Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.

Low Distortion of Noise Filter Realization with 6.34 V/µs Fast Slew Rate and 120 mVp-p Output Noise Signal.

In order to reduce Gaussian noise, this paper proposes a method via taking the average of the upper and lower envelopes generated by capturing the high and low peaks of the input signal. The designed fast response filter has no cut-off frequency, so the high order harmonics of the actual signal remain unchanged. Therefore, it can immediately respond to the changes of input signal and retain the integrity of the actual signal. In addition, it has only a small phase delay. The slew rate, phase delay and frequency response can be confirmed from the simulation results of Multisim 13.0. The filter outlined in this article can retain the high order harmonics of the original signal, achieving a slew rate of 6.34 V/µs and an almost zero phase difference. When using our filter to physically test the input signal with a noise level of 3 Vp-p Gaussian noise, a reduced noise signal of 120 mVp-p is obtained. The noise can be suppressed by up to 4% of the raw signal.

Pyrolyzed biowastes deactivated potentially toxic metals and eliminated antibiotic resistant genes for healthy vegetable production.

Potentially toxic metals (PTEs) and antibiotic resistance genes (ARGs) present in bio-wastes were the major environmental and health risks for soil use. If pyrolyzing bio-wastes into biochar could minimize such risks had not been elucidated. This study evaluated PTE pools, microbial and ARGs abundances of wheat straw (WS), swine manure (SM) and sewage sludge (SS) before and after pyrolysis, which were again tested for soil amendment at a 2% dosage in a pot experiment with a vegetable crop of pak choi (Brassica campestris L.). Pyrolysis led to PTEs concentration in biochars but reduced greatly their mobility, availability and migration potential, as revealed respectively by leaching, CaCl2 extraction and risk assessment coding. In SM and SS after pyrolysis, gene abundance was removed by 4-5 orders for bacterial, by 2-3 orders for fungi and by 3-5 orders for total ARGs. With these material amended, PTEs available pool decreased by 25%-85% while all ARGs eliminated to background in the pot soil. Unlike a >50% yield decrease and a >30% quality decline with unpyrolyzed SM and SS, their biochars significantly increased biomass production and overall quality of pak choi grown in the amended soil. Comparatively, amendment of the biochars decreased plant PTEs content by 23-57% and greatly reduced health risk of pak choi, with total target hazard quotient values well below the guideline limit for subsistence diet by adult. Furthermore, biochar soil amendment enabled a synergic improvement on soil fertility, product quality, and biomass production as well as metal stabilization in the soil-plant system. Thus, biowastes pyrolysis and reuse in vegetable production could help build up a closed loop of production-waste-biochar-production, addressing not only circular economy but healthy food and climate nexus also and contributing to achieving the United Nations sustainable development goals.

Endovascular Aortic Arch Reconstruction with Parallel Grafts: A Dilemma of Excessive Endograft Oversizing.

BACKGROUND: Preservation of supra-aortic branches in thoracic endovascular aortic repair plays a role in associated neurological outcomes, and the strategy varies. OBJECTIVES: This study aimed to evaluate the safety and efficacy of a parallel graft technique to reconstruct the aortic arch. METHODS: From August 2014 to July 2018, a total of 25 patients with thoracic aortic pathologies requiring arch reconstruction were included. All patients underwent thoracic aortic endovascular repair (TEVAR) with a zone 1 landing aortic stent graft, a chimney graft to preserve the left common carotid artery, and a periscope graft to preserve the left subclavian artery. The associated outcomes and complications were reported. RESULTS: Eighteen patients presented with aortic dissection, 4 with a thoracic aortic aneurysm, 1 with a penetrating aortic ulcer, 1 with a traumatic aortic injury, and 1 case of re-TEVAR. The technical success rate was 96% (24/25), but the case of immediate failure died of retrograde type A dissection. Over a mean follow-up of 32.33 months, another retrograde type A aortic dissection was detected in 1 month, and a case of early failure (< 1 year) and 3 cases of late failure (> 1 year) whose primary aortic problems recurred were detected. CONCLUSIONS: This study demonstrates a total endovascular approach to preserve supra-aortic branches with a parallel graft technique. However, the dilemma of excessive graft oversizing was disclosed due to the risk of retrograde type A dissections and an unsatisfactory durability in this small series.

Geobacillus strains that have potential value in microbial enhanced oil recovery.

Bacteria from the genus Geobacillus are generally obligately thermophilic, with a unique bioenergy production capacity and unique enzymes. Geobacillus species were isolated primarily from hot springs, oilfields, and associated soils. They often exhibit unique survival patterns in these extreme oligotrophic environments. With the development of the microbial resources found in oilfields, Geobacillus spp. have been proven as valuable bacteria in many reports related to oilfields. After the isolation of Geobacillus by culture methods, more evidence was found that they possess the abilities of hydrocarbon utilization and bioemulsifier production. This paper mainly summarizes some characteristics of the Geobacillus species found in the oilfield environment, focusing on the inference and analysis of hydrocarbon degradation and bioemulsifier synthesis based on existing research, which may reveal their potential value in microbial enhanced oil recovery. It also provides references for understanding microbes in extreme environments.

Effects of Structural Changes in Subchondral Bone on Articular Cartilage in a Beagle Dog Model.

OBJECTIVE: Using MR T2-mapping and histopathologic score for articular cartilage to evaluate the effect of structural changes in subchondral bone on articular cartilage. METHODS: Twenty-four male Beagle dogs were randomly divided into a subchondral bone defect group (n = 12) and a bone cement group (n = 12). Models of subchondral bone defectin the medial tibial plateau and subchondral bone filled with bone cement were constructed. In all dogs, the left knee joint was used as the experimental sideand the right knee as the sham side. The T2 value for articular cartilage at the medial tibial plateau was measured at postoperative weeks 4, 8, 16, and 24. The articular cartilage specimens were stained with hematoxylin and eosin, and evaluated using the Mankin score. RESULTS: There was a statistically significant difference (P < 0.05) in Mankin score between the bone defect group and the cement group at postoperative weeks 16 and 24. There was a statistically significant difference in the T2 values between the bone defect group and its sham group (P < 0.05) from week 8, and between the cement group and its sham group (P < 0.05) from week 16. There was significant difference in T2 values between the two experimental groups at postoperative week 24 (P < 0.01). The T2 value for articular cartilage was positively correlated with the Mankin score (ρ = 0.758, P < 0.01). CONCLUSION: Structural changes in subchondral bone can lead to degeneration of the adjacent articular cartilage. Defects in subchondral bone cause more severe degeneration of cartilage than subchondral bone filled with cement. The T2 value for articular cartilage increases with the extent of degeneration. MR T2-mapping images and the T2 value for articular cartilage can indicate earlycartilage degeneration.

Changes of gray matter volume and amplitude of low-frequency oscillations in amnestic MCI: An integrative multi-modal MRI study.

BACKGROUND: Numerous studies have reported that the amnestic-type mild cognitive impairment (aMCI) patients have impaired brain structural integrity and functional alterations separately. PURPOSE: To investigate the changes of gray matter and amplitude of low-frequency oscillations in patients with aMCI by combining structural and functional magnetic resonance imaging (fMRI). MATERIAL AND METHODS: Thirty-four patients with aMCI and 34 controls were recruited. We adopted optimized voxel-based morphometry to detect regions with gray matter volume (GMV) loss induced by aMCI. Then regional differences in amplitude of slow-4 band (0.027-0.073 Hz) oscillations among these regions between patients and healthy controls were examined. Both slow-4 amplitude of low-frequency fluctuations (ALFF) and slow-4 fractional ALFF (fALFF; the relative amplitude that resides in the low frequencies) were employed. RESULTS: Patients with aMCI demonstrated significant GMV loss in the ventral medial prefrontal cortex (vMPFC), posterior cingulate cortex (PCC), bilateral hippocampus, right superior parietal gyrus, left insula and left middle temporal gyrus (P < 0.01). The patients exhibited significant decreases of slow-4 ALFF in the left hippocampus (P = 0.05) and PCC (P = 0.02), while the decreased slow-4 fALFF was detected in PCC (P = 0.01) and increased slow-4 fALFF in vMPFC (P = 0.03). In PCC, aMCI and controls exhibited significant different GMV-fALFF correlation (P < 0.05), with opposite correlation trend. CONCLUSION: The correlates between anatomical deficits and functional alterations in aMCI suggest that anatomical and functional deficits are linked to each other. The differences of GMV-fALFF correlations demonstrated altered anatomical-functional relationship in aMCI.

Spatial measurement of mobility barriers: improving the environment of community-dwelling older adults in Taiwan.

Mobility barriers can impede physical activity, increase the fear of falling, and pose a threat to the ability of older adults to live independently. This study investigated outdoor mobility barriers within a nonretirement public housing community located in Tainan, Taiwan. Site observations and interviews with older adult residents determined that parked motor scooters, potted plants, the rubber tiles of play areas, and a set of steps were the most important barriers. In addition, the space syntax parameters of control value and mean depth were effectively able to quantitatively measure improvements in walkability resulting from the hypothesized removal of these four barriers. These measures of improved walkability can be included in a cost-benefit analysis of spatial improvement factors to help policymakers address the mobility and accessibility needs of older adults.

Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of oxidative enzyme expression and protein activation through inhibition of MAPK phosphorylation.

Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid that is currently prescribed to treat inflammatory diseases such as upper respiratory infections. Recently, several studies have shown that its anti-inflammatory activities have been strongly linked to the inhibition of secretion of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) pathways. Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies. At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose of this study was to assess these theories in a series of experiments on the suppressive effects of AP7Glu based on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological, myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells, cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and changed. Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

Type II GaSb quantum ring solar cells under concentrated sunlight.

A type II GaSb quantum ring solar cell is fabricated and measured under the concentrated sunlight. The external quantum efficiency confirms the extended absorption from the quantum rings at long wavelength coinciding with the photoluminescence results. The short-circuit current of the quantum ring devices is 5.1% to 9.9% more than the GaAs reference's under various concentrations. While the quantum ring solar cell does not exceed its GaAs counterpart in efficiency under one-sun, the recovery of the open-circuit voltages at higher concentration helps to reverse the situation. A slightly higher efficiency (10.31% vs. 10.29%) is reported for the quantum ring device against the GaAs one.

Type II GaSb quantum ring solar cells under concentrated sunlight.

A type II GaSb quantum ring solar cell is fabricated and measured under the concentrated sunlight. The external quantum efficiency confirms the extended absorption from the quantum rings at long wavelength coinciding with the photoluminescence results. The short-circuit current of the quantum ring devices is 5.1% to 9.9% more than the GaAs reference's under various concentrations. While the quantum ring solar cell does not exceed its GaAs counterpart in efficiency under one-sun, the recovery of the open-circuit voltages at higher concentration helps to reverse the situation. A slightly higher efficiency (10.31% vs. 10.29%) is reported for the quantum ring device against the GaAs one.

Factors influencing cognitive function in patients with Huntington's disease from China: A cross-sectional clinical study.

BACKGROUND AND AIM: Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. Cognitive decline contributes to the loss of daily activity in manifest HD. We aimed to examine the cognition status in a Chinese HD cohort and explore factors influencing the diverse cognitive domains. METHODS: A total of 205 participants were recruited in the study with the assessment by neuropsychological batteries, including the mini-mental state examination (MMSE), Stroop test, symbol digit modalities test (SDMT), trail making test (TMT), verbal fluency test (VFT), and Hopkins verbal learning test-revised, as well as motor and psychiatric assessment. Pearson correlation and multiple linear regression models were applied to investigate the correlation. RESULTS: Only 41.46% of patients had normal global function first come to our center. There was a significantly difference in MMSE, Stroop test, SDMT, TMT, and VFT across each stage of HD patients (p < .05). Apathy of PBA-s was correlated to MMSE, animal VFT and Stroop-interference tests performance. Severity of motor symptoms, functional capacity, age, and age of motor symptom onset were correlated to all neuropsychological scores, whereas education attainment and diagnostic delay were correlated to most neuropsychological scores except TMT. Severity of motor symptoms, functional capacity, and education attainment showed independent predicting effect (p < .05) in diverse cognitive domains. CONCLUSION: Cognitive impairment was very common in Chinese HD patients at the first visit and worse in the patients in advanced phase. The severity of motor symptoms and functional capacity were correlated to the diverse cognitive domains.

Korean Red Ginseng Suppresses Metastasis of Human Hepatoma SK-Hep1 Cells by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase Plasminogen Activator.

Korean red ginseng and ginsenosides have been claimed to possess wide spectrum of medicinal effects, of which anticancer effect is one. The present study was undertaken to investigate the antimetastatic effect of Korean red ginseng on human hepatoma as well as possible mechanisms. The inhibitory effect of the water extract of Korean red ginseng (WKRG) on the invasion and motility of SK-Hep1 cells was evaluated by the Boyden chamber assay in vitro. Without causing cytotoxicity, WKRG exerted a dose-dependent inhibitory effect on the invasion and motility, but not adhesion, of highly metastatic SK-Hep1 cells. Zymography analyses revealed significant downregulating effects on MMP-2, MMP-9, and uPA activities in SK-Hep1 cells. Western blot analyses also showed that WKRG treatment caused dose-dependent decreases in MMP-2 and MMP-9 protein expressions. Moreover, WKRG increased the levels of TIMP-1, TIMP-2, and PAI-1. The present study not only demonstrated that invasion and motility of cancer cells were inhibited by WKRG, but also indicated that such effects were likely associated with the decrease in MMP-2/-9 and uPA expressions of SK-Hep1 cells.

The complete chloroplast genome of Pseudosasa usawae (Poaceae: Bambusoideae: Arundinarieae) in Taiwan.

Pseudosasa usawae is an endemic species in Taiwan, and grows at an altitude of 600-1200 m. In this study, we fully characterized the complete chloroplast genome of P. usawae. The complete chloroplast sequence was 139,660 bp, including large single-copy (LSC), small single-copy (SSC), and a pair of invert repeats (IR) region of 83,271, 12,803, and 21,793 bp. Besides, the plastid genome comprised a total of 129 genes, including protein-coding, tRNA, and rRNA genes as 83, 38, and 8 genes. Phylogenetic analysis reveals that P. usawae is closely associated with Phyllostachys genus clade, sister to the lineage of Phyllostachys.

Spatial Distribution and Climate Warming Impact on Abies kawakamii Forest on a Subtropical Island.

Species distribution modeling (SDM) is currently the primary tool for predicting suitable habitats for species. In this study, we used Abies kawakamii, a species endemic to Taiwan. Being the only Abies species distributed in high mountains, it acts as an ecological indicator on the subtropical island. We analyzed a vegetation map derived from remote sensing and ground surveys using SDM. The actual distribution of A. kawakamii in Taiwan has a total area of 16,857 ha distributed at an altitude of 2700-3600 m, and it often forms a monodominant forest at 3100-3600 m with the higher altitude edge as a forest line. Exploring the potential distribution of A. kawakamii through MaxEnt showed that the suitable habitat was 73,151 ha under the current climate. Under the scenarios of temperature increases of 0.5, 1.0, 1.5, and 2.0 °C, suitable habitat for A. kawakamii will gradually decrease to 70.2%, 47.1%, 30.2%, and 10.0% of this area, respectively, indicating that A. kawakamii will greatly decline under these climate warming scenarios. Fire burning disturbance may be the most significant damage to A. kawakamii at present. Although A. kawakamii has been protected by conservation areas and its natural regeneration is in good condition, it rarely has the opportunity to migrate upwards during climate warming. We suggest that in the future, research on the natural regeneration and artificial restoration of A. kawakamii should be emphasized, especially in the forest line ecotone.

Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review.

There are controversies regarding the association of visfatin with overweight/obesity, type 2 diabetes mellitus, insulin resistance (IR), metabolic syndrome and cardiovascular disease in published articles. A meta-analysis was performed to identify the significance of visfatin in these diseases. We searched for relevant articles in Pubmed, Scopus and SCIE. A total of 1035 articles were surveyed and 46 articles were identified, with 14 reports reporting more than one of our investigated diseases. A total of 13 (n = 644), 19 (n = 2405), 20 (n = 2249), 5 (n = 527) and 5 (n = 851) articles/(participants) were included in each meta-analysis regarding the association of visfatin and overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases, respectively. Plasma visfatin concentrations were increased in participants diagnosed with overweight/obesity, type 2 diabetes mellitus, metabolic syndrome and cardiovascular diseases, with pooled log odds ratios of 1.164 [95% confidence interval (CI): 0.348 to 1.981, p = 0.005], 1.981 (95% CI: 1.377 to 2.584, p < 0.001), 1.094 (95% CI: 0.678 to 1.511, p < 0.001), and 2.902 (95% CI: 0.924 to 4.879, p < 0.005), respectively. The circulating visfatin level was positively associated with insulin resistance, with a Fisher's z of 0.089 (95% CI: 0.013 to 0.165, p = 0.022). No single study was found to affect the overall result of each analysis by sensitivity testing. No publication bias was found by the Egger test. Our study suggests that the use of visfatin may be promising for predicting obesity, diabetes status, insulin resistance, metabolic syndrome and cardiovascular disease.

[The clinical and magnetic resonance imaging studies of brain damages in neuromyelitis optica].

OBJECTIVE: To investigate the feature brain damage and clinical manifestations in neuromyelitis optica (NMO) patients; To investigate the relationship between serum NMO-IgG antibody and NMO brain damage. METHODS: Clinical data of 37 NMO patients and their head and spinal cord MRI by 1.5T superconducting MR scanner, were analyzed; serum NMO-IgG antibody were measured by immunofluorescence. RESULTS: 17 cases were found to have abnormal signals on MRI, which were mainly in the white matter, pons, medulla, ventricle, aqueduct, and around the corpus callosum; According to pathological changes, brain damage can be divided into scattered irregularity (13 cases), fusion (3 cases), multiple sclerosis-like (1 case), with scattered irregularity more common, 5 cases had clinical manifestations of brain damage: somnolence, vomiting, diplopia, visual rotation, 11 cases patients with brainstem damage show positive serum NMO-IgG antibodies. CONCLUSIONS: Brain damage can be seen in half of NMO patients, they often located in the high expression area of AQP4: brain white matter, periventricular, brainstem and so on. Clinical symptoms has nothing to do with the size of lesions but the location, they often occur when brainstem was involved. Serum NMO-IgG is helpful in differentiating NMO with brain damage and MS.

Quality Classification of Injection-Molded Components by Using Quality Indices, Grading, and Machine Learning.

Conventional methods for assessing the quality of components mass produced using injection molding are expensive and time-consuming or involve imprecise statistical process control parameters. A suitable alternative would be to employ machine learning to classify the quality of parts by using quality indices and quality grading. In this study, we used a multilayer perceptron (MLP) neural network along with a few quality indices to accurately predict the quality of "qualified" and "unqualified" geometric shapes of a finished product. These quality indices, which exhibited a strong correlation with part quality, were extracted from pressure curves and input into the MLP model for learning and prediction. By filtering outliers from the input data and converting the measured quality into quality grades used as output data, we increased the prediction accuracy of the MLP model and classified the quality of finished parts into various quality levels. The MLP model may misjudge datapoints in the "to-be-confirmed" area, which is located between the "qualified" and "unqualified" areas. We classified the "to-be-confirmed" area, and only the quality of products in this area were evaluated further, which reduced the cost of quality control considerably. An integrated circuit tray was manufactured to experimentally demonstrate the feasibility of the proposed method.