Variants in BSN gene associated with epilepsy with favourable outcome.

BACKGROUND: BSN gene encodes Bassoon, an essential protein to assemble the cytomatrix at the active zone of neurotransmitter release. This study aims to explore the relationship between BSN variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 313 cases (trios) with epilepsies of unknown causes. Additional cases with BSN variants were collected from China Epilepsy Gene V.1.0 Matching Platform. The Clinical Validity Framework of ClinGen was used to evaluate the relationship between BSN variants and epilepsy. RESULTS: Four pairs of compound heterozygous variants and one cosegregating heterozygous missense variant in BSN were identified in five unrelated families. These variants presented statistically higher frequency in the case cohort than in controls. Additional two de novo heterozygous nonsense variants and one cosegregating heterozygous missense variant were identified in three unrelated cases from the gene matching platform, which were not present in the Genome Aggregation Database. The missense variants tended to be located in C-terminus, including the two monoallelic missense variants. Protein modelling showed that at least one missense variant in each pair of compound heterozygous variants had hydrogen bond alterations. Clinically, two cases were diagnosed as idiopathic generalised epilepsy, two as focal epilepsy and the remaining four as epilepsy with febrile seizures plus. Seven out of eight probands showed infancy or childhood-onset epilepsy. Eight out of 10 affected individuals had a history of febrile convulsions. All the cases were seizure-free. The cases with monoallelic variants achieved seizure-free without treatment or under monotherapy, while cases with biallelic missense variants mostly required combined therapy. The evidence from ClinGen Framework suggested an association between BSN variants and epilepsy. CONCLUSION: The BSN gene was potentially a novel candidate gene for epilepsy. The phenotypical severity was associated with the genotypes and the molecular subregional effects of the variants.

Measurement method of the RDC for the IPS and FFS-LCD.

The residual direct current (RDC) almost always brings serious image sticking (IS) problems in LCDs and is mainly related to the liquid crystal (LC) and photoaligned polyimide. In this paper, we propose a novel method, to the best of our knowledge, to evaluate the RDC of the FFS-LCDs through an optical measurement system. By this means, the accumulation and release of the ions can be seen distinctly through the transmittance-time curves with the voltage regulation. Hence, it is helpful to compare and analyze the RDC problem of different displays. Moreover, this method possesses the advantage of high efficiency and simplicity in order to benefit the material design in photoaligned polyimide or the LC.

TFCP2, a binding protein of ATF3, promotes the progression of glioma by activating the synthesis of serine.

Glioma is one of the most common malignancies. De novo serine synthesis promotes glioma progression and therapeutic resistance. Therefore, clarifying the regulatory mechanism of serine synthesis is of great significance for glioma therapy. In this study, we found that the expression of TFCP2 was upregulated in glioma and that TFCP2 promoted glioma cell growth and sphere formation. Knockdown of TFCP2 expression inhibited glioma cell growth, sphere formation and tumorigenicity in nude mice. In terms of its molecular mechanism, TFCP2 was found to interact with ATF3 to cooperatively regulate the de novo synthesis of serine. Knockdown of TFCP2 expression significantly inhibited the binding of ATF3 to the promoter of PHGDH (a rate-limiting enzyme in the serine synthesis process). In conclusion, our studies proved that TFCP2 jointly regulates the de novo synthesis of serine through interaction with ATF3, thus promoting glioma progression. This study suggests that TFCP2 is a potential target for glioma therapy.

143D, a novel selective KRASG12C inhibitor exhibits potent antitumor activity in preclinical models.

The KRASG12C mutant has emerged as an important therapeutic target in recent years. Covalent inhibitors have shown promising antitumor activity against KRASG12C-mutant cancers in the clinic. In this study, a structure-based and focused chemical library analysis was performed, which led to the identification of 143D as a novel, highly potent and selective KRASG12C inhibitor. The antitumor efficacy of 143D in vitro and in vivo was comparable with that of AMG510 and of MRTX849, two well-characterized KRASG12C inhibitors. At low nanomolar concentrations, 143D showed biochemical and cellular potency for inhibiting the effects of the KRASG12C mutation. 143D selectively inhibited cell proliferation and induced G1-phase cell cycle arrest and apoptosis by downregulating KRASG12C-dependent signal transduction. Compared with MRTX849, 143D exhibited a longer half-life and higher maximum concentration (Cmax) and area under the curve (AUC) values in mouse models, as determined by tissue distribution assays. Additionally, 143D crossed the blood‒brain barrier. Treatment with 143D led to the sustained inhibition of KRAS signaling and tumor regression in KRASG12C-mutant tumors. Moreover, 143D combined with EGFR/MEK/ERK signaling inhibitors showed enhanced antitumor activity both in vitro and in vivo. Taken together, our findings indicate that 143D may be a promising drug candidate with favorable pharmaceutical properties for the treatment of cancers harboring the KRASG12C mutation.

Trans-base and trans-vault low-velocity penetrating brain injury: A retrospective comparative study of characteristics, treatment, and outcomes.

PURPOSE: Low-velocity penetrating brain injury (LVPBI) caused by foreign bodies can pose life-threatening emergencies. Their complexity and lack of validated classification data have prevented standardization of clinical management. We aimed to compare the trans-base and trans-vault phenotypes of LVPBI to help provide guidance for clinical decision-making of such injury type. METHODS: A retrospective study on LVPBI patients managed at our institution from November 2013 to March 2020 was conducted. We included LVPBI patients admitted for the first time for surgery, and excluded those with multiple injuries, gunshot wounds, pregnancy, severe blunt head trauma, etc. Patients were categorized into trans-base and trans-vault LVPBI groups based on the penetration pathway. Discharged patients were followed up by outpatient visit or telephone. The data were entered into the Electronic Medical Record system by clinicians, and subsequently derived by researchers. The demography and injury characteristics, treatment protocols, complications, and outcomes were analyzed and compared between the two groups. A t-test was used for analysis of normally distributed data, and a Mann-Whitney U test for non-parametric data. A generalized linear model was further established to determine whether the factors length of stay and performance scale score were influenced by each factor. RESULTS: A total of 27 LVPBI patients were included in this analysis, comprised of 13 (48.1%) trans-base cases and 14 (51.9%) trans-vault cases. Statistical analyses suggested that trans-base LVPBI was correlated with deeper wounds; while the trans-vault phenotype was correlated with injury by metal foreign bodies. There was no difference in Glasgow Coma Scale score and the risk of intracranial hemorrhage between the two groups. Surgical approaches in the trans-base LVPBI group included subfrontal (n = 5, 38.5%), subtemporal (n = 5, 38.5%), lateral fissure (n = 2, 15.4%), and distal lateral (n = 1, 7.7%). All patients in the trans-vault group underwent a brain convex approach using the foreign body as reference (n = 14, 100%). Moreover, the two groups differed in application prerequisites for intracranial pressure monitoring and vessel-related treatment. Trans-base LVPBI was associated with higher rates of cranial nerve and major vessel injuries; in contrast, trans-vault LVPBI was associated with lower functional outcome scores. CONCLUSION: Our findings suggest that trans-base and trans-vault LVPBIs differ in terms of characteristics, treatment, and outcomes. Further understanding of these differences may help guide clinical decisions and contribute to a better management of LVPBIs.

[Component analysis of excretory/secretory protein from Trichinella spiralis adult worm].

Objective: To analyze the component of adult worm excretory/secretory protein(AWESP) from Trichinella spiralis using the shotgun method, and find out the active component underlying its regulatory effect on colitis in humans. Methods: The T. spiralis AWESP was prepared, separated by SDS-PAGE, lysed with trypsin, and analyzed by shotgun LC-MS/MS. The protein components were determined with the Masco software and classified using the Gene Ontology(GO) method in cellular components, molecular functions, and biological processes. Results: The AWESPs isolated by SDS-PAGE had a Mr of 15 000-116 000. A total of 280 proteins were revealed by LC-MS/MS, of which 96 were identified by Masco software, 98 were putative, and the remaining 86 were unclear. Preliminary results showed that 4 proteins had regulatory potential for colitis, including cysteine protease inhibitor, serine protease, 53 000 excretory/secretory antigen, and glutathione-S-transferase. GO enrichment analysis showed that the identified proteins had 104 different molecular functions, involved in 363 biological processes. Conclusion: As revealed by the Masco software, T. spiralis AWESP has complex components and 96 have been identified in this study. Four of them are preliminarily shown to be associated with the anti-colitis effect of T. spiralis.

Type 1 Metallothionein (ZjMT) Is Responsible for Heavy Metal Tolerance in Ziziphus jujuba.

Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich, metal-binding proteins that are able to make cells to uptake heavy metals from the environment. Molecular and functional characterization of this gene family improves understanding of the mechanisms underlying heavy metal tolerance in higher organisms. In this study, a cDNA clone, encoding 74-a.a. metallothionein type 1 protein (ZjMT), was isolated from the cDNA library of Ziziphus jujuba. At the N- and C-terminals of the deduced amino acid sequence of ZjMT, six cysteine residues were arranged in a CXCXXXCXCXXXCXC and CXCXXXCXCXXCXC structure, respectively, indicating that ZjMT is a type 1 MT. Quantitative PCR analysis of plants subjected to cadmium stress showed enhanced expression of ZjMT gene in Z. jujuba within 24 h upon Cd exposure. Escherichia coli cells expressing ZjMT exhibited enhanced metal tolerance and higher accumulation of metal ions compared with control cells. The results indicate that ZjMT contributes to the detoxification of metal ions and provides marked tolerance against metal stresses. Therefore, ZjMT may be a potential candidate for tolerance enhancement in vulnerable plants to heavy metal stress and E. coli cells containing the ZjMT gene may be applied to adsorb heavy metals in polluted wastewater.

ATP6V1A variants are associated with childhood epilepsy with favorable outcome.

PURPOSE: ATP6V1A variants have been identified in patients with highly variable phenotypes such as autosomal dominant epileptic encephalopathy and autosomal recessive cutis laxa. However, the mechanism underlying phenotype variation is unknown. We screened ATP6V1A variants in patients with epilepsy and analyzed the genotype-phenotype correlation to explain the mechanism underlying phenotypic variations. METHODS: We performed trio-based whole-exome sequencing in people with epilepsy without acquired causes. All previously reported ATP6V1A variants were systematically retrieved from the HGMD and PubMed databases. RESULTS: Three novel de novo ATP6V1A variants, including c.749G>C/p.Gly250Ala, c.782A>G/p.Gln261Arg, and c.1103T>C/p.Met368Thr, were identified in three unrelated cases with childhood focal (partial) epilepsy. None of the variants were listed in any public population database and evaluated as likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics (ACMG). All persons showed good responses to anti-seizure medication and psychomotor development was normal. Further analysis showed that monoallelic missense variants were associated with epilepsy with variable severity, whereas biallelic variants resulted in developmental abnormalities of multisystem that may result in early lethality. CONCLUSION: Childhood focal epilepsy with favorable outcome was probably a novel phenotype of ATP6V1A. ATP6V1A variants are associated with a range of phenotypes that correlate with genotypes. The relationship between phenotype severity and the genotype (genetic impairment) of ATP6V1A variants helps explain the phenotypic variations.

Efficacy and safety of perampanel as the first add-on therapy for children with epilepsy: A real-world multicenter prospective observational study.

OBJECTIVE: Perampanel (PER) is a new anti-seizure medication (ASM) with a novel mechanism of action. This study aimed to determine the efficacy and safety of PER when added to monotherapy in children and adolescents (age, 4-18 years) with epilepsy. METHOD: A multicenter prospective observational study was performed on children and adolescents (age, 4-18 years) with epilepsy who did not respond to ASM monotherapy between July 2021 and October 2022. PER was used as the first add-on therapy for the enrolled patients. Seizure-free rate, response rate, inefficacy rate, and drug retention rate were the main observation indicators during the 6 months of treatment. The patients were grouped based on treatment efficacy, and factors affecting efficacy were statistically analyzed. Adverse reactions were also recorded. RESULTS: In this study, 93 patients with epilepsy were enrolled; among them, 9 patients were lost to follow-up (attrition rate, 9.7 %), and 84 were included in the analysis. Five patients with unknown efficacy discontinued taking PER early due to intolerable adverse reactions, and 79 patients (48 males, 31 females; mean age, 11.0 ± 3.9 years) finally remained. Genetic epilepsy and structural epilepsy were found in 22 patients and 36 patients, respectively. The mean duration of epilepsy history at the time of PER initiation was 4.0 ± 3.8 years, and the mean maintenance dosage of add-on PER was 4.5 ± 1.8 mg/day (equivalent to 0.14 ± 0.07 mg/kg/day). Among the 79 patients, 28 patients were diagnosed with epilepsy syndrome, including 13 patients having self-limited epilepsy with centrotemporal spikes, among whom 9 patients were seizure-free after adding PER during the 6-month follow-up (seizure-free rate, 69.2 %). For these 79 patients, the seizure-free, response, and retention rates at the end of follow-up were 45.6 %, 74.7 %, and 82.1 %, respectively. Among the 84 patients included in the analyses, adverse reactions occurred in 20 patients, mainly dizziness (8 patients), somnolence (6 patients), and irritability (4 patients), and 4 patients developed two adverse reactions simultaneously. Univariate analyses revealed statistically significant differences in efficacy between groups with structural and non-structural epilepsy and between groups with different baseline concomitant ASMs, suggesting that these factors affected the efficacy of PER as the first add-on therapy. CONCLUSION: The overall response rate of PER as the first add-on therapy for children and adolescents with epilepsy who were followed up for 6 months was 74.7 %, indicating a relatively favorable safety and tolerability profile. The group of the baseline concomitant ASM administered and the etiological classification of epilepsy as either structural or non-structural were the factors influencing the efficacy of PER as the first add-on therapy.

De novo GABRA1 variants in childhood epilepsies and the molecular subregional effects.

Background: The GABRA1 gene, encoding the GABRAR subunit α1, plays vital roles in inhibitory neurons. Previously, the GABRA1 gene has been identified to be associated with developmental and epileptic encephalopathy (DEE) and idiopathic generalized epilepsy (IGE). This study aims to explore the phenotypic spectrum of GABRA1 and molecular subregional effect analysis. Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported GABRA1 mutations were systematically reviewed to analyze the molecular subregional effects. Results: De novo GABRA1 mutations were identified in six unrelated patients with heterogeneous epilepsy, including three missense mutations (p.His83Asn, p.Val207Phe, and p.Arg214Cys) and one frameshift mutation (p.Thr453Hisfs*47). The two missense mutations, p.His83Asn and p.Val207Phe, were predicted to decrease the protein stability but no hydrogen bond alteration, with which the two patients also presented with mild genetic epilepsy with febrile seizures plus and achieved seizure-free status by monotherapy. The missense variant p.Arg214Cys was predicted to decrease protein stability and destroy hydrogen bonds with surrounding residues, which was recurrently identified in three cases with severe DEE. The frameshift variant p.Thr453Hisfs*47 was located in the last fifth residue of the C-terminus and caused an extension of 47 amino acids, with which the patients presented with moderated epilepsy with generalized tonic-clonic seizures alone (GTCA) but achieved seizure-free status by four drugs. The four variants were not presented in gnomAD and were evaluated as "pathogenic/likely pathogenic" according to ACMG criteria. Analysis of all reported cases indicated that patients with mutations in the N-terminal extracellular region presented a significantly higher percentage of FS and DEE, and the patients with variants in the transmembrane region presented earlier seizure onset ages. Significance: This study suggested that GABRA1 variants were potentially associated with a spectrum of epilepsies, including EFS+, DEE, and GTCA. Phenotypic severity may be associated with the damaging effect of variants. The molecular subregional effects help in understanding the underlying mechanism of phenotypic variation.

Clinicopathological value of hematopoietic cell kinase overexpression in laryngeal squamous cell carcinoma tissues.

Laryngeal squamous cell carcinoma (LSCC) is the most lethal cancer in head and neck tumors. Although hematopoietic cell kinase (HCK) has been proven to be an oncogene in several solid tumors, its roles in LSCC remain obscure. This is the first study to evaluate the clinical value of HCK in LSCC, with the aim of exploring its expression status and potential molecular mechanisms underlying LSCC. LSCC tissue-derived gene chips and RNA-seq data were collected for a quantitive integration of HCK mRNA expression level. To confirm the protein expression level of HCK, a total of 82 LSCC tissue specimens and 56 non-tumor laryngeal epithelial controls were collected for in-house tissue microarrays and immunohistochemical staining. Kaplan-Meier curves were generated to determine the ability of HCK in predicting overall survival, progress-free survival, and disease-free survival of LSCC patients. LSCC overexpressed genes and HCK co-expressed genes were intersected to preliminarily explore the enriched signaling pathways of HCK. It was noticed that HCK mRNA was markedly overexpressed in 323 LSCC tissues compared with 196 non-LSCC controls (standardized mean difference = 0.81, p < 0.0001). Upregulated HCK mRNA displayed a moderate discriminatory ability between LSCC tissues and non-tumor laryngeal epithelial controls (area under the curve = 0.78, sensitivity = 0.76, specificity = 0.68). The higher expression level of HCK mRNA could predict worse overall survival and disease-free survival for LSCC patients (p = 0.041 and p = 0.013). Lastly, upregulated co-expression genes of HCK were significantly enriched in leukocyte cell-cell adhesion, secretory granule membrane, and extracellular matrix structural constituent. Immune-related pathways were the predominantly activated signals, such as cytokine-cytokine receptor interaction, Th17 cell differentiation, and Toll-like receptor signaling pathway. In conclusion, HCK was upregulated in LSCC tissues and could be utilized as a risk predictor. HCK may promote the development of LSCC by disturbing immune signaling pathways.

DLG3 variants caused X-linked epilepsy with/without neurodevelopmental disorders and the genotype-phenotype correlation.

Background: The DLG3 gene encodes disks large membrane-associated guanylate kinase scaffold protein 3, which plays essential roles in the clustering of N-methyl-D-aspartate receptors (NMDARs) at excitatory synapses. Previously, DLG3 has been identified as the causative gene of X-linked intellectual developmental disorder-90 (XLID-90; OMIM# 300850). This study aims to explore the phenotypic spectrum of DLG3 and the genotype-phenotype correlation. Methods: Trios-based whole-exome sequencing was performed in patients with epilepsy of unknown causes. To analyze the genotype-phenotype correlations, previously reported DLG3 variants were systematically reviewed. Results: DLG3 variants were identified in seven unrelated cases with epilepsy. These variants had no hemizygous frequencies in controls. All variants were predicted to be damaging by silico tools and alter the hydrogen bonds with surrounding residues and/or protein stability. Four cases mainly presented with generalized seizures, including generalized tonic-clonic and myoclonic seizures, and the other three cases exhibited secondary generalized tonic-clonic seizures and focal seizures. Multifocal discharges were recorded in all cases during electroencephalography monitoring, including the four cases with generalized discharges initially but multifocal discharges after drug treating. Protein-protein interaction network analysis revealed that DLG3 interacts with 52 genes with high confidence, in which the majority of disease-causing genes were associated with a wide spectrum of neurodevelopmental disorder (NDD) and epilepsy. Three patients with variants locating outside functional domains all achieved seizure-free, while the four patients with variants locating in functional domains presented poor control of seizures. Analysis of previously reported cases revealed that patients with non-null variants presented higher percentages of epilepsy than those with null variants, suggesting a genotype-phenotype correlation. Significance: This study suggested that DLG3 variants were associated with epilepsy with/without NDD, expanding the phenotypic spectrum of DLG3. The observed genotype-phenotype correlation potentially contributes to the understanding of the underlying mechanisms driving phenotypic variation.

Intracranial Pressure after Closure of Dura Predicts Decompressive Craniectomy in Patients with Head Trauma.

This study aimed to address the risk factors of second decompressive craniectomy (DC) in patients with traumatic brain injury (TBI) who initially underwent mass lesion evacuation, but no primary DC. Patients were enrolled if they had had a hospital visit to Xiangya Hospital, Central South University with acute closed TBI from January 1, 2017 to December 31, 2019 and had undergone craniotomic mass lesion evacuation. Sociodemographic information, computed tomography (CT) information, clinical profiles, and surgical information were obtained from an electronic database. Twenty-four patients who had undergone a second decompressive craniectomy (SDC) and 39 patients who had not (NSO) were included in the analysis. The prevailing lesions differed between the groups (p = 0.010). The SDC group had more compressed/obliterated basal cisterns than the NSO group (p = 0.028). After closure of the dura, the SDC group also had higher intracranial pressure (ICP) than the NSO group (10.9 mm Hg vs. 6.5 mm Hg, p = 0.005). Binary logistical regression indicated that ICP after dura closure was an independent predictor of second DC (odds ratio [OR] = 1.317, p = 0.011). A model using ICP after dura closure alone had an area under the curve value of 0.757 in its receiver operating characteristic curve. An ICP >10.5 mm Hg after closure of dura for the prediction of a second DC had a sensitivity of 56.3% and a specificity of 92.6%.

Anti-Seizure Medication Treatment of Benign Childhood Epilepsy With Centrotemporal Spikes: A Systematic Review and Meta-analysis.

Background: This study aimed to evaluate the efficacy and tolerability of Anti-Seizure medication (ASM) treatment in patients with BECTS. Method: We searched PubMed, Cochrane Library, Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WANFANG DATA, and China Science and Technology Journal Database (VIP) between 1 Jan 1990, and 1 Sep 2021, for randomized controlled studies. Data on seizure freedom rate, rate of treatment withdrawal due to serious adverse events, rate of any adverse events and dropout, 50% remission rate, the proportion of patients whose EEG to be normalized, and improvement in cognitive function were extracted by two authors independently. The pooled data were meta-analyzed using a random effects model. Results: A total of 27 studies evaluating 9 ASMs were included, 19 of which were suitable for meta-analysis. Compared with sulthiame (STM), levetiracetam (LEV) was associated with a higher probability of treatment withdrawal due to serious adverse events [RR = 5.12, 95% CI (1.19, 22.01), I 2 = 0.0%], experiencing any adverse events [RR = 5.12, 95% CI (1.19, 22.01)], and dropping out for any reason [RR = 3.17, 95% CI (1.36, 10.11)], while it did not affect the seizure freedom rate [RR = 0.90, 95% CI (0.75, 1.06)]. LEV significantly improved cognitive performance relative to carbamazepine (CBZ) but had no effect on the proportion of any adverse events [RR = 0.62, 95% CI (0.25, 1.59)] and EEG to be normalized [RR = 1.27, 95% CI (0.94, 1.71)]. There was no higher probability of a 50% remission rate when comparing valproic acid (VPA) to LEV [RR = 0.96, 95% CI (0.57, 1.61)] and oxcarbazepine (OXC) [RR = 0.61, 95% CI (0.31, 1.20)]. In addition, STM was related to a higher probability of EEG normalization than placebo [RR = 4.61, 95% CI (2.12, 10.01)]. The included single studies also provided some evidence for the efficacy and/or tolerability of other ASMs in BECTS, including topiramate, lamotrigine, clobazam, and clonazepam. The risk of bias of the included studies was frequently low or unclear. Conclusion: This study indicated some discrepancies in efficacy and tolerability among ASMs used in patients with BECTS. More randomized controlled trials (RCTs) comparing ASMs with larger populations are required to ascertain the optimum antiepileptic drug treatment to guide clinicians.

Assessment of electroencephalography and event-related potentials in unresponsive patients with brain injury.

OBJECTIVE: To investigate the predictors of clinical outcomes in unresponsive patients with acquired brain injuries. METHODS: Patients with coma or disorders of consciousness were enrolled from August 2019 to March 2021. A retrospective analysis of demographics, etiology, clinical score, diagnosis, electroencephalography (EEG), and event-related potential (ERP) data from 1 week to 2 months after coma onset was conducted. Findings were assessed for predicting favorable outcomes at 6 months post-coma, and functional outcomes were determined using the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Of 68 patients, 22 patients had a good neurological outcome at 6 months, while 11 died. Univariate analysis showed that motor response (Motor-R; p < 0.001), EEG pattern (p = 0.015), sleep spindles (p = 0.018), EEG reactivity (EEG-R; p < 0.001), mismatch negativity (MMN) amplitude at electrode Fz (FzMMNA; p = 0.001), P3a latency (p = 0.044), and P3a amplitude at electrode Cz (CzP3aA; p < 0.001) were significantly correlated with patient prognosis. Multivariable logistic regression analysis showed that FzMMNA, CzP3aA, EEG-R, and Motor-R were significant independent predictors of a favorable outcome. The sensitivity and specificity of FzMMNA (dichotomized at 1.16 µV) were 86.4% and 58.5%, and of CzP3aA (cut-off value 2.76 µV) were 90.9% and 70.7%, respectively. ERP amplitude (ERP-A), a combination of FzMMNA and CzP3aA, improved prediction accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.884. A model incorporating Motor-R, EEG-R, and ERP-A yielded an outstanding predictive performance (AUC=0.921) for a favorable outcome. CONCLUSION: ERP-A and the prognostic model resulted in the efficient prediction of a favorable outcome in unresponsive patients.

Efficacy comparison of oxcarbazepine and levetiracetam monotherapy among patients with newly diagnosed focal epilepsy in China: A multicenter, open-label, randomized study.

AIMS: This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China. METHODS: Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods. RESULTS: In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups. CONCLUSIONS: OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

A quantitative roadmap for China towards carbon neutrality in 2060 using methanol and ammonia as energy carriers.

Carbon neutrality by 2060 is the recent expression of China's international commitment to reduce its carbon dioxide emissions. Energy and chemical sectors, the two main contributors for carbon dioxide emissions in China, are the biggest bottlenecks for reaching the objective of carbon neutrality. Moreover, coal-to-ammonia production and coal-to-methanol production are the major CO2 emission process contributors in China's coal chemical sector. Herein, a possible route to the carbon neutral target based on energy-chemical nexus for electricity generation as well as methanol and ammonia production is proposed in this study. The most cost-effective solution for meeting the commitment is identified by considering regional variations in renewable and non-renewable resources and adopting an optimized regional cooperation. According to the roadmap presented in this study, an optimized combination of fossil fuels and renewable energies forming "blue energy economy" is feasible and promising.

LHX9, a p53-binding protein, inhibits the progression of glioma by suppressing glycolysis.

PURPOSE: LHX9 methylation has been reported in many tumors, but its functions and related mechanisms in glioma are still unknown and need to be verified. METHODS: The protein level of LHX9 in glioma tissues was examined using western blotting and immunohistochemistry, and the functions of LHX9 in glioma cell lines were investigated using MTT and colony formation assays. In addition, the interaction between LHX9 and P53 was analyzed by immunoprecipitation, and the roles of LHX9 in cancer metabolism were explored by measuring metabolites. RESULTS: In this study, we found that the LHX9 expression level was decreased in glioma specimens, and the upregulation of LHX9 expression inhibited the growth of glioma cells in liquid medium and on soft agar. Regarding the molecular mechanism, we found that LHX9 interacted with p53, and downregulation of LHX9 promoted the expression of the glycolysis-related enzyme PGK1 and increased the lactic acid content. By interfering with the expression of LHX9, the tumorigenicity of glioma cells was promoted, an outcome blocked by further interference with PGK1 expression. CONCLUSION: In summary, the decreased expression of LHX9 in gliomas activates the expression of the glycolysis-related enzyme PGK1, thereby promoting the development of gliomas, suggesting that the LHX9-PGK1 signaling axis can be used as a target for the treatment of glioma.

ASH1L mutation caused seizures and intellectual disability in twin sisters.

ASH1L mutations have been identified with variable phenotypes, including intellectual disability, autism spectrum disorder (ASD), and multiple congenital anomalies (MCA). However, the mechanisms underlying this phenotypic variation remain unknown. Here, we present twin sisters exhibiting mild intellectual disability and seizures. Whole-exome sequencing of the family revealed a novel de novo heterozygous sequence variant, NM_018489.2: c.2678dup (p.Lys894*) in exon 3 of ASH1L which was estimated to be pathogenic. Furthermore, we reviewed previously reported ASH1L mutations in order to evaluate genotype-phenotype correlations for ASH1L variants. We found that patients with missense mutations in ASH1L appeared to present with more severe phenotypes and a higher likelihood of ASD than those with truncating mutations. The relationship between phenotype and genotype reported across several patients may help to explain the mechanisms underlying the phenotypic variation commonly observed between ASH1L mutations.

LncRNA NEAT1 promotes malignant phenotypes and TMZ resistance in glioblastoma stem cells by regulating let-7g-5p/MAP3K1 axis.

Glioblastoma multiforme (GBM) is one of the most malign brain tumors in adults. Temozolomide (TMZ) is an oral chemotherapy drug constituting the backbone of chemotherapy regimens utilized as first-line treatment of GBM. However, resistance to TMZ often leads to treatment failure. In the present study, we explored the expression and related mechanisms of nuclear enriched abundant transcript 1 (NEAT1) in glioma stem cells (GSCs). Quantitative real-time PCR (qRT-PCR) showed that NEAT1 was up-regulated in serum samples of GBM patients and GSCs isolated from U87, U251 cell lines. Functional experiments showed that NEAT1 knockdown restrained malignant behaviors of GSC, including proliferation, migration and invasion. Dual-luciferase assays identified let-7g-5p was a downstream target and negatively adjusted by NEAT1. Restoration of let-7g-5p impeded tumor progression by inhibiting proliferation, migration and invasion. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as a direct target of let-7g-5p, was positively regulated by NEAT1 and involved to affect the regulation of NEAT1 on GSCs' behaviors. In conclusion, our results suggested that NEAT1 promoted GSCs progression via NEAT1/let-7g-5p/MAP3K1 axis, which provided a depth insight into TMZ resistance mechanism.