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Water transportation to developing tissues relies on the structure and function of plant xylem cells. Plant microtubules govern the direction of cellulose microfibrils and guide secondary cell wall formation and morphogenesis. However, the relevance of microtubule-determined xylem wall thickening patterns in plant hydraulic conductivity remains unclear. In the present study, we identified a maize (Zea mays) semi-dominant mutant, designated drought-overly-sensitive1 (ZmDos1), the upper leaves of which wilted even when exposed to well-watered conditions during growth; the wilting phenotype was aggravated by increased temperatures and decreased humidity. Protoxylem vessels in the stem and leaves of the mutant showed altered thickening patterns of the secondary cell wall (from annular to spiral), decreased inner diameters, and limited water transport efficiency. The causal mutation for this phenotype was found to be a G-to-A mutation in the maize gene α-tubulin4, resulting in a single amino acid substitution at position 196 (E196K). Ectopic expression of the mutant α-tubulin4 in Arabidopsis (Arabidopsis thaliana) changed the orientation of microtubule arrays, suggesting a determinant role of this gene in microtubule assembly and secondary cell wall thickening. Our findings suggest that the spiral wall thickenings triggered by the α-tubulin mutation are stretched during organ elongation, causing a smaller inner diameter of the protoxylem vessels and affecting water transport in maize. This study underscores the importance of tubulin-mediated protoxylem wall thickening in regulating plant hydraulics, improves our understanding of the relationships between protoxylem structural features and functions, and offers candidate genes for the genetic enhancement of maize.
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As a potent antioxidant, the flavonoid compound quercetin (QUE) has been widely used in the farming of aquatic animals. However, there are fewer reports of the beneficial effects, especially in improving immunity of Penaeus vannamei by QUE. The aim of this study was to investigate the effects of dietary QUE on growth, apoptosis, antioxidant and immunity of P. vannamei. It also explored the potential mechanisms of QUE in improving the growth and immunity of P. vannamei. P. vannamei were fed diets with QUE for 60 days. The results revealed that QUE (0.5 or 1.0 g/kg) ameliorated the growth, and the expressions of genes related to apoptosis, antioxidant, and immunity. The differentially expressed genes (DEGs) and differential metabolites (DMs) obtained through transcriptomics and metabolomics, respectively, enriched in pathways related to nutritional metabolism such as lipid metabolism, amino acid metabolism, and carbohydrate metabolism. After QUE addition, especially at 0.5 g/kg, DEGs were enriched into the functions of response to stimulus and antioxidant activity, and the pathways of HIF-1 signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, and FoxO signaling pathway. In conclusion, dietary QUE can ameliorate growth, apoptosis, antioxidant and immunity of P. vannamei, the appropriate addition amount was 0.5 g/kg rather than 1.0 g/kg. Regulations of QUE on nutrient metabolism and immune-related pathways, and bioactive metabolites, were important factors for improving the aforementioned abilities in P. vannamei.
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Alimentación Animal , Dieta , Suplementos Dietéticos , Penaeidae , Quercetina , Transcriptoma , Animales , Penaeidae/inmunología , Penaeidae/crecimiento & desarrollo , Penaeidae/genética , Penaeidae/efectos de los fármacos , Quercetina/administración & dosificación , Quercetina/farmacología , Dieta/veterinaria , Transcriptoma/efectos de los fármacos , Alimentación Animal/análisis , Suplementos Dietéticos/análisis , Metabolómica , Inmunidad Innata/efectos de los fármacos , Perfilación de la Expresión Génica/veterinaria , Antioxidantes/metabolismoRESUMEN
Objective: This retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy. Methods: Clinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis. Results: Overall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0-2), and 21 patients had a poor prognosis (mRS 3-6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p<0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733-0.961; p < 0.001). Conclusions: Different AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Estudios de Cohortes , Pronóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Encefalitis Antirreceptor N-Metil-D-Aspartato/terapia , Autoanticuerpos , ChinaRESUMEN
We investigated the improvement effects of herbaceous (corn) and woody (oak sawdust) biochar with their calcium modification on saline alkali soil. The addition of unmodified biochar regardless of types had no significant effect on the soluble cations (Na+, Ca2+, and Mg2+) and the main indicators of soil salinity and alkalinity (pH, sodium adsorption ratio (SAR), exchangeable sodium percentage (ESP), and total alkalinity (TA)), but the addition of calcium modified biochar decreased these soluble cations and indicators, especially the addition of modified woody biochar (PBM). Compared to CK, TA decreased by 70.02% and 89.25% in PBM with 2% and 4% addition, respectively. Soil ESP and SAR showed a significantly positive correlation with pH and TA, which indicated that soil salinization and alkalization were synchronized. These results showed that the calcium modified biochar, especially the modified woody biochar, instead of the original biochar could be potential soil amendments for the improvement of saline-alkali soil.
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Calcio , Suelo , Carbón Orgánico , Álcalis , Sodio/análisis , CationesRESUMEN
Panax vietnamensis is a valuable medicinal resource with promising preclinical applications. Ginsenosides, which are triterpenoids, are the primary active components in P. vietnamensis. Oxidosqualene cyclases (OSCs) catalyze the formation of the basic skeleton of triterpenes from 2,3-oxidosqualene, which is a crucial step in the biosynthesis of triterpenoids. The OSCs involved in triterpenoid biosynthesis in P. vietnamensis have not yet been characterized. Four OSC genes (PvOSC1-4) were cloned from P. vietnamensis and functionally characterized via heterologous expression in yeast. Transgenic yeast expressing PvOSC1, PvOSC3, and PvOSC4 produced the corresponding products ß-amyrin, cycloartenol, and dammarenediol-II, respectively. PvOSC1, PvOSC3, and PvOSC4 are monofunctional OSCs. In this study, we characterized three PvOSC genes, providing a better understanding of the biosynthesis of triterpenoids in P. vietnamensis and the multiple choices of plant OSCs for metabolic engineering in yeast and other hosts.
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Panax , Triterpenos , Saccharomyces cerevisiae , Panax/metabolismo , Triterpenos/metabolismo , Clonación MolecularRESUMEN
BACKGROUND: Adenosine deaminase (ADA) is a key enzyme that catalyzes the deamination of adenosine into inosine, which eventually decomposes into uric acid (UA). A body of papers have reported that adenosine and UA are closely related to cerebrovascular events. However, the association between serum ADA activity and acute cerebral infarction (ACI) remains unclear. METHODS: 7913 subjects were enrolled, including 3968 ACI patients and 3945 controls, in this study. An automatic biochemistry analyzer was used to determine serum activity. RESULTS: Serum ADA activity was found that was significantly decreased in patients with ACI (10.10 ± 3.72 U/L) compared to those without ACI (11.07 ± 2.85 U/L, p < 0.001). After Logistic regression analysis, ADA concentrations were negatively correlated with ACI (OR = 1.161, 95% CI: 1.140-1.183, p < 0.001). Smoking and alcohol consumption decreased serum ADA concentrations in patients with ACI, whereas diabetes and hypertension had the opposite effect. CONCLUSIONS: Serum ADA concentrations in patients with ACI are markedly decreased, suggesting that the decreased ADA concentrations may be involved in the pathogenesis of ACI. We hypothesized that decreased ADA activity may be an adaptive mechanism to maintain adenosine levels and protect against ischemic brain injury.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Adenosina Desaminasa/análisis , Estudios Retrospectivos , Estudios de Casos y Controles , Adenosina , Infarto CerebralRESUMEN
Energy is essential for all cellular functions in a living organism. How cells coordinate their physiological processes with energy status and availability is thus an important question. The turnover of actin cytoskeleton between its monomeric and filamentous forms is a major energy drain in eukaryotic cells. However, how actin dynamics are regulated by ATP levels remain largely unknown in plant cells. Here, we observed that seedlings with impaired functions of target of rapamycin complex 1 (TORC1), either by mutation of the key component, RAPTOR1B, or inhibition of TOR activity by specific inhibitors, displayed reduced sensitivity to actin cytoskeleton disruptors compared to their controls. Consistently, actin filament dynamics, but not organization, were suppressed in TORC1-impaired cells. Subcellular localization analysis and quantification of ATP concentration demonstrated that RAPTOR1B localized at cytoplasm and mitochondria and that ATP levels were significantly reduced in TORC1-impaired plants. Further pharmacologic experiments showed that the inhibition of mitochondrial functions led to phenotypes mimicking those observed in raptor1b mutants at the level of both plant growth and actin dynamics. Exogenous feeding of adenine could partially restore ATP levels and actin dynamics in TORC1-deficient plants. Thus, these data support an important role for TORC1 in coordinating ATP homeostasis and actin dynamics in plant cells.
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Citoesqueleto de Actina , Adenosina Trifosfato , Proteínas de Arabidopsis , Arabidopsis , Diana Mecanicista del Complejo 1 de la Rapamicina , Fosfatidilinositol 3-Quinasas , Citoesqueleto de Actina/metabolismo , Actinas , Adenosina Trifosfato/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/fisiología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/fisiologíaRESUMEN
Recent studies showed that genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) is related to attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). However, no consistent conclusion has been determined. This meta-analysis aims to interrogate the relationship between MTHFR gene polymorphisms (677C>T and 1298A>C) and the occurrence of ADHD, BD and SCZ. We retrieved case-control studies that met the inclusion criteria from the PubMed database. Associations between MTHFR polymorphisms (677C>T and 1298A>C) and ADHD, BD and SCZ were measured by means of odds ratios (ORs) using a random effects model and 95% confidence intervals (CIs). Additionally, sensitivity analysis and publication bias were performed. After inclusion criteria were met, a total of five studies with ADHD including 434 cases and 670 controls, 18 studies with BD including 4167 cases and 5901 controls and 44 studies with SCZ including 16,098 cases and 19913 controls were finally included in our meta-analysis. Overall, our meta-analytical results provided evidence that the MTHFR 677C>T was associated with occurrence of BD and SCZ, while the 1298A>C polymorphism was related to ADHD and BD, and additionally the sensitivity analysis indicated these results were stable and reliable. This may provide useful information for relevant studies on the etiology of psychiatric disorders.
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Trastornos Mentales , Metilenotetrahidrofolato Reductasa (NADPH2) , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Trastornos Mentales/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Short tandem repeats (STRs) are consecutive repetition of a repeat motif and widely used in forensic medicine and human genetics because of their high polymorphism. SUBJECTS AND METHODS: In the current study, 23 autosomal STR loci were genotyped from 1263 unrelated healthy individuals living in Panjin City, Liaoning Province, Northeastern China using the VeriFilerTM Express PCR Amplification Kit. The population comparison was performed between the Panjin Han population and the other relevant groups to further explore the structure of Panjin Han and its relationship with the other groups. RESULTS: The results found 316 alleles across the 23 STRs and the corresponding allelic frequencies ranged from 0.5198 to 0.0004. Except for D3S1358, TPOX, TH01, and D3S1358, all STR loci were highly polymorphic (PIC > 0.7), with the Penta E locus having the highest degree of polymorphism (0.9147). For population comparison, the exact test of population differentiation found that no significant difference was observed between the Panjin Han and the other Han populations, except for Guangdong Han and Jiangxi Han. CONCLUSION: The Panjin Han population showed significant differences with the other ethnic groups in China (Bouyei, Dong, Hui, Miao, Tibetan, and Uygur) and the foreign ethnic groups.
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Genética de Población , Polimorfismo Genético , Humanos , Frecuencia de los Genes , Medicina Legal , China , Repeticiones de Microsatélite/genéticaRESUMEN
Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus causing AHPND (VPAHPND) is the most serious disease affecting shrimp farming. The PirAvp and PirBvp toxins of VPAHPND are known virulence factors. However, the corresponding target protein in shrimp that mediates their action has not been identified. By screening yeast two-hybrid cDNA libraries from intestine, stomach, and hepatopancreas of Litopenaeus vannamei, the protein with the largest increase in gene expression in shrimp hepatopancreas in response to VPAHPND challenge was identified and designated LvFABP. Analysis revealed high sequence homology of the LvFABP gene and a lipocalin/cytosolic fatty acid binding gene. Yeast two-hybrid pairwise analysis, GST-pull down assay, and far-western blot assay were performed to determine the interaction between LvFABP and PirBvp. LvFABP was able to directly bind to PirBvp. The expression of LvFABP in the hepatopancreas was significantly higher at P23 and P27 developmental stages of L. vannamei. RNA interference (RNAi) of LvFABP reduced the mortality, histopathological signs of AHPND in the hepatopancreas, and the number of virulent VPAHPND bacteria in the intestine, stomach, and hepatopancreas after VPAHPND challenge. We concluded that the LvFABP was involved in AHPND pathogenesis and acted as a VPAHPND toxin interacting protein. This is the first identification of VPAHPND toxin interacting protein from the shrimp digestive system by yeast two-hybrid library screening and were confirmed by in vitro protein interaction verification and in vivo challenge experiments. This study provides novel insight into the contributions of LvFABP towards AHPND pathogenesis in shrimp. The findings could inform AHPND preventative measures in shrimp farming.
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Toxinas Bacterianas , Penaeidae , Vibrio parahaemolyticus , Animales , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Necrosis , Penaeidae/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Objective: This study aimed to determine the clinical characteristics and evaluate the efficacy of immunotherapy and the long-term prognosis of severe autoimmune encephalitis (AE) in China. Methods: Clinical features, laboratory or radiological findings, and treatment outcomes of 60 severe patients with AE from January 1, 2014, to December 31, 2020, were collected. Continuous variables were compared using the t-test and the nonparametric Mann-Whitney U test, as appropriate. Univariate and multivariable logistic regression analyses were performed to assess the correlations between factors, treatment responses, and prognosis of severe AE. Results: The median age of symptom onset was 35 years. Tumors were identified in 23.3% of patients, and 36/60 (60%) patients responded to first-line immunotherapy. Second-line immunotherapy was implemented in 26/60 (43.3%) patients. A significant clinical benefit was observed in 19/26 (73.1%) patients treated with lower dosage rituximab; seven patients were still refractory and received bortezomib as an add-on therapy. During the last follow-up, 48/60 (80%) patients achieved good outcomes (mRS, 0-2), and 10 died. Seventeen patients experienced relapses. A high CD19+ B-cell count (OR, 1.197; 95% CI [1.043-1.496]; p = 0.041) and a lower neutrophil-to-lymphocyte ratio (NLR; OR, 0.686; 95% CI [0.472-0.884]; p = 0.015) predict the response to first-line treatment and good prognosis, respectively. Conclusions: Patients with severe AE were in critical condition at baseline but could be salvaged after effective rescue immunotherapy. A lower dosage of rituximab could be an optimal option for severe AE. CD19+ B-cell count and NLR may provide prognostic information for predicting treatment response and outcome of severe AE.
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Encefalitis , Enfermedad de Hashimoto , Adulto , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/terapia , Humanos , Factores Inmunológicos/uso terapéutico , Pronóstico , Receptores de Antígenos de Linfocitos B , Rituximab/uso terapéuticoRESUMEN
Purpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients. Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up. Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise. Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.
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Objective: This study was performed to assess the potential factors for poor short-term first-line treatment response, the appropriate further treatment options, and the prognosis in patients with autoimmune encephalitis (AE). Methods: This retrospective study consisted of 135 patients with AE. According to their short-term first-line treatment response, patients were divided into the response group and the non-response group. The demographics, clinical characteristics, main accessory examinations, immunotherapy, and outcomes of patients were compared between the two groups. Univariate and multivariate logistic regression models were used to analyze whether non-responders have poor long-term outcomes. Further treatment and prognosis of non-responders were also analyzed. Results: Of the 128 patients who were treated with first-line immunotherapy, 59 (46.1%) were non-responders. Patients in the non-response group had more symptoms and exhibited a higher proportion of mental behavior disorder, central hypoventilation, and autonomic nervous dysfunction. The modified Rankin scale (mRS) scores and neutrophil-to-lymphocyte ratio (NLR) levels were significantly higher and albumin, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (apoA) levels were significantly lower in the non-response group (p < 0.05, all). Multivariate logistic regression analysis showed that the number of clinical symptoms, mental behavior disorder, central hypoventilation, maximum mRS score, and albumin level was independently associated with non-response to short-term first-line treatment. Non-responders had poor long-term outcomes compared with the responders at all times of followed-up (p < 0.05, all). In multivariable analysis, initial first-line treatment response was independently associated with the long-term prognosis, both at 12-month [odds ratio (OR), 4.74, 95% CI, 1.44-15.59, and p=0.010] and 24-month follow-ups (OR, 8.81, 95% CI, 1.65-47.16; and p = 0.011). Among the non-responders, a higher improvement of mRS scores was observed in those who received second-line treatment than those who had no further treatment or repetition of first-line immunotherapy in the follow-up. However, the rate of a good outcome and median mRS scores were not significantly different among the three groups. Conclusion: Disease severity, clinical features, anti-N-methyl-D-aspartate receptor subtypes, antibody titers, NLR, albumin, HDL-C, and apoA levels were all associated with non-response to short-term first-line treatment. The short-term first-line treatment response is a valuable predictor of long-term outcomes in patients with AE. Second-line immunotherapy may be a more aggressive treatment option for patients who failed short-term first-line immunotherapy.
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BACKGROUND: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to investigate the relationship between lipid profiles and prognosis of autoimmune encephalitis (AE) patients. METHODS: This retrospective study consisted of 114 AE patients from September 2014 to September 2020. Data of clinical parameters, including age, sex, body mass index (BMI), clinical features, comorbidities, therapeutic management, lipid profiles, modified Rankin scale (mRS) scores, outcomes, and relapses were collected. Logistic regression models were used to examine the associations between lipid profiles and outcomes of AE. Correlations between lipid profiles and C-reactive protein (CRP), which is an inflammatory marker, were assessed. RESULTS: In the univariate logistic analysis, sex (P = 0.030), mental behavior disorder (P = 0.004), disturbance of consciousness (P = 0.002), mRS at study entry (P = 0.020), tumor comorbidity (P = 0.028), high-density lipoprotein cholesterol (HDL-C) (P = 0.029), apolipoprotein A-I (apoA-I) (P = 0.012), apolipoprotein B (apoB) (P = 0.036) and apoA-I/apoB (P = 0.001) levels were all associated with the unfavorable outcomes of patients. After adjustment for age, sex and mRS at study entry, lower apoA-I and apoA-I /apoB levels were still significantly associated with the unfavorable outcomes of patients. Low HDL-C (P = 0.048) and apoA-I levels (P = 0.026) were also significantly associated with the relapse of AE patients. HDL-C and apoA-I levels were negatively correlated with CRP levels in correlation analysis. CONCLUSIONS: Lipid profiles, especially low HDL-C and apoA-I levels, are significantly associated with the poor outcomes and relapse of AE patients, and seem associated with inflammatory responses. HDL-C and apoA-I levels may be good candidates for predicting prognosis of AE patients.
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Apolipoproteína A-I , Encefalitis , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/metabolismo , HDL-Colesterol , Enfermedad de Hashimoto , Humanos , Recurrencia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Abnormal expression of ionotropic glutamate receptor NMDA type subunit 1, the key subunit of the NMDA receptor, may be related to many neuropsychiatric disorders. In this study, we explored the functional sequence of the 5' regulatory region of the human GRIN1 gene and discussed the transcription factors that may regulate gene expression. MATERIALS AND METHODS: Twelve recombinant pGL3 vectors with gradually truncated fragment lengths were constructed, transfected into HEK-293, U87, and SK-N-SH cell lines, and analyzed through the luciferase reporter gene assay. JASPAR database is used to predict transcription factors. RESULTS: In SK-N-SH and U87 cell lines, regions from -337 to -159 bp, -704 to -556 bp inhibited gene expression, while -556 to -337 bp upregulated gene expression. In HEK-293 and U87 cell lines, the expression of fragment -1703 to + 188 bp was significantly increased compared to adjacent fragments -1539 to + 188 bp and -1843 to + 188 bp. The protein expressions of fragments -2162 to + 188 bp and -2025 to + 188 bp, -1539 to + 188 bp and -1215 to + 188 bp, -1215 to + 188 bp and -1066 to + 188 bp were significantly different in HEK-293 and SK-N-SH cells. According to the predictions of the JASPAR database, the transcription factors REST, EGR1, and CREB1/HIC2 may bind the DNA sequences of GRIN1 gene from the -337 to -159, -556 to -337, and -704 to -556, respectively. In addition, zinc finger transcription factors may regulate the expression of other differentially expressed fragments. CONCLUSIONS: Abnormal transcription regulation in the proximal promoter region of GRIN1 (-704 to + 188 bp) may be involved in the course of neuropsychiatric diseases.
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Regiones no Traducidas 5'/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Línea Celular Tumoral , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Genes Reporteros , Células HEK293 , Humanos , Regiones Promotoras Genéticas/genética , Factores de Transcripción/genética , Transcripción Genética/genética , Activación Transcripcional/genéticaRESUMEN
BACKGROUND: Schizophrenia is a complex brain disorder, the pathogenesis of which remains unclear. Regulator of G-protein signaling 4 is regarded as a candidate gene for schizophrenia risk. The association between the regulator of G-protein signaling 4 gene and the risk of schizophrenia is complicated and controversial, thus, an updated meta-analysis is needed. METHODS: A search strategy using Medical Subject Headings was developed in English (PubMed, SZGene) and Chinese (CNKI, Wanfang, and Weipu) databases. Inclusion and exclusion criteria were used to screen for eligible studies. Parameters, such as P value of Hardy-Weinberg equilibrium, odds ratios, 95% confidence intervals, P values of association, heterogeneity (Ph), and publication bias, were analyzed by the Stata software using a random effects model. Subgroup analyses were performed to detect heterogeneity. RESULTS: There were 15 articles regarding rs10917670 (8046 cases and 8837 controls), 16 regarding rs951436 (8990 cases and 10,568 controls), 15 regarding rs951439 (7995 cases and 8646 controls), 15 regarding rs2661319 (8320 cases and 9440 controls), and 4 regarding rs10759 (2752 cases and 2866 controls). The frequencies of rs10917670 and rs951439 were not significantly different between the case and control groups (Pâ>â.05). As shown by the East Asian and hospital-based subgroup analyses, the genotype TT of rs951436 might be related to the risk of schizophrenia. The genotypes CCâ+âCT of rs2661319 and CCâ+âCA of rs10759 were statistically different between the 2 groups, and the East Asian population contributed to these differences. CONCLUSION: The genotypes CCâ+âCT of rs2661319 and CCâ+âCA of rs10759 might be associated with the risk of schizophrenia.
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Proteínas RGS/genética , Esquizofrenia/genética , Proteínas de Unión al GTP , Predisposición Genética a la Enfermedad , Humanos , Metaanálisis como Asunto , Polimorfismo de Nucleótido Simple , Revisiones Sistemáticas como AsuntoRESUMEN
Personal identification of two individuals in mixed semen samples in forensic DNA testing in general usually involves analysis using autosomal and Y chromosome short tandem repeats (STRs). Results may exclude unrelated donors but cannot identify individuals. In this study, sperm cell capture based on ABH antigen differences was used to obtain the cells with the single ABO blood type. Immunohistochemical staining using labeled anti-A, anti-B, and anti-H antibodies and the laser microdissection system can be used to enrich sperm with different ABO types in mixed seminal stains from two individuals. Then, PCR amplification and capillary electrophoresis were performed to genotype the STR loci. To some extent, after sperm cell capture based on ABH antigen differences, autosomal STR typing using enriched single blood group cells can be utilized to partially identify different individuals in a mixed seminal stain sample from two individuals.
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Sistema del Grupo Sanguíneo ABO/metabolismo , Antígenos/metabolismo , Colorantes/metabolismo , Semen/metabolismo , Espermatozoides/metabolismo , Sistema del Grupo Sanguíneo ABO/genética , Antígenos/genética , ADN/genética , ADN/metabolismo , Dermatoglifia del ADN/métodos , Genotipo , Humanos , Captura por Microdisección con Láser/métodos , Masculino , Repeticiones de Microsatélite/genética , Coloración y Etiquetado/métodosRESUMEN
To explore the influence of weather conditions on the choice of the intercity travel mode of travelers, four modes of traveler transportation were studied in Xi'an, China, in March 2019: airplane, high-speed rail, conventional train, and express bus. The individual characteristics of travelers and intercity travel activity data were obtained, and they were matched with the weather characteristics at the departure time of the travelers. The Bayesian multinomial logit regression was employed to explore the relationship between the travel mode choice and weather characteristics. The results showed that temperature, relative humidity, rainfall, wind, air quality index, and visibility had significant effects on the travel mode selection of travelers, and the addition of these variables could improve the model's predictive performance. The research results can provide a scientific decision basis for traveler flow transfer and the prediction of traffic modes choice due to the effects of climate change.
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Contaminación del Aire , Contaminación del Aire/análisis , Teorema de Bayes , Transportes , Viaje , Tiempo (Meteorología)RESUMEN
Screening suitable reference genes is the premise of quantitative Real-time PCR(qRT-PCR)for gene expression analysis. To provide stable reference genes for expression analysis of genes in Aconitum vilmorinianum, this study selected 19 candidate re-ference genes(ACT1, ACT2, ACT3, aTUB1, aTUB2, bTUB, 18S rRNA, UBQ, eIF2, eIF3, eIF4, eIF5, CYP, GAPDH1, GAPDH2, PP2A1, PP2A2, ACP, and EF1α) based on the transcriptome data of A. vilmorinianum. qRT-PCR was conducted to profile the expression of these genes in the root, stem, leaf, and flower of A. vilmorinianum. The Ct values showed that 18S rRNA with high expression level and GAPDH2 with large expression difference among organs were not suitable as the reference genes. NormFinder and geNorm showed similar results of the expression stability of the other candidate reference genes and demonstrated PP2A1, EF1α, and CYP as the highly stable ones. However, BestKeeper suggested EF1α, ACT3, and PP2A1 as the top stable genes. In view of the different results from different softwares, the geometric mean method was employed to analyze the expression stability of the candidate re-ference genes, the results of which indicated that PP2A1, EF1α, and ACT3 were the most stable. Based on the comprehensive analysis results of geNorm, NormFinder, BestKeeper, and geometric mean method, PP2A1 and EF1α presented the most stable expression in different organs of A. vilmorinianum. PP2A1 and EF1α were the superior reference genes for gene expression profiling in different organs of A. vilmorinianum.
Asunto(s)
Aconitum , Perfilación de la Expresión Génica , Genes de Plantas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estándares de Referencia , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Treatment resistance leads to physiological, psychological, and economical effects among patients with anti-N-methyl d-aspartate receptor (anti-NMDAR) encephalitis, and the clinical and immune characteristics of these patients remain to be described. According to our clinical experience, bortezomib may be effective due to its plasma-cells depletion ability. Herein, the clinical presentations and immune parameters, including B cell and antibody secreting cell (ASC) abundance, of 5 enrolled treatment-resistant patients are described. When compared with 5 treatment-sensitive cases, the patients had serious clinical presentations but comparable B cells and ASCs. After receiving bortezomib, the ASC count and anti-NMDAR antibody titers decreased effectively. All 5 patients had a favorable prognosis (mRS ≤ 2) with a median follow-up of 31 months without severe side effects or relapse.