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Abstract This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression. Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database. Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance. Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores. Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group. We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

Abstract Background The impact of the Plan-Do-Check-Act (PDCA) cycle in improving the timeliness of electronic medical record documentation (EMRd) remains uncertain. EMRd that is completed beyond the specified time is classified as late EMRd, while unqualified EMRd refers to electronic medical records with important sections that are not completed on time according to the Chinese Basic Norms of Medical Records Writing. This study aimed to evaluate the effectiveness of PDCA management in improving the timeliness of EMRd among resident doctors. Method This study utilized a before and after design. Resident doctors rotating in the Head and Neck Oncology Department of West China Hospital, Sichuan University, from November 2021 to August 2022 were classified as the control group and did not receive specific training on the timeliness of EMRd. Those rotating from September 2022 to June 2023 were assigned to the PDCA group, which was managed using the PDCA cycle. The effectiveness of PDCA cycle management was evaluated by comparing the incidence of late EMRd and unqualified EMRd between two groups. Univariate and multivariate binary logistic regression analyses were conducted tocontrol for confounding factors. Results A total of 245 resident doctors were included, with 162 doctors in the PDCA group and 152 doctors in the control group. The incidences of late EMRd (5.40% vs. 2.56%, P = 0.005) and unqualified EMRd (1.05% vs. 0.00%, P

Abstract This study aimed to identify the specific site of pulmonary vein conduction recovery after radiofrequency ablation (RFA) of atrial fibrillation (AF) for improved outcomes and reduced recurrence. Patients who underwent RFA for AF at our institution were included. The ablation procedure was guided by the ablation index (AI) and left, and right atrial pressures were monitored before and after ablation. Additionally, the recovery time of the sinoatrial node under Burst 400/300 ms stimulation was examined. Among 60 repeat procedure patients, 48 had paroxysmal and 12 had persistent AF. The recovery sites were 36.6% in the left anterior superior, 35% in the right anterior superior, 20% in the left anterior inferior, 20% in the right anterior inferior, 13.3% in the right top, and 11.6% in the left top. Preoperative and postoperative left and right atrial pressures were significantly higher in the persistent AF group compared with the paroxysmal AF group (P

Abstract Ectomycorrhizal fungi (EMF) are key symbiotic microbial components for the growth and health of trees in urban greenspace habitats (UGSHs). However, the current understanding of EMF diversity in UGSHs remains poor. Therefore, in this study, using morphological classification and molecular identification, we aimed to investigate EMF diversity in three EMF host plants: Cedrus deodara in the roadside green belt, and C. deodara, Pinus massoniana, and Salix babylonica in the park roadside green belt, in Guiyang, China. A total of 62 EMF Operational Taxonomic Units (OTUs) were identified, including 13 EMF OTUs in the C. deodara roadside green belt, and 23, 31, and 9 EMF OTUs in the park green belts. C. deodara, P. massoniana, and S. babylonica were respectively identified in park green belts. Ascomycota and Basidiomycota were the dominant phylum in the EMF communities in roadside and park green habitat, respectively. The Shannon and Simpson indexes of the C. deodara EMF community in the park green belt were higher than those in the roadside green belt. EMF diversity of the tree species in the park green belt was P. massoniana > C. deodara > S. babylonica. Differences in EMF community diversity was observed among the different greening tree species in the UGSHs. UGSHs with different disturbance gradients had a significant impact on the EMF diversity of the same greening tree species. These results can be used as a scientific reference for optimizing the design and scientific management of UGSHs.

Abstract Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) has demonstrated efficacy in clinical trials of childhood allergic rhinitis (AR). Currently, there is a lack of some generally accepted biomarkers that may predict the clinical response to SCIT to eventually achieve personalized therapy. In this study, 28 children with AR received Der p SCIT for 26–30 months at baseline, and four efficacy endpoints, serum interleukin (IL)-5, periostin, Der p-specific IgE (sIgE), and Der p sIgG4, were measured by ELSIA. Clinical symptoms and characteristics were assessed by questionnaires, and the associations among periostin, Der p 2 sIgE and clinical efficacy were analyzed. The results showed that SCIT demonstrated a significant reduction in Der p 1 sIgE (P

Abstract Some cases of chronic rhinosinusitis (CRS) require surgical treatment and postoperative nasal packing, but bleeding and adhesion are common complications after nasal surgery. Biodegradable drug-loaded implants hold great therapeutic options for the treatment of CRS, but little data are available regarding the safety and efficacy of a novel drug-loaded haemostatic sponge (DLHS) in the sinus. The aim of this study was to investigate the safety and efficacy of DLHS in the sinus. We conducted a prospective, randomized, controlled, double-blind clinical trial. In this clinical trial, 49 patients were enrolled and randomly divided into 2 groups: group A (n = 25) had the DLHS containing 1 mg budesonide and 0.67 mg sodium hyaluronate placed into the sinus, and group B (n = 24) had the Nasopore placed after ESS. Endoscopic follow-up was performed for 12 weeks, and the findings were classified using the discharge, inflammation, polyps/oedema (DIP) endoscopic appearance scores. All patients completed questionnaires to evaluate their sinonasal symptoms by using the sinonasal outcome test-22 (SNOT-22) Chinese version and visual analogue scale (VAS). Serum cortisol concentration in group A was measured prior to surgery and at days 1, 3, 7, and 14 after nasal surgery. Comparing group A and group B, at 2 weeks, no significant differences were observed in either objective or subjective parameters. The mean value of VAS for rhinorrhoea and DIP for oedema and the mean value of nasal adhesion were significantly lower in Group A than in Group B at 6 and 12 weeks, but a significant difference did not occur in SNOT-22 and VAS for dysosmia between the two groups at 6 and 12 weeks. The mean serum cortisol concentrations in group A at the follow-up were within normal limits without remarkable fluctuations. This study demonstrates the safety and efficacy of a novel biodegradable DLHS with the possibility of being used in CRS patients, and this sponge may reduce inflammation and minimize adhesions via controlled local drug delivery without measurable systemic exposure.

Abstract Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking. Here, we analyzed the peptide spectrum in HCC tissues using peptidomic techniques and explored the potentially beneficial peptides involved in HCC. Changes in peptide profiles in HCC were examined using liquid chromatography-mass spectrometry (LC–MS/MS). Analyze the physicochemical properties and function of differently expressed peptides using bioinformatics. The effect of candidate functional peptides on HCC cell growth and migration was evaluated using the CCK-8, colony formation, and transwell assays. Transcriptome sequencing analysis and western blot were employed to delve into the mode of action of potential peptide on HCC. Peptidomic analysis of HCC tissue yielded a total of 8683 peptides, of which 452 exhibited up-regulation and 362 showed down-regulation. The peptides that were differentially expressed, according to bioinformatic analysis, were closely linked to carbon metabolism and the mitochondrial inner membrane. The peptide functional validation identified a novel peptide, PDLC (peptide derived from liver cancer), which was found to dramatically boost HCC cell proliferation through the Ras/Raf/MEK/ERK signaling cascade. Our research defined the peptide’s properties and pattern of expression in HCC and identified a novel peptide, PDLC, with a function in encouraging HCC progression, offering an entirely new potential therapeutic target the disease.

Abstract Understanding the combined effects of risk factors on all-cause mortality is crucial for implementing effective risk stratification and designing targeted interventions, but such combined effects are understudied. We aim to use survival-tree based machine learning models as more flexible nonparametric techniques to examine the combined effects of multiple physiological risk factors on mortality. More specifically, we (1) study the combined effects between multiple physiological factors and all-cause mortality, (2) identify the five most influential factors and visualize their combined influence on all-cause mortality, and (3) compare the mortality cut-offs with the current clinical thresholds. Data from the 1999–2014 NHANES Survey were linked to National Death Index data with follow-up through 2015 for 17,790 adults. We observed that the five most influential factors affecting mortality are the tobacco smoking biomarker cotinine, glomerular filtration rate (GFR), plasma glucose, sex, and white blood cell count. Specifically, high mortality risk is associated with being male, active smoking, low GFR, elevated plasma glucose levels, and high white blood cell count. The identified mortality-based cutoffs for these factors are mostly consistent with relevant studies and current clinical thresholds. This approach enabled us to identify important cutoffs and provide enhanced risk prediction as an important basis to inform clinical practice and develop new strategies for precision medicine.

Abstract Background Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations. Methods We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016–2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs). Results During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups. Conclusions We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent.

Abstract Background A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model’s performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. Methods A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). Results The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. Conclusions The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.

Abstract To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97–1.16), 0.95 (0.85–1.06), 0.94 (0.86–1.02) and 0.89 (0.80–0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA.

Abstract Background Cognitive dysfunction is the most common non-motor symptom in Parkinson’s disease (PD), and timely detection of a slight cognitive decline is crucial for early treatment and prevention of dementia. This study aimed to build a machine learning model based on intra- and/or intervoxel metrics extracted from diffusion tensor imaging (DTI) to automatically classify PD patients without dementia into mild cognitive impairment (PD-MCI) and normal cognition (PD-NC) groups. Methods We enrolled PD patients without dementia (52 PD-NC and 68 PD-MCI subtypes) who were assigned to the training and test datasets in an 8:2 ratio. Four intravoxel metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), and two novel intervoxel metrics, local diffusion homogeneity (LDH) using Spearman’s rank correlation coefficient (LDHs) and Kendall’s coefficient concordance (LDHk), were extracted from the DTI data. Decision tree, random forest, and eXtreme gradient boosting (XGBoost) models based on individual and combined indices were built for classification, and model performance was assessed and compared via the area under the receiver operating characteristic curve (AUC). Finally, feature importance was evaluated using SHapley Additive exPlanation (SHAP) values. Results The XGBoost model based on a combination of the intra- and intervoxel indices achieved the best classification performance, with an accuracy of 91.67%, sensitivity of 92.86%, and AUC of 0.94 in the test dataset. SHAP analysis showed that the LDH of the brainstem and MD of the right cingulum (hippocampus) were important features. Conclusions More comprehensive information on white matter changes can be obtained by combining intra- and intervoxel DTI indices, improving classification accuracy. Furthermore, machine learning methods based on DTI indices can be used as alternatives for the automatic identification of PD-MCI at the individual level.

Abstract Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single‐cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti‐inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the change of the epigenetic regulator enhancer of zeste homolog2 (EZH2) accompanied with the emergence of hepatic senescent cells while liver fibrosis regressed. Blocking EZH2 signaling by EPZ6438 reduced hepatic senescent cells and macrophages, decelerating liver fibrosis regression. Moreover, the promoter region of EZH2 was transcriptionally suppressed by Notch‐Hes1 (hairy and enhancer of split 1) signaling. Disruption of Notch in macrophages using Lyz2 (lysozyme 2) Cre‐RBP‐J (recombination signal binding protein Jκ) f/f transgenic mice, enhanced hepatic cellular senescence, and facilitated fibrosis regression by upregulating EZH2 and blocking EZH2 abrogated the above effects caused by Notch deficiency. Ultimately, adopting Notch inhibitor Ly3039478 or exosome‐mediated RBP‐J decoy oligodeoxynucleotides accelerated liver fibrosis regression by augmenting hepatic cellular senescence.

Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease first discovered in Ta-pieh Mountains in central China in 2009. It is caused by a novel bunyavirus infection (SFTSV). Since the first discovery of SFTSV, there have been case reports and epidemiological studies on SFTS in several East Asian countries, such as South Korea, Japan, Vietnam and so on. With the rising incidence of SFTS and the rapid spread of the novel bunyavirus around the world, it is clear that the virus has a pandemic potential and may pose a threat to global public health in the future. Early studies have suggested that ticks are an important medium for the transmission of SFTSV to humans; in recent years, it has been reported that there is also human-to-human transmission. In endemic areas, potential hosts include a variety of livestock and wildlife. When people are infected with SFTV, the main clinical manifestations are high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, liver and kidney function damage, and even MODS, with a mortality rate of about 10–30%. This article reviews the latest progress of novel bunyavirus, including virus transmission vector, virus genotypic diversity and epidemiology, pathogenesis, clinical manifestation and treatment.

Abstract Background Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates. Methods The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we (1) screened the survival-related DEGs by Cox regression analysis, (2) selected the cytogenetics risk-related DEGs by DESeq2 R package, and (3) filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of the present study. The following Multivariate.

Abstract By establishing a three-dimensional finite element model of ankle injury arising from supination and external rotation, the stress characteristics of the posterior malleolar surface can be obtained, and analysis of the corresponding stress on the lateral ankle can be conducted. Thin-layer computed tomography images of normal ankle joint in the supination and external rotation nonweight-bearing states was selected, to construct a three-dimensional data model of each ankle joint. A load was applied to examine different ankle joint stress values and pressure distributions on the surface of the posterior ankle joint. A 600 N vertical compressive and 10 Nm internal rotation load was applied in Stage III (removing the anterior tibiofibular ligament and the posterior tibiofibular ligament) of SER (supination-external rotation). When the lateral malleolar was intact, the maximum stress (132.7 MPa) was located at the point of attachment of the posterior tibiofibular ligament to the fibula, and the maximum pressure of the posterior malleolar surface was lower than 4.505 MPa. When a lateral malleolar fracture was present, the maximum stress (82.72 MPa) was located on the fibular fracture surface, and the maximum pressure of the posterior malleolar surface was 8.022 MPa. This study shows that reconstruction of the lateral malleolus in supination-external rotation ankle injuries significantly affects the stress distribution at the posterior malleolar joint surface. Through this reconstruction, the pressure distribution of the posterior malleolar joint surface can be significantly reduced.

Changes in altitude have a long-term and profound impact on mountain forest ecosystems. However, there have been few reports on changes in soil carbon, nitrogen, and phosphorus contents (SCNPC) along altitudinal gradients in subtropical karst mountain forests, as well as on the factors influencing such changes. We selected five Pinus massoniana forests with an altitudinal gradient in the karst mountain area of Southwest China as research objects and analyzed the changes in SCNPC along the altitudinal gradient, as well as the influencing factors behind these changes. Soil organic carbon, total nitrogen, and available nitrogen contents first increased and then decreased with increasing altitude, whereas the contents of total phosphorus and available phosphorus showed no obvious trend. In the karst mountain P. massoniana forest, SCNPC in the topsoil is most significantly affected by total glomalin-related soil protein (TG) and soil moisture content (SMC) (cumulative explanatory rate was 45.28–77.33%), indicating that TG and SMC are important factors that affect SCNPC in the karst mountain P. massoniana forest. In addition, the main environmental factors that affect SCNPC in the subsoil showed significant differences. These results may provide a better scientific reference for the sustainable management of the subtropical mountain P. massoniana forest.

Shifts in forest soil microbial communities over altitudinal gradients have long been attracting scientific interest. The distribution patterns of different soil microbial communities along altitudinal gradients in subtropical mountain forest ecosystems remain unclear. To better understand the changes in soil microbial communities along an altitude gradient, we used Illumina MiSeq metagenome sequencing technology to survey the soil microbial communities in a Pinus massoniana forest at four elevations (Mp1000, Mp1200, Mp1400, Mp1600) and in a tea garden in Guizhou Leigong Mountain in Southwestern China. We observed that the richness of bacteria, fungi, and viruses in the soil microbial community changed in a unimodal pattern with increasing elevation while that of Archaea first increased significantly, then decreased, and finally increased again. Euryarchaeota and Thaumarchaeota were the predominant Archaea, Proteobacteria and Acidobacteria were the predominant bacterial groups, Ascomycota and Basidiomycota were the predominant fungal groups, and Myoviridae, Podoviridae, and Siphoviridae were the predominant virus groups. Amino acid transport and metabolism, energy production and conversion, signal transduction mechanisms, and DNA replication, restructuring and repair were the predominant categories as per NOG function gene-annotation. Carbohydrate metabolism, global and overview map, amino acid metabolism, and energy metabolism were predominant categories in the KEGG pathways. Glycosyl transferase and glycoside hydrolase were predominant categories among carbohydrate enzyme-functional genes. Cluster, redundancy, and co-occurring network analyses showed obvious differences in the composition, structure, and function of different soil microbial communities along the altitudinal gradient studied. Our findings indicate that the different soil microbial communities along the altitudinal gradient have different distribution patterns, which may provide a better understanding of the mechanisms that determine microbial life in a mid-subtropical mountain forest ecosystem.

Abstract The osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) declines dramatically with aging. By using a calvarial defect model, we showed that a senolytic cocktail (dasatinib+quercetin; D + Q) improved osteogenic capacity of aged BMSC both in vitro and in vivo. The study presented a model to assess strategies to improve bone-forming potential on aged BMSCs. D + Q might hold promise for improving BMSC function in aged populations.

Abstract LncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor = − 0.15, P

Chyle leakage can be caused by abdo­minal surgery and managed succes­sfully without surgical treatment; how­ever, no preventive measures are available. Therefore, we introduce a new method to prevent post-operative chyle leakage. To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of chyle fistula formation after radical resection of right colon cancer. Five patients with a diagnosis of right colon cancer undergoing laparosco­pic radical colectomy with D3 lymph node dissection were examined in this study. At the end of the operation, two points of 2.5 mg ICG were injected subserosally at the proximal end of the anastomosis (1 ml per point). Then the surgical field was screened by using ICG fluorescence to accurately locate the chyle leakage. Chyle leakage was noted and repaired with a Hem-O-Lock. The volume of output of each drain after surgery was measured daily until the patients were discharged. We were able to observe ICG fluorescence in the lymphatic vessels within 3 minutes of ICG injection. This visualization allowed us to accurately locate and quickly repair chyle leakage within 5 minutes. Clinical observation after surgery and at a 1-month follow-up showed no chyle leakage in all 5 patients. Indocyanine green lymphangiography can feasibly guide the location and repair of chyle leakage after right colon cancer resection.

Abstract In this study, bismuth oxychloride/graphene oxide (BiOCl-GO) composite was fabricated by facile one pot hydrothermal method. The pure BiOCl and BiOCl-GO composite was characterized by X-ray diffraction, Transmission electron microscopy X-ray photoelectron spectroscopy and UV–Vis diffuse reflectance spectroscopy. The synthesized composite was then assessed for photocatalytic degradation of diclofenac sodium (DCF) in visible as well as direct solar light and UV irradiation. Results indicated that the photocatalytic removal efficiency of DCF was significantly affected by dose of catalysts, pH value and source of light. The results reveled that degradation efficiency of BiOCl-GO for DCF reduced from 100 to 34.4% with the increases in DCF initial concentration from 5 mg L−1 to 25 mg L−1. The solar light degradation of DCF using BiOCl-GO was achieved with apparent rate constant 0.0037 min−1. The effect of scavengers study revealed that superoxide ions and holes were mainly responsible for DCF degradation. The regeneration study indicates that BiOCl-GO composite can be successfully recycled up to the five cycles. The study revealed the effectiveness of one pot hydrothermal method for the fabrication of BiOCl-GO composite.

Abstract Background Kidney ischemia reperfusion injury (IRI) is a common cause of acute kidney injury and an unavoidable consequence of kidney transplantation and still lacks specific therapeutics. Recently, mesenchymal stem cell (MSC) has been emerging as a promising cell-based therapy for IRI in the context of transplantation. MSC negatively regulates the secretion of pro-inflammatory as well as the activation of immune cells during IRI through its unique immunosuppressive property. Methods We employed mice kidney IRI model and MSC cell line to monitor the IRI related checkpoints. siRNAs were utilized to knock down the potential key factors for mechanistic analysis. Statistical analysis was performed by using one-way ANOVA with Tukey’s post hoc procedure by SPSS. Results The expression of high-mobility group box 1 protein (HMGB1) is increased in the acute phase as well as the recovery stage of IRI. Importantly, the HMGB1 upregulation is correlated with the injury severity. HMGB1 diminishes the MSC induced immunosuppressive capacity in the presence of pro-inflammatory cytokines in vitro. Toll like receptor 4 (TLR4)-mediated inducible nitric oxide synthase (iNOS) inhibition contributes to the negative effect of HMGB1 on MSCs. HMGB1-TLR4 signaling inhibition augments the therapeutic efficacy of MSCs in mice renal IRI model. Conclusions These findings demonstrate that HMGB1 plays a crucial role in shaping the immunoregulatory property of MSCs within the microenvironments, providing novel insights into the crosstalk between MSCs and microenvironment components, suggesting HMGB1 signals as a promising target to improve MSC-based therapy.

Abstract Background Metabolic reprogramming, immune evasion and tumor-promoting inflammation are three hallmarks of cancer that provide new perspectives for understanding the biology of cancer. We aimed to figure out the relationship of tumor glycolysis and immune/inflammation function in the context of breast cancer, which is significant for deeper understanding of the biology, treatment and prognosis of breast cancer. Methods Using mRNA transcriptome data, tumor-infiltrating lymphocytes (TILs) maps based on digitized H&E-stained images and clinical information of breast cancer from The Cancer Genome Atlas projects (TCGA), we explored the expression and prognostic implications of glycolysis-related genes, as well as the enrichment scores and dual role of different immune/inflammation cells in the tumor microenvironment. The relationship between glycolysis activity and immune/inflammation function was studied by using the differential genes expression analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analyses (GSEA) and correlation analysis. Results Most glycolysis-related genes had higher expression in breast cancer compared to normal tissue. Higher phosphoglycerate kinase 1 (PGK1) expression was associated with poor prognosis. High glycolysis group had upregulated immune/inflammation-related genes expression, upregulated immune/inflammation pathways especially IL-17 signaling pathway, higher enrichment of multiple immune/inflammation cells such as Th2 cells and macrophages. However, high glycolysis group was associated with lower infiltration of tumor-killing immune cells such as NKT cells and higher immune checkpoints expression such as PD-L1, CTLA4, FOXP3 and IDO1. Conclusions In conclusion, the enhanced glycolysis activity of breast cancer was associated with pro-tumor immunity. The interaction between tumor glycolysis and immune/inflammation function may be mediated through IL-17 signaling pathway.

Background Climate change has altered global hydrological cycles mainly due to changes in temperature and precipitation, which may exacerbate the global and regional water shortage issues, especially in the countries along the Belt and Road (B&R). Methods In this paper, we assessed water supply, demand, and stress under three climate change scenarios in the major countries along the Belt and Road. We ensembled ten Global Climate Model (GCM) runoff data and downscaled it to a finer resolution of 0.1° × 0.1° by the random forest model. Results Our results showed that the GCM runoff was highly correlated with the FAO renewable water resources and thus could be used to estimate water supply. Climate change would increase water supply by 4.85%, 5.18%, 8.16% and water demand by 1.45%, 1.68%, 2.36% under RCP 2.6, 4.5, and 8.5 scenarios by 2050s, respectively. As a result, climate change will, in general, have little impact on water stress in the B&R countries as a whole. However, climate change will make future water resources more unevenly distributed among the B&R countries and regions, exacerbating water stress in some countries, especially in Central Asia and West Asia. Our results are informative for water resource managers and policymakers in the B&R countries to make sustainable water management strategies under future climate change.

Abstract Background Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia. Methods MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n = 10) and those with normotensive pregnancies (NP-MSC, n = 12). Sections of the frozen subcutaneous adipose tissue were assessed for inflammation by staining for tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1. Viability, proliferation, and migration were compared between PE-MSC vs. NP-MSC. Apoptosis and angiogenesis were assayed before and after treatment with a senolytic agent (1 μM dasatinib) using the IncuCyte S3 Live-Cell Analysis System. Similarly, staining for senescence-associated beta galactosidase (SABG) and qPCR for gene expression of senescence markers, p16 and p21, as well as senescence-associated secretory phenotype (SASP) components, IL-6, IL-8, MCP-1, and PAI-1, were studied before and after treatment with dasatinib and compared between PE and NP. Results After in vitro exposure to TNF-alpha, MSC demonstrated upregulation of SASP components, including interleukins-6 and -8 and MCP-1. Staining of the subcutaneous adipose tissue sections revealed a greater inflammatory response in preeclampsia, based on the higher levels of both TNF-alpha and MCP-1 compared to normotensive pregnancies (p

Abstract Visible light active g-C 3 N 4(0.94) /CeO 2(0.05) /Fe 3 O 4(0.01) ternary composite nanosheets were fabricated by facile co-precipitation routes. The density functional theory (DFT) computations investigated changes in geometry and electronic character of g-C3N4 with CeO2 and Fe3O4 addition. Chemical and surface characterizations were explored with XRD, XPS, SEM, TEM, PL, DRS and Raman measurements. DRS and PL spectroscopy evidenced the energy band gap tailoring from 2.68 eV for bulk g-C3N4 and 2.92 eV for CeO2 to 2.45 eV for the ternary nanocomposite. Efficient electron/hole pair separation, increase in red-ox species and high exploitation of solar spectrum due to band gap tailoring lead to higher degradation efficiency of g-C 3 N 4(0.94) /CeO 2(0.05) /Fe 3 O 4(0.01) . Superior sun light photocatalytic breakdown of 2-Chlorophenol was observed with g-C3N4 having CeO2 loading up to 5 wt%. In case of ternary nanocomposites deposition of 1 wt% Fe3O4 over g-C3N4/CeO2 binary composite not only showed increment in visible light catalysis as predicted by the DFT studies, but also facilitated magnetic recovery. The g-C 3 N 4(0.94) /CeO 2(0.05) /Fe 3 O 4(0.01) nanosheets showed complete mineralization of 25 mg.L−1 2-CP(aq) within 180 min exposure to visible portion of sun light and retained its high activity for 3 consecutive reuse cycles. The free radical scavenging showed superoxide ions and holes played a significant role compared to hydroxyl free radicals while chromatographic studies helped establish the 2-CP degradation mechanism. The kinetics investigations revealed 2.55 and 4.04 times increased rate of reactions compared to pristine Fe3O4 and CeO2, showing highest rate constant value of 18.2 × 10−3 min−1 for the ternary nanocomposite. We present very persuasive results that can be beneficial for exploration of further potential of g-C 3 N 4(0.94) /CeO 2(0.05) /Fe 3 O 4(0.01) in advance wastewater treatment systems.

Abstract. Background:. The clinical trials emerged centromere protein E inhibitor GSK923295 as a promising anticancer drug, but its function in hepatocellular carcinoma (HCC) remain needs to be fully elucidated, especially as chemotherapy after hepatectomy for liver tumors. We aimed to describe anti-HCC activities of GSK923295 and compare its antiproliferative effects on liver regeneration after partial hepatectomy (PH). Methods:. All subjects were randomized to treatment with either vehicle or GSK923295. Antitumor activity of GSK923295 was assessed by xenograft growth assays. The C57BL/6 mice were subjected to 70% PH and the proliferation was calculated by liver coefficient, further confirmed by immunohistochemistry. The proliferation and cell cycle analysis of liver cell AML12 and HCC cells LM3, HUH7, and HepG2 were investigated using the cell counting kit-8 assay and Flow Cytometry. The chromosome misalignment and segregation in AML12 cells were visualized by immunofluorescence. Results:. Treatment with GSK923295 induced antiproliferation in HCC cell lines. It also caused delay on HCC tumor growth instead of regression both in a HCC cell line xenograft model and patient-derived tumor xenograft model. With microarray analysis, CENtromere Protein E was gradually increased in mouse liver after PH. Exposure of liver cells to GSK923295 resulted in delay on a cell cycle in mitosis with a phenotype of misaligned chromosomes and chromosomes clustered. In 70% PH mouse model, GSK923295 treatment also remarkably reduced liver regeneration in later stage, in parallel with the mitotic marker phospho-histone H3 elevation. Conclusion:. The anticancer drug GSK923295 causes a significant delay on HCC tumor growth and liver regeneration after PH in later stage.

Abstract. Background:. Vasovagal syncope (VVS) is common in children and greatly affect both physical and mental health. But the mechanisms have not been completely explained. This study was designed to analyze the gut microbiota in children with VVS and explore its clinical significance. Methods:. Fecal samples from 20 VVS children and 20 matched controls were collected, and the microbiota were analyzed by 16S rRNA gene sequencing. The diversity and microbiota compositions of the VVS cases and controls were compared with the independent sample t test or Mann-Whitney U test. The correlation between the predominant bacteria and clinical symptoms was analyzed using Pearson or Spearman correlation test. Results:. No significant differences in diversity were evident between VVS and controls (P > 0.05). At the family level, the relative abundance of Ruminococcaceae was significantly higher in VVS children than in controls (median [Q1, Q3]: 22.10% [16.89%, 27.36%] vs. 13.92% [10.31%, 20.18%], Z = −2.40, P 4, P

Background: Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity. Methods: A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a-luciferase reporter and aged wild-type mice to determine the effects of fisetin on senescence markers, age-related histopathology, disease markers, health span and lifespan. Human adipose tissue explants were used to determine if results translated. Findings: Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. Interpretation: The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit. These characteristics suggest the feasibility to translation to human clinical studies. Fund: NIH grants P01 AG043376 (PDR, LJN), U19 AG056278 (PDR, LJN, WLL), R24 AG047115 (WLL), R37 AG013925 (JLK), R21 AG047984 (JLK), P30 DK050456 (Adipocyte Subcore, JLK), a Glenn Foundation/American Federation for Aging Research (AFAR) BIG Award (JLK), Glenn/AFAR (LJN, CEB), the Ted Nash Long Life and Noaber Foundations (JLK), the Connor Group (JLK), Robert J. and Theresa W. Ryan (JLK), and a Minnesota Partnership Grant (AMAY-UMN#99)-P004610401–1 (JLK, EAA). Keywords: Senolytic, Aging, Progeria, Healthspan, Lifespan, Senescence

Pancreatic cancer: Hormone gives cancer a helping hand A hormone found in high levels in pancreatic cancer sufferers helps the disease spread by co-ordinating cellular migration. Pancreatic cancer is one of the most deadly forms of cancer, being highly aggressive and likely to metastasize. Honggang Yu at Renmin Hospital of Wuhan University and scientists across China have demonstrated that gastrin, a hormone expressed at higher levels in patients with pancreatic cancer, helps to co-ordinate directional cell migration and ensure the disease spreads effectively. By activating two key molecules via a specific signalling pathway, gastrin ensures the correct orientation of the Golgi apparatus, a cellular organelle tasked with packaging proteins for transportation. This in turn activates directional migration of the cancer cells. The results explain why gastrin is over-expressed in both tumors and blood in cancer patients, and may inform future therapies.

Background: Pressure overload-induced myocardial hypertrophy is a key step leading to heart failure. Previous cellular and animal studies demonstrated that deteriorated excitation–contraction coupling occurs as early as the compensated stage of hypertrophy before the global decrease in left ventricular ejection fraction (LVEF). This study was to evaluate the cardiac electromechanical coupling time in evaluating cardiac systolic function in the early stage of heart failure. Methods: Twenty-six patients with Stage B heart failure (SBHF) and 31 healthy controls (CONs) were enrolled in this study. M-mode echocardiography was performed to measure LVEF. Tissue Doppler imaging (TDI) combined with electrocardiography (ECG) was used to measure cardiac electromechanical coupling time. Results: There was no significant difference in LVEF between SBHF patients and CONs (64.23 ± 8.91% vs. 64.52 ± 5.90%; P = 0.886). However, all four electromechanical coupling time courses (Qsb: onset of Q wave on ECG to beginning of S wave on TDI, Qst: onset of Q wave on ECG to top of S wave on TDI, Rsb: top of R wave on ECG to beginning of S wave on TDI, and Rst: top of R wave on ECG to top of S wave on TDI) of SBHF patients were significantly longer than those of CONs (Qsb: 119.19 ± 35.68 ms vs. 80.30 ± 14.81 ms, P < 0.001; Qst: 165.42 ± 60.93 ms vs. 129.04 ± 16.97 ms, P = 0.006; Rsb: 82.43 ± 33.66 ms vs. 48.30 ± 15.18 ms, P < 0.001; and Rst: 122.37 ± 36.66 ms vs. 93.25 ± 16.72 ms, P = 0.001), and the Qsb, Rsb, and Rst time showed a significantly higher sensitivity than LVEF (Rst: P =0.032; Rsb: P = 0.003; and Qsb: P = 0.004). Conclusions: The cardiac electromechanical coupling time is more sensitive than LVEF in evaluating cardiac systolic function.

Background: MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Methods: Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and 3H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. Results: The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = −2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.

Abstract Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a significant role in inhibiting T cell-related responses. This heterogeneous population of immature cells is involved in tumor immunity. Recently, the function and importance of MDSCs in transplantation have garnered the attention of scientists and have become an important focus of transplantation immunology research because MDSCs play a key role in establishing immune tolerance in transplantation. In this review, we summarize recent studies of MDSCs in different types of transplantation. We also focus on the influence of immunosuppressive drugs on MDSCs as well as future obstacles and research directions in this field.

Abstract Superlattices consisting of stacked nano-sized GeTe and Sb2Te3 blocks have attracted considerable attention owing to their potential for an efficient non-melting switching mechanism, associated with complex bonding between blocks. Here, we propose possible atomic models for the superlattices, characterized by different interfacial bonding types. Based on interplanar distances extracted from ab initio calculations and electron diffraction measurements, we reveal possible intercalation of dangling bonds as the GeTe content in the superlattice increases. The dangling bonds were further confirmed by X-ray photoelectron spectroscopy, anisotropic temperature dependent resistivity measurements down to 2 K and magnetotransport analysis. Changes of partially coherent decoupled topological surfaces states upon dangling bonds varying contributed to the switching mechanism. Furthermore, the topological surface states controlled by changing the bonding between stacking blocks may be optimized for multi-functional applications.

Abstract NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.

Abstract In heart failure (HF), energy metabolism pathway in cardiac muscle changes from fatty acid β-oxidation to glycolysis. However, the exact mechanism is unknown. Sarcoendoplasmic reticulum Ca2+α ATPase (SERCA) expression is downregulated and mitochondrial function is reduced in HF, perhaps partly due to a substantially reduced energy supply for excitation–contraction coupling resulting from a lower fatty acid β-oxidation rate. We investigated whether Astragaloside IV can activate peroxisome proliferator-activated receptor alpha (PPARα) to stimulate fatty acid β-oxidation and increase cardiac energy production, improving mitochondrial function and the efficiency of SERCA in HF. In pressure overload-induced HF mice and isolated hypertrophic myocardial cells, fatty acid β-oxidation and heart function were substantially strengthened following Astragaloside IV treatment, as demonstrated by the increased expression of PPARα and SERCA2a. In vitro, Astragaloside IV regulated energy metabolism by increasing ATP production and enhancing mitochondrial function, attributable to increased oxygen consumption and slightly increased mitochondrial Ca2+ uptake. In HF, Astragaloside IV switched glycolysis to fatty acid β-oxidation, as confirmed by reduced anaerobic glycolysis and an increased oxygen consumption ratio. These results suggest that Astragaloside IV can stimulate fatty acid β-oxidation and improve mitochondrial function, which may present a novel cardioprotective treatment that inhibits the progress of HF.

Abstract Haemodynamic disorders are common clinical findings in hypertension and lead to adverse cardiovascular events. However, the haemodynamic conditions in hypertension models are poorly understood. This study aimed to observe the characteristics of haemodynamics in spontaneously hypertensive rats (SHRs) and antihypertensive-treated SHRs. Twenty-four adult male SHRs and Wistar-Kyoto rats (WKYs) were randomly divided into four groups and treated for 7 days as follows: WKY-CON (WKYs + saline), WKY-NIF (WKYs + nifedipine, 50 mg/kg/day), SHR-CON (SHRs + saline), and SHR-NIF (SHRs + nifedipine). Aortic computational fluid dynamics (CFD) models were simulated to obtain the haemodynamic parameters. We found that in the hypertensive (SHR-CON) and blood pressure-controlled (SHR-NIF) groups, the oscillatory shear index (OSI) and relative residence time (RRT), which are key haemodynamics indices, were markedly elevated. Furthermore, there was a correlation between both the elevated OSI and RRT with the vascular wall thickening in regions near the inner wall of the aortic arch. Our research demonstrates that haemodynamics remains disturbed even if the blood pressure is normalized. In addition, vascular remodelling may play an important role in maintaining elevated OSI and RRT values.

Abstract Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM). The associations of alcohol intake with DR risk have demonstrated contradictory results. Relevant studies were identified by searching electronic databases (Medline, EMBASE and Web of Science) until May 2016. We identified a total of 12,875 DR cases among 37,285 participants in 15 observational studies. The pooled estimation of all the included observational studies was 0.91 (95% CI, 0.79 to 1.06) in a random-effect model. Analyses stratified by study design showed no significant association between alcohol intake and DR incidence in cohort, case control or cross-sectional studies. In the subgroup analyses, neither beer nor spirits intake were associated with DR risk. Furthermore, it was interesting to find that protective effects were detected in the wine (OR = 0.77, 95% CI = 0.64 to 0.92) and sherry (OR = 0.22, 95% CI = 0.05 to 0.95) groups. In conclusion, this current meta-analysis demonstrated that alcohol intake was not associated with risk of DR. Subgroup analysis by alcoholic beverage types showed that wine consumption would reduce the incidence of DR. In the future, more large-scale prospective studies with detailed alcohol subtypes and contents are still warranted to clarify the association.

Secondary metabolites have been extensively used in the treatment of various health problems. The role of solvent polarity on the phytochemical isolation and antioxidant capacity of Isatis tinctoria (woad) is elusive. In the present study, 14 solvents with different polarity were used in the extraction and total phenolic and flavonoid content (TPC and TFC) investigation. Ferricyanide, phosphomolybdenum, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods were used to calculate and compare the antioxidant/free radical scavenging capacity. Our results showed that solvent polarity greatly affects TPC and TFC yield, which is mainly increasing with increasing solvent polarity index and suddenly decreasing at very high polarity. The comparative results showed that TPC is directly correlated with reducing power, antioxidant, and free radical scavenging capacity. Taken together, we conclude that different woad plant parts contain different level of secondary metabolites with a specific polarity that requires a particular solvent with an appropriate polarity index for the extraction. The identification of these biologically active crude extracts and fractions are very important for the basic biological sciences, pharmaceutical applications, and future research for HPLC based active compounds isolation.

Atmospheric nitrogen (N) deposition increases N availability in soils, with consequences affecting the decomposition of soil carbon (C). The impacts of increasing N availability on surface soil C dynamics are well studied. However, subsurface soils have been paid less attention although more than 50% soil C stock is present below this depth (below 20 cm). This study was designed to investigate the response of surface (0–20 cm) and subsurface (20–40 cm and 40–60 cm) C dynamics to 0 (0 kg N ha−1), low (70 kg N ha−1) and high (120 kg N ha−1) levels of N enrichment. The soils were sampled from a cropland and a grass lawn and incubated at 25 °C and 60% water holding capacity for 45 days. Results showed that N enrichment significantly decreased soil C mineralization (Rs) in all the three soil layers in the two studied sites (p

Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC.

Background: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. Methods: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0–8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5–6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. Trial Registration: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Studies about the association between lead exposure and the elevation of blood pressure and risk of hypertension are varied, while available data on blood lead levels (BLL) in workers with lead-exposure are scarce. This research aimed to evaluate associations between BLL and blood pressure in an occupational population-based study in Jiangsu province, China. We enrolled 21,688 workers in this study. Information on socioeconomic and occupational background was obtained with face-to-face interviews. BLL, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured, and hypertension status was confirmed. We found that workers in mini-factories had the highest average BLL (20.3 μg/dL; 95% CI, 19.0-21.6 μg/dL) for overall participants. The employees in private factories had higher BLL (9.6 μg/dL; 95% CI, 9.5-9.8 μg/dL). However, BLL was much lower (4.0 μg/dL; 95%CI, 3.7-4.2 μg/dL) in state-owned factories. Participants working in the electrical machinery and equipment manufacturing industry had higher BLL (9.1 μg/dL; 95% CI, 9.0-9.3μg/dL). Compared to those workers with ≤ 4.6 μg/dL BLL, workers with > 17.5 μg/dL BLL presented 1.34 mmHg and 0.70 mmHg average difference in SBP and DBP, respectively. The adjusted OR for hypertension was 1.11 (95%CI, 1.08-1.15) compared to the workers with > 17.5 μg/dL BLL and to those with ≤ 4.6 μg/dL BLL. In summary, we found that BLL was positively associated with SBP and DBP and with the morbidity of hypertension in occupational populations with a high concentration of lead exposure. It is important to formulate new standards of blood lead levels to screen for elevated lead exposure. In addition, a series of new systems of risk assessment should be established to further reduce and prevent lead exposure.

Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson's trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230A. Our study suggested that aerobic exercise training could improve cardiac systolic function and alleviate LV chamber dilation, cardiac fibrosis and hypertrophy in HF mice. The mechanism responsible for the protective effects of aerobic exercise is associated with the activation of the β3-AR-nNOS-NO pathway.

In fungi, heterotrimeric guanine-nucleotide binding proteins (G-proteins) are key elements of signal transduction pathways, which control growth, asexual and sexual development, as well as virulence. In this study, we have identified two genes encoding heterotrimeric G protein alpha subunits, named Gvm2 and Gvm3, from Valsa mali, the causal agent of apple Valsa canker. Characterization of Gvm2 and Gvm3 mutants indicates that Gvm3 may be a crucial regulator of vegetative growth. Deletion of the corresponding gene results in a 20% reduction in growth rate. Besides, Gvm2 and Gvm3 seem to be involved in asexual reproduction, and mutants are hypersensitive to oxidative and cell membrane stresses. Interestingly, both G protein alpha subunits were most probably involved in V. mali virulence. In infection assays using Malus domestica cv. 'Fuji' leaves and twigs, the size of lesions caused by deletion mutants △Gvm2, or △Gvm3 are significantly reduced. Furthermore, many genes encoding hydrolytic enzymes-important virulence factors in V. mali-are expressed at a lower level in these deletion mutants. Our results suggest that Gvm2 and Gvm3 play an important role in virulence probably by regulation of expression of cell wall degrading enzymes. △Gvm2, and △Gvm3 mutants were further analyzed with respect to their impact on the transcript levels of genes in the cAMP/PKA pathway. The expression of the genes encoding adenylate cyclase VmAC, protein kinase A (PKA) regulatory subunit VmPKR, and PKA catalytic subunit VmPKA1 are down-regulated in both mutants. Further analyses indicated that intracellular cAMP level and PKA activity are down-regulated in the △Gvm3 mutant, but are basically unchanged in the △Gvm2 mutant. Overall, our findings indicate that both Gvm2 and Gvm3 play diverse roles in the modulation of vegetative growth, asexual development, and virulence in V. mali.

Black rice (Oryza sativa L.), whose pericarp is rich in anthocyanins (ACNs), is considered as a healthier alternative to white rice. Molecular species of ACNs in black rice have been well documented in previous studies; however, information about the metabolic mechanisms underlying ACN biosynthesis during black rice grain development is unclear.The aim of the present study was to determine changes in the metabolic pathways that are involved in the dynamic grain proteome during the development of black rice indica cultivar, (Oryza sativa L. indica var. SSP). Isobaric tags for relative and absolute quantification (iTRAQ) MS/MS were employed to identify statistically significant alterations in the grain proteome. Approximately 928 proteins were detected, of which 230 were differentially expressed throughout 5 successive developmental stages, starting from 3 to 20 days after flowering (DAF). The greatest number of differentially expressed proteins was observed on 7 and 10 DAF, including 76 proteins that were upregulated and 39 that were downregulated. The biological process analysis of gene ontology revealed that the 230 differentially expressed proteins could be sorted into 14 functional groups. Proteins in the largest group were related to metabolic process, which could be integrated into multiple biochemical pathways. Specifically, proteins with a role in ACN biosynthesis, sugar synthesis, and the regulation of gene expression were upregulated, particularly from the onset of black rice grain development and during development. In contrast, the expression of proteins related to signal transduction, redox homeostasis, photosynthesis and N-metabolism decreased during grain maturation. Finally, 8 representative genes encoding different metabolic proteins were verified via quantitative real-time polymerase chain reaction (qRT-PCR) analysis, these genes had differed in transcriptional and translational expression during grain development.Expression analyses of metabolism-related protein groups belonging to different functional categories and subcategories indicated that significantly upregulated proteins were related to flavonoid and starch synthesis. On the other hand, the downregulated proteins were determined to be related to nitrogen metabolism, as well as other functional categories and subcategories, including photosynthesis, redox homeostasis, tocopherol biosynthetic, and signal transduction. The results provide valuable new insights into the characterization and understanding of ACN pigment production in black rice.

[This corrects the article DOI: 10.1371/journal.pone.0122814.].

Traditional forecasting models fit a function approximation from dependent invariables to independent variables. However, they usually get into trouble when date are presented in various formats, such as text, voice and image. This study proposes a novel image-encoded forecasting method that input and output binary digital two-dimensional (2D) images are transformed from decimal data. Omitting any data analysis or cleansing steps for simplicity, all raw variables were selected and converted to binary digital images as the input of a deep learning model, convolutional neural network (CNN). Using shared weights, pooling and multiple-layer back-propagation techniques, the CNN was adopted to locate the nexus among variations in local binary digital images. Due to the computing capability that was originally developed for binary digital bitmap manipulation, this model has significant potential for forecasting with vast volume of data. The model was validated by a power loads predicting dataset from the Global Energy Forecasting Competition 2012.