Search

BackgroundHepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses.MethodsscRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC.ResultsThese analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results.ConclusionThese results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.

BackgroundCardioembolic Stroke (CS) and Atrial Fibrillation (AF) are prevalent diseases that significantly impact the quality of life and impose considerable financial burdens on society. Despite increasing evidence of a significant association between the two diseases, their complex interactions remain inadequately understood. We conducted bioinformatics analysis and employed machine learning techniques to investigate potential shared biomarkers between CS and AF.MethodsWe retrieved the CS and AF datasets from the Gene Expression Omnibus (GEO) database and applied Weighted Gene Co-Expression Network Analysis (WGCNA) to develop co-expression networks aimed at identifying pivotal modules. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared genes within the modules related to CS and AF. The STRING database was used to build a protein-protein interaction (PPI) network, facilitating the discovery of hub genes within the network. Finally, several common used machine learning approaches were applied to construct the clinical predictive model of CS and AF. ROC curve analysis to evaluate the diagnostic value of the identified biomarkers for AF and CS.ResultsFunctional enrichment analysis indicated that pathways intrinsic to the immune response may be significantly involved in CS and AF. PPI network analysis identified a potential association of 4 key genes with both CS and AF, specifically PIK3R1, ITGAM, FOS, and TLR4.ConclusionIn our study, we utilized WGCNA, PPI network analysis, and machine learning to identify four hub genes significantly associated with CS and AF. Functional annotation outcomes revealed that inherent pathways related to the immune response connected to the recognized genes might could pave the way for further research on the etiological mechanisms and therapeutic targets for CS and AF.

BackgroundWhile several studies have noted a higher SII correlates with multiple diseases, research on the association between SII and atopic dermatitis remains limited. Our cross-sectional study seeks to examine the association between SII and atopic dermatitis among outpatient US adults.MethodsThis compensatory cross-sectional study utilized NHANES data from 2001–2006 cycles, conducting sample-weighted multivariate logistic regression and stratified analysis of sub-groups.ResultsHigher levels of SII were positively associated with an increased risk of atopic dermatitis in adults with BMI

To realize transparent monitoring and resilience improvement of low-voltage distribution network, both the data acquisition scope and frequency have been greatly expanded. Cloud-edge collaboration leverages the edge server’s real-time response capabilities and the cloud server’s robust data processing power to enhance the performance of high-frequency data acquisition processing. Nonetheless, it continues to confront challenges such as the entanglement of optimization variables, the presence of uncertain information, and a lack of awareness regarding acquisition frequencies. In this paper, we propose a machine learning-based cloud-edge collaborative data processing optimization algorithm to minimize the weighted sum of data processing delay and device energy consumption for distribution network resilience improvement. The joint optimization problem is decoupled into device-edge data offloading subproblem and edge-cloud data splitting subproblem, which are solved by the proposed upper confidence bound (UCB) based frequency-aware device-edge data offloading optimization algorithm and the exponential-weight algorithm for exploration and exploitation (EXP3) based edge-cloud data splitting optimization algorithm, respectively. Simulation results show that the proposed algorithm is superior to existing algorithms in performances of energy consumption and total processing delay.

Background and purposeArteriosclerotic cerebral small vessel disease (aCSVD) is a cause of cognitive impairment, dementia, and stroke. Developing a better understanding of the risk factor of aCSVD is key to reducing the incidence of these conditions. This study investigated the association between intracranial arterial calcification (IAC) and total cerebral small vessel disease (CSVD) burden score.Materials and methodsThis is a retrospective study, the subjects were transient ischemic attack (TIA) or acute ischemic stroke (AIS) patients. The data of 303 inpatients admitted to our study hospital between December 2018 and July 2020 were analyzed. Four imaging markers of CSVD (lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces) were evaluated by magnetic resonance imaging, and a total CSVD burden score was calculated. The experimental group was divided into four subgroups according to total CSVD burden score (1–4 points). Patients without CSVD (0 points) served as the control group. Head computerized tomography (CT) scans were used to assess ICA, using Babiarz’s method. The correlations between IAC and single imaging markers of CSVD were determined using Spearman’s rank correlation. Binary logic regression analysis and multivariate ordered logic regression analysis were used to determine the associations between IAC and aCSVD.ResultsIAC was positively correlated with total CSVD burden score (r = 0.681), deep white matter hyperintensities (r = 0.539), periventricular white matter hyperintensities (r = 0.570), cerebral microbleeds (r = 0.479), lacunes (r = 0.541), and enlarged perivascular spaces (r = 0.554) (all p

PurposeLymph node-based staging protocols are frequently employed to evaluate the prognosis of esophageal cancer, yet their accuracy remains contentious. The present study was conducted to assess the prognostic significance of three lymph node staging systems, namely N stage, lymph node rate (LNR), and log odds of positive lymph nodes (LODDS), in patients diagnosed with advanced (T2-T4) esophageal squamous cell carcinoma (ESCC).MethodsThis cohort comprised 319 eligible patients, with an additional 409 individuals retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, forming the validation cohort. Differences in overall survival (OS) of patients between groups were assessed using the log-rank test. Prognostic independent risk variables were identified, and lymph nodes (LN) prognostic models were built using multivariate Cox regression analysis. Besides, the predictive accuracy of each model was evaluated utilizing the (-2) log-likelihood ratio (-2LLR), the likelihood ratio χ2 score (LRχ2), the Akaike information criterion (AIC), and Harrell’s concordance index (C-index). To further evaluate the potential superiority of the model, a nomogram was constructed for comparison with the conventional Tumor Node Metastasis (TNM) staging approach.ResultsIndependent prognostic factors for advanced ESCC include the N stage, LNR, and LODDS. Herein, LODDS presented higher values for C-index and LRχ2, and lower values for AIC and -2LLR in OS compared to the others. Consequently, a nomogram was constructed based on LODDS. Calibration curves exhibited strong agreement, and assessment through C-index, receiver operating characteristic (ROC) curves, and clinical decision curve analysis (DCA) demonstrated promising clinical applicability.ConclusionLODDS emerges as a promising future prognostic indicator. After surgery, the proposed model holds the potential to provide valuable treatment recommendations for patients with advanced ESCC.

Necroptosis is implicated in the pathogenesis of ischemic stroke. However, the mechanism underlying the sequential recruitment of receptor-interacting protein kinase 1 (RIPK1) and N-ethylmaleimide-sensitive fusion ATPase (NSF) in initiating necroptosis remains poorly understood, and the role of NSF in ischemic stroke is a subject of controversy. Here, we utilized a recently emerging RNA-targeting CRISPR system known as CasRx, delivered by AAVs, to knockdown Ripk1 mRNA and Nsf mRNA around the ischemic brain tissue. This approach resulted in a reduction in infarct and edema volume, as well as an improvement in neurological deficits assessed by Bederson score, RotaRod test, and Adhesive removal test, which were achieved by RIPK1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein signaling pathway involved in neuronal necroptosis. In conclusion, the downregulation of Ripk1 mRNA and Nsf mRNA mediated by CRISPR-CasRx holds promise for future therapeutic applications aimed at ameliorating cerebral lesions and neurological deficits following the ischemic stroke.

BackgroundPsoriasis is a chronic dermatological condition characterized by a complex pathogenesis that impacts approximately 3% of adults in the United States and brings enormous social burdens. For many diseases, the systemic immune-inflammatory index (SII), defined as neutrophils × platelets/lymphocytes, has been recognized as a prognostic indicator. Therefore, we conducted a cross-sectional study to assess the association between SII and psoriasis among outpatient US adults.MethodsIn this cross-sectional study, we used data on the US adults 20 to 59 years of age from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2006 and 2009–2014. Sample-weighted logistic regression and stratified analysis of subgroups were used.ResultsAmong the 16,831 adults, there were 8,801 women and 8,030 men, with a psoriasis prevalence rate of 3.0%. A fully adjusted model revealed a positive association between a SII higher than 479.15 × 109/L and a high risk of psoriasis. According to subgroup analysis and interaction testing (p for interaction > 0.05), age, sex, alcohol drinking status, marital status, and body mass index (BMI) were not significantly correlated with this positive association.ConclusionOur findings suggested that SII higher than 479.15 × 109/L was positively associated with a high risk of psoriasis among outpatient US adults. To the best of our knowledge, this is the first cross-sectional study using NHANES data focused on the risk of higher SII on psoriasis among outpatient US adults. The outcomes of this cross-sectional serve to supplement previous research, indicating a need for larger-scale prospective cohorts for further validation.

Against the backdrop of the unexpected COVID-19 epidemic, governments are facing significant challenges in mobilizing food resources, particularly fresh products. It is inevitable that there will be intermittent shortages of food during the pandemic. As a result, home food gardening has gained considerable attention from city residents and policymakers in modern cities. This is due to its potential to provide food during humanitarian emergencies and lockdown. Moreover, home food gardening is increasingly becoming a popular recreational activity in many countries, offering therapeutic benefits such as fostering social bonds through knowledge-sharing and fruit-sharing, improving mental and psychological well-being, promoting outdoor physical exercise, and strengthening the connection between humans and nature. This review provides a comprehensive summary of the latest advancements in home food gardening, including cultivated species, devices, technologies, and current issues. It also proposes perspectives based on current researches to serve as a reference for future research and development.

IntroductionIn recent years, the perceptual capabilities of robots have been significantly enhanced. However, the task execution of the robots still lacks adaptive capabilities in unstructured and dynamic environments.MethodsIn this paper, we propose an ontology based autonomous robot task processing framework (ARTProF), to improve the robot's adaptability within unstructured and dynamic environments. ARTProF unifies ontological knowledge representation, reasoning, and autonomous task planning and execution into a single framework. The interface between the knowledge base and neural network-based object detection is first introduced in ARTProF to improve the robot's perception capabilities. A knowledge-driven manipulation operator based on Robot Operating System (ROS) is then designed to facilitate the interaction between the knowledge base and the robot's primitive actions. Additionally, an operation similarity model is proposed to endow the robot with the ability to generalize to novel objects. Finally, a dynamic task planning algorithm, leveraging ontological knowledge, equips the robot with adaptability to execute tasks in unstructured and dynamic environments.ResultsExperimental results on real-world scenarios and simulations demonstrate the effectiveness and efficiency of the proposed ARTProF framework.DiscussionIn future work, we will focus on refining the ARTProF framework by integrating neurosymbolic inference.

BackgroundIn some observational studies, attention-deficit/hyperactivity disorder has been linked to allergic diseases, but the findings are debatable. This study aimed to determine whether attention-deficit/hyperactivity disorder (ADHD) is causally related to allergic asthma, allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis using the two-sample Mendelian Randomization (MR) approach.MethodsWe did a two-sample Mendelian randomization (MR) study, which chose single nucleotide polymorphisms (SNPs) that are highly associated with attention-deficit/hyperactivity disorder (ADHD) levels from the Psychiatric Genomics Consortium (PGC) on 20,183 cases and 35,191 controls as our instruments. Outcomes datasets included genome-wide association study (GWAS) meta-analysis (n = 1,415,804). The summary statistics of outcome data were obtained from the FinnGen datasets including allergic asthma (10,877 cases and 180,942 controls), allergic rhinitis (8,430 cases and 298,829 controls), pollen allergy (4555cases and 301,734 controls), allergic urticaria (1792 cases and 299,491 controls) and allergic conjunctivitis (15,567 cases and 293,587 controls). Inverse variance weighted, MR-Egger, weighted median, were used to estimate the causal association between ADHD and allergic diseases. Cochran’s Q test was used to quantify the heterogeneity of instrumental variables. MR-Egger intercept test, leave-one-out analysis, and the funnel plot were all used in sensitivity analyses.ResultsThe Mendelian randomization (MR) analysis indicated that ADHD in inverse variance weighted [odds ratio (OR) = 1.0612; 95% confidence interval (CI):1.0192–1.1049; p = 0.0039] lightly increased the risk of allergic asthma. In MR sensitivity analyses of the weighted median, a similar association was found. But no evidence for an effect of ADHD on allergic asthma risk was found in additional methods: MR-Egger (OR = 0.9592, 95% CI: 0.8384–1.0974, p = 0.5457), and weighted median (OR: =1.0341, 95% CI: 0.9785–1.0929, p = 0.2330). Also, no strong evidence for an effect of ADHD on other allergic diseases (allergic rhinitis, pollen allergy, allergic urticaria, and allergic conjunctivitis) incidence was found using the inverse variance weighted (IVW) method, weighted median method, and MR-Egger regression.ConclusionAlthough several studies have found a link between ADHD and allergic diseases, our findings do not support that ADHD could increase allergic diseases incidence. Randomized controlled trials or Mendelian randomization studies with larger samples are still needed to draw more precise conclusions.

Girdling is a horticultural technique that enhances fruit size by allocating more carbohydrates to fruits, yet its underlying mechanisms are not fully understood. In this study, girdling was applied to the main stems of tomato plants 14 days after anthesis. Following girdling, there was a significant increase in fruit volume, dry weight, and starch accumulation. Interestingly, although sucrose transport to the fruit increased, the fruit’s sucrose concentration decreased. Girdling also led to an increase in the activities of enzymes involved in sucrose hydrolysis and AGPase, and to an upregulation in the expression of key genes related to sugar transport and utilization. Moreover, the assay of carboxyfluorescein (CF) signal in detached fruit indicated that girdled fruits exhibited a greater ability to take up carbohydrates. These results indicate that girdling improves sucrose unloading and sugar utilization in fruit, thereby enhancing fruit sink strength. In addition, girdling induced cytokinin (CK) accumulation, promoted cell division in the fruit, and upregulated the expression of genes related to CK synthesis and activation. Furthermore, the results of a sucrose injection experiment suggested that increased sucrose import induced CK accumulation in the fruit. This study sheds light on the mechanisms by which girdling promotes fruit enlargement and provides novel insights into the interaction between sugar import and CK accumulation.

Urbanization in China has entered a stage of accelerated development that is accompanied by a range of issues concerning resource, ecological and society. Urban vegetable production (UVP), an important part of urban agriculture, has the potential to be an effective countermeasure for dealing with these problems. Here, we review the current state of UVP with its related technology and equipment, and show the major models of UVP in China with three representative implementation cases in Beijing. Through this review, we found the impact of UVP on urban vegetable supply should not be underestimated, while it is still considered as an urban entertainment by public now. Moreover, UVP extension is still limited when compared with China’s urbanization process. We analyze the possible reasons that restrict the development of UVP and give corresponding suggestions to improve it. Considering the scale of urbanization in China, and the potential contribution of UVP to food supply, environmental sustainability and social harmony, there is still much room for UVP development, which will bring opportunities and challenges to the government and scientific researchers.

IntroductionCholangiocarcinoma (CCA) is a malignant tumor of the biliary epithelium with a poor prognosis. The lack of biomarkers to predict therapeutic response and prognosis is one of the major challenges for CCA treatment. Tertiary lymphoid structures (TLS) provide a local and pivotal microenvironment for tumor immune responses. The prognostic value and clinical relevance of TLS in CCA remain unclear. We aimed to explore the characteristics and clinical significance of TLS in CCA.MethodsWe investigated the prognostic value and clinical relevance of TLS in CCA using a surgery cohort containing 471 CCA patients (cohort 1) and an immunotherapy cohort containing 100 CCA patients (cohort 2). Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were used to evaluate the maturity of TLS. Multiplex IHC (mIHC) was employed to characterize the composition of TLS.ResultsDifferent maturity of TLS were observed in CCA tissue sections. Strong staining of the four-gene signature including PAX5, TCL1A, TNFRSF13C, and CD79A were found in TLS regions. A high density of intra-tumoral TLS (T-score high) were significantly correlated with longer overall survival (OS) both in CCA cohort 1 (p = 0.002) and cohort 2 (p = 0.01), whereas a high density of peri-tumoral TLS (P-score high) were associated with shorter OS in these two cohorts (p = 0.003 and p = 0.03, respectively).ConclusionThe established four-gene signature efficiently identified the TLS in CCA tissues. The abundance and spatial distribution of TLS were significantly correlated with the prognosis and immune checkpoint inhibitors (ICIs) immunotherapy response of CCA patients. The presence of intra-tumoral TLS are positive prognostic factors for CCA, which provide a theoretical basis for the future diagnosis and treatment of CCA.

BackgroundHER2-targeted therapy provides survival benefits to HER2-mutant non-small cell lung cancer (NSCLC). A better understanding of the clinical and genomic characterization of treatment-naïve HER2-positive NSCLC, as well as the efficacy of and resistance to HER2-targeted therapy in HER2-altered NSCLC, could promote further improvement of HER2 targeted therapy.MethodsHER2-altered NSCLC patients was retrospectively included and their genomic profiles were performed by next-generation sequencing. The clinical outcomes included overall response rate, disease control rate and progression-free survival.ResultsAmong 176 treatment-naïve patients with HER2 alterations, 64.8% harbored HER2 mutations with/without HER2 amplification, and 35.2% carried HER2 amplification only. Molecular characterization was correlated with tumor stage that late-stage NSCLC with HER2 oncogenic mutations showed a higher prevalence of TP53 mutations and a higher tumor mutation burden. However, this correlation was not found in patients with HER2 amplification only. Twenty-one patients with HER2 alterations treated with pyrotinib or afatinib were retrospectively enrolled. Pyrotinib yielded a longer median progression-free survival than afatinib (5.9 [95% CI, 3.8-13.0] vs. 4.0 months [95% CI, 1.9-6.3], P = 0.06) in these patients. Analysis of the genomic profiles before and after anti-HER2 targeted therapies identified de novo HER2 copy number gain and G518W mutation, as well as mutations involving DNA damage repair signaling, SWI–SNF complex, and epigenetic regulations as potential resistance mechanisms.ConclusionHER2-mutant NSCLC had different molecular features from HER2-amplified NSCLC, and its genomic profile was dependent of tumor stage. Pyrotinib had superior therapeutic effects than afatinib in HER2-altered NSCLC, although larger cohorts are warranted to validate it. HER2-dependent and -independent resistance mechanisms to afatinib and pyrotinib were unveiled.

BackgroundDevelopment of endovascular interventional techniques gradually replaced traditional open surgery and has become the preferred treatment for renal aneurysms. This study aimed to analyze the clinical characteristics of renal artery aneurysm (RAA) and the safety and efficacy of intravascular interventional treatment.Materials and MethodsWe retrospectively analyzed the clinical characteristics and imaging data of 23 aneurysms in 18 patients with RAA. The technical success rate, complication rate, mortality rate, reintervention rate, and use of embolization materials were evaluated.ResultsIn 18 patients with RAA (age, 32–72 years, average age, 52.2 ± 11.2 years), a total of 23 aneurysms were found (diameter 0.5–5.5 cm, average diameter 2.2 ± 1.4 cm). Among them, 11 cases (61.1%) were discovered accidentally, and the remaining patients were diagnosed due to the following major complaints: four cases (22.2%) presented low back pain, two (11.1%) were due to high blood pressure, and one (5.5%) had low back pain with gross hematuria. A total of 14 aneurysms in 13 patients received endovascular interventional therapy. The technical success rate of 13 patients with renal aneurysms was 100%. Three of the 18 patients were lost to follow-up, and the remaining were followed up for 4–89 months. There was no recurrence of the aneurysm or displacement of the stent or coil.ConclusionEndovascular treatment for RAA has a high success rate, low complication rate, and low reintervention rate. It has the advantage of less trauma and is flexible and more targeted for different types of renal aneurysms.

Soil salinization has a serious influence on rice yield and quality. How to enhance salt tolerance in rice is a topical issue. In this study, 120 recombinant inbred line populations were generated through nonstop multi-generation selfing using a male indica rice variety Huazhan (Oryza sativa L. subsp. indica cv. ‘HZ’) and a female variety of Nekken2 (Oryza sativa L. subsp. japonica cv. ‘Nekken2’) as the parents. Germination under 80 mM NaCl conditions was measured and analyzed, and quantitative trait locus (QTL) mapping was completed using a genetic map. A total of 16 salt-tolerance QTL ranges were detected at bud stage in rice, which were situated on chromosomes 3, 4, 6, 8, 9, 10, 11, and 12. The maximum limit of detection was 4.69. Moreover, the qST12.3 was narrowed to a 192 kb region on chromosome 12 using map-based cloning strategy. Statistical analysis of the expression levels of these candidate genes under different NaCl concentrations by qRT-PCR revealed that qST12.3 (LOC_Os12g25200) was significantly down-regulated with increasing NaCl concentration, and the expression level of the chlorine-transporter-encoding gene LOC_Os12g25200 in HZ was significantly higher than that of Nekken2 under 0 mM NaCl. Sequencing analysis of LOC_Os12g25200 promoter region indicated that the gene expression difference between parents may be due to eight base differences in the promoter region. Through QTL mining and analysis, a plurality of candidate genes related to salt tolerance in rice was obtained, and the results showed that LOC_Os12g25200 might negatively regulate salt tolerance in rice. The results provide the basis for further screening and cultivation of salt-tolerant rice varieties and have laid the foundation for elucidating further molecular regulation mechanisms of salt tolerance in rice.

PurposeTo establish and evaluate multiregional T2-weighted imaging (T2WI)-based clinical-radiomics model for predicting lymph node metastasis (LNM) and prognosis in patients with resectable rectal cancer.MethodsA total of 346 patients with pathologically confirmed rectal cancer from two hospitals between January 2019 and December 2021 were prospectively enrolled. Intra- and peritumoral features were extracted separately, and least absolute shrinkage and selection operator regression was applied for feature selection. Radiomics signatures were built using the selected features from different regions. The clinical-radiomic nomogram was developed by combining the intratumoral and peritumoral radiomics signatures score (radscore) and the most predictive clinical parameters. The diagnostic performances of the nomogram and clinical model were evaluated using the area under the receiver operating characteristic curve (AUC). The prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis.ResultsThe intratumoral radscore (radscore 1) included four features, the peritumoral radscore (radscore 2) included five features, and the combined intratumoral and peritumoural radscore (radscore 3) included ten features. The AUCs for radscore 3 were higher than that of radscore 1 in training cohort (0.77 vs. 0.71, P=0.182) and internal validation cohort (0.76 vs. 0.64, P=0.041). The AUCs for radscore 3 were higher than that of radscore 2 in training cohort (0.77 vs. 0.74, P=0.215) and internal validation cohort (0.76 vs. 0.68, P=0.083). A clinical-radiomic nomogram showed a higher AUC compared with the clinical model in training cohort (0.84 vs. 0.67, P

With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant–soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination.

ObjectiveThe study aimed to examine the effects of hearing aids on cognitive function in middle-aged and older adults with hearing loss.Data sources and study selectionPubMed, Cochrane Library, and Embase were searched for studies published before 30 March 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) were included in the search. Restriction was set on neither types, severity, or the time of onset of hearing impairment nor cognitive or psychiatric statuses.Data extraction and synthesisTwo independent reviewers extracted data and assessed the study quality of RCTs. Cognitive function outcomes were descriptively summarized and converted to standardized mean difference (SMD) in the meta-analysis. Meta-analysis was conducted in RCTs. Sub-group analyses were conducted by cognitive statuses, psychiatric disorders, and cognitive domains.ResultsA total of 15 studies met the inclusion criteria, including five RCTs (n = 339) and 10 NRSIs (n = 507). Groups were classified as subjects without dementia or with normal global cognition, subjects with AD or dementia, and subjects with depressive symptoms. For subjects without dementia, improvements were found in global cognition, executive function, and episodic memory. For subjects with depressive symptoms, improvements were found in immediate memory, global cognition, and executive function. No improvement was found in subjects with AD or dementia. In total, four RCTs were included in the meta-analysis. For subjects without dementia (SMD = 0.11, 95% confidence interval [CI]: −0.15–0.37) and those with AD, no significant effect was found (SMD = −0.19, 95% CI: −0.65–0.28). For subjects without dementia, no significant effect was found in language (SMD = 0.14, 95% CI: −0.30–0.59) or general executive function (SMD = −0.04, 95% CI: −0.46–0.38). Further sub-group analysis found no significant effect in executive function (SMD = −0.27, 95% CI: −0.72–0.18) or processing speed (SMD = −0.02, 95% CI: −0.49–0.44).ConclusionHearing aids might improve cognitive performance in domains such as executive function in subjects without dementia. The effects on subjects with depressive symptoms remained unclear. No improvement was found in subjects with AD or dementia. Long-term RCTs and well-matched comparison-group studies with large sample sizes are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022349057.

BackgroundAlthough chronic low-grade inflammation has been linked to the development of erectile dysfunction (ED), the association between pro-inflammatory diets and ED is unclear. The dietary inflammation index (DII) is a novel method to quantify the inflammatory potential of a diet.ObjectiveOur objective was to investigate the association between the DII and ED among US males.DesignThis cross-sectional study included 3,693 males 20–85 year of age from the National Health and Nutrition Examination Survey (NHANES) 2001–2004. Multivariable-adjusted logistic regression models were used to assess the association between the DII and ED. All analyses accounted for the complex sampling design.ResultsThe mean ± SE of the DII was 0.8 ± 0.1 and 0.4 ± 0.1 among participants with and without ED, respectively. After adjusting for age, race/ethnicity, education, smoking status, physical activity, drinking status, hypertension, diabetes, cardiovascular disease, hypercholesterolemia, BMI, and eGFR, the DII score was associated with ED (odds ratio 1.12; 95% CI: 1.04–1.19). Moreover, this association was also stable in our subgroup analysis or sensitivity analyses.ConclusionDietary inflammatory potential, as estimated by the DII score, is positively associated with ED among US males.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have exhibited great promise in the treatment of tumors with homologous recombination (HR) deficiency, however, PARPi resistance, which ultimately recovers DNA repair and cell progress, has become an enormous clinical challenge. Recently, KP372-1 was identified as a novel potential anticancer agent that targeted the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce extensive reactive oxygen species (ROS) generation that amplified DNA damage, leading to cancer cell death. To overcome PARPi resistance and expand its therapeutic utility, we investigated whether a combination therapy of a sublethal dose of KP372-1 with a nontoxic dose of PARPi rucaparib would synergize and enhance lethality in NQO1 over-expressing cancers. We reported that the combination treatment of KP372-1 and rucaparib induced a transient and dramatic AKT hyperactivation that inhibited DNA repair by regulating FOXO3a/GADD45α pathway, which enhanced PARPi lethality and overcame PARPi resistance. We further found that PARP inhibition blocked KP372-1-induced PARP1 hyperactivation to reverse NAD+/ATP loss that promoted Ca2+-dependent autophagy and apoptosis. Moreover, pretreatment of cells with BAPTA-AM, a cytosolic Ca2+ chelator, dramatically rescued KP372-1- or combination treatment-induced lethality and significantly suppressed PAR formation and γH2AX activation. Finally, we demonstrated that this combination therapy enhanced accumulation of both agents in mouse tumor tissues and synergistically suppressed tumor growth in orthotopic pancreatic and non-small-cell lung cancer xenograft models. Together, our study provides novel preclinical evidence for new combination therapy in NQO1+ solid tumors that may broaden the clinical utility of PARPi.

We aimed to validate the performance of the ratio of the platelet count (PLT) to liver stiffness measurement (LSM) in excluding high-risk varices (HRVs) in patients with hepatitis B virus (HBV)-related compensated cirrhosis beyond Baveno VI criteria. A total of 310 patients were assessed. The performances of the PLT:LSM ratio (PLER), PLER adjusted for the international normalized ratio, etiology, age, and sex (PLEASE), and the sequential algorithm for HRV screening (VariScreen) in excluding HRVs were evaluated and compared with those of expanded Baveno VI criteria (LSM 110×109/L, EB6C); PLT >150×109/L and model for end-stage liver disease score = 6 (P150M6 criterion); PLT >120×109/L and albumin >36 g/L (P120A36 criterion); and albumin-bilirubin (ALBI) grade and PLT score (ALBI-PLT score). Among the enrolled patients, 43 (13.9%) had HRVs. The area under the receiver operating characteristic curve of PLER for predicting HRVs (0.771, 95% confidence interval, 0.720–0.817) was significantly higher than that for PLT and LSM (p < 0.01). PLER was an independent risk factor for HRVs. VariScreen, PLEASE, and PLER could spare 20 (6.5%), 91 (29.4%), and 60 (19.4%) endoscopies, with 0, 3 (3.3%), and 1 (1.7%) HRVs missed, respectively. The EB6C and P120A36 criteria could spare 45 (14.5%) and 36 (11.6%) endoscopies, with 1 (2.2%) and 1 (2.8%) HRVs missed, respectively. The P150M6 criterion and ALBI-PLT score missed 6.8% and 10.3% of HRVs, respectively. We found that PLER performed better than other non-invasive tests. VariScreen secured the screening of HRVs in patients with HBV-related cirrhosis beyond Baveno VI criteria.

BackgroundPlasma-derived β-amyloid, tau, and neurodegeneration (ATN) biomarkers can accurately diagnose Alzheimer’s disease (AD) and predict its progression. Few studies have investigated the relationship between plasma biomarkers and changes in plasma inflammatory markers in clinically diagnosed AD.MethodsSeventy-four participants were recruited, including 30 mild-to-moderate AD dementia patients and 44 normal controls (NC). All participants underwent neuropsychological testing and blood sampling for biomarker testing. AD was clinically diagnosed according to the National Institute on Aging-Alzheimer’s Association (NIA-AA) core criteria and required age-mismatched hippocampal atrophy. We performed Single Molecule Array (Simoa), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA), to examine plasma ATN markers, including β-amyloid (Aβ) 40, Aβ42, p-tau181, total (t)-tau, neurofilament protein light chain (NfL), and inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8).ResultsThe level of the plasma Aβ42/Aβ40 ratio was significantly declined and the levels of the plasma p-tau181, NfL and TNF-α were significantly higher in the AD group than the NC group, but there was no significant difference in the levels of plasma t-tau, IL-1β, IL-6, and IL-8 between the AD and NC groups. The levels of plasma p-tau181, NfL, Aβ42/Aβ40 ratio, and TNF-α were all associated with impairments in multiple cognitive domains. Among them, the plasma Aβ42/Aβ40 ratio, and the p-tau181 and TNF-α levels were associated with impairments in global cognition, memory, and visuospatial abilities, but not with executive function, only plasma NfL level was associated with executive function. Plasma NfL showed higher diagnostic performance in AD than in NC individuals (AUC = 0.833). A combined diagnostic prediction model of plasma Aβ42/Aβ40 ratio, p-tau 181, and NfL had the highest value than each factor alone (AUC = 0.902),with a sensitivity and specificity of 0.867 and 0.886, respectively.ConclusionThe levels of plasma ATN biomarkers (Aβ42/Aβ40 ratio, p-tua181, and NfL) were significantly changed in clinically diagnosed AD patients and they all associated with different domains of cognitive impairment. Plasma ATN biomarkers better differentiate mild-to-moderate AD dementia from NC when they are incorporated into diagnostic models together rather than individually. Plasma ATN biomarkers have the potential to be a screening tool for AD. However, the expression of inflammatory factors in AD patients requires further research.

With the high precision and stability of its frequency signal outputs, active hydrogen maser plays an important role in such fields as timing, satellite navigation, and communication. However, it needs to be lighter so as to be applied in space. We made a research, based on the calculation of the hydrogen flow and the adsorption efficiency of the adsorption unit, on the parameters of the vacuum system and the structural requirements, and designed a combined vacuum pump for the Space Active Hydrogen Maser (SAHM). This vacuum pump consists of a getter pump and a small ion pump, the total mass of which is about 5 kg. The pumping speed will be about 474 L/s by computation, when an amount, 2.5 MPa L, of hydrogen has been adsorbed by getters. Theoretically, the total source hydrogen inflow in lifetime is not higher than 20% of the total capacity getter pump, thus the design should amply meet the requirements of the SAHM vacuum system, and is of great significance for future SAHM applications.

Progestin and adipoQ receptor 5 (PAQR5) affects the development of various malignancies and is specifically expressed in kidney. However, the role of PAQR5 in renal carcinoma remains unclear. We assessed the state of PAQR5 expression in kidney renal clear cell carcinoma (KIRC) by The Cancer Genome Atlas and Gene Expression Omnibus datasets. Moreover, immunohistochemistry was performed to observe the expressions of PAQR5 protein in tumor tissues. The relationships between PAQR5 expression and clinical characteristics were investigated by UALCAN. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter were used to analyze the effect of PAQR5 expression levels on overall survival and relapse-free survival (RFS). The re lationships between clinical characteristics and survival were also evaluated by univariate and multifactorial Cox regression. Gene Ontology term analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed on PAQR5 to explain the enrichment pathways and functions. Protein and protein interactions were explained by GeneMANIA and STRING. We also explored the relevance of PAQR5 to tumor immune cell infiltration and immunomodulatory molecules by TIMER and GEPIA. Finally, we explored the correlation of PAQR5 with the pathway proteins STATs, HIF-1α, and mTOR using the GSE40435 dataset. PAQR5 expression was low in KIRC and correlated significantly with clinical characteristics including cancer stage, tumor grade, and nodal metastasis status. Low PAQR5 expression was significantly associated with poorer survival. Cox regression analysis indicated that upregulation of PAQR5 was an independent factor for a good prognosis of KIRC. PAQR5 downregulation was associated mainly with STAT3 target upregulation, tumorigenesis, and poor differentiation. PAQR5 expression also correlated positively with B cells, neutrophils, macrophages, and dendritic cells and negatively with the infiltration of FOXP3+ Treg cells and the immune checkpoint molecules PD-1, CTLA4, and LAG3. Moreover, PAQR5 expression in KIRC was negatively correlated with the pathway proteins STAT1/2/3/4/5A, HIF-1α, and mTOR. PAQR5 is an excellent predictor of KIRC prognosis and may be a potential molecular therapeutic target.

Plant lesion mimics refer to necrotic spots spontaneously produced by the plant without mechanical damage, pathogen invasion, and adversity stress. Here, we isolated and characterized two rice (Oryza sativa L) mutants, namely, spl88-1 (spotted leaf88-1) and spl88-2 (spotted leaf88-2), which were identified from an ethyl methanesulfonate-mutagenized japonica cultivar Xiushui 11 population. Physiological and biochemical experiments indicated that more ROS accumulated in spl88-1 and spl88-2 than in wild type. spl88-1 and spl88-2 displayed spontaneous cell death and enhanced their resistance to bacterial blight by affecting the expression of defense-related genes. We isolated SPL88 by map-based cloning, which encoded a highly conserved Cullin protein. A single base deletion was detected in spl88-1 and spl88-2, in which the 132nd base C of SPL88-1 and the 381th base T of SPL88-2 were deleted, causing premature termination of protein translation. SPL88 was expressed in root, stem, leaf, leaf sheath, and panicle. The Cullin protein was localized in the cytoplasm and nucleus. The aforementioned results indicate that SPL88 regulates the growth and development of rice by affecting the expression of defense-related genes.

ObjectiveIncreasing evidence suggests that a subcortical pathway from the superior colliculus (SC) through the pulvinar to the amygdala plays a crucial role in mediating non-conscious processing in response to emotional visual stimuli. Given the atypical eye gaze and response patterns to visual affective stimuli in autism, we examined the functional and white matter structural difference of the pathway in boys with autism spectrum disorder (ASD) and typically developing (TD) boys.MethodsA total of 38 boys with ASD and 38 TD boys were included. We reconstructed the SC-pulvinar-amygdala pathway in boys with ASD and TD using tractography and analyzed tract-specific measurements to compare the white matter difference between the two groups. A region of interest-based functional analysis was also applied among the key nodes of the pathway to explore the functional connectivity network.ResultsDiffusion tensor imaging analysis showed decreased fractional anisotropy (FA) in pathways for boys with ASD compared to TD. The FA change was significantly associated with the atypical communication pattern in boys with ASD. In addition, compared to TD, we found that the ASD group was associated with increased functional connectivity between the right pulvinar and the left SC.ConclusionOur results indicated that the functional and white matter microstructure of the subcortical route to the amygdala might be altered in individuals with autism. This atypical structural change of the SC-pulvinar-amygdala pathway may be related to the abnormal communication patterns in boys with ASD.

Adverse environmental conditions, such as low temperature (LT), greatly limit the growth and production of tomato. Recently, light-emitting diodes (LEDs) with specific spectra have been increasingly used in horticultural production facilities. The chosen spectrum can affect plant growth, development, and resistance, but the physiological regulatory mechanisms are largely unknown. In this study, we investigated the effects of LED light supplementation (W:B = 2:1, light intensity of 100 μmol⋅m–2⋅s–1, for 4 h/day from 9:00 to 13:00) from above and below the canopy on tomato resistance under sub-LT stress (15/8°C). The results showed that supplemental lighting from underneath the canopy (USL) promoted the growth of tomato seedlings, as the plant height, stem diameter, root activity, and plant biomass were significantly higher than those under LT. The activity of the photochemical reaction center was enhanced because of the increase in the maximal photochemical efficiency (Fv/Fm) and photochemical quenching (qP), which distributed more photosynthetic energy to the photochemical reactions and promoted photosynthetic performance [the maximum net photosynthetic rate (Pmax) was improved]. USL also advanced the degree of stomatal opening, thus facilitating carbon assimilation under LT. Additionally, the relative conductivity (RC) and malondialdehyde (MDA) content were decreased, while the soluble protein content and superoxide dismutase (SOD) activity were increased with the application of USL under LT, thereby causing a reduction in membrane lipid peroxidation and alleviation of stress damage. These results suggest that light supplementation from underneath the canopy improves the cold resistance of tomato seedlings mainly by alleviating the degree of photoinhibition on photosystems, improving the activity of the photochemical reaction center, and enhancing the activities of antioxidant enzymes, thereby promoting the growth and stress resistance of tomato plants.

BackgroundThe treatment of long-term sores and ulcers of breast cancer metastatic recurrence is a serious challenge with successful cases rarely being documented. Herein we reported a successful case using the internal vitality supporting method of Chinese herbal medicine (CHM).Case SummaryA 59-year-old female Chinese patient, 10 years after breast cancer surgery, developed metastatic lesions in the lung. Thereafter she received radiofrequency ablation and adjuvant treatments for 1 year with severe sequelae, a right unhealed sore and ulcer. She became frustrated and depressive. And subsequently sought exclusive treatment under the guidance of a Traditional Chinese Medicine (TCM) physician. The patient's condition was categorized as a Qi (or vitality) deficiency-related sore and ulcer. In the next six months, the patient still follows a traditional Chinese medicine therapeutic regimen based on the internal vitality supporting method of Chinese herbs.ConclusionThe sore and ulcer from the surgical wound were healed. Up to now, the tumor markers have remained stable. TCM personalized survivorship treatment and psychosocial support can help patients improve their quality of life after acute treatment and in the long-term for cancer survivors.

Brain metastases represent a major cause of mortality among patients with breast cancer, and few effective targeted treatment options are currently available. Development of new biomarkers and therapeutic targets for breast cancer brain metastases (BCBM) is therefore urgently needed. In this study, we compared the gene expression profiles of the brain metastatic cell line MDA-MB-231-BR (231-BR) and its parental MDA-MB-231, and identified a total of 84 genes in the primary screening through a series of bioinformatic analyses, including construction of protein-protein interaction (PPI) networks by STRING database, identification of hub genes by applying of MCODE and Cytohubba algorithms, identification of leading-edge subsets of Gene Set Enrichment Analysis (GSEA), and identification of most up-regulated genes. Eight genes were identified as candidate genes due to their elevated expression in brain metastatic 231-BR cells and prognostic values in patients with BCBM. Then we knocked down the eight individual candidate genes in 231-BR cells and evaluated their impact on cell migration through a wound-healing assay, and four of them (KRT19, FKBP10, GSK3B and SPANXB1) were finally identified as key genes. Furthermore, the expression of individual key genes showed a correlation with the infiltration of major immune cells in the brain tumor microenvironment (TME) as analyzed by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA), suggesting possible roles of them in regulation of the tumor immune response in TME. Therefore, the present work may provide new potential biomarkers for BCBM. Additionally, using GSEA, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis, we determined the top enriched cellular functions or pathways in 231-BR cells, which may help better understand the biology governing the development and progression of BCBM.

Thermal shock is one of the main causes for the fracture of ceramic materials due to their inherent brittleness. Aiming to explore the mechanism of thermal shock cracking behavior of ceramics under different thermal shock conditions, a novel temperature-dependent failure criterion of thermal shock fracture of the ceramic materials was deduced based on the force-heat equivalence energy density principle. Combining this failure criterion and the finite element method, the thermal shock cracking behaviors of the thin circular and rectangular ceramic slabs under different thermal shock initial temperature were simulated. Results show that the morphology, periodicity, hierarchy, and number of thermal shock cracks obtained by numerical simulation are in good agreement with the experimental results. These essential characteristics verify the validity of the temperature-dependent failure criterion for thermal shock fracture. Furthermore, the strain energy of tension produced by thermal shock is proved to be the dominated mechanism for thermal shock-induced fracture.

Near surface air temperature (NSAT) is one of the most important climatic parameters and its variability plays a vital role in natural processes associated with climate. Based on an improved ANUSPLIN (short for Australian National University Spline) model which considers more terrain-related factors, this study analyzed the trends, anomalies, change points, and variations of NSAT in Southwest China from 1969 to 2018. The results revealed that the improved approach performed the best in terms of Mean Absolute Error (MAE), Root Mean Square Error (RMSE) and R-squared (R2) comparing to the conventional ANUSPLIN and co-kriging methods. It has great potential for future meteorological and climatological research, especially in mountainous regions with diverse topography. In addition, Southwest China experienced an overall warming trend of 0.21°C/decade for annual mean NSAT in the period 1969–2018. The warming rate was much higher than mainland China and global averages, and statistically significant warming began in the late 1990s. Moreover, consistent warming and significant elevation-dependent warming (EDW) were observed in most parts of Southwest China, and the hiatus or slowdown phenomenon after the 1997/1998 EL Niño event was not observed as expected. Furthermore, the remarkable increase in winter and minimum NSATs contributed more to the whole warming than summer and maximum NSATs. These findings imply that Southwest China responds to global warming more sensitively than generally recognized, and climate change in mountainous regions like Southwest China should be of particular concern.

ObjectiveTo predict the sensitivity of nasopharyngeal carcinoma (NPC) to neoadjuvant chemotherapy (NACT) based on magnetic resonance (MR) radiomics and clinical nomograms prior to NACT.Materials and MethodsFrom January 2014 to July 2015, 284 consecutive patients with pathologically confirmed NPC underwent 3.0 T MR imaging (MRI) before initiating NACT. The patients’ data were randomly assigned to a training set (n = 200) or a test set (n = 84) at a ratio of 7:3. The clinical data included sex, tumor (T) stage, lymph node (N) stage, American Joint Committee on Cancer (AJCC) stage, and the plasma concentration of Epstein–Barr virus (EBV) DNA. The regions of interest (ROI) were manually segmented on the axial T2-weighted imaging (T2WI) and enhanced T1-weighted imaging (T1WI) sequences using ITK-SNAP software. The radiomics data were post-processed using AK software. Moreover, the Maximum Relevance Minimum Redundancy (mRMR) algorithm and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for dimensionality reduction to screen for the features that best predicted the treatment efficacy, and clinical risk factors were used in combination with radiomics scores (Rad-scores) to construct the clinical radiomics-based nomogram. DeLong’s test was utilized to compare the area under the curve (AUC) values of the clinical radiomics-based nomogram, radiomics model, and clinical nomogram. Decision curve analysis (DCA) was employed to evaluate each model’s net benefit.ResultsThe clinical nomogram was constructed based on data from patients who were randomly assigned according to T2WI and enhanced T1WI sequences. In the training set, the T2WI sequence-based clinical radiomics nomogram and the radiomics model outperformed the clinical nomogram in predicting the NACT efficacy (AUC, 0.81 vs. 0.60, p = 0.001279 and 0.76 vs. 0.60, p = 0.03026). These findings were well-verified in the test set. The enhanced T1WI sequence-based clinical radiomics nomogram exhibited better performance in predicting treatment efficacy than the clinical nomogram (AUC, 0.79 vs. 0.62, respectively; p = 0.0000834). The DCA revealed that the T2WI and clinical radiomics-based nomograms resulted in a net benefit in predicting the NACT efficacy.ConclusionThe clinical radiomics-based nomogram improved the prediction of NACT efficacy, with the T2WI sequence-based clinical radiomics achieving the best effect.

Cucumber is one of the most widely grown vegetables in China and an indispensable fresh fruit in the diet. With the development of society, the demand of people for cucumber quality is higher and higher. Therefore, cultivating high-quality cucumber varieties is one of the main goals of cucumber breeding. With the rapid development of biotechnology such as molecular marker, cucumber quality control network is becoming clear. In this review, we describe the formation mechanism of cucumber fruit quality from three aspects: (1) the commercial quality of cucumber fruit, (2) nutritional quality formation, and (3) flavor quality of cucumber fruit. In addition, the determinants of cucumber fruit quality were summarized from two aspects of genetic regulation and cultivation methods in order to provide ideas for cucumber researchers and cultivators to improve fruit quality.

Objective: Atrial fibrillation is the most prevalent persistent arrhythmia in patients with hypertrophic obstructive cardiomyopathy. Comparative analyses of the safety and effectiveness of septal myectomy with and without surgical ablation are limited. This study aimed to compare the outcomes of septal myectomy with and without the Cox-maze IV procedure in patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation.Methods: Ninety-four patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation who underwent septal myectomy were analyzed, we divided it into concomitant Cox maze surgery (Cox-maze group) and no concomitant Cox maze operation (no Cox-maze group). Freedom from atrial fibrillation recurrence and all-cause mortality after surgery were assessed.Results: Freedom from all-cause mortality after septal myectomy at 1, 3, and 5 years was 98.5 ± 1.5% each in the Cox-maze group and 90.8 ± 6.3%, 85.1 ± 8.1%, and 85.1 ± 8.1%, respectively, in the no Cox-maze group. Patients in the no Cox-maze group had lower survival, freedom from atrial fibrillation recurrence off antiarrhythmic drugs, and arrhythmia control rate (including patients with successful antiarrhythmic drug conversion) than those in the Cox-maze group (P = 0.046, P = 0.040, and P = 0.012, respectively). Patients who underwent the Cox-maze IV procedure had lower atrial fibrillation recurrence rate than those who did not (hazard ratio, 0.141; 95% confidence interval, 0.042–0.479; P = 0.002). Post-operative increases in left atrial diameters (hazard ratio, 1.099; 95% confidence interval, 1.024–1.179; P = 0.009) were associated with atrial fibrillation recurrence.Conclusions: The Cox-maze IV procedure combined with septal myectomy improved mid-term survival and reduced mid-term atrial fibrillation recurrence in patients with hypertrophic obstructive cardiomyopathy and atrial fibrillation. The concomitant Cox-maze IV procedure was associated with a lower atrial fibrillation recurrence in patients with surgical hypertrophic obstructive cardiomyopathy and atrial fibrillation.

iChain is an application which was created to help meet the growing demand of machine learning. It allows users to pay those with powerful machines to run machine learning tasks for them, bypassing the need for a significant investment in a powerful computer to run it themselves. This is similar to services like a render farm. Our application functions using the Ethereum blockchain which ensures security and decentralization, as well as providing a platform for payment transactions. This article will discuss the background on machine learning and blockchain, the application, how it works, how the data moves through it, and how to use it. We hope our application will enable many without the funds to build or buy a powerful computer to experiment with and utilize complex machine learning tasks.

Excessive application of fertilizers has become a major issue in croplands of intensive agricultural systems in China, resulting in severe non-point source pollution; thus, reduction in the use of chemical fertilizers has received significant attention. Improving the nutrient storage capacity of soils or substrates is an effective approach for solving this problem. Humic acids (HA) are excellent soil conditioners. Thus, in the present study, their ability to improve the physico-chemical properties of three substrates with different textures was evaluated. HA treatments included 1% HA root application in three different types of substrates, including pure sand, pure cocopeat, and a mixture of sand:cocopeat (1:1, v/v) and their relative controls. We examined the morphological parameters of cucumber seedlings as well as pH buffering capacity (pHBC), total organic carbon (TOC), organic matter (OM), cation exchange capacity (CEC), and nutrient storage capacity of the three substrates. The results show that HA application improved the morphological parameters of cucumber seedlings (plant height, stem diameter, and biomass) in pure cocopeat and cocopeat-sand mixture treatments. On the contrary, HA addition had harmful effects on the cucumber seedlings cultivated in sand due to the low pHBC of sand. The seedlings cultivated in pure cocopeat showed the best morphological parameter performances among the seedlings grown in the three substrates. Furthermore, pHBC, TOC, OM, and CEC were enhanced by HA application. Incorporation of HA improved ammonium (NH4+) and potassium (K+) storage capacity while decreasing phosphorus (P) storage. Pure cocopeat had the highest pHBC, TOC, OM, CEC, and nutrient storage capacity among the three substrates. In conclusion, mixing 1% HA into substrates promoted cucumber growth, improved substrate properties, and enhanced fertilizer use efficiency. Pure cocopeat is a suitable substrate for cucumber cultivation, and mixing cocopeat with sand amends the substrate properties and consequently improves plant growth.

Animal disease models are necessary in medical research, and an appropriate animal model is of great importance for studies about the prevention or treatment of cancer. The most important thing in the selection of animal models is to consider the similarity between animals and humans. The tree shrew (Tupaia belangeri) is a squirrel-like mammal which placed in the order Scandentia. Whole-genome sequencing has revealed that tree shrews are extremely similar to primate and humans than to rodents, with many highly conserved genes, which makes the data from studies that use tree shrews as models more convincing and the research outcomes more easily translatable. In tumor research, tree shrews are often used as animal models for hepatic and mammary cancers. As research has progressed, other types of tree shrew tumor models have been developed and exhibit clinical manifestations similar to those of humans. Combining the advantages of both rodents and primates, the tree shrew is expected to be the most powerful animal model for studying tumors.

The optimal range of blood pressure variability (BPV) for acute stroke patients with large-vessel occlusion (LVO) remains unclear. This study investigated the association between BPV from admission through the first 24 h after intra-arterial thrombectomy (IAT) and short-term outcome in LVO patients. We retrospectively analyzed 257 consecutive patients with LVO stroke who were treated with IAT. BP values were recorded at 2-h intervals from admission through the first 24 h after IAT. BPV, as reflected by pulse pressure variability (PPV), was determined based on standard deviation (SD), coefficient of variation (CV), successive variation (SV), and the difference between maximum and minimum blood pressure (ΔBP; systolic BP minus diastolic BP). The association between BPV and clinical outcome (Modified Rankin Scale score at 90 days) was analyzed by multivariate logistic regression analysis. Of the 257 included patients, 70 had a good outcome at 3 months. PPV from admission through the first 24 h after IAT was independently associated in a graded manner with poor outcome [multivariable-adjusted odds ratios (95% confidence interval) for the highest of PPV were 43.0 (8.7–212.8) for SD, 40.3 (9.8–165.0) for CV, 55.0 (11.2–271.2) for SV, and 40.1 (8.0–201.9) for ΔBP]. The area under the receiver operating characteristic curve (95% confidence interval) of the PPV parameters were 0.924 (0.882–0.965) for SD, 0.886 (0.835–0.938) for CV, 0.932 (0.891–0.973) for SV, and 0.892 (0.845–0.939) for ΔBP, and the Youden index values were 0.740, 0.633, 0.759, and 0.756, respectively. In summary, BPV from admission through the first 24 h after IAT was independently associated with poor outcome at 3 months in patients with LVO, with greater variability corresponding to a stronger association. Thus, PPV may be a clinically useful predictor of functional prognosis in LVO patients treated with IAT.

BackgroundThe rapid development of coronavirus disease 2019 (COVID-19) pandemic has become a great threat to global health. Its mortality is associated with inflammation-related airway mucus hypersecretion and dysfunction of expectoration, and the subsequent mucus blockage of the bronchioles at critical stage is attributed to hypoxemia, complications, and even death. Traditional Chinese medicine (TCM) has rich experience in expectorant, including treatment of COVID-19 patients with airway mucus dysfunction, yet little is known about the mechanisms. This study is aiming to explore the potential biological basis of TCM herbal expectorant for treating COVID-19.ObjectiveTo get core herbs with high used frequency applications in the actions of expectoration by using association rule algorithm and to investigate the multitarget mechanisms of core herbs in expectorant formulae for COVID-19 therapies.MethodsForty prescriptions for expectorant were retrieved from TCM Formulae. The ingredient compounds and targets of core herbs were collected from the TCMSP database, Gene-Cards, and NCBI. The protein interaction network (PPI) was constructed by SRING, and the network analysis was done by Cytoscape software. Bioconductor was applied for functional enrichment analysis of targets.ResultsThe core herbs of expectorant could regulate core pathways (MAP kinase activity, cytokine receptor binding, G-protein-coupled receptor binding, etc.) via interactions of ingredients (glycyrol, citromitin, etc.) on mucin family to eliminate phlegm.ConclusionTCM herbal expectorant could regulate MAPK and cytokine-related pathways, thereby modulating Mucin-family to affect mucus generation and clearance and eventually retarding the deterioration of COVID-19 disease.

BackgroundSome lung diseases are cell type-specific. It is essential to study the cellular anatomy of the normal human lung for exploring the cellular origin of lung disease and the cell development trajectory.MethodsWe used the Seurat R package for data quality control. The principal component analysis (PCA) was used for linear dimensionality reduction. UMAP and tSNE were used for dimensionality reduction. Muonocle2 was used to extract lung epithelial cells to analyze the subtypes of epithelial cells further and to study the development of these cell subtypes.ResultsWe showed a total of 20154 high quality of cells from human normal lung tissue. They were initially divided into 17 clusters cells and then identified as seven types of cells, namely macrophages, monocytes, CD8 + T cells, epithelial cells, endothelial cells, adipocytes, and NK cells. 4240 epithelial cells were extracted for further analysis and they were divided into seven clusters. The seven cell clusters include alveolar cell, alveolar endothelial progenitor, ciliated cell, secretory cell, ionocyte cell, and a group of cells that are not clear at present. We show the development track of these subtypes of epithelial cells, in which we speculate that alveolar epithelial progenitor (AEP) is a kind of progenitor cells that can develop into alveolar cells, and find six essential genes that determine the cell fate, including AGER, RPL10, RPL9, RPS18, RPS27, and SFTPB.ConclusionWe provide a transcription map of human lung cells, especially the in-depth study on the development of epithelial cell subtypes, which will help us to study lung cell biology and lung diseases.

Background: Differences in genomic profiling and immunity-associated parameters between germline BRCA and non-BRCA carriers in TNBC with high tumor burden remain unexplored. This study aimed to compare the differences and explore potential prognostic predictors and therapeutic targets.Methods: The study cohort included 21 consecutive TNBC cases with germline BRCA1/2 mutations and 54 non-BRCA carriers with a tumor size ≥ 2 cm and/or ≥1 affected lymph nodes. Differences in clinicopathological characteristics and genomic profiles were analyzed through next-generation sequencing. Univariate Kaplan–Meier analysis and Cox regression model were applied to survival analysis. Immunohistochemistry was used to confirm the consistency between CCNE1 amplification and cyclin E1 protein overexpression.Results: The cohort included 16 and five patients with germline BRCA1 and BRCA2 mutations, respectively. Patients with germline BRCA1/2 mutations were diagnosed at a significantly younger age and were more likely to have a family history of breast and/or ovarian cancer. Six non-BRCA carriers (11.11%) carried germline mutations in other cancer susceptibility genes, including five mutations in five homologous recombination repair (HRR) pathway genes (9.26%) and one mutation in MSH3 (1.85%). Somatic mutations in HRR pathway genes were found in 22.22 and 14.29% of the non-BRCA and BRCA carriers, respectively. PIK3CA missense mutation (p = 0.046) and CCNE1 amplification (p = 0.2) were found only in the non-BRCA carriers. The median tumor mutation burden (TMB) was 4.1 Muts/Mb, whereas none of the cases had high microsatellite instability (MSI). BRCA status did not affect disease-free survival (DFS, p = 0.15) or overall survival (OS, p = 0.52). CCNE1 amplification was an independent risk factor for DFS in non-BRCA carriers with TNBC (HR 13.07, 95% CI 2.47–69.24, p = 0.003). Consistency between CCNE1 amplification and cyclin E1 protein overexpression was confirmed with an AUC of 0.967 for cyclin E1 signal intensity.Conclusions: We found differences in genetic alterations between germline BRCA and non-BRCA carriers with TNBC and a high tumor burden. TMB and MSI may not be suitable predictors of TNBC for immune checkpoint inhibitors. Notably, CCNE1 amplification is a novel potential prognostic marker and therapeutic target for non-BRCA carriers with TNBC. Cyclin E1 may be used instead of CCNE1 to improve clinical applicability.

Background: Colorectal adenocarcinoma with mucinous component (AWMC) is a special entity of colorectal cancer. The study is aimed at analyzing the clinicopathological characteristics, mutation spectrum, and prognosis of AWMC and comparing it with classical adenocarcinoma (AC) in a Chinese cohort.Methods: One hundred eight AMWC and 204 AC patients were included. Targeted next-generation sequencing (NGS) was performed on formalin-fixed paraffin-embedded (FFPE) tissues. AWMC was further divided into two groups: AWMC with signet ring cell component and AWMC without signet ring cell component. Clinicopathological features, mismatch repair protein (MMR) status, genetic alterations, and survival outcomes were analyzed after tumor location was taken into consideration.Results: AWMC had larger tumor size (p = 0.014) and showed predilection for proximal colon (p < 0.001) compared with AC. Regardless of primary sites, AWMC was associated with less metastasis (p < 0.001) and earlier AJCC stage (p < 0.001). Mismatch repair protein deficiency (dMMR) was more commonly detected in AWMC than in AC for right-sided colon (p < 0.001), but the difference was not significant for left-sided colon (p = 0.081). The five most commonly mutated genes in AWMC were KRAS (45.4%), TP53 (39.8%), APC (22.2%), PIK3CA (22.2%), and SMAD4 (10.2%). AWMC showed a significantly lower mutation rate of TP53 than AC, both in right-sided colon and in left-sided colon (p < 0.001 and p = 0.033, respectively). In left-sided colon, AWMC with signet ring cell component had a significantly smaller size than tumors with signet ring cell component (p = 0.034). No dMMR cases were detected in AWMC with signet ring cell component (n = 7). Moreover, AWMC with signet ring cell component had a significantly lower KRAS mutation rate than AWMC without signet ring cell component, both in right-sided colon and in left-sided colon (p = 0.036 and p = 0.012, respectively). The disease-specific survival (DSS) for AWMC and AC were not statistically different (p = 0.0587). Multivariate analysis showed that AWMC was not an independent predictor of prognosis.Conclusion: Regardless of primary sites, AWMC demonstrates less metastasis, earlier stages, more frequent dMMR, and lower TP53 mutation rate than AC. Our results indicate that different molecular pathogenesis might underlie mucinous morphology in colorectal carcinoma. Mucinous component is not an independent factor of outcome.

Background and Purpose: The association of retinal microvascular abnormalities with the total cerebral small vessel disease (cSVD) burden found on brain MRI has not been determined. In the present study, we examined whether the retinopathy score could predict the total cSVD burden in ischemic stroke/transient ischemic attack (TIA) patients. A simple practical diagnostic tool may help identify candidates for MRI screening.Methods: We consecutively collected clinical data including retinal photography and cerebral MRI of ischemic stroke/TIA patients from August 2016 to August 2017 at our stroke center. The retinopathy score was assessed by the Keith-Wagener-Barker grading system for analyzing retinal microvascular abnormalities. To evaluate the total cSVD burden, the total cSVD score was assessed by awarding one point for the presence of each marker of cSVD on MRI. The clinical characteristics and retinopathy score were analyzed across patients for each total cSVD score. The association between the retinopathy score and the total cSVD score was analyzed.Results: Among the 263 enrolled patients, the frequency of hypertension in patients with a total cSVD score of 2, 3, or 4 was higher than that in patients with a score of 0 (69.5, 71.7, and 89.2% vs. 45.2% respectively, all P < 0.05). The retinopathy score was related to the total cSVD score (r = 0.687, P < 0.001). Adjusted multivariate ordinal regression showed that the retinopathy score was independently correlated with the total cSVD score (odds ratio [OR], 4.18; 95% confidence interval [CI], 3.07–5.70) after adjustment for age, history of hypertension, previous stroke/TIA and current smoking. The c statistics were 0.30 (95% CI, 0.24–0.37; P < 0.05), 0.46 (95% CI, 0.39–0.53; P = 0.303), 0.79 (95% CI, 0.72–0.86; P < 0.001), and 0.81 (95% CI, 0.74–0.88; P < 0.001) for predicting the total cSVD score of 1, 2, 3, and 4 respectively.Conclusions: These results suggest that retinal microvascular abnormalities have predictive value for severe total cSVD burden in ischemic stroke/TIA patients.

Background: Limited resection has been carried out increasingly in early stage NSCLC as an alternative to standard lobectomy. This study aimed to investigate the differences in survival and long-term cause-specific mortality between wedge resection and segmentectomy for treatment of stage IA lung adenocarcinoma.Method: Cases with primary lung adenocarcinoma that received wedge resection and segmentectomy between 2004 and 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching was performed to balance the baseline covariates. Long-term cause-specific mortality was investigated through competing risk analysis. The overall survival (OS) was estimated with the Kaplan-Meier method with the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors.Results: Of the 3,046 cases included, 2,360 and 686 cases underwent wedge resection and segmentectomy, respectively. After propensity score matching, 686 pairs were selected. Segmentectomy was associated with a significantly better OS in stage IA2, grade I/II, female, and married patients. The segmentectomy group had a higher lung-cancer specific mortality in 65–74 years of age, stage IA1 and IA3, male, and married patients, and a lower chronic obstructive pulmonary disease (COPD) specific mortality in ≤64 and 65–74 years of age, stage IA1, IA2, and IA3, all grade, male, and married patients. The cardiovascular disease (CVD) specific mortality was also lower in the segmentectomy group in ≥75 years of age, stage IA1 and IA3, and grade I/II patients.Conclusion: Wedge resection was inferior to segmentectomy in terms of OS regarding all included parameters. In most cases, the segmentectomy group had higher lung-cancer specific mortality and lower COPD and CVD specific mortality.

Background: The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys.Methods: Twelve monkeys underwent successful distal M1 segment of the left middle cerebral artery occlusion (MCAO) and were randomly and equally assigned to the MCAO-1.5 m, MCAO-6 m, and MCAO-12 m groups, which were sacrificed 1.5, 6, and 12 months after cerebral infarction induction, respectively. Four monkeys that underwent a sham operation were sacrificed 12 months later. The gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA sequencing and gas chromatography mass spectrometry, respectively. Histological examinations of the transverse colon were performed. Plasma D-lactate, zonulin, lipopolysaccharide (LPS), tumor necrosis factor (TNF-α), interferon (IFN)-γ, and interleukin (IL)-6 were detected by immunoassay kits.Results: The levels of the Bacteroidetes phylum and Prevotella genus were significantly increased, while the Firmicutes phylum as well as the Faecalibacterium, Oscillospira, and Lactobacillus genera were decreased after cerebral infarction. Gut-originating SCFAs were significantly decreased 6 and 12 months after cerebral infarction (P < 0.05). We observed intestinal mucosal damage, evaluated by Chiu's score. Plasma D-lactate, zonulin, LPS, TNF-α, IFN-γ, and IL-6 were significantly increased after cerebral infarction (P < 0.05). Additionally, the increases in plasma LPS, TNF-α, IFN-γ, and IL-6 after cerebral infarction coincided with overgrowth of the Bacteroidetes phylum (P < 0.001).Conclusion: Cerebral infarction induces persistent host gut microbiota dysbiosis, intestinal mucosal damage, and chronic systemic inflammation in cynomolgus monkeys.

Low light (LL) is one of the main limiting factors that negatively affect tomato growth and yield. Techniques of chemical regulation are effective horticultural methods to improve stress resistance. Strigolactones (SLs), newly discovered phytohormones, are considered as important regulators of physiological responses. We investigated the effects of foliage spray of GR24, a synthesized SLs, on tomato seedlings grown under LL stress conditions. The results showed that application of GR24 effectively mitigated the inhibition of plant growth and increased the fresh and dry weight of tomato plants under LL. Additionally, GR24 also increased the chlorophyll content (Chla and Chlb), the net photosynthetic rate (Pn), the photochemical efficiency of photosystem (PS) II (Fv/Fm), and the effective quantum yield of PSII and I [Y(II) and Y(I)], but decreased the excitation pressure of PSII (1-qP), the non-regulatory quantum yield of energy dissipation [Y(NO)] and the donor side limitation of PSI [Y(ND)] under LL. Moreover, application of GR24 to LL-stressed tomato leaves increased the electron transport rate of PSII and PSI [ETR(II) and ETR(I)], the ratio of the quantum yield of cyclic electron flow (CEF) to Y(II) [Y(CEF)/Y(II)], the oxidized plastoquinone (PQ) pool size and the non-photochemical quenching. Besides, GR24 application increased the activity and gene expression of antioxidant enzymes, but it reduced malonaldehyde (MDA) and hydrogen peroxide (H2O2) content in LL-stressed plants. These results suggest that exogenous application of GR24 enhances plant tolerance to LL by promoting plant utilization of light energy to alleviate the photosystem injuries induced by excess light energy and ROS, and enhancing photosynthesis efficiency to improve plant growth.

Background and Purpose: Extracranial artery stenosis (ECAS) is related to individual imaging markers of cerebral small vessel disease (cSVD). However, little has been reported on the association between ECAS and the total burden of cSVD as assessed by magnetic resonance imaging (MRI). The purpose of this study was to investigate the relationship between ECAS and cSVD burden in patients with ischemic stroke of suspected small or large artery origin.Methods: We reviewed consecutive patients with ischemic stroke of suspected small or large artery origin who underwent color Doppler ultrasonography and brain MRI. Bilateral extracranial cerebral arteries including common carotid artery, internal carotid artery (ICA), and proximal vertebral artery (VA, ostium, V2–3 segments) were assessed using color Doppler ultrasonography. ECAS severity was classified as no/mild stenosis, moderate stenosis, severe stenosis, or occlusion. The total cSVD score was assessed by awarding one point according to the load of each of these cSVD markers as determined using MRI; lacunar infarction, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces. The relationship between ECAS severity and cSVD burden according to MRI was examined.Results: Two hundred and twenty one patients were included in this study (mean age 61 ± 12 years, 75.6% male). Hypertension, current smoking, hyperlipidaemia, and diabetic mellitus were frequent among the patients (67.4, 45.7, 43.9, and 36.7%, respectively), while the other vascular risk factors including previous stroke or TIA and alcohol excess were less frequent (19.0 and 15.4%, respectively). Patients with higher total cSVD burden was significantly older and had severer ECAS. The frequency of hypertension was significantly higher in patients with higher total cSVD burden. This analysis indicated that that increasing ECAS severity (from no stenosis through to 100%) was independently associated with increasing total cSVD score after adjusting for other vascular risk factors (odds ratio 1.76, 95% CI [1.16–2.69]).Conclusions: In this study, high levels of ECAS from ultrasound evidence were associated with coexisting advanced cerebral cSVD in ischemic stroke patients of suspected small or large artery origin. Further studies are required to determine if and how extracranial arterial imaging helps reduce cSVD burden or improves cognitive function.

Lead is a ubiquitous pollutant that constitutes an environmental hazard worldwide. Although lead has been known as a carcinogenic factor in animal models, its role in human carcinogenesis is still a topic of debate with limited epidemiological evidence. Moreover, the association between urinary lead, as the most non-invasive and accessible way for lead measurement in human, and cancer mortality in general population has never been explored. We addressed this subject using continuous National Health and Nutrition Examination Survey 1999–2010 data and its Mortality Follow-Up Study. Of 5,316 subjects in study population, 161 participants died due to cancer. Cancer-specific mortality was associated with urinary lead levels after multivariable adjustment. Kaplan–Meier survival curve and cubic regression spline analyses indicated that high concentration of urinary lead exhibited significant association with raised death rate of cancer. Despite the marked decrease in environmental lead levels over the past three decades, lead exposure is still the significant determinant of cancer mortality in general population in U.S., and quantification of urinary lead may serve as a non-invasive approach to facilitate biomarker discovery and clinical translational research.