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Polygala tenuifolia is extensively used to treat amnesia in traditional Chinese medicine, and pharmacological studies have reported the beneficial effects of P. tenuifolia on intelligence and cognition. In the present study, the crude polysaccharide alkali-extracted from P. tenuifolia roots (PTB) inhibited lipopolysaccharide-induced microglia/astrocyte activation and significantly improved the learning and memory ability of Alzheimer's disease (AD) rats. To determine its bioactive components, a heteropolysaccharide (PTBP-1-3) was isolated from PTB. Structural analysis showed that PTBP-1-3 was composed of α-L-Araf-(1→, →3)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, β-D-Xylp-(1→, →2,3,4)-β-D-Xylp-(1→, α-L-Rhap-(1→, β-D-Galp-(1→, →4)-α-D-Galp-(1→, →6)-α-D-Galp-(1→, →6)-α-D-Glcp-(1→, →3,6)-α-D-Glcp-(1→, →6)-α-D-Manp-(1→, and →2,4)-β-D-Manp-(1→ residues. PTBP-1-3 decreased the production of NO, TNF-α, and IL-1β in lipopolysaccharide-activated BV2 microglia cells in a manner similar to that of minocycline. In conclusion, PTBP-1-3 exhibited a potent inhibitory effect on neuroinflammation, and could be one of the bioactive ingredients in PTB for anti-neuroinflammation. PTB and PTBP-1-3 may be potential therapeutic agents for the treatment of AD.

This paper studies the multi-modal recommendation problem, where the item multi-modality information (e.g., images and textual descriptions) is exploited to improve the recommendation accuracy. Besides the user-item interaction graph, existing state-of-the-art methods usually use auxiliary graphs (e.g., user-user or item-item relation graph) to augment the learned representations of users and/or items. These representations are often propagated and aggregated on auxiliary graphs using graph convolutional networks, which can be prohibitively expensive in computation and memory, especially for large graphs. Moreover, existing multi-modal recommendation methods usually leverage randomly sampled negative examples in Bayesian Personalized Ranking (BPR) loss to guide the learning of user/item representations, which increases the computational cost on large graphs and may also bring noisy supervision signals into the training process. To tackle the above issues, we propose a novel self-supervised multi-modal recommendation model, dubbed BM3, which requires neither augmentations from auxiliary graphs nor negative samples. Specifically, BM3 first bootstraps latent contrastive views from the representations of users and items with a simple dropout augmentation. It then jointly optimizes three multi-modal objectives to learn the representations of users and items by reconstructing the user-item interaction graph and aligning modality features under both inter- and intra-modality perspectives. BM3 alleviates both the need for contrasting with negative examples and the complex graph augmentation from an additional target network for contrastive view generation. We show BM3 outperforms prior recommendation models on three datasets with number of nodes ranging from 20K to 200K, while achieving a 2-9X reduction in training time. Our code is available at https://github.com/enoche/BM3., Comment: Accepted by Proceedings of the ACM Web Conference 2023 (WWW'23)

Two novel nitrogen-rich heterocyclic energetic compounds, 5-amino-3-azido-4-nitro-1H-pyrazole (3) and 5,5′-diazido-4,4′-dinitro-1H,1′H-2,2′-biimidazole(6), featuring ortho azido/nitro groups were designed and synthesized by reactions of diazonium salts with sodium azide. In addition, treatment of diazonium salts with a mixture of hydrazine monohydrate and sodium nitrite in acetic acid also gave the same products 3 and 6 in high yields. Both structures of the products were characterized by 1H NMR, 13C NMR, IR and elemental analysis, as well as single-crystal X-ray diffraction. Furthermore, their physicochemical and energetic properties were studied.

Klinefelter syndrome (KS, 47XXY) is a disorder characterized by sex chromosomal aneuploidy, which may lead to changes in epigenetic regulations of gene expression. To define epigenetic architectures in 47XXY, we annotated DNA methylation in euploid males (46XY) and females (46XX), and 47XXY individuals using whole genome bisulfite sequencing (WGBS) and integrated chromatin accessbilty, and detected abnormal hypermethylation in 47XXY. Furthermore, we detected altered chromatin accessibility in 47XXY, in particular in chromosome X, using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) in cultured amniotic cells. Our results construct the whole genome-wide DNA methylation map in 47XXY, and provide new insights into the early epigenomic dysregulation resulting from an extra chromosome X in 47XXY.

Background Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated. Aim We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage. Method The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. Results Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models. Conclusion This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.

To initiate its development into a plant, a small dark-grown seedling (prior to its emergence from the ground) must penetrate through the growth media. The path that the seedling takes during this journey has yet to be explained. As such, we conducted non-destructive tests using CT scans to observe the growth of dark-grown seedlings in soil over time; we also developed a model to simulate the dynamics of an emerging seedling, and to examine effects of various growth medium conditions, including Lunar soil. It was previously postulated that, with gravitropism in a terrestrial growth medium, a dark-grown seedling would grow directly upright. However, our CT scan results showed that dark-grown soybean seedlings departed from the vertical path in soil, as far as a lateral distance of approximately 10 mm. The phenomenon of the non-straight path was also demonstrated by the model results. Through simulations, we found that an emerging seedling naturally weaves through the particles of growth medium, in search for the path of least resistance. As a result, the seedling ends up travelling a longer distance. Compared with a seedling that was artificially forced to take a straight path in a growth media, the seedling taking the natural path encountered significantly lower resistances (20% lower) from the growth medium, while travelled 12% longer distance during the emergence process. A seedling encountered a much higher impedance in Lunar soil. Our results suggest that taking the path of least resistance, in addition to shaping and orientating itself for mechanical advantage, are strategies evolved by plant species that have contributed to its vast success. An understanding of plant behavior and survival strategies on Earth lay the foundation for future research in agriculture in novel environments, including on celestial bodies.

The aim of this study was to determine the severe bleeding safety of direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE).PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched up to 6 January 2021. The incidence of severe bleeding (major, gastrointestinal [GI], intracranial, and fatal) was investigated. Using frequentist network meta-analysis, interventions that were not compared directly could be compared indirectly by the 95% confidence interval (CI), making the search results more intuitive. Based on surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.Thirty-one randomised controlled trials (76 641 patients) were included. For the treatment of VTE, the risk of major bleeding with apixaban was significantly lower than dabigatran (odds ratio [OR] 2.10, 95% CI 1.07 - 4.12) and edoxaban (OR 2.64, 95% CI 1.36 - 5.15). The safety of the drugs was ranked from highest to lowest as follows: major bleeding: apixaban (SUCRA 98.0), rivaroxaban (SUCRA 69.6), dabigatran (SUCRA 50.7), edoxaban (SUCRA 26.5), and vitamin K antagonists (VKAs; SUCRA 5.1); GI bleeding: apixaban (SUCRA 80.7), rivaroxaban (SUCRA 66.8), edoxaban (SUCRA 62.3), VKAs (SUCRA 34.4), and dabigatran (SUCRA 5.8); intracranial bleeding: rivaroxaban (SUCRA 74.4), edoxaban (SUCRA 70.4), dabigatran (SUCRA 58.2), apixaban (SUCRA 44.4), and VKAs (SUCRA 5.6); fatal bleeding: edoxaban (SUCRA 82.7), rivaroxaban (SUCRA 59.2), dabigatran (SUCRA 48.6), apixaban (SUCRA 43.0), and VKAs (SUCRA 16.3). For the prevention of VTE, the risk of major bleeding with apixaban was significantly lower than rivaroxaban (OR 2.14, 95% CI 1.02 - 4.52). Among the four types of bleeding, apixaban had the lowest bleeding risk among DOACs (major bleeding: SUCRA 81.6; GI bleeding: SUCRA 75.4; intracranial bleeding: SUCRA 64.1; fatal bleeding: SUCRA 73.6).For the treatment of VTE, in terms of major bleeding and GI bleeding, apixaban had the lowest bleeding risk; in terms of intracranial bleeding, rivaroxaban had the lowest bleeding risk; in terms of fatal bleeding, edoxaban had the lowest bleeding risk. For the prevention of VTE, apixaban had the lowest bleeding risk.

The interactions between Chinese herbs and drugs pose a great challenge to the combined clinical application of Chinese herbs and drugs. Chinese medicinal products contain complex pharmacologically active components that may influence the in vivo processes of drugs in a variety of ways. In China, drugs based on Panax ginseng total saponins (PNS) are often combined with warfarin for the treatment of cardiovascular diseases.To assess the effects of Panax notoginseng saponins (PNS) on the pharmacokinetics of warfarin and its mechanism.Blood was collected for the determination of the prothrombin time (PT) and international normalized ratio (INR) from rats treated with warfarin alone or with warfarin + PNS. The plasma concentration of warfarin was determined by high-performance liquid chromatography. Western blot was used to detect the expression of cytochrome P450 (CYP) enzymes.When warfarin and PNS were co-administered, the PT and INR increased compared to when warfarin was given alone. 72 hours after administration, compared to the warfarin alone group, the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups showed 110%, 122%, and 126% increases in PT, respectively (all P0.05), as well as 111%, 124%, and 128% increases in INR (all P0.05). Compared with the warfarin alone group, the clearance rate (CL/F) of warfarin in the warfarin + low-dose PNS, warfarin + medium-dose PNS, and warfarin + high-dose PNS groups was 10% (P 0.05), 23% (P 0.05), and 33% (P 0.05) lower, respectively, while the systemic exposure (area under the concentration-time curve, AUCPNS can increase the blood concentration of warfarin, as well as the exposure time, and it can enhance the anticoagulant effect of warfarin by inhibiting the expression of the liver enzyme CYP3A4.

The hybrid with super-structures is an effective strategy to improve their electrochemical performance. The Fe7S8-C/ZnS-C@MoS2/rGO sample delivered high reversible capacities in Lithium/sodium storage.

A facile and efficient radical-mediated C–N bond activation method in a monocyclic pyrazole at room temperature was developed.

Absttract The synthesis of energetic compounds with high detonation performance and low sensitivity has always been the goal of the energetic material field. However, the synthetic chemistry of energetic compounds also plays a crucial role since it can provide new insights for designing new molecules and understanding reaction pathways. In this study, two unexpected compounds 2 and 3 were prepared from the reactions of 7-amino-8-nitrotetrazolo[1,5-c]pyrimidine (1) with acetone under an acidic condition and with different nitration reagents, respectively. Their structures were determined using 1H and 13C NMR spectroscopy, elemental analysis, and the single-crystal X-ray diffraction technology. Furthermore, the possible mechanisms for the transformation from 1 to 2 and 3 were studied.

The resistance of Salmonella to traditional antibiotics remains a serious challenge. Novel anti- Salmonella drugs are urgently needed to address the looming crisis.

Salmonella bacteria pose a significant threat to animal husbandry and human health due to their virulence and multidrug resistance. The lasso peptide MccY is a recently discovered antimicrobial peptide that acts against various serotypes of Salmonella. In this study, we further explore the resistance mechanism and activity of MccY. Mutants of Ton system genes, including

BackgroundEffective multicomponent interventions in the community targeted at preventing frailty in at-risk older adults can promote healthy ageing. However, there is a lack of studies exploring the effectiveness of technology-enabled autonomous multi-domain community-based interventions for frailty. We developed a novel end-to-end System for Assessment and Intervention of Frailty (SAIF) with exercise, nutrition, and polypharmacy components. This pilot study aimed to explore SAIF’s effectiveness in improving frailty status, physical performance and strength, and its usability in pre-frail older adults.Materials and methodsThis is a single arm 8-week pilot study in 20 community-dwelling older adults who were pre-frail, defined using the Clinical Frailty Scale (CFS) as CFS 3 + (CFS 3 and FRAIL positive) or CFS 4. For outcomes, we assessed frailty status using the modified Fried Frailty Phenotype (FFP) and CFS; physical performance using Short Physical Performance Battery (SPPB); and Hand Grip Strength (HGS) at baseline and 8-week. User experience was explored using the System Usability Scale (SUS), interest-enjoyment subscale of the Intrinsic Motivation Inventory and open-ended questions. We analyzed effectiveness using repeated-measures tests on pre-post scores, and usability using a convergent mixed-method approach via thematic analysis of open-ended responses and descriptive statistics of usability/interest-enjoyment scales.ResultsSixteen participants (71.8 ± 5.5 years) completed the 8-week study. There was a significant improvement in FFP score (−0.5, p < 0.05, effect size, r = 0.43), but not CFS (−1.0, p = 0.10, r = 0.29). Five (31.3%) improved in frailty status for both FFP and CFS. SPPB (+1.0, p < 0.05, r = 0.42) and HGS (+3.5, p < 0.05, r = 0.45) showed significant improvements. Three themes were identified: “Difficulty in module navigation” (barriers for SAIF interaction); “User engagement by gamification” (facilitators that encourage participation); and “Perceived benefits to physical health” (subjective improvements in physical well-being), which corroborated with SUS (68/100) and interest-enjoyment (3.9/5.0) scores. Taken together, user experience results cohere with the Senior Technology Acceptance and Adoption Model.ConclusionOur pilot study provides preliminary evidence of the effectiveness of SAIF in improving frailty status, physical performance and strength of pre-frail older adults, and offers user experience insights to plan the follow-up large-scale randomized controlled trial.

For an energetic molecule with a definite elemental composition, the substituent type and position are the most important factors to influence its detonation performance and mechanical sensitivities. In this work, two pairs of FOX-7-like energetic isomers based on (

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

Lasso peptides, a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) secreted by bacteria, have antimicrobial activity. Here, a novel lasso peptide, microcin Y (MccY), was discovered and characterized. The gene cluster for MccY synthesis was cloned for expression in Escherichia coli. This peptide was purified by HPLC and characterized by Q-TOF. MIC assays showed that some Bacillus, Staphylococcus, Pseudomonas, Shigella, and Salmonella strains were sensitive to MccY. Interestingly, Salmonellatyphimurium and Salmonella infantis were efficiently inhibited by MccY, while they were not affected by MccJ25, a lasso peptide that has antibacterial effects on many Salmonella strains. Furthermore, MccY-resistant strains of S. typhimurium were screened, and mutations were found in FhuA and SbmA, indicating the importance of these transporters for MccY absorption. This novel peptide can greatly broaden the antimicrobial spectrum of MccJ25 in Salmonella and is expected to be used in food preservation and animal feed additive areas.

A metal clad plate consists of a base layer and a clad layer of different materials. When testing clad plate using the eddy current (EC) method, the variation of EC density along the thickness dire...

Urban green space (UGS) is essential for sustainable urbanization and human well-being. The utilization status of UGS is closely related to the provision of ecosystem services for urban residents. Limitations on data availability, however, have led to the absence of a comprehensive approach for evaluating the actual utilization status of UGS at a large scale. Furthermore, differences in actual UGS utilization between intra-urban and peri-urban areas have not received enough attention. This study used big data analysis by combining point of interest (POI) and land use and cover change (LUCC) to quantify the spatial patterns of UGS utilization, and to evaluate the actual utilization status of UGS in 366 cities on the Chinese mainland. We also explored the differences in the actual utilization of UGS in intra-urban and peri-urban areas. The results showed that 94.01% of UGS resources in China had not been utilized. There was a clear pattern of spatial mismatch between the stock and the actual utilization of UGS, especially in the northwestern region indicated by the Hu Huanyong Line. The actual utilization rate of UGS was closely related to the regional development level. There was a certain mismatch between the actual utilization and stock of intraurban green space (IUGS). The hot spots of the actual utilization rate of IUGS were in Yunnan, Guizhou, and Sichuan Provinces in southwestern China. The differences in UGS actual utilization rates between IUGS and peri-urban green space (PUGS) were small in eastern China, but large in southwestern and northwestern China. The actual utilization rate of IUGS in most Chinese cities was significantly larger than that of PUGS, indicating that PUGS were not well utilized. Our results provide scientific support for urban and regional planners in targeting specific areas for UGS design and development, and in optimizing future UGS planning in China.

Proper development of the mammalian cerebral cortex relies on precise gene expression regulation, which is controlled by genetic, epigenetic, and epitranscriptomic factors. Here we generate RNA demethylase Fto and methyltransferase Mettl3 cortical-specific conditional knockout mice, and detect severe brain defects caused by Mettl3 deletion but not Fto knockout. Transcriptomic profiles using RNA sequencing indicate that knockout of Mettl3 causes a more dramatic alteration on gene transcription than that of Fto. Interestingly, we conduct ribosome profiling sequencing, and find that knockout of Mettl3 leads to a more severe disruption of translational regulation of mRNAs than deletion of Fto and results in altered translation of crucial genes in cortical radial glial cells and intermediate progenitors. Moreover, Mettl3 deletion causes elevated translation of a significant number of mRNAs, in particular major components in m6A methylation. Our findings indicate distinct functions of Mettl3 and Fto in brain development, and uncover a profound role of Mettl3 in regulating translation of major mRNAs that control proper cortical development.

Introduction: Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to nonmajor bleeding, which may lead to venous thromboembolism (VTE) recurrence. We aimed to determine the risk of nonmajor bleeding using different DOACs to prevent and treat VTE. Methods: PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception until January 6, 2021. The incidence of clinically relevant nonmajor bleeding and minor bleeding was investigated. In frequentist-based network meta-analysis, we analyzed the odds ratio (OR) with 95% CI and the surface under the cumulative ranking curves (SUCRA). Results: Twenty-seven randomized controlled trials (RCTs) (involving 64,493 patients) were included. For preventing VTE, the risk for clinically relevant nonmajor bleeding was lowest for apixaban, followed by that for low-molecular weight heparin (LMWH), dabigatran, edoxaban, and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban, LMWH, dabigatran, and edoxaban. For treating VTE, the risk for clinically relevant nonmajor bleeding was also lowest for apixaban, followed by that for edoxaban, vitamin K antagonists (VKAs), and rivaroxaban. The risk for minor bleeding was lowest for apixaban, followed by that for rivaroxaban and VKAs. Conclusions: Regardless of whether it was used for preventing or treating VTE, apixaban had the lowest risk of nonmajor bleeding. This suggests that apixaban may have a lower risk of nonmajor bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

The study of soil–plant–machine interaction (SPMI) examines the system dynamics at the interface of soil, machine, and plant materials, primarily consisting of soil–machine, soil–plant, and plant–machine interactions. A thorough understanding of the mechanisms and behaviors of SPMI systems is of paramount importance to optimal design and operation of high-performance agricultural machinery. The discrete element method (DEM) is a promising numerical method that can simulate dynamic behaviors of particle systems at micro levels of individual particles and at macro levels of bulk material. This paper presents a comprehensive review of the fundamental studies and applications of DEM in SPMI systems, which is of general interest to machinery systems and computational methods communities. Important concepts of DEM including working principles, calibration methods, and implementation are introduced first to help readers gain a basic understanding of the emerging numerical method. The fundamental aspects of DEM modeling including the study of contact model and model parameters are surveyed. An extensive review of the applications of DEM in tillage, seeding, planting, fertilizing, and harvesting operations is presented. Relevant methodologies used and major findings of the literature review are synthesized to serve as references for similar research. The future scope of coupling DEM with other computational methods and virtual rapid prototyping and their applications in agriculture is narrated. Finally, challenges such as computational efficiency and uncertainty in modeling are highlighted. We conclude that DEM is an effective method for simulating soil and plant dynamics in SPMI systems related to the field of agriculture and food production. However, there are still some aspects that need to be examined in the future.

A cost-effective harvesting method and equipment for small-scale farms is essential to ensure the viability and sustainability of their operations. This study aims to retrofit and test a pull-type combine harvester for effective and efficient operations in small grains. A 1960s-era functional combine harvester was retrofitted with a stripper header rotor in place of the sickle bar cutting system to increase the harvesting capacity. Preliminary field testing found that the original header auger and feeder house could not handle the changed crop composition at an increased capacity and did not properly convey the grain from the auger to the feeder house and onto the threshing system. Therefore, redesign modifications were conducted for the auger and feeder house to help increase the efficiency and capacity required to use the stripper header. Various design concepts were proposed, analyzed, and prototyped in this study. The machine performance of the material-conveying efficiency of the wheat-material-other-than-grain mixture was evaluated at various material throughput rates. The results showed that the auger shim and feeder house paddle redesign increased the efficiency from 80.68% to 98.56%, as compared to the original machine configuration. The cost-effective and high-performance pull-type combine harvester proposed in this study has a high potential in solving the bottleneck problem of local production of small grains by small-scale farming operations.

Extranodal diffuse large B cell lymphoma (EN DLBCL) often leads to poor outcomes, while the underlying mechanism remains unclear. As immune imbalance plays an important role in lymphoma pathogenesis, we hypothesized that immune genes might be involved in the development of EN DLBCL. Ninety-three differentially expressed immune genes (DEIGs) were identified from 1168 differentially expressed genes (DEGs) between tumor tissues of lymph node DLBCL (LN DLBCL) and EN DLBCL patients in TCGA database. Nine prognostic immune genes were further identified from DEIGs by univariate Cox regression analysis. A multivariate predictive model was established based on these prognostic immune genes. Patients were divided into high- and low-risk groups according to the median model-based risk score. Kaplan-Meier survival curves showed that patients in the high-risk group had a shorter survival time than those in the low-risk group (P < 0.001). Ubiquitin-specific peptidase 18 (USP18) was further recognized as the key immune gene in EN DLBCL on the basis of coexpression of differentially expressed transcription factors (DETFs) and prognostic immune genes. USP18 exhibited low expression in EN DLBCL, which was regulated by LIM homeobox 2 (LHX2) (R = 0.497, P < 0.001, positive). The potential pathway downstream of USP18 was the MAPK pathway, identified by gene set variation analysis (GSVA), gene set enrichment analysis (GSEA) and Pearson correlation analysis (R = 0.294, P < 0.05, positive). The "ssGSEA" algorithm and Pearson correlation analysis identified that activated dendritic cells (aDCs) were the cell type mostly associated with USP18 (R = 0.694, P < 0.001, positive), indicating that USP18 participated in DC-modulating immune responses. The correlations among key biomarkers were supported by multiomics database validation. Indeed, the USP18 protein was confirmed to be expressed at lower levels in tumor tissues in patients with EN DLBCL than in those with LN DLBCL by immunohistochemistry. In short, our study illustrated that the downregulation of USP18 was associated with reduced aDC number in the tumor tissues of EN DLBCL patients, indicating that targeting USP18 might serve as a promising therapy.

Virtual reality technology has begun to be gradually applied to clinical stroke rehabilitation. The study aimed to evaluate the effect of traditional plus virtual reality rehabilitation on motor function recovery, balance, and activities of daily living in stroke patients.Studies published in English before October 2020 were retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. This study used RevMan 5.3 software for meta-analysis.A total of 21 randomized controlled trials were included, which enrolled 619 patients. Traditional plus virtual reality rehabilitation is better than traditional rehabilitation in upper limb motor function recovery measured by Fugl-Meyer Assessment-Upper Extremity (mean difference = 3.49, 95% confidence interval = 1.24 to 5.73, P = 0.002) and manual dexterity assessed by Box and Block Test (mean difference = 6.59, 95% confidence interval = 3.45 to 9.74, P0.0001). However, there is no significant difference from traditional rehabilitation in activities of daily living assessed by Functional Independence Measure (mean difference = 0.38, 95% confidence interval = -0.26 to 1.02, P = 0.25) and balance assessed by Berg Balance Scale (mean difference = 2.18, 95% confidence interval = -0.35 to 4.71, P = 0.09).Traditional plus virtual reality rehabilitation therapy is an effective method to improve the upper limb motor function and manual dexterity of patients with limb disorders after stroke, and immersive virtual reality rehabilitation treatment may become a new option for rehabilitation after stroke.

Jianpin Ye,1,&ast; Zhiwei Zeng,2,&ast; Yuxian Chen,3 Zhenkun Wu,3 Qingwei Yang,4 Tao Sun2 1Outpatient Department Laboratory, Xiamen Aviation, Xiamen, Fujian, People’s Republic of China; 2Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian, People’s Republic of China; 3Taokang Institute of Neuro Medicine, Xiamen, Fujian, People’s Republic of China; 4Department of Neurology, Zhongshan Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Sun, Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian, People’s Republic of China, Email taosun@hqu.edu.cnBackground: Both genetic and environmental factors strongly affect serum uric acid (SUA) concentrations. The incidence of hyperuricemia tends to be younger in the Chinese population. In particular, we have found a high prevalence of hyperuricemia among Chinese flight attendants, aged from 20 to 40, in our survey. This study aims to evaluate whether there is an association between gene polymorphisms and hyperuricemia among Chinese flight attendants.Methods: A total of 532 flight attendants with high and normal serum uric acid levels were recruited. Allele-specific polymerase chain reaction (AS-PCR) was performed using blood samples of enrolled subjects.Results: Previous studies have reported single nucleotide polymorphisms (SNPs) that are tightly associated with uric acid levels. Among them, six SNPs that are strongly associated with SUA or gout in Asians, for instance ABCG2 (rs2231142, rs72552713 and rs2231137), GCKR (rs780094), SLC2A9 (rs1014290) and SLC17A1 (rs1183201), were selected for AS-PCR analyses. We found that SNPs such as ABCG2 rs2231142, GCKR rs780094 and SLC2A9 rs1014290 are strongly associated with hyperuricemia in male flight attendants, and SLC2A9 rs1014290 among female flight attendants.Conclusion: Our study provides evidences of an association between SNPs and hyperuricemia in the Chinese flight attendants, and highlights the significance of improving diagnostics and prevention of disease development in uric acid metabolism disorders and gout using these SNPs.Keywords: serum uric acid, hyperuricemia, single nucleotide polymorphisms, flight attendants