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Abstract Background Multiple system atrophy (MSA) is recognized as an atypical Parkinsonian syndrome, distinguished by a more rapid progression than that observed in Parkinson’s disease. Unfortunately, the prognosis for MSA remains poor, with a notable absence of globally recognized effective treatments. Although preliminary studies suggest that transcranial magnetic stimulation (TMS) could potentially alleviate clinical symptoms in MSA patients, there is a significant gap in the literature regarding the optimal stimulation parameters. Furthermore, the field lacks consensus due to the paucity of robust, large-scale, multicenter trials. Methods This investigation is a multi-center, randomized, double-blind, sham-controlled trial. We aim to enroll 96 individuals diagnosed with MSA, categorized into Parkinsonian type (MSA-P) and cerebellar type (MSA-C) according to their predominant clinical features. Participants will be randomly allocated in a 1:1 ratio to either the TMS or sham stimulation group. Utilizing advanced navigation techniques, we will ensure precise targeting for the intervention, applying theta burst stimulation (TBS). To assess the efficacy of TBS on both motor and non-motor functions, a comprehensive evaluation will be conducted using internationally recognized clinical scales and gait analysis. To objectively assess changes in brain connectivity, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) will be employed as sensitive indicators before and after the intervention. Discussion The primary aim of this study is to ascertain whether TBS can alleviate both motor and non-motor symptoms in patients with MSA. Additionally, a critical component of our research involves elucidating the underlying mechanisms through which TBS exerts its potential therapeutic effects. Ethics and dissemination All study protocols have been reviewed and approved by the First Affiliated Medical Ethics Committee of the Air Force Military Medical University (KY20232118-F-1). Trial registration Chinese Clinical Trial Registry ChiCTR2300072658. Registered on 20 June 2023.

In China, despite the continuous efforts to preserve traditional villages in recent years, a significant amount of cultural heritages continue to vanish. Commonly observed issues such as the lack of coordination between preservation and development, the imbalance in spatial environment conservation and utilization, are pervasive. Regrettably, there is a conspicuous absence of theoretical underpinning in addressing these challenges. In this study, The evaluation factor of spatial environmental protection was selected, and these factors were weighted through expert surveys and the Analytic Hierarchy Process, and applied the multi-objective linear weighting function method to obtain a comprehensive evaluation calculation formula. Subsequently, we conducted an assessment of 28 representative traditional villages in the southern Chinese regions of Guangdong, Fujian, and Jiangxi. Their current issues were systematically analyzed and cluster analysis was applied to discern 11 distinct typologies of traditional village development. Besides, the temporal evolution patterns of these villages were delved into, and their development were categorized into five stages: initiation, enhancement, prosperity, over-development, and decline. Ultimately, based on the spatial environment characteristics of each development type and evolution stage, corresponding guidelines for spatial environment conservation and utilization are proposed, which provides necessary theoretical frameworks for future work this region.

Objectives This study aims to investigate the satisfaction levels of inpatients and identify the determinants of inpatient satisfaction and hospital recommendations.Design A cross-sectional study was conducted in 2022.Setting A tertiary general hospital in Sichuan Province, China.Participants 271 inpatients were randomly selected and studied.Primary and secondary outcome measures A tailored questionnaire was developed to measure inpatient satisfaction and hospital recommendation. T-test and analysis of variance were employed to compare the differences in inpatients’ demographic characteristics across five satisfaction domains. Multivariate binary logistic regression was performed to identify determinants associated with inpatient satisfaction and hospital recommendation.Results The mean inpatient satisfaction score was 4.27 and the mean hospital recommendation score was 3.96. Inpatients showed the highest satisfaction with the physician care domain and the lowest satisfaction with the hospital environment domain. Statistically significant differences were observed in inpatient demographic characteristics among specific satisfaction domains. Older inpatients, those with Urban Employees and Residents Medical Insurance, from the internal medicine department, and inpatients from the hospital’s older region reported the highest levels of satisfaction. Multivariate binary logistic regression revealed that the nursing care domain was the strongest positive predictor of both inpatient overall satisfaction and hospital recommendation. Additionally, the medical procedure and hospital environment domains were strong positive predictors for hospital recommendation and inpatient overall satisfaction respectively. The hospital region domain was a strong negative predictor for inpatient overall satisfaction.Conclusions Higher satisfaction levels do not necessarily correlate with an increased likelihood of hospital recommendation. Inpatient satisfaction levels vary significantly based on factors such as age, gender, insurance type, hospital clinical department and region. The domains of nursing care and medical procedure are the influencing factors associated with inpatient overall satisfaction. The domains of nursing care, hospital environment and hospital region are the influencing factors of inpatient hospital recommendation.

ObjectivesThis cross-sectional study was designed to explore the completion of continuing medical education (CME) programs and identify the factors influencing their completion.MethodsThe data for this study were generated from the National CME Program Application and Information Feedback Online System and the Sichuan CME Administrative Platform. The data were processed using descriptive analysis, Chi-square test, and binary logistic regression methods. The completion of each CME program was determined by the research team members according to the criteria created by the Office of the Sichuan CME Commission.ResultsA total of 180 hospitals and 3,622 CME programs were included. Among the 3,622 CME programs, 2,936 (81.1%) were determined to be completed. Comparative analysis showed that in terms of hospital characteristics, specialist hospitals, county hospitals, hospitals with 500–1,000 beds, and hospitals in the regions with government medical expenditure input equal to or more than 3,000 million RMB displayed the highest completion rates. For program attributes, national programs, programs in the field of pharmacy, and programs with 1–3 duration days demonstrated the highest completion rates. The binary logistic regression analysis showed that hospital region with different government medical expenditure input had the strongest positive association with the completion of CME programs [OR = 2.922, 95%CI (1.642–5.198)], while the duration time showed the strongest negative association [OR = 0.235, 95%CI (0.141–0.393)].ConclusionThis is the first study in China to analyze the completion of CME programs and identify its influencing factors at the provincial level. It is recommended that the government in the region should pay great attention to the construction of measures regarding the factors affecting the completion of CME programs. This includes providing more financial support to CME providers to ensure the formal operation of their CME activities, formulating guidelines on the application of CME programs to reasonably allocate and control the distribution of accredited CME programs across different hospital scales and disciplines, especially offering more training support to county hospitals, promulgating administrative documents to raise attention to the completion of CME programs, and special scrutiny on CME programs with longer durations to provide and protect training opportunities for those in need.

AbstractLivingstone’s turaco, Tauraco livingstonii, belongs to the family Musophagidae. In this study, we obtained the complete mitochondrial genome sequence of Livingstone’s turaco by high-throughput sequencing technology and constructed a phylogenetic tree. It was found that the mitochondria of this species are 19,015 bp in length and contain a total of 37 genes, comprising 13 protein-coding genes, 22 tRNA genes, and 2 rRNA genes. The base composition of the mitochondrial genome is 31.61% A, 24.22% T, 30.64% C, and 13.52% G, with a GC content of 44%. Notably, an intriguing phenomenon of mitochondrial genome rearrangements was observed, characterized by the duplication of the tRNA Glu-L-CR gene order. In addition, the results of the phylogenetic tree analysis shed light on the taxonomic position of Livingstone’s turaco and supported the taxonomy of Otidimorphae. The study provides a basis for future phylogenetic and taxonomic investigations of Musophagiformes.

The utilization of micro-sample testing has demonstrated its effectiveness in conducting quantitative research on mechanical properties, damage evolutions and fracture features. For in-service equipment, millimicron sampling allows for non-destructive testing and analysis of mechanical performance evolution during operation. This paper presents a comparative study of the miniature uniaxial tensile test (MUTT) and small punch test (SPT) by experimental and finite element methods. As a comparison, the standard conventional-size tensile tests were also carried out. Detailed analyses of the elastoplastic behaviors and damage evolutions of MUTT and SPT were presented, followed by an application case illustrating the characterization of hydrogen embrittlement sensitivity based on MUTT and SPT. An inverse finite element modeling method of load–displacement curve reproduction was used to calibrate the variations of damage parameters of hydrogen-charged MUTT and SPT specimens. Hydrogen embrittlement (HE) indexes were determined by using different calculation methods. The results reveal that the HE sensitivity estimated by MUTT is higher than that measured by SPT, which is related to the different deformation processes and strain rates of the two testing methods.

Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-β (TGF-β) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-β pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-β pathway processes the variation of TGF-β receptor abundance using Liebig's law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-β receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-β receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.

Hypergolic ignition of H2O2 and MEA-NaBH4 by off-center collision of their droplets was experimentally studied, focusing on the characteristics and mechanism of droplet mixing, droplet heating and evaporation, and gas-phase ignition. The whole collision ignition process was divided into five stages, which were compared, respectively, with that of head-on collision. Under the condition of a slightly off-center collision (for cases where B < 0.35), H2O2 droplets penetrate MEA-NaBH4 droplets after the collision and coalesce with it, but the internal H2O2 drop inside the MEA-NaBH4 droplet does not form a stable sphere. Instead, it rotates and expands inside the mixed droplet. With B increasing to 0.59, the droplets no longer coalesce after collision but separate away, forming satellite droplets. In such cases, multi-ignition mode is observed. When B increases to a certain extent, specifically, 0.85, a grazing collision is observed such that no mass transfer exists during the interaction of droplets, which leads to ignition failure. A theoretical model quantifying droplet swelling rate was established to calculate the volume change of the droplet. It was found that the swelling can be attributed to the flash boiling of superheated internal H2O2 fluid. Meanwhile, the ignition delay time was found to linearly decrease with B at various Wes until the extent where the chemical reaction takes over control, leading to an almost constant time delay defined as RDT. Additionally, the regime of ignition modes corresponding to different droplet mixing features is summarized in the We-B parametric space.

Most historic villages in China are currently emphasizing conservation over utilization, paying close attention to planning above management. Management is often deficient or poorly implemented. After conducting questionnaires and interviews with relevant experts in village management, the analytic hierarchy process was used to determine factor priority, and a system for evaluating the management mechanisms of traditional Chinese villages was established. This system includes four first-level factors: management guidance, guarantee policy, publicity and education and public participation. Twenty-seven typical traditional villages in China’s Fujian, Guangdong and Jiangxi Provinces were included in the analysis of conservation and utilization factors and the management mechanisms of traditional villages. Through field research, data on the quantitative evaluation of the management mechanisms and the performance of conservation and utilization were obtained. Two sets of data were used for correlation analysis. A strong correlation was confirmed between the conservation and utilization performance and the management mechanism of traditional Chinese villages. The corresponding factors were also revealed. A summary is provided of the problems and their causes related to conservation and utilization as implemented in the traditional Chinese villages studied herein, and optimization strategies are proposed.

Pressure nozzles are widely used in spray drying and other industries. In order to improve the atomization characteristics of pressure cyclone nozzles, a new type of annular jet gas impingement atomization device is developed. We use high-speed imaging and digital image processing and other methods to analyze the spray characteristics of the different annular device configurations (using four, six, and eight tubes) and under different gas–liquid mass flow rates. It is shown that with an increase in the Air–Liquid mass Ratio (ALR), the liquid film breakup process changes from undulating sheet breakup to perforated sheet breakup and the breakup length decreases. The breakup length decreases the most under the condition of six-tube airflow with the range of 31–55%, while the Sauter mean diameter (SMD) basically does not change. With the increase in ALR and the Weber number of liquid (Wel), the droplet size distribution becomes more uniform. The spray characteristics of the atomizer assisted by gas jets reaches the best state when Wel = 4596.3 and m˙g = 1.97 g/s. The experimental conclusions have some guiding significance for the design and optimization of the atomization devices in spray drying towers.

The PTEN-induced kinase 1 (PINK1)-Parkin pathway plays a vital role in maintaining a healthy pool of mitochondria in higher eukaryotic cells. While the downstream components of this pathway are well understood, the upstream triggers remain less explored. In this study, we conducted an extensive analysis of inhibitors targeting various mitochondrial electron transport chain (ETC) complexes to investigate their potential as activators of the PINK1–Parkin pathway. We identified cloflucarban, an antibacterial compound, as a novel pathway activator that simultaneously inhibits mitochondrial complexes III and V, and V. RNA interference (RNAi) confirmed that the dual inhibition of these complexes activates the PINK1–Parkin pathway. Intriguingly, we discovered that albumin, specifically bovine serum albumin (BSA) and human serum albumin (HSA) commonly present in culture media, can hinder carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced pathway activation. However, cloflucarban’s efficacy remains unaffected by albumin, highlighting its reliability for studying the PINK1–Parkin pathway. This study provides insights into the activation of the upstream PINK1–Parkin pathway and underscores the influence of culture conditions on research outcomes. Cloflucarban emerges as a promising tool for investigating mitochondrial quality control and neurodegenerative diseases.

As the crucial part of a transmission assembly, the monitoring of the status of the crankshaft is essential for the normal working of a reciprocating machinery system. In consideration of the interaction between crankshaft system components, the fault vibration feature is typically non-stationary and nonlinear, and the single-scale feature extraction method cannot adequately assess the fault features, therefore a novel impact feature extraction method based on genetic algorithms to optimize multi-scale permutation entropy is proposed. Compared with other traditional feature extraction methods, the proposed method illustrates good robustness and high adaptability in the signal processing of crankshaft vibrations. Firstly, the improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) method is developed on the signal to obtain several intrinsic mode function (IMF) components, and the IMF components with a large kurtosis are selected for array reorganization. Then, the parameters of multi-scale permutation entropy (MPE) are optimized based on genetic algorithm (GA), the multi-scale permutation entropy is calculated and the feature vector set is constructed. The feature vector set is input into the support vector machine (SVM) and optimized by a particle swarm optimization (PSO) model for training and final pattern recognition, where the Variational Mode Decomposition(VMD)-GA-MPE with a PSO-SVM recognition model and the ICEEMDAN-MPE with PSO-SVM recognition model without GA optimization are constructed for a comparison with the proposed method. The research result illustrates that the proposed method, which inputs the genetic algorithm optimized multi-scale permutation entropy extracted from the ICEEMDAN decomposition into the PSO-SVM, performs well in impact feature extraction and the pattern recognition of crankshaft vibrations.

ObjectiveAlthough the seasonal variation of motor and non-motor symptoms in Parkinson's disease (PD) has been reported, the association between seasonal change and quality of life in patients with Parkinson's disease remains to be explored.MethodsWe recruited 1,036 patients with PD in this cross-sectional retrospective study. The patients were divided into four groups based on their date of assessment, according to the classical four seasons: group 1: March to May (n = 241); group 2: June to August (n = 259); group 3: September to November(n = 273); group 4: December to February (n = 263). The 39-item Parkinson's Disease Questionnaire (PDQ-39) and other clinical evaluation scales for motor and non-motor symptoms were administered. The determinants of the quality of life (QoL) were analyzed by multiple stepwise regression analyses.ResultsA significant difference in PDQ-39 was found between group 1 (spring months) and group 3 (autumn months) after correction (p = 0.002). The Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score was higher in group 1 (spring months) than in group 3 (the autumn months) (p = 0.033). The most severe determinant of QoL was the UPDRS-III score in group 1 and the Geriatric Depression Scale (GDS) score in groups 2, 3, and 4.InterpretationThe current study reported seasonal fluctuation of QoL in patients with PD, with higher scores during the spring months and lower scores in the autumn months. Since the determinants for QoL also vary by season, clinicians might need to focus on specific factors across seasons before initiating therapy.

Systems of difference equations frequently present dynamically unstable solutions in the long term, which could imply the appearance of complications in the application of vector autoregressive (VAR) models in the Johansen sense, regardless of the precision required. In this work the necessary conditions are presented to guarantee the dynamical convergence of the solutions from the approach of the systems in discrete time series with the stochastic processes. The main aim is to show the importance of dynamic stability in structural-type models with respect to estimator bias.

Abstract Pennisetum plants (Pennisetum alopecuroides L.), displaying a dwarfing phenotype along with delayed flowering and mosaic symptom on leaves, were found in Beijing, China. Flexuous filamentous particles with a size of approximate 15 × 850 nm were observed in symptomatic leaves via transmission electron microscopy. Deep sequencing of small RNAs (sRNA) from symptomatic leaves and analysis of sRNA populations were then conducted to determine the genome sequence of the viral agent in diseased plant tissues. It showed that the viral agent had one positive-sense and single-stranded RNA genome, which consisted of 9717 nucleotides (nts) excluding poly(A) tail. The complete viral genome contained a large open reading frame, encoding a polyprotein of 3131 amino acids (aa). Sequence comparison and phylogenetic analysis demonstrated that the viral agent belonged to the genus Potyvirus in the family Potyviridae. In the cladogram it was most closely related to johnsongrass mosaic virus, sharing 72% nt and 65% aa sequence identity. This viral agent was provisionally named pennisetum alopecuroides mosaic virus (PalMV). Subsequently, it was confirmed that PalMV is the causal agent of this new disease in P. alopecuroides by Koch’s postulates and reverse transcription-polymerase chain reaction analysis. Moreover, maize, millet, wheat, sorghum and rice plants were experimentally infected by PalMV via rub inoculation. Consequently, we proposed that PalMV could be a potentially dangerous virus threating a wide range of cereal crops.

Abstract Background The study was to evaluate initial antimicrobial regimen and clinical outcomes and to explore risk factors for clinical failure (CF) in elderly patients with community-acquired pneumonia (CAP). Methods 3011 hospitalized elderly patients were enrolled from 13 national teaching hospitals between January 1, 2014 and December 31, 2014 initiated by the CAP-China network. Risk factors for CF were screened by multivariable logistic regression analysis. Results The incidence of CF in elderly CAP patients was 13.1%. CF patients were older, longer hospital stays and higher treatment costs than clinical success (CS) patients. The CF patients were more prone to present hyperglycemia, hyponatremia, hypoproteinemia, pleural effusion, respiratory failure and cardiovascular events. Inappropriate initial antimicrobial regimens in CF group were significantly higher than CS group. Undertreatment, CURB-65, PH 10,000/mm3, pleural effusion and congestive heart failure were independent risk factors for CF in multivariable logistic regression analysis. Male and bronchiectasis were protective factors. Conclusions Discordant therapy was a cause of CF. Early accurate detection and management of prevention to potential causes is likely to improve clinical outcomes in elderly patients CAP. Trial registration A Retrospective Study on Hospitalized Patients With Community-acquired Pneumonia in China (CAP-China) (RSCAP-China), NCT02489578. Registered 16 March 2015, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0005E5S&selectaction=Edit&uid=U0000GWC&ts=2&cx=1bnotb

The PINK1/Parkin pathway plays an important role in maintaining a healthy pool of mitochondria. Activation of this pathway can lead to apoptosis, mitophagy, or mitochondrial-derived vesicle formation, depending on the nature of mitochondrial damage. The signaling by which PINK/Parkin activation leads to these different mitochondrial outcomes remains understudied. Here we present evidence that cannabidiol (CBD) activates the PINK1-Parkin pathway in a unique manner. CBD stimulates PINK1-dependent Parkin mitochondrial recruitment similarly to other well-studied Parkin activators but with a distinctive shift in the temporal dynamics and mitochondrial fates. The mitochondrial permeability transition pore inhibitor cyclosporine A exclusively diminished the CBD-induced PINK1/Parkin activation and its associated mitochondrial effects. Unexpectedly, CBD treatment also induced elevated production of mitochondrial-derived vesicles (MDV), a potential quality control mechanism that may help repair partial damaged mitochondria. Our results suggest that CBD may engage the PINK1-Parkin pathway to produce MDV and repair mitochondrial lesions via mitochondrial permeability transition pore opening. This work uncovered a novel link between CBD and PINK1/Parkin-dependent MDV production in mitochondrial health regulation.

Aberrant activation of calmodulin 1 (CALM1) has been reported in human cancers. However, comprehensive understanding of the role of CALM1 in most cancer types has remained unclear. We systematically analyzed the expression landscape, DNA methylation, gene alteration, immune infiltration, clinical relevance, and molecular pathway of CALM1 in multiple cancers using various online tools, including The Cancer Genome Atlas, cBioPortal and the Human Protein Atlas databases. Kaplan–Meier and receiver operating characteristic (ROC) curves were plotted to explore the prognostic and diagnostic potential of CALM1 expression. Multivariate analyses were used to evaluate whether the CALM1 expression could be an independent risk factor. A nomogram predicting the overall survival (OS) of patients was developed, evaluated, and compared with the traditional Tumor-Node-Metastasis (TNM) model using decision curve analysis. R language was employed as the main tool for analysis and visualization. Results revealed CALM1 to be highly expressed in most cancers, its expression being regulated by DNA methylation in multiple cancers. CALM1 had a low mutation frequency (within 3%) and was associated with immune infiltration. We observed a substantial positive correlation between CALM1 expression and macrophage and neutrophil infiltration levels in multiple cancers. Different mutational forms of CALM1 hampered immune cell infiltration. Additionally, CALM1 expression had high diagnostic and prognostic potential. Multivariate analyses revealed CALM1 expression to be an independent risk factor for OS. Therefore, our newly developed nomogram had a higher clinical value than the TNM model. The concordance index, calibration curve, and time-dependent ROC curves of the nomogram exhibited excellent performance in terms of predicting the survival rate of patients. Moreover, elevated CALM1 expression contributes to the activation of cancer-related pathways, such as the WNT and MAPK pathways. Overall, our findings improved our understanding of the function of CALM1 in human cancers.

In order to quickly and accurately detect whether a chef is wearing a hat and mask, a kitchen standard dress detection method based on the YOLOv5s embedded model is proposed. Firstly, a complete kitchen scene dataset was constructed, and the introduction of images for the wearing of masks and hats allows for the low reliability problem caused by a single detection object to be effectively avoided. Secondly, the embedded detection system based on Jetson Xavier NX was introduced into kitchen standard dress detection for the first time, which accurately realizes real-time detection and early warning of non-standard dress. Among them, the combination of YOLOv5 and DeepStream SDK effectively improved the accuracy and effectiveness of standard dress detection in the complex kitchen background. Multiple sets of experiments show that the detection system based on YOLOv5s has the highest average accuracy of 0.857 and the fastest speed of 31.42 FPS. Therefore, the proposed detection method provided strong technical support for kitchen hygiene and food safety.

This prospective, single-center study evaluated the clinical utility of annenxin (Anx)A1 level as a biomarker for determining the severity of illness and predicting the risk of death in hospitalized patients with community-acquired pneumonia (CAP). A total of 105 patients (53 with severe [S]CAP, 52 with non-SCAP) were enrolled from December 2020 to June 2021. Demographic and clinical data were recorded. Serum AnxA1 concentration on days one and six after admission was measured by enzyme-linked immunosorbent assay. AnxA1 level at admission was significantly higher in SCAP patients than in non-SCAP patients (p < 0.001) irrespective of CAP etiology and was positively correlated with Pneumonia Severity Index and Confusion, Uremia, Respiratory Rate, Blood Pressure, and Age ≥ 65 Years score. AnxA1 level was significantly lower on day six after treatment than on day one (p = 0.01). Disease severity was significantly higher in patents with AnxA1 level ≥254.13 ng/mL than in those with a level p < 0.001). Kaplan–Meier analysis of 30-day mortality showed that AnxA1 level ≤670.84 ng/mL was associated with a significantly higher survival rate than a level >670.84 ng/mL. These results indicate that AnxA1 is a useful biomarker for early diagnosis and prognostic assessment of CAP.

Emissions of airborne particulate matter are a major cause of air pollution. A numerical approach was used to establish a single-filter-bag cleaning model based on the discrete phase particle deposition distribution law to study the effect of pulse backflushing operation parameters on the cleaning performance of the specific structure of the dust collector. It was found that increasing the pulse blowing pressure (0.2 MPa to 0.6 MPa) and extending the pulse width (0.02 s to 0.1 s) resulted in an increase in the side wall pressure of the filter bag and, thus, improved its cleaning effect. The influence of the injection pressure on the side wall pressure peak of the filter bag was more obvious than that of the pulse width. However, it cannot be concluded that the greater the injection pressure and pulse width, the better the cleaning effect. Therefore, in the actual production application, the operating cost of the equipment needs to be taken into account, as well as the amount of dust on the surface of the filter bag.

This paper studies the dynamic filtration behavior of coal particles in metal fiber felt, by developing a three-dimensional model based on microstructure and arrangement mode of metal fiber felt identified by scanning electron microscope. Discrete element method (DEM) is coupled with Computational fluid dynamics (CFD) to simulate filtration of coal particles in metal fiber felt. The simulation mainly studies the moving trail and deposition characteristics of spherical coal particles. The results demonstrated that coal particles can bypass the metal fibers and enter the inside of the metal fiber felt through mesh channels. The moving trail of coal particles is similar to a broken line. It is also shown that most coal particles are trapped due to the deep filtration of metal fiber felt and the distribution pattern of them is inhomogeneous. The number of particles trapped by metal fiber felt is reduced in the direction of thickness. It is found that coal particles can be trapped not only by randomly arranged metal fibers, but also by coal particles deposited previously. Finally, the kinetic energy loss of coal particles mainly occurs in the initial stage when particles pass through metal fiber felt. And the velocity of coal particles inside metal fiber felt is maintained at 0.15–0.25 m/s. Highlights A more realistic three-dimensional model was reconstructed according to scanning electron microscope pictures. The particle trajectory, deposition mode of particle groups and speed change of particles were investigated using CFD–DEM in the paper. The simulation method was validated by the experiment.

Through the appearance observation of suspension rod in the metro gearbox, macro and micro observation of the fracture and quantitative analysis of the fracture, combined with the metallographic and hardness examination results of the boom, the finite element model was established and the force analysis of suspension rod was carried out to explore the causes of the fracture of the gearbox boom. The results show that the nature of suspension rod fracture is fatigue. The cause of its fatigue fracture is related to the low fatigue tolerance for booms in metro operation, and the surface shallow decarburization plays a role in promoting the fatigue fracture of suspension rod. The life of fatigue crack growth in the boom is 819 stations (or 1210 km), and the fatigue initiation life is 522,452 km.

Magnesium alloys play an important role in lightweight structures, which are extensively used in different industries due to their excellent mechanical and physical properties. In this paper, the formability of the AZ31B magnesium alloy sheet was studied by using tensile tests at different temperatures (from 25 to 250 °C) and strain rates (from 0.017 s−1 to 0.34 s−1). The results showed that the material behaves with positive temperature sensitivity when forming at a temperature lower than 200 °C. The effect of the strain rates on the formability of AZ31B was larger at high temperatures. The metallography of AZ31B at different temperatures and strain rates was observed by OM. The results showed that the partially recrystallized structure was exhibited at a temperature of 150 °C. With the increase in temperature, the approximate complete recrystallization was exhibited at a temperature of 250 °C. The fracture morphology of AZ31B was observed at different strain rates and temperatures by SEM. Additionally, the main fracture pattern was quasi-cleavage at room temperature. However, with the increase in temperature, the fracture pattern was transited from a quasi-cleavage pattern to a ductile fracture pattern. The ductile fracture pattern was the main fracture pattern at a temperature of 250 °C.

The differentially weighted operator-splitting Monte Carlo (DWOSMC) method is further developed to describe the droplet aerosol dynamic behaviors, including coagulation, deposition, condensation, and evaporation processes. It is first proposed that the droplet aerosols will experience firstly condensation and then evaporation, and this phenomenon is first implemented into the Monte Carlo method and sectional method with considering coagulation, deposition, and condensation/evaporation processes in both single-component and two-component aerosol particle systems. It is found that the calculated results of the DWOSMC method agree well with both the analytical solutions and the sectional method. The further developed DWOSMC method can predict the variation of particle number density, total particle volume, mean particle diameter, particle size distributions, and the component-related particle volume densities in both single component and two-component droplet aerosol systems considering coagulation, deposition, and condensation/evaporation processes.

Abstract Background Limited information exists on the clinical characteristics predictive of mortality in patients aged ≥65 years in many countries. The impact of adherence to current antimicrobial guidelines on the mortality of hospitalized elderly patients with community-acquired pneumonia (CAP) has never been assessed. Methods A total of 3131 patients aged ≥65 years were enrolled from a multi-center, retrospective, observational study initiated by the CAP-China network. Risk factors for death were screened with multivariable logistic regression analysis, with emphasis on the evaluation of age, comorbidities and antimicrobial treatment regimen with regard to the current Chinese CAP guidelines. Results The mean age of the study population was 77.4 ± 7.4 years. Overall in-hospital and 60-day mortality were 5.7% and 7.6%, respectively; these rates were three-fold higher in those aged ≥85 years than in the 65–74 group (11.9% versus 3.2% for in-hospital mortality and 14.1% versus 4.7% for 60-day mortality, respectively). The mortality was significantly higher among patients with comorbidities compared with those who were otherwise healthy. According to the 2016 Chinese CAP guidelines, 62.1% of patients (1907/3073) received non-adherent treatment. For general-ward patients without risk factors for Pseudomonas aeruginosa (PA) infection (n = 2258), 52.3% (1094/2090) were over-treated, characterized by monotherapy with an anti-pseudomonal β-lactam or combination with fluoroquinolone + β-lactam; while 71.4% of intensive care unit (ICU) patients (120/168) were undertreated, without coverage of atypical bacteria. Among patients with risk factors for PA infection (n = 815), 22.9% (165/722) of those in the general ward and 74.2% of those in the ICU (69/93) were undertreated, using regimens without anti-pseudomonal activity. The independent predictors of 60-day mortality were age, long-term bedridden status, congestive heart failure, CURB-65, glucose, heart rate, arterial oxygen saturation (SaO2) and albumin levels. Conclusions Overtreatment in general-ward patients and undertreatment in ICU patients were critical problems. Compliance with Chinese guidelines will require fundamental changes in standard-of-care treatment patterns. The data included herein may facilitate early identification of patients at increased risk of mortality. Trial registration The study was registered at ClinicalTrials.gov (NCT02489578).

Endogenous microRNAs (miRNAs) play pivotal roles in plant development and responses to various biotic or abiotic stresses. Up to now, more than 500 maize miRNAs have been identified. However, functions of these identified miRNAs remained largely unknown due mainly to the lack of rapid and reliable tools. We previously reported a cucumber mosaic virus strain ZMBJ (ZMBJ-CMV)-based gene silencing vector for rapid and efficient gene function studies in maize lines with agronomical importance. Because ZMBJ-CMV induces very mild disease symptoms but strong gene silencing in maize, we decided to further modify this vector to suppress miRNA expressions in maize. The newly developed ZMBJ-CMV-2bN81-STTM vector expresses a short tandem target mimic (STTM) containing two target-mimic sequences separated by a short spacer sequence. Our results showed that ZMBJ-CMV-2bN81-STTM can be used to investigate miRNA function in Nicotiana benthamiana and maize seedlings. The ZMBJ-CMV-2bN81-STTM-based downregulation of Nbe-miR165/166 or Nbe-miR159 induced specific and strong miRNA-sequestering phenotypes, and increased the expressions of their predicted target genes. For maize, the ZMBJ-CMV-2bN81-STTM based downregulation of zma-miR167 or zma-miR482 caused a decrease of lateral roots growth and a plant stunting phenotypes, respectively. In both cases, the target genes of zma-miR167- or zma-miR482 were increased significantly. Thus, we consider ZMBJ-CMV based VbMS system as a useful tool for high-throughput investigations of miRNA functions in maize.

Glycophosphatidylinositol-anchored proteins (GPI-APs) play essential roles in physiology, but their biogenesis and trafficking have not been systematically characterized. Here, we took advantage of the recently available haploid genetics approach to dissect GPI-AP pathways in human cells using prion protein (PrP) and CD59 as model molecules. Our screens recovered a large number of common and unexpectedly specialized factors in the GPI-AP pathways. PIGN, PGAP2, and PIGF, which encode GPI anchor-modifying enzymes, were selectively isolated in the CD59 screen, suggesting that GPI anchor composition significantly influences the biogenesis of GPI-APs in a substrate-dependent manner. SEC62 and SEC63, which encode components of the ER-targeting machinery, were selectively recovered in the PrP screen, indicating that they do not constitute a universal route for the biogenesis of mammalian GPI-APs. Together, these comparative haploid genetic screens demonstrate that, despite their similarity in overall architecture and subcellular localization, GPI-APs follow markedly distinct biosynthetic and trafficking pathways.

To reveal the effect of stress triaxiality on plastic damage evolution and failure mode, 316L notched specimens with different notch sizes are systematically investigated by digital image correlation (DIC) observation, plastic damage analysis by finite element simulation, and void mesoscopic observation. It was found that the plastic damage evolution and failure mode are closely related with notch radius and stress triaxiality. The greater the stress triaxiality at the root is, the greater the damage value at the root is and the earlier the fracture occurs. Moreover, void distribution by mesoscopic observation agrees well with damage distribution observed by finite element simulation with the Gurson-Tvergaard-Needleman (GTN) damage model. It is worth noting that, with the increase in stress triaxiality, the failure mode of notched specimen changes from ductility fracture with void coalescence at the center position to crack initiation at the notch root, from both mesoscopic observation and damage simulation.

This report described the complete mitochondrial genome of the Saiga antelope, Saiga tatarica, from the Gansu Endangered Animal Research Center (GEARC) in Gansu Province, China. The mitogenome was a circular molecule of 16,376 bps (Genbank accession number: MF497028). It contained 13 protein-coding, 22 tRNA and two rDNA genes. The protein-coding genes had ATA or ATG as the initiation codon, and were terminated by the typical stop codon TAA, except for NAD2 and NAD3. The complete mitogenome sequence would be useful for further understanding origination, evolution and conservation genetics of S. tatarica population in China.

Neurofibrillary tangles are aggregates of hyperphosphorylated tau that are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by a balance of kinase and phosphatase activities. Our previous study has demonstrated that ginsenoside Rd, one of the principal active ingredients of Pana notoginseng, inhibits okadaic acid-induced tau phosphorylation in vivo and in vitro, but the underlying mechanism(s) is unknown. In this study, we showed that ginsenoside Rd pretreatment inhibited tau phosphorylation at multiple sites in beta-amyloid (Aβ)-treated cultured cortical neurons, and in vivo in both a rat and transgenic mouse model. Ginsenoside Rd not only reduced Aβ-induced increased expression of glycogen synthase kinase 3beta (GSK-3β), the most important kinase involved in tau phosphorylation, but also inhibited its activity by enhancing and attenuating its phosphorylation at Ser9 and Tyr216, respectively. Moreover, ginsenoside Rd enhanced the activity of protein phosphatase 2A (PP-2A), a key phosphatase involved in tau dephosphorylation. Finally, an in vitro biochemical assay revealed that ginsenoside Rd directly affected GSK-3β and PP-2A activities. Thus, our findings provide the first evidence that ginsenoside Rd attenuates Aβ-induced pathological tau phosphorylation by altering the functional balance of GSK-3β and PP-2A.

A new chemical component, cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide, was isolated from Angelica sinensis and its structure elucidated from its NMR and MS spectra and confirmed by X-ray single crystal diffraction analysis. We also explored the antioxidative properties of cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide on human umbilical vein endothelial cells (HUVECs) against injuries induced by hydrogen peroxide (H2O2) using an MTT assay and flow cytometry analysis. In addition, the activities of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), nitric oxide (NO) and reactive oxygen species (ROS) were determined. We found that cis-Z,Z'-3a.7a',7a.3a'-dihydroxyligustilide increased the viability of HUVECs injured by H2O2 in a dose-dependent manner, reduced the apoptosis of HUVEC, and enhanced HUVEC proliferation. Our results demonstrated the remarkable in vitro antioxidative activities of this compound, indicating that it could be a potential antioxidant with protective effects against H2O2-induced HUVEC injuries.

Abstract Mammalian cells can decode the concentration of extracellular transforming growth factor‐β (TGF‐β) and transduce this cue into appropriate cell fate decisions. How variable TGF‐β ligand doses quantitatively control intracellular signaling dynamics and how continuous ligand doses are translated into discontinuous cellular fate decisions remain poorly understood. Using a combined experimental and mathematical modeling approach, we discovered that cells respond differently to continuous and pulsating TGF‐β stimulation. The TGF‐β pathway elicits a transient signaling response to a single pulse of TGF‐β stimulation, whereas it is capable of integrating repeated pulses of ligand stimulation at short time interval, resulting in sustained phospho‐Smad2 and transcriptional responses. Additionally, the TGF‐β pathway displays different sensitivities to ligand doses at different time scales. While ligand‐induced short‐term Smad2 phosphorylation is graded, long‐term Smad2 phosphorylation is switch‐like to a small change in TGF‐β levels. Correspondingly, the short‐term Smad7 gene expression is graded, while long‐term PAI‐1 gene expression is switch‐like, as is the long‐term growth inhibitory response. Our results suggest that long‐term switch‐like signaling responses in the TGF‐β pathway might be critical for cell fate determination.

Understanding how cells migrate individually and collectively during development and cancer metastasis can be significantly aided by a computation tool to accurately measure not only cellular migration speed, but also migration direction and changes in migration direction in a temporal and spatial manner. We have developed such a tool for cell migration researchers, named Pathfinder, which is capable of simultaneously measuring the migration speed, migration direction, and changes in migration directions of thousands of cells both instantaneously and over long periods of time from fluorescence microscopy data. Additionally, we demonstrate how the Pathfinder software can be used to quantify collective cell migration. The novel capability of the Pathfinder software to measure the changes in migration direction of large populations of cells in a spatiotemporal manner will aid cellular migration research by providing a robust method for determining the mechanisms of cellular guidance during individual and collective cell migration.

Protein ubiquitination plays an important role in the regulation of almost every aspect of eukaryotic cellular function; therefore, its destabilization is often observed in most human diseases and cancers. Consequently, developing inhibitors of the ubiquitination system for the treatment of cancer has been a recent area of interest. Currently, only a few classes of compounds have been discovered to inhibit the ubiquitin-activating enzyme (E1) and only one class is relatively selective in E1 inhibition in cells. We now report that Largazole and its ester and ketone analogs selectively inhibit ubiquitin conjugation to p27(Kip1) and TRF1 in vitro. The inhibitory activity of these small molecules on ubiquitin conjugation has been traced to their inhibition of the ubiquitin E1 enzyme. To further dissect the mechanism of E1 inhibition, we analyzed the effects of these inhibitors on each of the two steps of E1 activation. We show that Largazole and its derivatives specifically inhibit the adenylation step of the E1 reaction while having no effect on thioester bond formation between ubiquitin and E1. E1 inhibition appears to be specific to human E1 as Largazole ketone fails to inhibit the activation of Uba1p, a homolog of E1 in Schizosaccharomyces pombe. Moreover, Largazole analogs do not significantly inhibit SUMO E1. Thus, Largazole and select analogs are a novel class of ubiquitin E1 inhibitors and valuable tools for studying ubiquitination in vitro. This class of compounds could be further developed and potentially be a useful tool in cells.

The revelation that the human genome encodes only approximately 25,000 genes and thus cannot account for phenotypic complexity has been one of the biggest surprises in the post-genomic era. However, accumulating evidence suggests that transcriptional regulation may be in large part responsible for this observed mammalian complexity. Consequently, there has been a strong drive to locate cis-regulatory regions in mammalian genomes in order to understand the unifying principles governing these regions, including their genomic distribution. Although a number of systematic approaches have been developed, these all discount coding sequence.Using the computational tool PRI (Pattern-defined Regulatory Islands), which does not mask coding sequence, we identified a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2. We demonstrate through a combination of chromatin immunoprecipitation and reporter gene studies that this region can not only bind the myogenic transcription factors MYOD and myogenin and the E-protein HEB but can also function as a very strong myogenic transcriptional enhancer.Thus, we report the identification and detailed characterization of an exonic enhancer. Ultimately, this leads to the interesting question of why evolution would be so parsimonious in the functional assignment of sequence.

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