Discovery of Potent, Selective, and Orally Available IRE1α Inhibitors Demonstrating Comparable PD Modulation to IRE1 Knockdown in a Multiple Myeloma Model.

The lack of selective and safe in vivo IRE1α tool molecules has limited the evaluation of IRE1α as a viable target to treat multiple myeloma. Focus on improving the physicochemical properties of a literature compound by decreasing lipophilicity, molecular weight, and basicity allowed the discovery of a novel series with a favorable in vitro safety profile and good oral exposure. These efforts culminated in the identification of a potent and selective in vivo tool compound, G-5758, that was well tolerated following multiday oral administration of doses up to 500 mg/kg. G-5758 demonstrated comparable pharmacodynamic effects to induced IRE1 knockdown as measured by XBP1s levels in a multiple myeloma model (KMS-11).

Alkali-Driven Photoinduced N-Dealkylation of Aryl Tertiary Amines and Amides.

By extending the photoinduced oxidative mechanism of aryl tertiary amines proposed earlier to an alkaline environment based on the prediction of quantum mechanics computations and the validation of meticulous experiments, we discovered a photoinduced oxidative N-dealkylation method for both aryl tertiary amines and amides. The dealkylation was achieved in an alkaline environment under mild conditions accompanied by excellent functional group tolerance.

Community-based rehabilitation interventions on quality of care for people with schizophrenia in China (CRISC): study protocol for a cluster-randomized controlled trial.

BACKGROUND: International consensus shows that community-based rehabilitation (CBR) service is an effective way to improve functioning and negative symptoms and address the treatment gap for schizophrenia. Rigorous trials are needed in China to demonstrate effective and scalable CBR interventions to significantly improve outcomes for people with schizophrenia and to provide evidence of the economic benefits. The objectives of this trial are to examine the effectiveness of CBR as an adjunct to test the usual facility-cased care (FBC) in comparison to FBC alone in improving a range of outcomes in people with schizophrenia and their caregivers. METHODS: This trial is a cluster randomized controlled trial design in China. The trial will be conducted at three districts of Weifang city, Shandong province. Eligible participants will be identified from the psychiatric management system where community-dwelling patients with schizophrenia have been registered. Participants will be recruited after providing informed consent. 18 sub-districts will be randomly allocated in a 1:1 ratio to facility-based care (FBC) plus CBR (intervention arm) or FBC alone (control arm). The structured CBR intervention will be delivered by trained psychiatric nurses or community health workers. We aim to recruit 264 participants. The primary outcomes include symptoms of schizophrenia, personal and social function, quality of life, family burden of caring, etc. The study will be conducted according to good ethical practice, data analysis and reporting guidelines. DISCUSSION: If the hypothesized clinical benefit and cost-effectiveness of CBR intervention are confirmed, this trial will provide significant implications for policy makers and practitioners to scale up rehabilitation services, as well as for people with schizophrenia and their family to promote recovery and social inclusion, and to alleviate the burden of care. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200066945). Registered December 22, 2022.

USP22 aggravated diabetic renal tubulointerstitial fibrosis progression through deubiquitinating and stabilizing Snail1.

Renal tubulointerstitial fibrosis (TIF) is one of the main pathological changes induced by diabetic kidney disease (DKD), and epithelial-to-mesenchymal transition (EMT) induced by high glucose (HG) can promote TIF. Our previous study has shown that ubiquitin-specific protease 22 (USP22) could affect the process of DKD by deubiquitinating and stabilizing Sirt1 in glomerular mesangial cells. However, whether USP22 could regulate EMT occurrence in renal tubular epithelial cells and further aggravate the pathological process of TIF in DKD remains to be elucidated. In this study, we found that USP22 expression was upregulated in kidney tissues of db/db mice and HG-treated NRK-52E cells. In vitro, USP22 overexpression promoted the EMT process of NRK-52E cells stimulated by HG and further increased the levels of extracellular matrix (ECM) components such as fibronectin, Collagen I, and Collagen Ⅳ. Meanwhile, USP22 deficiency exhibited the opposite effects. Mechanism studies showed that USP22, depending on its deubiquitinase activity, deubiquitinated and stabilized the EMT transcriptional factor Snail1. In vivo experiment showed that interfering with USP22 could improve the renal pathological damages and renal function of the db/db spontaneous diabetic mice by decreasing Snail1 expression, which could inhibit EMT occurrence, and reduce the production of ECM components. These results suggested that USP22 could accelerate renal EMT and promote the pathological progression of diabetic TIF by deubiquitinating Snail1, providing an experimental basis for using USP22 as a potential target for DKD.

Multi-omics of Circular RNAs and Their Responses to Hormones in Moso Bamboo (Phyllostachys edulis).

Circular RNAs (circRNAs) are endogenous non-coding RNAs with covalently closed structures, which have important functions in plants. However, their biogenesis, degradation, and function upon treatment with gibberellins (GAs) and auxins (1-naphthaleneacetic acid, NAA) remain unknown. Here, we systematically identified and characterized the expression patterns, evolutionary conservation, genomic features, and internal structures of circRNAs using RNase R-treated libraries from moso bamboo (Phyllostachys edulis) seedlings. Moreover, we investigated the biogenesis of circRNAs dependent on both cis- and trans-regulation. We explored the function of circRNAs, including their roles in regulating microRNA (miRNA)-related genes and modulating the alternative splicing of their linear counterparts. Importantly, we developed a customized degradome sequencing approach to detect miRNA-mediated cleavage of circRNAs. Finally, we presented a comprehensive view of the participation of circRNAs in the regulation of hormone metabolism upon treatment of bamboo seedlings with GA and NAA. Collectively, our study provides insights into the biogenesis, function, and miRNA-mediated degradation of circRNAs in moso bamboo.

Transcriptome Profiling of Stem-Differentiating Xylem in Response to Abiotic Stresses Based on Hybrid Sequencing in Cunninghamia lanceolata.

Cunninghamia lanceolata (C. lanceolata) belongs to Gymnospermae, which are fast-growing and have desirable wood properties. However, C. lanceolata's stress resistance is little understood. To unravel the physiological and molecular regulation mechanisms under environmental stresses in the typical gymnosperm species of C. lanceolata, three-year-old plants were exposed to simulated drought stress (polyethylene glycol 8000), salicylic acid, and cold treatment at 4 °C for 8 h, 32 h, and 56 h, respectively. Regarding the physiological traits, we observed a decreased protein content and increased peroxidase upon salicylic acid and polyethylene glycol treatment. Superoxide dismutase activity either decreased or increased at first and then returned to normal under the stresses. Regarding the molecular regulation, we used both nanopore direct RNA sequencing and short-read sequencing to reveal a total of 5646 differentially expressed genes in response to different stresses, of which most had functions in lignin catabolism, pectin catabolism, and xylan metabolism, indicating that the development of stem-differentiating xylem was affected upon stress treatment. Finally, we identified a total of 51 AP2/ERF, 29 NAC, and 37 WRKY transcript factors in C. lanceolata. The expression of most of the NAC TFs increased under cold stress, and the expression of most of the WRKY TFs increased under cold and SA stress. These results revealed the transcriptomics responses in C. lanceolata to short-term stresses under this study's experimental conditions and provide preliminary clues about stem-differentiating xylem changes associated with different stresses.

New Dimension on Quality of Life Differences among Older Adults: A Comparative Analysis of Digital Consumption in Urban and Rural Areas of China.

The purpose of this study was to compare the variability in quality of life in the area of digital consumption among older adults in urban and rural China during the COVID-19 pandemic. This study proposed a low-cost mixed research method, and the methodology used a quantitative study of a large regional sample combined with a qualitative study of a small regional sample. Data for the large-scale area sample were obtained from the China family panel study (CFPS) dataset, and data for the small-scale regional sample were obtained from Nanjing, China. The quantitative analysis of the large-scale regional sample used the least squares regression analysis (OSL) and propensity score matching (PSM). The qualitative analysis of the small-scale regional sample used the selection optimization and compensation (SOC) model. The findings show that economic income is a direct driver of digital consumption. Digital consumption had a significant positive relationship with the quality of life for urban and rural older adults. In addition, the study established the semantic network relationships of the coping strategies of digital consumption of older adults and their drivers. Finally, the theoretical and practical implications of these findings are discussed in the context of other related studies.

Clinical features of multifocal papillary thyroid carcinoma and risk factors of cervical metastatic lymph nodes.

OBJECTIVE: To analyze the clinical features of multifocal papillary thyroid carcinoma (PTC) and the risk factors of cervical metastatic lymph nodes. METHODS: A total of 1524 patients with papillary thyroid carcinoma admitted in Gansu Provincial Cancer Hospital from January 2020 to August 2021 were enrolled, including 492 cases of multifocal PTC and 1032 cases of unifocal PTC. The clinicopathologic features of multifocal PTC and unifocal PTC were analyzed by comparing their differences in gender, ethnicity, age, body mass index, accompanying diabetes mellitus, accompanying hypertension, preoperative thyroid stimulating hormone and thyroglobulin levels, location of lesions, maximum diameter of lesions, sum of lesion diameters, central metastatic lymph nodes, lateral cervical metastatic lymph nodes, presence of Hashimoto's thyroiditis, and thyroid capsule invasion. Patients were also assessed according to the presence or absence of central metastatic lymph nodes and lateral cervical metastatic lymph nodes to understand clinicopathological parameter differences, and multivariate logistic regression analysis was used to explore the risk factors. RESULTS: Compared with unifocal PTC group, multifocal PTC group had significantly higher proportion of patients aged over 55 years, accompanying hypertension, central metastatic lymph nodes or cervical metastatic lymph nodes, Hashimoto's thyroiditis and capsule invasion (all P<0.05); 55.1% of patients with multifocal PTC had lesions distributed bilaterally, and the maximum diameter and diameter sum of the lesions were greater than those in unifocal PTC group (all P<0.01). Multivariate logistic regression analysis showed that male, maximum diameter of lesion more than 7 mm, capsular invasion were independent risk factors for central metastatic lymph nodes (all P<0.05); while male, maximum diameter of lesion more than 7 mm, preoperative thyroglobulin more than 55 ng/mL, and central metastatic lymph nodes were risk factors for lateral cervical metastatic lymph nodes in patients with multifocal PTC (all P<0.05). CONCLUSION: Patients with multifocal PTC have significantly higher central and lateral cervical metastatic lymph nodes, particularly for male patients with a maximum diameter of lesion more than 7 mm, invasion of capsule, and preoperative thyroglobulin more than 55 ng/mL.

[Dissolved organic matter dynamics and spectral characteristics of twig litter from different Castanopsis carlesii forests in the middle subtropical region, China]. / ä¸­äºšçƒ­å¸¦ä¸åŒç±»åž‹ç±³æ§ æž—å‡‹è½æžæº¶è§£æ€§æœ‰æœºè´¨åŠ¨æ€åŠå ‰è°±å­¦ç‰¹æ€§.

To assess the dynamics and spectral characteristics of dissolved organic matter of twig litter in continuous increase stage, peak stage, and continuous decrease stage of twig litter production in different types of Castanopsis carlesii forest in middle subtropical China, a field experiment was conducted in C. carlesii natural forest, secondary forest and plantation. The results showed that litter production stage and forest type significantly affected the content and spectral characteristics of dissolved organic matter of twig litter were . Compared with the secondary forest and plantation, natural forest had higher dissolved organic carbon (DOC) content and lower special ultraviolet-visible absorption values at 254, 260 and 280 nm (SUVA254, SUVA260, SUVA280) at the continuous decrease stage of twig litter production, indicating high twig litter quality of natural forest and high cycling efficiency with dissolved organic matter in the natural forest at this stage. In contrast, the higher contents of total nitrogen (TN), total phosphorus (TP), total dissolved nitrogen (TDN), total dissolved phosphorus (TDP), and lower DOC:TDP and TDN:TDP ratios of twig litter in the plantation were observed at the peak stage of twig litter production, while no differences were detected in dissolved organic matter contents and spectral values in the secondary forest among the stages. In addition, the DOC, TDN, TDP of twig litter were negatively correlated with temperature and precipitation in the natural forests and secondary forests, but TDN and TDP of twig litter were positively correlated with temperature and precipitation in the plantations. These results suggested that the higher nutrient content at the peak stage of twig litter production in the C. carlesii plantation might lead to more efficient material cycling and that there would be a higher efficiency of material cycling for twig litter dissolved organic matter in C. carlesii natural forest at reduction stage of twig litter production.

Finger Movement Recognition via High-Density Electromyography of Intrinsic and Extrinsic Hand Muscles.

Surface electromyography (sEMG) is commonly used to observe the motor neuronal activity within muscle fibers. However, decoding dexterous body movements from sEMG signals is still quite challenging. In this paper, we present a high-density sEMG (HD-sEMG) signal database that comprises simultaneously recorded sEMG signals of intrinsic and extrinsic hand muscles. Specifically, twenty able-bodied participants performed 12 finger movements under two paces and three arm postures. HD-sEMG signals were recorded with a 64-channel high-density grid placed on the back of hand and an 8-channel armband around the forearm. Also, a data-glove was used to record the finger joint angles. Synchronisation and reproducibility of the data collection from the HD-sEMG and glove sensors were ensured. The collected data samples were further employed for automated recognition of dexterous finger movements. The introduced dataset offers a new perspective to study the synergy between the intrinsic and extrinsic hand muscles during dynamic finger movements. As this dataset was collected from multiple participants, it also provides a resource for exploring generalized models for finger movement decoding.

An Ultrasonic Motor Using a Carbon-Fiber-Reinforced/Poly-Phenylene-Sulfide-Based Vibrator with Bending/Longitudinal Modes.

In this study, a linear ultrasonic motor (USM) with carbon-fiber-reinforced/poly-phenylene-sulfide (PPS/CF) was developed and the feasibility of using PPS/CF to achieve a lightweight USM was tested. Here, anisotropic Young's moduli of PPS/CF possibly enhance the driving force when the slider's moving direction is orthogonal to the carbon-fibers' filling direction. Further, PPS/CF's low density may help avoid excessive enhancement in weight. Initially, we measured anisotropic Young's moduli of PPS/CF, and determined the vibration modes, configuration, and dimensions of the PPS/CF vibrating body through finite element analysis. Subsequently, we fabricated a 45.7-mm-long 30-mm-diameter vibrator to form a linear motor. Finally, we evaluated the load characteristics of the PPS/CF-based motor and made comparisons with isotropic-material-based USMs. At 30.2 kHz frequency, the PPS/CF-based vibrator worked in the 2nd bending and 2nd longitudinal modes as predicted. The PPS/CF-based motor yielded the maximal thrust, no-load speed, and maximal output power of 392 mN, 1103 mm/s, and 62 mW, respectively. Moreover, the thrust force density and power density reached 20.3 N/kg and 3.2 W/kg, respectively, which were relatively high compared to those of the PPS- and aluminum-based USMs with the same vibration modes and similar structures. This preliminary study implies PPS/CF's feasibility for achieving lightweight USMs, and provides a candidate material for designing micro/meso USMs.

A Hierarchical View Pooling Network for Multichannel Surface Electromyography-Based Gesture Recognition.

Hand gesture recognition based on surface electromyography (sEMG) plays an important role in the field of biomedical and rehabilitation engineering. Recently, there is a remarkable progress in gesture recognition using high-density surface electromyography (HD-sEMG) recorded by sensor arrays. On the other hand, robust gesture recognition using multichannel sEMG recorded by sparsely placed sensors remains a major challenge. In the context of multiview deep learning, this paper presents a hierarchical view pooling network (HVPN) framework, which improves multichannel sEMG-based gesture recognition by learning not only view-specific deep features but also view-shared deep features from hierarchically pooled multiview feature spaces. Extensive intrasubject and intersubject evaluations were conducted on the large-scale noninvasive adaptive prosthetics (NinaPro) database to comprehensively evaluate our proposed HVPN framework. Results showed that when using 200 ms sliding windows to segment data, the proposed HVPN framework could achieve the intrasubject gesture recognition accuracy of 88.4%, 85.8%, 68.2%, 72.9%, and 90.3% and the intersubject gesture recognition accuracy of 84.9%, 82.0%, 65.6%, 70.2%, and 88.9% on the first five subdatabases of NinaPro, respectively, which outperformed the state-of-the-art methods.

PSDX: A Comprehensive Multi-Omics Association Database of Populus trichocarpa With a Focus on the Secondary Growth in Response to Stresses.

Populus trichocarpa (P. trichocarpa) is a model tree for the investigation of wood formation. In recent years, researchers have generated a large number of high-throughput sequencing data in P. trichocarpa. However, no comprehensive database that provides multi-omics associations for the investigation of secondary growth in response to diverse stresses has been reported. Therefore, we developed a public repository that presents comprehensive measurements of gene expression and post-transcriptional regulation by integrating 144 RNA-Seq, 33 ChIP-seq, and six single-molecule real-time (SMRT) isoform sequencing (Iso-seq) libraries prepared from tissues subjected to different stresses. All the samples from different studies were analyzed to obtain gene expression, co-expression network, and differentially expressed genes (DEG) using unified parameters, which allowed comparison of results from different studies and treatments. In addition to gene expression, we also identified and deposited pre-processed data about alternative splicing (AS), alternative polyadenylation (APA) and alternative transcription initiation (ATI). The post-transcriptional regulation, differential expression, and co-expression network datasets were integrated into a new P. trichocarpa Stem Differentiating Xylem (PSDX) database (http://forestry.fafu.edu.cn/db/SDX), which further highlights gene families of RNA-binding proteins and stress-related genes. The PSDX also provides tools for data query, visualization, a genome browser, and the BLAST option for sequence-based query. Much of the data is also available for bulk download. The availability of PSDX contributes to the research related to the secondary growth in response to stresses in P. trichocarpa, which will provide new insights that can be useful for the improvement of stress tolerance in woody plants.

Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion.

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was recently implicated as a synthetic lethal target in cancers with deletion of the methylthioadenosine phosphorylase (MTAP) gene, which is adjacent to the CDKN2A tumor suppressor and codeleted with CDKN2A in approximately 15% of all cancers. Previous attempts to target MAT2A with small-molecule inhibitors identified cellular adaptations that blunted their efficacy. Here, we report the discovery of highly potent, selective, orally bioavailable MAT2A inhibitors that overcome these challenges. Fragment screening followed by iterative structure-guided design enabled >10 000-fold improvement in potency of a family of allosteric MAT2A inhibitors that are substrate noncompetitive and inhibit release of the product, S-adenosyl methionine (SAM), from the enzyme's active site. We demonstrate that potent MAT2A inhibitors substantially reduce SAM levels in cancer cells and selectively block proliferation of MTAP-null cells both in tissue culture and xenograft tumors. These data supported progressing AG-270 into current clinical studies (ClinicalTrials.gov NCT03435250).

Genome-wide profiling of circular RNAs, alternative splicing, and R-loops in stem-differentiating xylem of Populus trichocarpa.

Circular RNAs (circRNAs) are a recently discovered type of non-coding RNA derived from pre-mRNAs. R-loops consist of a DNA:RNA hybrid and the associated single-stranded DNA. In Arabidopsis thaliana, circRNA:DNA R-loops regulate alternative splicing (AS) of SEPALLATA3 (SEP3). However, the occurrence and functions of circRNAs and R-loops in Populus trichocarpa are largely unexplored. Here, we performed circRNA-enriched sequencing in the stem-differentiating xylem (SDX) of P. trichocarpa and identified 2,742 distinct circRNAs, including circ-CESA4, circ-IRX7, and circ-GUX1, which are generated from genes involved in cellulose, and hemicellulose biosynthesis, respectively. To investigate the roles of circRNAs in modulating alternative splicing (AS), we detected 7,836 AS events using PacBio Iso-Seq and identified 634 circRNAs that overlapped with 699 AS events. Furthermore, using DNA:RNA hybrid immunoprecipitation followed by sequencing (DRIP-seq), we identified 8,932 R-loop peaks that overlapped with 181 circRNAs and 672 AS events. Notably, several SDX-related circRNAs overlapped with R-loop peaks, pointing to their possible roles in modulating AS in SDX. Indeed, overexpressing circ-IRX7 increased the levels of R-loop structures and decreased the frequency of intron retention in linear IRX7 transcripts. This study provides a valuable R-loop atlas resource and uncovers the interplay between circRNAs and AS in SDX of P. trichocarpa.

Antibody-Mediated Delivery of Chimeric BRD4 Degraders. Part 2: Improvement of In Vitro Antiproliferation Activity and In Vivo Antitumor Efficacy.

Heterobifunctional compounds that direct the ubiquitination of intracellular proteins in a targeted manner via co-opted ubiquitin ligases have enormous potential to transform the field of medicinal chemistry. These chimeric molecules, often termed proteolysis-targeting chimeras (PROTACs) in the chemical literature, enable the controlled degradation of specific proteins via their direction to the cellular proteasome. In this report, we describe the second phase of our research focused on exploring antibody-drug conjugates (ADCs), which incorporate BRD4-targeting chimeric degrader entities. We employ a new BRD4-binding fragment in the construction of the chimeric ADC payloads that is significantly more potent than the corresponding entity utilized in our initial studies. The resulting BRD4-degrader antibody conjugates exhibit potent and antigen-dependent BRD4 degradation and antiproliferation activities in cell-based experiments. Multiple ADCs bearing chimeric BRD4-degrader payloads also exhibit strong, antigen-dependent antitumor efficacy in mouse xenograft assessments that employ several different tumor models.

Whole-genome characterization of chronological age-associated changes in methylome and circular RNAs in moso bamboo (Phyllostachys edulis) from vegetative to floral growth.

In mammals, DNA methylation is associated with aging. However, age-related DNA methylation changes during phase transitions largely remain unstudied in plants. Moso bamboo (Phyllostachys edulis) requires a very long time to transition from the vegetative to the floral phase. To comprehensively investigate the association of DNA methylation with aging, we present here single-base-resolution DNA methylation profiles using both high-throughput bisulfite sequencing and single-molecule nanopore-based DNA sequencing, covering the long period of vegetative growth and transition to flowering in moso bamboo. We discovered that CHH methylation gradually accumulates from vegetative to reproductive growth in a time-dependent fashion. Differentially methylated regions, correlating with chronological aging, occurred preferentially at both transcription start sites and transcription termination sites. Genes with CG methylation changes showed an enrichment of Gene Ontology (GO) categories in 'vegetative to reproductive phase transition of meristem'. Combining methylation data with mRNA sequencing revealed that DNA methylation in promoters, introns and exons may have different roles in regulating gene expression. Finally, circular RNA (circRNA) sequencing revealed that the flanking introns of circRNAs are hypermethylated and enriched in long terminal repeat (LTR) retrotransposons. Together, the observations in this study provide insights into the dynamic DNA methylation and circRNA landscapes, correlating with chronological age, which paves the way to study further the impact of epigenetic factors on flowering in moso bamboo.

Minimalizing Non-point Source Pollution Using a Cooperative Ion-Selective Electrode System for Estimating Nitrate Nitrogen in Soil.

Nitrate nitrogen ( NO 3 - -N) in the soil is one of the important nutrients for growing crops. During the period of precipitation or irrigation, an excessive NO 3 - -N readily causes its leaching or runoff from the soil surface to rivers due to inaccurate fertilization and water management, leading to non-point source pollution. In general, the measurement of the NO 3 - -N relies upon the laboratory-based absorbance, which is often time-consuming, therefore not suitable for the rapid measurements in the field directly. Ion-selective electrodes (ISEs) support the possibility of NO 3 - -N measurement by measuring the nitrate ( NO 3 - ) ions in soil quickly and accurately due to the high water solubility and mobility of NO 3 - ions. However, such a method suffers from a complicated calibration to remove the influences caused by both temperature and other ions in the measured solution, thus limiting field use. In this study, a kind of all-solid ISE system combined with a temperature sensor and a pH electrode is proposed to automatically measure the concentrations of the NO 3 - -N. In this study, a soil water content calibration function was established, which significantly reduces a relative error (RE) by 13.09%. The experimental results showed that the stabilization time of this electrode system was less than 15 s with a slope of -51.63 mV/decade in the linear range of 10-5-10-2.2 mol/L. Both the limit of detection of 0.5 ppm of the NO 3 - -N and a relative SD of less than 3% were obtained together with the recovery rate of 90-110%. Compared with the UV-Vis spectroscopy method, a correlation coefficient (R 2) of 0.9952 was obtained. The performances of this all-solid ISE system are satisfied for measuring the NO 3 - -N in the field.

Towards Integration of Domain Knowledge-Guided Feature Engineering and Deep Feature Learning in Surface Electromyography-Based Hand Movement Recognition.

As a machine-learning-driven decision-making problem, the surface electromyography (sEMG)-based hand movement recognition is one of the key issues in robust control of noninvasive neural interfaces such as myoelectric prosthesis and rehabilitation robot. Despite the recent success in sEMG-based hand movement recognition using end-to-end deep feature learning technologies based on deep learning models, the performance of today's sEMG-based hand movement recognition system is still limited by the noisy, random, and nonstationary nature of sEMG signals and researchers have come up with a number of methods that improve sEMG-based hand movement via feature engineering. Aiming at achieving higher sEMG-based hand movement recognition accuracies while enabling a trade-off between performance and computational complexity, this study proposed a progressive fusion network (PFNet) framework, which improves sEMG-based hand movement recognition via integration of domain knowledge-guided feature engineering and deep feature learning. In particular, it learns high-level feature representations from raw sEMG signals and engineered time-frequency domain features via a feature learning network and a domain knowledge network, respectively, and then employs a 3-stage progressive fusion strategy to progressively fuse the two networks together and obtain the final decisions. Extensive experiments were conducted on five sEMG datasets to evaluate our proposed PFNet, and the experimental results showed that the proposed PFNet could achieve the average hand movement recognition accuracies of 87.8%, 85.4%, 68.3%, 71.7%, and 90.3% on the five datasets, respectively, which outperformed those achieved by the state of the arts.

Migration inhibitory factor in spinal tuberculosis: -173G/C polymorphisms, and transcript and protein levels in a northern province of China.

The aim of this study was to elucidate the possible association between migration inhibitory factor (MIF)-173G/C gene polymorphisms and transcript and plasma levels of MIF in spinal tuberculosis (TB) patients. Clinical data were collected from 254 spinal TB patients and 262 healthy controls participating in the study. The genotype of the MIF-173G/C gene was amplified by polymerase chain reaction and genotyped by DNA sequencing technology. The level of mRNA expression was determined by real-time polymerase chain reaction and MIF plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. The frequency of the C allele and GC+CC genotype in MIF-173G/C was over-represented in spinal TB patients. The mean MIF mRNA level in spinal TB patients and patients with the GG and GC+CC genotype were significantly lower than controls; however, our study also indicated that the MIF concentration in spinal TB patients and patients with the GG and GC+CC genotypes were significantly higher than controls. Spinal TB patients with the GG genotype had higher MIF plasma levels than patients with the GC+CC genotype. The C-reactive protein level and erythrocyte sedimentation rate was correlated with the MIF plasma level. In summary, the association between the MIF-173G/C genetic polymorphism, reduced transcript and increased plasma levels of MIF in spinal TB patients, and MIF may play an important role in the occurrence, development, and damage of spinal TB in the northern Province population of China.