Identification of a novel Src inhibitor K882 derived from quinazoline-based stilbenes with anti-NSCLC effect.

The growing concern about drug resistance to KRAS G12C inhibitors emphasizes the urgent need for effective therapies targeting NSCLC with KRAS G12C mutation. In this research, a series of quinazoline-based stilbene derivatives were designed, synthesized and assayed for cytotoxic activities against human KRAS G12C mutant NSCLC NCI-H358 cells. Among them, K882 (4e) exhibited remarkable inhibitory activities on tumor cell proliferation, migration and invasion, as well as tumor organoids growth in vitro.

Genetic and phenotypic analysis of 225 Chinese children with developmental delay and/or intellectual disability using whole-exome sequencing.

Developmental delay (DD), or intellectual disability (ID) is a very large group of early onset disorders that affects 1-2% of children worldwide, which have diverse genetic causes that should be identified. Genetic studies can elucidate the pathogenesis underlying DD/ID. In this study, whole-exome sequencing (WES) was performed on 225 Chinese DD/ID children (208 cases were sequenced as proband-parent trio) who were classified into seven phenotype subgroups.

Seizure course of PCDH19 clustering epilepsy in female children: A multicentre cohort study in China.

Aim: To investigate the seizure course of PCDH19 clustering epilepsy (PCDH19-CE) in a cohort of female children in China.

Method: This ambidirectional cohort study examined 113 female patients with PCDH19-CE through multicentre collaboration. Prognostic factors for seizure freedom were evaluated by multivariate Cox regression analysis.

Competitive adsorption characteristics of VOCs and water vapor by activated carbon prepared from Fe/N-doped pistachio shell.

Various materials have been developed to capture volatile organic compounds (VOCs) to mitigate air pollution. However, sorbent materials with excellent resistance to water are rare. Here, several Fe/N-doped activated carbons (ACs) have been prepared to capture VOCs in humid environments.

The effects of early combined training on the physical development of preterm infants with different gestational ages.

Objective: To investigate the effects of early combined training on the physical development of preterm infants of different gestational ages.

Methods: A total of 144 preterm infants from our hospital's neonatal intensive care unit (NICU) between 2019 and 2020 were selected as the research participants and randomly divided into an intervention group (77 cases) and a control group (67 cases). The physical development and catch-up growth satisfaction rate of preterm infants in the intervention and control groups were compared at 40 weeks, 3 months, 6 months and 12 months of corrected age.

Case Report: Identification of Two Variants of in Families With or Without Seizure and Binocular Strabismus: Phenotypic Spectrum Analysis.

Genetic causes in most affected children with intellectual disability and/or development delay remain unknown. To identify potential variants responsible for these disorders, we recruited 161 affected families and performed whole-exome sequencing and associated bioinformatics analysis. In the present study, we report the identification of variants in the gene in two of the families.

Effect of nitrogen functional groups on competitive adsorption between toluene and water vapor onto nitrogen-doped spherical resorcinol-formaldehyde resin-based activated carbon.

To elucidate the effect of nitrogen functional groups on the competitive adsorption of toluene and water vapor, a series of N-doped resorcinol-formaldehyde resin-based activated carbons using g-CN as the nitrogen source were prepared, which possessed different N contents (1.29-6.14%).

A Novel Variant of the Gene Associated With Developmental Delay and Myoclonic Epilepsy.

Pathogenic variants in have been reported to have a wide range of phenotypic variability in neurodevelopmental disorders, such as early-onset epileptic encephalopathy, developmental delay, and behavior problems. So far, there is no clear correlation between genotypes and phenotypes. This study reports a Chinese patient with a novel heterozygous mutation (c.

Adsorption/desorption characteristics of low-concentration semi-volatile organic compounds in vapor phase on activated carbon.

The adsorption/desorption behaviors of semi-volatile organic compounds (SVOCs: 1,2,3,4-tetrachlorobenzene (TCB) and phenol) in vapor phase by activated carbon (AC) were investigated by the experiments and density functional theory calculation. Investigations showed that at 100-160 °C, the adsorption capacities of TCB and phenol on AC were in the range of 176.6-342.

Alkylation modified pistachio shell-based biochar to promote the adsorption of VOCs in high humidity environment.

The objective of this work was to evaluate the adsorption capacity of alkylated modified porous biochar prepared by esterification and etherification (PSAC-2) for low concentrate volatile organic compounds (VOCs, toluene and ethyl acetate) in high humidity environment by experiments and theoretical calculations. Results showed that PSAC-2 has a large specific surface area and weak surface polarity, at 80% relative humidity, its capacities for toluene and ethyl acetate adsorption could be maintained at 92% and 87% of the initial capacities (169.9 mg/g and 96.

Generation of an iPSC line (SMCPGi001-A) from a patient with Bain type X-linked mental retardation syndrome carrying HNRNPH2 gene mutation.

Bain type X-linked mental retardation syndrome is an X-linked dominant neurodevelopmental disorder characterized by psychomotor developmental delay and intellectual disability. The rare syndrome is caused by HNRNPH2 gene mutation. In this study, the iPSC cell line (SMCPGi001-A) was acquired by Sendai virus-mediated iPSC reprogramming from the peripheral blood mononuclear cells (PBMCs) obtained from a 1-year-old girl with de novo p.

The adsorption properties of microporous activated carbon prepared from pistachio nut shell for low-concentration VOCs under low-medium temperatures.

The control of low-concentration VOCs in coal-fired flue gas is one of the research hotspots at present. In this work, KCO and KCO-KCl were employed to activate the agricultural wastes (pistachio nut shell) to prepare activated carbon (AC), named PSAC-1 and PSAC-2, respectively. By testing the adsorption performance of the prepared AC and commercial activated carbon (CAC) for the five target VOCs, it was observed that the adsorption capacity of PSAC-2 was the best compared to the other two.

Removal characteristics of organic pollutants by the adsorbent injection coupled with bag filtering system.

Activated carbon (AC) injection coupled with bag filtering (ACI+BF) is a promising technology for the organic pollutant treatment in the flue gas of coal-fired power plants. The removal characteristics of six volatile organic compounds (VOCs) and adsorption pathways were investigated in a self-designed ACI+BF system. The results suggested that o-xylene had the highest removal efficiency and that was the lowest for benzene, which was influenced by their boiling points and saturated vapor pressures.

Three intellectual disability-associated de novo mutations in MECP2 identified by trio-WES analysis.

Background: To date, at least 746 genes have been identified to cause intellectual disability (ID). Among them, mutations in the Methyl CpG binding protein 2 (MECP2) gene are the leading cause of Rett syndrome and associated ID.

Methods: Considering the large number of ID-associated genes, we applied trio-based whole-exome sequencing (trio-WES) and in silico analysis for genetic diagnosis of 294 children with ID.

Gene-Focused Networks Underlying Phenotypic Convergence in a Systematically Phenotyped Cohort With Heterogeneous Intellectual Disability.

The broad spectrum of intellectual disability (ID) patients' clinical manifestations, the heterogeneity of ID genetic variation, and the diversity of the phenotypic variation represent major challenges for ID diagnosis. By exploiting a manually curated systematic phenotyping cohort of 3803 patients harboring ID, we identified 704 pathogenic genes, 3848 pathogenic sites, and 2075 standard phenotypes for underlying molecular perturbations and their phenotypic impact. We found the positive correlation between the number of phenotypes and that of patients that revealed their extreme heterogeneities, and the relative contribution of multiple determinants to the heterogeneity of ID phenotypes.

De novo SCN1A, SCN8A, and CLCN2 mutations in childhood absence epilepsy.

This study aimed to identify monogenic mutations from Chinese patients with childhood absence epilepsy (CAE) and summarize their characteristics. A total of 100 patients with CAE were recruited in Peking University First Hospital from 2005 to 2016 and underwent telephone and outpatient follow-up review. We used targeted disease-specific gene capture sequencing (involving 300 genes) to identify pathogenic variations for these patients.

Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing.

Background The mutations of thiamine pyrophosphokinase-1 (TPK1) gene have been frequently studied in some patients with thiamine metabolism dysfunction syndrome-5 (THMD5), while TPK1 mutations in Chinese patients have been investigated by only homozygous. A search of the literature on the mutations in the Chinese population currently published revealed that no reports of compound heterozygous mutations were reported. Here, we report a Chinese patient with compound heterozygous TPK1 mutations who underwent magnetic resonance imaging (MRI), whole exome sequencing (WES), molecular diagnosis, bioinformatics analysis, and three-dimensional (3D) protein structure analysis.

Two novel L2HGDH mutations identified in a rare Chinese family with L-2-hydroxyglutaric aciduria.

Background: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons.

Case Presentation: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results.

[Detection of subtelomeric copy number variations in children with intellectual disability].

Objective: To detect subtelomeric copy number variations in children with genetic intellectual disability (ID) using multiplex ligation-dependent probe amplification (MLPA), and to investigate the pathogenesis of genetic ID.

Methods: A total of 68 children with ID who had normal results of G-banding karyotype analysis were included in the study. Their subtelomeric copy number variations were detected using MLPA P036.

[Analysis of MLC1 gene mutation in a Chinese family with megalencephalic leukoencephalopathy with subcortical cysts].

The clinical data of a patient with megalencephalic leukoencephalopathy (MLC) with subcortical cysts and her parents were collected. MLC1 gene mutation was detected by polymerase chain reaction and direct DNA sequencing. The patient presented with motor developmental delay and giant skull, and brain magnetic resonance imaging showed diffuse white matter swelling accompanied by subcortical cysts in bilateral frontal and parietal lobes.

Perinatal occipital lobe injury in children: analysis of twenty-one cases.

This study used magnetic resonance imaging to analyze causes and clinical courses of pediatric occipital lobe injury. Patients undergoing magnetic resonance imaging for suspected bilateral occipital lobe injury at our Neurodevelopmental Department between July 2007 and June 2011 were included. We evaluated magnetic resonance imaging characteristics, clinical courses, electroencephalogram monitoring, and Denver Development Screen Test scores.

Epilepsy in children with methylmalonic acidemia: electroclinical features and prognosis.

Objective: To summarize the electroclinical features and prognosis of epilepsy in children with methylmalonic acidemia (MMA).

Methods: The medical records of hospitalized MMA patients associated with epilepsy were retrospectively reviewed. The clinical manifestations, laboratory examination results, and treatment modalities were analyzed.

Analysis of SCN1A mutation and parental origin in patients with Dravet syndrome.

Dravet syndrome (DS) or severe myoclonic epilepsy of infancy is an intractable epileptic syndrome that is caused by mutations in the neuronal voltage-gated sodium channel alpha1 subunit gene SCN1A. We investigated SCN1A mutations in 63 Chinese patients with DS and analyzed its inheritance. Genomic DNA was extracted from peripheral blood lymphocytes of DS patients and their available parents.

Childhood absence epilepsy: Elctroclinical features and diagnostic criteria.

Objective: To analyze the electroclinical features of children with childhood absence epilepsy (CAE) and discuss the diagnostic criteria for CAE.

Methods: The video-electroencephalogram (VEEG) database in our hospital was searched using "absence seizures" and "3-Hz generalized spike and waves (GSW)" as key-words. Other epileptic syndromes with typical absence seizures were carefully excluded.