Search

Summary: In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.

BackgroundRing enhancement on magnetic resonance imaging (MRI) is an important characteristic of GBM. Though patients suffering from glioblastoma multiforme (GBM) with BRAF mutation (MUT BRAF) in V600E benefit from BRAF-targeted inhibitors, the relationship between ring enhancement and MUT BRAF remains elusive. The purpose of this study was to investigate the relationship between BRAF mutation status and the appearance of ring enhancement so as to guide preoperative targeted therapy for MUT BRAF GBM.MethodsPatient’s population, clinical data and characteristic ring enhancement appearances on MRI were compared between GBM with MUT BRAF and GBM with WT BRAF. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the differential diagnostic significance. A nomogram was developed to predict the mutation status of BRAF. Moreover, all the variables were re-analyzed between epithelioid GBM (E-GBM) with or without MUT BRAF.ResultsCompared to GBM with WT BRAF, GBM with MUT BRAF had specific ring enhancement appearances with multiple rings, multiple located lobes, regular shape of ring, uniform thickness of ring and smaller diameter of ring. Area under the curve (AUC) of all the variables’ combination was 0.929. The nomogram was developed and validated. The re-analyzed results between E-GBM with or without MUT BRAF were similar to these above. AUC of the combination of quantity of ring, quantity of located lobe and shape of ring was 0.962.ConclusionThe characteristic ring enhancement appearances of GBM may play an important role in predicting BRAF mutation status preoperatively, especially in E-GBM. Further study with larger cases may provide more evidences to guide the pretreatment of targeted medicine for GBM patients with MUT BRAF in future.

BackgroundGlioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued.PurposeHere, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM.MethodsGlioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB).ResultsSix IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB.ConclusionHerein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

B3GALT6 is a well-documented disease-related gene. Several B3GALT6-recessive variants have been reported to cause Ehlers–Danlos syndrome (EDS). To the best of our knowledge, no dominant B3GALT6 variant that causes human disease has been reported. In 2012, we reported on a three-generation, autosomal-dominant family with multiple members who suffered from radioulnar joint rotation limitation, scoliosis, thick vermilion of both lips, and others, but the genetic cause was unknown. Here, exome sequencing of the family identified mutant B3GALT6 as the cause of the multiplex affected family. We observed that, in the compound heterozygous pattern (i.e., c.883C>T:p.R295C and c.510_517del:p.L170fs*268), mutant B3GALT6 led to severe consequences, and in the dominant pattern, an elongated B3GALT6 variant co-segregated with moderate phenotypes. The functional experiments were performed in vitro. The R295C variant led to subcellular mislocalization, whereas the L170fs*268 showed normal subcellular localization, but it led to an elongated protein. Given that most of the catalytic galactosyltransferase domain was disrupted for the L170fs*268 (it is unlikely that such a protein has activity), we propose that the L170fs*268 occupies the normal B3GALT6 protein position in the Golgi and exerts a dominant-negative effect.

This article proposes to utilize linear-quadratic tracking (LQT) control to reduce the air brake system response time and vehicle stopping distance, and hence, to significantly improve the system performance of a commercial vehicle air brake system equipped with electro-pneumatic proportional valve actuators. The nonlinear dynamic model of the air brake system, consisting of a control actuator (a proportional valve) and braking actuator (the brake chamber), is developed and linearized using the q-Markov COVariance Equivalent Realization (q-Markov Cover) method in our early work. Based on the linearized dynamic model, an infinite horizon LQT controller is designed along with Kalman state estimation at each linearized operational condition. To apply the LQT control law over a wide operational range to track the target pressure, the designed controller was interpolated between the neighboring controllers to have a control law cover the entire operational range. To validate this control law, the control scheme is implemented into a dSPACE unit and validated through bench tests under different supply and reference pressures. The LQT control performance is also compared with the PID (proportional-integral-derivative) one. The bench test results confirm the effectiveness of the proposed control scheme.

The increasing number of quick response (QR) code mobile payment users heralds the coming of a cashless society. However, the extent to which the coronavirus disease 2019 (COVID-19) pandemic accelerated the adoption of QR code mobile payment has not been sufficiently researched. Based on social learning theory, this study models how external interaction with the environment has affected the internal appraisal and behavioral intention to adopt QR code mobile payment during COVID-19. Empirical results from 248 respondents revealed that perceived severity and social influence positively affected the perception of utilitarian and health benefits of respondents, which in turn influenced the behavioral intention to use the QR code mobile payment. The theoretical contribution and managerial implications of this study are also discussed.

BackgroundGlioblastoma (GBM) is one of the most malignant types of tumors in the central nervous system, and the 5-year survival remains low. Several studies have shown that preoperative peripheral blood tests and preoperative conventional Magnetic Resonance Imaging (MRI) examinations affect the prognosis of GBM patients. Therefore, it is necessary to construct a risk score based on a preoperative peripheral blood test and conventional MRI and develop a multielement prognostic nomogram for GBM.MethodsThis study retrospectively analyzed 131 GBM patients. Determination of the association between peripheral blood test variables and conventional MRI variables and prognosis was performed by univariate Cox regression. The nomogram model, which was internally validated using a cohort of 56 GBM patients, was constructed by multivariate Cox regression. RNA sequencing data from Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA datasets were used to determine peripheral blood test-related genes based on GBM prognosis.ResultsThe constructed risk score included the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), albumin/fibrinogen (AFR), platelet/lymphocyte ratio (PLR), and center point–to-ventricle distance (CPVD). A final nomogram was developed using factors associated with prognosis, including age, sex, the extent of tumor resection, IDH mutation status, radiotherapy status, chemotherapy status, and risk. The Area Under Curve (AUC) values of the receiver operating characteristic curve (ROC) curve were 0.876 (12-month ROC), 0.834 (24-month ROC) and 0.803 (36-month ROC) in the training set and 0.906 (12-month ROC), 0.800 (18-month ROC) and 0.776 (24-month ROC) in the validation set. In addition, vascular endothelial growth factor A (VEGFA) was closely associated with NLR and LMR and identified as the most central negative gene related to the immune microenvironment and influencing immune activities.ConclusionThe risk score was established as an independent predictor of GBM prognosis, and the nomogram model exhibit appropriate predictive power. In addition, VEGFA is the key peripheral blood test-related gene that is significantly associated with poor prognosis.

Brusatol (Bru), a Chinese herbal extract, has a variety of anti-tumor effects. However, little is known regarding its role and underlying mechanism in glioblastoma cells. Here, we found that Bru could inhibit the proliferation of glioblastoma cells in vivo and in vitro. Besides, it also had an inhibitory effect on human primary glioblastoma cells. RNA-seq analysis indicated that Bru possibly achieved these effects through inhibiting the expression of extracellular matrix protein 1 (ECM1). Down-regulating the expression of ECM1 via transfecting siRNA could weaken the proliferation and invasion of glioblastoma cells and promote the inhibitory effect of Bru treatment. Lentivirus-mediated overexpression of ECM1 could effectively reverse this weakening effect. Our findings indicated that Bru could inhibit the proliferation and invasion of glioblastoma cells by suppressing the expression of ECM1, and Bru might be a novel effective anticancer drug for glioblastoma cells.

Abstract Speech emotion recognition methods combining articulatory information with acoustic features have been previously shown to improve recognition performance. Collection of articulatory data on a large scale may not be feasible in many scenarios, thus restricting the scope and applicability of such methods. In this paper, a discriminative learning method for emotion recognition using both articulatory and acoustic information is proposed. A traditional ℓ 1-regularized logistic regression cost function is extended to include additional constraints that enforce the model to reconstruct articulatory data. This leads to sparse and interpretable representations jointly optimized for both tasks simultaneously. Furthermore, the model only requires articulatory features during training; only speech features are required for inference on out-of-sample data. Experiments are conducted to evaluate emotion recognition performance over vowels /AA/, /AE/, /IY/, /UW/ and complete utterances. Incorporating articulatory information is shown to significantly improve the performance for valence-based classification. Results obtained for within-corpus and cross-corpus categorical emotion recognition indicate that the proposed method is more effective at distinguishing happiness from other emotions.

Diesel engines are widely used in agricultural tractors. During field operations, the tractors operate at low speed and high load for a long time, the fuel efficiency is only about 15% to 35%, and the exhaust waste heat accounts for 38% to 45% of the energy released from the fuel. The use of tractor exhaust waste heat can effectively reduce fuel consumption and pollutant emissions, of which the organic Rankine cycle (ORC)-based waste heat recovery conversion efficiency is the highest. First, the diesel engine map is achieved through the test rig, a plate-fin evaporator is trial-produced based on the tractor size, and the thermodynamic and economic performance model of the ORC are established. Then, taking the thermal efficiency of ORC and the specific investment cost (SIC) as the objective function, the particle swarm optimization (PSO) algorithm and the technique for order of preference by similarity to ideal solution (TOPSIS) decision method were used to obtain the optimal operating parameter set under all working conditions. Finally, the results showed that the ORC thermal efficiency could reach a maximum of 12.76% and the corresponding SIC value was 8539.66 $/kW; the ORC net output power could be up to 8.31 kW compared with the system without ORC; and the maximum brake specific fuel consumption (BSFC) could be reduced by 8.3%. The improvement in the thermodynamic performance will lead to a sacrifice in economic performance, and at high speeds, the economic benefits and thermal efficiency reach a balance and show a better thermal economic performance. Recovering exhaust heat energy through ORC can reduce tractor fuel consumption and pollution emissions, which is one of the effective technical means to achieve “carbon neutrality” in agricultural production. At the same time, through the PSO algorithm, the optimal combination of ORC operating parameters is obtained, which ensures that the exhaust heat energy can be effectively recovered during the tractor field operation, and provides a basis for the adjustment of real-time work strategies for future research.

In order to solve the problem of high labor intensity of a traditional pontoon lotus root machine with manual pushing operation, a riding pontoon digging lotus root machine was proposed in this paper. The working principle of the digging machine was introduced, the key components were designed, and the buoyancy of the pontoon was calculated and analyzed. The performance of the digging machine was tested in a lotus root pond, the lotus root digging rate was 76%, and hydraulic flushing generated by the digging machine can disperse the soil within 30 cm under water. In addition, the best flushing effect was achieved when the number of working nozzles was controlled to three. Finally, according to the test results, the optimization measures of the hydraulic lotus root digging machine were proposed, and the CFD-DEM coupled simulation model was used to simulate and analyze the soil disturbance effect of hydraulic flushing upward from the bottom of the lotus root. The results showed the relationship between nozzle diameter, angle and hydraulic flushing depth. When the nozzle angle was fixed, the soil disturbance effect decreased with increasing flushing depth and increased with decreasing nozzle diameter. When the nozzle depth was fixed, both the diameter and the angle had a significant effect on the soil disturbance effect. When the nozzle diameter was fixed, the interaction of angle and depth had no significant effect on the soil disturbance effect.

In response to the problems of small working width and low operating efficiency of existing hydraulic scouring lotus root harvesters, a wide-width hydraulic scouring system was designed based on a wide-width self-propelled lotus root harvester. The main parameters of the key components were determined through theoretical analysis of the water flow energy of the hydraulic scouring system pipelines. An experimental study was also carried out on the main factors affecting the working performance of this hydraulic scouring system. Through hydrodynamic simulation tests, the effect of nozzle type and constriction section structure on the turbulence intensity at the nozzle outlet and the pressure loss per unit mass of fluid between the nozzle inlet and outlet sections were compared and analysed. The test yielded conical-cylindrical nozzle geometry parameters for nozzle inlet diameter of 40 mm, shrinkage angle of 30°, nozzle outlet straight section length of 20 mm, nozzle outlet diameter of 16 mm, the nozzle had better flushing performance. Single-factor tests were carried out with nozzle outlet pressure, scouring angle and nozzle height from the mud surface as influencing factors. Based on the optimum effective scour depth, a three-factor, three-level Box–Behnken central combination design test was completed. The primary and secondary factors affecting the effective scouring depth were obtained in the following order: nozzle height from the mud surface, nozzle outlet pressure, and scouring angle. Finally, the performance test of the hydraulic scouring system was completed. Results showed that when the nozzle outlet pressure of 0.30 MPa, the scouring angle of 60° and the nozzle height from the mud surface of 0 mm, the effective scouring depth was 395 mm, the lotus root floating rate was 90% and the damage rate was 5%, which meet the requirements of lotus root harvesting operations.

Hydraulic scouring is the most effective approach to harvest lotus roots, but its application is largely restricted by the low harvesting rate. After hydraulic scouring, some mature lotus roots are still partially buried in the soil. Therefore, it is highly necessary to develop an appropriate approach to harvest semi-buried lotus roots. In this work, we for the first time studied the interaction between semi-buried lotus roots and soil, as well as analyzing the pull-out process and the factors affecting the pull-out force of semi-buried lotus roots. Firstly, a simple testing platform was designed based on the virtual prototype technology and the tests on pull-out force were conducted on five lotus roots with similar shape but different weights, with the burial depth and pull-out speed as the experimental factors. The results revealed that the maximum pull-out force is not significantly affected by the pull-out speed, whereas it is significantly influenced by the burial depth and the surface area of lotus roots. The maximum pull-out force increased with increasing lotus root surface area and burial depth. In addition, the discrete element method was employed to simulate the pull-out process of lotus root at different pull-out speeds. The simulation results indicated that a higher pull-out speed would result in a greater pull-out force at the same displacement of the lotus root from the soil. Both experimental and simulation results revealed that soil adhesion contributes the most to the pull-out resistance. It was also observed that a slight loosening of semi-buried lotus roots could drastically reduce the pull-out force. These results suggest that some kind of mechanical structure or improvement of water flow can be applied to the existing lotus root harvester to reduce the adhesion between lotus roots and soil. Overall, our findings provide a novel direction for optimizing hydraulic harvesting machines of lotus roots.

Drawing on social cognitive theory, we propose a moderated-mediation model to examine when and why workplace ostracism impairs employee creativity in China. We collected 195 valid questionnaires with a two-wave employee-supervisor dyadic research design from one large Chinese company. Results indicate workplace ostracism affects employee creativity negatively. Moreover, the negative effect of workplace ostracism on employee creativity is not only mediated by employee creative self-efficacy (CSE), but the mediation effects of employee CSE are also found to be stronger when employee collectivism orientation is high. Finally, the theoretical and practical implications of these findings are discussed.

High-speed railway (HSR) traction transformer, as a connection between traction power supply system and the power grid, is critical in electrified railway design, which requires a drastic change of traction load and frequent external short circuits. In the actual operation process, the traction transformer can produce minor faults that are difficult to detect such as the deformation of the winding, which may result in a serious problem. This study analyses the topology structures and winding fault characteristics of six HSR traction transformers consisting of single phase, Vv, YNd11, Scott, YNvd and impedance matching wiring. Both circuit models of normal operation and fault operation of HSR traction transformer are established. Results show that real-time diagnosis of HSR traction transformer can be accomplished through measuring the voltage signal of the input and output points during operation and establishing real-time monitoring statistics of small faults standardisation（I^2 and squared prediction error）based on fast independent component analysis algorithm, as well as the signal statistics distribution, thereby improving the safety and reliability of HSR operation.

Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a prototype for lysosomal transport disorders. To date, several CTNS mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the CTNS mutation is very rarely reported. For the Chinese population, no literature on CTNS mutation screening for IC is available to date. In this paper, by using the whole exome sequencing and Sanger sequencing, we identified two novel CTNS splicing deletions in a Chinese IC family, one at the donor site of exon 6 of CTNS (IVS6+1, del G) and the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give information for the genetic counseling of the IC that occurred in Chinese population.

The COVID-19 pandemic increased online shopping, including for potted plants; however, research on plant-purchasing behaviors outside of physical stores is limited. This study examined key factors that influence online plant purchases. Initially, 47 factors related to online plant purchases were identified. Personal factors encompassed gender, age, educational level, monthly income, gardening education, online purchase frequency, and living environment. Age quota sampling was used and 400 valid questionnaires were collected. Six common factors and 21 items were identified: consumer assurance, plant care and safety, well-being, service quality, pricing and promotions, and size and habits. Well-being was the most influential for online plant purchases. Service quality, data security, after-sales service, and pricing strategies were also important, with plant care and safety as secondary factors. Compared with men, women emphasized wellbeing and plant care more. Environmental factors such as naturalness and building density affected purchasing decisions. This study highlights the need for tailored marketing strategies focusing on service quality and emotional benefits to meet diverse consumer needs and preferences. [ABSTRACT FROM AUTHOR]