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Abstract How to utilize modern technological means to provide both accurate scoring and objective feedback for martial arts movements has become an issue that needs to be addressed in the field of physical education. This study proposes an intelligent scoring method based on machine learning. Firstly, the key features are extracted by the feature alignment technique, which eliminates the influence of athletes’ movement speed, rhythm and duration on the scoring, thus reflecting the athletes’ skill level more realistically. Second, to further improve the objectivity and accuracy, an adaptive weighted multi-model decision-making strategy is proposed. In addition, this study is the first to use interpretable artificial intelligence to provide feedback for teaching and learning Wushu. Experimental results indicate that the integrated model using the weighted average strategy not only outperforms other algorithms after feature alignment (on the XSQ dataset MAE is 0.237, RMSE is 0.442, sMAPE is 8.569, R $$^{2}$$ is 0.633, Pearson’s correlation is 0.807, ICC is 0.856. on the UMONS-Taichi dataset, MAE is 0.29, RMSE is 0.438, sMAPE is 10.01, R $$^{2}$$ is 0.844, Pearson correlation is 0.921, and ICC is 0.954. on the PBB dataset, MAE is 0.261, RMSE is 0.351, sMAPE is 6.765, R $$^{2}$$ is 0.557, Pearson correlation is 0.753, and ICC is 0.82), but is also close to the performance of human experts. In conclusion, this study not only achieves a performance of movement evaluation comparable to human experts, but also provides a technical framework for the rapid realizing of automatic scoring in other martial arts styles, which will promote the popularization and development of martial arts education.

Abstract Background Pumpkin (Cucurbita moschata) is an important vegetable crop that often suffers from low-temperature stress during growth. However, the molecular mechanism involved in its response to chilling stress remains unknown. In this study, we comprehensively investigated the effect of chilling stress in pumpkin seedlings by conducting physiological, transcriptomic, and metabolomic analyses. Results Under chilling stress, there was an overall increase in relative electrical conductivity, along with malondialdehyde, soluble sugar, and soluble protein contents, but decreased superoxide dismutase and peroxidase activities and chlorophyll contents in seedling leaves compared with controls. Overall, 5,780 differentially expressed genes (DEGs) and 178 differentially expressed metabolites (DEMs) were identified under chilling stress. Most DEGs were involved in plant hormone signal transduction and the phenylpropanoid biosynthesis pathway, and ERF, bHLH, WRKY, MYB, and HSF transcription factors were induced. Metabolomic analysis revealed that the contents of salicylic acid (SA), phenylalanine, and tyrosine increased in response to chilling stress. The findings indicated that the SA signaling and phenylpropanoid biosynthesis pathways are key to regulating the responses to chilling stress in pumpkins. Conclusion Overall, our study provides valuable insights into the comprehensive response of C. moschata to chilling stress, enriching the theoretical basis of this mechanism and facilitating the development of molecular breeding strategies for pumpkin tolerance to chilling stress.

IntroductionBASIC PENTACYSTEINE (BPC) is a small transcription factor family known for its role in various developmental processes in plants, particularly in binding GA motifs and regulating flower and seed development. However, research on the functional characteristics and target genes of BPCs in coconut (Cocos nucifera) is limited.MethodsIn this study, we systematically characterized the gene structure, conserved protein domains, gene expansion, and target genes of CnBPCs in the coconut genome. We conducted yeast one-hybrid (Y1H) and dual-luciferase assay to explore gene interactions. We identified genes with the GA motif in their promoter regions and combined this information with a weighted gene co-expression network to identify the target genes of CnBPCs.ResultsEight CnBPCs were identified, including three Class I CnBPCs from triplication, four Class II CnBPCs (with CnBPC6A and CnBPC6B resulting from segmental duplication), and one Class III CnBPC (CnBPC7). Three conserved DNA-binding motifs were detected, exhibiting variation in certain sites. Widespread BPC gene expansion was detected in coconut and other plant species, while only three BPCs were found in the most basal extant flowering plant. Notably, 92% of protein-coding genes contained at least one GA motif, with the (GA)3 motif being most prevalent. Genes containing the GA motif that exhibit a high expression correlation with CnBPCs, tend to interact strongly with the corresponding CnBPCs. Additionally, promoters rich in the GA motif tend to interact with all members of CnBPC. The dual-luciferase assay showed that CnBPCs could activate or repress the transcriptional activities of promoters containing either (GA)3 or (GA)11 motif but with a bias toward certain genes. Furthermore, we constructed co-expressed networks identifying 426 genes with GA motifs as potential CnBPC targets.DiscussionOur findings suggest that CnBPCs may play significant roles in seed germination, flower development, and mesocarp development by interacting with genes such as CnAG1, CnAG2, CnSTK, CnMFT, and CnCS. This study characterized CnBPCs’ binding motif and possible target genes, laying a theoretical foundation to reveal CnBPCs’ function in flower and seed development.

AbstractAcute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.

Segmenting plant organs is a crucial step in extracting plant phenotypes. Despite the advancements in point-based neural networks, the field of plant point cloud segmentation suffers from a lack of adequate datasets. In this study, we addressed this issue by generating Arabidopsis models using L-system and proposing the surface-weighted sampling method. This approach enables automated point sampling and annotation, resulting in fully annotated point clouds. To create the Arabidopsis dataset, we employed Voxel Centroid Sampling and Random Sampling as point cloud downsampling methods, effectively reducing the number of points. To enhance the efficiency of semantic segmentation in plant point clouds, we introduced the Plant Stratified Transformer. This network is an improved version of the Stratified Transformer, incorporating the Fast Downsample Layer. Our improved network underwent training and testing on our dataset, and we compared its performance with PointNet++, PAConv, and the original Stratified Transformer network. For semantic segmentation, our improved network achieved mean Precision, Recall, F1-score and IoU of 84.20, 83.03, 83.61 and 73.11%, respectively. It outperformed PointNet++ and PAConv and performed similarly to the original network. Regarding efficiency, the training time and inference time were 714.3 and 597.9 ms, respectively, which were reduced by 320.9 and 271.8 ms, respectively, compared to the original network. The improved network significantly accelerated the speed of feeding point clouds into the network while maintaining segmentation performance. We demonstrated the potential of virtual plants and deep learning methods in rapidly extracting plant phenotypes, contributing to the advancement of plant phenotype research.

Adopting drought-tolerant (DT) cultivars is an effective strategy to sustain maize (Zea mays L.) production under water shortage. Optimizing plant density is an important management practice for improving maize yield. In a two-year field trial, the response of yield, actual evapotranspiration (ETc act), and water productivity (WP) to plant density (6, 7.5, 9 plants m−2) was assessed under irrigated and rainfed conditions using a DT (ZD958) and a drought-susceptible (DS, ZY309) maize cultivar, and additionally, the comparison of soil water depletion will be conducted among soils growing different DT maize varieties. Under rainfed, average yield, ETc act, and WP were 24.7%, 8.6% and 14.8% greater in ZD958 than ZY309, respectively. When density increased from 6 to 9 plants m−2, for ZD958 and ZY309 ETc act remained relatively constant, whereas their yield and WP first increased and then decreased and ultimately reached their maximum at 7.5 plants m−2. Under irrigation, increasing density (6–9 plants m−2) significantly increased yield and WP for ZD958, but for ZY309, yield and WP were not significantly impacted. Yield across seasons did not differ between cultivars at 6 and 7.5 plants m−2, and ZD958 had a 10.2% yield advantage over ZY309 at 9 plants m−2. The findings imply that DT cultivar showed greater high density tolerance than DS cultivar and thus higher optimal density under irrigation. Under rainfed, both cultivars had similar density tolerance and optimum density, whereas DT cultivar had stronger drought tolerance than DS cultivar, which could explain DT cultivar’s greater yield and WP. This study indicate that DT cultivar showed higher and more stable yields than DS cultivar across rainfed and irrigated conditions when grown at optimal densities. Thus, sustainable maize production could be achieved by adopting DT cultivars and optimizing density for different conditions in the study region.

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6–7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9–64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals.

Abstract Background Heterosis is widely used in agriculture. However, its molecular mechanisms are still unclear in plants. Here, we develop, sequence, and record the phenotypes of 418 hybrids from crosses between two testers and 265 rice varieties from a mini-core collection. Results Phenotypic analysis shows that heterosis is dependent on genetic backgrounds and environments. By genome-wide association study of 418 hybrids and their parents, we find that nonadditive QTLs are the main genetic contributors to heterosis. We show that nonadditive QTLs are more sensitive to the genetic background and environment than additive ones. Further simulations and experimental analysis support a novel mechanism, homo-insufficiency under insufficient background (HoIIB), underlying heterosis. We propose heterosis in most cases is not due to heterozygote advantage but homozygote disadvantage under the insufficient genetic background. Conclusion The HoIIB model elucidates that genetic background insufficiency is the intrinsic mechanism of background dependence, and also the core mechanism of nonadditive effects and heterosis. This model can explain most known hypotheses and phenomena about heterosis, and thus provides a novel theory for hybrid rice breeding in future.

Abstract Background Rice is the world’s second largest food crop and accelerated global climate change due to the intensification of human activities has a huge impact on rice. Research on the evolution of different rice ecotypes is essential for enhancing the adaptation of rice to the unpredictable environments. Results The sequencing data of 868 cultivated and 140 wild rice accessions were used to study the domestication history and signatures of adaptation in the distinct rice ecotypes genome. The different populations had formed distinct rice ecotypes by phylogenetic analyses and were domesticated independently in the two subspecies of rice, especially deepwater and upland rice. The domestication history of distinct rice ecotypes was confirmed and the four predicted admixture events mainly involved gene flow between wild rice and cultivated rice. Importantly, we identified numerous selective sweeps that have occurred during the domestication of different rice ecotypes and one candidate gene (LOC_Os11g21804) for deepwater based on transcriptomic evidence. In addition, many regions of genomic differentiation between the different rice ecotypes were identified. Furthermore, the main reason for the increase in genetic diversity in the ecotypes of xian (indica) rice was the high proportion of alternative allele frequency in new mutations. Genome-wide association analysis revealed 28 QTLs associated with flood tolerance which contained 12 related cloned genes, and 20 candidate genes within 13 deepwater QTLs were identified by transcriptomic and haplotype analyses. Conclusions These results enhanced our understanding of domestication history in different rice ecotypes and provided valuable insights for genetic improvement and breeding of rice in the current changing environments.

Abstract Background Accurate segmentation of unruptured cerebral aneurysms (UCAs) is essential to treatment planning and rupture risk assessment. Currently, three-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA) has been the most commonly used method for screening aneurysms due to its noninvasiveness. The methods based on deep learning technologies can assist radiologists in achieving accurate and reliable analysis of the size and shape of aneurysms, which may be helpful in rupture risk prediction models. However, the existing methods did not accomplish accurate segmentation of cerebral aneurysms in 3D TOF-MRA. Methods This paper proposed a CCDU-Net for segmenting UCAs of 3D TOF-MRA images. The CCDU-Net was a cascade of a convolutional neural network for coarse segmentation and the proposed DU-Net for fine segmentation. Especially, the dual-channel inputs of DU-Net were composed of the vessel image and its contour image which can augment the vascular morphological information. Furthermore, a newly designed weighted loss function was used in the training process of DU-Net to promote the segmentation performance. Results A total of 270 patients with UCAs were enrolled in this study. The images were divided into the training (N = 174), validation (N = 43), and testing (N = 53) cohorts. The CCDU-Net achieved a dice similarity coefficient (DSC) of 0.616 ± 0.167, Hausdorff distance (HD) of 5.686 ± 7.020 mm, and volumetric similarity (VS) of 0.752 ± 0.226 in the testing cohort. Compared with the existing best method, the DSC and VS increased by 18% and 5%, respectively, while the HD decreased by one-tenth. Conclusions We proposed a CCDU-Net for segmenting UCAs in 3D TOF-MRA, and the obtained results show that the proposed method outperformed other existing methods.

IntroductionThe flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine for their anti-inflammatory properties, and they have played an important role in the fight against SARS COVID-19 and other major epidemics. However, due to the lack of scientific and accurate variety identification methods and national unified standards, scattered and non-standardized management in flower bud production has led to mixed varieties that have caused significant difficulties in the cataloging and preservation of germplasm resources and the identification, promotion, and application of new L. japonica varieties.MethodsIn this study, we evaluated the population structure, genetic relationships, and genetic fingerprints of 39 germplasm resources of Lonicera in China using simplified genome sequencing technology.ResultsA total of 13,143,268 single nucleotide polymorphisms (SNPs) were identified. Thirty-nine samples of Lonicera were divided into four subgroups, and the population structure and genetic relationships among existing Lonicera germplasm resources were determined using principal component analysis, population structure analysis, and phylogenetic tree analysis. Through several stringent selection criteria, 15 additional streamlined, high-quality DNA fingerprints were filtered out of the validated 50 SNP loci and verified as being able to effectively identify the 39 Lonicera varieties.DiscussionTo our knowledge, this is the first comprehensive study measuring the diversity and population structure of a large collection of Lonicera varieties in China. These results have greatly broadened our understanding of the diversity, phylogeny, and population structure of Lonicera. The results may enhance the future analysis of genetic diversity, species identification, property rights disputes, and molecular breeding by providing a scientific basis and reference data for these efforts.

Grain of indica rice accumulates more toxic cadmium (Cd) than japonica, but the underlying genetic basis is unclear. Here, the authors show that natural variation of OsCd1 contributes to divergence in grain Cd accumulation and transferring japonica allele to indica rice leads to reduced Cd accumulation.

Background: Hereditary hearing loss (HHL) is the most common sensory deficit, which highly afflicts humans. With gene sequencing technology development, more variants will be identified and support genetic diagnoses, which is difficult for human experts to diagnose. This study aims to develop a machine learning-based genetic diagnosis model of HHL-related variants of GJB2, SLC26A4 and MT-RNR1. Methods: This case-control study included 1898 subjects, among which 1354 were HHL patients and 544 were carriers. Risk assessment models were established based on variants at 144 sites in three genes related to HHL by building six machine learning (ML) models. We compared the ML models with the genetic risk score (GRS) and expert interpretation (EI) to verify the clinical performance. Findings: Among the six ML models, the support vector machine (SVM) showed the best performance. For the prediction of HHL-related gene sites in subjects with variants, the area under the receiver operating characteristic (AUC) of the SVM model was 0.803 (0.680–0.814) in the 10-fold stratified cross-validation and 0.751 (0.635–0.779) in external validation. The predicted results were better than both EI and GRS. Furthermore, 11 sites were identified as the smallest feature set that can be accurately predicted. Interpretation: The developed SVM model has great potential to be an efficient and effective tool for HHL prediction when high throughput sequencing data are available.

Cucurbita maxima belong to the genus Cucurbita and are of nutritional and economic importance. Physiological activity, transcriptome, and metabolome analyses of leaf samples from the C. maxima inbreding line IL7 treated at 5 °C and 25 °C were performed. Cold stress resulted in a significant increase in the malondialdehyde content, relative electrical conductivity, soluble protein, sugar content, and catalase activity. A total of 5,553 differentially expressed genes were identified, of which 2,871 were up-regulated and 2,682 down-regulated. In addition, the transcription of differentially expressed genes in the plant hormone signal transduction pathway and transcription factor families of AP2/ERF, bHLH, WRKY, MYB, and HSF was activated. Moreover, 114 differentially expressed metabolites were identified by gas chromatography time-of-flight mass spectrometry, particularly through the analysis of carboxylic acids and derivatives, and organooxygen compounds. The demonstration of a series of potential metabolites and corresponding genes highlighted a comprehensive regulatory mechanism. These findings will provide novel insights into the molecular mechanisms associated with the response to cold stress in C. maxima.

Background: Radiation-induced xerostomia is one of the most common symptoms experienced by cancer patients. The aim of our study is to evaluate the preventive and therapeutic effect of acupuncture for radiation-induced xerostomia in cancer patients. Methods: Eight databases were searched for all published randomized clinical trials (RCTs) on acupuncture for radiation-induced xerostomia in cancer patients up to December 31, 2019. Manual searching included other conference abstracts and reference lists. Meta-analysis was conducted using Revman V.5.3, and risks of bias for included studies was assessed following the Cochrane Handbook. Results: Eight clinical trials (725 participants) were analyzed, and 3 were included in a meta-analysis. All included trials had a high risk of bias, such as selection, performance, and detection bias. Analysis indicated favorable effects of acupuncture regarding the improvement of xerostomia symptoms (MD −3.05, P = 0.02, 95% CI −5.58 to −0.52), compared with sham acupuncture. There were no significant differences between real acupuncture and sham acupuncture regarding the stimulated salivary flow rate (MD 0.37, P = 0.08, 95% CI −0.05 to 0.79) and unstimulated salivary flow rate (MD 0.09, P = 0.12, 95% CI −0.02 to 0.21), which were whole salivary flow rate. Compared with no acupuncture (standard oral care, usual care, or no treatment), acupuncture produced a significant improvement in patient-reported xerostomia, without causing serious adverse effects. However, a Grading of Recommended Assessments analysis revealed that the quality of all acupuncture outcome measures was low. Conclusion: The present meta-analysis and systematic review suggests that acupuncture is effective at improving xerostomia symptoms in cancer patients but not at objective salivary flow measurements. The evidence is still limited due to the low quality of the published studies.

Introduction There is a growing number of randomised controlled trials (RCTs) that focus on functional changes in the brain detected by functional MRI (fMRI) and gut microbiota composition changes after using probiotics.However, the effect of probiotics on functional changes in the brain through gut microbiota remains controversial in existing RCTs. Furthermore, to our knowledge, there is no systematic review to evaluate the effect of probiotics on functional changes in the brain through gut microbiota. Therefore, we aim to summarise literatures evaluating the potential association between probiotics, gut microbiota and functional changes in the brain to elucidate whether probiotics influence gut microbiota and affect functional changes in the brain through gut microbiota.Methods and analysis China National Knowledge Infrastructure, Wanfang Data, VIP Databases (the Chongqing VIP Chinese Science and Technology Periodical Database), SinoMed, PubMed, Web of Science, MEDLINE (The National Library of Medicine), EMBASE (Excerpt Medica Database), Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov will be searched until July 2019. The Grey Literature in Europe (OpenSIGLE) database and Google search engine will also be used. The reference lists of each included study will be reviewed to determine whether there are any further relevant studies. RCTs using probiotics compared with a placebo/control will be included. We will use risk of bias assessment and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. The results of the systematic review will be synthesised narratively in the domains of the three primary outcome measures: (1) Increased/decreased activity in brain regions or altered functional connectivity (FC) of brain detected by fMRI and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (2) Changes in composition and diversity of the gut microbiota and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (3) Increased/decreased activity in brain regions or altered FC of brain detected by fMRI and the changes in composition or diversity of the gut microbiota after administration of probiotics.Ethics and dissemination The results will be disseminated through a peer-reviewed publication. As no private and confidential patient data will be included in the reporting, there are no ethical considerations associated with this protocol.PROSPERO registration number CRD42019145114.

Introduction Xerostomia is a common symptom in patients with cancer. Currently available methods to manage xerostomia include stringent oral hygiene using fluoride agents and antimicrobials, saliva substitutes and sialagogic agents, but side effects such as headache, dizziness and sweating can occur with these therapies. Clinical trials have shown that acupuncture may be effective in treating xerostomia. The objective of this systematic review is to assess the effectiveness and safety of acupuncture treatment for xerostomia caused by cancer.Methods and analysis This systematic review will incorporate articles identified by electronically searching the following databases: PubMed, MEDLINE, the Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science Online, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, the Wanfang Database and China Biology Medicine Disc from inception to 1 December 2019. Other sources including conference proceedings and reference lists of identified publications and existing systematic reviews will also be searched. Two reviewers will independently search the databases, perform data extraction and assess the quality of studies. Data will be synthesised using either a fixed-effects model or a random-effects model, according to heterogeneity testing. Patient-reported change in the Visual Analogue Scale or the Xerostomia Inventory will be assessed as the primary outcome. Saliva collection, whole saliva production and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 will be evaluated as secondary outcomes. RevMan V. 5.3 will be employed for data analysis. The results will be expressed as risk ratios for dichotomous data and mean differences for continuous data.Ethics and dissemination This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports.Trial registration number CRD42019129069.

Avoidance of disadvantageous genetic correlations among growth duration and yield traits is critical in developing crop varieties that efficiently use light and energy resources and produce high yields. To understand the genetic basis underlying the correlations among heading date and three major yield traits in rice, we investigated the four traits in a diverse and representative core collection of 266 cultivated rice accessions in both long-day and short-day environments, and conducted the genome-wide association study using 4.6 million single nucleotide polymorphisms (SNPs). There were clear positive correlation between heading date and grain number per panicle, and negative correlation between grain number per panicle and panicle number, as well as different degrees of correlations among other traits in different subspecies and environments. We detected 47 pleiotropic genes in 15 pleiotropic quantitative trait loci (pQTLs), 18 pleiotropic genes containing 37 pleiotropic SNPs in 8 pQTLs, 27 pQTLs with r2 of linkage disequilibrium higher than 0.2, and 39 pairs of interactive genes from 8 metabolic pathways that may contribute to the above phenotypic correlations, but these genetic bases were different for correlations among different traits. Distributions of haplotypes revealed that selection for pleiotropic genes or interactive genes controlling different traits focused on genotypes with weak effect or on those balancing two traits that maximized production but sometimes their utilization strategies depend on the traits and environment. Detection of pQTLs and interactive genes and associated molecular markers will provide an ability to overcome disadvantageous correlations and to utilize the advantageous correlations among traits through marker-assisted selection in breeding.

Dissolved oxygen (DO) is a key factor that influences the healthy growth of fishes in aquaculture. The DO content changes with the aquatic environment and should therefore be monitored online. However, traditional measurement methods, such as iodometry and other chemical analysis methods, are not suitable for online monitoring. The Clark method is not stable enough for extended periods of monitoring. To solve these problems, this paper proposes an intelligent DO measurement method based on the fluorescence quenching mechanism. The measurement system is composed of fluorescent quenching detection, signal conditioning, intelligent processing, and power supply modules. The optical probe adopts the fluorescent quenching mechanism to detect the DO content and solves the problem, whereas traditional chemical methods are easily influenced by the environment. The optical probe contains a thermistor and dual excitation sources to isolate visible parasitic light and execute a compensation strategy. The intelligent processing module adopts the IEEE 1451.2 standard and realizes intelligent compensation. Experimental results show that the optical measurement method is stable, accurate, and suitable for online DO monitoring in aquaculture applications.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustainedrelease behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP doublemodified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-a and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE. [ABSTRACT FROM AUTHOR]

A resilient innovation ecosystem is an important guarantee for enhancing industrial competitiveness. Knowledge spillover is the key driving force to enhance system resilience. Firstly, we use the MEREC-CoCoSo method to calculate the resilience level of the integrated circuit (IC) innovation ecosystem and analyze the evolution trajectory of the resilience before and after the emergence of the “stuck-neck” problem. Secondly, based on the panel data of 30 provinces (autonomous regions and municipalities directly under the central government) in China from 2011 to 2021, this paper analyzes the mechanism of the impact of intra-regional knowledge spillovers on the resilience of IC innovation ecosystems using the fixed-effect model and analyzes the spatial effect of inter-regional knowledge spillovers on the resilience of innovation ecosystems using the spatial Durbin model under the human capital matrix. Finally, we analyze the regulating role of contractual and relational governance mechanisms and try to open the “black box” of governance. The result shows the following: (1) The polarization of innovative ecosystem resilience of integrated circuits is gradually increasing, with strong spatial agglomeration, high–high agglomeration, low–low agglomeration, and low–high dispersion, and there is an obvious “matthew effect” and “siphon effect”. (2) Both intra- and inter-regional knowledge spillovers contribute significantly to the resilience of IC innovation ecosystems. The contractual governance mechanism can effectively enhance the impact of knowledge spillovers on the resilience of innovation ecosystems in the region, and the relational governance mechanism has a positive impact on the resilience of innovation ecosystems in neighboring regions. (3) Heterogeneity results show that knowledge spillovers within the Pan-PRD region have a significant positive impact on innovation ecosystem resilience. Knowledge spillovers between regions with low innovation capacity have a double effect on innovation ecosystem resilience, and knowledge spillovers between regions with “talent highlands” have a facilitating effect on innovation ecosystem resilience. Accordingly, policy recommendations are put forward to open up channels for innovation knowledge spillover, realize effective allocation of innovation resources, and optimize the system of innovation talents.

BackgroundReducing the occurrence of diabetes is considered a primary criterion for evaluating the effectiveness of interventions for prediabetes. There is existing evidence that early lifestyle-based interventions can significantly decrease the incidence of diabetes. However, whether effective interventions can reduce long-term outcomes in patients, including all-cause mortality, cardiovascular risks, and the occurrence of microvascular complications, which are the most concerning issues for both patients and clinicians, remains a subject of inconsistent research findings. And there is no direct evidence to answer whether effective intervention has long-term benefits for prediabetic patients. Therefore, we conducted a systematic review and meta-analysis to assess the relationship between early effective intervention and macrovascular and microvascular complications in prediabetic patients.MethodsPubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for the randomized controlled trials of lifestyle or/and drugs intervention in prediabetes from inception to 2023.9.15. Two investigators independently reviewed the included studies and extracted relevant data. Random or fixed effects model meta-analysis to derive overall relative risk (RR) with 95% CI for all-cause mortality, cardiovascular events, and microvascular complications.ResultsAs of September 15, 2023, a total of 7 effective intervention studies were included, comprising 26 articles out of 25,671 articles. These studies involved 26,389 patients with a total follow-up duration of 178,038.6 person-years. The results indicate that effective intervention can significantly reduce all-cause mortality in prediabetic patients without a history of cardiovascular disease by 17% (RR 0.83, 95% CI 0.70-0.98). Additionally, effective intervention reduced the incidence of retinopathy by 38% (RR 0.62, 95% CI 0.70-0.98). Furthermore, the study results suggest that women and younger individuals have lower all-cause mortality and cardiovascular mortality. Subsequently, we conducted an in-depth analysis of patients without a history of cardiovascular disease. The results revealed that prediabetic patients with a 10-year cardiovascular risk >10% experienced more significant benefits in terms of all-cause mortality (P=0.01). When comparing the results of all-cause mortality and cardiovascular mortality from the Da Qing Diabetes Prevention Outcome Study longitudinally, it was evident that the duration of follow-up is a key factor influencing long-term benefits. In other words, the beneficial effects become more pronounced as the intervention duration reaches a certain threshold.ConclusionEarly effective intervention, which significantly reduces the incidence of diabetes, can effectively lower all-cause mortality in prediabetic patients without a history of cardiovascular disease (especially those with a 10-year cardiovascular risk >10%), with women and younger individuals benefiting more significantly. Additionally, the duration of follow-up is a key factor influencing outcomes. The conclusions of this study can provide evidence-based guidance for the clinical treatment of prediabetic patients to prevent cardiovascular and microvascular complications.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020160985.

Diabetic nephropathy (DN) and diabetic retinopathy (DR), as microvascular complications of diabetes mellitus, are currently the leading causes of end-stage renal disease (ESRD) and blindness, respectively, in the adult working population, and they are major public health problems with social and economic burdens. The parallelism between the two in the process of occurrence and development manifests in the high overlap of disease-causing risk factors and pathogenesis, high rates of comorbidity, mutually predictive effects, and partial concordance in the clinical use of medications. However, since the two organs, the eye and the kidney, have their unique internal environment and physiological processes, each with specific influencing molecules, and the target organs have non-parallelism due to different pathological changes and responses to various influencing factors, this article provides an overview of the parallelism and non-parallelism between DN and DR to further recognize the commonalities and differences between the two diseases and provide references for early diagnosis, clinical guidance on the use of medication, and the development of new drugs.

Sluggish diffusion effect of high entropy alloy limits its diffusion bonding with other components in practical applications. In this paper, the surface mechanical attrition treatment (SMAT) strategy for performing diffusion bonding joints of high entropy alloy (HEA) at a relative lower temperature is proposed. The EDS results demonstrate that the diffusion distance of Fe atoms increases significantly after SMAT since more gain boundaries are formed after SMAT. Furthermore, with this method the HEA/stainless steel joint can achieve a useable strength of 320 MPa at relative lower temperature of 850 °C (∼0.63 Tm, Temperature of melting). Molecular dynamics simulations show that the apparent diffusivity of Fe in the polycrystalline model is significantly higher than in the single-crystalline model because of fast diffusion at grain boundaries, i.e., the grain boundaries are fast diffusion channels. More detailed microstructure analysis indicates that although the density of dislocations increases after SMAT, its elemental diffusion ability is much weaker compared with grain boundaries. This study provides a feasible avenue for the application of diffusion bonding in HEAs, which could greatly broaden the applications fields of HEAs.

Objective: Evaluate the impact of adjusting the overall dose, Gypsum Fibrosum [Mineral; Gypsum] (ShiGao, SG) dose, and Prunus armeniaca L. [Rosaceae; Semen Armeniacae Amarum] (KuXingRen, KXR) dose on the efficacy of MaXingShiGan Decoction (MXSG) in treating children with bronchial pneumonia (Wind-heat Blocking the Lung), in order to provide strategy supported by high-quality evidence for the selection of rational clinical doses of MXSG.Methods: Based on the basic dose of MXSG, we conducted three randomized, double-blind, dose parallel controlled, multicenter clinical trials, involving adjustments to the overall dose, SG dose, and KXR dose, and included 120 children with bronchial pneumonia (Wind-heat Blocking the Lung) respectively. And the patients were divided into low, medium, and high dose groups in a 1:1:1 ratio, with 40 cases in each group. The intervention period lasted for 10 days. The primary outcome was the clinical cured rate, while the secondary outcomes included the effectiveness in alleviating major symptoms of bronchial pneumonia (including fever, cough, dyspnea, and phlegm congestion). And the occurrence of adverse events was recorded.Results: We first recorded and analyzed the baseline characteristics of the three studies, including age, gender, height, and so on. The results indicated that there were no significant differences among the dose groups within each study. For the study adjusting the overall dose of MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher clinical cured rates compared to the low-dose group (Chi-square value 9.01, p = 0.0111). However, there was no significant benefit between the high-dose group and the medium-dose group (81.58% vs. 81.08%). Regarding phlegm congestion, excluding fever, cough, and dyspnea, both the medium-dose group and high-dose group had significantly higher clinical cured rates than the low-dose group (Chi-square value 6.31, p = 0.0426), and there was no significant benefit between the high-dose group and the medium-dose group (69.23% vs. 75.00%). A total of 5 adverse events were observed, of which only 1 case in the medium-dose group was possibly related to the experimental medication. For the study adjusted the SG dose in MXSG, the results showed that the high-dose group had the highest clinical cured rate, but the inter-group difference was not statistically significant (Chi-square value 3.36, p = 0.1864). The area under the curve (AUC) for cough in the medium-dose group was significantly lower than in the low-dose group and high-dose group (F-test value 3.14, p = 0.0471). Although no significant differences were observed in fever and dyspnea among the groups, the AUC in the high-dose group was lower than in the medium-dose and low-dose groups. In comparing the complete defervescence time, both the high-dose group (p < 0.0001) and the medium-dose group (p = 0.0015) achieved faster than the low-dose group. The high-dose group slightly outperformed the medium-dose group (0.50 (0.50, 0.80) vs. 0.80 (0.40, 1.40)), although the difference was not significant. In the medium-dose group, 1 adverse event was observed, but it was not related to the experimental medication. For the study adjusted the KXR dose in MXSG, the results showed that both the medium-dose group and high-dose group had significantly higher cured rates compared to the low-dose group (Chi-square value 47.05, p < 0.0001). However, there was no significant benefit comparing the high-dose group to the medium-dose group (90.00% vs. 92.50%). Regarding clinical symptoms, the results indicated that for cough (F-test value 3.16, p = 0.0460) and phlegm congestion (F-test value 3.84, p = 0.0243), the AUC for both the medium-dose group and high-dose group were significantly lower than in the low-dose group. Although there was benefit in the high-dose group compared to the medium-dose group, it was not statistically significant. No adverse events were observed during the study period.Conclusion: The synthesis of the three conducted clinical studies collectively indicates that for children with bronchial pneumonia (Wind-heat Blocking the Lung), the basic clinical dose of MXSG may represents an optimal intervention dose based on the accumulated clinical experience of doctors. If the dose is insufficient, the clinical effects might be compromised, but using a higher dose does not significantly enhance benefits. Concerning different symptoms, increasing the overall formula’s dose has a favorable impact on improving phlegm congestion, increasing the SG is effective in improving symptoms such as fever, cough, and dyspnea, while higher dose of KXR is effective in alleviating cough and phlegm congestion. These findings suggest that for MXSG, achieving the optimal intervention dose is crucial to achieve better clinical efficacy. For the SG and KXR, if certain symptoms are more severe, increasing the dose can be considered within safe limits, can lead to significant clinical benefits in symptom improvement. This also explains why the dose of MXSG might vary among clinical doctors, while maintaining a balance between safety and effectiveness. Of course, our study is still exploratory clinical trials, and further studies are needed to confirm our findings.Clinical Trial Registration:https://www.chictr.org.cn/index.html; Identifier: ChiCTR-TRC-13003093, ChiCTR-TRC-13003099.

Introduction There is a growing number of randomised controlled trials (RCTs) that focus on functional changes in the brain detected by functional MRI (fMRI) and gut microbiota composition changes after using probiotics. However, the effect of probiotics on functional changes in the brain through gut microbiota remains controversial in existing RCTs. Furthermore, to our knowledge, there is no systematic review to evaluate the effect of probiotics on functional changes in the brain through gut microbiota. Therefore, we aim to summarise literatures evaluating the potential association between probiotics, gut microbiota and functional changes in the brain to elucidate whether probiotics influence gut microbiota and affect functional changes in the brain through gut microbiota. Methods and analysis China National Knowledge Infrastructure, Wanfang Data, VIP Databases (the Chongqing VIP Chinese Science and Technology Periodical Database), SinoMed, PubMed, Web of Science, MEDLINE (The National Library of Medicine), EMBASE (Excerpt Medica Database), Scopus, the Cochrane Central Register of Controlled Trials and ClinicalTrials. gov will be searched until July 2019. The Grey Literature in Europe (OpenSIGLE) database and Google search engine will also be used. The reference lists of each included study will be reviewed to determine whether there are any further relevant studies. RCTs using probiotics compared with a placebo/control will be included. We will use risk of bias assessment and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of evidence. The results of the systematic review will be synthesised narratively in the domains of the three primary outcome measures: (1) Increased/decreased activity in brain regions or altered functional connectivity (FC) of brain detected by fMRI and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (2) Changes in composition and diversity of the gut microbiota and their association with changes in behaviour, gastrointestinal/emotional symptoms after using probiotics. (3) Increased/decreased activity in brain regions or altered FC of brain detected by fMRI and the changes in composition or diversity of the gut microbiota after administration of probiotics. Ethics and dissemination The results will be disseminated through a peer-reviewed publication. As no private and confidential patient data will be included in the reporting, there are no ethical considerations associated with this protocol. [ABSTRACT FROM AUTHOR]

Abstract Diabetic kidney disease (DKD) is more prevalent with an increase in diabetes mellitus. Oxidative stress is a major factor in the occurrence and progression of DKD. Defending against oxidative stress and restoring antioxidant defense might be key to preventing and treating DKD. The purpose of this article is to provide an explanation of how oxidative stress affects DKD, conduct a systematic review and meta-analysis on DKD, and examine the effect of antioxidants on the disease. An analysis of 19 randomized controlled trials showed that the use of antioxidants could reduce UAE (albumin excretion rate) in patients with DKD (SMD: − 0.31; 95% CI [− 0.47, − 0.14], I2 = 0%), UACR (urine albumin/creatinine ratio) (SMD: − 0.60; 95% CI [− 1.15, − 0.06], I2 = 89%), glycosylated hemoglobin (hbA1c) (MD: − 0.61; 95% CI [− 1.00, − 0.21], I2 = 93%) and MDA (malonaldehyde) (SMD:-1.05; 95% CI [− 1.87, − 0.23], I2 = 94%), suggesting that antioxidants seemed to have therapeutic effects in patients with DKD, especially in reducing proteinuria and hbA1c. The purpose of this study is to provide new targets and ideas for drug research and clinical treatment of DKD.

BackgroundPrevious studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial.MethodsData were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed.ResultsFor 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c < 6.5% (p = 0.046) and 2hPG (< 10 mmol/L, 11.1 mmol/L) (p < 0.001), compared with the control group. The standard-reaching rate of HbA1c < 7% (p = 0.06) and FBG < 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p < 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p < 0.05). The mean change in total symptom score from baseline to week 12 was −5.45 ± 3.98 in the treatment group and −2.38 ± 3.11 in the control group, with statistically significant differences (p < 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo.ConclusionJinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.

Introduction Xerostomia is a common symptom in patients with cancer. Currently available methods to manage xerostomia include stringent oral hygiene using fluoride agents and antimicrobials, saliva substitutes and sialagogic agents, but side effects such as headache, dizziness and sweating can occur with these therapies. Clinical trials have shown that acupuncture may be effective in treating xerostomia. The objective of this systematic review is to assess the effectiveness and safety of acupuncture treatment for xerostomia caused by cancer. Methods and analysis This systematic review will incorporate articles identified by electronically searching the following databases: PubMed, MEDLINE, the Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science Online, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, the Wanfang Database and China Biology Medicine Disc from inception to 1 December 2019. Other sources including conference proceedings and reference lists of identified publications and existing systematic reviews will also be searched. Two reviewers will independently search the databases, perform data extraction and assess the quality of studies. Data will be synthesised using either a fixed-effects model or a random-effects model, according to heterogeneity testing. Patient-reported change in the Visual Analogue Scale or the Xerostomia Inventory will be assessed as the primary outcome. Saliva collection, whole saliva production and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 will be evaluated as secondary outcomes. RevMan V. 5.3 will be employed for data analysis. The results will be expressed as risk ratios for dichotomous data and mean differences for continuous data. Ethics and dissemination This protocol will not evaluate individual patient information or affect patient rights and therefore does not require ethical approval. Results from this review will be disseminated through peer-reviewed journals and conference reports. [ABSTRACT FROM AUTHOR]

Abstract Objective To explore the effect of Ludangshen oral liquid for treatment of convalescent patients with coronavirus disease 2019 (COVID-19) with randomized, double-blind, placebo-controlled multicenter method. Methods 200 convalescent COVID-19 patients who had symptoms related to decreased digestive and respiratory function were randomly divided to either receive Ludangshen oral liquid or placebo for 2 weeks. The severity of clinical symptoms including fatigue, anorexia, abdominal distension, loose stools, and shortness of breath were assessed by visual analogue scale and observed at before and after treatment. The improvement and resolution rates of clinical symptoms were evaluated. Full analysis set (FAS) and per-protocol set (PPS) were used for statistical analyses. Adverse events were recorded during the study. Results 8 patients did not complete the study. After 2 weeks of treatment, both FAS and PPS results showed that patients in Ludangshen group had significantly lower score of fatigue, anorexia, loose stools, and shortness of breath than placebo group (P 0.05). The improvement rate of fatigue, anorexia, distension, loose stools and shortness of breath were significantly higher in Ludangshen group (P 0.05). There were two cases of adverse events, with one nose bleeding in Ludangshen group and one headache in placebo group. Conclusion The study suggested that two weeks of Ludangshen oral liquid treatment may have certain effects for convalescent COVID-19 patients on improving digestive and respiratory symptoms including fatigue, anorexia, loose stools and shortness of breath, which may be one of the choices for management of convalescent COVID-19 patients with digestive and respiratory symptoms.

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19), traditional Chinese medicine (TCM) has made an important contribution to the prevention and control of the epidemic. This review aimed to evaluate the efficacy and explore the mechanisms of TCM for COVID-19. We systematically searched 7 databases from their inception up to July 21, 2021, to distinguish randomized controlled trials (RCTs), cohort studies (CSs), and case–control studies (CCSs) of TCM for COVID-19. Two reviewers independently completed the screening of literature, extraction of data, and quality assessment of included studies. Meta-analysis was performed using Review Manager 5.4 software. Eventually, 29 RCTs involving 3060 patients and 28 retrospective studies (RSs) involving 12,460 patients were included. The meta-analysis demonstrated that TCM could decrease the proportion of patients progressing to severe cases by 55% and the mortality rate of severe or critical patients by 49%. Moreover, TCM could relieve clinical symptoms, curtail the length of hospital stay, improve laboratory indicators, and so on. In addition, we consulted the literature and obtained 149 components of Chinese medicinal herbs that could stably bind to antiviral targets or anti-inflammatory or immune-regulating targets by the prediction of molecular docking. It suggested that the mechanisms involved anti-virus, anti-inflammation, and regulation of immunity. Our study made a systematic review on the efficacy of TCM for COVID-19 and discussed the possible mechanisms, which provided clinical reference and theoretical basis for further research on the mechanism of TCM for COVID-19.

Objectives This study aims to assess the volunteer motivation and stress load of patient volunteers in the Fangcang shelter hospitals (FSHs), examine their associations, and explore the potential influence factors of volunteer motivation.Design Cross-sectional online survey conducted from 21 April to 20 May 2022.Setting Questionnaires were collected from patient volunteers selected by random cluster sampling in the FSHs in Shanghai, China.Participants 197 participants who met the inclusion criteria as patients who were asymptomatic or presenting with mild symptoms in the FSHs and who volunteered to assist with routine work under quarantined settings.Outcome measures We investigated sociodemographic information, stress load and volunteer motivation through an online survey using the Volunteer Function Inventory and the Stress Overload Scale. Comparisons between groups were conducted by applying t-tests or analysis of variance. The correlation between volunteer motivation and stress was analysed by Pearson correlation. Influencing factors of volunteer motivation were determined by multivariable linear regression models. A value of p

Diabetic peripheral neuropathy (DPN) is a chronic and prevalent metabolic disease that gravely endangers human health and seriously affects the quality of life of hyperglycemic patients. More seriously, it can lead to amputation and neuropathic pain, imposing a severe financial burden on patients and the healthcare system. Even with strict glycemic control or pancreas transplantation, peripheral nerve damage is difficult to reverse. Most current treatment options for DPN can only treat the symptoms but not the underlying mechanism. Patients with long-term diabetes mellitus (DM) develop axonal transport dysfunction, which could be an important factor in causing or exacerbating DPN. This review explores the underlying mechanisms that may be related to axonal transport impairment and cytoskeletal changes caused by DM, and the relevance of the latter with the occurrence and progression of DPN, including nerve fiber loss, diminished nerve conduction velocity, and impaired nerve regeneration, and also predicts possible therapeutic strategies. Understanding the mechanisms of diabetic neuronal injury is essential to prevent the deterioration of DPN and to develop new therapeutic strategies. Timely and effective improvement of axonal transport impairment is particularly critical for the treatment of peripheral neuropathies.

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or insulin resistance as the main cause, and causes damage to various target organs including the heart, kidney and neurovascular. In terms of the pathological and physiological mechanisms of DM, oxidative stress is one of the main mechanisms leading to DM and is an important link between DM and its complications. Oxidative stress is a pathological phenomenon resulting from an imbalance between the production of free radicals and the scavenging of antioxidant systems. The main site of reactive oxygen species (ROS) production is the mitochondria, which are also the main organelles damaged. In a chronic high glucose environment, impaired electron transport chain within the mitochondria leads to the production of ROS, prompts increased proton leakage and altered mitochondrial membrane potential (MMP), which in turn releases cytochrome c (cyt-c), leading to apoptosis. This subsequently leads to a vicious cycle of impaired clearance by the body’s antioxidant system, impaired transcription and protein synthesis of mitochondrial DNA (mtDNA), which is responsible for encoding mitochondrial proteins, and impaired DNA repair systems, contributing to mitochondrial dysfunction. This paper reviews the dysfunction of mitochondria in the environment of high glucose induced oxidative stress in the DM model, and looks forward to providing a new treatment plan for oxidative stress based on mitochondrial dysfunction.

The severe acute respiratory syndrome coronavirus - 2 (SARS - CoV - 2) was reported to cause the Wuhan outbreak of the corona virus disease 2019(COVID-19). To date, the COVID-19 has infected more than 600 million people gloabally. As a growing number of patients recover from acute infections and are discharged from hospitals, the proportion of patients in the recovery period is gradually increasing. Many of these individuals have been reported to experience multiple symptoms during the convalescence, such as fatigue, dyspnea and pain which are designated as “long-COVID”, “post-COVID syndrome” or “recovery sequelae. We searched for recent articles published in PubMed on COVID-19 convalescence and found that the pathogenesis of COVID-19 convalescence is not yet well recognized. It may be associated with incomplete recovery of immune system, parenchymal organ damage (liver or lung), coagulation abnormalities, “second hit” caused by viral infection, and Phenomenon of Cell Senescence-Associated Secretory Phenotype (SASP). Some drugs and psychological factors of patients also play a non-negligible role in it. We also found that the effect of traditional Chinese medicine (TCM) is effective in the treatment of the COVID-19 recovery phase, which can not only relieve the corresponding symptoms, but also improve the indicators and pulmonary fibrosis. Bufei Huoxue Capsule, as the only drug explicitly mentioned for COVID-19 recovery period, can exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19. In addition, in previous studies, traditional Chinese medicine has been confirmed to have the ability to resist cytokine storms, as well as improve coagulation and myocardial damage, which makes it have potential therapeutic advantages in targeting the hyperimmune response, coagulation abnormalities and myocardial damage existing in the recovery period. In conclusion, the clinical symptoms of patients convalescing from COVID-19 are complex, and its pathogenesis has not been elucidated. traditional Chinese medicine, as a traditional treatment, its specific action and mechanism need to be confirmed by more studies, so that it can play a better role.

In terms of treatment, a particularly targeted drug is needed to combat the COVID-19 pandemic. Although there are currently no specific drugs for COVID-19, traditional Chinese medicine(TCM) is clearly effective. It is recommended that through data analysis and mining of TCM cases (expert experience) and population evidence (RCT and cohort studies), core prescriptions for various efficacy can be obtained. Starting from a multidimensional model of regulating immunity, improving inflammation, and protecting multiple organs, this paper constructs a multidimensional model of targeted drug discovery, integrating molecular, cellular, and animal efficacy evaluation. Through functional activity testing, biophysical detection of compound binding to target proteins, multidimensional pharmacodynamic evaluation systems of cells (Vero E6, Vero, Vero81, Huh7, and caca2) and animals (mice infected with the new coronavirus, rhesus macaques, and hamsters), the effectiveness of effective preparations was evaluated, and various efficacy effects including lung moisturizing, dehumidification and detoxification were obtained. Using modern technology, it is now possible to understand how the immune system is controlled, how inflammation is reduced, and how various organs are protected. Complete early drug characterization and finally obtain effective targeted TCM. This article provides a demonstration resource for the development of new drugs specifically for TCM.

Introduction Metformin (MET) can regulate glucose and lipid levels, and the gut microbiota may be involved in the control of metabolism. We hypothesized that MET alleviates glucolipid metabolism disorder by modulating gut microbiota and microbial metabolites.Research design and methods A total of 24 male C57BL/6 J mice were equally divided into three groups (normal control, model control (MC), and MET-treated groups). Model mice were established by feeding a high-fat diet for 6 weeks. The MET-treated group was administered MET solution (2.5 g/100 mL, 250 mg/kg). Fecal samples were collected to characterize the microbiota system using metagenomic shotgun sequencing and gas chromatography–time of flight–mass spectrometry analysis. Phenotypic and biochemical indices were obtained for further correlation analysis.Results Compared with the MC group, MET reduced the levels of weight, glucose, areas under the glucose curve in the glucose tolerance test, triglyceride (TG), and total cholesterol (TC). A decreasing abundance of bacteria, including Parabacteroides distasonis, and an increasing abundance of bacteria, including Bacteroides vulgatus, were observed in the MET-treated group. The 2-deoxytetronic acid declined after MET intervention and was positively correlated with species over-represented in the MC group and negatively correlated with species enriched in the MET-treated group. Additionally, species enriched in the MET-treated group negatively correlated with glucose, areas under the glucose curve in the glucose tolerance test, and TGs. Further, the correlation between the differential metabolites, which decreased after MET intervention, and the phenotypic indices was positive.Conclusions MET-induced restoration of intestinal homeostasis correlates with the amelioration of host glucolipid metabolism.

IntroductionDiabetic kidney disease (DKD) is a severe and growing health problem, associated with a worse prognosis and higher overall mortality rates than non-diabetic renal disease. Chinese herbs possess promising clinical benefits in alleviating the progression of DKD due to their multi-target effect. This real-world retrospective cohort trial aimed to investigate the efficacy and safety of Naoxintong (NXT) capsules in the treatment of DKD. Our study is the first real-world study (RWS) of NXT in the treatment of DKD based on a large database, providing a basis for clinical application and promotion.MethodsThe data was collected from Tianjin Healthcare and Medical Big Data Platform. Patients with DKD were enrolled from January 1, 2011, to March 31, 2021. NXT administration was defined as the exposure. The primary outcome was the change in estimated glomerular filtration rate (eGFR). We employed the propensity score matching (PSM) method to deal with confounding factors.ResultsA total of 1,798 patients were enrolled after PSM, including 899 NXT users (exposed group) and 899 non-users (control group). The eGFR changes from baseline to the end of the study were significantly different in the exposed group compared to the control group (-1.46 ± 21.94 vs -5.82 ± 19.8 mL/(min·1.73m2), P< 0.01). Patients in the NXT group had a lower risk of composite renal outcome event (HR, 0.71; 95%CI, 0.55 to 0.92; P = 0.009) and deterioration of renal function (HR, 0.74; 95% CI, 0.56 to 0.99; P = 0.039).ConclusionNXT can significantly slow the decline of eGFR and reduce the risk of renal outcomes. However, large cohort studies and RCTs are needed to further confirm our results.

The Hippo signaling pathway is involved in cell growth, proliferation, and apoptosis, and it plays a key role in regulating organ size, tissue regeneration, and tumor development. The Hippo signaling pathway also participates in the occurrence and development of various human diseases. Recently, many studies have shown that the Hippo pathway is closely related to renal diseases, including renal cancer, cystic kidney disease, diabetic nephropathy, and renal fibrosis, and it promotes the transformation of acute kidney disease to chronic kidney disease (CKD). The present paper summarizes and analyzes the research status of the Hippo signaling pathway in different kidney diseases, and it also summarizes the expression of Hippo signaling pathway components in pathological tissues of kidney diseases. In addition, the present paper discusses the positive therapeutic significance of traditional Chinese medicine (TCM) in regulating the Hippo signaling pathway for treating kidney diseases. This article introduces new targets and ideas for drug development, clinical diagnosis, and treatment of kidney diseases.

Background: As one of the most commonly used Chinese medicine formula in the manage of respiratory diseases, Maxing Ganshi Decoction (MGD) has been demonstrated to improve the clinical symptoms of pneumonia. To evaluate the efficacy and safety of MGD in treating children with community-acquired pneumonia (CAP), we conducted the clinical trial.Methods: A randomized, double-blind, placebo-controlled, multicenter trial was conducted in 3 study sites in Tianjin, China. MDG or placebo were randomly given to patients aged 3–6 years with onset of CAP within 48 h. Changes in disease efficacy during the study period (which was measured as recovery, significant effect, improvement and no effect) was evaluated as the primary outcome. Time from enrollment to fever resolution was assessed as the secondary outcome. The adverse event was analyzed as safety evaluation.Results: A total of 71 patients (36 in MGD and 35 in placebo) were randomized and completed the whole study. The patient demographics and other characteristics at baseline were similar between the 2 groups (p > 0.05). After 10 days of intervention, the proportion of recovered and significant effective patients was increased significantly in the MGD group (34.85% [95% CI, 12.44%–57.26%]; p < 0.05) compared with the control group. Besides, the symptom score of the MGD group was lowered significantly (p < 0.001). The estimated time to fever resolution in the MGD group was also reduced compared with the control group (p < 0.05). During the whole study, no side effects were observed in both MGD and control groups.Conclusion: MGD was effective in improving disease efficacy, clinical symptoms and reducing time to fever resolution in patients with childhood CAP, which suggested that MGD may be used as an alternative therapy in the treatment of childhood CAP.Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=5612, identifier 13003955.