = 1.11; 95% CI 1.07–1.15; p < 0.001) and family history of hypertension (OR = 1.69; 95% CI 1.58–1.81; p < 0.001) were risk factors of hypertension for workers. Male workers had a relatively higher hypertension risk than female workers (OR = 1.61; 95% CI 1.54–1.69; p < 0.001). Ear protective measures could not reduce the risk of hypertension in workers. Our nomogram has good predictive accuracy and validity. A dynamic nomogram to predict the workers' risk of hypertension was established publicly available online.ConclusionOccupational noise exposure may elevate workers' hypertension risk. More effective and relevant prevention measures should be taken. Our nomogram may help identify high-risk workers and facilitate timely interventions.

As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts in vitro. Since then, the intestinal organoid technology has been used to delineate cellular signaling in ISC biology. However, the cultured organoids consist of heterogeneous cell populations, and it was technically challenging to introduce genomic changes into three-dimensional organoids. Thus, there was a technical necessity to develop a two-dimensional ISC culture system for effective genomic manipulations. In this study, we established a conditionally immortalized mouse intestinal crypt (ciMIC) cell line by using a piggyBac transposon-based SV40 T antigen expression system. We showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition, retained the biological characteristics of intestinal epithelial stem cells, and could form intestinal organoids in three-dimensional culture. While in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic, the ciMICs overexpressing oncogenic β-catenin and/or KRAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in vivo. Collectively, these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

Abstract Introduction Given that many pregnant women have chronic hepatitis B virus (HBV) infection and that gestational diabetes mellitus (GDM) is linked to poor maternal and neonatal outcomes, we looked into the relationship between the hepatitis B surface antigen (HBsAg) and GDM to see if a high HBV DNA load is linked to a higher risk of GDM in chronic maternal HBsAg carriers. Materials and methods Our study included 39,539 pregnant women who gave birth at the Third Affiliated Hospital of Guangzhou Medical University in Guangzhou, China, between January 1, 2009, and December 31, 2019. The patients were divided into two groups: HBsAg negative (36,500) and positive (3039). The viral load levels of 1250 HBsAg-positive women who had tested their HBV DNA load during pregnancy were separated into three groups. We utilized univariate and multivariable logistical regression analysis to determine the relationship between maternal chronic HBsAg carrier and GDM. Results Being HBsAg positive was discovered to be an independent risk factor for GDM.Pre-pregnancy Obesity and advanced age were linked to an increased incidence of GDM. Those with a high HBV DNA load (> 106 IU/mL) had a higher risk of GDM than HBsAg-positive women with a low viral load (

Abstract QseC, a histidine sensor kinase of the QseBC two-component system, acts as a global regulator of bacterial stress resistance, biofilm formation, and virulence. The function of QseC in some bacteria is well understood, but not in Pasteurella multocida. We found that deleting qseC in P. multocida serotype A:L3 significantly down-regulated bacterial virulence. The mutant had significantly reduced capsule production but increased resistance to oxidative stress and osmotic pressure. Deleting qseC led to a significant increase in qseB expression. Transcriptome sequencing analysis showed that 1245 genes were regulated by qseC, primarily those genes involved in capsule and LPS biosynthesis and export, biofilm formation, and iron uptake/utilization, as well as several immuno-protection related genes including ompA, ptfA, plpB, vacJ, and sodA. In addition to presenting strong immune protection against P. multocida serotypes A:L1 and A:L3 infection, live ΔqseC also exhibited protection against P. multocida serotype B:L2 and serotype F:L3 infection in a mouse model. The results indicate that QseC regulates capsular production and virulence in P. multocida. Furthermore, the qseC mutant can be used as an attenuated vaccine against P. multocida strains of multiple serotypes.

Abstract Background Brain metastasis (BM) is thought to be related to the mortality and poor prognosis of non-small cell lung cancer (NSCLC). Despite promising development of NSCLC treatment, the treatment of NSCLC BM is still not optimistic due to the existence of the blood-brain barrier (BBB) that prevent drug penetration, as well as the short median survival time of the patients left for treatment. In this context, further development of quick and effective pre-clinical models is needed in NSCLC BM treatment. Here, we report a model system using zebrafish to promote the development of drugs for patients with NSCLC BM. Methods Three different NSCLC cell lines (H1975, A549 and H1299) were used to establish zebrafish BM models. The embryo age and cell number for injection were first optimized. Metastatic cells were observed in the brain blood vessels of zebrafish and were verified by hematoxylin-eosin (HE) staining. Then, the metastasis potentials of H1975 and A549 with manipulated microRNA-330-3p (miR-330-3p) expression were also investigated. Finally, sensitivities of H1975 and A549 to osimertinib and gefitinib were tested. Results This zebrafish BM model could distinguish NSCLC cell lines with different BM potential. Over-expressed miR-330-p significantly improved the BM potential of the A549 cells while knockdown miR-330-p reduced the BM ability of the H1975 cells. Both osimertinib and gefitinib showed inhibition effect in zebrafish BM model with the inhibition rate higher than 50 %. H1975 cell showed much higher sensitivity to osimertinib rather than gefitinib both in vivo and in vitro. Conclusions We established zebrafish brain metastasis model for studying mechanism and treatment of NSCLC BM. This study provided a useful model for NSCLC brain metastasis that could be used to study the mechanism that drive NSCLC cells to the brain as well as identify potential therapeutic options.

Abstract Background Trees such as Populus are planted extensively for reforestation and afforestation. However, their successful establishment greatly depends upon ambient environmental conditions and their relative resistance to abiotic and biotic stresses. Polyphenol oxidase (PPO) is a ubiquitous metalloproteinase in plants, which plays crucial roles in mediating plant resistance against biotic and abiotic stresses. Although the whole genome sequence of Populus trichocarpa has long been published, little is known about the PPO genes in Populus, especially those related to drought stress, mechanical damage, and insect feeding. Additionally, there is a paucity of information regarding hormonal responses at the whole genome level. Results A genome-wide analysis of the poplar PPO family was performed in the present study, and 18 PtrPPO genes were identified. Bioinformatics and qRT-PCR were then used to analyze the gene structure, phylogeny, chromosomal localization, gene replication, cis-elements, and expression patterns of PtrPPOs. Sequence analysis revealed that two-thirds of the PtrPPO genes lacked intronic sequences. Phylogenetic analysis showed that all PPO genes were categorized into 11 groups, and woody plants harbored many PPO genes. Eighteen PtrPPO genes were disproportionally localized on 19 chromosomes, and 3 pairs of segmented replication genes and 4 tandem repeat genomes were detected in poplars. Cis-acting element analysis identified numerous growth and developmental elements, secondary metabolism processes, and stress-related elements in the promoters of different PPO members. Furthermore, PtrPPO genes were expressed preferentially in the tissues and fruits of young plants. In addition, the expression of some PtrPPOs could be significantly induced by polyethylene glycol, abscisic acid, and methyl jasmonate, thereby revealing their potential role in regulating the stress response. Currently, we identified potential upstream TFs of PtrPPOs using bioinformatics. Conclusions Comprehensive analysis is helpful for selecting candidate PPO genes for follow-up studies on biological function, and progress in understanding the molecular genetic basis of stress resistance in forest trees might lead to the development of genetic resources.

Abstract Background Pulmonary tuberculosis (PTB) remains the world’s deadliest infectious killer. Serum CA-125 test are useful in the diagnosis of PTB. Although studies on the relation between CA-125 and PTB have been reported, the specificity and sensitivity of serum CA-125 in diagnosing PTB vary widely among different studies. The present study was performed to evaluate the accuracy of CA-125 for the diagnosis of PTB via a meta-analysis of data obtained from previous studies. Methods English and Chinese medical electronic databases were searched for eligible studies published up to February 2020. STATA software was used to obtain a pooled estimation of the diagnostic accuracy of CA-125 and analyze the heterogeneity of the recruited studies. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the obtained studies. Results A total of 16 articles were included in this study. The pooled sensitivity and specificity of CA-125 were 0.85 [95% confidence interval (CI) 0.75–0.91] and 0.87 (95% CI 0.78–0.93), respectively. Moreover, the pooled positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR) of CA-125 were 6.65 (95% CI 3.62–12.20), 0.18 (95% CI 0.10–0.31), and 37.82 (95% CI 13.17–108.60), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.93. Conclusions Taken together, the results indicate that serum CA-125 presents potential practical value for diagnosing PTB, but its clinical applicability must be further examined.

Abstract Background Lupus enteritis (LEn) is a rare complication of systemic lupus erythematosus (SLE). Timely diagnosis and treatment of LEn are necessary to prevent the most serious consequences — intestinal perforation, gastrointestinal bleeding, and death. We compared the clinical features of SLE patients with and without LEn. Methods The clinical data of LEn inpatients at Suining Central Hospital from July 2012 to June 2020 were examined. These LEn patients were matched (1:2 ratio) with concurrently hospitalized SLE patients who did not have LEn. The two groups were compared using multivariate logistic regression. Results We compared SLE inpatients with LEn (n = 43) and SLE inpatients without LEn (n = 86) at our institution. Multivariate logistic regression showed that ascites (odds ratio [OR]: 9.961, 95%CI: 2.215–44.802, P = 0.003), hydronephrosis (OR: 28.060, 95%CI: 2.303–341.962, P = 0.009), leukopenia (OR: 5.890, 95%CI: 1.813–19.135, P = 0.003), reduced complement C3 level (OR: 4.791, 95%CI: 1.605–14.300, P = 0.005), and elevated immunoglobin (Ig)A level (OR: 4.040, 95%CI: 1.307–12.487, P = 0.015) were independently associated with LEn. Within the LEn group, abdominal pain was the most common abdominal symptom (88.4%), and increased mesenteric fat attenuation (74.4%) and bowel wall thickening (58.1%) were the most common computed tomography (CT) findings. Most LEn patients (88.4%) required high-dose glucocorticoid therapy (≥ 80 mg methylprednisolone/day), and cyclophosphamide was the most commonly used immunosuppressant (62.8%). Conclusions Abdominal pain was the most common clinical symptom of LEn. Abdominal CT provides important information for detection and diagnosis of LEn. Ascites, hydronephrosis, leukopenia, hypocomplementemia (C3), and increased IgA were independently associated with LEn.

Abstract Background Stem CO2 efflux (E S) plays a critical role in the carbon budget of forest ecosystems. Thinning is a core practice for sustainable management of plantations. It is therefore necessary and urgent to study the effect and mechanism of thinning intensity (TI) on E S. Methods In this study, five TIs were applied in Larix principis-rupprechtii Mayr 21-, 25-, and 41-year-old stands in North China in 2010. Portable infrared gas analyzer (Li-8100 A) was used to measure E S and its association with environmental factors at monthly intervals from May to October in 2013 to 2015. In addition, nutrients, wood structure and nonstructural carbon (NSC) data were measured in August 2016. Results The results show that E S increased with increasing TI. The maximum E S values occurred at a TI of 35 % (3.29, 4.57 and 2.98 µmol∙m-2∙s-1) and were 1.54-, 1.94- and 2.89-fold greater than the minimum E S value in the CK stands (2.14, 2.35 and 1.03 µmol∙m-2∙s-1) in July for the 21-, 25- and 41-year-old forests, respectively. The E S of the trees in low-density stands was more sensitive to temperature than that of the trees in high-density stands. Soluble sugars (SS) and temperature are the main factors affecting E S. When the stand density is low enough as 41-year-old L. principis-rupprechtii forests with TI 35 %, bark thickness (BT) and humidity should be considered in addition to air temperature (T a), wood temperature (T w), sapwood width (SW), nitrogen concentration (N) and SS in the evaluation of E S. If a change in stand density is ignored, the CO2 released from individual 21-, 25- and 41-year-old trees could be underestimated by 168.89 %, 101.94 % and 200.49 %, respectively. CO2 release was estimated based on the stem equation in combination with the factors influencing E S for reference. Conclusions We suggest that it is not sufficient to conventional models which quantify E S only by temperature and that incorporating the associated drivers (e.g. density, SS, SW and N) based on stand density into conventional models can improve the accuracy of E S estimates.

In this study we aimed to determine whether treatment with maternal Bifidobacterium bifidum TMC3115 could affect the composition of the gut microbiota and the development of the immune system and intestinal tract of offspring, and protect the offspring from IgE-mediated allergic disease. Pregnant BALB/c mice were gavaged with TMC3115 until delivery. Offspring were sensitized with ovalbumin from postnatal days 21 to 49. After maternal treatment with TMC3115, the microbiota of the offspring’s feces, intestinal contents, and stomach contents (a proxy for breast milk) at the newborn and weaning stages exhibited the most change, and levels of immunoglobulin in the sera and stomach contents and of splenic cytokines, as well as the mRNA levels of colonic intestinal development indicators were all significantly altered in offspring at different stages. After sensitization with ovalbumin, there were no significant changes in the levels of serum IgE or ovalbumin-specific IgE/IgG1 in the TMC3115 group; however, IgM, the expression of intestinal development indicators, and the production of fecal short chain fatty acid (SCFA) were significantly increased, as were the relative abundances of Lactobacillus and the Lachnospiraceae NK4A136 group. Our results suggested that maternal treatment with TMC3115 could have a profound modulatory effect on the composition of the gut microbiota and the development of the immune system and intestinal tissue in offspring at different stages of development, and may induce immune tolerance to allergens in ovalbumin-stimulated offspring by modulating the gut microbiota and SCFA production.

ObjectiveExcessive carbohydrate intake is a high risk factor for increased morbidity of type 2 diabetes (T2D). A novel regimen for the dietary care of diabetes that consists of a highly active α-amylase inhibitor derived from white common bean extract (WCBE) and sufficient carbohydrates intake was applied to attenuate T2D and its complications. Furthermore, the role of gut microbiota in this remission was also investigated.MethodsWe conducted a 4-month randomized double-blinded placebo-controlled trial. During the intense intervention period, ninety subjects were randomly assigned to the control group (Group C) and WCBE group (Group W). Subjects in Group C were supplemented with 1.5 g of maltodextrin as a placebo. Subjects in Group W took 1.5 g of WCBE half an hour before a meal. Fifty-five participants continued the maintenance intervention receiving the previous dietary intervention whereas less frequent follow-up. The variation in biochemical, vasculopathy and neuropathy indicators and the structure of the fecal microbiota during the intervention was analyzed.ResultGlucose metabolism and diabetic complications showed superior remission in Group W with a 0.721 ± 0.742% decline of glycosylated hemoglobin after 4 months. The proportion of patients with diabetic peripheral neuropathy (Toronto Clinical Scoring System, TCSS ≥ 6) was significantly lower in Group W than in Group C. Both the left and right sural sensory nerve conduction velocity (SNCV-left sural and SNCV-right sural) slightly decreased in Group C and slightly increased in Group W. Additionally, the abundances of Bifidobacterium, Faecalibacterium and Anaerostipes were higher in Group W, and the abundances of Weissella, Klebsiella, Cronobacter and Enterobacteriaceae_unclassified were lower than those in Group C at month 2. At the end of month 4, Bifidobacterium remained more abundant in Group W.ConclusionTo our knowledge, this is the first report of improvement to diabetes complications by using a dietary supplement in such a short-term period. The enrichment of SCFA-producing bacteria might be responsible for the attenuation of T2D and its complications.Clinical trial registration numberhttp://www.chictr.org.cn/edit.aspx?pid=23309&htm=4, identifier ChiCTR-IOR-17013656

This study aims to understand the temporal and spatial characteristics of public concern for "children's mental health" in China in the context of the COVID-19 epidemic. Baidu Index is a research tool to collect and analyze massive data on Chinese netizens' behaviors. Using Baidu Index as the research tool, this paper analyzes the trend and distribution of Chinese netizens' attention to "children's mental health" from December 1st, 2019 to March 20th, 2022 from three aspects of trend research, demand map, and crowd portrait. The study found that since the outbreak of COVID- 19, the search trend of "children's mental health" has shown a cyclical change, peaking in May and valley around the Spring Festival and National Day, and stable in other periods. "Mental health", "handwritten newspaper on mental health" and "youth mental health" are the most popular buzzwords among the public. The groups concerned with "children's mental health" is mainly distributed in Guangdong, Jiangsu, Beijing, and the majority are women between 30 and 39 years old. Meanwhile, search trends for "mental health" are like that for "children's mental health." The factors influencing the search volume change of "children's mental health" include Chinese traditional holidays, Spring Festival, National Day, Chinese Mental Health Day, and policies and instructions on children's mental health issued by the PRC Ministry of Education. The public would like to know about "mental health", "handwritten newspaper on mental health" and "adolescent mental health".

BackgroundAttention-deficit/hyperactive disorder (ADHD) is a neurodevelopmental disorder that commonly occurs in children with a prevalence ranging from 3.4 to 7.2%. It profoundly affects academic achievement, well-being, and social interactions. As a result, this disorder is of high cost to both individuals and society. Despite the availability of knowledge regarding the mechanisms of ADHD, the pathogenesis is not clear, hence, the existence of many challenges especially in making correct early diagnosis and provision of accurate management.ObjectivesWe aimed to review the pathogenic pathways of ADHD in children. The major focus was to provide an update on the reported etiologies in humans, animal models, modulators, therapies, mechanisms, epigenetic changes, and the interaction between genetic and environmental factors.MethodsReferences for this review were identified through a systematic search in PubMed by using special keywords for all years until January 2022.ResultsSeveral genes have been reported to associate with ADHD: DRD1, DRD2, DRD4, DAT1, TPH2, HTR1A, HTR1B, SLC6A4, HTR2A, DBH, NET1, ADRA2A, ADRA2C, CHRNA4, CHRNA7, GAD1, GRM1, GRM5, GRM7, GRM8, TARBP1, ADGRL3, FGF1, MAOA, BDNF, SNAP25, STX1A, ATXN7, and SORCS2. Some of these genes have evidence both from human beings and animal models, while others have evidence in either humans or animal models only. Notably, most of these animal models are knockout and do not generate the genetic alteration of the patients. Besides, some of the gene polymorphisms reported differ according to the ethnic groups. The majority of the available animal models are related to the dopaminergic pathway. Epigenetic changes including SUMOylation, methylation, and acetylation have been reported in genes related to the dopaminergic pathway.ConclusionThe dopaminergic pathway remains to be crucial in the pathogenesis of ADHD. It can be affected by environmental factors and other pathways. Nevertheless, it is still unclear how environmental factors relate to all neurotransmitter pathways; thus, more studies are needed. Although several genes have been related to ADHD, there are few animal model studies on the majority of the genes, and they do not generate the genetic alteration of the patients. More animal models and epigenetic studies are required.

Myasthenia gravis is an organ-specific autoimmune disease. Currently there is no universal guidelines for childhood-onset myasthenia gravis, therefore, treatment strategies are usually based on the guidelines from adult myasthenia gravis patients. In order to contribute in the process of the development of the universal childhood-onset myasthenia gravis guideline, we have summarized the clinical characteristics, treatment strategies, outcome and the related predictors of childhood-onset myasthenia gravis. We recruited 343 childhood-onset myasthenia gravis cases who were followed up at the Department of Pediatrics, Xiangya Hospital from June, 2010 to December, 2019. The data about clinical characteristics, treatments and outcome were collected and analyzed. Among of the 343 cases, 164 cases were followed up for longer than 2 years, of whom 142 still remained with ocular myasthenia gravis at the endpoint. About the treatments, 27 cases (27/164) accepted pyridostigmine only while the rest accepted glucocorticoid and/or other immunosuppressants. At the endpoint, the proportion of optimal outcome was 66.2% in the group remaining with ocular myasthenia gravis and 31.8% in the generalized myasthenia gravis group. Multivariate logistic regression analysis revealed that generalized myasthenia gravis type and positive status of antibodies against acetylcholine receptors were the independent risk factors for poor outcome. In conclusion, our childhood-onset myasthenia gravis patients present mainly as ocular myasthenia gravis, adequate immunotherapy improve the long-term outcome, and generalized myasthenia gravis phenotype as well as positive status of antibodies against acetylcholine receptors relate to poor outcome.

BackgroundIntracranial hypotension (IH) is usually associated with cerebrospinal fluid (CSF) leakage and/or CSF hypotension, and epidural blood patch (EBP) therapy has been proven to be effective for treating spontaneous IH and post-dural puncture headaches. Tarlov cysts (TCs) are common lesions of the sacral spine. They have rarely been reported in thoracic locations and are even less common in the posterior mediastinum, which can lead to their misdiagnosis as neurogenic tumors.Case presentationHere, we report the case of a 60-year-old woman who developed an orthostatic headache after the thoracoscopic resection of a TC in the posterior mediastinum that was presumed to be a schwannoma preoperatively. The patient was finally diagnosed with IH caused by a subarachnoid-pleural fistula (SPF) and was cured by targeted EBP treatment.ConclusionThis is a case to show that a single targeted EBP treatment is effective for a patient with IH caused by an SPF after thoracoscopic resection of a TC. This case reminds us to be vigilant that a TC may be masquerading as a posterior mediastinal neurogenic tumor, and a detailed examination should be performed to identify it before deciding on a surgical procedure. In addition, postural headache after thoracoscopic spinal surgery should be alert to the possibility of IH induced by an SPF. Once it occurs, early treatment is necessary, and targeted EBP treatment can serve as a safe and effective alternative when conservative treatment fails.

The effective use of environmental covariates in characterizing soil–environment relationships is key to successful digital soil mapping. The typical way to use environmental covariates in digital soil mapping is by selecting diverse environmental covariates considering the overall geographical characteristics of the study area and considering these covariates to have consistent applicability across the whole area. However, this practice ignores the fact that the applicability of each environmental covariate in characterizing soil–environment relationships varies over complex environmental conditions, especially in large areas. This study proposed a method to adaptively consider covariate applicability in large-area digital soil mapping using soil–environment relationships. The applicability of each covariate at each location was quantified from the terrain conditions using the newly designed fuzzy functions in the study. Then the covariate applicability was regarded as the importance weight and integrated into an existing representative method, iPSM (individual predictive soil mapping). The integration was separately performed at the similarity calculation and soil estimation stages of iPSM to generate two new methods: iPSM weighting on the applicability of all covariates (iPSM_WCovar_all), and iPSM weighting on the applicability of the limiting covariate (i.e., the covariate with the minimum similarity between two locations that constrains the overall similarity) (iPSM_WCovar_limit). Experiments were carried in Anhui Province, China. The two new methods were used to predict the soil organic matter content of topsoil and outperformed the original iPSM and random forest kriging methods. The root mean square error of the iPSM_WCovar_all, iPSM_WCovar_limit, iPSM and random forest kriging methods were 8.14, 8.00, 8.88 and 9.65 g/kg, respectively, while the mean absolute error of those methods were 6.48, 6.31, 6.61 and 6.82 g/kg. Both proposed methods outperformed the iPSM method and the other commonly used method, i.e., random forest kriging. Moreover, the performance was stable under different parameter settings. Experimental results indicate that the idea of adaptively considering covariate applicability in digital soil mapping is feasible and effective.

Arthrinium phaeospermum is the main pathogen that causes Bambusa pervariabilis × Dendrocalamopsis grandis blight. It secretes the cutinase transcription factor ApCtf1β, which has been shown to play an important role in B. pervariabilis × D. grandis virulence. However, knowledge about the interaction target genes of ApCtf1β in B. pervariabilis × D. grandis remains limited. A cDNA library for the yeast two-hybrid system was constructed from B. pervariabilis × D. grandis shoots after 168 h treatment with A. phaeospermum. The library was identified as 1.20 × 107 cfu, with an average insert >1,000 bp in size and a 100% positive rate, providing a database for the subsequent molecular study of the interaction between A. phaeospermum and B. pervariabilis × D. grandis. The yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and glutathione-S-transferase (GST) pull-down assays were used to screen for and identify two ApCtf1β interacting target proteins, BDUbc and BDSKL1, providing a reliable theoretical basis to study the molecular mechanism underlying B. pervariabilis × D. grandis resistance in response to A. phaeospermum, which would, in turn, establish a platform to develop new strategies for the sustainable and effective control of the blight diseases of forest trees.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, associated with an outcome of hepatic fibrosis/cirrhosis and hepatocellular carcinoma. However, limited exploration of the underlying mechanisms hinders its prevention and treatment. To investigate the mechanisms of epigenetic regulation in NAFLD, the expression profile of circular RNA (circRNA) of rodents in which NAFLD was induced by a high-fat, high-cholesterol (HFHC) diet was studied. Modeling of the circRNA-microRNA (miRNA) -mRNA regulatory network revealed the functional characteristics of NAFLD-specific circRNAs. The targets and effects in the liver of such NAFLD-specific circRNAs were further assessed. Our results uncovered that the downregulation of 28 annotated circRNAs characterizes HFHC diet-induced NAFLD. Among the downregulated circRNAs, long intergenic non-protein coding RNA, P53 induced transcript (LNCPINT) -derived circRNAs (circ_0001452, circ_0001453, and circ_0001454) targeted both miR-466i-3p and miR-669c-3p. Their deficiency in NAFLD abrogated the circRNA-based inhibitory effect on both miRNAs, which further inactivated the AMPK signaling pathway via AMPK-α1 suppression. Inhibition of the AMPK signaling pathway promotes hepatic steatosis, depending on the transcriptional and translational upregulation of lipogenic genes, such as those encoding sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) in hepatocytes. The levels of LNCPINT-derived circRNAs displayed a negative association with hepatic triglyceride (TG) concentration. These findings suggest that loss of LNCPINT-derived circRNAs may underlie NAFLD via miR-466i-3p- and miR-669c-3p-dependent inactivation of the AMPK signaling pathway.

Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.

Both nitrogen (N) deposition and heavy metal pollution are important environmental concerns that threaten ecosystem stability and ecological safety. Limited research has been conducted on the effects of N deposition on the physiological processes and allocation patterns of heavy metals (HMs) in poplars, especially under combined pollution. In our study, we used Populus deltoides as a model to investigate the effects of two levels of N addition (LN, 6 g N·m−2·a−1; HN, 12 g N·m−2·a−1) on growth, activities of antioxidant enzymes, profiles of low-molecular-weight organic acids, as well as accumulation and allocation of HMs among different organs and root orders under single Cd (30 mg kg−1) or Mn pollution (168.6 mg kg−1), and their combination. The effects of N addition depended on the dosage effects of N and the types of HMs. The combined pollution did not have more negative effects on overall growth and oxidative damage in the root tips of P. deltoides compared to single Cd or Mn pollution. Both levels of N deposition, especially LN, promoted growth in P. deltoides to varying extents under all HM pollution conditions. However, N addition only mitigated oxidative damage to the fine roots under Cd-containing pollution, which may be attributed to higher levels of low-molecular-weight organic acids such as citric acid and malic acid. In contrast, HN decreased the levels of key organic acids, such as lactic acid and pantothenic acid, potentially exacerbating Mn toxicity under Mn pollution. Both levels of N addition decreased the total amount of Cd accumulated in P. deltoides under Cd pollution alone but increased the accumulation of Cd in combined pollution (especially under LN). However, under Mn-containing pollution, the addition of N increased the accumulation of Mn and its transfer to leaves, potentially aggravating Mn toxicity. Therefore, N deposition, especially under HN, may lead to more severe HM stress for plants in soils polluted by combined Cd and Mn.

Dairy mastitis is an inflammatory reaction caused by mechanical injury and stress within the mammary gland, during which microbial changes and abnormal lipid metabolism occur. However, the underlying mechanism is still unclear. The present study used a combination of 16S rDNA sequencing technology and lipidomics techniques to reveal the effects of mastitis on lactic microbiota and metabolites in the milk of dairy cows. Twenty multiparous Holstein dairy cows (2–3 parities) with an average body weight of 580 ± 30 kg were selected for this study. The dairy cows were allocated to control group (4 cells /mL)) and mastitis group (>5 × 106 cells /mL) based on the somatic cell count. The results showed that mastitis caused a decrease trend in milk production (p = 0.058). The results of the 16 s sequencing indicated a significant decrease (p < 0.05) in the number of Proteobacteria, Tenericutes colonized in mastitis milk, and the number of Firmicutes, Bacteroidetes and Actinobacteria communities increased significantly (p < 0.05). The lipidomics results revealed that the changes in lipid content in mastitis milk were correlated with arachidonic acid metabolism, α -linolenic acid metabolism and glycerol phospholipid metabolism. The results showed that mastitis may cause abnormal lipid metabolism in milk by regulating the diversity of milk microflora, and ultimately affect the milk quality.

Titanium alloy Ti6Al4V is a commonly used bone implant material, primarily prepared as a porous material to better match the elastic modulus of human bone. However, titanium alloy is biologically inert and does not have antibacterial properties. At the same time, the porous structure with a large specific surface area also increases the risk of infection, leading to surgical failure. In this paper, we prepared three porous samples with different porosities of 60%, 75%, and 85%, respectively (for short, 3D-60, 3D-75, and 3D-85) using 3D printing technology and clarified the mechanical properties. Through tensile experiments, when the porosity was 60%, the compressive modulus was within the elastic modulus of human bone. Anodic oxidation technology carried out the surface modification of a 3D-printed porous titanium alloy with 60% porosity. Through change, the different voltages and times on the TiO2 oxide layer on the 3D-printed porous titanium alloy are different, and it reveals the growth mechanism of the TiO2 oxide layer on a 3D-printed unique titanium alloy. The surface hydrophilic and antibacterial properties of 3D-printed porous titanium alloy were significantly improved after modification by anodic oxidation.

Insufficient calcium intake during growth is a global public health concern. The aim of this study was to investigate the effects of dietary menaquinone-7 (MK-7) on bone accrual in growing Sprague–Dawley rats under calcium restriction. Following 13 weeks of treatment, various bone quality parameters, including microarchitecture, were measured. Fecal and cecal samples were subjected to microbiome (16S rRNA gene sequencing) analyses, while metabolomics analysis of the cecum and humerus samples was analyzed based on UHPLC-Q/TOF-MS. We found that calcium deficiency diminished the richness of the microbiome and disrupted microbiome composition, accompanied by an elevation in the relative abundance of Parasutterella. Furthermore, calcium insufficiency escalated the level of isovaleric acid and modified the metabolic profiles. MK-7 supplementation significantly increased the cortical thickness, cortical bone area, and the calcium content of the femur. Apart from improving bone calcium deposition and diminishing bone resorption, the mechanisms underlying the beneficial effects of MK on bone quality also involve the modulation of the host’s metabolic pathways and the composition of gut microbiota. The gut–bone axis holds promise as an efficacious target for ameliorating calcium deficiency in children’s bone quality, and MK-7 is a promising dietary supplement from this perspective.

The present study aimed to investigate whether gut dysbiosis induced by ceftriaxone in early life could influence pediatric blood pressure regulation in childhood with or without exposure to a high-fat diet (HFD). Sixty-three newborn pups of Sprague-Dawley rats were administered ceftriaxone sodium or saline solution until weaning at 3 weeks, and the rats were fed a HFD or regular diet from 3 to 6 weeks. Tail-cuff blood pressure, the expression levels of genes of the renin-angiotensin system (RAS), the concentrations of IL-1β, IL-6, and TNF-α in the colon and prefrontal cortex, and the composition of fecal microbiota were analyzed. Ceftriaxone treatment significantly increased the diastolic blood pressure of male rats at 3 weeks. At 6 weeks, systolic blood pressure (SBP) was significantly increased only in ceftriaxone treated male rats fed with HFD. The RAS showed increased activation in the kidney, heart, hypothalamus, and thoracic and abdominal aorta of male rats, but only in the kidney, heart, and hypothalamus of female rats. HFD-fed female rats showed a decreased level of IL-6 in the colon. α diversity of gut microbiota decreased and the Firmicutes to Bacteroidetes ratio increased in both male and female rats at 3 weeks; however, these parameters recovered to various degrees in female rats at 6 weeks. These results revealed that early-life gut dysbiosis induced by antibiotics combined with a HFD in childhood could be involved in pediatric blood pressure regulation and an increase in SBP in juvenile rats, and these effects occurred in a sex-dependent manner.

Abstract Background SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years. Methods In the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder. Results Two maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients’ clinical manifestations vary in genders and individuals, even in the same pedigree. Conclusion We firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.

Introduction: Little attention has been paid to the interacting effect of specific intensities of physical activities (PAs) and sedentary lifestyle, like television watching, and genetic predisposition on body composition indices among Chinese adults. Herein, we aimed to examine whether specific types of PAs and sedentary behaviors (SBs) were associated with body composition indices among Chinese adults and to further explore whether these associations interacted with the genetic predisposition to high BMI. Methods: Cross-sectional data regarding PAs and time spent on SBs and dietary intake of 3,976 Chinese adults (54.9% women) aged 25–65 years in Southwest China were obtained via questionnaires in 2013–2015. Weight, height, and waist circumference (WC) were measured, and BMI, percentage of body fat (%BF), fat mass index (FMI), and fat-free mass index (FFMI) of the participants were calculated. Genetic risk score (GRS) was calculated on 9 established BMI-associated SNPs among Chinese adults. Results: When the participants were stratified by GRS for BMI, significant associations were only found for adults with high GRS for BMI: moderate-to-vigorous physical activity (MVPA) was negatively associated with WC and %BF and positively related to FFMI. The adjusted positive relationship of time spent watching television with BMI, WC, %BF, and FMI were also just found between adults with high weighted GRS for high BMI: for every 1 h increment in television watching, the BMI, WC, %BF, and FMI of the participants increased by 0.2 kg/m2, 0.9 cm, 0.3%, and 0.1 kg/m2, respectively (p < 0.02). Conclusion: MVPA may be a protective factor against obesity, and prolonged television watching may accentuate adiposity. These putative effects may be more pronounced among individuals with a high genetic risk of a high BMI.

Abstract While tumor infiltration by CD8+ T cells is now widely accepted to predict outcomes, the clinical significance of intratumoral B cells is less clear. We hypothesized that spatial distribution rather than density of B cells within tumors may provide prognostic significance. We developed statistical techniques (fractal dimension differences and a box-counting method ‘occupancy’) to analyze the spatial distribution of tumor-infiltrating lymphocytes (TILs) in human triple-negative breast cancer (TNBC). Our results indicate that B cells in good outcome tumors (no recurrence within 5 years) are spatially dispersed, while B cells in poor outcome tumors (recurrence within 3 years) are more confined. While most TILs are located within the stroma, increased numbers of spatially dispersed lymphocytes within cancer cell islands are associated with a good prognosis. B cells and T cells often form lymphocyte clusters (LCs) identified via density-based clustering. LCs consist either of T cells only or heterotypic mixtures of B and T cells. Pure B cell LCs were negligible in number. Compared to tertiary lymphoid structures (TLS), LCs have fewer lymphocytes at lower densities. Both types of LCs are more abundant and more spatially dispersed in good outcomes compared to poor outcome tumors. Heterotypic LCs in good outcome tumors are smaller and more numerous compared to poor outcome. Heterotypic LCs are also closer to cancer islands in a good outcome, with LC size decreasing as they get closer to cancer cell islands. These results illuminate the significance of the spatial distribution of B cells and LCs within tumors.

ABSTRACT: Objectives: Achromobacter xylosoxidans is widely distributed in the environment and is increasingly recognised as a significant nosocomial pathogen in healthcare settings. However, the genomic and phylogenetic characteristics of this pathogen are not fully understood. Here we report the first genome sequence of a multidrug-resistant A. xylosoxidans ST273 strain (MTYH1) isolated from a wound infection in China. Methods: Whole-genome sequencing of the strain was performed using an Illumina NovaSeq 6000 platform. Generated short reads were de novo assembled into contigs using SPAdes v.3.13.0. Antimicrobial resistance genes (ARGs) were identified using ResFinder 4.0. Phylogenetic analysis was conducted using NJ/UPGMA phylogeny (MAFFT v.7) based on core genome single nucleotide polymorphism data. Results: The draft genome sequence of A. xylosoxidans ST273 strain MTYH1 consists of 45 contigs comprising 6 643 045 bp with a GC content of 67.5%. According to the Achromobacter spp. multilocus sequence typing (MLST) scheme, MTYH1 belongs to ST273. MTYH1 is resistant to aminoglycosides, ciprofloxacin, aztreonam and cephalosporins. Five ARGs belonging to three different classes were identified in the genome, namely aac(6′)-IIa, ant(2′')-Ia, blaCARB-2, blaOXA-114g and sul1. Phylogenetic analysis showed that MTYH1 was not epidemiologically related to any of the strains retrieved from the NCBI GenBank database. Conclusion: We unravelled the genome sequence of multidrug-resistant A. xylosoxidans ST273 clinical strain MTYH1 recovered from a wound infection in China. Our data may help to understand the antimicrobial resistance mechanisms, genomic features and phylogenetic characteristic of this bacterial pathogen.

This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL/6J mice aged 3 weeks were divided into four groups (n = 20). The NCD group was fed with a normal diet, and the HFD, HFD+ORL, and HFD+EZE groups were fed with HFD for 20 weeks. From the 13th week onward, the HFD+ORL and HFD+EZE groups were administered with orlistat and ezetimibe, respectively. The glucose and lipid metabolism of the tested mice were evaluated by analyzing blood biochemical indicators during the intervention. Furthermore, the changes in the structure of the fecal microbiota and the fecal SCFA content were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry, respectively. HFD induced the obesity phenotype in mice. Compared to the HFD group, the body weight, visceral fat-to-body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and oral glucose tolerance test (OGTT) of the HFD+ORL group significantly decreased, whereas fecal butyric acid levels significantly increased. Ezetimibe intervention significantly reduced the OGTT, serum TC, and HDL-C levels only. The α-diversity of the gut microbiota significantly decreased after intervention with orlistat and ezetimibe. Orlistat altered the relative abundance of some bacteria in the fecal microbiota. The populations of Firmicutes, Alistipes, and Desulfovibrio decreased, whereas those of Verrucomicrobia and Akkermansia significantly increased. Ezetimibe caused changes only in some low-abundance bacteria, as manifested by a decrease in Proteobacteria and Desulfovibrio, and an increase in Bacteroides. The administration of orlistat and ezetimibe can characteristically influence the body weight and serum lipid metabolism, and glucolipid levels in diet-induced obese mice and is accompanied by significant changes in the gut microbiota and SCFAs. These results suggest that the two drugs might exert their own specific anti-obesity effects by modulating the gut microbiota in a different manner. The enhanced health-promoting effect of orlistat might result from its stronger ability to alter the gut microbiota and SCFAs, at least partly.

Gut microbiota depletion may result in cognitive impairment and emotional disorder. This study aimed to determine the possible association between host gut microbiota, cognitive function, and emotion in various life stages and its related underlying mechanisms. Seventy-five neonatal mice were randomly divided into five groups (n = 15 per group). Mice in the vehicle group were administered distilled water from birth to death, and those in the last four groups were administered antibiotic cocktail from birth to death, from birth to postnatal day (PND) 21 (infancy), from PND 21 to 56 (adolescence), and from PND 57 to 84 (adulthood), respectively. Antibiotic exposure consistently altered the gut microbiota composition and decreased the diversity of gut microbiota. Proteobacteria were the predominant bacteria instead of Firmicutes and Bacteroidetes after antibiotic exposure in different life stages. Long-term and infant gut microbiota depletion resulted in anxiety- and depression-like behaviors, memory impairments, and increased expression of γ-aminobutyric acid type A receptor α1 of adult mice. Long-term antibiotic exposure also significantly decreased serum interleukin (IL)-1β, IL-10, and corticosterone of adult mice. Gut microbiota depletion in adolescence resulted in anxiety-like behaviors, short-term memory decline, decreased serum interferon-γ (IFN-γ), mRNA expression of 5-hydroxytryptamine receptor 1A, and neuropeptide Y receptor Y2 in the prefrontal cortex of adult mice. Antibiotic exposure in adulthood damaged short-term memory and decreased serum IL-10, IFN-γ, and increased γ-aminobutyric acid type B receptor 1 mRNA expression of adult mice. These results suggest that antibiotic-induced gut microbiota depletion in the long term and infancy resulted in the most severe cognitive and emotional disorders followed by depletion in adolescence and adulthood. These results also suggest that gut microbes could influence host cognitive function and emotion in a life stage-dependent manner by affecting the function of the immune system, hypothalamic-pituitary-adrenal axis, and the expression of neurochemicals in the brain.

Non-point source pollution caused by surface runoff has been a popular hydrological and environmental safety issue and has attracted extensive attention from global scholars. To identify the optimal vegetation coverage of Festuca arundinacea grassland for controlling soil erosion and purifying surface runoff, bare land was chosen as the control in this experiment. Simulated rainfall experiments were carried out with three levels of coverage (low coverage, moderate coverage and full coverage) under four slope conditions (flat slope, gentle slope, medium slope, and steep slope) and at four rainfall intensities (moderate rainfall, heavy rainfall, rainstorm and heavy rainstorm). The comprehensive evaluation results suggested that the capacity of Festuca arundinacea grassland for reducing the surface runoff, sediment yield, suspended solids (SS), total nitrogen (TN), total phosphorus (TP) and chemical oxygen demand (COD) decreased with increasing rainfall intensity and slope but increased with increasing vegetation coverage. Structural equation model (SEM) results suggested that there were positive relationships between the vegetation coverage and purification capacity index and negative correlations between the rainfall intensity and slope and the purification capacity index. The response surface analysis results suggested that the optimal vegetation coverage should be higher than 84% and that the slope should be smaller than 10° for controlling soil erosion and avoiding pollution via diffusion with surface runoff in Festuca arundinacea grassland. This study proposes recommendations for the vegetation configuration pattern in the development and management of runoff purification systems.

ObjectiveAlthough many unexplained intellectual disability/global developmental delay (ID/GDD) individuals have benefited from the excellent detection yield of copy number variations and next-generation sequencing testing, many individuals still who suffer from ID/GDD of unexplained etiology. In this study, we investigated the applicability of fragile X syndrome (FXS) testing in unexplained ID/GDD individuals with negative or absent genetic testing.MethodsIn this study, we used the triplet repeat primed polymerase chain reaction to evaluate the value and application of fragile X testing in unexplained ID/GDD individuals with negative or absent genetic testing (n = 681) from three hospitals.ResultsOf the 681 ID/GDD individuals with negative or absent genetic testing results detected by FXS testing, 12 men and one woman were positive. This corresponded to a diagnostic yield of 1.9% for FXS testing in our cohort. All FXS individuals had either a family history of ID/GDD or suggestive clinical features. The detection yield of FXS testing in ID/GDD individuals who completed genetic testing (2.70%, 12/438) was significantly higher than in individuals without any genetic testing (0.40%, 1/243).ConclusionsThis is the first report of FXS testing in ID/GDD individuals who lacked previous genetic testing, which promotes standardization of the FXS diagnostic process. These results highlight the utility of FXS testing of unexplained ID/GDD individuals with negative results from standard genetic testing. In the era of next-generation sequencing, FXS testing is more suitable as a second-tier choice and provides clinicians and geneticists with auxiliary references for tracing the etiology of ID/GDD.

Inflammatory bowel disease (IBD) is a chronic intestinal disease characterized by microbiota disturbance and intestinal mucosal damage. The current study aimed to investigate the preventive effects of Bifidobacterium bifidum BD-1 (BD-1) against long-term IBD and possible mechanism by which it alters the gut microbiota, immune response, and mucosal barrier. Our study found that early treatment of BD-1 + Ceftri (ceftriaxone followed by BD-1) and BD-1 confers a certain protective effect against the occurrence of long-term Dextran sulfate sodium-induced colitis, which manifests as a decrease in inflammation scores and MPO activity levels, as well as a relatively intact intestinal epithelial structure. Moreover, compared to BD-1, Ceftri, and NS, early treatment with BD-1 + Ceftri promoted greater expression levels of mucosal barrier-related proteins [KI67, MUC2, ZO-1, secretory immunoglobulin A (slgA), Clauding-1, and Occludin], better local immune responses activation, and moderately better modulation of systemic immune responses during long-term colitis. This may be due to the fact that BD-1 + Ceftri can deliberately prolong the colonization time of some beneficial microbiota (e.g., Bifidobacterium) and reduce the relative abundance of inflammation-related microbiota (e.g., Escherichia/Shigella and Ruminococcus). Interestingly, we found that the changes in the gut barrier and immunity were already present immediately after early intervention with BD-1 + Ceftri, implying that early effects can persist with appropriate intervention. Furthermore, intervention with BD-1 alone in early life confers an anti-inflammatory effect to a certain degree in the long-term, which may be due to the interaction between BD-1 and the host’s native gut microbiota affecting intestinal metabolites. In conclusion, BD-1 was not as effective as BD-1 + Ceftri in early life, perhaps due to its failure to fully play the role of the strain itself under the influence of the host’s complex microbiota. Therefore, further research is needed to explore specific mechanisms for single strain and native microbiota or the combination between probiotics and antibiotics.

Cadmium (Cd), as one of the heavy metals with biological poisonousness, seriously suppresses plant growth and does harm to human health. Hence, phytoremediation was proposed to mitigate the negative effects from Cd and restore contaminated soil. However, the internal mechanisms of detoxification of Cd used in phytoremediation are not completely revealed. In this study, we cloned the cytochrome P450 gene PscCYP716A1 from hybrid poplar “Chuanxiang No. 1” and found that the PscCYP716A1 was transcriptionally upregulated by Cd stress and downregulated by the exogenous brassinolide (BR). Meanwhile, PscCYP716A1 significantly promoted the poplar growth and enhanced the Cd accumulation in poplar. Compared to wild-type poplars, overexpressed PscCYP716A1 lines produced higher levels of endogenous BR and showed a stronger tolerance to Cd, which revealed that PscCYP716A1 may reduce the oxidative stress damage induced by Cd stress through accelerating BR synthesis. In general, PscCYP716A1 has a potential superiority in regulating the plant's tolerance to Cd stress, which will provide a scientific basis and a new type of gene-modified poplar for Cd-pollution remediation.

Cadmium (Cd) pollution has detrimental effects on the ecological environment and human health. Currently, phytoremediation is considered an environmentally friendly way to remediate Cd pollution. The application of transgenic plants to remediate soil pollution is a new technology that has emerged in recent years. In this study, PyWRKY75 was isolated and cloned from Populus yunnanensis, and the functionality of PyWRKY75 in woody plants (poplar) under Cd stress was verified. The increase in plant height of the OE-41 line (overexpression poplar) was 33.2% higher than that of the wild type (WT). Moreover, PyWRKY75 significantly promoted the absorption and accumulation of Cd in poplar, which increased by 51.32% in the OE-41 line when compared with the WT. The chlorophyll content of transgenic poplar leaves was higher than that of the WT, which reflected a protective mechanism of PyWRKY75. Other antioxidants, such as POD, SOD, CAT, APX, AsA, GSH and PCs, also made the transgenic poplars more tolerant to Cd, and they behaved differently in roots, stems and leaves. In general, PyWRKY75 played a potential role in regulating plant tolerance to Cd stress. This study provides a scientific basis and a new type of modified poplar for Cd pollution remediation.

Summary: The spine has essential roles in supporting body weight, and passaging the neural elements between the body and the brain. In this study, we used integrated single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to reveal the cellular heterogeneity, lineage, and transcriptional regulatory network of the developing human spine. We found that EPYC + HAPLN1+ fibroblasts with stem cell characteristics could differentiate into chondrocytes by highly expressing the chondrogenic markers SOX9 and MATN4. Neurons could originate from neuroendocrine cells, and MEIS2 may be an essential transcription factor that promotes spinal neural progenitor cells to selectively differentiate into neurons during early gestation. Furthermore, the interaction of NRP2_SEMA3C and CD74_APP between macrophages and neurons may be essential for spinal cord development. Our integrated map provides a blueprint for understanding human spine development in the early and midgestational stages at single-cell resolution and offers a tool for investigating related diseases.

ABSTRACT To fulfill virus replication and persistent infection in hosts, viruses have to find ways to compromise innate immunity, including timely impedance on antiviral RNases and inflammatory responses. Porcine reproductive and respiratory syndrome virus (PRRSV) is a major swine pathogen causing immune suppression. MALT1 is a central immune regulator in both innate and adaptive immunity. In this study, MALT1 was confirmed to be induced rapidly upon PRRSV infection and mediate the degradation of two anti-PRRSV RNases, MCPIP1 and N4BP1, relying on its proteolytic activity, consequently facilitating PRRSV replication. Multiple PRRSV nsps, including nsp11, nsp7β, and nsp4, contributed to MALT1 elicitation. Interestingly, the elevated expression of MALT1 began to decrease once intracellular viral expression reached a high enough level. Higher infection dose brought earlier MALT1 inflection. Further, PRRSV nsp6 mediated significant MALT1 degradation via ubiquitination-proteasome pathway. Downregulation of MALT1 suppressed NF-κB signals, leading to the decrease in proinflammatory cytokine expression. In conclusion, MALT1 expression was manipulated by PRRSV in an elaborate manner to antagonize precisely the antiviral effects of host RNases without excessive and continuous activation of inflammatory responses. These findings throw light on the machinery of PRRSV to build homeostasis in infected immune system for viral settlement. IMPORTANCE PRRSV is a major swine pathogen, suppresses innate immunity, and causes persistent infection and coinfection with other pathogens. As a central immune mediator, MALT1 plays essential roles in regulating immunity and inflammation. Here, PRRSV was confirmed to manipulate MALT1 expression in an accurate way to moderate the antiviral immunity. Briefly, multiple PRRSV nsps induced MALT1 protease to antagonize anti-PRRSV RNases N4BP1 and MCPIP1 upon infection, thereby facilitating viral replication. In contrast, PRRSV nsp6 downregulated MALT1 expression via ubiquitination-proteasome pathway to suppress the inflammatory responses upon infection aggravation, contributing to immune defense alleviation and virus survival. These findings revealed the precise expression control on MALT1 by PRRSV for antagonizing antiviral RNases, along with recovering immune homeostasis. For the first time, this study enlightens a new mechanism of PRRSV adapting antiviral innate immunity by modulating MALT1 expression.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel plays a critical role in regulating the resting membrane potential and integrating synaptic transmission. Variants of HCN1 have been recognized as causes of epilepsy, and mutant HCN1 channels could act with loss-of-function (LOF), loss- and gain-of-function (LOF and GOF) and gain-of-function (GOF) mechanisms. However, phenotypes and pathogenesis of HCN1-related epilepsy are still poorly understood. This study enrolled five epileptic cases carrying five different HCN1 variants: two pathogenic variants (I380F and S710Rfs*71), two likely pathogenic variants (E240G and A395G), and a paternally inherited variant (V572A). Four variants were novel. Electrophysiological experiments revealed impaired biophysical properties of the identified mutants, including current densities and activation/deactivation kinetics. Moreover, three variants exerted effects on the biophysical properties of wild-type HCN1 channels in heterozygous conditions. Immunofluorescence experiments showed that two variants reduced the protein expression of HCN1channels in neurons. Neurons expressing E240G (GOF) variant showed increased input resistance. However, the variant of I380F (LOF) increased the neuronal firing rate, thus leading to neuronal hyperexcitability. In conclusion, the present study expands the genotypic and phenotypic spectrum of patients with HCN1-related epilepsy and clarifies the underlying mechanisms. We reported five new cases including four unreported likely/pathogenic variants. We provided assessments of biophysical function for each variant, which could help patients to receive individual therapy in the future. We confirmed that HCN1 variants contributed to neuronal hyperexcitability by regulating input resistance and the action potential firing rate, and we have shown that they can affect protein expression in neurons for the first time.