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Abstract Objective To perform an evidence-based evaluation of the clinical efficacy of Taijiquan, Baduanjin, Yijinjing and Wuqinxi in interventions for type 2 diabetes. Design A systematic review and network meta-analysis. Methods The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpta Medica Database (Embase), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, VIP and China Biomedical Literature Database (CBM). Clinical randomized controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Taijiquan, Baduanjin, Yijinjing and Wuqinxi, were retrieved. The search time was conducted from the establishment of the database to 30 October 2022. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language, Stata and ADDIS statistical software programs were used to conduct statistics and analysis of intervention measures. Results A total of 33 randomized controlled trials with 2609 patients were identified. All patients were from China. The results of the network meta-analysis showed that Taijiquan ranked the best for improving HbA1c, 2-h postprandial blood glucose (2hPG), low-density lipoprotein cholesterol (LDL-C) and insulin sensitivity index indicator levels; Yijinjing reduced fasting plasma glucose (FPG) and total cholesterol (TC) indicator levels for the best probability ranking; Baduanjin improved the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) probability ranking the most. When the training period was less than 12 weeks, Baduanjin had better effects in improving 2hPG, TC, TG, HDL-C and LDL-C indicator levels. Taijiquan had better effects in reducing FPG levels. When the training period was 12 weeks, the effect of Yijinjing in improving FPG, HbAlc, TC and HDL-C levels was better than that in other traditional Chinese exercise, and Taijiquan had better effects in improving 2hPG, TG and LDL-C indicator levels. When the training period was longer than 12 weeks, Taijiquan had better effects in improving FPG, HbAlc, 2hPG and LDL-C indicator levels, and Baduanjin had better effects in improving TC, TG and HDL-C indicator levels. Conclusion The four traditional Chinese exercise therapies can improve blood glucose levels, blood lipid levels and insulin-related indicators of type 2 diabetes to varying degrees. Studies have shown that Taijiquan has a better targeted treatment effect on type 2 diabetes. Systematic review registration CRD42020214786. Protocol published We published the protocol article “Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: Protocol for a systematic review” in the BMJ Open magazine 2021, Issue 11, Volume 7.

Genetic transformation is widely used to improve target traits and to study gene function in wheat. However, transformation efficiency depends on the physiological status of the recipient genotype and that is affected by several factors including powdery mildew (PM) infection. The widely used recipient variety Fielder is very susceptible to PM. Therefore, it would be beneficial to develop PM resistant derivatives with high regeneration ability for use in genetic transformation. In the present study PM resistant lines CB037 and Pm97033 carrying genes Pm21 and PmV, respectively, were backcrossed to Fielder with selection for PM resistance. Five lines, NT89, NT90, NT154, and WT48 with Pm21 and line FL347 with PmV were developed, identified by molecular markers and genomic in situ hybridization (GISH) or fluorescent in situ hybridization (FISH), and further subjected to detailed assessment of agronomic traits and regeneration ability following genetic transformation capacity. Lines FL347, WT48, NT89 and NT154 assessed as being equal to, or superior, to Fielder in regeneration and transformation ability are recommended as suitable materials for the replacement of Fielder for wheat gene transfer and genome editing study.

Background As a three-dimensional network involving glycosaminoglycans (GAGs), proteoglycans (PGs) and other glycoproteins, the role of extracellular matrix (ECM) in tumorigenesis is well revealed. Abnormal glycosylation in liver cancer is correlated with tumorigenesis and chemoresistance. However, the role of galactosyltransferase in HCC (hepatocellular carcinoma) is largely unknown. Methods Here, the oncogenic functions of B4GALT7 (beta-1,4-galactosyltransferase 7) were identified in HCC by a panel of in vitro experiments, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, transwell and flow cytometry assay. The expression of B4GALT7 in HCC cell lines and tissues were examined by qPCR (real-time quantitative polymerase chain reaction) and western blot assay. The binding between B4GALT7 and miR-338-3p was examined by dual-luciferase reporter assay. Results B4GALT7 encodes galactosyltransferase I and it is highly expressed in HCC cells and human HCC tissues compared with para-tumor specimens. MiR-338-3p was identified to bind the 3′ UTR (untranslated region) of B4GALT7. Highly expressed miR-338-3p suppressed HCC cell invasive abilities and rescued the tumor-promoting effect of B4GALT7 in HCC. ShRNA (short hairpin RNA) mediated B4GALT7 suppression reduced HCC cell invasive abilities, and inhibited the expression of MMP-2 and Erk signaling. Conclusion These findings identified B4GALT7 as a potential prognostic biomarker and therapeutic target for HCC.

Background Patients often experience postoperative nausea and vomiting (PONV) after catheter ablation of atrial fibrillation (AF) because of the use of opioids for anaesthesia and analgesia during the procedure. Some clinical trials have demonstrated that acupuncture-assisted anaesthesia (AAA) reduces opioid consumption and prevents PONV. Although several studies have been conducted on AAA, its safety and efficacy in AF catheter ablation remain unclear due to small sample sizes and a paucity of methodologically rigorous designs. Therefore, this trial was designed to evaluate the safety and efficacy of AAA in reducing PONV and morphine hydrochloride consumption during catheter ablation.Methods This single-centre, patient-blinded, randomised, non-penetrating sham-controlled trial will be conducted in China. A total of 100 patients will be randomly assigned to the AAA and conventional anaesthesia (CA) groups in a ratio of 1:1. The patients will receive AAA or CA plus sham acupuncture during catheter ablation and will be followed up for 30 days. The primary outcomes include the total amount of morphine hydrochloride consumed during catheter ablation and PONV within the first 24 hours after the procedure. The secondary outcomes include pain, nausea and vomiting, anxiety, patient’s ability to cope during catheter ablation, AF recurrence and quality of life, as assessed using the numeric rating scale. Adverse events will be recorded and their influence will be analysed at the end of the trial.Discussion This study will help in evaluating the safety and efficacy of AAA applied for AF catheter ablation in reducing opioid doses during the procedure and the occurrence of PONV.Ethics and dissemination The study has been approved by the Medical Ethics Committee of Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The results of the study will be published in peer-reviewed journals and presented at conferences if possible.Trial registration number ChiCTR 2100042646; Chinese Clinical Trial Registry.

BackgroundIn recent years, Chinese and international studies have reported that traditional Chinese exercises (TCEs) have good therapeutic effects on pulmonary function, endurance capacity, and quality of life in patients with chronic obstructive pulmonary disease (COPD). However, only a few studies have reported the differences in the efficacy of different TCEs in the treatment of COPD.ObjectiveThe objective of this study is to compare the effects of five TCEs on patients with COPD, including Taijiquan (TJQ), Baduanjin (BDJ), Liuzijue (LZJ), Wuqinxi (WQX), and Yijinjing (YJJ).MethodsAll randomized controlled trials (RCTs) of TCEs for patients with COPD were searched in PubMed, Web of Science, Cochrane Library, Excerpt Medica Database (EMBASE), China National Knowledge Infrastructure (CNKI), China Biology Medicine database (CBM), China Scientific Journal Database (VIP), and Wanfang database. The search period was from the establishment of each database to August 16, 2021. The quality of the included studies was assessed according to the Cochrane handbook of systematic review, and the network meta-analysis was conducted with R 4.0.2 (Ross Ihaka, Auckland, New Zealand) and ADDIS 1.16.8 (Gert vsn Valkenhoef, Groningen, Netherlands). The effect size was evaluated using the mean difference (MD) and 95% confidence interval (CI).ResultsA total of 53 RCTs involving 3,924 patients were included. The network meta-analysis results showed that WQX was the most effective in improving FEV1/FVC% score and 6-MWT score. The difference was statistically significant (MD = 8.62, 95% CI 4.46 to 13.04, P < 0.05), (MD = 74.29, 95% CI 47.67 to 102.24, P < 0.05). However, YJJ was the most effective in reducing the CAT score, and the difference was statistically significant (MD = −8.38, 95% CI −13.24 to −3.28, P < 0.05).ConclusionThe existing evidence shows that WQX has advantages over other TCEs in improving pulmonary function and endurance capacity in patients with COPD, while YJJ has advantages in improving the quality of life. Although TCEs show no significant adverse effects, more large-scale, double-blind, and high-quality RCTs are needed in the future to verify the findings of this study.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021293640.

ObjectiveThis study aims to systematically evaluate the effect of non-invasive brain stimulation (NIBS) on neuropathic pain (NP) after spinal cord injury and compare the effects of two different NIBS.MethodsRandomized controlled trials (RCTs) about the effect of NIBS on NP after spinal cord injury (SCI) were retrieved from the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM from inception to September 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane handbook of systematic review. Statistical analysis was conducted with Stata (version 16) and R software (version 4.0.2).ResultsA total of 17 studies involving 507 patients were included. The meta-analysis showed that NIBS could reduce the pain score (SMD = −0.84, 95% CI −1.27 −0.40, P = 0.00) and the pain score during follow-up (SMD = −0.32, 95%CI −0.57 −0.07, P = 0.02), and the depression score of the NIBS group was not statistically significant than that of the control group (SMD = −0.43, 95%CI −0.89–0.02, P = 0.06). The network meta-analysis showed that the best probabilistic ranking of the effects of two different NIBS on the pain score was repetitive transcranial magnetic stimulation (rTMS) (P = 0.62) > transcranial direct current stimulation (tDCS) (P = 0.38).ConclusionNIBS can relieve NP after SCI. The effect of rTMS on NP is superior to that of tDCS. We suggest that the rTMS parameters are 80–120% resting motion threshold and 5–20 Hz, while the tDCS parameters are 2 mA and 20 min. However, it is necessary to carry out more large-scale, multicenter, double-blind, high-quality RCT to explore the efficacy and mechanism of NIBS for NP after SCI.

Introduction Traditional Chinese exercise therapy, as one of the commonly used exercise interventions for the treatment of type 2 diabetes patients in China, has been proven effective by many clinical practices, but there is still a lack of evidence-based research. This study aims to integrate clinical randomised controlled correlations via network meta-analysis evidence.Methods and analysis The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpt Medica Database (EMBASE), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database (VIP), China Biomedical Literature Database (CBM). Clinical randomised controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Tai Chi, Ba Duan Jin, Yi Jin Jing and Wu Qin Xi were retrieved. The search time was conducted from the establishment of the database to 30 October 2020. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table, and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language and ADDIS statistical software were used to conduct statistics and analysis of intervention measures.PROSPERO registration number CRD42020214786

Background The satisfactory prognostic indicator of gastric cancer (GC) patients after surgery is still lacking. Perioperative plasma extracellular vesicular programmed cell death ligand-1 (ePD-L1) has been demonstrated as a potential prognosis biomarker in many types of cancers. The prognostic value of postoperative plasma ePD-L1 has not been characterized.Methods We evaluated the prognostic value of preoperative, postoperative and change in plasma ePD-L1, as well as plasma soluble PD-L1, in short-term survival of GC patients after surgery. The Kaplan-Meier survival model and Cox proportional hazards models for both univariate and multivariate analyzes were used. And the comparison between postoperative ePD-L1 and conventional serum biomarkers (carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and CA72-4) in prognostic of GC patients was made.Results The prognostic value of postoperative ePD-L1 is superior to that of preoperative ePD-L1 on GC patients after resection, and also superior to that of conventional serum biomarkers (CEA, CA19-9 and CA72-4). The levels of postoperative ePD-L1 and ePD-L1 change are independent prognostic factors for overall survival and recurrence free survival of GC patients. High plasma level of postoperative ePD-L1 correlates significantly with poor survival, while high change in ePD-L1 level brings the significant survival benefit.Conclusions The level of plasma postoperative ePD-L1 could be considered as a candidate prognostic biomarker of GC patients after resection.

Background. Dysphagia is a common sequelae after stroke. Noninvasive brain stimulation (NIBS) is a tool that has been used in the rehabilitation process to modify cortical excitability and improve dysphagia. Objective. To systematically evaluate the effect of NIBS on dysphagia after stroke and compare the effects of two different NIBS. Methods. Randomized controlled trials about the effect of NIBS on dysphagia after stroke were retrieved from databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM, from inception to June 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using RevMan 5.3 and ADDIS 1.16.8. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Results. Ultimately, 18 studies involving 738 patients were included. Meta-analysis showed that NIBS could improve the dysphagia outcome and severity scale (DOSS) score (standard mean difference SMD=1.44, 95% CI 0.80 to 2.08, PtDCS P=0.48, the best probabilistic ranking of the SSA score is rTMS P=0.72>tDCS P=0.28, and the best probabilistic ranking of the PAS score is rTMS P=0.68>tDCS P=0.32. Conclusion. Existing evidence showed that NIBS could improve swallowing dysfunction and reduce the occurrence of aspiration after stroke, and that rTMS is better than tDCS. Limited by the number of included studies, more large-sample, multicenter, double-blind, high-quality clinical randomized controlled trials are still needed in the future to further confirm the results of this research.

High-field strain and its temperature stability of (1–x) K0.48Na0.52Nb0.96Ta0.04O3-xBaZrO3+8%MnO+3%ZrO2 (in mole, KNNT-xBZ+8Mn) ceramics sintered in reducing atmosphere are improved simultaneously via defect design in A and B site. There is a conducting type transition from n-type to p-type at x = 0.07. The BaZrO3 dopant not only induces the increase of defects (ZrNb′, BaNa·, BaK·) concentration, but also results in the increase of defect (MnNb‴) concentration, because more Mn ions as +2 oxidation state in ceramics is triggered by BaZrO3 doping modification. Defect dipoles (MnNb′′′−Vo··, ZrNb′-Vo··, BaNa·-VNa′, BaK·-VK′) in poled and aged ceramics enhance the reversibility of the non–180° domains switching, which increases the high-field strain of KNNT-xBZ+8Mn ceramics. The reversibility of non–180° domain switching can be preserved to high temperature due to stable defect dipoles (BaNa·-VNa′, BaK·-VK′) in A-site. The KNNT-xBZ+8Mn ceramics at x = 0.07 show the largest high-field strain coefficient (543 pm/V@20 kV/cm) and the highest temperature stability (125 °C). The KNNT-xBZ+8Mn ceramic is a lead-free material with great potential to be applied in the fabrication of multilayer ceramic actuators with Ni inner electrodes in the future.

Abstract Studies on the piezoelectric materials capable of efficiently outputting high electrostrains at low electric fields are driven by the demand for precise actuation in a wide range of applications. Large electrostrains of piezoceramics in operation require high driving fields, which limits their practical application due to undesirable nonlinearities and high energy consumption. Herein, a strategy is developed to enhance the electrostrains of piezoceramics while maintaining low hysteresis by incorporating lead magnesium niobate relaxors into lead zirconate titanium at the morphotropic phase boundary. An ultrahigh inverse piezoelectric coefficient $${d}_{33}^{*}$$ d 33 * of 1380 pm/V with a reduced hysteresis of 11.5% is achieved under a low electric field of 1 kV/mm, outperforming the major lead-based piezoelectric materials. In situ synchrotron X-ray diffraction and domain wall dynamics characterization with sub-microsecond temporal resolution reveal that the outstanding performances originate from facilitated domain wall movement, which in turn is due to reduced lattice distortion and miniaturized domain structures. These findings not only address the pending challenges of effective actuation under reduced driving conditions but also lay the foundation for a more systematic approach to exploring the origin of large electrostrains.

Abstract The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies.

Abstract DC distribution networks (DCDNs) possess the advantages of high power efficiency, low operation loss, and favourable control flexibility, and are regarded as an essential form of future power distribution systems. In order to increase the voltage transient performance of DCDNs against disturbances, this paper proposes a methodology for realising the active voltage support control of DCDNs based on virtual inertia coordination. Firstly, the impact of the inertia of DCDNs towards the transient voltage change is analysed, and the active voltage support mechanism considering the variable droop inertia control and virtual DC motor inertia (VDCMI) control is explored. Then, a time sequence coordination strategy based on the voltage grading of DCDNs is developed, and an adaptive inertia coefficient is designed to achieve the inertia adjustment in terms of the voltage sag and recovery processes. Using MATLAB/Simulink, a detailed model of the double‐terminal DCDNs is created to check the efficacy of the proposed approach. Different voltage disturbance scenarios are imitated, and the comparative simulations demonstrate that the proposed approach can fully utilise the inertia potential of the DCDNs to suppress the voltage sag and smooth the voltage recovery procedure. The proposed method's validity and feasibility can be well validated. The cover image is based on the Original Article Investigation of active voltage support control approach of DC distribution networks based on virtual inertia coordination by Lei Chen et al., https://doi.org/10.1049/esi2.12123.

As the frequency of extreme weather events continues to rise, there is an urgent need to strengthen the safe and stable operation of active distribution networks (ADNs), and it is of great value to establish highly resilient ADNs to withstand multi-faults caused by extreme weather events. This paper proposes a multi-period restoration approach for the resilience increase of ADNs by considering fault rapid recovery and component repair under typhoon disasters. Firstly, based on the structural reliability theory, the failure rate model of the main components is established, and in light of the system information entropy, the typical fault scenario selection strategy is designed to determine the branches with high fault probability. Then, according to the fault islanding division and network reconfiguration, a fault rapid recovery method is suggested for the ADNs, where the impact of typhoon disasters on the output features of distributed generators (DGs) are taken into account, and meanwhile, the network structure and the output power of the DGs are jointly optimized to minimize the operating cost of the ADNs. Further, a fault component repair model is formulated by adopting the adaptive ant colony algorithm, and a multi-period restoration approach is proposed for the ADNs to fulfill a rolling optimization of the network reconfiguration and fault component repair. The improved IEEE 33-node and IEEE 118-node systems are used for the approach verification, and the results show that the proposed approach can effectively improve the overall load restoration level and increase the component repair efficiency. Following a multi-criteria resilience evaluation system, the proposed approach enables the ADNs to more effectively withstand typhoon disasters, offering a resilience increase of 6.93 % and 32.24 % regarding the 33-node and 118-node systems.

AbstractBackground We aimed to investigate the associations between thyroid hormone sensitivity indices and diabetes in euthyroid adults in the United States and China.Methods 2296 euthyroid adults from the NHANES in the United States and 8319 euthyroid adults from the SPEED-Shunde in China were involved. The thyroid sensitivity indices, namely TFQIFT4 and TFQIFT3, were calculated. Multivariable logistic regression, restricted cubic spline analysis, and general ordinal logit regression were utilized.Results In the NHANES, compared with participants in quartile 1st (Q1), those in Q4 of TFQIFT3 (OR 2.12, 95% CI (1.18, 3.81)) and those in Q3 of TFQIFT4 (OR 2.31, 95% CI (1.18, 4.53)) (both P for trend < 0.05) were associated with a greater prevalence of diabetes. In the SPEED-Shunde, compared with participants in Q1, those in Q4 of TFQIFT3 had a greater prevalence of diabetes (OR 1.36, 95% CI (1.11, 1.66) (P for trend < 0.05), while no significant associations between TFQIFT4 and diabetes were found.Conclusions TFQIFT3 was associated with a higher prevalence of diabetes both in the United States and China. However, TFQIFT4 was only associated with a higher prevalence of diabetes in the United States, not in China. Further prospective cohort studies are necessary to validate these findings.

Colchicine is an alkaloid with antitumor effect isolated from Colchicum autumnale plants, it has been reported in multiple studies as a potential treatment for coronavirus disease-19 and this study applied network pharmacology and bioinformatics analysis to explore the potential mechanism of colchicine against non-small cell lung cancer and coronavirus disease-19. The R software was used to determine the differentially expressed genes of non-small cell lung cancer/coronavirus disease-19, and carry out prognostic analysis and clinical analysis of the differentially expressed genes, the targets of colchicine were obtained from various databases, the protein-protein interaction network of intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 was constructed, enrichment analysis of gene ontology and kyoto encyclopedia of genes and genomes pathways was performed by Metascape database and the molecular docking and molecular dynamics simulation were completed. We obtained a total of 716 differentially expressed genes and identified 13 potential prognostic genes associated with the clinical characterization of non-small cell lung cancer/coronavirus disease-19 patients. C-C motif chemokine ligand 2, toll like receptor 4, intercellular adhesion molecule 1, peroxisome proliferator activated receptor gamma, interleukin 17A, interferon gamma, angiotensin I converting enzyme, fos proto-oncogene, nuclear factor kappa B inhibitor alpha, TIMP metallopeptidase inhibitor 1 and secreted phosphoprotein 1 were core targets. The intersection targets of colchicine and non-small cell lung cancer/coronavirus disease-19 were mainly enriched in biological processes such as inflammatory response, response to cytokine and response to lipopolysaccharide, as well as signal pathways such as interleukin 17 signaling pathway, hypoxia inducible factor 1 signaling pathway and nucleotide binding oligomerization domain-like receptor signaling pathway. The results of molecular docking showed that the colchicine is better combined with the core targets. Analysis of molecular dynamics simulation showed that the protein and ligand form a stabilizing effect. Based on bioinformatics analysis and network pharmacology, we obtained biomarkers that may be used for the prognosis of non-small cell lung cancer/coronavirus disease-19 patients and revealed that colchicine may play a potential role in the treatment of non-small cell lung cancer/coronavirus disease-19 by regulating multiple targets and multiple signaling pathways and participating in multiple biological processes. [ABSTRACT FROM AUTHOR]

An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.

Background: This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine-to-free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods: The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results: Individuals in fourth quartile (Q4) had lower all-cause mortality than those in first quartile (Q1) of FT3/FT4 ratio (hazard ratio (HR): 0.70, 95% CI: 0.51, 0.94). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (HR: 1.43, 95% CI: 1.05, 1.96) (P < 0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions: Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/ FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Abstract Free-viewpoint video allows the user to view objects from any virtual perspective, creating an immersive visual experience. This technology enhances the interactivity and freedom of multimedia performances. However, many free-viewpoint video synthesis methods hardly satisfy the requirement to work in real time with high precision, particularly for sports fields having large areas and numerous moving objects. To address these issues, we propose a free-viewpoint video synthesis method based on distance field acceleration. The central idea is to fuse multi-view distance field information and use it to adjust the search step size adaptively. Adaptive step size search is used in two ways: for fast estimation of multi-object three-dimensional surfaces, and synthetic view rendering based on global occlusion judgement. We have implemented our ideas using parallel computing for interactive display, using CUDA and OpenGL frameworks, and have used real-world and simulated experimental datasets for evaluation. The results show that the proposed method can render free-viewpoint videos with multiple objects on large sports fields at 25 fps. Furthermore, the visual quality of our synthetic novel viewpoint images exceeds that of state-of-the-art neural-rendering-based methods.

Abstract Over the past decade, the role of the 14–3-3 protein has received increasing interest. Seven subtypes of 14–3-3 proteins exhibit high homology; however, each subtype maintains its specificity. The 14–3-3ε protein is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cell cycle regulation, repolarization of cardiac action, cardiac development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant role in the development and progression of various diseases, such as cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancer. These immense and various involvements of 14–3-3ε in diverse processes makes it a promising target for drug development. Although extensive research has been conducted on 14–3-3 dimers, studies on 14–3-3 monomers are limited. This review aimed to provide an overview of recent reports on the molecular mechanisms involved in the regulation of binding partners by 14–3-3ε, focusing on issues that could help advance the frontiers of this field. Video Abstract

Abstract Tumour cell dormancy is critical for metastasis and resistance to chemoradiotherapy. Polyploid giant cancer cells (PGCCs) with giant or multiple nuclei and high DNA content have the properties of cancer stem cell and single PGCCs can individually generate tumours in immunodeficient mice. PGCCs represent a dormant form of cancer cells that survive harsh tumour conditions and contribute to tumour recurrence. Hypoxic mimics, chemotherapeutics, radiation and cytotoxic traditional Chinese medicines can induce PGCCs formation through endoreduplication and/or cell fusion. After incubation, dormant PGCCs can recover from the treatment and produce daughter cells with strong proliferative, migratory and invasive abilities via asymmetric cell division. Additionally, PGCCs can resist hypoxia or chemical stress and have a distinct protein signature that involves chromatin remodelling and cell cycle regulation. Dormant PGCCs form the cellular basis for therapeutic resistance, metastatic cascade and disease recurrence. This review summarises regulatory mechanisms governing dormant cancer cells entry and exit of dormancy, which may be used by PGCCs, and potential therapeutic strategies for targeting PGCCs.

Abstract Background This study aims to evaluate the clinical efficacy and side effects of setting up a high-risk clinical target volume (CTV-hr) alongside simultaneous integrated boost intensity-modulated radiotherapy (IMRT-SIB) in patients diagnosed with stage IIB-IVA cervical cancer. Methods This study retrospectively analysed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University between November 2014 and September 2019. The patients were divided into experimental and control groups based on whether CTV-hr was set. All patients received a combined treatment of radiotherapy and chemotherapy. The dosage for paclitaxel was 135 mg/m2, while for cisplatin it was 75 mg/m2 or for carboplatin it was AUC 4–6, given in a cycle of 21 days. Radiotherapy (RT) included external beam radiation therapy (EBRT) and intracavitary brachytherapy (ICBT). In the control group, positive lymph nodes (GTV-n) were treated at a dose of 58–62 Gy/26–28 fractions(f), while clinical target volumes (CTV) were treated with a dose of 46–48 Gy/26-28f. The experimental group received a simultaneous integrated boost (SIB) to CTV-hr at a dose of 54–56 Gy/26-28f, with the same CTV and GTV-n as the control group. Both groups were combined with brachytherapy with a total dose (EQD2, the equivalent dose in 2 Gy/f) of 80-90 Gy. The study measured objective remission rate (ORR), 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, recurrence rate, and side effects as endpoints. Results The study enrolled 217 patients, with 119 in the experimental group and 98 in the control group. Results showed that the experimental group had a higher 3-year OS rate (87.4% vs. 71.4%, p = 0.001) and 3-year PFS rate (72.3% vs. 51.0%, p = 0.000) compared to the control group. Additionally, the experimental group had significantly lower rates of overall recurrence (26.1% vs. 50.0%, p = 0.003), in-field recurrence (15.1% vs. 36.7%, p = 0.000), and out-field recurrence(13.4% vs. 35.7%, p = 0.000) compared to the control group. All observed differences were found to be statistically significant. However, the experimental and control groups had no statistically significant difference in ORR and radiological side effects, such as radiation cystitis and enteritis (p > 0.05). Conclusions Setting CTV-hr and performing IMRT-SIB on patients with stage IIB-IVA cervical cancer effectively increased the 3-year OS rate, 3-year PFS rate and reduced recurrence rate, with no significant differences in side effects.

Abstract The nasal mucosa is constantly exposed to inhaled pathogens and is the first defence against respiratory infections. Here, we investigated the structural and compositional characteristics of the nasal mucosa of commercial pigs at various growth stages. The epithelial thickness, number of capillaries, and secretion function of the nasal mucosa dramatically increased with age; however, underlying lymphoid follicles in the respiratory region were rarely observed across the growth stages. The nasal mucosa was explored at the epithelial, immunological, and biological (commensal microbiota) barriers. In the epithelial barrier, the proliferative capacity of the nasal epithelia and the expression of tight junction proteins were high after birth; however, they decreased significantly during the suckling stage and increased again during the weaning stage. In the immunological barrier, most pattern recognition receptors were expressed at very low levels in neonatal piglets, and the innate immune cell distribution was lower. During the suckling stage, increased expression of Toll-like receptor (TLR) 2 and TLR4 was observed; however, TLR3 expression decreased. TLR expression and innate immune cell quantity significantly increased from the weaning to the finishing stage. In the biological barrier, Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes comprised the dominant phyla in neonatal piglets. A dramatic decrease in nasal microbial diversity was observed during the suckling stage, accompanied by an increase in potentially pathogenic bacteria. Proteobacteria, Bacteroidetes, and Firmicutes were identified as the core phyla of the nasal microbiota; among these, the three dominant genera, Actinobacter, Moraxella, and Bergerella, may be opportunistic pathogens in the respiratory tract. These characteristics comprise an essential reference for respiratory infection prevention at large-scale pig farms.

Over time, natural materials have evolved to be lightweight, high-strength, tough, and damage-tolerant due to their unique biological structures. Therefore, combining biological inspiration and structural design would provide traditional materials with a broader range of performance and applications. Here, the application of an ink-based three-dimensional (3D) printing strategy to the structural design of a Lunar regolith simulant-based geopolymer (HIT-LRS-1 GP) was first reported, and high-precision carbon fiber/quartz sand-reinforced biomimetic patterns inspired by the cellular sandwich structure of plant stems were fabricated. This study demonstrated how different cellular sandwich structures can balance the structure–property relationship and how to achieve unprecedented damage tolerance for a geopolymer composite. The results presented that components based on these biomimetic architectures exhibited stable non-catastrophic fracture characteristics regardless of the compression direction, and each structure possessed effective damage tolerance and anisotropy of mechanical properties. The results showed that the compressive strengths of honeycomb sandwich patterns, triangular sandwich patterns, wave sandwich patterns, and rectangular sandwich patterns in the Y-axis (Z-axis) direction were 15.6, 17.9, 11.3, and 20.1 MPa (46.7, 26.5, 23.8, and 34.4 MPa), respectively, and the maximum fracture strain corresponding to the above four structures could reach 10.2%, 6.7%, 5.8%, and 5.9% (12.1%, 13.7%, 13.6%, and 13.9%), respectively.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.

In this paper, a delayed diffusive predator-prey model with the Allee effect and nonlocal competition in prey and hunting cooperation in predators is proposed. The local stability of coexisting equilibrium and the existence of Hopf bifurcation are studied by analyzing the eigenvalue spectrum. The property of Hopf bifurcation is also studied by the center manifold theorem and normal form method. Through numerical simulation, the analysis results are verified, and the influence of these parameters on the model is also obtained. Firstly, increasing the Allee effect parameter $ \beta $ and hunting cooperation parameter $ \alpha $ is not conducive to the stability of the coexistence equilibrium point under some parameters. Secondly, the time delay can also affect the stability of coexisting equilibrium and induce periodic solutions. Thirdly, the nonlocal competition in prey can affect the dynamic properties of the predator-prey model and induce new dynamic phenomena (stably spatially inhomogeneous bifurcating periodic solutions).

Key points The compressed SENSE could significantly shorten the scan time in NCMRA. The image quality tended to decrease with the decrease in scan time. The image quality tended to decrease with the decrease in scan time. The image quality of proximal vessels was higher than that of distal vessels.

As a widely used taut-wire mooring system for deepwater platforms, the Vertically Loaded Anchor (VLA) has better performance in bearing capacity, angle adaptability, and deepwater installation than other systems. However, the installation process of the VLA and its motion characteristics are significantly impacted by multi-layered seabed soil. In this paper, the coupled Eulerian‒Lagrangian (CEL) large deformation finite element analysis method has been applied to analyse the continuous penetration of a VLA in nonuniform clay with an interbedded stiff layer. A detailed parametric study has been carried out to explore the trajectory, drag angle, movement direction and drag force of the VLA in layered clay with different embedded depths, thicknesses and undrained shear strength of the stiff layer. The CEL numerical analysis results have been validated by comparison with the analytical solutions from the inverse catenary equation. Excellent agreement has been obtained between the results from the CEL analyses and the analytical solutions. The stiff layer leads to concave and convex shapes on the trend lines of the movement direction angle and drag forces, respectively. The embedded depth of the stiff layer determines where the concave and convex shapes appear on the trend lines, while the thickness affects the sizes of the openings of the shapes. The most decisive parameter, an abrupt variation in the undrained shear strength, causes predominant rotation at the interface of layered clay. It diminishes the final embedment depth and ultimate stable drag force, meaning that the bearing capacity of the VLA severely declined in layered clay.

Abstract Rice kernel smut (RKS), caused by the fungus Tilletia horrida, has become a major disease in rice-growing areas worldwide, especially since the widespread cultivation of high-yielding hybrid rice varieties. The disease causes a significant yield loss during the production of rice male sterile lines by producing masses of dark powdery teliospores. This review mainly summarizes the pathogenic differentiation, disease cycle, and infection process of the T. horrida, as well as the decoding of the T. horrida genome, functional genomics, and effector identification. We highlight the identification and characterization of virulence-related pathways and effectors of T. horrida, which could foster a better understanding of the rice–T. horrida interaction and help to elucidate its pathogenicity molecular mechanisms. The multiple effective disease control methods for RKS are also discussed, included chemical fungicides, the mining of resistant rice germplasms/genes, and the monitoring and early warning signs of this disease in field settings.

Extreme events occur frequently and increase faults in power systems, providing negative effects on the safe and stable operation. In this regard, introducing efficient fault recovery methods to strengthen the resilience of active distribution networks (ADNs) against extreme events is very critical. This paper puts forward a novel fault recovery method for ADNs based on an improved binary particle swarm optimization (BPSO) algorithm, and the topology constraints are specially considered to accelerate the recovery operation. In addition, a resilience evaluation system is built for the ADNs for checking the performance of the proposed fault recovery method. The mathematical model, the fault recovery strategy, as well as the architecture of the resilience evaluation system, are stated in detail. Using MATLAB, an IEEE 33-node system with multiple distributed generators (DGs) is built, and different fault scenarios are imitated for verifying the effectiveness and suitability of the proposed method. From the comparative analysis of the fault recovery schemes with the traditional and improved BPSO algorithms, the proposed method enables to more effectively reduce the node voltage deviation, decrease the power loss and assist the important load recovery. In consequence, the resilience of the ADNs will be appreciatively boosted.

IntroductionAlthough several studies have explored the associations between single essential metals and serum uric acid (SUA), the study about the essential metal mixture and the interactions of metals for hyperuricemia remains unclear.MethodsWe performed a cross-sectional study to explore the association of the SUA levels with the blood essential metal mixture, including magnesium (Mg), calcium (Ca), iron (Fe), copper (Cu), zinc (Zn), manganese (Mn) in Chinese community-dwelling adults (n=1039). The multivariable linear regression, the weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were conducted to estimate the associations of blood essential metals with SUA levels and the BKMR model was also conducted to estimate the interactions of the essential metals on SUA.ResultsIn the multivariable linear regression, the association of blood Mg, Mn, and Cu with SUA was statistically significant, both in considering multiple metals and a single metal. In WQS regression [β=13.59 (95%CI: 5.57, 21.60)] and BKMR models, a positive association was found between the mixture of essential metals in blood and SUA. Specifically, blood Mg and Cu showed a positive association with SUA, while blood Mn showed a negative association. Additionally, no interactions between individual metals on SUA were observed.DiscussionIn conclusion, further attention should be paid to the relationship between the mixture of essential metals in blood and SUA. However, more studies are needed to confirm these findings.

Abstract Background The sustainable development of rice production is facing severe threats by a variety of pathogens, such as necrotrophic Rhizoctonia solani and hemibiotrophic Xanthomonas oryzae pv. oryzae (Xoo). Mining and applying resistance genes to increase the durable resistance of rice is an effective method that can be used to control these diseases. Results In this research, we isolated and characterized CYP716A16, which is a positive regulator of rice to R. solani AG1-IA and Xoo, and belongs to the cytochrome P450 (CYP450) protein 716A subfamily. Overexpression (OE) of CYP716A16 resulted in enhanced resistance to R. solani AG1-IA and Xoo, while RNA interference (RNAi) of CYP716A16 resulted in increased susceptibility compared with wild-type (WT) plants. Additionally, jasmonic acid (JA)-dependent defense responses and reactive oxygen species (ROS) were activated in the CYP716A16-OE lines after R. solani AG1-IA inoculation. The comparative transcriptomic and metabolomics analysis of CYP716A16-OE and the WT lines showed that OE of CYP716A16 activated the biosynthesis of flavonoids and increased the amounts of narcissoside, methylophiopogonanone A, oroxin A, and amentoflavone in plants. Conclusion Based on these results, we suggest that JA-dependent response, ROS level, multiple resistance-related proteins, and flavonoid contents play an important role in CYP716A16-regulated R. solani AG1-IA and Xoo resistance. Our results broaden our knowledge regarding the function of a P450 protein 716A subfamily in disease resistance and provide new insight into the molecular mechanism of rice immune response.

Accurately predicting proton flux in the space radiation environment is crucial for satellite in-orbit management and space science research. This paper proposes a proton flux prediction method based on a hybrid neural network. This method is a predictive approach for measuring proton flux profiles via a satellite during its operation, including crossings through the SAA region. In the data preprocessing stage, a moving average wavelet transform was employed to retain the trend information of the original data and perform noise reduction. For the model design, the TPA-LSTM model was introduced, which combines the Temporal Pattern Attention mechanism with a Long Short-Term Memory network (LSTM). The model was trained and validated using 4,174,202 proton flux data points over a span of 12 months. The experimental results indicate that the prediction accuracy of the TPA-LSTM model is higher than that of the AP-8 model, with a logarithmic root mean square error (logRMSE) of 3.71 between predicted and actual values. In particular, an improved accuracy was observed when predicting values within the South Atlantic Anomaly (SAA) region, with a logRMSE of 3.09.

Objective: Colorectal cancer (CRC) patients respond differently to treatments and are sub-classified by different approaches. We evaluated a deep learning model, which adopted endoscopic knowledge learnt from AI-doscopist, to characterise CRC patients by histopathological features. Results: Data of 461 patients were collected from TCGA-COAD database. The proposed framework was able to 1) differentiate tumour from normal tissues with an Area Under Receiver Operating Characteristic curve (AUROC) of 0.97; 2) identify certain gene mutations (MYH9, TP53) with an AUROC > 0.75; 3) classify CMS2 and CMS4 better than the other subtypes; and 4) demonstrate the generalizability of predicting KRAS mutants in an external cohort. Conclusions: Artificial intelligent can be used for on-site patient classification. Although KRAS mutants were commonly associated with therapeutic resistance and poor prognosis, subjects with predicted KRAS mutants in this study have a higher survival rate in 30 months after diagnoses.

The upconversion detection is a promising method to detect infrared radiation. It is proved that the focused beam makes a contribution to improving the upconversion efficiency. A near-infrared detector at room-temperature based on sum frequency generation(SFG) with focused beams is demonstrated. To enhance the upconversion efficiency, the signal and pump beams are tightly focused by the same focal lens. To reduce that the dispersion of the focal lens has a negative effect on upconversion efficiency in a tightly focusing system, the relation between the upconversion efficiency and the focused beams in our system is investigated. In the setup, the signal and pump beams are combined by a polarization maintaining wavelength division multiplexer (PMWDM) that is connected on a collimator. The mixed beam is focused into a periodically poled lithium niobate (PPLN) bulk by a lens of 35 mm focal length. The signal pulse at 1550 nm is converted to 863 nm with a 172 mW continuous-wave pump beam at 1950 nm. The converted signal is measured by a photomultiplier tube(PMT) and results shows the maximum upconversion efficiency is $5.23 \times 10^{-4}$ while the pump power is 172 mW.

Although previous studies have examined the hepatotoxicity of single metal exposure, the associations between metal mixture and non-alcoholic fatty liver disease (NAFLD) or fibrosis remain unclear. This study investigated the associations of urinary metal mixture with the risks of NAFLD and liver fibrosis in US adults using data from the National Health and Nutrition Examination Survey (NHANES) from 2017.01 to 2020.03. Vibration-controlled transient elastography was used to detect the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), which are indicators of NAFLD and liver fibrosis respectively. Three novel mixture modeling approaches including the Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regression and quantile g-computation (qgcomp) were used to estimate the associations of the urinary fourteen-metal mixture with Ln CAP and Ln LSM. There were 2283 adults aged over 18 years (1209 women and 1074 men) were included. Among women, urinary metal mixture was positively associated with Ln CAP in the BKMR and qgcomp models (both P 0.05). The metal mixture was not associated with Ln LSM in the three models regardless of genders (all P > 0.05). In conclusion, we observed sex-specific associations between urinary metal mixture and the prevalence of NAFLD in US adults. These findings emphasize the role of environmental heavy metal exposure in the development of NAFLD, and confirm the need for more prospective cohort studies on sex-specific manner.

ObjectiveAlthough phthalates are common environmental pollutants, few studies have focused on the relationship of phthalates exposure with non-alcoholic fatty liver disease (NAFLD) or liver fibrosis, and especially, the alternative phthalates have been questioned in recent years about whether they are better choices. Thus, this study aimed to explore the associations of exposure to major phthalates or alternative phthalates with NAFLD and liver fibrosis.MethodsData of 1450 adults from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 were collected. The urinary metabolite concentrations of di-2-ethylhexyl phthalate (DEHP), diisononyl phthalate (DINP) and diisodecyl phthalate (DIDP) were detected. Controlled attenuation parameter (CAP) and median liver stiffness measurement (LSM) were acquired for quantitative diagnosis of NAFLD and liver fibrosis by vibration-controlled transient elastography. Multivariate logistic regression analysis and linear regression analysis were performed to examine the associations between phthalates and NAFLD and liver fibrosis.ResultsAfter adjustment of the potential factors, the prevalence of NAFLD was significantly elevated among those in the fourth quartile of mono-(2-ethyl-5-carboxypentyl) phthalate (OR, 95%CI = 2.719, 1.296, 5.700, P = 0.016), mono (2-ethyl-5-hydroxyhexyl) phthalate (OR, 95%CI = 2.073, 1.111, 3.867, P = 0.037). No significant association was found between the alternative phthalates and NAFLD. The similar result was gained by linear regression analysis that MECPP was still significantly associated with Ln CAP (Q4 vs. Q1: β, 95%CI = 0.067, 0.017, 0.118, P = 0.027). After adjustment for the same covariates, no significant association between phthalates and liver fibrosis was found in logistics regression analysis.ConclusionsAll in all, higher prevalence of NAFLD is correlated with DEHP but not DINP or DIDP in American adults. There is no significant relationship between phthalates and liver fibrosis defined as LSM ≥ 8 Kpa. Nevertheless, further research is needed to provide evidence of causality.

BackgroundClinical research results on the relationship between folate and non-alcoholic fatty liver disease are contradictory. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed concept. Evidence about the relationship between serum folate and MAFLD, especially considering the status of serum vitamin C, is scarce. This study was aimed to investigate the association of serum folate levels with the prevalence of MAFLD, and further to analyze the potential impact of serum vitamin C status on their association.MethodsTotally 2,797 participants from National Health and Nutrition Examination Survey (NHANES) 2017–2018 were included. Vibration-controlled transient elastography was used to detect liver steatosis and fibrosis. Participants were divided in groups based on the tertiles of serum folate or vitamin C, and the serum folate or vitamin C level in T1 was low. Logistic regression analysis in the complex sample module was performed to illustrate the association of serum folate levels with the prevalence of MAFLD. Stratification analysis by serum vitamin C status was performed as well.ResultsCompared with the serum folate levels of T1 group, participants in the T3 group had 47.9% lower risk of MAFLD [OR = 0.521 (95% CI: 0.401–0.677)]. However, when participants were stratified by serum vitamin C levels, there was no association between the serum folate levels and MAFLD in the T1 or T2 group. Among participants in the T3 group of vitamin C status, participants in the T3 group of serum folate had a 63.6% lower risk of MAFLD compared with the T1 group [OR = 0.364 (95% CI: 0.147–0.903)].ConclusionsHigh serum folate level is associated with lower prevalence of MAFLD, especially in participants with sufficient vitamin C.

ABSTRACT The thick mucus layer covering of the intestinal epithelium has received increasing attention, owing to its protective role in intestinal infection. However, the exact mechanisms by which the mucus increases intestinal resistance against viral infection remain largely unclear. Here, we identify prominent antiviral activity of the small intestinal mucus and extracted total mucus proteins, as evidenced by their inhibitory effects against porcine epidemic diarrhea virus (PEDV) infection. Of all the extracted mucus proteins, mucin 2 and fraction III (~70 kDa) exhibited potent antiviral activity. We further evaluated the antiviral effects of three candidate factors in fraction III and found that calpain-1 contributed substantially to its antiviral activity. In vivo studies demonstrated that oral administration of calpain-1 provided effective protection against intestinal PEDV infection. As a calcium-activated cysteine protease, calpain-1 inhibited viral invasion by binding to and hydrolyzing the S1 domain of the viral spike protein. The region between amino acids 297 and 337 in the b domain of PEDV S1 protein was critical for calpain-1-mediated hydrolysis. Further investigation indicated that calpain-1 could be produced by goblet cells between intestinal epithelia. Taken together, the results of our study revealed calpain-1 to be a novel antiviral protein in porcine small intestinal mucus, suggesting that calpain-1 has potential for defending against intestinal infections. IMPORTANCE Although the antiviral activity of the intestinal mucus was recognized 20 years ago, the antiviral active ingredients in the mucus are poorly understood. Currently, most research on antiviral molecules in the intestinal mucus remains limited to members of the mucin family. This study identified the cysteine protease calpain-1 as a novel antiviral protein in porcine small intestinal mucus and revealed its underlying protective mechanism for the first time. This mechanism involves inhibiting porcine epidemic diarrhea virus (PEDV) invasion by binding and hydrolyzing the S1 domain of the viral spike protein. Furthermore, the results of our PEDV-challenge experiment in piglets indicated that calpain-1 provides effective protection against intestinal PEDV infection. Our findings provide new insights into the protective function of the small intestinal mucus. In addition to potential therapeutic implications for the swine industry, our analysis of antiviral proteins in the small intestinal mucus may have implications for the prevention and control of coronavirus infection in humans.

Follistatin-like protein 3 (FSTL3) is a type of FSTLs. By interacting with a disintegrin and metalloproteinase 12 (ADAM12), transforming growth factor-β ligands (activin, myostatin and growth differentiation factor (GDF) 11), FSTL3 can either activate or inhibit these molecules in human non-tumor pathophysiologies and cancers. The FSTL3 gene was initially discovered in patients with in B-cell chronic lymphocytic leukemia, and subsequent studies have shown that the FSTL3 protein is associated with reproductive development, insulin resistance, and hematopoiesis. FSTL3 reportedly contributes to the development and progression of many cancers by promoting tumor metastasis, facilitating angiogenesis, and inducing stem cell differentiation. This review summarizes the current pathophysiological roles of FSTL3, which may be a putative prognostic biomarker for various diseases and serve as a potential therapeutic target.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor 7 (BC-05). BC-05 exhibited potent inhibitory activity on both human CD13 (IC50 = 0.13 μM) and the 20S proteasome (IC50 = 1.39 μM). Although BC-05 displayed lower anti-proliferative activity than that of ixazomib in vitro, an advantage was established in the in vivo anti-cancer efficacy and prolongation of survival time, which may be due to its anti-metastatic and immune-stimulating activity. A pharmacokinetic study revealed that BC-05 is a potentially orally active agent with an F% value of 24.9%. Moreover, BC-05 showed more favorable safety profiles than those of ixazomib in preliminary toxicity studies. Overall, the results indicate that BC-05 is a promising drug candidate for the treatment of multiple myeloma.

Due to their high bending stiffness, high torsional stiffness, and high local stability, rectangular section members of Al alloy space structures are frequently utilized as load-bearing elements. However, the joint construction is more complex because of the closed cross-section. To join rectangular section members without drilling holes in them, a variety of blind bolts that can be placed and fastened on one side have been devised. The blind bolts researched in this paper is known as BOM bolt. The shear resistance of BOM-bolted Al alloy connections is investigated using shear testing and finite element calculations of individual bolts and bolt groups. According to the test and numerical simulation results, the formulas for the compressive strength of the aluminum plate and the shear capacity reduction factor of BOM-bolted long connections are derived.

Abstract Background Rice (Oryza sativa) bacterial leaf blight (BLB), caused by the hemibiotrophic Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases affecting the production of rice worldwide. The development and use of resistant rice varieties or genes is currently the most effective strategy to control BLB. Results Here, we used 259 rice accessions, which are genotyped with 2 888 332 high-confidence single nucleotide polymorphisms (SNPs). Combining resistance variation data of 259 rice lines for two Xoo races observed in 2 years, we conducted a genome-wide association study (GWAS) to identify quantitative trait loci (QTL) conferring plant resistance against BLB. The expression levels of genes, which contains in GWAS results were also identified between the resistant and susceptible rice lines by transcriptome analysis at four time points after pathogen inoculation. From that 109 candidate resistance genes showing significant differential expression between resistant and susceptible rice lines were uncovered. Furthermore, the haplotype block structure analysis predicted 58 candidate genes for BLB resistance based on Chr. 7_707158 with a minimum P-value (–log 10 P = 9.72). Among them, two NLR protein-encoding genes, LOC_Os07g02560 and LOC_Os07g02570, exhibited significantly high expression in the resistant line, but had low expression in the susceptible line of rice. Conclusions Together, our results reveal novel BLB resistance gene resources, and provide important genetic basis for BLB resistance breeding of rice crops.

Background and objectiveSerum uric acid (UA) is related to many metabolic diseases. However, the association of UA with liver diseases was not very clear. The objective of this study is to clarify the relationship of UA with liver steatosis and fibrosis.MethodsThis is a cross-sectional study of 4364 people of National Health and Nutrition Examination Survey (NHANES) 2017-2018. Liver steatosis and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) using Vibration-controlled transient elastography (VCTE). Linear and logistic regressions were performed.ResultsAfter adjusting for potential confounders, UA levels were associated with the prevalence of liver steatosis [OR=2.097 (95%CI: 1.245, 3.534)] and liver fibrosis [OR=2.983 (95%CI: 1.797, 4.952)]. Furthermore, the results were consistent in the subgroup analyses of males and females.ConclusionsUA levels were positively associated with the prevalence of liver steatosis and fibrosis.

Abstract We have designed a deep-learning model, an “Artificial Intelligent Endoscopist (a.k.a. AI-doscopist)”, to localise colonic neoplasia during colonoscopy. This study aims to evaluate the agreement between endoscopists and AI-doscopist for colorectal neoplasm localisation. AI-doscopist was pre-trained by 1.2 million non-medical images and fine-tuned by 291,090 colonoscopy and non-medical images. The colonoscopy images were obtained from six databases, where the colonoscopy images were classified into 13 categories and the polyps’ locations were marked image-by-image by the smallest bounding boxes. Seven categories of non-medical images, which were believed to share some common features with colorectal polyps, were downloaded from an online search engine. Written informed consent were obtained from 144 patients who underwent colonoscopy and their full colonoscopy videos were prospectively recorded for evaluation. A total of 128 suspicious lesions were resected or biopsied for histological confirmation. When evaluated image-by-image on the 144 full colonoscopies, the specificity of AI-doscopist was 93.3%. AI-doscopist were able to localise 124 out of 128 polyps (polyp-based sensitivity = 96.9%). Furthermore, after reviewing the suspected regions highlighted by AI-doscopist in a 102-patient cohort, an endoscopist has high confidence in recognizing four missed polyps in three patients who were not diagnosed with any lesion during their original colonoscopies. In summary, AI-doscopist can localise 96.9% of the polyps resected by the endoscopists. If AI-doscopist were to be used in real-time, it can potentially assist endoscopists in detecting one more patient with polyp in every 20–33 colonoscopies.

The basidiomycete fungus Tilletia horrida causes rice kernel smut (RKS), a crucial disease afflicting hybrid-rice-growing areas worldwide, which results in significant economic losses. However, few studies have investigated the pathogenic mechanisms and functions of effectors in T. horrida. In this study, we found that the candidate effector ThSCSP_12 caused cell necrosis in the leaves of Nicotiana benthamiana. The predicted signal peptide (SP) of this protein has a secreting function, which is required for ThSCSP_12 to induce cell death. The 1- 189 amino acid (aa) sequences of ThSCSP_12 are sufficient to confer it the ability to trigger cell death in N. benthamiana. The expression of ThSCSP_12 was induced and up-regulated during T. horrida infection. In addition, we also found that ThSCSP_12 localized in both the cytoplasm and nucleus of plant cells and that nuclear localization of this protein is required to induce cell death. Furthermore, the ability of ThSCSP_12 to trigger cell death in N. benthamiana depends on the (RAR1) protein required for Mla12 resistance but not on the suppressor of the G2 allele of Skp1 (SGT1), heat shock protein 90 (HSP90), or somatic embryogenesis receptor-like kinase (SERK3). Crucially, however, ThSCSP_12 induced a defense response in N. benthamiana leaves; yet, the expression of multiple defense-related genes was suppressed in response to heterologous expression in host plants. To sum up, these results strongly suggest that ThSCSP_12 operates as an effector in T. horrida–host interactions.

Tilletia horrida is a biotrophic basidiomycete fungus that causes rice kernel smut, one of the most significant diseases in hybrid rice-growing areas worldwide. Little is known about the pathogenic mechanisms and functions of effectors in T. horrida. Here, we performed functional studies of the effectors in T. horrida and found that, of six putative effectors tested, only ThSCSP_14 caused the cell death phenotype in epidermal cells of Nicotiana benthamiana leaves. ThSCSP_14 was upregulated early on during the infection process, and the encoded protein was secreted. The predicted signal peptide (SP) of ThSCSP_14 was required for its ability to induce the necrosis phenotype. Furthermore, the ability of ThSCSP_14 to trigger cell death in N. benthamiana depended on suppressing the G2 allele of Skp1 (SGT1), required for Mla12 resistance (RAR1), heat-shock protein 90 (HSP90), and somatic embryogenesis receptor-like kinase (SERK3). It is important to note that ThSCSP_14 induced a plant defense response in N. benthamiana leaves. Hence, these results demonstrate that ThSCSP_14 is a possible effector that plays an essential role in T. horrida–host interactions.