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Multi-parent populations (MPPs) are attractive for genetic and breeding studies because they combine genetic diversity with an easy-to-control population structure. Most methods for mapping QTLs in MPPs focus on the detection of QTLs in single environments. Little attention has been given to mapping QTLs in multienvironment trials (METs) and to detecting and modeling QTL-by-environment interactions (QEIs). We present mixed model approaches for the detection and modeling of consistent versus environment-dependent QTLs, i.e., QTL-by-environment interaction (QEI). QTL effects are assumed to be normally distributed with variances expressing consistency or dependence on environments and families. The entries of the corresponding design matrices are functions of identity-by-descent (IBD) probabilities between parents and offspring and follow from the parental origin of offspring DNA. A polygenic effect is added to the models to account for background genetic variation. We illustrate the wide applicability of our method by analyzing several public MPP datasets with observations from METs. The examples include diallel, nested association mapping (NAM), and multi-parent advanced inter-cross (MAGIC) populations. The results of our approach compare favorably with those of previous studies that used tailored methods.

Intermediate nerve neuralgia (INN) is a rare craniofacial pain syndrome. The diagnosis of INN is challenging because of the complex ear sensory innervation that results in a clinical overlap with both trigeminal neuralgia (TN) and glossopharyngeal neuralgia (GPN). A 76-year-old woman with a remarkable medical history presented with right otalgia and mandibular pain for 7 years. Neurological examination revealed a diminished sensation in the distribution of the intermediate nerve (IN). Magnetic resonance imaging demonstrated an impression of the anterior inferior cerebellar artery (AICA) on the facial–vestibulocochlear nerve complex (VII/VIII complex). The patient underwent microvascular decompression (MVD) after long-term oral medication. We confirmed that the responsible vessel was close to the VII/VIII complex and isolated the vessel under the microscope via a right-sided suboccipital retrosigmoid approach. The patient's otalgia and mandibular pain disappeared after the operation. There were no additional neurological deficits. In conclusion, MVD is a safe and feasible option for patients with INN who fail to respond to adequate pharmacotherapy.

The rumen microbiota and metabolites play an important role in energy metabolism and immune regulation of the host. However, the regulatory mechanism of rumen microbiota and metabolite interactions with host on Tibetan sheep’s plateau adaptability is still unclear. We analyzed the ruminal microbiome and metabolome, host transcriptome and serum metabolome characteristics of Tibetan sheep at different ages. Biomarkers Butyrivibrio, Lachnospiraceae_XPB1014_group, Prevotella, and Rikenellaceae_RC9_gut_group were found in 4 months, 1.5 years, 3.5 years, and 6 years Tibetan sheep, respectively. The rumen microbial metabolites were mainly enriched in galactose metabolism, unsaturated fatty acid biosynthesis and fatty acid degradation pathways, and had significant correlation with microbiota. These metabolites further interact with mRNA, and are co-enriched in arginine and proline metabolism, metabolism of xenobiotics by cytochrome P450, propanoate metabolism, starch and sucrose metabolism, gap junction pathway. Meanwhile, serum metabolites also have a similar function, such as chemical carcinogenesis − reactive oxygen species, limonene and pinene degradation, and cutin, suberine and wax biosynthesis, thus participating in the regulation of the body’s immune and energy-related metabolic processes. This study systematically revealed that rumen microbiota, metabolites, mRNA and serum metabolites of Tibetan sheep were involved in the regulation of fermentation metabolic function and immune level of Tibetan sheep at different ages, which provided a new perspective for plateau adaptability research of Tibetan sheep at different ages.

Background: The invasive brownrat (Rattus norvegicus) and the Oriental rats (Rattus tanezumi) are common commensal murid that are important hosts for rodent-borne diseases in southeast Asia. Understanding their population structure and genetic diversity is essential to uncover their invasion biology and distribution dynamics that are essential for controlling rodent-borne diseases.Methods: TA total of 103 R. norvegicus and 85 R. tanezumi were collected from 13 to 9 coastal areas of six provincial monitoring sentinel sites, respectivelyto assess patterns in their microsatellite loci and their mitochondrial coxl gene region.Results: Eleven sampled populations of R. norvegicus were divided into two major clusters by region. The observed heterozygosity values of all regional populations were smaller than expected genetic diversity heterozygosity values and deviated from Hardy-Weinberg equilibrium Nine sample populations of R. tanezumi were divided into three clusters; two that included sample from Hainan and Fujian provinces, and one that included samples from the other provinces and cities. The genetic diversity of R. tanezumi was highest in samples from Jiangsu and Guangdong provinces.Conclusion: The data in this paper confirm the two invasive rodent species from the southeastern coastal region of China may have relied on maritime transport to spread from the southern region of China to the Yangtze River basin. R. tanezumi may then hanve migrated unidirectionally, along the southeastern provinces of China towards the north, while R. norvegicus spread in a complex and multidirectional manner in Hainan, Fujian, Zhejiang and Jiangsu Provinces of the country.

BackgroundPostpartum depression (PPD) is a type of depressive episode related to parents after childbirth, which causes a variety of symptoms not only for parents but also affects the development of children. The causal relationship between potential risk factors and PPD remains comprehensively elucidated.MethodsLinkage disequilibrium score regression (LDSC) analysis was conducted to screen the heritability of each instrumental variant (IV) and to calculate the genetic correlations between effective causal factors and PPD. To search for the causal effect of multiple potential risk factors on the incidence of PPD, random effects of the inverse variance weighted (IVW) method were applied. Sensitivity analyses, including weighted median, MR-Egger regression, Cochrane’s Q test, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), were performed to detect potential Mendelian randomization (MR) assumption violations. Multivariable MR (MVMR) was conducted to control potential multicollinearity.ResultsA total of 40 potential risk factors were investigated in this study. LDSC regression analysis reported a significant genetic correlation of potential traits with PPD. MR analysis showed that higher body mass index (BMI) (Benjamini and Hochberg (BH) corrected p = 0.05), major depression (MD) (BH corrected p = 5.04E-19), and schizophrenia (SCZ) (BH corrected p = 1.64E-05) were associated with the increased risk of PPD, whereas increased age at first birth (BH corrected p = 2.11E-04), older age at first sexual intercourse (BH corrected p = 3.02E-15), increased average total household income before tax (BH corrected p = 4.57E-02), and increased years of schooling (BH corrected p = 1.47E-11) led to a decreased probability of PPD. MVMR analysis suggested that MD (p = 3.25E-08) and older age at first birth (p = 8.18E-04) were still associated with an increased risk of PPD.ConclusionIn our MR study, we found multiple risk factors, including MD and younger age at first birth, to be deleterious causal risk factors for PPD.

The field of human-computer interaction is expanding, especially within the domain of intelligent technologies. Scene understanding, which entails the generation of advanced semantic descriptions from scene content, is crucial for effective interaction. Despite its importance, it remains a significant challenge. This study introduces RGBD2Cap, an innovative method that uses RGBD images for scene semantic description. We utilize a multimodal fusion module to integrate RGB and Depth information for extracting multi-level features. And the method also incorporates target detection and region proposal network and a top-down attention LSTM network to generate semantic descriptions. The experimental data are derived from the ScanRefer indoor scene dataset, with RGB and depth images rendered from ScanNet's 3D scene serving as the model's input. The method outperforms the DenseCap network in several metrics, including BLEU, CIDEr, and METEOR. Ablation studies have confirmed the essential role of the RGBD fusion module in the method's success. Furthermore, the practical applicability of our method was verified within the AI2-THOR embodied intelligence experimental environment, showcasing its reliability.

Yaks are tough animals living in Tibet’s hypoxic stress environment. However, the metabolite composition of yak milk and its role in hypoxic stress tolerance remains largely unexplored. The similarities and differences between yak and human milk in hypoxic stress tolerance are also unclear. This study explored yak colostrum (YC) and yak mature milk (YMM) using GC–MS, and 354 metabolites were identified in yak milk. A comparative metabolomic analysis of yak and human milk metabolites showed that over 70% of metabolites were species-specific. Yak milk relies mainly on essential amino acids- arginine and essential branched-chain amino acids (BCAAs): L-isoleucine, L-leucine, and L-valine tolerate hypoxic stress. To slow hypoxic stress, human breast milk relies primarily on the neuroprotective effects of non-essential amino acids or derivates, such as citrulline, sarcosine, and creatine. In addition, metabolites related to hypoxic stress were significantly enriched in YC than in YMM. These results reveal the unique metabolite composition of yak and human milk and provide practical information for applying yak and human milk to hypoxic stress tolerance.

ObjectiveThis research employed a network meta-analysis (NMA) to examine the effectiveness of five traditional Chinese medicine (TCM) monomers for promoting motor function recovery in rats with blunt spinal cord injury (SCI).MethodsWangfang, China National Knowledge Infrastructure, Web of Science, Embase, Chinese Scientific Journal Database, PubMed, and the Chinese Biomedical Literature Databases were searched for retrieving relevant articles published from their inception to December 2022. Two reviewers performed screening of search results, data extraction, and literature quality assessment independently.ResultsFor this meta-analysis, 59 publications were included. Based on the recovery of motor function at weeks 1, 2, 3, and 4 in NMA, almost all TCM groups had significantly increased positive effects than the negative control animals. In terms of cumulative probability, the tanshinone IIA (TIIA) group ranked first in restoring motor function in the first week after blunt SCI, and the resveratrol (RSV) group ranked first during the last 3 weeks.ConclusionThe NMA revealed that TCM monomers could effectively restore motor function in the rat model of blunt SCI. In rats with blunt SCI, TIIA may be the most effective TCM monomer during the first week, whereas RSV may be the most effective TCM monomer during the last 3 weeks in promoting motor function recovery. For better evidence reliability in preclinical investigations and safer extrapolation of those findings into clinical settings, further research standardizing the implementation and reporting of animal experiments is required.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202310070.

Introduction: Glioblastoma is one of the most lethal cancers and leads to more than 200,000 deaths annually. However, despite lots of researchers devoted to exploring novel treatment regime, most of these attempts eventually failed to improve the overall survival of glioblastoma patients in near 20 years. Immunotherapy is an emerging therapy for cancers and have succeeded in many cancers. But most of its application in glioblastoma have been proved with no improvement in overall survival, which may result from the unique immune microenvironment of glioblastoma. Arginine is amino acid and is involved in many physiological processes. Many studies have suggested that arginine and its metabolism can regulate malignancy of multiple cancers and influence the formation of tumor immune microenvironment. However, there is hardly study focusing on the role of arginine metabolism in glioblastoma.Methods: In this research, based on mRNA sequencing data of 560 IDH-wildtype glioblastoma patients from three public cohorts and one our own cohort, we aimed to construct an arginine metabolism-related genes signature (ArMRS) based on four essential arginine metabolism-related genes (ArMGs) that we filtered from all genes with potential relation with arginine metabolism. Subsequently, the glioblastoma patients were classified into ArMRS high-risk and low-risk groups according to calculated optimal cut-off values of ArMRS in these four cohorts.Results: Further validation demonstrated that the ArMRS was an independent prognostic factor and displayed fine efficacy in prediction of glioblastoma patients’ prognosis. Moreover, analyses of tumor immune microenvironment revealed that higher ArMRS was correlated with more immune infiltration and relatively “hot” immunological phenotype. We also demonstrated that ArMRS was positively correlated with the expression of multiple immunotherapy targets, including PD1 and B7-H3. Additionally, the glioblastomas in the ArMRS high-risk group would present with more cytotoxic T cells (CTLs) infiltration and better predicted response to immune checkpoint inhibitors (ICIs).Discussion: In conclusion, our study constructed a novel score system based on arginine metabolism, ArMRS, which presented with good efficacy in prognosis prediction and strong potential to predict unique immunological features, resistance to immunotherapy, and guide the application of immunotherapy in IDH-wild type glioblastoma.

It is difficult for laser scanning confocal microscopy to obtain high- or ultra-high-resolution laser confocal images directly, which affects the deep mining and use of the embedded information in laser confocal images and forms a technical bottleneck in the in-depth exploration of the microscopic physiological and biochemical processes of plants. The super-resolution reconstruction model (SRGAN), which is based on a generative adversarial network and super-resolution reconstruction model (SRResNet), which is based on a residual network, was used to obtain single and secondary super-resolution reconstruction images of laser confocal images of the root cells of the hyperaccumulator Solanum nigrum. Using the peak signal-to-noise ratio (PSNR), structural similarity (SSIM) and mean opinion score (MOS), the models were evaluated by the image effects after reconstruction and were applied to the recognition of endocytic vesicles in Solanum nigrum root cells. The results showed that the single reconstruction and the secondary reconstruction of SRGAN and SRResNet improved the resolution of laser confocal images. PSNR, SSIM, and MOS were clearly improved, with a maximum PSNR of 47.690. The maximum increment of PSNR and SSIM of the secondary reconstruction images reached 21.7% and 2.8%, respectively, and the objective evaluation of the image quality was good. However, overall MOS was less than that of the single reconstruction, the perceptual quality was weakened, and the time cost was more than 130 times greater. The reconstruction effect of SRResNet was better than that of SRGAN. When SRGAN and SRResNet were used for the recognition of endocytic vesicles in Solanum nigrum root cells, the clarity of the reconstructed images was obviously improved, the boundary of the endocytic vesicles was clearer, and the number of identified endocytic vesicles increased from 6 to 9 and 10, respectively, and the mean fluorescence intensity was enhanced by 14.4% and 7.8%, respectively. Relevant research and achievements are of great significance for promoting the application of deep learning methods and image super-resolution reconstruction technology in laser confocal image studies.

BackgroundDiffuse gliomas possess a kind of malignant brain tumor with high mortality. Glutamine represents the most abundant and versatile amino acid in the body. Glutamine not only plays an important role in cell metabolism but also involves in cell survival and malignancies progression. Recent studies indicate that glutamine could also affect the metabolism of immune cells in the tumor microenvironment (TME).Materials and methodsThe transcriptome data and clinicopathological information of patients with glioma were acquired from TCGA, CGGA, and West China Hospital (WCH). The glutamine metabolism-related genes (GMRGs) were retrieved from the Molecular Signature Database. Consensus clustering analysis was used to discover expression patterns of GMRGs, and glutamine metabolism risk scores (GMRSs) were established to model tumor aggressiveness-related GMRG expression signature. ESTIMATE and CIBERSORTx were applied to depict the TME immune landscape. The tumor immunological phenotype analysis and TIDE were utilized for predicting the therapeutic response of immunotherapy.ResultsA total of 106 GMRGs were retrieved. Two distinct clusters were established by consensus clustering analysis, which showed a close association with the IDH mutational status of gliomas. In both IDH-mutant and IDH-wildtype gliomas, cluster 2 had significantly shorter overall survival compared with cluster 1, and the differentially expressed genes between the two clusters enriched in pathways related to malignant transformation as well as immunity. In silico TME analysis of the two IDH subtypes revealed not only significantly different immune cell infiltrations and immune phenotypes between the GMRG expression clusters but also different predicted responses to immunotherapy. After the screening, a total of 10 GMRGs were selected to build the GMRS. Survival analysis demonstrated the independent prognostic role of GMRS. Prognostic nomograms were established to predict 1-, 2-, and 3-year survival rates in the four cohorts.ConclusionDifferent subtypes of glutamine metabolism could affect the aggressiveness and TME immune features of diffuse glioma, despite their IDH mutational status. The expression signature of GMRGs could not only predict the outcome of patients with glioma but also be combined into an accurate prognostic nomogram.

Parkinson’s disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and there is less research on the relationship between immunity and PD. In this study, the protein-protein interaction networks (PPI) data, 2747 human immune-related genes (HIRGs), 2078 PD-related genes (PDRGs), and PD-related datasets (GSE49036 and GSE20292) were downloaded from the Human Protein Reference Database (HPRD), Amigo 2, DisGeNET, and Gene Expression Omnibus (GEO) databases, respectively. An immune- or PD-directed neighbor co-expressed network construction (IOPDNC) was drawn based on the GSE49036 dataset and HPRD database. Furthermore, a PD-directed neighbor co-expressed network was constructed. Modular clustering analysis was performed on the genes of the gene interaction network obtained in the first step to obtain the central core genes using the GraphWeb online website. The modules with the top 5 functional scores and the number of core genes greater than six were selected as PD-related gene modules. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of different module genes were performed. The single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to calculate the immune cell infiltration of the PD and the normal samples. The quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) was performed to investigate the expression of module genes. An IOPDNC and PD-directed neighbor co-expressed network (PDNC network) were constructed. Furthermore, a total of 5 immune-PD modules were identified which could distinguish between PD and normal samples, and these module genes were strongly related to PD in protein interaction level or gene expression level. In addition, functional analysis indicated that module genes were involved in various neurodegenerative diseases, such as Alzheimer disease, Huntington disease, Parkinson disease, and Long-term depression. In addition, the genes of the 6 modules were significantly associated with these 4 differential immune cells (aDC cells, eosinophils, neutrophils, and Th2 cells). Finally, the result of qRT-PCR manifested that the expression of 6 module genes was significantly higher in normal samples than in PD samples. In our study, the immune-related genes were found to be strongly related to PD and might play key roles in PD.

Glioma is one of the most lethal cancers and causes more than 200,000 deaths every year. Immunotherapy was an inspiring therapy for multiple cancers but failed in glioma treatment. The importance of serine and glycine and their metabolism has been well-recognized in the physiology of immune cells and microenvironment in multiple cancers. However, their correlation with prognosis, immune cells, and immune microenvironment of glioma remains unclear. In this study, we investigated the relationships between the expression pattern of serine and glycine metabolism-related genes (SGMGs) and clinicopathological features, prognosis, and tumor microenvironment in glioma based on comprehensive analyses of multiple public datasets and our cohort. According to the expression of SGMGs, we conducted the consensus clustering analysis to stratify all patients into four clusters with remarkably distinctive clinicopathological features, prognosis, immune cell infiltration, and immune microenvironment. Subsequently, a serine and glycine metabolism-related genes signature (SGMRS) was constructed based on five critical SGMGs in glioma to stratify patients into SGMRS high- and low-risk groups and tested for its prognostic value. Higher SGMRS expressed genes associated with the synthesis of serine and glycine at higher levels and manifested poorer prognosis. Besides, we confirmed that SGMRS was an independent prognostic factor and constructed nomograms with satisfactory prognosis prediction performance based on SGMRS and other factors. Analyzing the relationship between SGMRS and immune landscape, we found that higher SGMRS correlated with ‘hotter’ immunological phenotype and more immune cell infiltration. Furthermore, the expression levels of multiple immunotherapy-related targets, including PD-1, PD-L1, and B7-H3, were positively correlated with SGMRS, which was validated by the better predicted response to immune checkpoint inhibitors. In conclusion, our study explored the relationships between the expression pattern of SGMGs and tumor features and created novel models to predict the prognosis of glioma patients. The correlation of SGMRS with immune cells and microenvironment in gliomas suggested an essential role of serine and glycine metabolism in reforming immune cells and microenvironment. Finally, the results of our study endorsed the potential application of SGMRS to guide the selection of immunotherapy for gliomas.

Glioma is the most common malignant tumor in the central nervous system. The impact of metabolism on cancer development and the immune microenvironment landscape has recently gained broad attention. Purines are involved in multiple metabolic pathways. It has been proved that purine metabolism could regulate malignant biological behaviors and response to immune checkpoint inhibitors in multiple cancers. However, the relationship of purine metabolism with clinicopathological features and the immune landscape of glioma remains unclear. In this study, we explored the relationships between the expression of purine metabolism-related genes (PuMGs) and tumor features, including prognosis and microenvironment of glioma, based on analyses of 1,523 tumors from 4 public databases and our cohort. Consensus clustering based on 136 PuMGs classified the glioma patients into two clusters with significantly distinguished prognosis and immune microenvironment landscapes. Increased immune infiltration was associated with more aggressive gliomas. The prognostic Purine Metabolism-Related Genes Risk Signature (PuMRS), based on 11 critical PuMGs, stratified the patients into PuMRS low- and high-risk groups in the training set and was validated by validation sets from multiple cohorts. The high-risk group presented with significantly shorter overall survival, and further survival analysis demonstrated that the PuMRS was an independent prognostic factor in glioma. The nomogram combining PuMRS and other clinicopathological factors showed satisfactory accuracy in predicting glioma patients’ prognosis. Furthermore, analyses of the tumor immune microenvironment suggested that higher PuMRS was correlated with increased immune cell infiltration and gene expression signatures of “hotˮ tumors. Gliomas in the PuMRS high-risk group presented a higher expression level of multiple immune checkpoints, including PD-1 and PD-L1, and a better-predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the relationship between the expression level of PuMGs and the aggressiveness of gliomas. Our study also endorsed the application of PuMRS to construct a new robust model for the prognosis evaluation of glioma patients. The correlations between the profiles of PuMGs expression and tumor immune microenvironment potentially provided guidance for immunotherapy in glioma.

Glioma is the most common malignant tumor in the central nervous system with no significant therapeutic breakthrough in recent years. Most attempts to apply immunotherapy in glioma have failed. Tryptophan and its metabolism can regulate malignant features of cancers and reshape immune microenvironment of tumors. However, the role of tryptophan metabolism in glioma remains unclear. In current study, we explored the relationships between the expression pattern of tryptophan metabolism-related genes (TrMGs) and tumor characteristics, including prognosis and tumor microenvironment of gliomas through analyzing 1,523 patients’ samples from multiple public databases and our own cohort. Based on expression of TrMGs, K-means clustering analysis stratified all glioma patients into two clusters with significantly different TrMG expression patterns, clinicopathological features and immune microenvironment. Furthermore, we constructed a tryptophan metabolism-related genes signature (TrMRS) based on seven essential TrMGs to classify the patients into TrMRS low- and high-risk groups and validated the prognostic value of the TrMRS in multiple cohorts. Higher TrMRS represented for potentially more active tryptophan catabolism, which could subsequently lead to less tryptophan in tumor. The TrMRS high-risk group presented with shorter overall survival, and further analysis confirmed TrMRS as an independent prognostic factor in gliomas. The nomograms uniting TrMRS with other prognostic factors manifested with satisfactory efficacy in predicting the prognosis of glioma patients. Additionally, analyses of tumor immune landscapes demonstrated that higher TrMRS was correlated with more immune cell infiltration and “hot” immunological phenotype. TrMRS was also demonstrated to be positively correlated with the expression of multiple immunotherapy targets, including PD1 and PD-L1. Finally, the TrMRS high-risk group manifested better predicted response to immune checkpoint inhibitors. In conclusion, our study illustrated the relationships between expression pattern of TrMGs and characteristics of gliomas, and presented a novel model based on TrMRS for prognosis prediction in glioma patients. The association between TrMRS and tumor immune microenvironment of gliomas indicated an important role of tryptophan and its metabolism in reshaping immune landscape and the potential ability to guide the application of immunotherapy for gliomas.

Glioma is one of the most malignant intracerebral tumors, whose treatment means was limited, and prognosis was unsatisfactory. Lactate metabolism patterns have been shown to be highly heterogenous among different tumors and produce diverse impact on the tumor microenvironment. To understand the characteristics and implications of lactate metabolism gene expression, we developed a lactate metabolism-related gene expression signature of gliomas based on RNA-sequencing data of a total of 965 patient samples from TCGA, CGGA, and our own glioma cohort. Sixty-three lactate metabolism-related genes (LMGs) were differentially expressed between glioma and normal brain tissue, and consensus clustering analysis identified two clusters distinct LMG expression patterns. The consensus clusters differed in prognosis, molecular characteristics and estimated immune microenvironment landscape involving immune checkpoint proteins, T cell dysfunction and exclusion, as well as tumor purity. Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) Cox hazard regression was applied in determining of prognosis-related lactate metabolism genes (PRLMGs), on which prognostic lactate metabolism risk score (PLMRS) was constructed. The high PLMRS group was associated with significantly poorer patient outcome. A nomogram containing PLMRS and other independent prognostic variables was established with remarkable predictive performance on patient survival. Exploration on the somatic mutations and copy number variations of the high- and low-PLMRS groups demonstrated their distinct genetic background. Together, our results indicated that the expression signature of LMG was associated with the prognosis of glioma patients and influenced the activity of immune cells in the tumor microenvironment, which may serve as a potential biomarker for predicting response of gliomas to immunotherapy.

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) showed a benefit-risk profile superior to that of warfarin in atrial fibrillation (AF) patients with mild to moderate chronic kidney disease. However, the effectiveness and safety of NOACs in AF patients with end-stage renal disease (ESRD) on dialysis remain unclear. Therefore, we performed a meta-analysis regarding the effect of NOACs vs. warfarin in AF patients undergoing dialysis.MethodsA search of the Pubmed and EMBASE databases until November 2021 was performed. Adjusted risk ratios (RRs) and 95%confidence intervals (CIs) were pooled by a random-effects model with an inverse variance method.ResultsSix studies involving 3,744 NOAC- and 26,973 warfarin- users were deemed to meet the criteria. In the pooled analysis, the use of mixed NOACs had similar incidences of effectiveness and safety outcomes compared with warfarin use. And factor Xa inhibitors (rivaroxaban or apixaban) did not have significantly better effectiveness than warfarin. For the safety outcomes, the use of factor Xa inhibitors was associated with a reduced risk of gastrointestinal bleeding (RR = 0.81, 95% CI 0.70–0.95), but not major bleeding and intracranial bleeding.ConclusionCompared with warfarin, the use of NOACs, especially factor Xa inhibitors (rivaroxaban or apixaban), showed at least similar effectiveness and safety outcomes in AF patients on dialysis.

Grain weight is a major determinant in rice yield, which is tightly associated with grain size. However, the underlying molecular mechanisms that control this trait remain unclear. Here, we report a rice (Oryza sativa) mutant, low grain weight (lgw), which shows that reduced grain length is caused by decreased cell elongation and proliferation. Map-based cloning revealed that all mutant phenotypes resulted from a nine-base pair (bp) deletion in LGW, which encodes the kinesin-like protein BRITTLE CULM12 (BC12). Protein sequence alignment analysis revealed that the mutation site was located at the nuclear localization signal (NLS) of LGW/BC12, resulting in the lgw protein not being located in the nucleus. LGW is preferentially expressed in both culms and roots, as well as in the early developing panicles. Overexpression of LGW increased the grain length, indicating that LGW is a positive regulator for regulating grain length. In addition, LGW/BC12 is directly bound to the promoter of GW7 and activates its expression. Elevating the GW7 expression levels in lgw plants rescued the small grain size phenotype. We conclude that LGW regulates grain development by directly binding to the GW7 promoter and activating its expression. Our findings revealed that LGW plays an important role in regulating grain size, and manipulation of this gene provides a new strategy for regulating grain weight in rice.

Hadal zones are unique habitats characterized by high hydrostatic pressure (HHP) and scarce food supplies. The ability of eggs of species dwelling in hadal zones to develop into normal embryo under high hydrostatic pressure is an important evolutionary and developmental trait. However, the mechanisms underlying the development of eggs of hadal-dwelling species remain unknown due to the difficulty of sampling ovigerous females. Here, morphological and transcriptome analyses of eggs of the “supergiant” amphipod Alicella gigantea collected from the New Britain Trench were conducted. The morphology of A. gigantea eggs, including size, was assessed and the ultrastructure of the eggshell was investigated by scanning electron microscopy. Transcriptome sequencing and molecular adaptive evolution analysis of A. gigantea eggs showed that, as compared with shallow-water Gammarus species, genes exhibiting accelerated evolution and the positively selected genes were mostly related to pathways associated with “mitosis” and “chitin-based embryonic cuticle biosynthetic process”, suggesting that “normal mitosis maintenance” and “cuticle development and protection” are the two main adaptation strategies for survival of eggs in hadal environments. In addition, the concentration of trimethylamine oxide (TMAO), an important osmotic regulator, was significantly higher in the eggs of hadal amphipods as compared to those of shallow-water species, which might promote the eggs’ adaptation abilities. Morphological identification, evolutionary analysis, and the trimethylamine oxide concentration of A. gigantea eggs will facilitate a comprehensive overview of the piezophilic adaptation of embryos in hadal environments and provide a strategy to analyze embryogenesis under high hydrostatic pressure.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The mid-blastula transition (MBT) is a developmental milestone when maternal RNAs are cleared and the zygotic genome programmed asynchronous cell division begins to drive embryogenesis. While mechanisms underlying MBT have been intensively revealed, factors regulating cell proliferation at the transition remain largely unknown. We report here a microRNA, miR-202-3p to be a key factor that determines embryonic fate during MBT in zebrafish. A miR-202-3p antagomir specifically terminated embryo development at the mid-blastula stage. In vivo deletion of the miR-202 locus recapitulated the fatal phenotypes, which were rescued only by miR-202-3p or its precursor. Transcriptome comparison revealed >250 RNAs including both maternal and zygotic origins were dysregulated at MBT in the miR-202−/− embryos, corresponding with arrays of homeostatic disorders leading to massive apoptosis. A trio of genes: nfkbiaa, perp and mgll, known to be intimately involved with cell proliferation and survival, were identified as direct targets of miR-202-3p. Importantly, over- or under-expression of any of the trio led to developmental delay or termination at the blastula or gastrula stages. Furthermore, nfkbiaa and perp were shown to inter-regulate each other. Thus, miR-202-3p mediates a regulatory network whose components interact closely during MBT to determine embryonic viability and development.

Triple-negative breast cancer (TNBC) is the most lethal breast cancer subtype owing to the lack of targeted therapeutic strategies. Immunogenic cell death (ICD), a modality of regulated cancer cell death, offered a novel option for TNBC via augmenting tumor immunogenic microenvironment. However, few ICD-inducing agents are currently available. Here, we showed that Trametes robiniophila Murr (Huaier) triggered ICD in TNBC cells by promoting cell surface calreticulin (CRT) exposure, and increasing release of adenosine triphosphate (ATP) and high-mobility group protein B1 (HMGB1). Co-culturing with Huaier-treated TNBC cells efficiently enhanced the maturation of dendritic cells (DCs), which was further validated via cell-based vaccination assay. In the xenograft mouse model, oral administration of Huaier led to tumor-infiltrating lymphocytes (TILs) accumulation and significantly delayed tumor growth. Besides, depletion of endogenous T cells obviously abrogated the effect. Mechanically, Huaier could elicit endoplasmic reticulum (ER) stress-associated ICD through eIF2α signaling pathway. Further studies revealed that circCLASP1 was involved in the Huaier-induced immunogenicity by binding with PKR in the cytoplasm and thus blocking its degradation. Taken together, we highlighted an essential role of circCLASP1/PKR/eIF2α axis in Huaier-induced ICD. The findings of our study carried significant translational potential that Huaier might serve as a promising option to achieve long-term tumor remission in patients with TNBC.

Aluminum grating has wide applications in laser systems and photoelectric equipment. Research on the laser damage characteristics of aluminum grating has guiding significance and application value for improving the laser damage resistance. The aim of this study is to investigate the characteristics of damage induced by nanosecond pulsed lasers on the aluminum grating. To better understand the laser damage characteristics of aluminum grating, herein, Maxwell’s equations were numerically solved according to the finite difference time-domain method, and the electric field model of 1,064 nm Gaussian laser damage aluminum grating was established. The simulation results showed that the light field is modulated by the grating; furthermore, the maximum value of the electric field occurred at the ridge of the grating when the laser is irradiated vertically. Analysis suggested that the electric field distribution is in accordance with the laser energy distribution, and the distribution region of the maximum electric field is a vulnerable location. To further verify the local electric field enhancement effect, based on the 1-on-1 laser damage measurement method, an experimental study of the nanosecond laser (@1,064 nm, 6.5 ns) damage to the aluminum grating was carried out. Moreover, the damage morphology was analyzed using a scanning electron microscope (SEM), and the simulation results showed good agreement with the experimental results.

Human milk contains large amounts of small extracellular vesicles (sEVs) and their microRNA cargos, whereas infant formulas contain only trace amounts of sEVs and microRNAs. We assessed the transport of sEVs across the blood-brain barrier (BBB) and sEV accumulation in distinct regions of the brain in brain endothelial cells and suckling mice. We further assessed sEV-dependent gene expression profiles and effects on the dendritic complexity of hippocampal granule cells and phenotypes of EV depletion in neonate, juvenile and adult mice. The transfer of sEVs across the BBB was assessed by using fluorophore-labeled bovine sEVs in brain endothelial bEnd.3 monolayers and dual chamber systems, and in wild-type newborn pups fostered to sEV and cargo tracking (ECT) dams that express sEVs labeled with a CD63-eGFP fusion protein for subsequent analysis by serial two-photon tomography and staining with anti-eGFP antibodies. Effects of EVs on gene expression and dendritic architecture of granule cells was analyzed in hippocampi from juvenile mice fed sEV and RNA-depleted (ERD) and sEV and RNA-sufficient (ERS) diets by using RNA-sequencing analysis and Golgi-Cox staining followed by integrated neuronal tracing and morphological analysis of neuronal dendrites, respectively. Spatial learning and severity of kainic acid-induced seizures were assessed in mice fed ERD and ERS diets. bEnd.3 cells internalized sEVs by using a saturable transport mechanism and secreted miR-34a across the basal membrane. sEVs penetrated the entire brain in fostering experiments; major regions of accumulation included the hippocampus, cortex and cerebellum. Two hundred ninety-five genes were differentially expressed in hippocampi from mice fed ERD and ERS diets; high-confidence gene networks included pathways implicated in axon guidance and calcium signaling. Juvenile pups fed the ERD diet had reduced dendritic complexity of dentate granule cells in the hippocampus, scored nine-fold lower in the Barnes maze test of spatial learning and memory, and the severity of seizures was 5-fold higher following kainic acid administration in adult mice fed the ERD diet compared to mice fed the ERS diet. We conclude that sEVs cross the BBB and contribute toward optimal neuronal development, spatial learning and memory, and resistance to kainic acid-induced seizures in mice.

BackgroundThis study aimed to assess brain oxygenation status and cerebral autoregulation function in subjects with cognitive dysfunction.MethodsThe Montreal Cognitive Assessment (MoCA) was applied to divide the subjects into three groups: cognitive impairment (Group CI, 72.50 ± 10.93 y), mild cognitive impairment (Group MCI, 72.02 ± 9.90 y), and normal cognition (Group NC, 70.72 ± 7.66 y). Near-infrared spectroscopy technology and a non-invasive blood pressure device were used to simultaneously measure changes in cerebral tissue oxygenation signals in the bilateral prefrontal lobes (LPFC/RPFC) and arterial blood pressure (ABP) signals from subjects in the resting state (15 min). The coupling between ABP and cerebral oxyhemoglobin concentrations (Δ [O2Hb]) was calculated in very-low-frequency (VLF, 0.02–0.07 Hz) and low-frequency (LF, 0.07–0.2 Hz) bands based on the dynamical Bayesian inference approach. Pearson correlation analyses were used to study the relationships between MoCA scores, tissue oxygenation index, and strength of coupling function.ResultsIn the interval VLF, Group CI (p = 0.001) and Group MCI (p = 0.013) exhibited significantly higher coupling strength from ABP to Δ [O2Hb] in the LPFC than Group NC. In the interval LF, coupling strength from ABP to Δ [O2Hb] in the LPFC was significantly higher in Group CI than in Group NC (p = 0.001). Pearson correlation results showed that MoCA scores had a significant positive correlation with the tissue oxygenation index and a significant negative correlation with the coupling strength from ABP to Δ [O2Hb].ConclusionThe significantly increased coupling strength may be evidence of impaired cerebral autoregulation function in subjects with cognitive dysfunction. The Pearson correlation results suggest that indicators of brain oxygenation status and cerebral autoregulation function can reflect cognitive function. This study provides insights into the mechanisms underlying the pathophysiology of cognitive impairment and provides objective indicators for screening cognitive impairment in the elderly population.

Hepcidin is a small peptide composed of signal peptide, propeptide, and the bioactive mature peptide from N terminal to C terminal. Mature hepcidin is an antibacterial peptide and iron regulator with eight highly conserved cysteines forming four intramolecular disulfide bonds, giving it a β sheet hairpin-like structure. Hepcidin homologs are found in a variety of vertebrates, especially fish, and their diversity may be associated with different habitats and different levels of pathogens. Dissostichus mawsoni, an Antarctic notothenioid fish that lives in the coldest water unlike most places of the world, with at least two hepcidin variants with eight cysteines. We confirmed the formation process of activated mature hepcidins from D. mawsoni in Chinese hamster ovary (CHO) cell line, obtained recombinant hepcidin protein from prokaryotes, and characterized its binding ability and antibacterial activity against varying bacteria. The expression of hepcidin in CHO cell line showed that the prepropeptide of Dmhep_8cysV1 and Dmhep_8cysV2 cleavage into smaller mature peptide. The antibacterial assay and flow cytometry showed that Dmhep_8cysV1, Dmhep_8cysV2, and Drhep bound to different bacteria and killed them with different minimum inhibitory concentration. These data suggest that hepcidin plays an important role in the innate immunity of D. mawsoni and is of great value in improving resistance to pathogens.

ObjectiveVirtual reality (VR) grasping exercise training helps patients participate actively in their recovery and is a critical approach to the rehabilitation of hand dysfunction. This study aimed to explore the effects of active participation and VR grasping on brain function combined with the kinematic information obtained during VR exercises.MethodsThe cerebral oxygenation signals of the prefrontal cortex (LPFC/RPFC), the motor cortex (LMC/RMC), and the occipital cortex (LOC/ROC) were measured by functional near-infrared spectroscopy (fNIRS) in 18 young people during the resting state, grasping movements, and VR grasping movements. The EPPlus plug-in was used to collect the hand motion data during simulated interactive grasping. The wavelet amplitude (WA) of each cerebral cortex and the wavelet phase coherence (WPCO) of each pair of channels were calculated by wavelet analysis. The total difference in acceleration difference of the hand in the VR grasping movements was calculated to acquire kinematic characteristics (KCs). The cortical activation and brain functional connectivity (FC) of each brain region were compared and analyzed, and a significant correlation was found between VR grasping movements and brain region activation.ResultsCompared with the resting state, the WA values of LPFC, RPFC, LMC, RMC, and ROC increased during the grasping movements and the VR grasping movements, these changes were significant in LPFC (p = 0.0093) and LMC (p = 0.0007). The WA values of LMC (p = 0.0057) in the VR grasping movements were significantly higher than those in the grasping movements. The WPCO of the cerebral cortex increased during grasping exercise compared with the resting state. Nevertheless, the number of significant functional connections during VR grasping decreased significantly, and only the WPCO strength between the LPFC and LMC was enhanced. The increased WA of the LPFC, RPFC, LMC, and RMC during VR grasping movements compared with the resting state showed a significant negative correlation with KCs (p < 0.001).ConclusionThe VR grasping movements can improve the activation and FC intensity of the ipsilateral brain region, inhibit the FC of the contralateral brain region, and reduce the quantity of brain resources allocated to the task. Thus, ordered grasping exercises can enhance active participation in rehabilitation and help to improve brain function.

PurposeTo investigate the intravitreal injection of conbercept as a treatment strategy for proliferative diabetic retinopathy (PDR) with or without center-involved diabetic macular edema (CI-DME) and evaluate its effect on the microvascular changes in the eyes.MethodsIn this prospective study, 43 patients including 29 cases (56 eyes) in CI-DME with PDR patients, and 14 cases (26 eyes) in the non-center involving diabetic macular edema (NCI-DME) with PDR patients were involved in this study. The best corrected visual acuity (BCVA), central retinal thickness (CRT), foveolar avascular zone (FAZ), and macular capillary vessel density (VD) of the superficial retinal capillary plexus (SCP) and deep retinal capillary plexus (DCP) were assessed before and after conbercept treatments for 1, 3, or 6 months.ResultsThe BCVA was significantly increased after conbercept treatment in the eyes of CI-DME patients. After 6 months of treatment with the conbercept, microvascular density of the inferior area in SCP and the central fovea area in DCP increased significantly, regardless of the central fovea involvement. The effect of the conbercept treatment on the VD of NCI-DME was higher than that of CI-DME. Then, after 6 months of treatment, the CRT of patients with CI-DME and NCI-DME were decreased significantly.ConclusionsIn this study, an intravitreal injection of conbercept significantly improved vision, alleviated macular edema in patients with DME. Conbercept treatment also altered the microvascular density in the retina.

BackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID-19. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.MethodsWe analysed serum and PBMC from 17 subjects with a previous PCR-confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after overnight incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.ResultsSeven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.ConclusionsOur results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation.

The problem of residual film pollution in farmland caused by polyethylene mulching films is serious. The application effects of different mulching films combined with drip irrigation on maize planting in the Ili area, Xinjiang, China, were explored. In this study, four types of mulching films and non-mulching treatment were used to study the degradation properties of different plastic mulching and their effects on the dynamic changes of soil moisture, heat, and crop yields of maize under drip irrigation. The results showed that after 160 days of mulching film, only small cracks appeared in polyethylene mulching films. The degradation performance of white oxo-biodegradable film treatment was optimal than the black oxo-biodegradable film treatment. The quality loss rate of the two biodegradable films were 52.26 and 48.48%, respectively. Various mulching film treatments could increase soil moisture in the early stage of maize growth. At the 0–60 cm soil layer, the soil moisture under the white oxo-biodegradable mulching film and black oxo-biodegradable mulching film treatments were lower by 2.75 and 2.66% (p < 0.05) than the white polyethylene mulching film and black polyethylene mulching film treatments. The soil water consumption was highest in the non-mulching treatment, followed by biodegradable film, and the small least value was observed in the polyethylene film treatment. The average soil temperature at depth of 0–15 cm in white polyethylene mulching film, black polyethylene mulching film, white oxo-biodegradable mulching film, and black oxo-biodegradable mulching film treatments were 1.43, 1.16, 0.72 and 0.64°C higher than the non-mulching treatment, respectively. Mulching films treatment played a critical role in increasing production and improving water use efficiency. The black polyethylene mulching film treatment had the highest yield and the best water use efficiency. The black oxo-biodegradable mulching film treatment only reduces the yield by 0.33% compared to the black polyethylene mulching film treatment, and the water use efficiency was only reduced by 0.90% (p > 0.05). Comprehensive analysis showed that black oxo-biodegradable mulching film could be used as a substitute for polyethylene mulching film and can be applied to the production practice of drip irrigation maize in the Ili area.

Hadal trenches are commonly referred to as the deepest areas in the ocean and are characterized by extreme environmental conditions such as high hydrostatic pressures and very limited food supplies. Amphipods are considered the dominant scavengers in the hadal food web. Alicella gigantea is the largest hadal amphipod and, as such, has attracted a lot of attention. However, the adaptive evolution and gigantism mechanisms of the hadal “supergiant” remain unknown. In this study, the whole-body transcriptome analysis was conducted regarding the two hadal amphipods, one being the largest sized species A. gigantea from the New Britain Trench and another the small-sized species Bathycallisoma schellenbergi from the Marceau Trench. The size and weight measurement of the two hadal amphipods revealed that the growth of A. gigantea was comparatively much faster than that of B. schellenbergi. Phylogenetic analyses showed that A. gigantea and B. schellenbergi were clustered into a Lysianassoidea clade, and were distinct from the Gammaroidea consisting of shallow-water Gammarus species. Codon substitution analyses revealed that “response to starvation,” “glycerolipid metabolism,” and “meiosis” pathways were enriched among the positively selected genes (PSGs) of the two hadal amphipods, suggesting that hadal amphipods are subjected to intense food shortage and the pathways are the main adaptation strategies to survive in the hadal environment. To elucidate the mechanisms underlying the gigantism of A. gigantea, small-sized amphipods were used as the background for evolutionary analysis, we found the seven PSGs that were ultimately related to growth and proliferation. In addition, the evolutionary rate of the gene ontology (GO) term “growth regulation” was significantly higher in A. gigantea than in small-sized amphipods. By combining, those points might be the possible gigantism mechanisms of the hadal “supergiant” A. gigantea.

Hepatocellular carcinoma is a common malignant tumor with poor prognosis, poor treatment effect, and lack of effective biomarkers. In this study, bioinformatics analysis of immune-related genes of hepatocellular carcinoma was used to construct a multi-gene combined marker that can predict the prognosis of patients. The RNA expression data of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and immune-related genes were obtained from the IMMPORT database. Differential analysis was performed by Wilcox test to obtain differentially expressed genes. Univariate Cox regression analysis, lasso regression analysis and multivariate Cox regression analysis were performed to establish a prognostic model of immune genes, a total of 5 genes (HDAC1, BIRC5, SPP1, STC2, NR6A1) were identified to construct the models. The expression levels of 5 genes in HCC tissues were significantly different from those in paracancerous tissues. The Kaplan-Meier survival curve showed that the risk score calculated according to the prognostic model was significantly related to the overall survival (OS) of HCC. The receiver operating characteristic (ROC) curve confirmed that the prognostic model had high accuracy. Independent prognostic analysis was performed to prove that the risk value can be used as an independent prognostic factor. Then, the gene expression data of hepatocellular carcinoma in the ICGC database was used as a validation data set for the verification of the above steps. In addition, we used the CIBERSORT software and TIMER database to conduct immune infiltration research, and the results showed that the five genes of the model and the risk score have a certain correlation with the content of immune cells. Moreover, through Gene Set Enrichment Analysis (GSEA) and the construction of protein interaction networks, we found that the p53-mediated signal transduction pathway is a potentially important signal pathway for hepatocellular carcinoma and is positively regulated by certain genes in the prognostic model. In conclusion, this study provides potential targets for predicting the prognosis and treatment of hepatocellular carcinoma patients, and also provides new ideas about the correlation between immune genes and potential pathways of hepatocellular carcinoma.

BackgroundRecent years, the global prevalence of breast cancer (BC) was still high and the underlying molecular mechanisms remained largely unknown. The investigation of prognosis-related biomarkers had become an urgent demand.ResultsIn this study, gene expression profiles and clinical information of breast cancer patients were downloaded from the TCGA database. The differentially expressed genes (DEGs) were estimated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A risk score formula involving five novel prognostic associated biomarkers (EDN2, CLEC3B, SV2C, WT1, and MUC2) were then constructed by LASSO. The prognostic value of the risk model was further confirmed in the TCGA entire cohort and an independent external validation cohort. To explore the biological functions of the selected genes, in vitro assays were performed, indicating that these novel biomarkers could markedly influence breast cancer progression.ConclusionsWe established a predictive five-gene signature, which could be helpful for a personalized management in breast cancer patients.

Background: Targeted urinalysis has been suggested to improve screening efficiency in adults. However, there is no well-defined target population in children yet, with limited information on the risk factors for urinalysis abnormalities.Methods: Children from infants to 17 years old were randomly selected. Dipstick urinalysis was initially performed. Among those who were abnormal, a repeat dipstick or dipstick with microscopic urinalysis was performed for confirmation.Results: In total, 70,822 children were included, with 37,866 boys and 32,956 girls. Prevalence of abnormal urinalysis was 4.3%. Age was significantly associated with abnormal urinalysis, with the highest prevalence among 12–14-year-olds. Girls were 2.0 times more likely to exhibit abnormalities. Compared with children whose guardians had a college degree or higher, those whose guardians had a high school degree or lower had a higher likelihood of abnormalities. Geographic location was also associated with abnormal results.Conclusion: Girls, children aged 12–14 years old, and children whose guardians had a low educational level and children in certain geographic locations were significantly associated with abnormal urinalysis. Identification of children at high risk would contribute to targeted urinalysis screening.

Ralstonia solanacearum, which causes bacterial wilt in a broad range of plants, is considered a “species complex” due to its significant genetic diversity. Recently, we have isolated a new R. solanacearum strain HA4-1 from Hong’an county in Hubei province of China and identified it being phylotype I, sequevar 14M (phylotype I-14M). Interestingly, we found that it can cause various disease symptoms among different potato genotypes and display different pathogenic behavior compared to a phylogenetically related strain, GMI1000. To dissect the pathogenic mechanisms of HA4-1, we sequenced its whole genome by combined sequencing technologies including Illumina HiSeq2000, PacBio RS II, and BAC-end sequencing. Genome assembly results revealed the presence of a conventional chromosome, a megaplasmid as well as a 143 kb plasmid in HA4-1. Comparative genome analysis between HA4-1 and GMI1000 shows high conservation of the general virulence factors such as secretion systems, motility, exopolysaccharides (EPS), and key regulatory factors, but significant variation in the repertoire and structure of type III effectors, which could be the determinants of their differential pathogenesis in certain potato species or genotypes. We have identified two novel type III effectors that were probably acquired through horizontal gene transfer (HGT). These novel R. solanacearum effectors display homology to several YopJ and XopAC family members. We named them as RipBR and RipBS. Notably, the copy of RipBR on the plasmid is a pseudogene, while the other on the megaplasmid is normal. For RipBS, there are three copies located in the megaplasmid and plasmid, respectively. Our results have not only enriched the genome information on R. solanacearum species complex by sequencing the first sequevar 14M strain and the largest plasmid reported in R. solanacearum to date but also revealed the variation in the repertoire of type III effectors. This will greatly contribute to the future studies on the pathogenic evolution, host adaptation, and interaction between R. solanacearum and potato.

Spinal cord injury (SCI) affects more than 2.5 million people worldwide. Spinal cord edema plays critical roles in the pathological progression of SCI. This study aimed to delineate the roles of aquaporin 4 (AQP4) and Na+-K+-Cl− cotransporter 1 (NKCC1) in acute phase edema and tissue destruction after SCI and to explore whether inhibiting both AQP4 and NKCC1 could improve SCI-induced spinal edema and damage. Rat SCI model was established by modified Allen's method. Spinal cord water content, cerebrospinal fluid lactose dehydrogenase (LDH) activity, AQP4 and NKCC1 expression, and spinal cord pathology from 30 min to 7 days after SCI were monitored. Additionally, aforementioned parameters in rats treated with AQP4 and/or NKCC1 inhibitors were assessed 2 days after SCI. Spinal cord water content was significantly increased 1 h after SCI while AQP4 and NKCC1 expression and spinal fluid LDH activity elevated 6 h after SCI. Spinal cord edema and spinal cord destruction peaked around 24 h after SCI and maintained at high levels thereafter. Treating rats with AQP4 inhibitor TGN-020 and NKCC1 antagonist bumetanide significantly reduced spinal cord edema, tissue destruction, and AQP4 and NKCC1 expression after SCI in an additive manner. These results demonstrated the benefits of simultaneously inhibiting both AQP4 and NKCC1 after SCI.

The metabolic disease hyperuricemia (HUA) is caused by presence of excessive serum uric acid (UA), which leads to an increased risk of chronic kidney disease and gout. As a widely used traditional Chinese medicine, Euodiae fructus (ER) has strong anti-inflammatory and analgesic effects, however, its therapeutic effects on HUA and gout have not been investigated. To investigate the potential effects and underlying mechanisms, the effect of ER on proinflammatory cytokines and NLRP3 inflammasome activation was studied in mouse bone marrow macrophages. Moreover, a mouse model of HUA and gouty arthritis was established by coadministration of potassium oxonate (PO) and monosodium urate crystals to mice fed a high-fat diet (HFD) for 37 consecutive days. Oral administration of ER aqueous extract was given 1 hour later after the injection of PO for 10 days. Our study showed that ER is a powerful NLRP3 inhibitor in mouse macrophages. Most importantly, ER (0.75 g/kg) treatment substantially decreased the ankle joint thickness ratio, serum UA, creatinine and blood urea nitrogen levels (p < 0.05). Additionally, ER (0.75 g/kg) dramatically reversed the increases in renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) as well as the decreases in organic anion transporter 1 (OAT1) and ATP binding cassette subfamily G member 2 (ABCG2) levels (p < 0.05). Moreover, ER (0.75 g/kg) markedly ameliorated the production of the serum inflammatory cytokines IL-1β and TNF-α (p < 0.01), and improved the activation of NLRP3 inflammasome signaling in the kidneys. Taken together, these data indicate that ER, a powerful and specific NLRP3 inhibitor, has multiple anti-HUA, anti-gout and anti-inflammatory effects. Our investigation is designed to experimentally support the conventional use of ER-containing classical herbal formulas in the treatment of HUA-related disorders and may add a new dimension to the clinical application of ER.

Patients with atrial fibrillation who take a high bleeding risk and are not candidates for oral anticoagulation therapy are increasingly being referred for left atrial appendage closure (LAAC) as an alternative method of stroke prevention. However, certain manipulations performed during the LAAC procedure, such as transseptal puncture (TSP), may potentially result in vessel injury and lead to cardiac tamponade or even fatality. Clinical significance and management strategies associated with these complications remain controversial. A 74-year-old female patient with atrial fibrillation was referred for left atrial appendage occlusion. During the puncture of the atrial septum, the catheter sheath inadvertently exited through the roof of the right atrium and continued to advance, resulting in pulmonary artery perforation. The patient underwent immediate pericardiocentesis and drainage, followed by surgical exploration for suturing the tear in the pulmonary artery and ligation of the left atrial appendage. This represents the first reported case of a pulmonary artery perforation occurring during a transseptal puncture procedure for left atrial appendage closure. The case exemplifies the feasibility of emergency cardiac surgery as a therapeutic intervention.

BackgroundCommando procedure, the surgical replacement of the mitral and aortic valves combined with reconstruction of the fibrosa fibrous body, is a technical challenge in patients with small aortic and mitral annuli. In this study, we evaluated the safety and early outcomes of the “Chimney” modality of the Commando procedure, in patients with small aortic and mitral annuli, after prior valve surgery, using a self-assembled valved conduit.MethodsFrom April 2021 to April 2022, 30 consecutive cases of the “Chimney” Commando procedure, with a self-assembled valved conduit and other combined cardiac procedures, were fully performed for re-operative patients with small aortic roots. Data were obtained through a medical record review, at the Asian Heart Hospital in Wuhan, China.ResultsThe patient's mean age was 52.7 ± 13.53 years, with 93.3% females. All patients had a previous heart valve surgery, 90% of which had double valve replacement (DVR). Hospital death occurred in 3.3% (n = 1) of the patients, due to malignant arrhythmias and multiorgan failure. Postoperative echocardiogram exams showed that the sizes of the aortic and mitral valve prostheses were 24.23 ± 1.60 mm and 28.33 ± 1.21 mm, respectively. All patients had intact intervalvular fibrosa (IVF) repair and no patient had any aberration in the left heart chamber communication. With the exception of one postoperative sick sinus syndrome and one re-sternotomy for bleeding, there were no significant postoperative complications, such as mortality, renal failure requiring ongoing dialysis, or mediastinitis. Echocardiography exams in the sixth postoperative month showed that the mean gradients of the aortic and mitral valves were 16.26 ± 6.44 mmHg and 11.24 ± 4.90 mmHg, respectively.ConclusionsIn comparison with the standard Commando operation, the early outcomes and safety of the “Chimney” Commando procedure proved to be a feasible therapeutic option for patients with small aortic and mitral annuli, after prior valve operations. This approach enables the enlargement of the aortic and mitral annuli and the implantation of the necessary valve prosthesis.

Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity via multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent.

Although COVID-19 is primarily a respiratory disease, its neurological complications, such as ischemic stroke (IS), have aroused growing concerns and reports. However, the molecular mechanisms that underlie IS and COVID-19 are not well understood. Therefore, we implemented transcriptomic analysis from eight GEO datasets consist of 1191 samples to detect common pathways and molecular biomarkers in IS and COVID-19 that help understand the linkage between them. Differentially expressed genes (DEGs) were detected for IS and COVID-19 separately for finding shared mechanisms and we found that immune-related pathways were outlined with statistical significance. JAK2, which was identified as a hub gene, was supposed to be a potential therapeutic gene targets during the immunological process of COVID-19 and IS. Besides, we found a decrease in the proportion of CD8+ T and T helper 2 cells in the peripheral circulation of both COVID and IS patients, and NCR3 expression was significantly correlated with this change. In conclusion, we demonstrated that transcriptomic analyses reported in this study could make a deeper understanding of the common mechanism and might be promising for effective therapeutic for IS and COVID-19.

Based on human motivation theory and self-determination theory, this study investigated the impact of coaches’ transformational leadership on athletes’ well-being, and the influences of gender and athletes’ basic psychological needs. The survey objects comprised of 432 athletes participating in the Hebei Games in China. The results showed that coaches’ transformational leadership could significantly and positively predict athletes’ well-being. Basic psychological needs had a mediating effect on the relationship between coaches’ transformational leadership and athletes’ well-being. Gender significantly moderated the effect between athletes’ basic psychological needs satisfaction and subjective well-being. Compared with male athletes, female athletes had their basic psychological needs met, and the improvement in their well-being was more significant than the males. Coaches should adapt their transformational leadership to directly improve athletes’ well-being and indirectly achieve their well-being by satisfying the athletes’ basic psychological needs.

AimAlzheimer’s disease (AD) and ischemic stroke (IS), two major neurological diseases, are suggested to be associated in clinical and pathophysiological levels. Previous studies have provided some insights into the possible genetic mechanisms behind the correlation between AD and IS, but this issue is still not clear. We implemented transcriptomic analysis to detect common hub genes and pathways to help promote the understanding of this issue.Materials and methodsFour gene expression profiling datasets (GSE16561, GSE58294, GSE63060, and GSE63061) of peripheral whole blood, which contain 108 IS samples, 284 AD samples, and 285 matched controls, were employed to detect differentially expressed genes (DEGs) for AD and IS, which were further analyzed for shared biological pathways, candidate drugs, and transcription factors. Protein-protein interaction (PPI) network and drug-target interaction analysis were applied to identify hub genes and drug targets, respectively. Result verification was done with other independent datasets (GSE37587, GSE46480, and GSE140829). The difference in proportions of various immune cells in the peripheral blood of AD and IS patients were evaluated using CIBERSORT.ResultsWe identified 74 DEGs and 18 biological processes with statistical significance shared by AD and IS, 9 of which were immune-related pathways. Five hub genes scored high in the topological analysis of the PPI network, and we also found eight drug target genes and candidate drugs which were associated with AD and IS. As for immunological changes, an increase in the proportion of M0 macrophages was found in the peripheral circulation of both AD and IS patients, and SOD1 expression was significantly correlated with this change.ConclusionCollectively, the common DEGs and shared pathways found in this study suggest a potential shared etiology between AD and IS, behind which immune system, particularly the M0 macrophage elevation, might have important roles. While, the shared hub genes, potential therapeutic gene targets and drugs reported in this study provide promising treatment strategies for AD and IS.

ObjectiveAt present, urban community aging has become a new way to solve aging problem and has made outstanding contributions to alleviate current aging dilemma. However, there are still deficiencies in the services provided by this new method of community-based elderly care for the elderly who are left alone. Therefore, this paper explores the problems of government policies, facilities and services for the elderly who have lost their independence, analyzes the reasons behind them, and proposes countermeasures.MethodThis paper introduces and compares the government's current services for the elderly who are left alone in the city at the level of community-based elderly care services. From the existing literature, we find that most researchers have studied the single-parent family as an individual, exploring its elderly care dilemma, analyzing the causes and proposing countermeasures. It introduces and summarizes the situation of the elderly left alone in Taiyuan, the government's policies on the elderly left alone and community elderly care, the current community elderly care construction in Taiyuan, and the service models provided by the government.Results/DiscussionThis paper provides a detailed description and in-depth analysis of the lack of elderly care protection in communities, and analyzes the underlying causes. Activity theory suggests that even though older people are no longer in the same mental state as younger people, they can still enhance their self-worth through active participation in social activities and gain a sense of social identity through social activities. The services provided by social organizations are typical services purchased by the Health and Welfare Commission for the elderly who are left alone, and it is feasible to gradually extend the services to provide more specialized community-based elderly care services for the elderly who are left alone. Therefore, this study takes the use of services provided by social organizations as an example to understand the current situation of services received and used by the elderly who are left alone, and concludes that the services are weakly accessible, and finally proposes suggestions to improve the accessibility of services in three aspects: supply, delivery, and use.

Fusarium proliferatum is the principal etiological agent of rice spikelet rot disease (RSRD) in China, causing yield losses and fumonisins contamination in rice. The intraspecific variability and evolution pattern of the pathogen is poorly understood. Here, we performed whole-genome resequencing of 67 F. proliferatum strains collected from major rice-growing regions in China. Population structure indicated that eastern population of F. proliferatum located in Yangtze River with the high genetic diversity and recombinant mode that was predicted as the putative center of origin. Southern population and northeast population were likely been introduced into local populations through gene flow, and genetic differentiation between them might be shaped by rice-driven domestication. A total of 121 distinct genomic loci implicated 85 candidate genes were suggestively associated with variation of fumonisin B1 (FB1) production by genome-wide association study (GWAS). We subsequently tested the function of five candidate genes (gabap, chsD, palA, hxk1, and isw2) mapped in our association study by FB1 quantification of deletion strains, and mutants showed the impact on FB1 production as compared to the wide-type strain. Together, this is the first study to provide insights into the evolution and adaptation in natural populations of F. proliferatum on rice, as well as the complex genetic architecture for fumonisins biosynthesis.

The incidence of hyperuricemia (HUA) and gout continuously increases and has become a major public health problem. The gut microbiota, which colonizes the human intestine, has a mutually beneficial and symbiotic relationship with the host and plays a vital role in the host’s metabolism and immune regulation. Structural changes or imbalance in the gut microbiota could cause metabolic disorders and participate in the synthesis of purine-metabolizing enzymes and the release of inflammatory cytokines, which is closely related to the occurrence and development of the metabolic immune disease HUA and gout. The gut microbiota as an entry point to explore the pathogenesis of HUA and gout has become a new research hotspot. This review summarizes the characteristics of the gut microbiota in patients with HUA and gout. Meanwhile, the influence of different dietary structures on the gut microbiota, the effect of the gut microbiota on purine and uric acid metabolism, and the internal relationship between the gut microbiota and metabolic endotoxemia/inflammatory factors are explored. Moreover, the intervention effects of probiotics, prebiotics, and fecal microbial transplantation on HUA and gout are also systematically reviewed to provide a gut flora solution for the prevention and treatment of related diseases.

Background: Blocking and even reversing gastric precancerous lesions (GPL) is a key measure to lower the incidence of gastric cancer. Atractylenolide III (AT-III) is a mainly active component of the Atractylodes rhizome and has been widely used in tumor treatment. However, the effects of AT-III on GPL and its mechanisms have not been reported.Methods: H & E staining and AB-PAS staining were employed to evaluate the histopathology in the gastric mucosa. In parallel, CD34 immunostaining was performed for angiogenesis assessment, and transmission electron microscope for microvessel ultrastructural observation. Investigation for the possible mechanism in vivo and in vitro was conducted using immunohistochemistry, RT-qPCR and western blotting.Results: In most GPL specimens, AT-III treatment reduced microvascular abnormalities and attenuated early angiogenesis, with the regression of most intestinal metaplasia and partial dysplasia. Meanwhile, the expression of VEGF-A and HIF-1α was enhanced in GPL samples of model rats, and their expressions were decreased in AT-III-treated GPL rats. Moreover, DLL4 mRNA and protein expression were higher in GPL rats than in control rats. DLL4 protein expression was significantly enhanced in human GPL tissues. In addition, AT-III treatment could diminish DLL4 mRNA level and protein expression in the MNNG-induced GPL rats. In vitro study showed that in AGS and HGC-27 cells, DLL4 mRNA level and protein expression were significantly decreased after AT-III treatment. However, AT-III had no significant regulatory effect on Notch1 and Notch4.Conclusion: AT-III treatment is beneficial in lessening gastric precancerous lesions and attenuating angiogenesis in rats, and that may be contributed by the decrease of angiogenesis-associated HIF-1α and VEGF-A, and downregulation of DLL4.

The relationship between pore architecture and structure performance needs to be explored, as well as confirm the optimized porous structure. Because of the linear correlation between constant C and pore architecture, triply periodic minimal surface (TPMS) based porous structures could be a controllable model for the investigation of the optimized porous structure. In the present work, three types of TPMS porous scaffolds (S, D and G) combined with four constants (0.0, 0.2, 0.4 and 0.6) were designed, and built successfully via the selective laser melting (SLM) technology. The designed feature and mechanical property of porous scaffolds were investigated through mathematical method and compression test. And the manufactured samples were co-cultured with rMSCs for the compatibility study. The results indicated that the whole manufacturing procedure was good in controllability, repeatability, and accuracy. The linear correlation between the porosity of TPMS porous scaffolds and the constant C in equations was established. The different TPMS porous scaffolds possess the disparate feature in structure, mechanical property and cell compatibility. Comprehensive consideration of the structure features, mechanical property and biology performance, different TPMS structures should be applied in appropriate field. The results could guide the feasibility of apply the different TPMS architectures into the different part of orthopedic implants.

A promising large-scale energy storage is underground compressed air energy storage (CAES) in lined rock caverns. To ensure the safety and stability of storage caverns because of the influence of periodic injection during production, it is crucial to understand the mechanical behavior of lining concrete under different complex stress paths. In this study, three types of uniaxial compressive fatigue test and uniaxial creep test were conducted on concrete. The following conclusions were obtained from the results. 1) The irreversible deformation after the interval was larger than that before the interval in the discontinuous multi-step cyclic loading (DMCL) test. 2) Loading velocity significantly influenced concrete fatigue, and the irreversible deformation in the cycle of low loading velocity was greater than that in the cycle of high loading velocity. 3) The residual strain increased with an increase in stress level. 4) The creep strain increased with an increase in stress level during the multi-step creep loading test; the fractional derivative results were more consistent with the experimental results. 5) The permeability of concrete increased rapidly under the influence of an external force when the stress level exceeded 0.73.