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Critical size bone defects represent a significant challenge worldwide, often leading to persistent pain and physical disability that profoundly impact patients’ quality of life and mental well-being. To address the intricate and complex repair processes involved in these defects, we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue. Specifically, we observed a decrease in progenitor lineage cells and endothelial cells, coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue. Furthermore, our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects, notably influenced by reduction of Spp1 and Cxcl12 expression. This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells, underscoring its significance in the regeneration process. In response to these findings, we developed an innovative approach to enhance bone regeneration in critical size bone defects. Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12. This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo. To evaluate the efficacy of our approach, we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects. Our results demonstrated restored angiogenesis, accelerated bone regeneration, alleviated pain responses and improved mobility in treated mice.

Gynecological cancers rank among the leading causes of death for women worldwide. Traditional treatment methods, including surgery, chemotherapy, and radiotherapy, are commonly employed in patients with these tumors. However, the effectiveness of these approaches remains suboptimal due to issues like treatment resistance and challenges in early detection. As an alternative, immunotherapy has shown promise by offering improved anti-tumor responses and fewer side effects. In recent years, there have been significant advances in nanoparticle (NP) and nanoengineering technologies, paving the way for the development of nano-immunotherapy—an approach designed to enhance the effectiveness of immunotherapy. Thanks to the flexibility, adaptability, small size, and responsiveness of NP platforms to the tumor microenvironment (TME), nano-immunotherapy has demonstrated improved anti-tumor activity and safety. This is achieved through enhanced tumor targeting, better delivery of immune agents, and reduced toxicity and side effects. Recently, researchers have explored the application of nano-immunotherapy in treating gynecological cancers, aiming to slow tumor progression and improve patient outcomes. In this review, we provide an overview of the latest advances in nano-immunotherapy for gynecological cancers, including ovarian, cervical, and endometrial cancers. Additionally, we discuss the challenges facing the clinical translation of nano-immunotherapy from the lab to real-world applications.

Objective To conduct a systematic review and meta-analysis to assess the impact of transcranial electrical stimulation (TES), proposed as a potential therapy for post-stroke dysphagia, on swallowing function in stroke survivors. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant studies on TES for post-stroke dysphagia. Search results were reviewed following PRISMA guidelines, and the following data were extracted from included studies: study characteristics, demographics, and outcomes. Bias was assessed using the Cochrane tool. Heterogeneity and effect sizes were analysed using I 2 statistics and appropriate effects models. The study protocol was registered with PROSPERO (registration No. CRD42024578243) Results Six randomized controlled trials met the inclusion criteria (I 2 = 0.0%). The meta-analysis indicated a significant improvement in dysphagia with TES (standardized mean difference [SMD] 0.43, 95% confidence interval [CI] 0.13, 0.73). Subgroup analysis suggested that low-intensity TES was effective (SMD 0.46, 95% CI 0.09, 0.82), whereas high-intensity TES showed no significant improvement (SMD 0.37, 95% CI –0.17, 0.91). No publication bias was detected. Conclusion TES may improve swallowing in stroke patients, with potential benefits from low-intensity protocols.

The warming and drying trend accompanying climate change challenges global ecosystem stability. Vegetation phenology, which can serve as a sensitive indicator of climate change, is crucial in understanding ecosystem carbon cycling and climate-carbon cycle feedback. Therefore, assessing the phenological responses to drought is essential for addressing climate change. In this study, vegetation phenology data [including the start and end of season (SOS, EOS) and length of growing season (LOS)] and the Palmer drought severity index (PDSI) were employed to analyze the impacts of drought on plant phenology in China by maximum Pearson correlation coefficients and partial least squares regression. The findings showed that drought significantly affected the timing of phenology, delaying senescence in approximately 62% of China and extending the growing season in about 53% of the country, indicating the critical role of water availability in vegetation biomass. Preseason nocturnal warming was found to advance SOS, delay EOS, and extend LOS across China, with significant effects observed in approximately 60% of the country. Meanwhile, daytime warming delayed SOS, delayed EOS and extended LOS in 50∼60% of the regions. Moreover, preseason precipitation is conducive to advanced SOS, delayed EOS and extended LOS in northern China and areas susceptible to drought. It is suggested that vegetation management should be strengthened to mitigate the impact of climate change in temperate and drought-prone regions in China since climate warming will lead to frequent droughts.

Acetylene (C2H2) is often employed to assess soil total denitrification (N2O + N2) due to its ease of implementation. However, this technique underestimates soil denitrification in soils with low nutrient contents, particularly those supporting grain yields. To our knowledge, there are limited studies that have specifically investigated the impact of C2H2 on nutrient-rich vegetable soils, especially concerning the emissions of N2 and N2O and the nitrogenous gas product ratio (i.e., N2O/(N2O + N2)). In this study, we conducted both anoxic and oxic incubations at various C2H2 concentrations (0%, 0.01%, and 10%, v/v) and utilized a robotized sampling and analysis system to quantify soil N2, N2O, and CO2 emissions. Our findings revealed that the cumulative N2O production in soil treated with 10%C2H2 was significantly lower than that in soil treated with 0.01%C2H2 and soil without C2H2. Contrarily, high concentrations of C2H2 (10%, v/v) led to increased N2 production. Similar trends were observed under oxic conditions, where 10%C2H2 concentration did not enhance N2O production but markedly increased N2 and CO2 emissions. Moreover, the N2O/(N2O + N2) product ratio was notably higher in soils treated with 0%C2H2 compared to the 10%C2H2 treatment under anoxic conditions. These findings indicate that high concentrations of acetylene could facilitate the reduction of N2O to N2 and lead to underestimated soil total denitrification in vegetable soil, regardless of anoxic or oxic conditions. This discovery underscores the drawbacks when employing high concentrations of acetylene to evaluate actual total denitrification in intensive greenhouse vegetable soils, highlighting the necessity for further investigation into alternative methodologies.

BackgroundEnhanced recovery after surgery (ERAS) has been widely used in adult surgery. However, few studies have reported the efficacy of ERAS in paediatric patients with Meckel's diverticulum (MD), the aim of the study was to prospectively evaluate the safety and efficacy of ERAS in treating MD.MethodsA prospective randomised controlled study of children with MD admitted to our hospital from Jan 1, 2021 to Dec 31, 2023 were conducted, we developed and implemented an ERAS program for this patients. All cases were strictly selected according to the inclusion and exclusion criteria. Among these patients, they were randomly assigned to the ERAS group or the traditional (TRAD) group with random number table row randomization. The main observational indicators were operation time, intraoperative hemorrhage, FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery, length of postoperative stay (LOPS), time to first defecation, time to first eating after surgery, time to discontinuation of intravenous infusion, total treatment cost, incidence of postoperative complications, 30-day readmission rate and parental satisfaction rate.ResultsA total of 50 patients underwent Meckel's diverticulectomy during this period, 7 patients were excluded, 23 patients were assigned to the ERAS group and 20 patients were assigned to the TRAD group. There were no significant differences in demographic data and operation time, intraoperative hemorrhage. The FLACC pain scale results on 2 h, 6 h, 12 h, 24 h after surgery were significantly lower in the ERAS group. The LOPS was 6.17 ± 0.89 days in the ERAS group and 8.30 ± 1.26 days in the TRAD group, resulting in a significantly shorter LOPS in ERAS group. ERAS could also reduce the first postoperative defecation time, the time to first eating after surgery and the time to discontinuation of intravenous infusion. The treatment cost was decreased in the ERAS group. The rate of complications and 30-day readmission were not significantly different between the two groups.ConclusionsIn this single-center study, the ERAS protocol for patients with MD requiring surgery was safe and effective.

Abstract Background Epigenome-wide association studies of ambient fine particulate matter (PM2.5) have been reported. However, few have examined PM2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions Our findings showed that the effects of PM2.5 on DNAm varied by its PMCs and sources.

Abstract Background Lung cancer has significantly higher incidence and mortality rates worldwide. In this study, we analyzed the metabolic profiles of non‐small cell lung cancer (NSCLC) patients and constructed prediction models for smokers and nonsmokers with internal validation. Methods Plasma was collected from all patients enrolled for metabolic profiling by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The total population was divided into two groups according to smoking or not. Statistical analysis of metabolites was performed separately for each group and prediction models were constructed. Results A total of 1723 patients (1109 NSCLC patients and 614 healthy controls) were enrolled from the affiliated hospital during 2018 to 2021. After grouping by smoking history, each group was statistically analyzed and prediction models were constructed, which resulted in eight indicators (propionylcarnitine, arginine, citrulline, etc.) significantly associated with lung cancer risk for smokers and eight indicators (dodecanoylcarnitine, hydroxybutyrylcarnitine, asparagine, etc.) for nonsmokers (p

This work presents a modified etching method for the synthesis of Ti3C2 MXene. The process involves two steps: washing Ti3AlC2 with a low concentration of HF and etching Ti3AlC2 with varying concentrations of FeCl3. FeCl3 can etch the Al layers of Ti3AlC2 by a metal displacement reaction at room temperature, resulting in Ti3C2 nanosheets with an accordion-like morphology. The obtained Ti3C2 MXene was tested as a working electrode for supercapacitors, achieving a maximum specific capacitance of 213.2F/g at 0.5 A/g in a 6 M KOH electrolyte solution, which is higher than that of a Ti3C2 electrode without modification. The method is simple, efficient and reduces the use of HF. This work shows the possibility of synthesizing various MXene-based frameworks using metallic cations with higher redox potentials.

Abstract Tumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. Here, we found that PVT1 was highly expressed in endometrial cancers and ECSCs, correlated with poor patient prognosis, promoted the malignant behavior and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which was lowly expressed in endometrial cancer and ECSCs, had the opposite effect, and knockdown miR-136 inhibited the anticancer effects of down-regulated PVT1. PVT1 affected miR-136 specifically binding the 3’ UTR region of Sox2 by competitively “sponging” miR-136, thus positively saving Sox2. Sox2 promoted the malignant behavior and the stemness of ECCs and ECSCs, and overexpression Sox2 inhibited the anticancer effects of up-regulated miR-136. Sox2 can act as a transcription factor to positively regulate Up-frameshift protein 1 (UPF1) expression, thereby exerting a tumor-promoting effect on endometrial cancer. In nude mice, simultaneously downregulating PVT1 and upregulating miR-136 exerted the strongest antitumor effect. We demonstrate that the PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.

Abstract Background Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder with insidious onset. Some scholars believe that there is a close relationship between pyroptosis and AD. However, studies with evidence supporting this relationship are lacking. Materials and methods The microarray data of AD were retrieved from the Gene Expression Omnibus (GEO) database with the datasets merged using the R package inSilicoMerging. R software package Limma was used to perform the differential expression analysis to identify the differentially expressed genes (DEGs). We further performed the enrichment analyses of the DEGs based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to identify the metabolic pathways with a significant difference. The Gene Set Enrichment Analysis (GSEA) was applied to identify the significant pathways. The protein-protein interaction (PPI) network was constructed based on the STRING database with the hub genes identified. Quantitative real-time PCR (qRT-PCR) analyses based on HT22 cells were performed to validate the findings based on the microarray analysis. Gene expression correlation heatmaps were generated to evaluate the relationships among the genes. Results A new dataset was derived by merging 4 microarray datasets in the hippocampus of AD patients in the GEO database. Differential gene expression analysis yielded a volcano plot of a total of 20 DEGs (14 up-regulated and 6 down-regulated). GO analysis revealed a group of GO terms with a significant difference, e.g., cytoplasmic vesicle membrane, vesicle membrane, and monocyte chemotaxis. KEGG analysis detected the metabolic pathways with a significant difference, e.g., Rheumatoid arthritis and Fluid shear stress and atherosclerosis. The results of the Gene Set Enrichment Analysis of the microarray data showed that gene set ALZHEIMER_DISEASE and the gene set PYROPTOSIS were both up-regulated. PPI network showed that pyroptosis-related genes were divided into two groups. In the Aβ-induced HT22 cell model, three genes (i.e., BAX, IL18, and CYCS) were revealed with significant differences. Gene expression correlation heatmaps revealed strong correlations between pyroptotic genes and AD-related genes. Conclusion The pyroptosis-related genes BAX, IL18, and CYCS were significantly different between AD patients and normal controls.

IntroductionThe aim of this study was to cluster patients with chronic complications of type 2 diabetes mellitus (T2DM) by cluster analysis in Dalian, China, and examine the variance in risk of different chronic complications and metabolic levels among the various subclusters.Methods2267 hospitalized patients were included in the K-means cluster analysis based on 11 variables [Body Mass Index (BMI), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Glucose, Triglycerides (TG), Total Cholesterol (TC), Uric Acid (UA), microalbuminuria (mAlb), Insulin, Insulin Sensitivity Index (ISI) and Homa Insulin-Resistance (Homa-IR)]. The risk of various chronic complications of T2DM in different subclusters was analyzed by multivariate logistic regression, and the Kruskal-Wallis H test and the Nemenyi test examined the differences in metabolites among different subclusters.ResultsFour subclusters were identified by clustering analysis, and each subcluster had significant features and was labeled with a different level of risk. Cluster 1 contained 1112 inpatients (49.05%), labeled as “Low-Risk”; cluster 2 included 859 (37.89%) inpatients, the label characteristics as “Medium-Low-Risk”; cluster 3 included 134 (5.91%) inpatients, labeled “Medium-Risk”; cluster 4 included 162 (7.15%) inpatients, and the label feature was “High-Risk”. Additionally, in different subclusters, the proportion of patients with multiple chronic complications was different, and the risk of the same chronic complication also had significant differences. Compared to the “Low-Risk” cluster, the other three clusters exhibit a higher risk of microangiopathy. After additional adjustment for 20 covariates, the odds ratios (ORs) and 95% confidence intervals (95%CI) of the “Medium-Low-Risk” cluster, the “Medium-Risk” cluster, and the”High-Risk” cluster are 1.369 (1.042, 1.799), 2.188 (1.496, 3.201), and 9.644 (5.851, 15.896) (all p

This paper explores the impact of retailers' corporate social responsibility (CSR) and manufacturers' overconfidence on manufacturers' carbon reduction in sustainable supply chains. We analyze the profits of manufacturers and retailers under different scenarios and explore the social welfare and environmental impacts under CSR. Our results suggest that retailers' CSR and manufacturers' overconfidence contribute positively to promoting carbon mitigation and reducing environmental impacts under certain conditions. However, with increasing CSR and manufacturer overconfidence levels, manufacturers are more likely to lead to worse environmental impacts and carbon emission reduction. In addition, we show that when the manufacturer's overconfidence level is high, manufacturers and retailers are more profitable and contribute to carbon emission reductions in the manufacturer without overconfidence (retailer without CSR) scenario. Moreover, we find that firms have the higher potential to capture optimal overall social welfare in the presence of retailers with CSR and manufacturer overconfidence.

Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging. We analyzed data from 607 male participants (mean age 73.2 years) of the VA Normative Aging Study with one to two study visits from 1999 to 2007 (observations = 956). Stress was assessed via the 14-item Perceived Stress Scale (PSS). Epigenetic age was calculated from DNA methylation measured in leukocytes with the HumanMethylation450 BeadChip. In linear mixed effects models adjusted for demographic/lifestyle/health factors, a standard deviation (sd) increase in PSS was associated with Horvath (β = −0.35-years, 95%CI: −0.61, −0.09, P = 0.008) and Intrinsic (β = −0.40-years, 95%CI: −0.67, −0.13, P = 0.004) epigenetic age deceleration. However, in models limited to participants with the highest levels of stress (≥75th-percentile), Horvath (β = 2.29-years, 95%CI: 0.16, 4.41, P = 0.04) and Intrinsic (β = 2.06-years, 95%CI: −0.17, 4.28, P = 0.07) age acceleration associations were observed. Our results reinforce the complexity of psychological stress and epigenetic aging relationships and lay a foundation for future studies that explore longitudinal relationships with other adult stress metrics and factors that can influence stress such as resilience measures.

As an internal modification of transcripts, RNA methylation determines RNA fate by changing RNA–protein binding affinity. In plants, RNA methylation is ubiquitous and is involved in all aspects of RNA post-transcriptional regulation. For instance, long-distance mobile RNAs, strongly influenced by their methylation status, play important roles in plant growth, development and environmental adaptation. Cucumber/pumpkin heterografts are widely used to improve stress tolerance of cucumber and to study mobile RNA signals due to their strong developed vasculature system. Here, we developed the Cucume (Cucurbit RNA methylation, http://cucume.cn/) database for these two important vegetables, cucumber (Cucumis sativus L.) and pumpkin (Cucurbita moschata) with high productivity worldwide. We identified mRNAs harboring 5-methylcytosine (m5C) and N6-methyladenosine (m6A) sites in pumpkin and cucumber at the whole genome level via Methylated RNA Immunoprecipitation sequencing (MeRIP-seq) of different tissues and the vascular exudates. In addition to RNA methylation sites, the Cucume database includes graft-transmissible systemic mRNAs identified in previous studies using cucumber/pumpkin heterografts. The further integration of cucumber genome-wide association analysis (GWAS) and quantitative trait loci (QTL) allows the study of RNA methylation-related genetic and epigenetic regulation in cucurbits. Therefore, the here developed Cucume database will promote understanding the role of cucurbit RNA methylation in RNA mobility and QTL, ultimately benefitting future breeding of agronomic crop germplasms.

Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl3 (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H2O2) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B2 production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H2O2 cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B2 production, and granule release, but also in delaying blood coagulation, FeCl3-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.

Natural peptides (NPs) are ubiquitous throughout the organism with diversified structures and wide dynamic concentration range, which leads to serious challenge for their comprehensive analysis. Herein, a pseudotargeted peptidomics strategy based on dynamic multiple reaction monitoring (DMRM) with high-throughput data acquisition and accurate quantification was established. Specifically, an in-house software Pep-MRMer was developed for extraction of ions information of peptides, followed by de-redundancy and fusion to construct a transition list. Additionally, retention time (RT) calibration method was optimized by using high content components for effective transference of ion pairs between different detection conditions (e.g., instruments, chromatographic gradients). This strategy was applied for profiling NPs and screening signature peptides for species authentication of Pheretima, a multi-source animal-derived drug widely used in Asian countries. In all, a total of 3307 peptides had excellent quantitative detection after transference. Subsequently, nine signature peptides with extraordinary specificity were screened, identified, and confirmed by comparing with the synthetic standards. Ultimately, a 10 min specific chromatogram based on signature peptides was developed, which realized rapid and accurate identification of Pheretima. Taken together, this research provides a robust strategy for species discrimination of animal-derived drugs without adequate quality control measures.

Abstract Background Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer’s disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. Methods The ameliorating effect of miR-22-3p on apoptosis of the Aβ-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. Results The miR-22-3p played an important role in ameliorating apoptosis in the Aβ-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aβ deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. Conclusion Our study showed that miR-22-3p could improve apoptosis and reduce Aβ deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.

Abstract Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of pathological processes involving cancer. However, the exact molecular mechanisms of lncRNA regulation in endometrial carcinoma (EC) remain poorly defined. The aim of this study was to illustrate the mechanism of LINC00958 in regulating the function of IGF2BP3, an RNA binding protein involved in mRNA stability, and their clinical implications in EC. First, we investigated the clinical role of IGF2BP3 in EC and demonstrated its prognostic value. Loss-of-function and gain-of-function studies showed that IGF2BP3 promoted EC cell proliferation, migration and invasion. Then, we carried out RNA immunoprecipitation sequencing (RIP-seq) analysis, RNA pulldown and immunofluorescence-RNA fluorescence in situ hybridization to identify LINC00958 that interacted with IGF2BP3 in the cytoplasm of EC cells. Rescue experiments indicated that knockdown of LINC00958 partially offset the EC cell progression mediated by IGF2BP3. After that, RNA sequencing was used to screen out the downstream genes of IGF2BP3 and LINC00958. The results revealed that IGF2BP3 upregulated E2F3 expression by interacting with LINC00958. Furthermore, RNA stability assays demonstrated that silencing LINC00958 partially rescued the IGF2BP3-mediated promoting effect on the mRNA stability of E2F3. Collectively, this study suggests that LINC00958, as an oncogene, assists IGF2BP3 in stabilizing E2F3 mRNA and ultimately promotes EC progression, providing a promising therapeutic target for patients with EC.

ObjectivesThis study aimed to investigate the effect of vascular risk factors on the outcomes of endolymphatic sac decompression (ESD) surgery in patients with Meniere’s disease.MethodsThe study included 56 patients with Meniere’s disease, who had undergone unilateral ESD surgery. The patients’ vascular risk factors were assessed based on the preoperative 10-year atherosclerotic cardiovascular diseases risk classification. Those with no or low risk were defined as the low-risk group, while those with medium, high, or very high risk were defined as the high-risk group. The correlation between the vascular risk factors and ESD efficacy was evaluated by the comparison of vertigo control grade between the two groups. The functional disability score was also assessed to investigate whether ESD improved the quality of life in Meniere’s disease patients with vascular risk factors.ResultsAfter ESD, 78.95 and 81.08% of patients from the low-risk and high-risk groups, respectively, demonstrated at least grade B vertigo control; no statistically significant difference was observed (p = 0.96). The postoperative functional disability scores in both groups were significantly lower compared with those before surgery (p

Objective To develop a nomogram that discriminates lung cancer from benign lung nodules through metabolic profiling. Methods This was a retrospective cohort study that recruited 848 participants who were randomized into training and validation sets at a 7:3 ratio. Clinical characteristics and metabolic profiles were retrieved. Variables in the training set with statistically significant differences were selected for further least absolute shrinkage and selection operator (LASSO) regression. The nomogram was built from 13 variables identified by stepwise regression analysis. Receiver operating characteristic, calibration curve, and decision curve analyses were conducted to evaluate the performance of the nomogram by internal validation. Results Thirteen variables were selected through LASSO regression to build the nomogram: age, sex, ornithine, tyrosine, glutamine, valine, serine, asparagine, arginine, methylmalonylcarnitine, tetradecenoylcarnitine, 3-hydroxyisovaleryl carnitine/2-methyl-3-hydroxybutyrylcarnitine, and hydroxybutyrylcarnitine. The nomogram had good discrimination for the training set, with an area under the curve of 0.836 (95% confidence interval: 0.830–0.890). Moreover, the calibration curve with 1000 bootstrap resamples showed that the predicted value coincided well with the actual value. Decision curve analysis described a net benefit superior to baseline within the threshold probability range of 15% to 93%. Conclusions The nomogram constructed from metabolic profiling accurately predicted risk of lung cancer.

Apple ring rot caused by Botryosphaeria dothidea is an important disease that leads to severe quality deterioration and yield loss at pre-harvest and postharvest stages. Therefore, it is urgent to develop safe and efficient measures to control this disease. The objective of the present study was to investigate the biocontrol features of Pseudomonas syringae B-1 against B. dothidea and explore its mechanism of action utilizing in vitro and in vivo assays. The results showed that P. syringae B-1 strongly reduced the incidence of apple ring rot and lesion diameter by 41.2 and 90.2%, respectively, in comparison to the control fruit. In addition, the control efficiency of strain B-1 against B. dothidea infection depended on its concentration and the interval time. P. syringae B-1 cells showed higher inhibitory activities than its culture filtrates on the mycelial growth and spore germination of B. dothidea. Moreover, P. syringae B-1 treatment alleviated electrolyte leakage, lipid peroxidation, and H2O2 accumulation in B. dothidea-infected apple fruit by increasing antioxidant enzyme activities, including peroxidase, catalase, superoxide dismutase, and ascorbate peroxidase. We also found that strain B-1 treatment enhanced four defense-related enzyme activities and stimulated the accumulation of three disease-resistant substances including phenolics, lignin, and salicylic acid (SA) in apple fruit. In addition, strain B-1 triggered the upregulated expression of defense-related genes such as PR genes (PR1, PR5, GLU, and CHI) and two genes involved in the biosynthesis of SA (SID2 and PAD4) to promote the resistance potential in apple fruit. Hence, our results suggest that P. syringae B-1 is a promising strategy against B. dothidea, mainly through reducing oxidative damage, activating defense-related enzymes, accumulating disease-resistant substances, and triggering the expression of resistance-correlated genes in apple fruit.

Abstract Endometrial cancer stem cells (ECSCs) play a vital role in endometrial cancer (EC) metastasis, relapse, and chemoresistance. However, the molecular mechanisms that sustain ECSCs remain elusive. Here, we showed that the expression of UPF1 was upregulated in EC tissues and ECSCs and correlated with poor clinicopathological characteristics. UPF1 silencing suppressed ECSC hallmarks, such as sphere formation ability, carboplatin resistance, migration and invasion, and cell cycle progression. UPF1 regulated the behavior and fate of ECSCs by stabilizing LINC00963. LINC00963 further shares the same miRNA response element with the core transcription factor SOX2 and relieved the suppression of SOX2 by miR-508-5p in self-renewing ECSCs. Notably, inhibition of UPF1 and LINC00963 in combination severely impaired the in vivo tumorigenic potential of ECSCs. We demonstrate that the UPF1/LINC00963/miR-508-5p/SOX2 axis has potential value in modulating ECSC maintenance, chemoresistance, and tumorigenesis in EC, which highlights a novel promising target for EC treatment.

Alzheimer’s disease (AD) is defined as a severe chronic degenerative neurological disease in human. The pathogenic mechanism of AD has been convincingly elucidated by the “amyloid cascade hypothesis” with the main focus of the pathological accretion of β-amyloid (Aβ) peptides outside the cell. However, increasing evidence suggests that this hypothesis is weak in explaining the pathogenesis of AD. Neuroinflammation is crucial in the development of AD, which is proven by the elevated levels of inflammatory markers and the identification of AD risk genes relevant to the innate immune function. Here, we summarize the effects of microglia-mediated neuroinflammation on AD, focusing on the temporal and spatial changes in microglial phenotype, the interactions among microglia, Aβ, tau, and neurons, and the prospects and recent advances in neuroinflammation as a diagnostic and therapeutic target of AD.

Background: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes. Methods: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015. Our exposures were defined as same-day, two-day, three-day, one-week, two-week, and three-week moving averages of PM2.5, NO2, O3, and temperature which were derived from high-resolution spatio-temporal models. The ex-miRNA profiles of the subjects were obtained during follow-up visits. We analyzed the data using a longitudinal quantile regression model adjusted for individual covariates, batch effects, and time trends. We adjusted for multiple comparisons using a false discovery rate (FDR) correction. Ex-miRNAs that were significantly associated with exposures were further investigated using pathway analyses. Results: We found that all the examined exposures were associated with changes in ex-miRNA profiles in our study, particularly PM2.5 which was responsible for most of the statistically significant results. We found 110 statistically significant exposure-outcome relationships that revealed associations with the levels of 52 unique ex-miRNAs. Pathway analyses showed these ex-miRNAs have been linked to target mRNAs, genes, and biological mechanisms that could affect virtually every organ system, and as such may be linked to multiple clinical disease presentations such as cardiovascular disease, respiratory disease, and neurological disease. Conclusions: Air pollution and temperature exposures were significantly associated with alterations in the ex-miRNA profiles of NAS subjects with possible biological consequences.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive wheat diseases worldwide. Understanding the effects of cultivar mixture on disease control and population genetic structure of Pst could promote the effective application of cultivar mixtures. This study designed nine cultivar mixtures composed of different component cultivars with field experiments in Zitong County, Sichuan Province in two seasons from 2016 to 2018. Diseased leaves were collected in each plot of treatment in the spring and, in total, 835 and 568 isolates were obtained and genotyped with 10 pairs of simple sequence repeat markers in the 2 years, respectively. The observed and theoretical values of the area under the disease progress curve (AUDPC), wheat yield, Pst genotypic diversity, and the frequency of Pst dominant genetic groups were compared among cultivar mixtures. With the 2 years’ experiments, there were three and two cultivar mixtures, respectively, showing significant effect on the relative reduction of AUDPC; there were no significant effects on the relative yield increase in all mixtures in the 2 years. There were four and five cultivar mixtures showing positive effects on the relative increase of Pst genotypic diversity in the 2 years, respectively. Moreover, all cultivar mixtures could decrease the frequencies of Pst dominant genetic groups on highly susceptible component cultivar compared with their theoretical frequencies.[Figure: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Comorbidities, any other coexisting diseases in patients with a particular index disease, are known to increase the mortality of a stroke. However, the association of pre-existing comorbidities with stroke risk has not been fully studied. Methods This study included 16,246 adults from a prospective community-based cohort with a baseline survey conducted in 2013 in China. Participants were followed up with hospitalization records and the Cause of Death Registry. The association of eight pre-existing comorbidities (coronary heart disease, hyperlipidemia, hypertension, diabetes, previous stroke, chronic obstructive pulmonary disease, nephropathy, and cancer) with stroke risk was analyzed using the Cox proportional hazard model in 2020. Results At a median follow-up of 5.5 years, a total of 449 participants (206 men and 243 women) developed a stroke. Four pre-existing comorbidities (hypertension, congenital heart disease, previous stroke, and diabetes) were independently and positively associated with the risk for all types of stroke. The adjusted hazard ratios for participants with only 1 and ≥ 2 pre-existing comorbidities compared with those without pre-existing conditions were 1.96 (95% CI: 1.44, 2.67; P

This work demonstrates a distinctive almost HF-free route of etching Ti3AlC2 MAX phase by metal displacement reaction at room temperature. The Ti3AlC2 particles are directly etched by CuCl2 solutions in different concentrations instead of HF. The etchant is reduced to nano CuCl particles, adhering to the surface of Ti3C2 layers to form the Ti3C2@CuCl composite which is evaluated as working electrodes for supercapacitors. Due to the synergistic effect between CuCl and Ti3C2 matrix, the appropriate amount of CuCl enhances the specific capacitance to 508.7 F·g−1 at 1A·g−1 in 6 M KOH electrolyte solution, which is much higher than pure Ti3C2 electrode. This work shows the possibility of synthesis of various Mxene-based frameworks by other metallic cations with lower metal activity.

Accurate identification of the botanical origins of Rhizoma Alismatis (RA) is pivotal to its precise clinical usage. We herein present a strategy, by integrating untargeted metabolomics, data cross validation, absolute quantification, and vector machine model, for species discrimination and source recognition of Rhizoma Alismatis for the first time. An ultra-high-performance liquid chromatography/LTQ-Orbitrap mass spectrometry with precursor ions list-including data-dependent acquisition approach was developed for metabolite profiling. Holistic, continuous, and pattern recognition chemometrics could make it feasible to unveil forty-one markers, with “multi-duplicated and traceability samples comparison” cross validation to narrow down to twelve robust markers, some of which were further validated by absolute quantification. A support vector machine model was eventually developed to distinguish these two species and predict origins of commercially available varieties. This was the first report on systematic comparison and discrimination of two original species of RA. This integral strategy, in contrast to conventional approaches, renders more convincing data supporting for the discovery of multi-source chemical makers of traditional Chinese medicines (TCM).

Drought poses a serious threat to plant growth. Plant growth-promoting bacteria (PGPB) have great potential to improve plant nutrition, yield, and drought tolerance. Sphingomonas is an important microbiota genus that is extensively distributed in the plant or rhizosphere. However, the knowledge of its plant growth-promoting function in dry regions is extremely limited. In this study, we investigated the effects of PGPB Sphingomonas sp. Hbc-6 on maize under normal conditions and drought stress. We found that Hbc-6 increased the biomass of maize under normal conditions and drought stress. For instance, the root fresh weight and shoot dry weight of inoculated maize increased by 39.1% and 34.8% respectively compared with non-inoculated plant, while they increased by 61.3% and 96.3% respectively under drought conditions. Hbc-6 also promoted seed germination, maintained stomatal morphology and increased chlorophyll content so as to enhance photosynthesis of plants. Hbc-6 increased antioxidant enzyme (catalase, superoxide, peroxidase) activities and osmoregulation substances (proline, soluble sugar) and up-regulated the level of beneficial metabolites (resveratrol, etc.). Moreover, Hbc-6 reshaped the maize rhizosphere bacterial community, increased its richness and diversity, and made the rhizosphere bacterial community more complex to resist stress; Hbc-6 could also recruit more potentially rhizosphere beneficial bacteria which might promote plant growth together with Hbc-6 both under normal and drought stress. In short, Hbc-6 increased maize biomass and drought tolerance through the above ways. Our findings lay a foundation for exploring the complex mechanisms of interactions between Sphingomonas and plants, and it is important that Sphingomonas sp. Hbc-6 can be used as a potential biofertilizer in agricultural production, which will assist finding new solutions for improving the growth and yield of crops in arid areas.

Cr2AlC MAX phase coating exhibited excellent oxidation resistance and hot corrosion, but it typically suffered from low hardness and toughness as well as lack of lubrication at high temperature. With a solid solution design on M-site, we demonstrated that the hardness of the Cr2AlC MAX phase coating was enhanced by 34.3% when Cr was partially substituted with V (47 at.%), and the coating toughness was improved simultaneously. Furthermore, according to the high-temperature tribometer test, both the friction coefficient and the wear rate of the coatings at 900 °C against Al2O3 balls were significantly reduced at 47 at.% V. This could be attributed to the formation of a large number of molten V2O5 wrapped (Cr, Al)2O3 hard crystal grains, which not only provided a wide range of liquid-phase lubrication, but also prevented the coating from being apt to wear out. Different from the multi-phase compositing, this study suggested a promising strategy to enhance the combined mechanical and tribological performance of MAX phase coatings by M-site V solid solution for harsh applications at a high temperature of 900 °C.

Controversy continues over the functional prevalence of long non-coding RNAs (lncRNAs) despite their being widely investigated in all kinds of cells and organisms. In animals, lncRNAs have aroused general interest from exponentially increasing transcriptomic repertoires reporting their highly tissue-specific and developmentally dynamic expression, and more importantly, from growing experimental evidence supporting their functionality in facilitating organogenesis and individual fitness. In mammalian testes, while a great multitude of lncRNA species are identified, only a minority of them have been shown to be useful, and even fewer have been demonstrated as true requirements for male fertility using knockout models to date. This noticeable gap is attributed to the virtual existence of a large number of junk lncRNAs, the lack of an ideal germline culture system, difficulty in loss-of-function interrogation, and limited screening strategies. Facing these challenges, in this review, we discuss lncRNA functionality in organismal development and especially in mouse testis, with a focus on lncRNAs with functional screening.

Abstract Glucose metabolism is fundamental for the functions of all tissues, including cartilage. Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development, little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis. We show here that genetic deletion of the glucose transporter Glut1 in postnatal cartilage impairs cell proliferation and matrix production in growth plate (GPs) but paradoxically increases cartilage remnants in the metaphysis, resulting in shortening of long bones. On the other hand, articular cartilage (AC) with Glut1 deficiency presents diminished cellularity and loss of proteoglycans, which ultimately progress to cartilage fibrosis. Moreover, predisposition to Glut1 deficiency severely exacerbates injury-induced osteoarthritis. Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions, both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability. However, uncontrolled glutamine flux causes collagen overmodification, thus affecting extracellular matrix remodeling in both cartilage compartments. These results uncover the pivotal and distinct roles of Glut1-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.

Epithelial-mesenchymal transition (EMT) promotes tumorigenesis and metastasis and increases tumor tolerance to treatment intervention. Abnormal activation of transforming growth factor β (TGF-β) and Wnt pathway induces EMT. Long non-coding RNAs (lncRNAs) significantly influence EMT regulation. Herein, we show that MIR210HG is overexpressed in endometrial cancer tissues, which is associated with poor prognosis. MIR210HG silencing significantly inhibited proliferation, migration, invasion, and EMT phenotype formation in vitro as well as tumorigenesis in vivo. Mechanistically, bioinformatics analyses, RNA binding protein immunoprecipitation (RIP) assays, and luciferase assays showed that MIR210HG acts as a molecular sponge of miR-337-3p and miR-137 to regulate the expression of HMGA2. Additionally, MIR210HG overexpression significantly enriched the Wnt/β-catenin and TGF-β/Smad3 signaling pathway genes, while MIR210HG or HMGA2 knockdown suppressed the Wnt/β-catenin and TGF-β/Smad3 signaling pathway. Our findings on the MIR210HG-miR-337-3p/137-HMGA2 axis illustrate its potential as a target for endometrial cancer therapeutic development.

Abstract Atrophic fracture nonunion poses a significant clinical problem with limited therapeutic interventions. In this study, we developed a unique nonunion model with high clinical relevance using serum transfer-induced rheumatoid arthritis (RA). Arthritic mice displayed fracture nonunion with the absence of fracture callus, diminished angiogenesis and fibrotic scar tissue formation leading to the failure of biomechanical properties, representing the major manifestations of atrophic nonunion in the clinic. Mechanistically, we demonstrated that the angiogenesis defect observed in RA mice was due to the downregulation of SPP1 and CXCL12 in chondrocytes, as evidenced by the restoration of angiogenesis upon SPP1 and CXCL12 treatment in vitro. In this regard, we developed a biodegradable scaffold loaded with SPP1 and CXCL12, which displayed a beneficial effect on angiogenesis and fracture repair in mice despite the presence of inflammation. Hence, these findings strongly suggest that the sustained release of SPP1 and CXCL12 represents an effective therapeutic approach to treat impaired angiogenesis and fracture nonunion under inflammatory conditions.

ABSTRACT: Tigecycline, a new first-in-class glycylcycline antibiotic, has shown promising efficacy against a broad range of micro-organisms. It is widely prescribed for various infections, with most prescriptions being considered for off-label use. However, only a few years after its approval by the US Food and Drug Administration (FDA), tigecycline is suspected of increasing all-cause mortality. Some clinicians have suggested such unfavourable outcomes correlate with inadequate drug exposure at the infection site. The pharmacokinetic/pharmacodynamic (PK/PD) profile of a drug plays an important role in predicting its antibiotic effect, which for tigecycline is determined as the ratio of area under the concentration–time curve (AUC) to minimum inhibitory concentration (MIC). In this study, PK/PD targets based on infection sites, bacterial isolates and patient populations are discussed. Generally, a higher dosage of tigecycline for the treatment of serious infections has been recommended in previous reports. However, the latest finding of tigecycline's atypical protein binding property requires consideration when recommending further use. In addition, combination therapy with other antibiotics provides another option by potentially lowering the MICs of multidrug-resistant bacteria.

ABSTRACT Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a crucial disease for wheat worldwide and constantly threatens wheat production in southwestern and northwestern China, where the environment is a good fit for Pst oversummering and overwintering. However, the underlying genetic dynamics of spring epidemic Pst populations across large areas of continuous planting in the southwestern and northwestern regions are poorly understood. A total of 2,103 Pst isolates were sampled in the spring of 2019 from the two agroecosystems and grouped into three horizontal spatial scales (countywide, provincial, and regional subpopulations) and two vertical spatial scales that consisted of elevational and geomorphic subpopulations. A total of 776 multilocus genotypes were identified, with the highest genetic diversity found in the northern and Sichuan populations, particularly in the Ningxia and Sichuan Basins, while the lowest genetic diversity was found in the Yunnan and Guizhou populations. Multivariate discriminant analysis of principal components (DAPC) and STRUCTURE (STRUCTURE 2.3.4) analyses revealed variation in the genotypic compositions of the molecular groups on horizontal and vertical dimensions from north to south or vice versa and from low to high or vice versa, respectively. The regional neighbor-joining tree revealed three large spatial structures consisting of the southwestern, the northwestern, and the Xinjiang regions, while the Tibetan population connected the southwestern and northwestern regions. The isolates of the Sichuan Basin were scattered over the four quartiles by principal coordinate analysis, which indicated frequent genotype interchange with others. Greater genetic differentiation was observed between the southwestern and northwestern regions. Linkage equilibrium (P ≥ 0.05) was detected on different spatial scales, suggesting that Pst populations are using sexual reproduction or mixed reproduction (sexual and clonal reproduction) in southwestern and northwestern China. IMPORTANCE Understanding the epidemiology and population genetics of plant pathogens is crucial to formulate efficient predictions of disease outbreaks and achieve sustainable integrated disease management, especially for pathogens with migratory capability. Here, this study covers the genetic homogeneity and heterogeneity of different geographical Pst populations on broad to fine spatial scales from the key epidemic regions of the two agroecosystems in China, where wheat stripe rust occurs annually. We provide knowledge of the population genetics of Pst and reveal that, for instance, there is greater genetic diversity in northwestern China, there are close genetic relationships between Yunnan and Guizhou and between Gansu-Ningxia and Qinghai, and there are effects of altitude on genetic compositions, etc. All of these findings clarify the genetic relationships and expand the insights into the population dynamics and evolutionary mechanisms of Pst in southwestern and northwestern China, providing a theoretical basis for achieving sustainable control of wheat stripe rust in key epidemic regions.

Objective T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.Methods Peripheral blood CD4+ and CD8+ T cells and their subsets were determined by flow cytometry. Forty-one active SLE patients were selected, including 28 new-onset patients and 13 relapsing patients. One hundred healthy controls (HCs) were enrolled as the control group. The percentages of these cell subsets between patients with SLE and HCs and their relationships with disease activity and autoantibody titers were analysed. Thirteen of 28 new-onset SLE patients were assessed before and after treatment. The changes in the frequencies of these cell subsets and their relationships with renal response were analysed.Results There was a broad range of anomalies in the proportion of T cell subsets in patients with SLE compared with that of the HCs. Compared with the HCs, a higher frequency of memory T cells and a lower frequency of naïve T cells were noted in patients with SLE. In addition, an imbalance of CD28+ and CD28− cells in CD4+ T cells was observed in patients with SLE. We found that the expanded CD4+CD28− T cells did not decrease after treatment in patients who had impaired renal responses. It was very interesting to exhibit a negative correlation in the frequency between the CD4+CD28− T cells and T regulatory (Treg) cells and a positive correlation between the frequency of CD4+CD28+ T cells and Treg cells in this study. Increased CD8+HLADR+ T cell and CD8+CD38+HLADR+ T cell counts were observed in patients with SLE, suggesting an impaired cytotoxic capacity of CD8+ T cells in SLE. Additionally, we found that CD8+CD38+HLADR+ T cells were closely associated with disease activity, autoantibody titres and renal prognosis. CD4+ CXCR5−PD1+ T cells were expanded in patients with SLE in this study and were associated with disease activity in SLE. Th1 (T helper type 1) cells and Treg cells were decreased, but frequencies of T follicular helper (Tfh) cells, Th2 cells, Th17 cells and Tfh17 cells were increased. A strong correlation between Th17 cells and Tregs with renal involvement was observed in this study.Conclusion The proportions of CD4+CD28− T cells, CD4+CXCR5−PD1+ T cells, CD8+HLADR+ T cells and CD8+CD38+HLADR+ T cells increased in patients with SLE and could be associated with disease activity and renal prognosis.

ObjectiveThis study aimed to explore the association between dietary patterns and hypertension based on a community–based survey in Suzhou, Eastern China.MethodsThis cross–sectional analysis was undertaken from the subset of the Suzhou Food Consumption and Health State Survey in 2018–2019. Adults aged ≥ 18 years were invited to participate in this survey. Dietary intake was collected by a 24–h dietary recall and a weighing method over three consecutive days (including two weekdays and one weekend day). Dietary patterns were defined using factor analysis. Association between the dietary patterns and hypertension was examined by multivariable logistic regression models with adjustment for covariates. Moreover, sensitivity analysis was used to reinforce our findings.ResultsA total of 2,718 participants were included in the final analysis. Rice-vegetable pattern, fast food pattern, fruit-dairy pattern, and wheat-meat pattern were identified. We observed that the fruit-dairy pattern was inversely associated with hypertension after adjustment for all the covariates (OR = 0.55; 95% CI: 0.40, 0.75; P = 0.002). The association between the wheat-meat pattern and hypertension was attenuated and became statistically nonsignificant in sensitivity analyses. The other two patterns were not significantly associated with hypertension (P > 0.05).ConclusionThe fruit-dairy pattern was inversely associated with the risk of hypertension among Chinese adults. Our findings further emphasize the important role of optimal diet combination in the prevention of hypertension.

As a transportation hub connecting sea and land, the seismic safety of an undersea tunnel is very important. Based on the structural and stress characteristics of a shield tunnel, a seismic response analysis of a coastal nuclear power plant under a complex foundation is carried out in this paper. Firstly, adopting the lateral and longitudinal response displacement methods, the authors study the variation and distribution features of the rate of diameter change and joint-stretching value of the shield tunnel segments. On this basis, a three-dimensional refined finite element model of a sinking tube–soil mass under a complex soil foundation is established. Finally, when the joints and segments of the shield tunnel are subjected to ground motion, the deformation and internal force distribution of its lining segments are studied. The findings show that under influence of SL-2-magnitude ground motion, the soft–hard stratum junction is the weak point of the shield tunnel structure’s longitudinal seismic resistance. When the silt layer at the position of the shield segment is thicker and the geological conditions are relatively poorer, the internal force, diameter deformation rate, and joint-stretching value will be larger. The research results can provide a reference for seismic research on shield tunnels in sea areas under complex foundations.

Abstract Background Hysteroscopy is a commonly used technique for diagnosing endometrial lesions. It is essential to develop an objective model to aid clinicians in lesion diagnosis, as each type of lesion has a distinct treatment, and judgments of hysteroscopists are relatively subjective. This study constructs a convolutional neural network model that can automatically classify endometrial lesions using hysteroscopic images as input. Methods All histopathologically confirmed endometrial lesion images were obtained from the Shengjing Hospital of China Medical University, including endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyps, and submucous myomas. The study included 1851 images from 454 patients. After the images were preprocessed (histogram equalization, addition of noise, rotations, and flips), a training set of 6478 images was input into a tuned VGGNet-16 model; 250 images were used as the test set to evaluate the model’s performance. Thereafter, we compared the model’s results with the diagnosis of gynecologists. Results The overall accuracy of the VGGNet-16 model in classifying endometrial lesions is 80.8%. Its sensitivity to endometrial hyperplasia without atypia, atypical hyperplasia, endometrial cancer, endometrial polyp, and submucous myoma is 84.0%, 68.0%, 78.0%, 94.0%, and 80.0%, respectively; for these diagnoses, the model’s specificity is 92.5%, 95.5%, 96.5%, 95.0%, and 96.5%, respectively. When classifying lesions as benign or as premalignant/malignant, the VGGNet-16 model’s accuracy, sensitivity, and specificity are 90.8%, 83.0%, and 96.0%, respectively. The diagnostic performance of the VGGNet-16 model is slightly better than that of the three gynecologists in both classification tasks. With the aid of the model, the overall accuracy of the diagnosis of endometrial lesions by gynecologists can be improved. Conclusions The VGGNet-16 model performs well in classifying endometrial lesions from hysteroscopic images and can provide objective diagnostic evidence for hysteroscopists.

The present two-year longitudinal study aimed to examine the relationship between depression and reasoning ability in adolescents, and further investigated the modulation effect of growth mindset on this relationship. A total of 1,961 and 1,667 Chinese adolescents participated in the study for the first year (T1) and second year (T2), respectively. The results showed that T1 depression was negatively correlated with T1 growth mindset (r = −0.35, p < 0.001), T1 reasoning (r = −0.30, p < 0.001), and T2 reasoning (r = −0.23, p < 0.001). Regression analysis revealed that T1 depression and the interaction between T1 depression and T1 growth mindset significantly predicted T1 reasoning (β = −0.220/−0.044, all ps < 0.05). After controlling for gender, age, family socioeconomic status, and T1 reasoning ability, both T1 depression and the interaction between T1 depression and T1 growth mindset still significantly predicted T2 reasoning (β = −0.104/β = 0.054, all ps < 0.05). The simple slope analysis found that the negative correlation between depression and reasoning in the high growth mindset group was weaker than that of the low growth mindset group in both T1 and T2, suggesting that growth mindset plays a significant moderating role in the relationship between depression and reasoning. In conclusion, depression was negatively correlated with reasoning ability in adolescents, in addition, growth mindset moderated the relationship between depression and reasoning.

With the rapid development of the take-out industry, taste and hygiene ratings as social-based information have been frequently used by online food-ordering platforms to facilitate consumer purchases. The present study aims to uncover the effects of taste and hygiene ratings on online food-ordering decision by incorporating behavioral and neural approaches. The behavioral results showed that a high taste rating induced a higher ordering intention than a low taste rating, and that a high hygiene rating induced a higher ordering intention than a low hygiene rating. The effect of hygiene rating on ordering intention was moderated by taste rating. Hygiene rating had a greater impact on ordering intention when the taste rating was high (vs. low). In addition, inconsistency between taste and hygiene ratings increased the cognitive load and took more time for decision-making. The event-related potential (ERP) data revealed that consumers paid more attention to a high (vs. low) taste rating in the early cognitive process, which was reflected by a larger P2. Subsequently, a more negative N2 was elicited by conflicting ratings than consistent ratings when the taste rating was low. In the relatively late decision-making process, a larger P3 was evoked by consistent than conflicting ratings, suggesting that consumers had more confidence in their decisions for consistent ratings. These findings could help restaurants understand the roles of taste and hygiene rating cues in affecting consumer behavior and prompt those restaurants to adopt effective measures to increase online sales.

Although underlying mechanisms of long-term exposure to air pollution and cardiovascular disease remain obscure, effects might partially act through changes in DNA methylation. We examined the associations between long-term ambient fine particulate matter (PM2.5) and methylation, considering both a global measure and methylation at several specific inflammation-related loci, in two random sub-cohorts selected from a nationwide prospective study of US women. In one sub-cohort we measured long interspersed nucleotide element (LINE-1); in the other, we measured methylation at three candidates CpG loci related to inflammatory pathways [tumour necrosis factor-alpha (TNF-α) and toll-like receptor-2 (TLR-2)]. Annual average contemporaneous ambient PM2.5 concentrations were estimated for the current residence. We used both classical least-squares and quantile regression models to estimate the long-term effects. The women in sub-cohorts 1 (n = 491) and 2 (n = 882) had mean ages of 55.8 and 56.7, respectively. Neither modelling approach showed an association between long-term PM2.5 and LINE-1 methylation or between PM2.5 and either of the two CpG sites in TLR-2. Using linear regression, there was an estimated change of −6.5% (95% confidence interval CI: −13.34%, 0.35%) in mean methylation of TNF-α per 5 µg/m3 increase in PM2.5. Quantile regression showed that the downward shift was mainly in the lower half of the distribution of DNA methylation. Long-term residence in regions with higher ambient PM2.5 may be associated with increased TNF-α through a reduction in methylation, particularly in the lower tail. Epigenetic markers and quantile regression might provide insight into mechanisms underlying the relationship between air pollution and cardiovascular disease.

Background: Several epigenome-wide association studies (EWAS) of ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) have been reported. However, EWAS of PM2.5 elements (PEs), reflecting different emission sources, are very limited. Objectives: We performed EWAS of short- and intermediate-term exposure to PM2.5 and 13 PEs. We hypothesized that significant changes in DNAm may vary by PM2.5 mass and its elements. Methods: We repeatedly collected blood samples in the Normative Aging Study and measured leukocyte DNA methylation (DNAm) with the Illumina HumanMethylation450K BeadChip. We collected daily PM2.5 and 13 PEs at a fixed central site. To estimate the associations between each PE and DNAm at individual cytosine-phosphate-guanine (CpG) sites, we incorporated a distributed-lag (0–27 d) term in the setting of median regression with subject-specific intercept and examined cumulative lag associations. We also accounted for selection bias due to loss to follow-up and mortality prior to enrollment. Significantly differentially methylated probes (DMPs) were identified using Bonferroni correction for multiple testing. We further conducted regional and pathway analyses to identify significantly differentially methylated regions (DMRs) and pathways. Results: We included 695 men with 1,266 visits between 1999 and 2013. The subjects had a mean age of 75 years. The significant DMPs, DMRs, and pathways varied by to PM2.5 total mass and PEs. For example, PM2.5 total mass was associated with 2,717 DMPs and 10,470 DMRs whereas Pb was associated with 3,173 DMPs and 637 DMRs. The identified pathways by PM2.5 mass were mostly involved in mood disorders, neuroplasticity, immunity, and inflammation, whereas the pathways associated with motor vehicles (BC, Cu, Pb, and Zn) were related with cardiovascular disease and cancer (e.g., “PPARs signaling”). Conclusions: PM2.5 and PE were associated with methylation changes at multiple probes and along multiple pathways, in ways that varied by particle components.

Music expertise is known to be beneficial for cognitive function and development. In this study, we conducted 1-year music training for school children (n = 123; 7–11 years of age before training) in China. The children were assigned to music or second-language after-class training groups. A passive control group was included. We aimed to investigate whether music training could facilitate working memory (WM) development compared to second-language training and no training. Before and after the training, auditory WM was measured via a digit span (DS) task, together with the vocabulary and block tests of the Wechsler Intelligence Scale for Child IV (WISC-IV). The results of the DS task revealed superior development in the music group compared to the other groups. However, further analysis of DS forward and backward tasks indicated that the performance of the three training/non-training groups only differed significantly in DS backward scores, but not in the DS forward scores. We conclude that music training may benefit the central executive system of WM, as reflected by the DS backward task.

Tomato (Solanum lycopersicum) gray leaf spot disease is a predominant foliar disease of tomato in China that is caused mainly by the necrotrophic fungal pathogen Stemphylium lycopersici. Little is known regarding the pathogenic mechanisms of this broad-host-range pathogen. In this study, a comparative transcriptomic analysis was performed and more genetic information on the pathogenicity determinants of S. lycopersici during the infection process in tomato were obtained. Through an RNA sequencing (RNA-seq) analysis, 1,642 and 1,875 genes upregulated during the early infection and necrotrophic phases, respectively, were identified and significantly enriched in 44 and 24 pathways, respectively. The induction of genes associated with pectin degradation, adhesion, and colonization was notable during the early infection phase, whereas during the necrotrophic phase, some structural molecule activity-related genes were prominently induced. Additionally, some genes involved in signal regulation or encoding hemicellulose- and cellulose-degrading enzymes and extracellular proteases were commonly upregulated during pathogenesis. Overall, we present some putative key genes and processes that may be crucial for S. lycopersici pathogenesis. The abilities to adhere and colonize a host surface, effectively damage host cell walls, regulate signal transduction to manage infection, and survive in a hostile plant environment are proposed as important factors for the pathogenesis of S. lycopersici in tomato. The functional characterization of these genes provides an invaluable resource for analyses of this important pathosystem between S. lycopersici and tomato, and it may facilitate the generation of control strategies against this devastating disease.

Commerce has had positive impacts on the whole agri-food value chain at different stages, it was developed rapidly in rural China in the past few years. E-commerce participation can promote the use intensity of organic fertilizers (OF) and this could achieve many benefits for different stakeholders including ensuring food safety, positive environmental impacts and promoting the adoption of green production technologies. Therefore, this study has used primary data collected from 733 fruit farmers in rural China to explore the impact of e-commerce participation on fruit farmers' use intensity of (OF). Unlike previous studies investigating the dichotomous decision of (OF) adoption, this study captures the use intensity of (OF) from both input quantity and cost aspects. We employed an endogenous switching regression (ESR) model to address selectivity bias caused by observed and unobserved factors. The results show that e-commerce participation significantly increases the use intensity of (OF) in input quantity and cost by 19.48% and 29.50%, respectively. Heterogeneous analysis further reveals that compared to fruit farmers with a low e-commerce participation level, fruit farmers with a high e-commerce participation level have higher (OF) use intensity. The findings also show that risk preference, human capital, cultivated area, cooperative membership and government restraint mechanisms positively and significantly affect the probability of fruit farmers' participation in e-commerce and fruit farmers' use intensity of (OF). The results emphasize that e-commerce promotion is an efficient way to encourage farmers to adopt (OF), which help improve product quality and promote sustainable agricultural development.

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome). Methods: We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets. Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.