RESUMO
Whole-brain analysis of single-neuron morphology is crucial for unraveling the complex structure of the brain. However, large-scale neuron reconstruction from terabyte and even petabyte data of mammalian brains generated by state-of-the-art light microscopy is a daunting task. Here, we developed 'Gapr' (Gapr accelerates projectome reconstruction) that streamlines deep learning-based automatic reconstruction, 'automatic proofreading' that reduces human workloads at high-confidence sites, and high-throughput collaborative proofreading by crowd users through the Internet. Furthermore, Gapr offers a seamless user interface that ensures high proofreading speed per annotator, on-demand conversion for handling large datasets, flexible workflows tailored to diverse datasets and rigorous error tracking for quality control. Finally, we demonstrated Gapr's efficacy by reconstructing over 4,000 neurons in mouse brains, revealing the morphological diversity in cortical interneurons and hypothalamic neurons. Here, we present Gapr as a solution for large-scale single-neuron reconstruction projects.
RESUMO
This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 â, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.
Assuntos
Medicamentos de Ervas Chinesas , Lamiaceae , Cinamatos , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Ácido RosmarínicoRESUMO
INTRODUCTION AND HYPOTHESIS: Hysteropreservation and hysterectomy for uterine prolapse have been compared in several randomized controlled trials (RCTs), as the best treatment has not been definitively determined. This study aimed to summarize the available evidence in RCTs of hysteropreservation versus hysterectomy. METHODS: We performed electronic searches in the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for eligible RCTs from inception to June 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated for categorical and continuous variables using random-effects models. RESULTS: Twelve RCTs involving 1177 patients were selected for meta-analysis. There were no significant differences between hysteropreservation and hysterectomy for the incidences of recurrence (RR, 0.55; 95% CI, 0.26-1.19; P = 0.130) and reoperation (RR, 1.15; 95% CI, 0.56-2.37; P = 0.705). Moreover, neither hysteropreservation nor hysterectomy had any significant effect on the risk of constipation (RR, 0.72; 95% CI, 0.15-3.46; P = 0.681), voiding dysfunction (RR, 0.99; 95% CI, 0.54-1.84; P = 0.981), intraoperative bleeding (RR, 0.35; 95% CI, 0.05-2.26; P = 0.271), upper leg dullness (RR, 0.70; 95% CI, 0.15-3.17; P = 0.643), dyspareunia (RR, 1.47; 95% CI, 0.69-3.13; P = 0.317), and wound infection (RR, 1.38; 95% CI, 0.24-7.80; P = 0.714). Furthermore, hysteropreservation was associated with less intraoperative blood loss (WMD, -25.68; 95% CI, -44.39 to -6.96; P = 0.007), shorter duration of surgery (WMD, -11.30; 95% CI, -19.04 to -3.55; P = 0.004), and shorter duration of hospitalization (WMD, -0.63; 95% CI, -1.10 to -0.16; P = 0.009) compared with hysterectomy. CONCLUSION: This study found that both hysteropreservation and hysterectomy have similar effects on recurrence and reoperation rates, while hysteropreservation was superior to hysterectomy in reducing intraoperative blood loss and shortening the duration of surgery and hospitalization.
Assuntos
Dispareunia , Prolapso Uterino , Perda Sanguínea Cirúrgica , Dispareunia/cirurgia , Feminino , Humanos , Histerectomia/efeitos adversos , Reoperação , Prolapso Uterino/cirurgiaRESUMO
Individuals of many species fight with conspecifics to gain access to or defend critical resources essential for survival and reproduction. Such intraspecific fighting is evolutionarily selected for in a species-, sex-, and environment-dependent manner when the value of resources secured exceeds the cost of fighting. One such example is males fighting for chances to mate with females. Recent advances in new tools open up ways to dissect the detailed neural circuit mechanisms that govern intraspecific, particularly inter-male, aggression in the model organism Mus musculus (house mouse). By targeting and functional manipulating genetically defined populations of neurons and their projections, these studies reveal a core neural circuit that controls the display of reactive male-male attacks in mice, from sensory detection to decision making and action selection. Here, we summarize these critical results. We then describe various modulatory inputs that route into the core circuit to afford state-dependent and top-down modulation of inter-male attacks. While reviewing these exciting developments, we note that how the inter-male attack circuit converges or diverges with neural circuits that mediate other forms of social interactions remain not fully understood. Finally, we emphasize the importance of combining circuit, pharmacological, and genetic analysis when studying the neural control of aggression in the future.
Assuntos
Agressão/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Núcleos Septais/fisiologia , Comportamento Sexual Animal/fisiologia , Núcleo Hipotalâmico Ventromedial/fisiologia , Animais , Tomada de Decisões/fisiologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Instinto , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Sistema Nervoso , Neurônios/fisiologia , Sensação/fisiologiaRESUMO
BACKGROUND: Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C. RESULTS: We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I2 = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I2 = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I2 = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I2 = 23%). CONCLUSIONS: Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.
Assuntos
Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Diabetes Mellitus/prevenção & controle , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Ácidos Dicarboxílicos/efeitos adversos , Regulação para Baixo , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/epidemiologia , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.
Assuntos
Adaptação Fisiológica/genética , Altitude , DNA/genética , Variação Genética , Hominidae/genética , Animais , Povo Asiático/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Frequência do Gene , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , TibetRESUMO
Surfactant cetyltrimethylammonium bromide enhanced molybdenum disulfide was used as an adsorbent in pipette-tip solid-phase extraction for the pretreatment of sulfonamides in environmental water samples. The factors affecting the extraction recoveries of the analytes, including the sample pH value, amount of sorbent, type and volume of eluent solution, and salt concentration were optimized. This pipette-tip solid-phase extraction method demonstrated good linearity (0.05-10.0 µg/L) with a coefficient of determination of 0.9984-0.9996, limit of detection (0.2-0.4 ng/L) and limit of quantitation (0.5-1.0 ng/L), good analyte recoveries (76-91), and acceptable limit of quantitation (<10%) under the optimized conditions. These results indicated that the proposed method was a good tool for monitoring sulfonamides in environmental water samples.
RESUMO
AIM: Maternal dietary protein restriction reduces nephron number in offspring and increases the risk of cardiovascular and chronic kidney diseases. Perlecan is the major basement membrane/extracellular matrix heparan sulfate proteoglycan (HSPG) that plays a crucial role in nephron formation. This study was to determine whether maternal dietary protein restriction during pregnancy leads to an abnormal perlecan expression pattern during kidney development and a correlation with aberrant cell proliferation and apoptosis. METHODS: Pregnant Sprague-Dawley rats were divided into two groups, maintained on either a low-protein diet (MLP group) or a normal-protein diet (MNP group). Kidneys were dissected from embryos of different kidney development stages. Real-time PCR and immunohistochemistry were performed to detect the transcript level of rHSPG2, the coding gene of perlecan, and its protein expression pattern. Apoptosis and proliferation cell were detected by TUNEL system and Ki67 marker. RESULTS: Embryonic weights and nephron number were significantly affected by maternal low protein diets. The transcript level of rHSPG2 in the MLP group was significantly lower at embryonic day 18 and the neonatal period. Immunohistochemistry study was consistent with the RT-PCR results. The proliferation level of the MLP group was significantly lower than the MNP group at E18 and more apoptotic cells was detected in MLP newborn. CONCLUSION: Maternal protein restriction reduced the expression of perlecan and lead aberrant cell proliferation and apoptosis during mid-metanephrogenesis in offspring. This data may provide new evidence to understand the mechanism of reduced nephron number due to maternal protein restriction and enlighten solution.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Dieta com Restrição de Proteínas , Proteoglicanas de Heparan Sulfato/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Néfrons/metabolismo , Animais , Apoptose , Proliferação de Células , Regulação para Baixo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Proteoglicanas de Heparan Sulfato/genética , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Néfrons/embriologia , Estado Nutricional , Organogênese , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Objective: To investigate the prevalence of parasitic infections in Lhasa, Tibet. Methods: The residents in Chengguan District, Dangxiong County, Dazi County and Qushui County were selected to participate in the study in 2014, using the stratified random sampling method. Infections with the soil-borne nematodes in feces were examined in triplicates using the Kato-Katz method. Further, the Enterobius vermicularis were examined using the cellophane anal swab method in children aged 3-12 years, and the intestinal protozoa were detected by iodine staining. The parasitic infection was analyzed by sex, age, and occupation. Comparisons were made using Chi-square test. Results: A total of 1 015 residentsï¼39.3±18.2 years: age range, 1-89 yearsï¼ participated in the study, including 391 malesï¼38.6%ï¼ and 623 femalesï¼61.4%ï¼. Two hundred and forty-nine participants were positive for parasitic infections, with an overall infection rate of 24.5%ï¼249/1 015ï¼. The infection rate was 21.7%ï¼220/1 015ï¼ for Taenia sp., 0.2%ï¼2/1 015ï¼ for Trichuris trichiura and E. vermicularis respectively, 4.1%ï¼42/1 015ï¼ for Entamoeba coli, 0.4%ï¼4/1 015ï¼ for Giardia lamblia, 0.2%ï¼2/1 015ï¼ for Iodamoeba butschlii. No infection was found for other parasites. There was no significant sexual difference in the infection rate of Taenia (male 21.2%, 83/391; female 22.0%, 137/624), T. trichiura (male 0; female 0.3%, 2/624), E. vermicularis (male 0.3%, 2/391; female 0.2%, 1/624), E. coli (male 5.4%, 21/391; female 3.4%, 21/624), G. lamblia (male 0.8%, 3/391; female 0.2%, 1/624), or I. butschlii (male 0; female 0.3%, 2/624) (P>0.05). The Taenia sp. infection rate in the age groups of 0-17, 18-29, 30-39, 40-49, 50-59 and ≥ 60 years was 10.9%ï¼18/165ï¼, 14.0%ï¼18/129ï¼, 23.0%ï¼43/187ï¼, 25.3%ï¼61/241ï¼, 26.5%ï¼41/155ï¼, and 28.3%ï¼39/138ï¼, respectively, with significant differences between groups of 0-17 and 40-49 years and between groups of 50-59 and ≥ 60 years (P<0.01). The infection rate of E. coli, T. trichiura and I. butschlii was highest in the age group of 50-59 yearsï¼6.5%, 10/155; 0.7%, 1/155; 1.3%, 2/155 respectivelyï¼. Among various occupations, farmers showed the highest infection rate for Taeniaï¼44.5%, 147/330ï¼, E. coliï¼6.4%, 21/33ï¼, E. vermicularis ï¼0.6%, 2/330ï¼ and I. butschliiï¼0.3%, 1/330ï¼; housewives had the highest infection rate for T. trichiuraï¼2.5%, 1/40ï¼; and the students had the highest infection rate for G. lamblia (0.7%, 1/134). Conclusion: There are infections with various intestinal parasites in the participants of Lhasa City, among which taenia infection reaches 20.7% while others have a low level of infection.
Assuntos
Enteropatias Parasitárias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Enterobius , Escherichia coli , Fazendeiros , Fezes , Feminino , Helmintos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nematoides , Prevalência , Solo , Inquéritos e Questionários , Teníase , Tibet/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To study the clinical characteristics of childhood Henoch-Schonlein purpura (HSP) on the Tibetan Plateau, China. METHODS: One hundred and twenty-five HSP children admitted to Shannan People's Hospital, Tibet, were assigned to the observation group, and 96 HSP children admitted to Wuhan Children's Hospital were assigned to the control group. The disease characteristics, clinical manifestations, treatment, and prognosis in both groups were retrospectively analyzed and compared. RESULTS: The mean age of HSP onset and the female-to-male ratio in the observation group were both significantly higher than in the control group (P<0.05). There was a significant difference in seasonal onset between two groups. Significant differences in the etiological factors were observed between the two groups (P<0.05). The gastrointestinal manifestation was more prominent in the observation group compared with that in the control group (P<0.05). Laboratory findings showed that the mean erythrocyte sedimentation rate, counts of white blood cells and platelets, and percentage of neutrophil leucocytes were significantly lower, while the hemoglobin level was significantly higher in the observation group than in the control group (P<0.05). A total of 124 HSP patients (99.2%) in the observation group had a full recovery or improvement, and the overall cure rate and improvement rate showed no significant differences between two groups (P>0.05). Only 2.4% of the patients (3 cases) in the observation group had recurrent attack during follow-up, which was significantly lower than that in the control group (16.7%; P<0.05). CONCLUSIONS: Childhood HSP on the Tibetan Plateau shows partial differences in disease characteristics, clinical manifestations, and laboratory measurements compared with that in the plain area. The overall prognosis is better and the recurrent rate is lower among HSP children on the Tibetan Plateau.
Assuntos
Vasculite por IgA/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/etiologia , Masculino , Prognóstico , TibetRESUMO
Intestinal microbiota community is an important factor affecting the nutritional and health status of poultry, and its balance is crucial for improving the overall health of poultry. The study aimed to investigate the effect of dietary supplementation with Glycyrrhiza uralensis extract (GUE), Lactobacillus acidophilus (Lac) and their combination (GL) on growth performance and intestinal health in broilers in an 84-day feeding experiment. Supplementary 0.1% GUE and 4.5×107 CFU/g Lac significantly increased average daily gain (ADG), and GL (0.1% GUE and 4.5×107 CFU/g Lac) increased ADG and average daily feed intake (ADFI), and decreased feed conversion rate (FCR) in broilers aged 29 to 84 d and 1 to 84 d. Dietary GUE, Lac and GL increased the superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity and decreased Malondialdehyde (MDA) content in the jejunum mucosa of broilers, and increased secretory IgA (sIgA) content in broilers at 84 d. Moreover, GUE, Lac and GL increased cecal microbial richness and diversity, and modulated microbial community composition. Both GUE and Lac reduced the harmful bacteria Epsilonbacteraeota, Helicobacter, and H. pullorum at 28 d and Proteobacteria, Escherichia, and E. coli at 84 d, while Lac and GL increased beneficial bacteria Lactobacillus and L. gallinarum at 28 d. Compared with individual supplementation, GL markedly increased the SOD activity and the sIgA content, and reduced Helicobacter and Helicobacter pullorum. In conclusion, GUE and Lactobacillus acidophilus as feed additives benefit growth performance and intestinal health, and their combined use shows an even more positive effect in broilers.
RESUMO
BACKGROUND: Mutations in canonical transient receptor potential channel 6 (TRPC6) have been identified as responsible for the development of focal segmental glomerulosclerosis, a proteinuric disease with steroid resistance and poor prognosis. This study explores the prevalence of TRPC6 variants in Chinese children with idiopathic nephrotic syndrome (INS), the genotype/phenotype correlation of TRPC6 variants, the therapeutic response, and the underlying molecular mechanism. METHODS: Fifty-one children with sporadic INS were enrolled: 23 steroid-sensitive cases and 28 steroid-resistant cases Polymerase chain reaction was used to amplify 13 exons and the promoter sequences of TRPC6 before sequencing. The expression of TRPC6 in renal tissues was illustrated by immunohistochemistry staining. The transcriptional activity of variants in TRPC6 promoter was measured by the luciferase assay. RESULTS: Three variants (-254C>G, rs3824934; +43C/T, rs3802829; and 240 G>A, rs17096918) were identified. The allele frequency of the -254C>G single-nucleotide polymorphism (SNP) in the steroid-resistant nephrotic syndrome (SRNS) patients (40.5%) was higher than that in the steroid-sensitive nephrotic syndrome subjects (27.1%; P = 0.046). The -254C>G SNP enhanced transcription from TRPC6 promoter in vitro and was associated with increased TRPC6 expression in renal tissues of SRNS patients. CONCLUSION: -254C>G, a SNP underlying enhanced TRPC6 transcription and expression, may be correlated with the development of steroid resistance in Chinese children with INS.
Assuntos
Povo Asiático/genética , Síndrome Nefrótica/congênito , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Canais de Cátion TRPC/genética , Transcrição Gênica/genética , Sequência de Bases , Criança , Éxons/genética , Frequência do Gene , Humanos , Imuno-Histoquímica , Rim/metabolismo , Luciferases , Dados de Sequência Molecular , Síndrome Nefrótica/genética , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Canal de Cátion TRPC6RESUMO
This study investigated the geographic and pairwise distances of nine Chinese local Cashmere goat populations through the analysis of 20 microsatellite DNA markers. Fluorescence PCR was used to identify the markers, which were selected based on their significance as identified by the Food and Agriculture Organization of the United Nations (FAO) and the International Society for Animal Genetics (ISAG). In total, 206 alleles were detected; the average allele number was 10.30; the polymorphism information content of loci ranged from 0.5213 to 0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat populations exhibited rich genetic diversity. Further, the Wright's F-statistics of subpopulation within total (FST) was 0.1184; the genetic differentiation coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All pairwise FST values among the populations were highly significant (p<0.01 or p<0.001), suggesting that the populations studied should all be considered to be separate breeds. Finally, the clustering analysis divided the Chinese Cashmere goat populations into at least four clusters, with the Hexi and Yashan goat populations alone in one cluster. These results have provided useful, practical, and important information for the future of Chinese Cashmere goat breeding.
RESUMO
Decades of knockout analyses have highlighted the crucial involvement of estrogen receptors and downstream genes in controlling mating behaviors. More recently, advancements in neural circuit research have unveiled a distributed subcortical network comprising estrogen-receptor or estrogen-synthesis-enzyme-expressing cells that transforms sensory inputs into sex-specific mating actions. This review provides an overview of the latest discoveries on estrogen-responsive neurons in various brain regions and the associated neural circuits that govern different aspects of male and female mating actions in mice. By contextualizing these findings within previous knockout studies of estrogen receptors, we emphasize the emerging field of "circuit genetics", where identifying mating behavior-related neural circuits may allow for a more precise evaluation of gene functions within these circuits. Such investigations will enable a deeper understanding of how hormone fluctuation, acting through estrogen receptors and downstream genes, influences the connectivity and activity of neural circuits, ultimately impacting the manifestation of innate mating actions.
Assuntos
Estrogênios , Receptores de Estrogênio , Animais , Masculino , Feminino , Camundongos , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Neurônios/fisiologia , Encéfalo/fisiologiaRESUMO
Sex differences in emotional behaviors and affective disorders have been widely noted, of which sexually dimorphic secretion of gonadal steroid hormones such as estrogen is suspected to play a role. However, the underlying neural mechanisms remain poorly understood. We noted that the expression of estrogen receptor 2 (Esr2, or ERß), a key mediator of estrogen signaling in the brain, was enriched in the dorsal raphe nucleus (DRN), a region involved in emotion regulation. To investigate whether DRN Esr2 expression confers sex-specific susceptibility or vulnerability in emotional behaviors, we generated a conditional allele of Esr2 that allowed for site-specific deletion of Esr2 in the DRN via local injection of Cre-expressing viruses. DRN-specific Esr2 deletion mildly increased anxiety behaviors in females, as shown by decreased time spent in the center zone of an open field in knockout females. By contrast, DRN Esr2 deletion had no effects on anxiety levels in males, as demonstrated by knockout males spending comparable time in the center zone of an open field and open arms of an elevated-plus maze. Furthermore, in the tail suspension test, DRN Esr2 deletion reduced immobility, a depression-like behavior, in a male-biased manner. Together, these results reveal sex-specific functions of DRN Esr2 in regulating emotional behaviors and suggest targeted manipulation of DRN Esr2 signaling as a potential therapeutic strategy to treat sex-biased affective disorders.
Assuntos
Núcleo Dorsal da Rafe , Receptor beta de Estrogênio , Feminino , Masculino , Humanos , Núcleo Dorsal da Rafe/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Ansiedade/genética , Ansiedade/metabolismo , Depressão/genética , Depressão/metabolismo , Estrogênios/metabolismoRESUMO
BACKGROUND: This study aimed to investigate the role of osteopontin and its receptor, integrin αv, in gallstone formation using human tissue specimens and a guinea pig lithogenic model. MATERIAL/METHODS: The nucleation role of osteopontin was determined in patients' and normal gallbladder bile samples in vitro. Normal gallbladder was the control, and gallstone gallbladders were divided into group I (with normal epithelia) and group II (with degenerated epithelia) based on pathology change. Immunostaining, mRNA and protein expressions of osteopontin and integrin αv were analyzed. The animals were randomly divided into a lithogenic diet group and a normal diet group; the osteopontin mRNA expression in gallbladder and liver and osteopontin concentrations were determined. RESULTS: Osteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin αv in human gallbladder tissues showed a higher reactivity in Group I than control group and Group II. The immunostaining in Group II was weaker than control group; similar results were observed for mRNA and protein expression of osteopontin and integrin αv. In the animal assay, the mRNA expression and concentration of osteopontin in gallbladder and liver gradually increased at initial stages and decreased in later stages. The concentrations of osteopontin in bile and serum of guinea pig showed similar trends. CONCLUSIONS: Our results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin αv and calcium.
Assuntos
Bile/metabolismo , Dieta , Cálculos Biliares/metabolismo , Integrina alfaV/metabolismo , Osteopontina/metabolismo , Animais , Western Blotting , Cálcio/metabolismo , Feminino , Vesícula Biliar/metabolismo , Cálculos Biliares/patologia , Cobaias , Humanos , Imuno-Histoquímica , Fígado/metabolismo , Masculino , Osteopontina/sangue , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The maternal genetic effects on estimating genetic parameters for growth traits and wool traits of Qinghai fine-wool sheep were investigated.The genetic parameters for production traits of Qinghai fine-wool sheep were estimated by average information restricted maximum likelihood (AIREML) with different animal models, and the differences between different animal models were tested by likelihood ratio test. Fixed effects, direct genetic effects, and residual effects were included all models; and random effects were individual permanence environmental effects, maternal genetic effects, and maternal permanence environmental effects. The six models differ in the way of considering random effects: in model 1 individual permanence environmental effects, maternal genetic effects, and maternal permanence environmental effects were not contained; in model 2 maternal permanence environmental effects were included; in model 3 maternal genetic effects were included; in model 4 both maternal genetic effects and maternal permanence environmental effects were include; in model 5 both individual permanence environmental effects and maternal genetic effects were contained;in model 6 all random effects were contained. The direct heritabilities were 0.1896~0.3781, 0.2537~0.2890, 0.2244~0.3225, 0.2205~0.3983, 0.1218~0.1490, 0.0983~0.4802, and 0.1170~0.1311 for birth weight, weaning weight, yearling weight, hogget weight,greasy fleece weight, fiber diameter, and staple length,respectively. Compared with model 1, model 3 was-significant(P<0.01) for birth weight and weaning weight, other models were not significant (P>0.05)for Yearling weight, Hogget weight; and paralleled with model 6, both model 4 and model 5 were significant(P<0.01) for fiber diameter,model 4 was significant(P<0.05) for staple length, and other models were not significant(P>0.05) for greasy fleece weight by likelihood ratio test.The maternal effects were important determinants of estimated the genetic parameters for birth weight, weaning weigh, fiber diameter, and staple length, but were not significant for yearling weight, and hogget weight, and was slightly significant for greasy fleece weight.
Assuntos
Ovinos/genética , Lã , Animais , Modelos Animais , Ovinos/crescimento & desenvolvimentoRESUMO
Spin-orbit torque (SOT) efficiency is one of the key issues of spintronics. However, enhancing the SOT efficiency is usually limited by the positive correlation between resistivity and the spin Hall ratio, where a high resistivity often accompanies a large spin Hall ratio. Here, we demonstrate that sub-nanometer ß-W intercalation has a considerable impact on the SOT efficiency in α-W (6 nm)/Co (8 nm)/Pt (3 nm) samples. The damping-like SOT efficiency per unit current density, ξDLj, of α-W (5.7 nm)/ß-W (0.3 nm)/Co (8 nm)/Pt (3 nm) shows a â¼ 296% enhancement compared to that of the α-W/Co/Pt system. Meanwhile, a resistivity similar to that of α-W and the spin Hall ratio larger than ß-W induce a giant damping-like SOT efficiency per applied electric field, ξDLE, which is about 12.1 times larger than that of ß-W. Our findings will benefit the SOT devices by reducing energy consumption.
RESUMO
OBJECTIVE: To assess the efficacy and safety of corticosteroid therapy including oral corticosteroid and intra-articular corticosteroid in patients with hand osteoarthritis (OA), to provide treatment recommendations, and provide data-driven suggestions for future studies. METHODS: A systematic review of the literature was performed from inception to February 19, 2020, and the study was conducted on February 20, 2020. All controlled trials in Ovid MEDLINE, EMBASE, and Cochrane library reporting the efficacy on pain, functional recovery, and adverse events of corticosteroids in hand osteoarthritis were selected. The primary outcome was pain assessed on a visual analogue scale (VAS) lasting for up to 24 weeks. Pooled mean difference (MD) for continuous variable and risk ratio (RR) for dichotomous variable, with 95% confidence intervals (CIs), was assessed by a random effects model. RESULTS: Overall, seven trials totaling 511 participants were included in this study. The pooled analysis showed a significant difference in VAS pain (MD, - 5.75; 95% CI, - 10.08 to - 1.42, I2 = 40%). No significant differences were observed in any of the adverse events. CONCLUSION: Our data suggest corticosteroids in hand OA might improve local pain and promote functional recovery. However, since these findings were based on only 7 studies and due to significant heterogeneity across the included studies, these findings need to be confirmed by future clinical trials with a higher number of patients. KEY POINTS: ⢠Current evidences of glucocorticoids for the management of hand osteoarthritis (OA) were insufficient and more evidences were needed. ⢠The results of the present meta-analysis revealed corticosteroids in hand OA might improve local pain and promote functional recovery. ⢠These findings need to be confirmed by future clinical trials with a higher number of patients.
Assuntos
Osteoartrite , Corticosteroides , Humanos , Injeções Intra-Articulares , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Dor/etiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Finding an effective way to greatly tune spin Hall angle in a low power manner is of fundamental importance for tunable and energy-efficient spintronic devices. Recently, topological insulator of Bi2Se3, having a large intrinsic spin Hall angle, show great capability to generate strong current-induced spin-orbit torques. Here we demonstrate that the spin Hall angle in Bi2Se3 can be effectively tuned asymmetrically and even enhanced about 600% reversibly by applying a bipolar electric field across the piezoelectric substrate. We reveal that the enhancement of spin Hall angle originates from both the charge doping and piezoelectric strain effet on the spin Berry curvature near Fermi level in Bi2Se3. Our findings provide a platform for achieving low power consumption and tunable spintronic devices.