Association Between Wnt Target Genes and Cortical Volumes in Alzheimer's Disease.

The disproportionate cortical atrophy is an established biomarker for the pathophysiological process of Alzheimer's disease (AD). However, the genetic basis underlying the cortical atrophy remains poorly defined. Herein, we aim to illustrate the effect of the Wnt target genes on the cortical volumes of AD patients. 82 sporadic AD patients were recruited. All the subjects had history survey, blood biochemical examination, cognitive assessment, MRI morphometry and whole exome sequencing. This report focused on 84 common variants (minor allele frequency > 0.01) of 32 Wnt target genes, including the APC, DAAM1, DACT1, DISC1, LATS2, TLR2, WDR61, and the AXIN, DVL, FZD, LRP, TCF/LEF, WNT family genes. The Wnt target genes showed asymmetric effects on the cortical volumes of AD patients. The right temporal/parietal/occipital cortices were more affected than left temporal/parietal/occipital cortices. Nevertheless, the reverse applied to the frontal cortex. The DACT1 affected the cortical thickness most, followed by the TCF3 and APC. The DACT1 rs698025-GG genotype displayed greater right temporal pole and left medial orbito-frontal gyrus than rs698025-GA genotype (2.4 ± 0.4 vs. 2.0 ± 0.6, P = 0.005; 5.2 ± 0.6 vs. 5.0 ± 0.6, P = 0.001). The brain region most influenced by the Wnt target genes was the right calcarine cortex. In conclusion, the common variants of the Wnt target genes exert asymmetric effects on the cortical volumes of AD patients. The Wnt signaling pathway may play a role in the cortical atrophy of AD patients.

Genotypic and phenotypic heterogeneity among Chinese pediatric genetic white matter disorders.

BACKGROUND: The pediatric genetic white matter disorders are characterized by a broad disease spectrum. Genetic testing is valuable in the diagnosis. However, there are few studies on the clinical and genetic spectrum of Chinese pediatric genetic white matter disorders. METHODS: The participants were enrolled from the cohort of Peking Union Medical College Hospital. They all received history collection, brain MRI and gene sequencing. Their neurologic complaints which were related to white matter disorders occurred before 18. Brain MRI indicated periventricular and/or deep white matter lesions, fazekas grade 2-3. RESULTS: Among the 13 subjects, there were 11 males and two females. The average age of onset was 10.0 ± 5.5 years old. The potential genetic variants were found in 84.6% (11/13) subjects. The ABCD1 showed the greatest mutation frequency (30.8%, 4/13). The EIF2B3 A151fs, EIF2B4 c.885 + 2T > G, EIF2B5 R129X and MPV17 Q142X were novel pathogenic/likely pathogenic variants. 100% (4/4) ABCD1 carriers were accompanied by visual impairment, whereas 100% (3/3) EIF2B carriers developed dysuria. 100% (4/4) ABCD1 carriers exhibited diffuse white matter hyperintensities mainly in the posterior cortical regions, while the EIF2B4 and EIF2B5 carriers were accompanied by cystic degeneration. CONCLUSION: There is genotypic and phenotypic heterogeneity among Chinese subjects with pediatric genetic white matter disorders. The knowledge of these clinical and genetic characteristics facilitates an accurate diagnosis of these diseases.

WGCNA and transcriptome profiling reveal hub genes for key development stage seed size/oil content between wild and cultivated soybean.

BACKGROUND: Soybean is one of the most important oil crops in the world. The domestication of wild soybean has resulted in significant changes in the seed oil content and seed size of cultivated soybeans. To better understand the molecular mechanisms of seed formation and oil content accumulation, WDD01514 (E1), ZYD00463 (E2), and two extreme progenies (E23 and E171) derived from RILs were used for weighted gene coexpression network analysis (WGCNA) combined with transcriptome analysis. RESULTS: In this study, both seed weight and oil content in E1 and E171 were significantly higher than those in E2 and E23, and 20 DAF and 30 DAF may be key stages of soybean seed oil content accumulation and weight increase. Pathways such as "Photosynthesis", "Carbon metabolism", and "Fatty acid metabolism", were involved in oil content accumulation and grain formation between wild and cultivated soybeans at 20 and 30 DAF according to RNA-seq analysis. A total of 121 oil content accumulation and 189 seed formation candidate genes were screened from differentially expressed genes. WGCNA identified six modules related to seed oil content and seed weight, and 76 candidate genes were screened from modules and network. Among them, 16 genes were used for qRT-PCR and tissue specific expression pattern analysis, and their expression-levels in 33-wild and 23-cultivated soybean varieties were subjected to correlation analysis; some key genes were verified as likely to be involved in oil content accumulation and grain formation. CONCLUSIONS: Overall, these results contribute to an understanding of seed lipid metabolism and seed size during seed development, and identify potential functional genes for improving soybean yield and seed oil quantity.

Potential toxicity of bisphenol A to α-chymotrypsin and the corresponding mechanisms of their binding.

Bisphenol A (BPA) is an endocrine disruptor widely existing in plastics and resins, which can accumulate in animals and human bodies, posing a potential threat to the physiological and biochemical reactions of human beings or other organisms. α-Chymotrypsin is a kind of proteolytic enzyme existing in humans and animals, which can cause diseases when its activity is excessive. However, there is a lack of research on the mechanism of endocrine disruptors affecting α-chymotrypsin activity. In this study, the interaction between BPA and α-chymotrypsin was proved via multiple spectroscopic approaches, enzyme activity change, isothermal titration calorimetry and molecular docking. Results showed that α-chymotrypsin's polypeptide chains were unfolded, and protein skeletons were loosened with the exposure to BPA. α-Helix content increased and ß-sheet content was decreased. The particle size of the BPA-α-chymotrypsin complex became smaller. Fluorescence sensitization may also be explained by a perturbation of the chromophore Trp 141. The thermodynamic parameters of the binding reaction were measured by isothermal titration calorimetry (ITC), which showed that there was hydrophobic interaction between BPA and α-chymotrypsin, which was consistent with the results of molecular docking. Moreover, BPA may stop near the active center of α-chymotrypsin and interact with the key residues His 57 and Ser 195. The above phenomenon explained the result that the activity of α-chymotrypsin increased to 139% when exposed to high dose BPA (40 µM). Taken together, the effects of BPA on the structure and function of α-chymotrypsin were clarified at the molecular level, which made up the gap in the mechanism of BPA on the proteolytic enzyme, and provided a reliable basis for disease avoidance and prevention.

Clinical-neuroimaging-pathological relationship analysis of adult onset Neuronal Intranuclear Inclusion Disease (NIID).

BACKGROUND: Neuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. We aim to analysis the relationship between clinical manifestations, neuroimaging and skin pathology in a Chinese NIID cohort. METHODS: Patients were recruited from a Chinese cohort. Detail clinical information were collected. Visual rating scale was used for evaluation of neuroimaging. The relationship between clinical presentations and neuroimaging, as well as skin pathology was statistically analyzed. RESULTS: Thirty-two patients were recruited. The average onset age was 54.3 y/o. 28.1% had positive family history. Dementia, autonomic nervous system dysfunction, episodic attacks were three main presentations. CSF analysis including Aß42 and tau level was almost normal. The most frequently involved on MRI was periventricular white matter (100%), frontal subcortical and deep white matter (96.6%), corpus callosum (93.1%) and external capsule (72.4%). Corticomedullary junction DWI high intensity was found in 87.1% patients. Frontal and external capsule DWI high intensity connected to form a "kite-like" specific image. Severity of dementia was significantly related to leukoencephalopathy (r = 0.465, p = 0.0254), but not cortical atrophy and ventricular enlargement. Grey matter lesions were significantly associated with encephalopathy like attacks (p = 0.00077) but not stroke like attacks. The density of intranuclear inclusions in skin biopsy was not associated with disease duration, severity of leukoencephalopathy and dementia. CONCLUSIONS: Specific distribution of leukoencephalopathy and DWI high intensity were indicative. Leukoencephalopathy and subcortical mechanism were critical in pathogenesis of NIID. Irrelevant of inclusion density and clinical map suggested the direct pathogenic factor need further investigation.

Comparisons of constitutive resistances to soybean cyst nematode between PI 88788- and Peking-type sources of resistance in soybean by transcriptomic and metabolomic profilings.

Soybean cyst nematode (SCN) is a serious damaging disease in soybean worldwide. Peking- and PI 88788-type sources of resistance are two most important germplasm used in breeding resistant soybean cultivars against this disease. However, until now, no comparisons of constitutive resistances to soybean cyst nematode between these two types of sources had been conducted, probably due to the influences of different backgrounds. In this study, we used pooled-sample analysis strategy to minimize the influence of different backgrounds and directly compared the molecular mechanisms underlying constitutive resistance to soybean cyst nematode between these two types of sources via transcriptomic and metabolomic profilings. Six resistant soybean accessions that have identical haplotypes as Peking at Rgh1 and Rhg4 loci were pooled to represent Peking-type sources. The PI88788-type and control pools were also constructed in a same way. Through transcriptomic and metabolomics anaylses, differentially expressed genes and metabolites were identified. The molecular pathways involved in the metabolism of toxic metabolites were predicted to play important roles in conferring soybean cyst nematode resistance to soybean. Functions of two resistant candidate genes were confirmed by hairy roots transformation methods in soybean. Our studies can be helpful for soybean scientists to further learn about the molecular mechanism of resistance to soybean cyst nematode in soybean.

Outcomes in patients with rheumatoid versus osteoarthritis for total hip arthroplasty: A meta-analysis and systematic review.

OBJECTIVE: Total hip arthroplasty(THA) in patients with osteoarthritis(OA) are considered to be a successful procedure, but with little being known about outcomes in patients with rheumatoid arthritis (RA). The aim of this study was to compare rates of THA complications in patients with RA versus OA. METHODS: The PUBMED, EMBASE, and Cochrane Library databases were searched for all available studies comparing the outcomes of THA in RA and OA patients. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). Meta-analysis was performed using Stata 12.0 software. RESULTS: Twenty-three studies with a total of 877,695 patients were included. Results showed that patients in the RA group were more likely to have revision (OR=1.15, 95% CI, 1.02-1.29; P = 0.019), hip dislocation (OR=2.31, 95% CI, 1.67-3.20; P<0.01), periprosthetic infection (OR=1.44, 95% CI, 1.29-1.61; P<0.01), wound infection (OR=2.15, 95% CI, 1.19-3.90; P = 0.01), and revision for late infection (ES=1.71, 95% CI, 0.54-1.80; P<0.01) than those in the OA group. Subgroup analysis showed no significant difference in revision rates (OR=1.12, 95%CI, 0.94-1.31; P = 0.21) between the two groups in studies published before 2010, while studies published after 2010 showed significantly higher revision rates (OR=1.15, 95%CI, 1.02-1.30; P = 0.04) in the RA group. There were no significant differences in mortality (OR=1.20,95% CI, 0.89-1.61; P = 0.23), deep vein thrombosis (OR=0.52, 95% CI, 0.12-2.34; P = 0.40) between the groups. THA can improve the function and reduce pain of patients with RA. CONCLUSION: Our study indicated that compared with OA, patients with RA are at higher risk of complications after THA. But THA can relieve pain, improve function and the quality of life of patients with RA, and did not increase mortality risk. Therefore, THA can be used as a treatment option for RA patients who failed to respond to conservative treatment. Patients should be fully informed of the benefits and possible risks of surgery, individualized treatment strategy should be made.

Evaluation of fluorene-caused ecotoxicological responses and the mechanism underlying its toxicity in Eisenia fetida: Multi-level analysis of biological organization.

Fluorene is an important toxic chemical that exists ubiquitously in the environment, and it has also been suggested to exert potential deleterious effects on soil invertebrates. However, knowledge about the toxic effects of fluorene and its underlying mechanisms of the effects on key soil organism earthworms remains limited. From this view point, this study was undertaken to explore the potential effects of fluorene and its underlying mechanisms in Eisenia fetida at the level of experimental animals, tissue, cell, and molecule. It was concluded that fluorene exerted lethal activity to adult E. fetida on day 14 with the LC50 determined to be 88.61 mg/kg. Fluorene-induced ROS caused oxidative stress in E. fetida, resulting in DNA damage, protein carbonylation, and lipid peroxidation. Moreover, changed antioxidative enzymatic activities, non-enzymatic antioxidative activities, and total antioxidative capacity in E. fetida by fluorene stress are associated with antioxidative and protective effects. High-dose fluorene (> 2.5 mg/kg) exposure significantly caused histopathological lesions including the microstructure of body wall, intestine, and seminal vesicle of earthworms. Also, the reproductive system of E. fetida was clearly disrupted by fluorene stress, leading to poor reproduction ability (decreased cocoon and juvenile production) in earthworms. It is found that E. fetida growth was significantly inhibited when treated with high-dose fluorene, thereby causing normal growth disorders. Additionally, fluorene stress triggered the abnormal mRNA expression related to oxidative stress (e.g., metallothionein and heat shock protein 70), growth (translationally controlled tumour protein), reproduction (annetocin precursor) in E. fetida. Together, both high-dose and long-term exposure elicited more severe poisoning effects on earthworms using the Integrated Biological Response (IBR) index, and E. fetida coelomocyte DNA was the most negatively affected by fluorene stress. This study comprehensively evaluated fluorene-induced toxicity in E. fetida, and its underlying molecular mechanisms mediating the toxic responses have been elucidated. These findings provide valuable data for assessing potential ecological risks posed by fluorene-contaminated soil.

Generation of a human induced pluripotent stem cell (iPSC) line from skin fibroblasts of a patient carrying an E363Q mutation in PSEN1 gene.

Alzheimer's disease (AD) is a common neurodegenerative disease characterized by cognitive decline even leading to incapacity, which prevalence estimates that about 5% of AD cases are caused by mutations in genes such as Presenilin-1 (PSEN1). Here we report the generation and characterization of an iPSC line derived from a patient carrying an E363Q mutation in PSEN1 gene. The iPSC line we generated presented a typical morphology, normal karyotype, free from Sendai viral vectors and exogenous factors, expressed endogenous pluripotency marker genes and proteins, which could form embryoid bodies in vitro and form teratoma in vivo as well, demonstrating its pluripotency.

Colour, chemical compounds, and antioxidant capacity of Astragali Radix based on untargeted metabolomics and targeted quantification.

INTRODUCTION: Astragali Radix has been used for over 2000 years in traditional Chinese medicine. Its secondary xylem "Jinjing" and secondary phloem "Yulan" are important for evaluating the quality of the Daodi medicinal material in China. However, its systematic characterisation has not been conducted. OBJECTIVE: This study aims to investigate the colour, chemical compounds, and antioxidant capacity of the secondary xylem and phloem of Astragali Radix on the basis of untargeted metabolomics, broadening the application scope of Astragali Radix in food and pharmaceutical industries. METHODS: The L*, a*, and b* of the secondary xylem and phloem were measured by colorimetry, and the chemical compounds were identified and quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography-diode array detector-evaporative light scattering detection. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays were conducted to evaluate their antioxidant capacity. RESULTS: Thirty-one compounds were identified by UPLC-Q-TOF-MS. The secondary xylem exhibited high parameter b*, flavonoid content, and antioxidant capacity, while the secondary phloem was rich in astragalosides. The colour parameters of well-defined type A significantly varied from those of the other types. Well-defined type A also exhibited the highest antioxidant activity and flavonoid content, followed by middle type A-like, middle type B-like, and yellow shading type B. CONCLUSION: The colour parameters, chemical compounds, and antioxidant capacity among the different transverse sections of secondary xylem and phloem varied. The yellow colour of secondary xylem was correlated to high flavonoid content and antioxidant activity, and well-defined type A of Astragali Radix had better quality than other types.

Discrepancy of apoptotic events in mouse hepatocytes and catalase performance: Size-dependent cellular and molecular toxicity of ultrafine carbon black.

The diversification of the production process and application of ultrafine carbon black (UFCB), one of the nanomaterials, make the difference in particle sizes that exposed to environment. Currently, few size-dependent toxicity studies of UFCB pay attention to targeted effects on detoxification organs. And there is a research gap in the size-dependent molecular toxicity of UFCB. Based on this, mouse hepatocytes and catalase (CAT) were used as targeted receptors for UFCB size-dependent cellular and molecular toxicity studies. Results indicate that UFCB13 nm induced higher ROS and lipid peroxidation levels. And the cell viability decreased to 22.5%, which is sharp contrast to UFCB50 nm (45.3%) and UFCB95 nm (55.1%). Mitochondrial dysfunction and a 25.2% early apoptosis rate are the further manifestation of the stronger cytotoxicity of UFCB13 nm. At the molecular level, the exposure of UFCB with better dispersity resulted in more significant changes in the CAT backbone and secondary structure, fluorescence sensitization and enzyme function inhibition. The combined experiments show that the cellular uptake and dispersity of UFCB are the dominating factors for the discrepancy in size-dependent cellular and molecular toxicity, respectively. This study provides a theoretical basis for the necessary circumvention and substitution of UFCB in engineering applications.

Outcomes of hip arthroplasty in Parkinson's disease: a meta-analysis and systematic review.

PURPOSE: Hip arthroplasty in Parkinson's disease (PD) is considered to be associated with higher mortality, perioperative complications, and worse clinical outcomes. The purpose of this study was to evaluate the outcomes of hip arthroplasty in PD. METHODS: The PUBMED, EMBASE, and Cochrane Library databases were searched for all available studies comparing the outcomes of hip arthroplasty in PD and non-PD patients. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). Meta-analysis was performed using Stata 12.0 software. RESULTS: Six retrospective cohort studies with a total of 59,878 patients were included. Among them, there were 15,313 patients in the Parkinson's group and 44,565 in the non-Parkinson's group. Results showed that patients in the Parkinson's group were more likely to have periprosthetic fracture (OR = 7.93, 95% CI, 1.96-32.04; P = 0.004), revision surgery (OR = 2.33, 95% CI, 1.37-3.98; P = 0.002), deep vein thrombosis (OR = 2.34, 95% CI, 1.56-3.49; P < 0.01), and urinary tract infection (OR = 1.34, 95% CI, 1.20-1.49; P < 0.01) than those in the non-Parkinson's group. The Parkinson's group had a longer hospital stay (WMD = 0.38, 95% CI, 0.24-0.52; P < 0.01) and higher hospitalization costs (WMD = 2487.08, 95% CI, 225.99-4748.17; P = 0.03), but there was no significant difference in short-term postoperative mortality (OR = 1.07, 95% CI, 0.65-1.73; P = 0.80). Hip arthroplasty can significantly improve the function of patients with PD and reduce pain. CONCLUSION: Although hip arthroplasty in patients with PD is associated with a higher revision rate and potential risk, it does not increase short-term mortality and can reduce pain, improve function, and improve quality of life. The periprosthetic fracture risk and revision rate are significantly higher and should be accounted for when deciding on operative treatment and communicated to patient with PD.

The combination of ultrafine carbon black and lead provokes cytotoxicity and apoptosis in mice lung fibroblasts through oxidative stress-activated mitochondrial pathways.

Ultrafine particulates (UFPs) are considered one of the most hazardous of all air pollutants, which can be directly inhaled into the human body and cause direct damage to lung tissues. Lung fibroblasts (LF) play an important role in the structure and function of lung and there are few studies on primary cells at present. So, the article focuses on LF as the research objective and ultrafine carbon black (UFCB) and Pb-UFCB (loaded with lead) as a representative of UFPs to study the effect on LF. The results showed that UFCB and Pb-UFCB inhibited LF proliferation due to cell cycle arrested in the S phase, and induced apoptosis. Additionally, UFCB or Pb-UFCB could induce oxidative stress manifested as the increase of intracellular reactive oxygen species. The redox imbalance was further confirmed by measuring the changes of related enzymes, including the activity of superoxide dismutase and catalase and the level of reduced glutathione and malondialdehyde in cells. Moreover, the elevated lactate dehydrogenase in the culture medium indicated that cell membrane had been injured. And mitochondrial function was impaired by the imbalance of ATP synthesis and hydrolysis. In summary, both induced oxidative stress, which is the main driving force of LF early apoptosis, disruption of cell membrane integrity and mitochondrial function. Here, we provide a meaningful and challenging subject to explore the toxic effect and mechanism between UFPs and lung tissue at cellular levels, and theoretical basics for the possible changes of lung tissue function in vivo.

The differential diagnosis of pneumonia in two patients infected by atypical pathogens.

The current study presents two patients who lived in a rural family with close contact and suffered from rapidly progressive pneumonia. Chest computed tomography images and lymphocytopenia indicated the possibility of COVID-19 infection, but antibody and nucleic acid tests excluded this possibility. Negative results were obtained from corresponding tests for pneumococcal, adenovirus, fungal and legionella infection. Metagenomics analysis and subsequent antibody tests confirmed mycoplasma pneumonia. After treating with moxifloxacin, both patients recovered well and left the hospital. In terms of complicated infectious disease, consideration of atypical pathogens and medical and epidemiological history were important for differential diagnosis of COVID-19; metagenomics analysis was useful to provide direct references for diagnosis.

Study on the osteogenesis of rat mesenchymal stem cells and the long-term antibacterial activity of Staphylococcus epidermidis on the surface of silver-rich TiN/Ag modified titanium alloy.

The main causes of failure of orthopedic implants are infection and poor bone ingrowth. Surface modification of the implants to allow for long-term antibacterial and osteogenic functions is an effective solution to prevent failure of the implants. We developed silver-rich TiN/Ag nano-multilayers on the surface of titanium alloy with different doses of Ag+ . The antibacterial stability and osteogenesis of the silver-rich surface were determined by evaluating the adhesion and proliferation of Staphylococcus epidermidis, and the adhesion, proliferation, alkaline phosphatase activity, extracellular matrix mineralization, and the expression level of genes involved in osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs). The results demonstrated that the antibacterial rates (Ra) of 5 × 1016 -Ag, 1 × 1017 -Ag, 5 × 1017 -Ag, and 1 × 1018 -Ag were respectively 46.21%, 85.66%, 94.99%, 98.48%, and 99.99%. After subcutaneous implantation in rats or immersion in phosphate buffered saline for up to 12 weeks, the silver-rich surface of the titanium alloy showed long-term stable inhibition of Staphylococcus epidermidis. Furthermore, in vitro and in vivo studies indicated that the Ag-implanted titanium did not show apparent cytotoxicity and that lower Ag+ implanted groups (5 × 1016 -Ag, 1 × 1017 -Ag) had better viability and biological safety when compared with higher Ag+ implanted groups. In addition, when compared with the Ti6Al4V-group, all Ag-implanted groups exhibited enhanced osteogenic indicators in rat BMSCs. Regarding osteogenic indicators, the surfaces of the 5 × 1017 -Ag group had better osteogenic effects than those of other groups. Therefore, the proper dose of Ag+ implanted TiN/Ag nano-multilayers may be one of the options for the hard tissue replacement materials with antibacterial activity and osteogenic functions.

Epidemiology of traumatic brain injury-associated epilepsy in western China: An analysis of multicenter data.

OBJECTIVES: This study aims to explore the probability of developing posttraumatic epilepsy (PTE) in the following 8 years after traumatic brain injury (TBI), the risk factors associated with PTE and its cumulative prevalence. METHODS: This is a retrospective follow-up study of patients with traumatic brain injury (TBI) discharged from the West China Hospital between January 1, 2011 and December 31, 2017, Chengdu Shang Jin Nan Fu Hospital and Sichuan Provincial People's Hospital from January 1, 2013 to March 1, 2015. We used forward stepwise method to build the final multivariate cox proportional hazard regression model to obtain estimates of hazard ratio (HR) of PTE and 95% confidence intervals (CI). We also conducted Kaplan-Meier survival analysis to investigate the cumulative prevalence of PTE. RESULTS: The cumulative incidence of PTE rose from 6.2% in one year to 10.6% in eight years. There were more male patients in PTE group and generally older. Besides, patients with PTE tended to have abnormal CT scan results. The risk factors of PTE were male (HR = 1.6, 95% CI: 1.1-2.2, P = 0.009), early posttraumatic seizures (HR = 2.9, 95% CI: 2.2-4.1, P < 0.001), TBI severity (moderate TBI: HR = 3.0, 95% CI: 1.8-5.0, P = 0.001; severe TBI: HR = 4.3, 95% CI: 2.3-7.6, P < 0.029), loss of consciousness (LOC) more than 30 min (30 min-24 h: HR = 1.8, 95% CI: 1.02-3.1, P = 0.041; >24 h: HR = 2.4, 95% CI: 1.4-2.4, P = 0.001), subdural hematoma (SDH) (HR = 1.9, 95% CI: 1.4-2.5, P < 0.001), brain contusion sites (frontal-temporal lobe: HR = 2.7, 95% CI: 1.9-3.9, P < 0.001; other sites: HR = 1.5, 95% CI: 1.01-2.3, P = 0.042) and cranial surgery (HR = 1.7, 95% CI: 1.3-2.3, P < 0.001). SIGNIFICANCE: The probability of developing PTE increased during the study period. In addition, the risk of developing PTE was significantly associated with gender, EPTS, LOC time, SDH, brain contusion sites, surgery and TBI severity. However, further researches may be needed to predict the risk of PTE in combination with quantitative factors.

The tolerability and safety profile of eslicarbazepine acetate in neurological disorders.

OBJECTIVES: This study aimed to assess the tolerability and safety profile of eslicarbazepine acetate (ESL). METHODS: Placebo controlled, double-blind randomized controlled trials (RCTs) were enrolled by searching Pubmed, Embase, Cochrane Online Library, and clinicaltrial.gov. Studies evaluating the safety of ESL on any neurological disorders were included. Adverse events (AEs), serious AEs and AEs-related withdrawals were pooled by direct or indirect meta-analysis. RESULTS: A total of 4067 patients in 13 RCTs (5 for refractory partial epilepsy, 2 for bipolar I disorder, 1 for migraine, 1 for fibromyalgia, 2 for diabetic neuropathic pain, and 2 for post-herpetic neuralgia) were included. Meta-analysis revealed that ESL treatment had a higher incidence of serious AEs and AEs-related withdrawals than the placebo. Of 35 reported AEs, 13 were significantly associated with ESL treatment, including blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, hyponatraemia, increased gamma-glutamyl transferase, and dysarthria. Subgroup analysis revealed that dizziness was the only AE significant at 400 mg/day, while diplopia, nausea, vomiting, dizziness, somnolence, rash, and hyponatremia at 800 mg/day, and blurred vision, diplopia, vertigo, nausea, vomiting, fatigue, dizziness, somnolence, headache, rash, and hyponatremia at 1200 mg/day were significant. Adjunctive use of ESL in refractory epilepsy significantly led to higher risk for vestibulocerebellar AEs than other disorders. CONCLUSIONS: ESL treatment was related to a range of AEs, especially at high doses or when used as adjunctive therapy in epilepsy. While the majority of AEs of ESL were related to the vestibulocerebellar system, hyponatremia and rash should also be noted by clinicians.

Quantitative trait loci analysis of seed oil content and composition of wild and cultivated soybean.

BACKGROUND: Soybean oil is a major source of edible oil, and the domestication of wild soybean has resulted in significant changes in oil content and composition. Extensive efforts have been made to identify genetic loci that are related to soybean oil traits. The objective of this study was to identify quantitative trait loci (QTLs) related to soybean seed oil and compare the fatty acid composition between wild and cultivated soybean. RESULTS: Using the specific-locus amplified fragment sequencing (SLAF-seq) method, a total of 181 recombinant inbred lines (RILs) derived from a cross between wild soybean ZYD00463 (Glycine soja) and cultivated soybean WDD01514 (Glycine max) were genotyped. Finally, a high-density genetic linkage map comprising 11,398 single-nucleotide polymorphism (SNP) markers on 20 linkage groups (LGs) was constructed. Twenty-four stable QTLs for seed oil content and composition were identified by model-based composite interval mapping (CIM) across multiple environments. Among these QTLs, 23 overlapped with or were adjacent to previously reported QTLs. One QTL, qPA10_1 (5.94-9.98 Mb) on Chr. Ten is a novel locus for palmitic acid. In the intervals of stable QTLs, some interesting genes involved in lipid metabolism were detected. CONCLUSIONS: We developed 181 RILs from a cross between wild soybean ZYD00463 and cultivated soybean WDD01514 and constructed a high-density genetic map using the SLAF-seq method. We identified 24 stable QTLs for seed oil content and compositions, which includes qPA10_1 on Chr. 10, a novel locus for palmitic acid. Some interesting genes in the QTL regions were also detected. Our study will provide useful information for scientists to learn about genetic variations in lipid metabolism between wild and cultivated soybean.

Artificial selection on GmOLEO1 contributes to the increase in seed oil during soybean domestication.

Increasing seed oil content is one of the most important breeding goals for soybean due to a high global demand for edible vegetable oil. However, genetic improvement of seed oil content has been difficult in soybean because of the complexity of oil metabolism. Determining the major variants and molecular mechanisms conferring oil accumulation is critical for substantial oil enhancement in soybean and other oilseed crops. In this study, we evaluated the seed oil contents of 219 diverse soybean accessions across six different environments and dissected the underlying mechanism using a high-resolution genome-wide association study (GWAS). An environmentally stable quantitative trait locus (QTL), GqOil20, significantly associated with oil content was identified, accounting for 23.70% of the total phenotypic variance of seed oil across multiple environments. Haplotype and expression analyses indicate that an oleosin protein-encoding gene (GmOLEO1), colocated with a leading single nucleotide polymorphism (SNP) from the GWAS, was significantly correlated with seed oil content. GmOLEO1 is predominantly expressed during seed maturation, and GmOLEO1 is localized to accumulated oil bodies (OBs) in maturing seeds. Overexpression of GmOLEO1 significantly enriched smaller OBs and increased seed oil content by 10.6% compared with those of control seeds. A time-course transcriptomics analysis between transgenic and control soybeans indicated that GmOLEO1 positively enhanced oil accumulation by affecting triacylglycerol metabolism. Our results also showed that strong artificial selection had occurred in the promoter region of GmOLEO1, which resulted in its high expression in cultivated soybean relative to wild soybean, leading to increased seed oil accumulation. The GmOLEO1 locus may serve as a direct target for both genetic engineering and selection for soybean oil improvement.

Predictors of seizure reduction outcome after vagus nerve stimulation in drug-resistant epilepsy.

PURPOSE: To evaluate the predictors of seizure reduction outcome after vagus nerve stimulation (VNS) in patients with drug-resistant epilepsy (DRE). METHODS: A meta-analysis was performed using relevant research from databases such as PubMed, Embase, Cochrane Online Library, and Clinicaltrials.gov. Studies were selected according to predefined inclusion and exclusion criteria. The quality of studies was evaluated by using the Newcastle-Ottawa Scale (NOS) scale. All data was pooled by STATA 12.0 software for meta-analysis. RESULTS: The review considered 1281 articles, and 16 articles with NOS score ≥6 were included in the analysis. The meta-analysis showed that at 6 m, 1, 2, 3, 4, 6 and 12 years after implantation, 33.99, 43.42, 46.50, 63.31, 52.71, 54.64, 70.37 and 82.90% of patients exhibited >50% reduction of seizure frequency after VNS. The duration of epilepsy showed a significant difference between the good responders and poor responders (p = 0.038), whereas age at VNS implantation (p = 0.305), age at seizure onset (p = 0.530), seizure type (p = 0.11), etiology (p = 0.187), and history of previous epilepsy surgery (p = 0.075) were not predictors of seizure reduction outcome after VNS. Several features about the electroencephalogram (EEG) feature and heart rhythm complexity (HRV) have not been analyzed by a sufficient number of studies. CONCLUSIONS: DRE patients with shorter duration of epilepsy may be better candidates for VNS rather than those who are younger at onset and implantation. Several EEG or HRV features may have predictive value but more research is needed.