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Abstract Purpose In this study, we aim to explore the efficacy of paxlovid on reducing mortality of COVID-19 patients in clinical setting, especially whether paxlovid modifies the risk of death in these severe and critical patients. Methods Our retrospective cohort study was conducted on the medical records of patients, consecutively admitted for COVID-19 to five hospitals in Chongqing, China from Dec 8, 2022 to Jan 20, 2023. Based on whether patients received paxlovid during their hospitalization, patients were grouped as paxlovid group and non-paxlovid group. We used 1:1 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between groups. Statistical analysis were performed by SPSS 23.0. The differences in 28-day mortality between these two groups and its influencing factors were the main results we focused on. Results There were 1018 patients included in our study cohort. With 1:1 ratio PSM, each of the paxlovid group and non-paxlovid group included 237 patients. The results showed that patients using paxlovid have a lower 28-day mortality in overall population either before PSM (OR 0.594, 95% CI 0.385–0.917, p = 0.019) or after PSM (OR 0.458, 95% CI 0.272–0.774, p = 0.003) with multivariable adjusted logistic regression models. Meanwhile, in severe subgroup, it showed similar findings.With paxlovid treatment, it showed a significantly lower 28-day mortality in severe subgroup both before PSM (28% vs.41%, p = 0.008) and after PSM (19% vs.32%, p = 0.007). Conclusion Paxlovid can significantly reduce the risk of 28-day mortality in overall population and severe subgroup patients.This study distinguished the severe subgroup patients with COVID-19 who benefit more from paxlovid treatment.

Abstract Background UNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A’s functions in gliomas. Methods Online databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity. Results By comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p

BackgroundObservational studies and clinical trials have implicated polyunsaturated fatty acids (PUFAs) in potentially safeguarding against diabetic microvascular complication. Nonetheless, the causal nature of these relationships remains ambiguous due to conflicting findings across studies. This research employs Mendelian randomization (MR) to assess the causal impact of PUFAs on diabetic microvascular complications.MethodsWe identified instrumental variables for PUFAs, specifically omega-3 and omega-6 fatty acids, using the UK Biobank data. Outcome data regarding diabetic microvascular complications were sourced from the FinnGen Study. Our analysis covered microvascular outcomes in both type 1 and type 2 diabetes, namely diabetic neuropathy (DN), diabetic retinopathy (DR), and diabetic kidney disease (DKD). An inverse MR analysis was conducted to examine the effect of diabetic microvascular complications on PUFAs. Sensitivity analyses were performed to validate the robustness of the results. Finally, a multivariable MR (MVMR) analysis was conducted to determine whether PUFAs have a direct influence on diabetic microvascular complications.ResultsThe study indicates that elevated levels of genetically predicted omega-6 fatty acids substantially reduce the risk of DN in type 2 diabetes (odds ratio (OR): 0.62, 95% confidence interval (CI): 0.47–0.82, p = 0.001). A protective effect against DR in type 2 diabetes is also suggested (OR: 0.75, 95% CI: 0.62–0.92, p = 0.005). MVMR analysis confirmed the stability of these results after adjusting for potential confounding factors. No significant effects of omega-6 fatty acids were observed on DKD in type 2 diabetes or on any complications in type 1 diabetes. By contrast, omega-3 fatty acids showed no significant causal links with any of the diabetic microvascular complications assessed.ConclusionsOur MR analysis reveals a causal link between omega-6 fatty acids and certain diabetic microvascular complications in type 2 diabetes, potentially providing novel insights for further mechanistic and clinical investigations into diabetic microvascular complications.

This study employed Mendelian randomization (MR) analysis to systematically investigate the potential connections between gut microbiota and the risk of glioblastoma (GBM). We identified 12 microbial groups closely associated with the incidence risk of GBM. Subsequently, MR analysis was conducted on 1,091 blood metabolites and 309 metabolite ratios, revealing 19 metabolites that exert an impact on the occurrence of GBM. Hypothesizing that gut microbiota may influence the risk of glioblastoma multiforme by modulating these metabolites, we performed MR analyses, considering each microbial group as exposure and each metabolite as an outcome. Through these analyses, we constructed a regulatory network encompassing gut microbiota, metabolites, and GBM, providing a novel perspective for a deeper understanding of the role of the gut-brain axis in the pathogenesis of GBM. This research offers crucial insights into how gut microbiota may affect the risk of GBM by regulating specific metabolites. The identified regulatory network of the gut-brain axis may play a significant role in the formation and development of GBM, providing valuable information for future research and therapeutic interventions.

As a unique geological hazard in a high-geo-stress environment, rockburst happens with strong suddenness, randomness, and destructiveness, but the mechanism of its occurrence in a deep-buried tunnel in a high-geo-stress environment needs further study. Based on the analyses of the stress field of the rockburst section of Ping’an Tunnel, which is over-long and deep-buried, the occurrence mechanism of rockburst is figured out. Furtherly, the intensity and location of rockburst are predicted by using the rockburst criterion. Results show that there exists large compressive stress at the side wall of the tunnel, which is the main cause of rockburst. Under a high-geo-stress condition, due to the existence of unfavorable factors like structural planes, high intensity rockburst is likely to happen in the middle of the tunnel face after the sudden release of original rock stress. Arranging stress-releasing holes in the rockburst section can effectively reduce the possibility of rockburst by releasing the original rock stress in advance. The research results can deepen the understanding of the mechanism of rockburst in a high-geo-stress environment and provide scientific basis for the prevention and control of rockburst in similar engineering projects.

Abstract Purpose The specific neurovascular compression (NVC) event responsible for the symptomatic manifestation of hemifacial spasm (HFS) remains difficult to assess accurately using magnetic resonance imaging (MRI). We aim to evaluate the MRI characteristics of HFS. Method We retrospectively included patients with HFS and divided them into a test group (n = 186) and a validation group (n = 28). The presence, severity, and offending vessel type of NVC in each portion, and the orientation of the offending vessel around the facial nerve, were recorded. Conditional logistic regression analyses were performed to evaluate correlations using test group. The validation group was used to verify whether our findings improved diagnostic performance. Results Deformity in the proximal cisternal segment was significantly correlated with HFS occurrence (odds ratio [OR]: 256.58, p = .002), whereas contact was not (p = .233). Both contact and deformity in the root detachment point (OR: 19.98 and 37.22, p

Abstract Glioblastoma (GBM) is notorious for malignant neovascularization that contributes to undesirable outcome. However, its mechanisms remain unclear. This study aimed to identify prognostic angiogenesis‐related genes and the potential regulatory mechanisms in GBM. RNA‐sequencing data of 173 GBM patients were obtained from the Cancer Genome Atlas (TCGA) database for screening differentially expressed genes (DEGs), differentially transcription factors (DETFs), and reverse phase protein array (RPPA) chips. Differentially expressed genes from angiogenesis‐related gene set were extracted for univariate Cox regression analysis to identify prognostic differentially expressed angiogenesis‐related genes (PDEARGs). A risk predicting model was constructed based on 9 PDEARGs, namely MARK1, ITGA5, NMD3, HEY1, COL6A1, DKK3, SERPINA5, NRP1, PLK2, ANXA1, SLIT2, and PDPN. Glioblastoma patients were stratified into high‐risk and low‐risk groups according to their risk scores. GSEA and GSVA were applied to explore the possible underlying GBM angiogenesis‐related pathways. CIBERSORT was employed to identify immune infiltrates in GBM. The Pearson's correlation analysis was performed to evaluate the correlations among DETFs, PDEARGs, immune cells/functions, RPPA chips, and pathways. A regulatory network centered by three PDEARGs (ANXA1, COL6A1, and PDPN) was constructed to show the potential regulatory mechanisms. External cohort of 95 GBM patients by immunohistochemistry (IHC) assay demonstrated that ANXA1, COL6A1, and PDPN were significantly upregulated in tumor tissues of high‐risk GBM patients. Single‐cell RNA sequencing also validated malignant cells expressed high levels of the ANXA1, COL6A1, PDPN, and key DETF (WWTR1). Our PDEARG‐based risk prediction model and regulatory network identified prognostic biomarkers and provided valuable insight into future studies on angiogenesis in GBM.

Abstract Background Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. Methods We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. Results In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1%. During the 7-year follow-up, 575 cases (15.5%) of incident diabetes were identified. Participants with possible sarcopenia were more likely to have new-onset T2DM than those without possible sarcopenia (hazard ratio: 1.27, 95% confidence interval: 1.07–1.50; p = 0.006). In subgroup analysis, we found a significant association between possible sarcopenia and T2DM in individuals aged

Hemorrhagic stroke (HS) is associated with severe morbidity and high mortality. Identifying the trigger factors for HS is critical for disease prevention. This study aimed to assess the associations between short-term environmental triggers (STETs) and HS risk. We systematically searched six databases for articles published up to September 9, 2022. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using random-effect models to evaluate the associations between STETs and the risk of HS. Heterogeneity was assessed using Cochran Q and I2 tests. A total of 63 studies were included for analysis. Of these, 40 focused on air pollutants and 23 on meteorological factors. Pooling results showed that exposure to particulate matter 2.5 (PM2.5; OR, 1.003 per 10 μg/m3; 95% CI, 1.001–1.007), sulfur dioxide (SO2; OR, 1.022 per 10 ppb; 95% CI, 1.005–1.040), and nitrogen dioxide (NO2; OR, 1.026 per 10 ppb; 95% CI, 1.004–1.047) was associated with an increase in HS risk. Moreover, exposure to PM2.5 (OR, 1.018 per 10 μg/m3; 95% CI, 1.009–1.027) and SO2 (OR, 1.102 per 10 ppb; 95% CI, 1.010–1.204) was positively associated with the risk of intracerebral hemorrhage. In addition, extreme temperature, high pressures, high and low relative humidity were potentially associated with HS risk. Targeted preventive measures to limit the effect of these air pollutants and extreme meteorological factors should be taken to reduce the HS disease burden. Further studies are warranted to verify these findings.

ObjectivesObservational studies have revealed that socioeconomic status is associated with neurological disorders and aging. However, the potential causal effect between the two remains unclear. We therefore aimed to investigate the causal relationship between household income status and genetic susceptibility to neurological diseases using a bidirectional Mendelian randomization (MR) study.MethodsAn MR study was conducted on a large-sample cohort of the European population pulled from a publicly available genome-wide association study dataset, using a random-effects inverse-variance weighting model as the main standard. MR-Egger regression, weighted median, and maximum likelihood estimation were also performed concurrently as supplements. A sensitivity analysis, consisting of a heterogeneity test and horizontal pleiotropy test, was performed using Cochran’s Q, MR-Egger intercept, and MR-PRESSO tests to ensure the reliability of the conclusion.ResultsThe results suggested that higher household income tended to lower the risk of genetic susceptibility to Alzheimer’s disease (odds ratio [OR]: 0.740, 95% confidence interval [CI] = 0.559–0.980, p-value = 0.036) and ischemic stroke (OR: 0.801, 95% CI = 0.662–0.968, p-value = 0.022). By contrast, higher household income tended to increase the risk of genetic susceptibility to Parkinson’s disease (OR: 2.605, 95% CI = 1.413–4.802, p-value = 0.002). No associations were evident for intracranial hemorrhage (OR: 1.002, 95% CI = 0.607–1.653, p-value = 0.993), cerebral aneurysm (OR: 0.597, 95% CI = 0.243–1.465, p-value = 0.260), subarachnoid hemorrhage (OR: 1.474, 95% CI = 0.699–3.110, p-value = 0.308), or epilepsy (OR: 1.029, 95% CI = 0.662–1.600, p-value = 0.899). The reverse MR study suggested no reverse causal relationship between neurological disorders and household income status. A sensitivity analysis verified the reliability of the results.ConclusionOur results revealed that the populations with a superior household income exhibit an increased predisposition of genetic susceptibility to Parkinson’s Disease, while demonstrating a potential decreased genetic susceptibility to ischemic stroke and Alzheimer’s disease.

In order to promote the integration of leisure agriculture and red cultural tourism, this paper improves the big data technology and combines the actual needs of tourism data fusion to construct an integrated analysis system of leisure agriculture and red cultural tourism-based big data. Through the data collection layer and the data information provided by the third party, this paper uses various technologies such as cloud computing and fuzzy recognition to classify and store massive amounts of data and information and establish a data warehouse to integrate various information resources to serve various smart applications. In addition, this paper combines the characteristics of leisure agriculture and red cultural tourism to integrate the two and builds an intelligent system with the support of big data technology. Finally, this paper carries out the performance verification of this system through experimental research. From the research results, it can be seen that the system constructed in this paper meets the needs of the integration of leisure agriculture and red cultural tourism.

Abstract Problem background Early detection of acute ischemic stroke (AIS) may provide patients with benefits against harmful health and financial impacts. The use of non-contrast computed tomography images for early detect of the infarct remains controversial. Materials & methods Here, we used the UCATR algorithm to extract the pixel values of the infarct and the corresponding contralateral healthy area as the control surface in each NCCT slice for the whole brain. Magnetic resonance imaging results were used to verify both areas. We found significant pathological changes in the infarct compared with the corresponding contralateral healthy area in each NCCT slice. Attained results Our approach validated that NCCT can be used to detect the lesion area in the early stage of AIS. Conclusions With obvious advantages such as saving time and the ability to quantify the infarct volume, this approach could help more patients survive the fatal and irreversible pathological process of AIS and improve their quality of life after AIS treatment.

Sensitive detection and accurate diagnosis/prognosis of glioma remain urgent challenges. Herein, dispersed magnetic covalent organic framework nanospheres (MCOF) with uniformed Fe3O4 nano-assembly as cores and high-crystalline COF as shells were prepared by monomer-mediated in-situ interface growth strategy. Based on the unique interaction between MCOF and hairpin DNA, a fluorescent signal amplified miRNA biosensor was constructed. It could realize the sensitive detection of miRNA-182 in different matrixes, where the detection limit, linearity range and determination coefficient (R2) in real blood samples reached 20 fM, 0.1 pM–10 pM and 0.991, respectively. Also, it possessed good stability and precision as observed from the low intra-day/inter-day RSD and high extraction recovery. As a result, it could quantify miRNA-182 in serum of glioma patients, the concentration of which was significantly higher than that of healthy people and obviously decreased after surgery. Finally, a proof-of-concept capillary chip system using this biosensor was proposed to realize the visualized detection of miRNA-182 in microsample. These findings suggest a robust way for sensitive detection and accurate diagnosis/prognosis of glioma.

Few methods exist to add a carbon and nitrogen atom across an unfunctionalized alkene. Here the authors show a method to regio- and diastereoselectively add aryl and amino groups to terminal and internal alkenes, via nickel catalysis and a removable directing group.

The planting of Cyperus esculentus, a member of the grass family Cyperaceae which includes nut sedge weeds, is being increasingly promoted in northern China’s semi-arid and arid regions. Yet the effects of planting C. esculentus upon soil quality and soil microbial characteristics of sandy land remain unclear. This study examined the short-term (1 year) impact of this grass species on soil microbial biomass indices, enzymatic activities, and microbiome characteristics in the Horqin Sandy Land area of China. The results show that planting C. esculentus could increase microbial biomass in the form of carbon (MBC), nitrogen (MBN), and phosphorus (MBP), but it negligibly influenced the enzymatic activities of soil β-1,4-glucosidase (BG), cellobiohydrolase (CBH), leucine aminopeptidase (LAP), and β-1,4-N-acetaminoglycosidase (NAG). Over 1 year, we found that planting C. esculentus significantly increased the soil bacterial richness and diversity of sandy land, yet also altered community composition of soil bacteria and eukaryotes in way that could promote their homogenization. In this respect, the relative abundances of Acidobacteria and Proteobacteria significantly decreased and increased, respectively; hence, they may be considered for use as important indicators of soil nutrient-rich conditions. Overall, the results could be explained by greater soil organic carbon (SOC) and total nitrogen (TN), mainly derived from cumulative plant litter input to soils, which then increased the sandy soil’s C:N ratio. Future research should focus on exploring the long-term effects of planting C. esculentus on soil quality and soil microbial characteristics of sandy lands in China and abroad.

ObjectiveAs an important biomarker to reflect tumor cell proliferation and tumor aggressiveness, Ki-67 is closely related to the high early recurrence rate and poor prognosis, and pretreatment evaluation of Ki-67 expression possibly provides a more accurate prognosis assessment and more better treatment plan. We aimed to develop a nomogram based on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) combined with T1 mapping to predict Ki-67 expression in hepatocellular carcinoma (HCC).MethodsThis two-center study retrospectively enrolled 148 consecutive patients who underwent preoperative Gd-EOB-DTPA-enhanced MRI T1 mapping and surgically confirmed HCC from July 2019 to December 2020. The correlation between quantitative parameters from T1 mapping, ADC, and Ki-67 was explored. Three cohorts were constructed: a training cohort (n = 73) and an internal validation cohort (n = 31) from Shunde Hospital of Southern Medical University, and an external validation cohort (n = 44) from the Sixth Affiliated Hospital, South China University of Technology. The clinical variables and MRI qualitative and quantitative parameters associational with Ki-67 expression were analyzed by univariate and multivariate logistic regression analyses. A nomogram was developed based on these associated with Ki-67 expression in the training cohort and validated in the internal and external validation cohorts.ResultsT1rt-Pre and T1rt-20min were strongly positively correlated with Ki-67 (r = 0.627, r = 0.607, P < 0.001); the apparent diffusion coefficient value was moderately negatively correlated with Ki-67 (r = -0.401, P < 0.001). Predictors of Ki-67 expression included in the nomogram were peritumoral enhancement, peritumoral hypointensity, T1rt-20min, and tumor margin, while arterial phase hyperenhancement (APHE) was not a significant predictor even included in the regression model. The nomograms achieved good concordance indices in predicting Ki-67 expression in the training and two validation cohorts (0.919, 0.925, 0.850), respectively.ConclusionsT1rt-Pre and T1rt-20min had a strong positive correlation with the Ki-67 expression in HCC, and Gd-EOB-DTPA enhanced MRI combined with T1 mapping-based nomogram effectively predicts high Ki-67 expression in HCC.

Colletotrichum siamense infected the petiole and crown of strawberry (Fragaria × ananassa), and this anthracnose threatens strawberry production heavily in Hubei province. Characteristic the variation of transcript caused by C. siamense is important for anthracnose control of strawberry. In this study, RNA-seq analysis was used to monitor the strawberry transcripts in response of C. siamense at 0- and 6-days post-inoculation based on lesion measurement and hypha observation. The number of clean reads achieved for each sample was ranged from 5.68 to 8.12 Gb. The 0DPM vs 0DPI group had seven significantly differentially expressed transcripts, whereas the 6DPM vs 6DPI group exhibited 12,097 significantly differentially expressed transcripts. The differentially expressed transcripts of 6DPM vs 6DPI group were enriched in ‘metabolic process’ and ‘biological process’ in the biological process category and ‘oxidoreductase activity’ in the molecular function category by GO analysis. While ‘Starch and sucrose metabolism’, ‘Plant hormone signal transduction’ and ‘Phenylpropanoid biosynthesis’ pathways were significantly enriched by KEGG analysis. The expression of MYC2 in JA, the ETR in Eth and, the SnRK2 and ABF in ABA signal transduction pathways were promoted, whereas expression of the PR1 in SA, JZA1 in JA, and ERF in Eth signal transduction pathways were inhibited. In addition, the transcripts that encode enzymes involved in the ‘Phenylpropanoid biosynthesis’ pathway, such as PAL, CYP73A, CSE, 4CL, HTC, GSE and COMT were all inhibited showed by RNA-seq and qRT-PCR. This study provided basic information of strawberry responding to C. siamense infection.

Histone acetyltransferase (HAT) and histone deacetylase (HDAC) family members control histone acetylation levels to regulate gene expression and play significant roles in microbe interactions and abioticstress responses. However, the HAT and HDAC family members in citrus have not yet been identified, and their responses to drought (abiotic stress) and arbuscular mycorrhizal fungi (AMF) colonization, remain unknown. In the present study, HAT and HDAC family genes were characterized in the citrus genome. A total of 14 CsHATs and 11 CsHDACs were identified in the citrus genome, of which 8 CsHATs and 7 CsHDACs showed syntenic relationships with Arabidopsis HATs and HDACs, respectively. Furthermore, the 14 CsHATs were classified into GNAT-MYST, TAFII250, MYST, CBP, and one citrus-unique family. The 11 CsHDACs were classified into SIR2, HD2, and RPD3/HDA1. Gene expression analysis showed AMF colonizationor drought induced the expression of CsHAT1, 2, 6, 7, 9, 11, 12, and 14, and repressed CsHDAC1, 2, 5, 6, 8, and 10. The regulation of HAT and HDAC expression was not always consistent with the cis-elements identified in their promoters. The present study offers useful insights into the citrus HAT and HDAC gene families and their expression in response to AMF colonization and drought stress.

Summary: Precipitation may increase or decrease by different intensities, but the pattern and mechanism of soil microbial community assembly under various precipitation changes remain relatively underexplored. Here, although ±30% precipitation caused a small decrease (∼19%) in the within-treatment taxonomic compositional dissimilarity through the deterministic competitive exclusion process in a steppe ecosystem, ±60% precipitation caused a large increase (∼35%) in the dissimilarity through the stochastic ecological drift process (random birth/death), which was in contrast with the traditional thought that increasing the magnitude of environmental changes (e.g., from +30% to +60%) would elevate the importance of deterministic relative to stochastic processes. The increased taxonomic dissimilarity/stochasticity under ±60% precipitation translated into functional dissimilarity/stochasticity at the gene, protein, and enzyme levels. Overall, our results revealed the distinctive pattern and mechanism of precipitation changes affecting soil microbial community assembly and demonstrated the need to integrate microbial taxonomic information to better predict their functional responses to precipitation changes.

Crown rot is one of the most destructive diseases of cultivated strawberry. The DOF family transcription factors, which involved in biotic stress, has not been studied in responding to strawberry crown rot. In this study, the DOFs of Fragaria × ananassa, F. iinumae, F. nilgerrensis, F. viridis, and F. vesca were characterized. One hundred and eighteen FaDOFs, twenty-two FiDOFs, twenty-three FnDOFs, twenty-five FviDOFs and thirty-seven FvDOFs were identified. Gene cluster analysis showed nearly seventy segmental duplication and seventeen tandem duplications for DOF family expansion in octaploid strawberry. In addition, 59 FaDOFs showed syntenic relationships with 32 AtDOFs, which were located on all F.×ananassa chromosomes except Fvb4-1 and Fvb4-2. Except for five DOFs of diploid strawberries had syntenic relationships to one FaDOF, most of them corresponded to multiple FaDOFs. Gene expression analysis revealed that 107 FaDOFs were expressed in crown, and most of them were downregulated by crown rot, while some FaDOFs such as FaDOF107, 12, 82, 91, 90 and 101 were upregulated, whose regulation was not always consistent with the cis-elements in their promoters. Together, these results provided a basis for further functional studies of the FaDOFs.

The calcium-dependent protein kinases (CDPKs, also termed CPKs) are a large, diverse protein family that play significant roles in biotic and abiotic stress responses in plants. However, CDPKs in citrus are relatively unknown, as are their responses to drought stress (abiotic stress) and arbuscular mycorrhizal fungi (AMF) colonization. In this study, the citrus CDPKs were characterized by analyzing the presence of EF-hand and Pkinase domains and searching the citrus genome. Twenty-nine Citrus sinensis CDPKs (CsCDPKs) were identified on at least nine chromosomes in the citrus genome. Three clusters were found on chromosome 4 with three or two CsCDPKs, and 17 CsCDPKs showed syntenic relationships with Arabidopsis thaliana CPKs (AtCPKs). Twenty-nine CsCDPKs were expressed in the roots, and the regulation of the CsCDPKs was not always consistent with the cis-elements in their promoters. CsCDPK1, 2, 5, 6, 7, 8, 9, 13, 17, 18, 19, 21, 24, 25, 26, 27 and 29 were upregulated by AMF colonization, and CsCDPK3, 7 and 28 were downregulated. Drought-repressed expression of CsCDPK10, 11, 12, 15 and 16 induced CsCDPK20 and 22. Furthermore, AMF colonization and drought stress exerted synergistic effects; the expression levels of CsCDPK20 and CsCDPK22 were repressed in W_AMF treatment (well-watered with AMF) but induced in D_AMF treatment (drought stress with AMF). Together, these results provide a basis for further functional studies of the CsCDPK proteins and their responses to AMF and drought stress.

Crown rot (Colletotrichum siamense) of strawberry is a severe disease in Jingzhou, Hubei Province, China. Pathogen identification is the basis for disease prevention and resistance breeding. Nearly fifty isolates were achieved from 192 crown rot samples in this study. A number of 21 isolates were characterized as the pathogen of crown rot of strawberry by Koch’s postulates, and they were identified as Colletotrichum spp. by conidia morphology observation. The 21 isolates were divided into three groups based on colony morphology, and SCR-7, SCR-11 and SCR-16 belonged to each group were clustered into one group with C. siamense isolates by phylogenetic analysis of actin, β-Tubulin 2 and calmodulin sequences. In addition, the isolates of C. siamense SCR-7 showed the strongest pathogenicity of the three which caused highest values of lesion length and leaf temperature, and lowest leaf water content, photosynthetic rate, stomatal conductivity and even transpiration rate values. This study contributes to updating the Colletotrichum species associated with strawberry of China.

PurposeIntracranial aneurysms (IA) comprise a multifactorial disease with unclear physiological mechanisms. The lysyl oxidase (LOX) family genes (LOX, LOX–like 1–4) plays important roles in extracellular matrix (ECM) reconstruction and has been investigated in terms of susceptibility to IA in a few populations. We aimed to determine whether polymorphisms in LOX family genes are associated with susceptibility to IA in a Chinese population.MethodsThis case-control study included 384 patients with IA and 384 healthy individuals without IA (controls). We genotyped 27 single nucleotide polymorphisms (SNPs) of LOX family genes using the Sequenom MassARRAY® platform. These SNPs were adjusted for known risk factors and then, odds ratios (OR) and 95% confidence intervals (CI) were evaluated using binary logistic regression analysis.ResultsThe result showed that LOX rs10519694 was associated with the risk of IA in recessive (OR, 3.88; 95% CI, 1.12–13.47) and additive (OR, 1.56; 95%CI, 1.05–2.34) models. Stratified analyses illustrated that LOX rs10519694 was associated with the risk of single IA in the recessive (OR, 3.95; 95%CI, 1.04–15.11) and additive (OR, 1.64; 95%CI, 1.04–2.56) models. The LOXL2 rs1010156 polymorphism was associated with multiple IA in the dominant model (OR, 1.92; 95%CI, 1.02–3.62). No associations were observed between SNPs of LOXL1, LOXL3, and LOXL4 and risk of IA.ConclusionLOX and LOXL2 polymorphisms were associated with risk of single IA and multiple IA in a Chinese population, suggesting potential roles of these genes in IA. The effects of these genes on IA require further investigation.

In this study, ground observation data were selected from January 2016 to January 2020. First, six machine learning methods were used to predict visibility. We verified the accuracy of the method with and without principal components analysis (PCA) by combining actual examples with the European Centre for Medium-Range Weather Forecast (ECMWF) data and National Centers for Environmental Prediction (NECP) data. The results show that PCA can improve visibility prediction. Neural networks have high accuracy in machine learning algorithms. The initial visibility data plays an important role in the visibility forecast and can effectively improve forecast accuracy.

Emerging evidence indicates that microRNA (miR)-193a-3p is involved in the tumor progression of various cancers. However, the biological functions and precise molecular mechanisms of miR-193a-3p in gliomas have not been well documented. Accordingly, this study focused on the tumor suppressor role and molecular mechanisms of miR-193a-3p in glioma cells. miR-193a-3p expression was determined by qRT-PCR in glioma tissues and cell lines. U251 and U87 glioma cells were transfected with a miR-193a-3p mimic. The effects of miR-193a-3p on cell growth and apoptosis were investigated using MTT, colony-forming, and flow cytometry assays. Overexpression of miR-193a-3p in U87 cells also significantly suppressed tumorigenicity and induced apoptosis in the xenograft mouse model. Luciferase assays were conducted to determine if ALKBH5 is a direct target of miR-193a-3p in glioma cells. Immunoprecipitation was used to explore the interaction between ALKBH5 and RAC-serine/threonine-protein kinase 2 (AKT2) in glioma cells. miR-193a-3p was downregulated in glioma tissues and cell lines. miR-193a-3p treatment suppressed proliferation and promoted apoptosis in both U251 and U87 cells. Bioinformatics analysis and luciferase reporter assay identified a novel miR-193a-3p target, ALKBH5. Notably, the antitumor effect of miR-193a-3p transfection in glioma cells may be due to the miR-193a-3p–induced inhibition of AKT2 expression caused by the suppression of ALKBH5 expression. Furthermore, immunoprecipitation indicated that ALKBH5 physically interacted with AKT2 through an RNA-independent mechanism in glioma cells. miR-193a-3p directly targets ALKBH5 to inhibit the growth and promote the apoptosis of glioma cells by suppressing the AKT2 pathway both in vitro and in vivo, and the physical interaction between ALKBH5 and AKT2 is essential for suppressing cell apoptosis by upregulating miR-193a-3p in glioma cells. Our study revealed that the antitumor effects of miR-193a-3p on glioma cells is due to ALKBH5 mediation of the AKT2-induced intrinsic apoptosis signaling pathway.

The gold nanostructure is regarded as the most promising photothermal agent due to its strong localized surface plasma resonance (LSPR) effect. In particular, the gold nanostructures with sharp spikes on the surface have higher optical signal enhancement, owing to the sharp tips drastically enhancing the intense nanoantenna effect. However, current approaches for the synthesis of spiky gold nanostructures are either costly, complicated, or uncontrollable. Herein, we report a novel strategy to synthesize gold nano-chestnuts (SGNCs) with sharp spikes as an excellent photothermal agent. The SGNCs were prepared by a facile one-pot interfacial synthetic method, and their controllable preparation mechanism was acquired. The SGNCs exhibited ideal full-spectrum absorption and showed excellent photothermal effect. They have a photothermal conversion efficiency (η) as high as 52.9%, which is much higher than traditional photothermal agents. The in vitro and in vivo results show that the SGNCs could efficiently ablate the tumor cells. Thus, the SGNCs have great potential in photothermal therapy applied in malignant tumors.

ABSTRACT It is a central ecological goal to explore the effects of global change factors on soil microbial communities. The vast functional gene repertoire of soil microbial communities is composed of both core and accessory genes, which may be governed by distinct drivers. This intuitive hypothesis, however, remains largely unexplored. We conducted a 5-year nitrogen and water addition experiment in the Eurasian steppe and quantified microbial gene diversity via shotgun metagenomics. Nitrogen addition led to an 11-fold increase in the abundance (based on quantitative PCR [qPCR]) of ammonia-oxidizing bacteria, which have mainly core community genes and few accessory community genes. Thus, nitrogen addition substantially increased the relative abundance of many core genes at the whole-community level. Water addition stimulated both plant diversity and microbial respiration; however, increased carbon/energy resources from plants did not counteract increased respiration, so soil carbon/energy resources became more limited. Thus, water addition selected for microorganisms with genes responsible for degrading recalcitrant soil organic matter. Accordingly, many other microorganisms without these genes (but likely with other accessory community genes due to relatively stable average microbial genome size) were selected against, leading to the decrease in the diversity of accessory community genes. In summary, nitrogen addition primarily affected core community genes through nitrogen-cycling processes, and water addition primarily regulated accessory community genes through carbon-cycling processes. Although both gene components may significantly respond as the intensity of nitrogen/water addition increases, our results demonstrated how these common global change factors distinctly impact each component. IMPORTANCE Our results demonstrated increased ecosystem nitrogen and water content as the primary drivers of the core and accessory components of soil microbial community functional diversity, respectively. Our findings suggested that more attention should be paid to certain components of community functional diversity under specific global change conditions. Our findings also indicated that microbial communities have adapted to nitrogen addition by strengthening the function of ammonia oxidization to deplete the excess nitrogen, thus maintaining ecosystem homeostasis. Because community gene richness is primarily determined by the presence/absence of accessory community genes, our findings further implied that strategies such as maintaining the amount of soil organic matter could be adopted to effectively improve the functional gene diversity of soil microbial communities subject to global change factors.

Objective(s): It has been widely reported that Mori cortex extract (MCE) is used for the treatment of diabetes mellitus in traditional medicine. The present study was designed to investigate its mechanism of action in the treatment of diabetic nephropathy (DN). We assessed whether MCE preventive treatment ameliorates kidney damage in high-fat diet and streptozotocin (STZ)-induced type 2 diabetic rats. Materials and Methods: Rats were fed a high-fat diet and injected with STZ. MCE was given to rats daily at 10 g/kg. Fasting blood glucose (FBG) and postprandial plasma glucose were measured. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated. Results: Prevention with MCE significantly decreased FBG and homoeostasis model assessment (HOMA) of IR (HOMA-IR) levels and increased insulin levels in diabetic rats. MCE prevention significantly decreased levels of KW/BW, BUN, Cr, and 24 hr urinary protein. MCE inhibited glomerular basement membrane thickening, tubular epithelial cell hypertrophy, and glomerular capillary dilation. MCE also prevented the disappearance of bowman’s space and renal tubular lumen and decreased collagen deposition in rat kidney. Moreover, MCE reduced the levels of inflammatory factors (MCP-1 and TNF-α) and fibrosis factors (collagen IV and fibronectin). Conclusion: MCE prevents DN through inhibition of inflammation and fibrosis in a rat model. It might provide a safe and effective way to prevent DN.

OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients. RESULTS: A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P

Rockbursts are one of the prominent problems faced by deep underground engineering. Not only do they affect the construction progress, but they also threaten the safety of construction personnel and equipment, and may even induce earthquakes. Therefore, the prediction of rockbursts has very important engineering significance for the excavation of deeply buried tunnels. In this paper, a new indicator for stability and optimization evaluation of hard, brittle surrounding rock under high geo-stresses, namely the minimum energy storage limit of surrounding rock induced by transient unloading, is proposed. In addition, the time for erecting support for tunnel excavation in the rockburst area and the impact of excavation dimensions on rockburst are investigated. The results show that transient unloading during the tunnel excavation process will reduce the energy storage limit of the rock mass. When the strain energy density of the local surrounding rock exceeds the minimum energy storage limit of the rock mass, the rock mass energy is suddenly released, and rockburst occurs. Rockburst is most likely to occur at 0.42−0.65 D away from the working face. The increasing length of a round adopted in high geo-stress areas will make the surrounding rock unstable and increase the probability of rockburst.

BACKGROUND:There is no consensus regarding the relationship between HBV DNA and liver fibrosis, and the relationship between HBV DNA and the degree of liver cirrhosis has not been reported in patients with chronic HBV infection. METHODS:From January 2011 to December 2016, liver biopsies were performed on 396 patients with chronic hepatitis B and cirrhosis. Assessments of liver fibrosis and cirrhosis were based on the Laennec staging system. RESULTS:Serum levels of HBV DNA were correlated with fibrosis and cirrhosis (KW = 73.946, P

Several studies have demonstrated that mild hypothermia exhibits a neuroprotective role and it can inhibit endothelial cell apoptosis following ischemia/reperfusion injury by decreasing casp-ase-3 expression. It is hypothesized that mild hypothermia exhibits neuroprotective effects on neurons exposed to ischemia/reperfusion condition produced by oxygen-glucose deprivation. Mild hypothermia significantly reduced the number of apoptotic neurons, decreased the expression of pro-apoptotic protein Bax and increased mitochondrial membrane potential, with the peak of anti-apoptotic effect appearing between 6 and 12 hours after the injury. These findings indicate that mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury by protecting the mitochondria and that the effective time window is 6-12 hours after ischemia/reperfusion injury

Aroma is important in assessing the quality of fresh fruit and their processed products, and could provide good indicators for the development of local cultivars in the mango industry. In this study, the volatile diversity of 25 mango cultivars from China, America, Thailand, India, Cuba, Indonesia, and the Philippines was investigated. The volatile compositions, their relative contents, and the intervarietal differences were detected with headspace solid phase microextraction tandem gas chromatography-mass spectrometer methods. The similarities were also evaluated with a cluster analysis and correlation analysis of the volatiles. The differences in mango volatiles in different districts are also discussed. Our results show significant differences in the volatile compositions and their relative contents among the individual cultivars and regions. In total, 127 volatiles were found in all the cultivars, belonging to various chemical classes. The highest and lowest qualitative abundances of volatiles were detected in 'Zihua' and 'Mallika' cultivars, respectively. Based on the cumulative occurrence of members of the classes of volatiles, the cultivars were grouped into monoterpenes (16 cultivars), proportion and balanced (eight cultivars), and nonterpene groups (one cultivars). Terpene hydrocarbons were the major volatiles in these cultivars, with terpinolene, 3-carene, caryophyllene and α-Pinene the dominant components depending on the cultivars. Monoterpenes, some of the primary volatile components, were the most abundant aroma compounds, whereas aldehydes were the least abundant in the mango pulp. β-Myrcene, a major terpene, accounted for 58.93% of the total flavor volatile compounds in 'Xiaofei' (Philippens). γ-Octanoic lactone was the only ester in the total flavor volatile compounds, with its highest concentration in 'Guiya' (China). Hexamethyl cyclotrisiloxane was the most abundant volatile compound in 'Magovar' (India), accounting for 46.66% of the total flavor volatiles. A typical aldehydic aroma 2,6-di-tert-butyl-4-sec-butylphenol, was detected in 'Gleck'. A highly significant positive correlation was detected between Alc and K, Alk and Nt, O and L. Cultivars originating from America, Thailand, Cuba, India, Indonesia and the Philippines were more similar to each other than to those from China. This study provides a high-value dataset for use in development of health care products, diversified mango breeding, and local extension of mango cultivars.

Genetic maps are particularly important and valuable tools for quantitative trait locus (QTL) mapping and marker assisted selection (MAS) of plant with desirable traits. In this study, 173 F1 plants from a cross between Mangifera indica L. ‘Jin-Hwang’ and M. indica L. ‘Irwin’ and their parent plants were subjected to high-throughput sequencing and specific-locus amplified fragment (SLAF) library construction. After preprocessing, 66.02 Gb of raw data containing 330.64 M reads were obtained. A total of 318,414 SLAFs were detected, of which 156,368 were polymorphic. Finally, 6,594 SLAFs were organized into a linkage map consisting of 20 linkage groups (LGs). The total length of the map was 3148.28 cM and the average distance between adjacent markers was 0.48 cM. This map could be considered, to our knowledge, the first high-density genetic map of mango, and might form the basis for fine QTL mapping and MAS of mango.

Though loss of function in CBP/p300, a family of CREB-binding proteins, has been causally associated with a variety of human neurological disorders, such as Rubinstein–Taybi syndrome, Huntington's disease and drug addiction, the role of EP300 interacting inhibitor of differentiation 1 (EID1), a CBP/p300 inhibitory protein, in modulating neurological functions remains completely unknown. Through the examination of EID1 expression and cellular distribution, we discovered that there is a significant increase of EID1 nuclear translocation in the cortical neurons of Alzheimer's disease (AD) patient brains compared to that of control brains. To study the potential effects of EID1 on neurological functions associated with learning and memory, we generated a transgenic mouse model with a neuron-specific expression of human EID1 gene in the brain. Overexpression of EID1 led to an increase in its nuclear localization in neurons mimicking that seen in human AD brains. The transgenic mice had a disrupted neurofilament organization and increase of astrogliosis in the cortex and hippocampus. Furthermore, we demonstrated that overexpression of EID1 reduced hippocampal long-term potentiation and impaired spatial learning and memory function in the transgenic mice. Our results indicated that the negative effects of extra nuclear EID1 in transgenic mouse brains are likely due to its inhibitory function on CBP/p300 mediated histone and p53 acetylation, thus affecting the expression of downstream genes involved in the maintenance of neuronal structure and function. Together, our data raise the possibility that alteration of EID1 expression, particularly the increase of EID1 nuclear localization that inhibits CBP/p300 activity in neuronal cells, may play an important role in AD pathogenesis.

Formation and accumulation of amyloid-beta (Aβ) plaques are associated with declined memory and other neurocognitive function in Alzheimer’s disease (AD) patients. However, the effects of Aβ plaques on neural progenitor cells (NPCs) and neurogenesis from NPCs remain largely unknown. The existing data on neurogenesis in AD patients and AD-like animal models remain controversial. For this reason, we utilized the nestin second-intron enhancer controlled LacZ (pNes-LacZ) reporter transgenic mice (pNes-Tg) and Bi-transgenic mice (Bi-Tg) containing both pPDGF-APPSw,Ind and pNes-LacZ transgenes to investigate the effects of Aβ plaques on neurogenesis in the hippocampus and other brain regions of the AD-like mice. We chose transgenic mice at 2, 8 and 12 months of age, corresponding to the stages of Aβ plaque free, plaque onset and plaque progression to analyze the effects of Aβ plaques on the distribution and de novo neurogenesis of (from) NPCs. We demonstrated a slight increase in the number of NPCs in the hippocampal regions at the Aβ plaque free stage, while a significant decrease in the number of NPCs at Aβ plaque onset and progression stages. On the other hand, we showed that Aβ plaques increase neurogenesis, but not gliogenesis from post-mitotic NPCs in the hippocampus of Bi-Tg mice compared with age-matched control pNes-Tg mice. The neurogenic responses of NPCs to Aβ plaques suggest that experimental approaches to promote de novo neurogenesis may potentially improve neurocognitive function and provide an effective therapy for AD.

Obstructive sleep apnea (OSA) syndrome has been recognized as a highly prevalent public health problem and is associated with major neurobehavioral morbidity. Chronic intermittent hypoxia (CIH), a major pathological component of OSA, increases oxidative damage to the brain cortex and decreases neurocognitive function in rodent models resembling human OSA. We employed in vitro and in vivo approaches to identify the specific phases and subcellular compartments in which enhanced reactive oxygen species (ROS) are generated during CIH. In addition, we utilized the cell culture and animal models to analyze the consequences of enhanced production of ROS on cortical neuronal cell damage and neurocognitive dysfunction. In a primary cortical neuron culture system, we demonstrated that the transition phase from hypoxia to normoxia (NOX) during CIH generates more ROS than the transition phase from NOX to hypoxia or hypoxia alone, all of which generate more ROS than NOX. Using selective inhibitors of the major pathways underlying ROS generation in the cell membrane, cytosol, and mitochondria, we showed that the mitochondria are the predominant source of enhanced ROS generation during CIH in mouse cortical neuronal cells. Furthermore, in both cell culture and transgenic mice, we demonstrated that overexpression of MnSOD-decreased CIH-mediated cortical neuronal apoptosis, and reduced spatial learning deficits measured with the Morris water maze assay. Together, the data from the in vitro and in vivo experiments indicate that CIH-mediated mitochondrial oxidative stress may play a major role in the neuronal cell loss and neurocognitive dysfunction in OSA. Thus, therapeutic strategies aiming at reducing ROS generation from mitochondria may improve the neurobehavioral morbidity in OSA.

The GTPase-activating protein RLIP76 is overexpressed in and correlates with the pathological grade of many malignant tumor cells. But the potential correlation between RLIP76 and clinical outcomes in patients with meningioma remains unknown. In this study, we examined the expression of RLIP76 in meningioma and correlated the RLIP76 expression to the patient outcome. RLIP76 expression in tumor tissues was examined with immunohistochemistry, quantitative reverse-transcription polymerase chain reaction(RT-PCR) and Western-blot. Immunohistochemistry showed an increased RLIP76 immunostaining score in anaplastic and atypical meningiomas versus classical meningiomas. Statistical analyses revealed that RLIP76 immunostaining positively correlated with immunostaining for Ki-67, a nuclear protein highly expressed in proliferating cells(r=0.29, p=0.034 by Spearman's correlation coefficient). Clinicopathological evaluation suggested that RLIP76 expression be associated with tumor grade and recurrence(P