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A method for the remote regioselective alkynylation of unactivated C(sp3)–H bonds in diverse aliphatic amides by photogenerated amidyl radicals has been developed. The site-selectivity is dominated via a 1,5-hydrogen atom transfer (HAT) process of the amide. Mild reaction conditions and high regioselectivity are demonstrated in this methodology. [ABSTRACT FROM AUTHOR]

Fivefold twin (FFT) and lamellar (LAM) structures are the primary configurations during the crystallization of alloys. However, the co-existence of these two structures in one system and the conversion mechanism are barely explored. In this study, we investigated the rapid solidification process of a Ti3Al alloy by using molecular dynamics simulation and discussed the evolution of the microstructure under two first-order phase transitions in detail. The first phase transition followed Ostwald's step rule, and the nucleation pathway in the system was supercooled liquid → BCC → FCC/HCP. A new phase transition pattern of FFTs transformed into a LAM structure leading to a second phase transition was found. The FFT atoms first transformed into other atoms as the partition interface, and then the LAM structure consumed Other atoms and grew further. The interconversions between different clusters were unstable and required complex intermediate states to reach stability. These findings provide a new understanding of the relationship between the FFT and LAM structures, especially for the metal that underwent two-phase transitions. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients. Methods: CTCs/CTECs and their subtypes were determined using SE‐iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression‐free survival (PFS), and overall survival (OS) were analyzed. Results: CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive‐stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC‐white blood cell (CTC‐WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC‐WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4–48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1–18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values. Conclusions: The presence of CTC‐WBC clusters at baseline and after two‐cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first‐line treatment. [ABSTRACT FROM AUTHOR]

• Calibrate whole body segments with only three predefined postures using orientation measurements. • Segmentation procedure segments calibration postures automatically. • Intrinsic average algorithm significantly reduce effect of body shaking. • Iterative hand-eye calibration algorithm directly determine the transformation matrix. This study aims to propose a novel sensor to segment calibration method for magnetic and inertial measurement unit (M-IMU) based human motion capture systems. The calibration procedure is designed to be easily performed by the subject, which can calibrate the whole body segments with only three predefined postures. Firstly, the orientation measurements for each body segment are collected during calibration process. Secondly, a segmentation procedure based on a moving average window algorithm and double-threshold technique is introduced to recognize and segment the calibration postures automatically. To suppress the shaking during the calibration process, an intrinsic average algorithm is presented to smooth the orientation measurements. Finally, an iteration hand-eye calibration approach is utilized to retrieve the sensor to segment calibration matrices. The error due to the ungraded calibration postures can be reduced observably, and we also define an indicator to evaluate the quality of the performed calibration postures. The calibration procedure has been validated on several subjects using a wearable M-IMU based motion capture system. Experiment results show that the proposed calibration method can suppress the shaking disturbances effectively, and has good repeatability. [ABSTRACT FROM AUTHOR]

Time sequence averaging under dynamic time warping (DTW) is a non-trivial problem, and its exact solution requires unrealistic computational complexity in practice. The DTW barycenter averaging (DBA) method is one of the most effective iterative approximation solutions to date. However, there are still a few drawbacks in the DBA method. First, the length of the resulting average sequence depends on the selected initial average sequence; second, the discrepancy distance between the resulting average sequence and target sequence set is highly sensitive to the initialization, as we have demonstrated through the experiments described here. In this study, we propose an adaptive DBA (ADBA) algorithm to address these drawbacks. We define a scaling coefficient based on the DTW alignments such that the temporal aberrations between the average sequence and target sequence set can be qualitatively captured. The algorithm is realized by an iterative process. For each iteration, the temporary average sequence and target sequence set are partitioned into several aligned subsequence sets according to the variation in the signs of the scaling coefficients. Then, these partitioned average subsequences are adaptively compressed or stretched such that the average discrepancy distance and overall temporal aberration can be locally minimized. The comparison experiments carried out on the standard datasets illustrate that the proposed algorithm achieves lower average discrepancy distance, overall temporal aberration, and higher robustness than the available methods. Additionally, the proposed algorithm is verified by an accelerometer-based hand gesture recognition system, where ADBA produces more effective gesture templates. [ABSTRACT FROM AUTHOR]

Aim: Pantothenate-kinase-associated neurodegeneration (PKAN), which is characterised by iron accumulation in the basal ganglia, is a rare autosomal recessive neurodegenerative disorder caused by pantothenate kinase 2 (PANK2) gene mutations. The PANK2 gene is located on chromosome 20p13 and encodes pantothenate kinase. Herein, we identified one patient with PKAN who had mutations in the PANK2 gene. Materials and methods: We performed clinical and radiographic investigations, and diagnosed this disease at the clinical and genetic levels. Results: It is worth mentioning that the patient displayed an eye-of-the-tiger sign. Through scanning the exons and flanking intronic sequences of PANK2 in patient and control subjects, we report a compound heterozygote c. 260A > G (NM_001324191) and c.405dupC (NM_153638) for PANK2 mutations in a Chinese patient with clinical manifestation of progressive prosopospasm, dysarthria and gait disturbance. Bioinformatics analysis showed that two variants exhibited highly conserved residues across species. Conclusion: we reported a patient presenting with atypical PKAN, and identified novel compound heterozygous PANK2 gene mutations.. [ABSTRACT FROM AUTHOR]

Recently, a genome-wide association study of a Caucasian population identified variant rs3794087 in intron 4 of the SLC1A2 gene, which may increase the risk of essential tremor (ET). Considering the overlap in the pathological features and clinical manifestations of ET and Parkinson's disease (PD), several studies on the association between rs3794087 and PD were later performed in other populations. However, results about the role of SLC1A2 rs3794087 in PD were inconsistent. We thus performed a case-control study in a Chinese Han population to investigate the role of SLC1A2 rs3794087 in Chinese patients with PD. Overall, 1096 subjects comprising 546 patients with PD and 550 control subjects were genotyped. A meta-analysis of the data obtained from the current sample-set and those available from prior studies was performed. Taking all patients and controls into consideration, rs3794087 was found to have no significant effect on PD susceptibility in analyses using allelic ( p  = .486), genotype ( p  = .736), additive ( p  = .764), dominant ( p  = .438), and recessive ( p  = .878) genetic models. The results of the meta-analysis were in agreement with our findings (the pooled OR was 0.97 and 95% CI = 0.85, 1.10). Our study suggested that rs3794087 does not lead to an increased risk of PD in the Chinese Han population. The role of single nucleotide polymorphism rs3794087 in the development of PD remains to be further studied. [ABSTRACT FROM AUTHOR]

Brain metastasis (BM) is common in patients with non-small cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have now been included as standard treatment options for NSCLC harboring EGFR-activating mutations, only a few prospective reports demonstrate the efficacy of these agents in a BM setting. We report a case of a patient with advanced NSCLC, in which oral gefitinib documented a significant antitumor effect on parallel progression of extracranial lesion and BM occurred during chemotherapy. [ABSTRACT FROM AUTHOR]

Background To compare the overall survival ( OS) of patients with advanced lung adenocarcinoma in China before and after the approved use of gefitinib, and analyze clinical factors that may affect OS. Methods Clinical data of 558 patients with advanced lung adenocarcinoma who received chemotherapy from January 2002 to December 2010 were retrospectively analyzed. According to the matched-pair case-control study design, 255 patients who only received chemotherapy and 255 patients who received gefitinib treatment after its approval were stringently matched by age, gender, and smoking history and enrolled in the study. Clinical factors including age, gender, smoking history, Eastern Cooperative Oncology Group ( ECOG) performance status ( PS), tumor stage, organ metastasis, and the number of prior chemotherapies were analyzed to determine their correlations with OS. Results The median survival time ( MST) of the 510 enrolled patients with advanced lung adenocarcinoma was 22.8 months. The MST of the patients who received gefitinib treatment was significantly longer than that of patients who did not receive gefitinib treatment (33.5 vs. 14.1 months, P < 0.001). The OS in patients who received gefitinib treatment was significantly longer than in patients who did not receive gefitinib treatment in almost all clinical factor-based subgroups, including age, gender, smoking history, ECOG PS 0-1, tumor stage, the presence or absence of lung, pleural, bone, brain, adrenal gland and liver metastasis, and the number of prior chemotherapies (all P < 0.001), except in the ECOG PS ≥2 subgroup. Conclusions Gefitinib treatment significantly improved the survival of patients with advanced lung adenocarcinoma in China. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of apigenin lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. In this study, the anti-inflammatory effects of apigenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with apigenin prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio in total leukocyte number and neutrophil percent in the bronchoalveolar lavage fluid (BALF) and in IL-6 and IL-1β, the tumor neurosis factor-α (TNF-α) in the BALF. These results showed that anti-inflammatory effects of apigenin against the LPS-induced ALI may be due to its ability of primary inhibition of cyclooxygenase-2 (COX-2) gene expression and nuclear factor kB (NF-kB) gene expression of lung. The results presented here suggest that the protective mechanism of apigenin may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of COX-2 and NF-kB activation. The results support that use of apigenin is beneficial in the treatment of ALI. [ABSTRACT FROM AUTHOR]

Background The echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase ( EML4- ALK) fusion gene defines a novel molecular subset of non-small-cell lung cancer ( NSCLC). However, the clinicopathological features of patients with the EML4- ALK fusion gene have not been defined completely. Methods Clinicopathological data of 200 Chinese patients with advanced NSCLC were analyzed retrospectively to explore their possible correlations with EML4- ALK fusions. Results The EML4- ALK fusion gene was detected in 56 (28.0%) of the 200 NSCLC patients, and undetected in 22 (11.0%) patients because of an insufficient amount of pathological tissue. The median age of the patients with positive and negative EML4- ALK was 48 and 55 years, respectively. Patients with the EML4- ALK fusion gene were significantly younger ( P < 0.001). The detection rate of the EML4- ALK fusion gene in patients who received primary tumor or metastatic lymph node resection was significantly higher than in patients who received fine-needle biopsy ( P = 0.003). The detection rate of the EML4- ALK fusion gene in patients with a time lag from obtainment of the pathological tissue to EML4- ALK fusion gene detection ≤48 months was significantly higher than in patients >48 months ( P = 0.020). The occurrence of the EML4- ALK fusion gene in patients with wild-type epidermal growth factor receptor ( EGFR) was significantly higher than in patients with mutant-type EGFR (42.5% [37/87] vs. 6.3% [1/16], P = 0.005). Conclusions Younger age and wild-type EGFR were identified as clinicopathological characteristics of patients with advanced NSCLC who harbored the EML4- ALK fusion gene. The optimal time lag from the obtainment of the pathological tissue to the time of EML4- ALK fusion gene detection is ≤48 months. [ABSTRACT FROM AUTHOR]

Background: This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods: ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results: The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions: Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. [ABSTRACT FROM AUTHOR]

Abstract: The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases. In 2010, four missense mutations in the prodynorphin (PDYN) gene were found in two families and two sporadic cases of SCA type 23 (SCA23) from the Netherlands. In addition, one missense mutation in PDYN was also found in one sporadic SCA23 case in America in 2012. To date, there have been no reports of PDYN gene mutations in mainland China. To investigate the frequency of SCA23 among the Chinese Han population, we performed polymerase chain reaction (PCR) and DNA direct sequencing of the PDYN gene in 305 unrelated ataxia patients. Although no SCA23 mutation was identified, one novel single nucleotide polymorphism (c.255G>A, p.Lys85Lys) in exon 4 of the PDYN gene was found. This suggests that SCA23 is a rare form of dominant ataxia in the Chinese Han population. [Copyright &y& Elsevier]

A general palladium‐catalyzed method for the direct alkynylation of unactivated alkenes via C−H activation, was successfully developed, with the assistance of 8‐aminoquinoline. It is applicable to both internal and terminal unactivated alkenes with a broad functionality tolerance. This method shows good regio‐ and diastereoselectivity and provides an alternative approach for directing construct of conjugated 1,3‐enynes. [ABSTRACT FROM AUTHOR]

A general and convenient method for the direct transition‐metal‐free intermolecular chlorodifluoromethylthiolation of a variety of unactivated alkenes and alkynes has been described. This methodology exhibits good functional group tolerance and is operationally simple. Mechanistic studies indicated an electrophilic substitution mechanism, and the strong electrophilic difluoromethylthiolating reagent HCF2SCl was generated in situ under standard reaction conditions. The developed protocol fulfils the requirements of sustainable and green chemistry. [ABSTRACT FROM AUTHOR]

• The impact of people's subjective perception on their acceptance of high-level autonomous vehicle (AV) were analyzed. • People concerned high-level AVs' usefulness for increasing traveling efficiency at most. • People's using attitude, perceived benefit and safety, and trust greatly affected their acceptance of high-level AVs. • Male and female have different preferences for the AVs on the self-driving function and attitude to social influence. The automated vehicles (AV) is an important driving force for intelligent transportation technologies. Previous studies have found significant influence of people's subjective perception on their acceptance of AVs, but how people's perception impose influence their acceptance has not reached consensus. This study reviewed published papers addressing this topic to provide some insights of this issue. The preferred reporting items for systematic reviews and meta-analysis method (PRISMA) is used to select qualified papers across major databases. The impacts of nine subjective perception factors on public acceptance of AVs revealed by the papers are reanalysed following a rigorous meta-analytic process. The results show that people's perceived usefulness of AVs and attitude toward using strongly affect their acceptance of AVs. The increase of perceived ease of use could slightly increase the acceptance. Lower perceived risk often leads to higher acceptance of AVs. Social influence hardly affects people accepting AVs. Males and females had different degrees of trust, perceived benefit and effort expectancy on AVs. Peoples from different countries perceived benefits and effort expectancy of AVs in their own ways. Based on paper reviewing results, some suggestions for survey design, data collection and analysis are proposed for future studies. [ABSTRACT FROM AUTHOR]

The microstructural characterization of Basalt Fiber Reinforced Polymer (BFRP) bars under seawater deterioration (dry–wet cycles modes and immersion modes) was performed by scanning electron microscopy (SEM) and X-ray energy spectrum analyzer (EDS). Then, uniaxial compressive tests were carried out on the corroded BFRP bars to explore the effects of different corrosion periods, diameters, and slenderness ratios on the degradation of compressive performance and durability in seawater corrosion and constraint condition. The results showed that dry–wet cycles of seawater caused patchy pitting on the surfaces of BFRP bar, and white granular foams adhered to the bar surface after seawater immersion. The internal microstructure of BFRP bar was deteriorated, and the bonding force between the fiber and resin was reduced with the increase of dry–wet cycles. Five failure modes of BFRP bars occurred in uniaxial compressive tests, namely crushing failure, transverse cracking failure, shearing failure, splitting failure, and buckling failure. The increase of corrosion cycles significantly decreased the bearing capacity and compressive strength, but had little effect on the compressive elastic modulus of BFRP bars. The dry–wet cycles of seawater was more harmful to the mechanical properties of BFRP bars than immersion corrosion. Meanwhile, the mechanical properties of BFRP bars were affected by their diameters and slenderness ratios to some extent. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid, Diaphorina citri Kuwayama, is among the most important pests of citrus. It is the main vector of the Huanglongbing (HLB) pathogen Candidatus Liberibacter asiaticus (CLas), which causes severe losses in citrus crops. Control of D. citri is therefore of paramount importance to reduce the spread of HLB. In this regard, using RNA interference (RNAi) to silence target genes is a useful strategy to control psyllids. In this study, using RNAi, we examined the biological functions of the V‐ATPase subunit E (V‐ATP‐E) gene of D. citri, including its effect on acquisition of CLas. The amino acid sequence of V‐ATP‐E from D. citri had high homology with proteins from other insects. V‐ATP‐E was expressed at all D. citri life stages analyzed, and the expression level in mature adults was higher than that of teneral adults. Silencing of V‐ATP‐E resulted in a significant increase in mortality, reduced body weight, and induced cell apoptosis of the D. citri midgut. The reduced expression of V‐ATP‐E was indicated to inhibit CLas passing through the midgut and into the hemolymph, leading to a majority of CLas being confined to the midgut. In addition, double‐stranded RNA of D. citri V‐ATP‐E was safe to non‐target parasitic wasps. These results suggest that V‐ATP‐E is an effective RNAi target that can be used in D. citri control to block CLas infection. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease. • SMARCAL1 is overexpressed and inversely associated with overall survival of SCLC patients. • PAR6B is upregulated by SMARCAL1 and mediates the effects of SMARCAL1 on DNA damage repair and cell proliferation. • Pixantrone is a SMARCAL1 inhibitor that exhibits potent anti-SCLC activity in vitro and in a PDX model. [ABSTRACT FROM AUTHOR]

Abstract: Spinocerebellar ataxia type 35 (SCA35) is an autosomal dominant neurodegenerative disorder. In our previous study, using exome sequencing and linkage analysis, two missense mutations of the transglutaminase 6 (TGM6) gene were identified as causative for SCA35. TGM6 encodes transglutaminase 6 (TG6), a member of the transglutaminase family of enzymes that catalyze the formation of a covalent bond between a free amine group and the γ-carboxamide group of protein- or peptide-bound glutamine. However, the precise role of TG6 in contributing to SCA35 remains unclear. In this study, we analyzed the subcellular distribution, expression and in vitro activity of two missense mutations of TG6 (D327G, L517W) and found that both mutants exhibited decreased transglutaminase activity and stability. Furthermore, overexpressing the TG6 mutants sensitized cells to staurosporine-induced apoptosis by increasing the activity of caspases. We propose that the pro-apoptotic role of these mutants might underlie the pathogenesis of SCA35. [Copyright &y& Elsevier]

Background: Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population. Methods: We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. Results: The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression‐free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. Conclusions: This study provides real‐world evidence of the survival and prognosis of ES‐SCLC patients which will enable better evaluation and clinical decision‐making in the future. [ABSTRACT FROM AUTHOR]

• Our study reported a family with limb-girdle myasthenia with tubular aggregates. • The study detected novel compound heterozygous mutations in GFPT1. • GFPT1 should be considered in transient muscle weakness and fatigue patients. Limb-girdle myasthenia with tubular aggregates, a subtype of congenital myasthenic syndrome, is an extremely rare autosomal recessive genetic disease characterized by prominent limb-girdle weakness and good response to acetylcholinesterase inhibitor therapy. Herein, we reported two novel mutations of GFPT1 gene in a Chinese pedigree. Two siblings presented with fatigue, weakness of limb-girdle and decrement of the muscle action potential with repetitive nerve stimulation. Thus, myasthenia gravis was initially suspected, but anti-AChR antibodies were negative. Two novel missense mutations (p.Lys154Asn and p.Asn363Ser) in GFPT1 were identified through genetic testing conducted on 167 well-established genes associated with muscular diseases by targeted high throughput sequencing. Both mutations have not been recorded in the dsSNP database, Exome Aggregation Consortium database and 1000 Genomes Project database. The mutation sites were co-segregated with the phenotype and conserved between the different species. The mutations were not found in the 200 unrelated normal controls. Muscle biopsies revealed tubular aggregates, in accordance with previous reports with GFPT1 mutations. Subsequently, dramatic improvement in strength occurred following anti-cholinesterase therapy. Our study will be helpful for the diagnosis and treatment for Limb-girdle myasthenia with tubular aggregates. [ABSTRACT FROM AUTHOR]

Background: Recently, rs2421947 in DNM3 (dynamin 3) was reported as a genetic modifier of age at onset (AAO) of LRRK2 G2019S-related Parkinson's disease (PD) in a genome-wide association study in Arab-Berber population. Rs356219 in SNCA (α-synuclein) was also reported to regulate the AAO of LRRK2-related PD in European populations, and GAK (Cyclin G-associated kinase) rs1524282 was reported to be associated with an increased PD risk with an interaction with SNCA rs356219. G2019S variant is rare in Asian populations, whereas two other Asian-specific LRRK2 variants, G2385R and R1628P, are more frequent with a twofold increased risk of PD. Methods: In this study, we investigated whether rs2421947, rs356219 and rs1524282 modified AAO in LRRK2-related PD patients in Han Chinese population. We screened LRRK2 G2385R and R1628P variants in 732 PD patients and 1992 healthy controls, and genotyped DNM3 rs2421947, SNCA rs356219 and GAK rs1524282 among the LRRK2 carriers. Results: The SNCA rs356219-G allele was found to increase the risk of PD in LRRK2 carriers (OR 1.50, 95%CI 1.08–2.01, P = 0.016), and the AAO of AG + GG genotypes was 4 years earlier than AA genotype (P = 0.006). Nonetheless, no similar association was found in DNM3 rs2421947 and GAK rs1524282. Conclusions: Our results show that SNCA but not DNM3 or GAK is associated with AAO of LRRK2-PD patients in Chinese population. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate the genetic and clinical features of a Chinese family exhibiting an autosomal dominant inheritance pattern of lissencephaly. Methods Clinical examinations and cranial imaging studies were performed for all members of the family (two unaffected members and three surviving members from a total of four affected members). In addition, whole-exome sequencing analysis was performed for DNA from an affected patient to scan for candidate mutations, followed by Sanger sequencing to verify these candidate mutations in the entire family. A total of 200 ethnicity-matched healthy controls without neuropsychiatric disorder were also included and analyzed. Results We identified a novel missense mutation, c.412G > A, p.(E138K), that cosegregated with the disease in exon 6 of the platelet activating factor acetylhydrolase 1b regulatory subunit 1 (PAFAH1B1) gene in the affected members; this mutation was not found in the 200 controls. Multiple sequence alignments showed that codon 138, where the mutation (c.G412A) occurred, was located within a phylogenetically conserved region. Brain magnetic resonance imaging revealed calcification within the bilateral globus pallidus in all three affected members. Conclusions We identified a novel missense mutation, c.412G > A, p.(E138K), in the PAFAH1B1 gene of a Chinese family with lissencephaly. In addition, our findings suggest that basal ganglia calcification is a novel clinical feature of PAFAH1B1- related lissencephaly. [ABSTRACT FROM AUTHOR]

Purpose: Cerebral cavernous malformations (CCMs) are vascular anomalies predominantly in the central nervous system but may include lesions in other tissues, such as the retina, skin and liver. The main clinical manifestations include seizures, hemorrhage, recurrent headaches and focal neurological deficits. Previous studies of familial CCMs (FCCMs) have mainly reported in Hispanic and Caucasian cases. Here, we report on FCCMs in a Chinese family further characterized by a novelCCM1gene mutation.Materials and methods: We investigated clinical and neuroradiological features of a Chinese family of 30 members. Furthermore, we used exome capture sequencing to identify the causing gene. TheCCM1mRNA expression level in three patients of the family and 10 wild-type healthy individuals were detected by real-time quantitative polymerase chain reaction (real-time RT-PCR).Results: Brain magnetic resonance imaging demonstrated multiple intracranial lesions in seven members. The clinical manifestation of CCM was found in five of these cases, including recurrent headaches, weakness, hemorrhage and seizures. Moreover, we identified a novel nonsense mutation c.1159G>T (p. E387*) in theCCM1gene in the pedigree. Based on real-time RT-PCR results, we have found that theCCM1mRNA expression level in three patients was reduced by 35% than that in wild-type healthy individuals.Conclusions: Our finding suggests that the novel nonsense mutation c.1159G>T inCCM1gene is associated with FCCM, and thatCCM1haploinsufficiency may be the underlying mechanism of CCMs. Furthermore, it also demonstrates that exome capture sequencing is an efficient and direct diagnostic tool to identify causes of genetically heterogeneous diseases. [ABSTRACT FROM PUBLISHER]

In the experimental teaching, phenanthroline spectrophotometry has been generally used to determinate the content of trace iron, because this method has less sampling, simple and high sensitivity. But in the course of the experimental teaching, it was found that many factors, such as the choice of the wavelength, the amount of buffer solution, the color time of color-developing agent, the amount of color-developing agent, and the selection of reductants and so on, had a certain impact on the final results. In addition, the different edition teaching materials have different operating methods. In order to better carry out the experimental teaching, the various factors effect on the absorbance were systematicaHy analyzed. And the optimal experimental conditions were determined. Compared with traditional experimental teaching, the improved experiment can not only save many chemical reagents, but also reduce certain environmental pollution. [ABSTRACT FROM AUTHOR]

Introduction: A founder mutation, p.L302P, in sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1), causing Niemann-Pick disease, a recessive lysosomal storage disorder, was reported to be associated with increased risk of Parkinson's disease (PD) in Ashkenazi Jewish population. Several other studies about the association between SMPD1 variants and PD were performed afterward in other populations. However, the results on the role of SMPD1 mutations for PD have been conflicting. This study aimed to investigate the role of mutations in SMPD1 in Chinese PD patients.Methods: We sequenced all the exons of this gene in 512 Chinese Han cases with sporadic Parkinson's disease and 495 matched healthy control subjects.Results: We identified Leu-Ala (Val) repeat variants and six known single nucleotide variants (p.A36V, p.D212D, p.P332R, p.G508R, p.P533L, p.T544T) in SMPD1 in both patients and normal controls. Case-control analysis showed the association between Leu-Ala (Val) repeat variants in SMPD1and Chinese Han patients with PD (χ2 = 8.771, p = 0.012), and the allele with less than seven LeuAla (Val) repeats may increase the risk of PD (p = 0.010).Conclusion: We identified association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with sporadic Parkinson's disease. Our results provide further support for the role of lysosomal pathways in PD development. [ABSTRACT FROM AUTHOR]

Highlights: [•] Previously, we identified TGM6 as the causative gene of SCA35 and SCA35-associated TGM6 mutants sensitize cells to apoptosis. [•] TG6 interacts and co-localizes with both normal and expanded polyQ proteins. [•] Overexpression of TG6 promotes the formation of polyQ aggregates. [•] Overexpression of TG6 promotes the conversion of soluble polyQ into insoluble polyQ aggregates. [Copyright &y& Elsevier]

Background: Gluten sensitivity (GS) is a spectrum of disorders with diverse manifestations. Recent evidence suggests that ataxia may be the only manifestation of GS and that it may be one of the causes of sporadic ataxia.Aim: To investigate the prevalence of gluten ataxia among patients with ataxia in China.Materials and Methods: Serum levels of anti-gliadin, anti-transglutaminase 2 (TG2), and anti-transglutaminase 6 (TG6) antibodies measured in 125 patients with ataxia (100 patients with sporadic ataxia and 25 patients with hereditary ataxia) and 51 healthy controls by enzyme-linked immunosorbent assay (ELISA).Results: The serum concentrations of anti-gliadin, anti-TG2 IgG, IgA, and TG6-IgG antibodies were elevated in ataxia patients, but the increase was not statistically significant. However, TG6-IgA serum levels were significantly higher in sporadic ataxia as compared to those in healthy controls (P < 0.05).Conclusions: These results provide evidence that sporadic ataxia in a subgroup of patients may be due to gluten ataxia in mainland China. Measurement of serum anti-TG6 antibodies along with anti-TG2 and anti-gliadin antibodies may be useful for diagnosing gluten ataxia. [ABSTRACT FROM AUTHOR]

We screened the RFC1 intronic AAGGG repeat expansions in late-onset ataxia cases, MSA patients and controls. The data suggested that no biallelic repeat expansion carrier was found in our cohort and the heterozygous intronic AAGGG repeat expansions may not lead to an increased risk of late-onset ataxia or MSA. [ABSTRACT FROM AUTHOR]

Recently, mutations of DNAJC12 gene were reported to be associated with early-onset parkinsonism, progressive neurodevelopmental delay, and dystonia in several unrelated pedigrees. This study aimed to evaluate DNAJC12 coding mutations in sporadic Chinese Han patients with Parkinson's disease (PD) and test whether an age-of-onset effect exists. Seven hundred two Chinese Han sporadic PD patients, including 181 early-onset PD and 521 late-onset PD, and 728 healthy controls were recruited. No documented disease-causing mutation of DNAJC12 was identified, but we found 7 single-nucleotide polymorphisms. Allele frequencies did not differ between all the PD patients and controls or between any 2 subgroups for all these single-nucleotide polymorphisms. Our study suggests that DNAJC12 mutation is not a risk factor of PD in Chinese Han population, and no age-of-onset effect was verified. [ABSTRACT FROM AUTHOR]

Recently, a variant p.R160W in the MC1R gene was identified that increased the risk of Parkinson's disease (PD) in Spanish population. To explore whether the MC1R gene variants are associated with sporadic PD in Chinese population, we performed a case-control comparison study for comprehensive MC1R variant screening in 510 Chinese Han patients and 495 healthy controls as ethnically matched controls. We identify 5 nonsynonymous variants, including rs34090186 (p.R67Q), rs2228479 (p.V92M), rs33932559 (p.I120T), rs885479 (p.R163Q), and rs372152373 (p.R223W). However, variants mentioned previously did not show association with PD. Our results suggest that variants in MC1R do not play a major role in PD in the Chinese population. [ABSTRACT FROM AUTHOR]

Mutations in CHCHD2 gene have been reported in autosomal dominant Parkinson's disease (ADPD). However, there is still lack of evidence supported CHCHD2 mutations lead to ADPD in other populations. We performed whole exome sequencing, positron emission tomography (PET), and haplotype analyses in an ADPD pedigree and then comprehensively screened for CHCHD2 gene mutations in additional 18 familial parkinsonism pedigrees, 364 sporadic PD patients, and 384 healthy controls to assess the frequencies of known and novel rare nonsynonymous CHCHD2 mutations. We identified a heterozygous variant (c.182C>T; p.Thr61Ile) in the CHCHD2 gene in the ADPD pedigree. PET revealed a significant reduction in dopamine transporter binding in the putamen and caudate nucleus of the proband, similar to idiopathic PD. The single nucleotide variant 5C>T (Pro2Leu) in CHCHD2 was confirmed to have a significantly higher frequency among sporadic PD patients than controls. Our results confirm that ADPD can be caused by CHCHD2 mutations and show that the Pro2Leu variant in CHCHD2 may be a risk factor for sporadic PD in Chinese populations. [ABSTRACT FROM AUTHOR]