MFPred: prediction of ncRNA families based on multi-feature fusion.

Non-coding RNA (ncRNA) plays a critical role in biology. ncRNAs from the same family usually have similar functions, as a result, it is essential to predict ncRNA families before identifying their functions. There are two primary methods for predicting ncRNA families, namely, traditional biological methods and computational methods. In traditional biological methods, a lot of manpower and resources are required to predict ncRNA families. Therefore, this paper proposed a new ncRNA family prediction method called MFPred based on computational methods. MFPred identified ncRNA families by extracting sequence features of ncRNAs, and it possessed three primary modules, including (1) four ncRNA sequences encoding and feature extraction module, which encoded ncRNA sequences and extracted four different features of ncRNA sequences, (2) dynamic Bi_GRU and feature fusion module, which extracted contextual information features of the ncRNA sequence and (3) ResNet_SE module that extracted local information features of the ncRNA sequence. In this study, MFPred was compared with the previously proposed ncRNA family prediction methods using two frequently used public ncRNA datasets, NCY and nRC. The results showed that MFPred outperformed other prediction methods in the two datasets.

MMGAT: a graph attention network framework for ATAC-seq motifs finding.

BACKGROUND: Motif finding in Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) data is essential to reveal the intricacies of transcription factor binding sites (TFBSs) and their pivotal roles in gene regulation. Deep learning technologies including convolutional neural networks (CNNs) and graph neural networks (GNNs), have achieved success in finding ATAC-seq motifs. However, CNN-based methods are limited by the fixed width of the convolutional kernel, which makes it difficult to find multiple transcription factor binding sites with different lengths. GNN-based methods has the limitation of using the edge weight information directly, makes it difficult to aggregate the neighboring nodes' information more efficiently when representing node embedding. RESULTS: To address this challenge, we developed a novel graph attention network framework named MMGAT, which employs an attention mechanism to adjust the attention coefficients among different nodes. And then MMGAT finds multiple ATAC-seq motifs based on the attention coefficients of sequence nodes and k-mer nodes as well as the coexisting probability of k-mers. Our approach achieved better performance on the human ATAC-seq datasets compared to existing tools, as evidenced the highest scores on the precision, recall, F1_score, ACC, AUC, and PRC metrics, as well as finding 389 higher quality motifs. To validate the performance of MMGAT in predicting TFBSs and finding motifs on more datasets, we enlarged the number of the human ATAC-seq datasets to 180 and newly integrated 80 mouse ATAC-seq datasets for multi-species experimental validation. Specifically on the mouse ATAC-seq dataset, MMGAT also achieved the highest scores on six metrics and found 356 higher-quality motifs. To facilitate researchers in utilizing MMGAT, we have also developed a user-friendly web server named MMGAT-S that hosts the MMGAT method and ATAC-seq motif finding results. CONCLUSIONS: The advanced methodology MMGAT provides a robust tool for finding ATAC-seq motifs, and the comprehensive server MMGAT-S makes a significant contribution to genomics research. The open-source code of MMGAT can be found at https://github.com/xiaotianr/MMGAT , and MMGAT-S is freely available at https://www.mmgraphws.com/MMGAT-S/ .

Computer-aided cognitive training combined with tDCS can improve post-stroke cognitive impairment and cerebral vasomotor function: a randomized controlled trial.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is the focus and difficulty of poststroke rehabilitation intervention with an incidence of up to 61%, which may be related to the deterioration of cerebrovascular function. Computer-aided cognitive training (CACT) can improve cognitive function through scientific training targeting activated brain regions, becoming a popular training method in recent years. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, can regulate the cerebral vascular nerve function, and has an effect on the rehabilitation of cognitive dysfunction after stroke. This study examined the effectiveness of both CACT and tDCS on cognitive and cerebrovascular function after stroke, and explored whether CACT combined with tDCS was more effective. METHODS: A total of 72 patients with PSCI were randomly divided into the conventional cognitive training (CCT) group (n = 18), tDCS group (n = 18), CACT group (n = 18), and CACT combined with tDCS group (n = 18). Patients in each group received corresponding 20-minute treatment 15 times a week for 3 consecutive weeks. Montreal Cognitive Assessment (MoCA) and the Instrumental Activities of Daily Living Scale (IADL) were used to assess patients' cognitive function and the activities of daily living ability. Transcranial Doppler ultrasound (TCD) was used to assess cerebrovascular function, including cerebral blood flow velocity (CBFV), pulse index (PI), and breath holding index (BHI). These outcome measures were measured before and after treatment. RESULTS: Compared with those at baseline, both the MoCA and IADL scores significantly increased after treatment (P < 0.01) in each group. There was no significantly difference in efficacy among CCT, CACT and tDCS groups. The CACT combined with tDCS group showed greater improvement in MoCA scores compared with the other three groups (P < 0.05), especially in the terms of visuospatial and executive. BHI significantly improved only in CACT combined with tDCS group after treatment (p ≤ 0.05) but not in the other groups. Besides, no significant difference in CBFV or PI was found before and after the treatments in all groups. CONCLUSION: Both CACT and tDCS could be used as an alternative to CCT therapy to improve cognitive function and activities of daily living ability after stroke. CACT combined with tDCS may be more effective improving cognitive function and activities of daily living ability in PSCI patients, especially visuospatial and executive abilities, which may be related to improved cerebral vasomotor function reflected by the BHI. TRIAL REGISTRATION NUMBER: The study was registered in the Chinese Registry of Clinical Trials (ChiCTR2100054063). Registration date: 12/08/2021.

Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.

BACKGROUND: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology. METHODS: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline. RESULTS: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart. CONCLUSIONS: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.

Fenton-like system of UV/Glucose-oxidase@Kaolin coupled with organic green rust: UV-enhanced enzyme activity and the mechanism of UV synergistic degradation of photosensitive pollutants.

This study introduces the UV/glucose-oxidase@Kaolin (GOD@Kaolin) coupled organic green rust (OGR) system (UV/OGR/GOD@Kaolin) to investigate the promotion of glucose oxidase activity by UV light and its synergistic degradation mechanism for photosensitive pollutants, specifically targeting the efficient degradation of 4-chlorophenol (4-CP). The enzyme system demonstrates its ability to overcome drawbacks associated with traditional Fenton systems, including a narrow pH range and high localized concentration of H2O2, by gradually releasing hydrogen peroxide in situ within a neutral environment. In the presence of UV radiation under specific conditions, enhanced enzyme activity is observed, resulting in increased efficiency in pollutant removal. The gradual release of hydrogen peroxide plays a crucial role in preventing unwanted reactions among active substances. These unique features facilitate the generation of highly reactive species, such as Fe(IV)O, •OH, and •O2-, tailored to efficiently target the organic components of interest. Additionally, the system establishes a positive iron cycle, ensuring a sustained reactive capability throughout the degradation process. The results highlight the UV/OGR/GOD@Kaolin system as an effective and environmentally friendly approach for the degradation of 4-CP, and the resilience of the enzyme extends the system's applicability to a broader range of scenarios.

Risk factor analysis and risk prediction study of obesity in steelworkers: model development based on an occupational health examination cohort dataset.

BACKGROUND: Obesity is increasingly recognized as a grave public health concern globally. It is associated with prevalent diseases including coronary heart disease, fatty liver, type 2 diabetes, and dyslipidemia. Prior research has identified demographic, socioeconomic, lifestyle, and genetic factors as contributors to obesity. Nevertheless, the influence of occupational risk factors on obesity among workers remains under-explored. Investigating risk factors specific to steelworkers is crucial for early detection, prediction, and effective intervention, thereby safeguarding their health. METHODS: This research utilized a cohort study examining health impacts on workers in an iron and steel company in Hebei Province, China. The study involved 5469 participants. By univariate analysis, multifactor analysis, and review of relevant literature, predictor variables were found. Three predictive models-XG Boost, Support Vector Machine (SVM), and Random Forest (RF)-were employed. RESULTS: Univariate analysis and cox proportional hazard regression modeling identified age, gender, smoking and drinking habits, dietary score, physical activity, shift work, exposure to high temperatures, occupational stress, and carbon monoxide exposure as key factors in the development of obesity in steelworkers. Test results indicated accuracies of 0.819, 0.868, and 0.872 for XG Boost, SVM, and RF respectively. Precision rates were 0.571, 0.696, and 0.765, while recall rates were 0.333, 0.592, and 0.481. The models achieved AUCs of 0.849, 0.908, and 0.912, with Brier scores of 0.128, 0.105, and 0.104, log losses of 0.409, 0.349, and 0.345, and calibration-in-the-large of 0.058, 0.054, and 0.051, respectively. Among these, the Random Forest model demonstrated superior performance. CONCLUSIONS: The research indicates that obesity in steelworkers results from a combination of occupational and lifestyle factors. Of the models tested, the Random Forest model exhibited superior predictive ability, highlighting its significant practical application.

A Wireless Passive Pressure-Sensing Method for Cryogenic Applications Using Magnetoresistors.

In this study, we developed a novel wireless, passive pressure-sensing method functional at cryogenic temperatures (-196 °C). The currently used pressure sensors are inconvenient and complicated in cryogenic environments for their weak low-temperature tolerances and long wires for power supply and data transmission. We propose a novel pressure-sensing method for cryogenic applications by only using low-temperature-tolerant passive devices. By innovatively integrating a magnetoresistor (MR) on a backscattering antenna, the pressure inside a cryogenic environment is transferred to a wirelessly obtainable return loss. Wireless passive measurement is thus achieved using a backscattering method. In the measurement, the pressure causes a relative displacement between the MR and a magnet. The MR's resistance changes with the varied magnetic field, thus modulating the antenna's return loss. The experimental results indicate that our fabricated sensor successfully identified different pressures, with high sensitivities of 4.3 dB/MPa at room temperature (24 °C) and 1.3 dB/MPa at cryogenic temperature (-196 °C). Additionally, our method allows for simultaneous wireless readings of multi sensors via a single reading device by separating the frequency band of each sensor. Our method performs low-cost, simple, robust, passive, and wireless pressure measurement at -196 °C; thus, it is desirable for cryogenic applications.

ESMSec: Prediction of Secreted Proteins in Human Body Fluids Using Protein Language Models and Attention.

The secreted proteins of human body fluid have the potential to be used as biomarkers for diseases. These biomarkers can be used for early diagnosis and risk prediction of diseases, so the study of secreted proteins of human body fluid has great application value. In recent years, the deep-learning-based transformer language model has transferred from the field of natural language processing (NLP) to the field of proteomics, leading to the development of protein language models (PLMs) for protein sequence representation. Here, we propose a deep learning framework called ESM Predict Secreted Proteins (ESMSec) to predict three types of proteins secreted in human body fluid. The ESMSec is based on the ESM2 model and attention architecture. Specifically, the protein sequence data are firstly put into the ESM2 model to extract the feature information from the last hidden layer, and all the input proteins are encoded into a fixed 1000 × 480 matrix. Secondly, multi-head attention with a fully connected neural network is employed as the classifier to perform binary classification according to whether they are secreted into each body fluid. Our experiment utilized three human body fluids that are important and ubiquitous markers. Experimental results show that ESMSec achieved average accuracy of 0.8486, 0.8358, and 0.8325 on the testing datasets for plasma, cerebrospinal fluid (CSF), and seminal fluid, which on average outperform the state-of-the-art (SOTA) methods. The outstanding performance results of ESMSec demonstrate that the ESM can improve the prediction performance of the model and has great potential to screen the secretion information of human body fluid proteins.

Discovery of 2,4-diphenyl-substituted thiazole derivatives as PRMT1 inhibitors and investigation of their anti-cervical cancer effects.

Cervical cancer is one of the most common cancers that affects middle-aged women and the discovery of new drugs to aid clinical management is needed. As an important member of the protein arginine methyltransferases (PRMTs) family, PRMT1 catalyzes the methylation of protein arginine, which can influence multiple biological processes of cancer cells, such as activating epithelial-mesenchymal transformation (EMT) and acquiring resistance to apoptosis. Therefore, PRMT1 can be considered as a potential drug target for cervical cancer. In the current study, a new sub-binding pocket was discovered by molecular modeling, and by introducing a third substitute on the thiazole group to occupy this pocket, a series of compounds were designed and synthesized as potential PRMT1 inhibitors. Of these, two compounds (ZJG51 and ZJG58) exhibited significant inhibitory activities against PRMT1 without significantly inhibiting PRMT5. Both ZJG51 and ZJG58 displayed potent inhibitory effects on the proliferation of four cancer-derived cell lines and ZJG51 exerted relative selectivity against the cervical cancer cell line, HeLa. Further studies showed that ZJG51 inhibited migration and induce the apoptosis of HeLa cells. Mechanistically, ZJG51 significantly regulated PRMT1 related proteins, and indicated that the induction of apoptosis and inhibition of migration by ZJG51 may involve the activation of Caspase 9 and the inhibition of EMT, respectively. Molecular dynamic simulation and free energy calculation showed that ZJG51 can bind to PRMT1 stably and the binding mode was predicted. These data indicated that introducing the third substitute on the five-membered ring could be a future direction for structure-based optimization of PRMT1 inhibitors, and ZJG51 could be an important lead compound to inform the design of more potent inhibitors.

Horseradish peroxidase (HRP) and glucose oxidase (GOX) based dual-enzyme system: Sustainable release of H2O2 and its effect on the desirable ping pong bibi degradation mechanism.

In this study, an adaptable HRP/GOX-Glu system was established due to the trait, efficient degradation of pollutants in the catalytic process of HRP named the ping-pong bibi mechanism and a sustained release of H2O2 in-situ under the catalysis of glucose oxidase (GOX). Compared with the traditional HRP/H2O2 system, the HRP was more stable in the HRP/GOX-Glu system based on the feature of persistent releasing H2O2 in-situ. Simultaneously, the high valent iron was found out to give a greater contribution to Alizarin Green (AG) removal through ping-pong mechanism, whereas the hydroxyl radical and superoxide free radical generated by Bio-Fenton were also the main active substances for AG degradation. Furthermore, on the basis of effect evaluation of the co-existence of two different degradation mechanisms in the HRP/GOX-Glu system, the degradation pathways of AG were proposed. Moreover, the optimum reaction conditions preferentially triggering ping-pong bibi mechanism instead of Bio-Fenton were determined by single factor analysis and degradation mechanism elaboration. This study would provide a reference for how to give full play to the advantages of ping-pong bibi mechanism in the dual-enzyme system based on HRP to degrade pollutants with high efficiency.

A nested case-control study of the effects of dust exposure, smoking on COPD in coal workers.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction. METHOD: A nested case-control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017-2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers. RESULTS: The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers. CONCLUSION: Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents.

Video Process Mining and Model Matching for Intelligent Development: Conformance Checking.

Traditional business process-extraction models mainly rely on structured data such as logs, which are difficult to apply to unstructured data such as images and videos, making it impossible to perform process extractions in many data scenarios. Moreover, the generated process model lacks analysis consistency of the process model, resulting in a single understanding of the process model. To solve these two problems, a method of extracting process models from videos and analyzing the consistency of process models is proposed. Video data are widely used to capture the actual performance of business operations and are key sources of business data. Video data preprocessing, action placement and recognition, predetermined models, and conformance verification are all included in a method for extracting a process model from videos and analyzing the consistency between the process model and the predefined model. Finally, the similarity was calculated using graph edit distances and adjacency relationships (GED_NAR). The experimental results showed that the process model mined from the video was better in line with how the business was actually carried out than the process model derived from the noisy process logs.

Comparative Efficacy of Neuromodulation Technologies for Overactive Bladder in Adults: A Network Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The aim of this study was to investigate the comparative efficacy of neuromodulation technologies for overactive bladder (OAB) syndrome in adults. DATA SOURCES: A computerized search was conducted of Cochrane Library, EMBASE, MEDLINE (via PubMed), Web of Science, CNKI, Wan Fang Data, and ClinicalTrials.gov up to April 21, 2022. STUDY SELECTION: The search selected clinical trials with random allocation to percutaneous tibial nerve stimulation (PTNS), transcutaneous tibial nerve stimulation (TTNS), vaginal electrical stimulation (VES), sacral neuromodulation (SNM), parasacral stimulation (PS), pudendal neuromodulation, or placebo. DATA EXTRACTION: The main outcomes were the voiding diary, OAB-related quality of life, and positive response rate. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias of each included study, and the Grading of Recommendations Assessment, Development, and Evaluation tool was used to evaluate the overall evidence quality of key outcomes. DATA SYNTHESIS: The study included 21 randomized controlled trials involving 1433 participants, and all trials were used for the meta-analysis. In the network meta-analyses, five of six neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, were related to higher efficacy than the placebo. Ranking probability showed that SNM was the most efficacious therapy for improving OAB-related quality of life, urinary episodes, and urinary frequency. For urgency incontinence episodes and the number of pads, PTNS and TTNS were the most efficacious modalities, respectively. CONCLUSION: Neuromodulation technologies, including PTNS, TTNS, VES, SNM, and PS, may be effective and safe solutions for OAB syndrome in adults. Moreover, SNM is the most efficacious regimen for OAB-related quality of life, urinary episodes, and urinary frequency. PTNS and TTNS are the most efficacious modalities for reducing urgency incontinence episodes and the number of pads, respectively. Future studies should pay more attention to the quality of study design and report, patients who may benefit the most from neuromodulation, and the long-term effect, cost-effectiveness, and satisfaction of neuromodulation.

Effects and parameters of community-based exercise on motor symptoms in Parkinson's disease: a meta-analysis.

BACKGROUND: Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise.  METHODS: We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect.  RESULTS: Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect. CONCLUSIONS: This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise. PROSPERO TRIAL REGISTRATION NUMBER: CRD42022327162.

Efficacy and safety of transcranial direct current stimulation for post-stroke spasticity: A meta-analysis of randomised controlled trials.

OBJECTIVES: To evaluate the efficacy and safety of transcranial direct current stimulation for post-stroke spasticity and to assess its evidence using a meta-analysis. METHODS: We searched the Cochrane Library, EMBASE, MEDLINE (via PubMed), PEDro, CBM, CNKI and Wan Fang Data from their inception to June 2021 for randomised clinical trials published in English or Chinese, which aimed to explore the effects of transcranial direct current stimulation on post-stroke spasticity. Two reviewers independently extracted the data and evaluated the methodological quality and overall evidence quality. RESULTS: Thirteen randomised clinical trials comprising 924 patients were included, 12 of which were included in the meta-analysis. The results showed that anodal stimulation (standard mean difference = -0.91; [95% CI; -1.63 to -0.19]) combined with other therapies was more effective in improving upper limb spasticity. More than 20 minutes of stimulation were found to be effective in improving spasticity. Transcranial direct current stimulation was superior to the control treatments for subacute (standard mean difference = -1.16; -1.75 to -0.57) and chronic stroke (standard mean difference = -0.68; -1.13 to -0.22) patients aged under 60 (standard mean difference = -1.07; -1.54 to -0.60). No severe adverse events were reported in any of the included studies. CONCLUSIONS: Low-quality evidence demonstrates that anodal transcranial direct current stimulation as an adjunct is effective and safe in reducing upper limb post-stroke spasticity when applied for more than 20 minutes in subacute and chronic stroke survivors aged under 60. Further high-quality studies are needed to explore its long-term efficacy and safety.

The Anti-Multidrug-Resistant Acinetobacter baumannii Study on 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline Compounds.

As a major public health problem, the prevalence of Acinetobacter baumannii (A. baumannii) infections in hospitals due to the pathogen's multiple-antibiotic resistance has attracted extensive attention. We previously reported a series of 1,3-diamino-7H-pyrrolo[3,2-f]quinazoline (PQZ) compounds, which were designed by targeting Escherichia coli dihydrofolate reductase (ecDHFR), and exhibited potent antibacterial activities. In the current study, based on our molecular-modeling study, it was proposed that PQZ compounds may function as potent A. baumannii DHFR (abDHFR)-inhibitors as well, which inspired us to consider their anti-A. baumannii abilities. We further found that three PQZ compounds, OYYF-171, -172, and -175, showed significant antibacterial activities against A. baumannii, including multidrug-resistant (MDR) strains, which are significantly stronger than the typical DHFR-inhibitor, trimethoprim (TMP), and superior to, or comparable to, the other tested antibacterial agents belonging to ß-lactam, aminoglycoside, and quinolone. The significant synergistic effect between the representative compound OYYF-171 and the dihydropteroate synthase (DHPS)-inhibitor sulfamethoxazole (SMZ) was observed in both the microdilution-checkerboard assay and time-killing assay, which indicated that using SMZ in combination with PQZ compounds could help to reduce the required dosage and forestall resistance. Our study shows that PQZ is a promising scaffold for the further development of folate-metabolism inhibitors against MDR A. baumannii.

Multilevel air quality evolution in Shenyang: Impact of elevated point emission reduction.

Visibility observed at different altitudes is favorable to understand the causes of air pollution. We conducted 4-years of observations of visibility at 2.8 and 60 m and particulate matter (PM) concentrations from 2015 to 2018 in Shenyang, a provincial city in Northeast China. The results indicated that visibility increased with the increasing height in winter (especially at night), and decreased with height in summer (especially at the daytime). PM concentration exhibited opposite vertical variation to visibility, reflecting that visibility degrades with the increase of aerosol concentration in the air. The radiosonde meteorological data showed that weak turbulence in the planetary boundary layer (PBL) in winter favored aerosols' accumulation near the surface. Whereas in summer, unstable atmospheric conditions, upper-level moister environment, and regional transport of air pollutants resulted in the deterioration of upper-level visibility. Inter-annual variation in the two-level visibility indicated that the upper-level visibility improved more significantly than low-level visibility, much likely due to the reduction in emission of elevated point sources in Shenyang. Our study suggested that strengthening the control of surface non-point emissions is a promising control strategy to improve Shenyang air quality.

Identification of M-NH2 -NH2 Intermediate and Rate Determining Step for Nitrogen Reduction with Bioinspired Sulfur-Bonded FeW Catalyst.

The multimetallic sulfur-framework catalytic site of biological nitrogenases allows the efficient conversion of dinitrogen (N2 ) to ammonia (NH3 ) under ambient conditions. Inspired by biological nitrogenases, a bimetallic sulfide material (FeWSx @FeWO4 ) was synthesized as a highly efficient N2 reduction (NRR) catalyst by sulfur substitution of the surface of FeWO4 nanoparticles. Thus prepared FeWSx @FeWO4 catalysts exhibit a relatively high NH3 production rate of 30.2 ug h-1 mg-1cat and a Faraday efficiency of 16.4 % at -0.45 V versus a reversible hydrogen electrode in a flow cell; these results have been confirmed via purified 15 N2 -isotopic labeling experiments. In situ Raman spectra and hydrazine reduction kinetics analysis revealed that the reduction of undissociated hydrazine intermediates (M-NH2 -NH2 ) on the surface of the bimetallic sulfide catalyst is the rate-determing step for the NRR process. Therefore, this work can provide guidance for elucidating the structure-activity relationship of NRR catalysts.

Hydrogel thin film with swelling-induced wrinkling patterns for high-throughput generation of multicellular spheroids.

Three-dimensional (3D) multicellular spheroids (MCSs) mimic the structure and function of real tissue much better than the conventional 2D cell monolayers, however, their application was severely hindered by difficulties in their generation. An ideal method for MCS fabrication should produce spheroids with narrow size distribution and allow for control over their size. The method should also be simple, cheap, and scalable. Here, we use patterned nonadhesive poly(2-hydroxyethyl methacrylate) hydrogel films to guide the self-assembly of cells. The films were fabricated directly in the wells of cell culture plates. They were patterned spontaneously by swelling in water, without the use of any template or specialized facilities. When cell suspension is added, the cells settle down by gravity to the bottom. Because of the presence of the wrinkling pattern composed of uniformed microcaves, the cells accumulate to the center of the microcaves and gradually self-assemble into MCSs. Using this method, monodisperse MCSs were generated. The size of the spheroids can be facilely controlled by the number of cells seeded. The method is compatible with the conventional monolayer cell culture method. Thousands of spheroids can be generated in a single well. We expect this method will pave the way for the application of MCSs in various biomedical areas.

Optimization of an optical inspection system based on the Taguchi method for quantitative analysis of point-of-care testing.

This study presents an optical inspection system for detecting a commercial point-of-care testing product and a new detection model covering from qualitative to quantitative analysis. Human chorionic gonadotropin (hCG) strips (cut-off value of the hCG commercial product is 25 mIU/mL) were the detection target in our study. We used a complementary metal-oxide semiconductor (CMOS) sensor to detect the colors of the test line and control line in the specific strips and to reduce the observation errors by the naked eye. To achieve better linearity between the grayscale and the concentration, and to decrease the standard deviation (increase the signal to noise ratio, S/N), the Taguchi method was used to find the optimal parameters for the optical inspection system. The pregnancy test used the principles of the lateral flow immunoassay, and the colors of the test and control line were caused by the gold nanoparticles. Because of the sandwich immunoassay model, the color of the gold nanoparticles in the test line was darkened by increasing the hCG concentration. As the results reveal, the S/N increased from 43.48 dB to 53.38 dB, and the hCG concentration detection increased from 6.25 to 50 mIU/mL with a standard deviation of less than 10%. With the optimal parameters to decrease the detection limit and to increase the linearity determined by the Taguchi method, the optical inspection system can be applied to various commercial rapid tests for the detection of ketamine, troponin I, and fatty acid binding protein (FABP).