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Abstract Digital empowerment is a dynamic process of complementary digital technology and production factors and plays a critical role in achieving the dual carbon objectives of the carbon peak by 2030 and carbon neutrality by 2060. Here, we use the input-output method, employing panel data on environmental and social factors from 30 provincial-level regions in China from 2012 to 2021. We explore the impact of digital empowerment development on agricultural carbon dioxide emissions and underlying mechanisms. We found that the relationship between digital empowerment and carbon dioxide emissions is nonlinear and follows an inverted U-curve. The carbon dioxide emissions increase as digital empowerment increases and decrease when digital empowerment crosses the inflection point of 0.0862. Digital empowerment reduces agricultural carbon emissions by optimizing carbon-intensive factor inputs such as fertilizers and improving factor allocation efficiency. Our research provides evidence for policymakers to enable the promotion of digital empowerment of farmers across Chinese provinces.

Recent studies have demonstrated that ferroptosis, a novel form of nonapoptotic regulated cell death plays an important role in doxorubicin (DOX)-induced cardiotoxicity (DoIC). Hydrogen sulfide (H2S) is emerging as the third important gaseous mediator in cardiovascular system. However, whether H2S has an effect on DOX-induced ferroptosis remains unknown. Here, we found that DOX not only triggered cardiomyocyte ferroptosis but also significantly inhibited the synthesis of endogenous H2S in the murine model of chronic DoIC. Application of NaHS, an H2S donor obviously activated the SLC7A11/GSH/GPx4 antioxidant pathway and thus alleviated DOX-induced ferroptosis and cardiac injury in mice. In contrast, cardiac-specific knockout of cystathionine γ-lyase gene (Cse) in mice (Csef/f/Cre+) to abolish the cardiac synthesis of endogenous H2S evidently exacerbated DOX-induced ferroptosis and cardiac dysfunction. A further suppression of SLC7A11/GSH/GPx4 pathway was obtained in Csef/f/Cre+ mice with DoIC, as compared to Csef/f/Cre− mice with DoIC. The aggravation caused by cardiac-specific Cse deficiency was remarkably rescued by exogenous supplementation of NaHS. Moreover, in DOX-stimulated H9c2 cardiomyocytes, pretreatment with NaHS dose-dependently enhanced the activity of SLC7A11/GSH/GPx4 pathway and subsequently mitigated ferroptosis and mitochondrial impairment. On the contrary, transfection with Cse siRNA in DOX-stimulated H9c2 cardiomyocytes markedly inhibited SLC7A11/GSH/GPx4 pathway, thus leading to aggravated ferroptosis and more damage to mitochondrial structure and function. In addition, the protective effect of NaHS on DOX-induced ferroptosis was closely related to the S-sulfhydrated Keap1, which in turn promoted nuclear translocation of Nrf2 and the transcription of SLC7A11 and GPx4. In conclusion, our findings suggest that H2S may exert protective effect on DoIC by inhibiting DOX-induced ferroptosis via Keap1/Nrf2-dependent SLC7A11/GSH/GPx4 antioxidant pathway.

Abstract Background A moderate intake of unsaturated fatty acids (UFA) is associated positively with improved insulin resistance. The aim of this study was to investigate the relationship between the dietary intake of unsaturated fatty acids/total fats (UFA/TF) and insulin resistance. Methods 15,560 participants were selected from the National Health and Nutrition Examination Survey (NHANES) database enrolled between March 2017 and 2020, and excluded those under 20 years of age, pregnant, or with missing data for key research items. Finally, 7,630 participants were included in the study. R software was used for data analysis that included: (1) general descriptive statistics; (2) comparison of differences in baseline information of three UFA/TF groups, namely low, medium, and high ratios; (3) calculation of the correlation between the UFA/TF ratio and markers of insulin resistance: triglyceride-glucose index (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR); (4) stratification of the study subjects into two groups, with or without insulin resistance, using a cut-off value of HOMA-IR ≥ 2, followed by logistic regression analysis to examine the relationship between UFA/TF and insulin resistance status in the two groups; and (5) further stratification of the subjects according to age, gender, body mass index (BMI), race, total energy intake, total protein, total carbohydrate, total sugars, total dietary fiber, total fat, alcohol consumption, diabetes, hypercholesterolemia to analyze the impact of UFA/TF on insulin resistance status in different subgroups. Results (1) A high UFA/TF level was associated with a low TyG index and HOMA-IR [β (vs. TyG index) = -0.559, 95% CI: (-0.821~-0.297), P

Abstract Numerous novel and effective therapeutic agents and clinical trials addressing castration-resistant prostate cancer (CRPC) were reported during the 2023 American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. Notably, radionuclide drug conjugates (RDC), specifically 177Lu/111In-J591 and 225Ac-J591, exhibited enhanced therapeutic efficacy in treating patients with CRPC. Furthermore, promising treatment approaches for CRPC included dual anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) blockade in rare tumors (DART)-Lorigerlimab, prostate stem cell antigen (PSCA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy-BPX-601, and protein kinase inhibitor (AKTi)-CAPltello-280. We have summarized the latest CRPC treatment strategies presented at the 2023 ASCO-GU Cancers Symposium, along with recent advances in CRPC clinical trials.

Abstract Antibody–drug conjugates (ADCs) combine the cytotoxicity of small-molecule drugs with antibody targeting. Due to their precise and powerful effect, they have become a new hotspot and an important trend in the research and development of anti-tumor antibody drugs. Every year, exciting new developments and innovations in the treatment of urological tumors are introduced at the American Society of Clinical Oncology-Genitourinary (ASCO-GU) Cancers Symposium. In this article, we summarize some of the most impressive advances in new clinical trials and clinical data on ADCs in the 2023 ASCO-GU Cancers Symposium for the treatment of urothelial carcinoma.

Abstract Bladder cancer (BC) is a clinical challenge worldwide with late clinical presentation, poor prognosis, and low survival rates. Traditional cystoscopy and tissue biopsy are routine methods for the diagnosis, prognosis, and monitoring of BC. However, due to the heterogeneity and limitations of tumors, such as aggressiveness, high cost, and limited applicability of longitudinal surveillance, the identification of tumor markers has attracted significant attention in BC. Over the past decade, liquid biopsies (e.g., blood) have proven to be highly efficient methods for the discovery of BC biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into the peripheral circulation and allows serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers are being extensively studied and have shown promising results in clinical applications of BC, including early detection, detection of microscopic residual disease, prediction of recurrence, and response to therapy. Therefore, in this review, we aim to provide an update on various novel blood-based liquid biopsy markers and review the advantages and current limitations of liquid biopsy in BC therapy. The role of blood-based circulating tumor cells, circulating tumor DNA, cell-free RNA, exosomes, metabolomics, and proteomics in diagnosis, prognosis, and treatment monitoring, and their applicability to the personalized management of BC, are highlighted.

Abstract Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.

We formulate an SEIR model for information propagation with the effect of a hot search in complex networks. Mathematical analysis is conducted in both a homogeneous network and heterogenous network. The results reveal that the dynamics are completely determined by the basic propagation number if the effect of a hot search is absent. On the other hand, when the effect of a hot search is taken into account, there exists no information-free equilibrium, and the information-propagating equilibrium is stable if the threshold is greater than 1. Numerical simulations were performed to examine the sensitivity of the parameters to the basic propagation number and the propagable nodes. Furthermore, the proposed model has been applied to fit the collected data for two types of information spreading in Sina Weibo, which confirmed the validity of our model and simulated the dynamical behaviors of information propagation.

This paper proposes a NH3/CO2 cascade refrigeration system that sets an auxiliary refrigeration loop in the high-temperature cycle to increase the subcooling degree in the low-temperature cycle (CRSS). Based on the basic principles of thermodynamics, a mathematical model is established and theoretical simulation is carried out to obtain the influence of key parameters on the cycle performance. Compared with the conventional cascade refrigeration system (CCRS), the conclusions find that there exists an optimal condensation temperature of low-temperature cycle (TMC.opt) to maximize COP. The maximum COP of CRSS is 4.58% higher than that of CCRS when the subcooling degree is 10 °C. The maximum exergy efficiency is 0.391, increasing by 4.40%. With the increase of the subcooling degree, both the COP and the TMC.optof CRSS increase. When the subcooling degree increases from 5 °C to 15 °C, the performance increment increases from 2.73% to 6.00%. When the evaporation temperature of the system changes, both the COP and exergy efficiency decreases slightly and it is found that the performance is better when the evaporation temperature is lower when condensation temperature is kept constant. Besides, the discharge temperature of the NH3 compressor in CRSS can be reduced by 9.9 °C when the evaporation temperature is −30 °C.

Helicobacter pylori (H. pylori), creating a global infection rate over 50%, presents great challenges in clinical therapies due to its complex pathological microenvironment in vivo. To improve the eradication efficacy, herein we fabricated a pharmaceutical vesicle RHL/Cl-Ch-cal where cholesterol-PEG, calcitriol and first-line antibiotic clarithromycin were co-loaded in the rhamnolipid-composed outer lipid layer. RHL/Cl-Ch-cal could quickly penetrate through gastric mucus layer to reach H. pylori infection sites, and then effectively destroyed the architecture of H. pylori biofilms, killed dispersed H. pylori and inhibited the re-adhesion of residual bacteria (called biofilms eradication tetralogy). Moreover, RHL/Cl-Ch-cal activated the host immune response to H. pylori by replenishing cholesterol to repair lipid raft on the cell membrane of host epithelial cells. Finally, RHL/Cl-Ch-cal killed the intracellular H. pylori through recovering the lysosomal acidification and assisting degradation. In experiments, RHL/Cl-Ch-cal demonstrated prominent anti-H. pylori efficacy in the classical H. pylori-infected mice model. Therefore, the study provides a “comprehensive attack” strategy for anti-H. pylori therapies including biofilms eradication tetralogy, immune activation and intracellular bacteria killing.

Objectives Most kidney stones contain calcium, which is closely associated with human bone health. Therefore, we aimed to determine the relationship between the history of kidney stones and human bone health. This study examined the associations between lumbar bone mineral density (BMD), serum 25-hydroxyvitamin D (25-OHD) and a history of kidney stones in individuals aged between 30 years and 69 years.Design and data analysis A multivariate logistic regression model was used to estimate the relationship between lumbar BMD, serum 25-OHD levels and kidney stones in this cross-sectional study. All models incorporated survey sample weights and were adjusted for covariates.Setting National Health and Nutrition Examination Survey (NHANES) 2011–2018. The exposure and outcomes of this study included the lumbar BMD and presence of kidney stones.Participants All the 7500 participants for this cross-sectional survey were selected from the NHANES between 2011 and 2018.Main outcome measures The main outcome of this study was the presence of kidney stones. The interviewers asked the questions on kidney stones while the respondents were at home, using a computer-assisted personal interview system.Results Lumbar BMD was negatively correlated with a history of kidney stones in all three multivariate linear regression models; the negative association existed in all genders after adjusting for all confounding factors. In the multiple regression analysis, there was an interaction between serum 25-OHD and lumbar BMD (p

Abstract Background Adipose tissue homeostasis is at the heart of many metabolic syndromes such as diabetes. Previously it has been demonstrated that adipose tissues from diabetic patients are senescent but whether this contributes to diabetic cardiomyopathy (DCM) remains to be elucidated. Methods The streptozotocin (STZ) type 1 diabetic mice were established as animal model, and adult mouse ventricular myocytes (AMVMs) isolated by langendorff perfusion as well as neonatal mouse ventricular myocytes (NMVMs) were used as cell models. Senescent associated β galactosidase (SA-β-gal) staining and RT-qPCR were used to identify the presence of adipose senescence in diabetic adipose tissue. Senescent adipose were removed either by surgery or by senolytic treatment. Large extracellular vesicles (LEVs) derived from adipose tissue and circulation were separated by ultracentrifugation. Cardiac systolic and diastolic function was evaluated through cardiac ultrasound. Cardiomyocytes contraction function was evaluated by the Ionoptix HTS system and live cell imaging, mitochondrial morphology and functions were evaluated by transmission electron microscope, live cell fluorescent probe and seahorse analysis. RNA-seq for AMVMs and miRNA-seq for LEVs were performed, and bioinformatic analysis combined with RT-qPCR and Western blot were used to elucidate underlying mechanism that senescent adipose derives LEVs exacerbates myocardial metabolism. Results SA-β-gal staining and RT-qPCR identified the presence of adipose tissue senescence in STZ mice. Through surgical as well as pharmacological means we show that senescent adipose tissue participates in the pathogenesis of DCM in STZ mice by exacerbates myocardial metabolism through secretion of LEVs. Specifically, expression of miRNA-326-3p was up-regulated in LEVs isolated from senescent adipose tissue, circulation, and cardiomyocytes of STZ mice. Up-regulation of miRNA-326-3p coincided with myocardial transcriptomic changes in metabolism. Functionally, we demonstrate that miRNA-326-3p inhibited the expression of Rictor and resulted in impaired mitochondrial and contractile function in cardiomyocytes. Conclusion We demonstrate for the first time that senescent adipose derived LEVs exacerbates myocardial metabolism through up-regulated miRNA-326-3p which inhibits Rictor in cardiomyocytes. Furthermore, reducing senescence burden in adipose tissue is capable of relieving myocardial metabolism disorder in diabetes mellitus.

Abstract In recent years, 5-methylcytosine (m5C) RNA modification has emerged as a key player in regulating RNA metabolism and function through coding as well as non-coding RNAs. Accumulating evidence has shown that m5C modulates the stability, translation, transcription, nuclear export, and cleavage of RNAs to mediate cell proliferation, differentiation, apoptosis, stress responses, and other biological functions. In humans, m5C RNA modification is catalyzed by the NOL1/NOP2/sun (NSUN) family and DNA methyltransferase 2 (DNMT2). These RNA modifiers regulate the expression of multiple oncogenes such as fizzy-related-1, forkhead box protein C2, Grb associated-binding protein 2, and TEA domain transcription factor 1, facilitating the pathogenesis and progression of cancers. Furthermore, the aberrant expression of methyltransferases have been identified in various cancers and used to predict the prognosis of patients. In this review, we present a comprehensive overview of m5C RNA methyltransferases. We specifically highlight the potential mechanism of action of m5C in cancer. Finally, we discuss the prospect of m5C-relative studies.

Comparison and analysis of the effects of three types of packaging treatments on the quality characteristics of pike eels during frozen storage. Pike eel were removed from the internal organs, cleaned and cut into pieces, then simply sealed bag packaging, vacuum packaging, soaked in 0.05 g/L stable chlorine dioxide solution for 10 minutes, then dried up and vacuum packaging treatment, which were recorded as simple packaging group, vacuum packaging group and antibacterial vacuum packaging group, respectively. The samples were stored at −18 ℃ for 120 days and sampled every 20 days. The total number of colonies, total volatile base nitrogen(TVB-N), color difference, myofibril fragmentation index(MFI), Ca2+-ATPase activity, carbonyl content, peroxide value and malondialdehyde content were measured. The effects of different packaging treatments on the quality characteristics of frozen pike eel were analyzed. The results showed that with the increase of storage time, the total number of colonies, TVB-N content, MFI value, carbonyl content, peroxide value and malondialdehyde content in each group increased, and the growth rate of the simple packaging group was significantly higher than the other two groups, and the preservation effect of the antibacterial vacuum packaging group was significantly better than the other two groups; the antibacterial vacuum packaging could effectively slow down the color change of pike eel during freezing; the Ca2+-ATPase activity of myogenic fibrin decreased with the extension of storage time, and the decreasing trend of the antibacterial vacuum packaging group was significantly smaller than the other two groups. In summary, the stable state chlorine dioxide combined with vacuum packaging treatment had a better effect on inhibiting the growth and reproduction of microorganisms in pike eels, and maintaining the freshness of fish pieces and muscle quality.

Abstract Background Biochemical recurrence (BCR) after initial treatment, such as radical prostatectomy, is the most frequently adopted prognostic factor for patients who suffer from prostate cancer (PCa). In this study, we aimed to construct a prognostic model consisting of gene expression profiles to predict BCR-free survival. Methods We analyzed 70 metabolic pathways in 152 normal prostate samples and 494 PCa samples from the UCSC Xena dataset (training set) via gene set enrichment analysis (GSEA) to select BCR-related genes and constructed a BCR-related gene risk score (RS) model. We tested the power of our model using Kaplan–Meier (K–M) plots and receiver operator characteristic (ROC) curves. We performed univariate and multivariate analyses of RS using other clinicopathological features and established a nomogram model, which has stronger prediction ability. We used GSE70770 and DFKZ 2018 datasets to validate the results. Finally, we performed differential expression and quantitative real-time polymerase chain reaction analyses of the UCSC data for further verification of the findings. Results A total of 194 core enriched genes were obtained through GSEA, among which 16 BCR-related genes were selected and a three-gene RS model based on the expression levels of CA14, LRAT, and MGAT5B was constructed. The outcomes of the K–M plots and ROC curves verified the accuracy of the RS model. We identified the Gleason score, pathologic T stage, and RS model as independent predictors through univariate and multivariate Cox analyses and constructed a nomogram model that presented better predictability than the RS model. The outcomes of the validation set were consistent with those of the training set. Finally, the results of differential expression analyses support the effectiveness of our model. Conclusion We constructed an RS model based on metabolic genes that could predict the prognosis of PCa patients. The model can be easily used in clinical applications and provide important insights into future research on the underlying mechanism of PCa.

Abstract In vitro diagnosis (IVD) is one vital component of medical tests that detects biological samples of tissues or bio‐fluids. Recently, mass spectrometry and spectroscopy have been increasingly employed in the field of IVD, due to their high accuracy, facile sample preparation, and rapid detection. Notably, the large datasets generated by these two technology methods provide a wealth of information but subsequently involve complex and time‐consuming processing works. Machine learning (ML), an important branch of artificial intelligence (AI), has emerged as a promising solution for the decoding of big data. ML imitates the human brain to process data, significantly improving accuracy and efficiency compared with traditional processing methods. In this review, we first introduce the commonly used ML algorithms and advanced mass spectrometry and spectroscopy techniques in the field of IVD, respectively. The ML algorithms are summarized as four aspects according to different learning tasks. Then, the combinations of ML with mass spectrometry, spectroscopy, and multi‐modal analysis for IVD are presented, and the roles of ML in these combinations are elucidated by some representative examples. This review aims to provide a systematic and comprehensive summary of the literature on ML‐assisted mass spectrometry or spectroscopy. We believe that it will facilitate researchers to select suitable ML algorithms for supplementing existing detection techniques or to develop the potential of coupling more detection techniques with ML, thus promoting the development of mass spectrometry and spectroscopy in IVD.

Abstract Background Primary bladder sarcoma (PBS) is a rare malignant tumor of the bladder with a poor prognosis, and its disease course is inadequately understood. Therefore, our study aimed to establish a prognostic model to determine individualized prognosis of patients with PBS. Patients and Methods Data of 866 patients with PBS, registered from 1973 to 2015, were extracted from the surveillance, epidemiology, and end result (SEER) database. The patients included were randomly split into a training (n = 608) and a validation set (n = 258). Univariate and multivariate Cox regression analyses were employed to identify the important independent prognostic factors. A nomogram was then established to predict overall survival (OS). Using calibration curves, receiver operating characteristic curves, concordance index (C-index), decision curve analysis (DCA), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), the performance of the nomogram was internally validated. We compared the nomogram with the TNM staging system. The application of the risk stratification system was tested using Kaplan–Meier survival analysis. Results Age at diagnosis, T-stage, N-stage, M-stage, and tumor size were identified as independent predictors of OS. C-index of the training cohort were 0.675, 0.670, 0.671 for 1-, 3- and 5-year OS, respectively. And that in the validation cohort were 0.701, 0.684, 0.679, respectively. Calibration curves also showed great prediction accuracy. In comparison with TNM staging system, improved net benefits in DCA, evaluated NRI and IDI were obtained. The risk stratification system can significantly distinguish the patients with different survival risk. Conclusion A prognostic nomogram was developed and validated in the present study to predict the prognosis of the PBS patients. It may assist clinicians in evaluating the risk factors of patients and formulating an optimal individualized treatment strategy.

Abstract Background In recent years, much attention has been given to AP2/ERF transcription factors because they play indispensable roles in many biological processes, such as plant development and biotic and abiotic stress responses. Although AP2/ERFs have been thoroughly characterised in many plant species, the knowledge about this family in the sweet potato, which is a vital edible and medicinal crop, is still limited. In this study, a comprehensive genome-wide investigation was conducted to characterise the AP2/ERF gene family in the sweet potato. Results Here, 198 IbAP2/ERF transcription factors were obtained. Phylogenetic analysis classified the members of the IbAP2/ERF family into three groups, namely, ERF (172 members), AP2 (21 members) and RAV (5 members), which was consistent with the analysis of gene structure and conserved protein domains. The evolutionary characteristics of these IbAP2/ERF genes were systematically investigated by analysing chromosome location, conserved protein motifs and gene duplication events, indicating that the expansion of the IbAP2/ERF gene family may have been caused by tandem duplication. Furthermore, the analysis of cis-acting elements in IbAP2/ERF gene promoters implied that these genes may play crucial roles in plant growth, development and stress responses. Additionally, the available RNA-seq data and quantitative real-time PCR (qRT-PCR) were used to investigate the expression patterns of IbAP2/ERF genes during sweet potato root development as well as under multiple forms of abiotic stress, and we identified several developmental stage-specific and stress-responsive IbAP2/ERF genes. Furthermore, g59127 was differentially expressed under various stress conditions and was identified as a nuclear protein, which was in line with predicted subcellular localization results. Conclusions This study originally revealed the characteristics of the IbAP2/ERF superfamily and provides valuable resources for further evolutionary and functional investigations of IbAP2/ERF genes in the sweet potato.

Abstract Background Raoultella ornithinolytica is a Gram-negative bacillus that resembles Klebsiella. This bacterium is present in many soil and aquatic environments and is a major causative agent of healthcare-associated infections (HAIs) in medical staff. Clinically, it has been reported to contribute to nosocomial infections in patients that include but are not limited to gastrointestinal, skin, and genitourinary tract infections. These complications are most common in hospitalized patients with underlying immunodeficiency, multiple comorbidities, or those receiving invasive surgery. Case presentation We present a case of a 25-year-old patient with a R. ornithinolytica infection. The patient had no history of any disease. Her main complaints were high fever, a scattered maculopapular rash, and superficial lymph node enlargement (SLNE). Peripheral blood samples were collected for high-throughput sequencing analysis to identify pathogenic microorganisms. The results confirmed a R. ornithinolytica infection, which was treated successfully using meropenem. Loratadine was also administered to treat the patient’s compromised skin condition caused by an allergic reaction. Conclusions To our knowledge, this is the first case of a systemic maculopapular rash and superficial lymphadenopathy caused by a R. ornithinolytica infection acquired at the community level. Based on this case, we recommend a combination of antibiotic and antiallergic drugs to treat a R. ornithinolytica infection and associated allergic reaction to the bacteria.

Spectrophotometric- and liquid chromatography/mass spectrometry (LC/MS)-based lipidomics analyses were performed to explore the changes of lipid profiles in pike eel (Muraenesox cinereus) under stable chlorine dioxides (ClO2) and vacuum-packed treatment during chilled storage. The peroxide value (PV) and malondialdehyde (MDA) content in ClO2 treated and vacuum-packaged (VP) samples were significantly reduced compared to simple-packaged (SP) samples during whole chilled storage. The LC/MS-based lipidomics analyses identified 2182 lipid species in the pike eel muscle classified into 39 subclasses, including 712 triglycerides (TGs), 310 phosphatidylcholines (PCs), 153 phosphatidylethanolamines (PEs), and 147 diglycerides (DGs), among others. Further, in comparison with fresh pike eel (FE) muscle, 354 and 164 higher and 420 and 193 lower abundant levels of differentially abundant lipids (DALs) were identified in SP samples and VP samples, respectively. Compared with the VP batch, 396 higher and 404 lower abundant levels of DALs were identified in the SP batch. Among these, PCs, PEs, TGs, and DGs were more easily oxidized/hydrolyzed, which could be used as biomarkers to distinguish FE, SP, and VP samples. This research provides a reference for controlling lipid oxidation in fatty fish.

Abstract Background Browning spot (BS) disorders seriously affect the appearance quality of ‘Huangguan’ pear and cause economic losses. Many studies on BS have mainly focused on physiological and biochemical aspects, and the molecular mechanism remains unclear. Results In the present study, the structural characteristics of ‘Huangguan’ pear with BS were observed via scanning electron microscopy (SEM), the water loss and brown spots were evaluated, and transcriptomic and metabolomics analyses were conducted to reveal the molecular mechanism underlying ‘Huangguan’ pear skin browning disorder. The results showed that the occurrence of BS was accompanied by a decrease in the wax layer and an increase in lignified cells. Genes related to wax biosynthesis were downregulated in BS, resulting in a decrease in the wax layer in BS. Genes related to lignin were upregulated at the transcriptional level, resulting in upregulation of metabolites related to phenylpropanoid biosynthesis. Expression of calcium-related genes were upregulated in BS. Cold-induced genes may represent the key genes that induce the formation of BS. In addition, the results demonstrated that exogenous NaH2PO4·2H2O and ABA treatment could inhibit the incidence of BS during harvest and storage time by increasing wax-related genes and calcium-related genes expression and increasing plant resistance, whereas the transcriptomics results indicated that GA3 may accelerate the incidence and index of BS. Conclusions The results of this study indicate a molecular mechanism that could explain BS formation and elucidate the effects of different treatments on the incidence and molecular regulation of BS.

Objective We aimed to construct and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) for patients with chromophobe renal cell carcinoma (chRCC) after nephrectomy.Design This study is a retrospective cohort study.Setting and participants There were 2810 patients with chRCC from Surveillance, Epidemiology and End Results database diagnosed between 2010 and 2015 included in the study who were randomly divided into a training cohort (n=1970) and a validation cohort (n=840). Another single-centre external validation cohort containing 124 patients from our hospital was also involved in our study.Primary and secondary outcome measures OS and CSS.Results Nomograms for OS and CSS include four and five variables, respectively, from the result of least absolute shrinkage and selection operator regression analyses. Nomograms reveal the accurate discrimination by the area under the curve of receiver operating characteristic (ROC) curves and C-indexes, with a C-index value of 0.777 (95% CI 0.728 to 0.826), 0.810 (95% CI 0.747 to 0.873) and 0.863 (95% CI 0.773 to 0.953) for the training cohort, the internal validation cohort and the external validation cohort in the nomogram for OS; and a C-index value of 0.884 (95% CI 0.829 to 0.939), 0.868 (95% CI 0.772 to 0.964) and 0.862 (95% CI 0.760 to 0.964) for the training cohort, the internal validation cohort and the external validation cohort in the nomogram for CSS. It was also proven that there was a high degree of conformance between the predicted and observation results by calibration plots. In addition, the comparison of ROC curves and C-indexes between nomograms and seventh tumour, node and metastasis stage demonstrated that nomograms were better in accuracy and efficacy ability.Conclusions We successfully constructed two accurate and effective nomograms to predict OS and CSS for patients with chRCC after nephrectomy, which can help clinical doctors choose individual treatment strategies for chRCC patients.

The high recurrence rate of non-muscle invasive bladder cancer (BC) and poor prognosis of advanced BC are therapeutic challenges that need to be solved. Bacillus Calmette-Guerin (BCG) perfusion was the pioneer immunotherapy for early BC, and the discovery of immune checkpoint inhibitors has created a new chapter in the treatment of advanced BC. The benefit of immunotherapy is highly anticipated, but its effectiveness still needs to be improved. In this review, we collated and analysed the currently available information and explored the mechaisms by which the internal immune imbalance of BC leads to tumour progression. The relationship between immunity and progression and the prognosis of BC has been explored through tests using body fluids such as blood and urine. These analytical tests have attempted to identify specific immuyne cells and cytokines to predict treatment outcomes and recurrence. The diversity and proportion of immune and matrix cells in BC determine the heterogeneity and immune status of tumours. The role and classification of immune cells have also been redefined, e.g., CD4 cells having recognised cytotoxicity in BC. Type 2 immunity, including that mediated by M2 macrophages, Th2 cells, and interleukin (IL)-13, plays an important role in the recurrence and progression of BC. Pathological fibrosis, activated by type 2 immunity and cancer cells, enhances the rate of cancer progression and irreversibility. Elucidating the immune status of BC and clarifying the mechanisms of action of different cells in the tumour microenvironment is the research direction to be explored in the future.

Chemical- and liquid chromatography coupled with mass spectrometry (LC–MS) based proteomics strategies were executed to investigate the alterations of protein profiles in pike eel (Muraenesox cinereus) muscle during chilling (CPE) and frozen (FPE) storage. Chemical results indicated that springiness and myofibrillar protein (MP) content of muscle tissues decreased significantly during 6 days of chilled and 120 days of frozen storage. LC–MS-based proteomics analysis suggested that great alterations occurred in muscle proteins mainly induced by cold stress. The differentially abundant proteins (DAPs) with low abundances in CPE and FPE samples included the annexins, fibronectin, ribosomal proteins, T-complex proteins, tubulin beta chain, and histones, which were mostly associated with the membrane structural constituents, cytoskeleton, and binding functional proteins. Results of eukaryotic cluster of orthologous group (KOG) verified that these identified DAPs were mainly converged in the cytoskeleton function resulting from cold conditions, which in turn affected the physical structure and chemical performances of muscle tissues.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high‐fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second‐generation and third‐generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second‐generation telomerase RNA component knockout (at 6 weeks) and third‐generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial‐specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride challenged murine model.

ObjectiveTo evaluate the association between perioperative estimated glomerular filtration rate (eGFR) and postoperative oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU),and to evaluate the effect of sex on this association.MethodsThe medical records of patients with UTUC who underwent RNU between January 2012 and December 2017 at our hospital were retrospectively reviewed. Patients were divided into three groups based on preoperative eGFRs: normal eGFR (>60 mL/min/1.73 m2; n = 179), moderately reduced eGFR (45–60 mL/min/1.73 m2; n = 45), and severely reduced eGFR (≤ 45 mL/min/1.73 m2; n = 36). Statistical analyses were performed to evaluate the prognostic impact of preoperative eGFR on prognosis.ResultsPatient mean age was 66.7 ± 9.6 years, and 47.9% were female. Multivariate regression analysis based on Cox proportional risk models and Kaplan-Meier survival rates showed that lower preoperative eGFR was associated with decreased OS, PFS, and CSS. In the adjusted Cox regression model, patients with normal and moderately reduced eGFRs had a decreased hazard for mortality, with adjusted hazard ratios of 0.13 [95% confidence interval (CI): 0.07–0.26] and 0.36 (95% CI: 0.18–0.73), respectively (P < 0.001). The smooth fitting curve suggested a linear relationship between eGFR and prognostic survival. Additionally, sensitivity subgroup analyses verified an inverse relationship between the reduced eGFR and OS. Women had a lower eGFR and worse oncological outcomes than men. A nomogram for OS was developed based on multivariate analysis with a C-index of 0.754 (95% CI: 0.728–0.779).ConclusionPreoperative renal insufficiency is strongly associated with a higher risk of cancer progression and a lower survival probability. It is important to identify preoperative renal insufficiency in patients with UTUC, particularly female patients.

In recent years, methylation modification regulators have been found to have essential roles in various tumor mechanisms. However, the relationships between N6-methyladenosine (m6A) and 5-methylcytosine (m5C) regulators and clear cell renal cell carcinoma (ccRCC) remain unknown. This study investigated these relationships using the data from The Cancer Genome Atlas database. We calculated risk scores using a Lasso regression analysis and divided the patient samples into two risk groups (tumor vs. normal tissues). Furthermore, we used univariate and multivariate Cox analyses to determine independent prognostic indicators and explore correlations between the regulatory factors and immune infiltrating cell characteristics. Finally, quantitative reverse transcriptase–polymerase chain reaction (PCR) and The Human Protein Atlas were used to verify signature-related gene expression in clinical samples. We identified expression differences in 35 regulatory factors between the tumor and normal tissue groups. Next, we constructed a five-gene risk score signature (NOP2 nucleolar protein [NOP2], methyltransferase 14, N6-adenosine-methyltransferase subunit [METTL14], NOP2/Sun RNA methyltransferase 5 [NSUN5], heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1], and zinc finger CCCH-type containing 13 [ZC3H13]) using the screening criteria (p < 0.01), and then divided the cases into high- and low-risk groups based on their median risk score. We also screened for independent prognostic factors related to age, tumor grade, and risk score. Furthermore, we constructed a Norman diagram prognostic model by combining two clinicopathological characteristics, which demonstrated good prediction efficiency with prognostic markers. Then, we used a single-sample gene set enrichment analysis and the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method to evaluate the tumor microenvironment of the regulatory factor prognostic characteristics. Moreover, we evaluated five risk subgroups with different genetic signatures for personalized prognoses. Finally, we analyzed the immunotherapy and immune infiltration response and demonstrated that the high-risk group was more sensitive to immunotherapy than the low-risk group. The PCR results showed that NSUN5 and HNRNPA2B1 expression was higher in tumor tissues than in normal tissues. In conclusion, we identified five m6A and m5C regulatory factors that might be promising biomarkers for future research.

The major objective of this paper is to build a cost prediction model for general aviation aircraft using artificial neural network (ANN) and principle component analysis (PCA) methods. A total number of 22 samples of general aviation aircraft collected from the literature are utilized to train and test the model. In the PCA, eigenvalues of PC1 and PC2 are 6.987 and 1.529, respectively, indicating that they have the strongest interpretation of the original variable information and are retained as cost influencing variables to train the ANN model. The pure multiple linear regression (MLR), stepwise regression (SR) and ANN models are built respectively for comparison. The comparative results reveal that the ANN method has better estimation effect than MLR and SR models in case of multi-collinearity of data. Combined with PCA, the ANN model is optimized, with MAPE, MAE, R and RMSE values of training and testing samples to be 0.009 and 0.015, 1.222 and 3, 0.9999 and 0.9994, 1.667 and 3.416, respectively. Finally, a more accurate and practical prediction model is developed. More importantly, this research can provide an important reference for general aviation aircraft companies in term of product cost planning and corporate sales strategy.

The introduction of frameshifting non-3n indels enables the identification of gene-trait associations. However, it has been hypothesised that recovery of the original reading frame owing to usage of non-canonical splice forms could cause rescue. To date there is very little evidence for organism-level rescue by such a mechanism and it is unknown how commonly indels induce, or are otherwise associated with, frame-restoring splice forms. We perform CRISPR/Cas9 editing of randomly selected loci in rice to investigate these issues. We find that the majority of loci have a frame-restoring isoform. Importantly, three quarters of these isoforms are not seen in the absence of the indels, consistent with indels commonly inducing novel isoforms. This is supported by analysis in the context of NMD knockdowns. We consider in detail the two top rescue candidates, in wax deficient anther 1 (wda1) and brittle culm (bc10), finding that organismal-level rescue in both cases is strong but owing to different splice modification routes. More generally, however, as frame-restoring isoforms are low abundance and possibly too disruptive, such rescue we suggest to be the rare exception, not the rule. Nonetheless, assuming that indels commonly induce frame-restoring isoforms, these results emphasize the need to examine RNA level effects of non-3n indels and suggest that multiple non-3n indels in any given gene are advisable to probe a gene's trait associations.

Riparian forest veg etation in the lower Tarim River desert often faces a water and nitrogen deficiency. To investigate the ecological effects of drought stress and nitrogen limitation of arbuscular mycorrhizal fungi (AMF) on Alhagi sparsifolia seedlings at the vulnerable stage of growth, a control experiment was conducted on Alhagi sparsifolia seedlings with indoor potted plants. The main findings are as follows: drought stress inhibited the normal growth and development of Alhagi sparsifolia seedlings. When Alhagi sparsifolia seedlings were inoculated with AMF and at the N1 (50 mmol·L−1) nitrogen addition level, the mycorrhizal infection rate of Alhagi sparsifolia seedlings was the best: 84.44% under sufficient moisture content and 77.78% under drought stress. Under the same nitrogen treatment, the relative growth rate of Alhagi sparsifolia seedling height and base diameter, plant biomass, root system indicators (total root length, root surface area, root volume, average root diameter, the number of tips, and root shoot ratio), chlorophyll content (except for the chlorophyll a/b content at the N0 (0 mmol·L−1) nitrogen addition level), Fv/Fm, total nitrogen content, idole acetic acid (IAA) and gibberellic acid (GA) content were initially decreased, then increased and finally decreased again. Each of these indicators was increased significantly after being inoculated with AMF, and they reached their maximum value under the normal moisture and AMF treatment; however specific root length (except for at the N0 (0 mmol·L−1) nitrogen addition level), minimal fluorescence (Fo), antioxidant enzyme activity, the contents of osmotic regulation substances, abscisic acid (ABA) and strigolactones (SLs) contents were initially increased, then decreased and finally increased again, and they reached their maximum value under drought stress and AMF treatment. Under the same CK (black control), D (drought stress), CK + A (inoculated with AMF under black control), and D + A (inoculated with AMF under drought stress) treatments, all of the above indicators, except for specific root length, chlorophyll a/b content, minimal fluorescence (Fo), maximum fluorescence (Fm) and malondialdehyde (MDA) content initially increased and then decreased with the increasing nitrogen addition rate, and they reached the maximum value at the N1 (50 mmol·L−1) nitrogen addition level. Therefore, in the arid and N-deficient lower Tarim River region, Alhagi sparsifolia seedlings established an efficient symbiotic structure with AMF, which improved the drought resistance of seedlings and promoted the rapid passage of seedlings through the growth vulnerability period. This indicates that AMF inoculation is a key link in the survival strategy of Alhagi sparsifolia.

Objective: To examine the clinical significance of the blood lactate (Lac)/serum albumin (Alb) ratio and the Lac/Alb × age score for assessing the severity and prognosis of patients with sepsis.Methods: A total of 8,029 patients with sepsis, aged >18 years were enrolled between June 2001 to October 2012 from the latest version of the Medical Information Mart for Intensive Care III (MIMIC-III v.1.4). The general data of the patients were obtained from hospital records and included gender, age, body mass index (BMI), laboratory indices, the sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS II). The patients were graded and scored according to their age and then divided into a survival or death group based on their prognosis. The Lac/Alb ratio after ICU admission was calculated and compared between the two groups. The risk factors for death in patients with sepsis were determined using multivariate logistic regression analysis, while mortality was examined using receiver operating characteristic (ROC) curve and survival curve plots. Finally, the values of the Lac/Alb ratio and Lac/Alb × age score for assessing prognosis of patients with sepsis were analyzed and compared.Results: After items with default values were excluded, a total of 4,555 patients with sepsis were enrolled (2,526 males and 2,029 females). 2,843 cases were classified as the death group and 1,712 cases in the survival group. (1) The mean age, BMI, SOFA and SAPS II scores were higher in the death group than those in the survival group. Significant differences in baseline data between the two groups were also observed. (2) The patients in the death group were divided further into four subgroups according to the quartile of the Lac/Alb ratio from low to high. Comparison of the four subgroups showed that the death rate rose with an increase in the Lac/Alb ratio, while analysis of the survival curve revealed that patients with a higher Lac/Alb ratio had a worse prognosis. (3) Multivariate logistic regression analysis showed that age ≥ 60 years, overweight (BMI ≥ 24 kg/m2), Lac/Alb ratio ≥ 0.16, SOFA score ≥ 2 points, and SAPS II ≥ 40 points were independent risk factors for death in patients with septic. (4) ROC curve analysis indicated that the SAPS II, Lac/Alb x age score, SOFA, and Lac/Alb ratio were the best predictors of death in patients with sepsis. The Lac/Alb × age score was characterized by its simple acquisition and ability to quickly analyze the prognosis of patients.Conclusion: (1)A high Lac/Alb ratio is an independent risk factor for death in patients with sepsis. (2) Although the prognosis of sepsis can be accurately and comprehensively assessed by multi-dimensional analysis of multiple indices, the Lac/Alb×age score is more accurate and convenient for providing a general assessment of prognosis, so is worthy of further clinical recognition.

The effects of vacuum-packaging and stable chlorine dioxide treatments on the quality of pike-eel fillets were investigated during chilled storage for a period of up to 10 days. The results reveal that the sensory scores, total volatile basic nitrogen (TVB-N) content, total viable count (TVC), malondialdehyde (MDA) content, and the myofibrillar protein (MP) content of pike-eel fillets with different packing treatments all decreased significantly over 10 days of storage. However, the vacuum-packaging and stable chlorine dioxide pretreatment showed positive effects on the protein stability of pike-eel samples. Compared with the simple packaging (SP) and vacuum packing (VP) treatments, the combination treatments (CP) significantly inhibited the rapid increases in the TVB-N content, TVC values, and MDA content. Moreover, the comparative stability in the MP and its carbonyl content were maintained. Furthermore, our volatile organic compounds (VOCs) analysis confirmed that the combined packaging treatments significantly hindered protein and lipid oxidation, inhibited the growth of spoilage bacteria, and maintained the volatile flavors of pike-eel samples during chilled storage.

ObjectiveSerum albumin-to-alkaline phosphatase ratio (AAPR) has been proven to be a prognostic indicator of many malignant tumors. However, whether it can predict the prognosis of bladder cancer (BC) patients who underwent radical cystectomy (RC) remains unclear. This study was designed to assess the relationship between AAPR and clinical outcomes in patients with BC treated with RC.MethodsThe clinicopathological data of 199 BC patients receiving RC in our institution from January 2012 to December 2017 were retrospectively collected and analyzed. They were divided into three groups based on the optimal cut-off values and the association between AAPR groups and their clinical outcomes were evaluated.ResultsThe average age of the patients was (64.0 ± 8.7) years and 79.9% were male. Based on the cut-off values of AAPR, patients were divided into three groups: low-AAPR group (AAPR < 0.37, n = 35), medium-AAPR group (AAPR = 0.37-0.59, n = 61) and high-AAPR group (AAPR > 0.59, n = 103). The median overall survival (OS) of each AAPR group was 12.5, 24, and 29 months, respectively (P value

Objective: To compare the functional outcome, safety and efficacy of sutureless and conventional laparoscopic partial nephrectomy.Methods: After the inclusion and exclusion criteria were applied, our study reviewed 379 patients with T1 stage renal tumors. We applied propensity score matching (PSM) to limit potential baseline confusion. Perioperative and functional outcomes between sutureless laparoscopic partial nephrectomy (sLPN) and conventional laparoscopic partial nephrectomy (cLPN) groups were compared and analyzed before and after PSM.Results: Of our 379 patients with T1 stage renal tumors, 199 and 180 were identified in the cLPN and sLPN groups, respectively. After applying PSM with preoperative features, 116 patients in the cLNP group were paired to 116 patients in the sLNP group. We found that all differences in preoperative baseline characteristics disappeared. All the preoperative characteristics (age, gender, tumor diameter, RENAL nephrometry score, side, preoperative eGFR, hypertension, diabetes mellitus, ASA score) were not statistically different between the two groups. The operative time (OT) (p < 0.001) and warm ischemia time (WIT) (p < 0.001) of the sLPN group were of shorter duration than that of the cLPN group. The eGFR baseline was almost equal, but there was a statistically smaller decrease in eGFR in the sLPN than in the cLPN group 1 week after surgery (14.3 vs. 7.4, p < 0.001) and after 6 months (11.9 vs. 5.0, p < 0.001). After both preoperative features and WIT were included in PSM, fifty-one pairs of patients were identified between the groups, the WIT difference between them disappeared, while the decrease in eGFR between the groups remained as it was previously at 1 week (15.4 vs. 8.6, p < 0.001) and at 6 months (13.0 vs. 6.2, p < 0.001).Conclusion: Sutureless laparoscopic partial nephrectomy is as safe and effective as conventional laparoscopic partial nephrectomy, and compared to cLPN, sLPN can effectively reduce the WIT, retain more renal parenchyma and protect renal function.

CTNNA3, first reported in association with arrhythmogenic right ventricular cardiomyopathy in 2003, is an unique component of both desmosomes and adherens junctions. Using Sendaivirus-mediated reprogramming, we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells of a child with arrhythmia. The iPSCs exhibited stable amplification, expressed pluripotent markers, and differentiated spontaneously into three germ layers in vitro. Additionally, this iPSC line was found to maintain a normal karyotype and retain the pathogenic mutation in CTNNA3, facilitating a platform to study the disease mechanisms of arrhythmia and dysfunctions related to CTNNA3 mutations.

Background: Cancer-associated fibroblasts (CAFs) are mainly involved in cancer progression and treatment failure. However, the specific signature of CAFs and their related clinicopathological parameters in renal cell carcinoma (RCC) remain unclear. Here, methods to recognize gene signatures were employed to roughly assess the infiltration of CAFs in RCC, based on the data from The Cancer Genome Atlas (TCGA). Weighted Gene Coexpression Network Analysis (WGCNA) was used to cluster transcriptomes and correlate with CAFs to identify the gene signature. Single-cell and cell line sequencing data were used to verify the expression specificity of the gene signature in CAFs. The gene signature was used to evaluate the infiltration of CAFs in each sample, and the clinical significance of each key gene in the gene signature and CAFs was analyzed. We observed that the CAF infiltration was higher in kidney cancer and advanced tumor stage and grade than in normal tissues. The seven key genes of the CAF gene signature identified using WGCNA showed high expression of CAF-related characteristics in the cell clustering landscape and fibroblast cell lines; these genes were found to be associated with extracellular matrix function, collagen synthesis, cell surface interaction, and adhesion. The high CAF infiltration and the key genes were verified from the TCGA and Gene Expression Omnibus data related to the advanced grade, advanced stage, and poor prognosis of RCC. In summary, our findings indicate that the clinically significant gene signature may serve as a potential biomarker of CAFs in RCC, and the infiltration of CAFs is associated with the pathological grade, stage, and prognosis of RCC.

Objectives To conduct a systematic review with meta-analysis of cohort studies to evaluate the association of coffee consumption with the risk of prostate cancer.Data sources PubMed, Web of Science and Embase were searched for eligible studies up to September 2020.Study selection Cohort studies were included.Data extraction and synthesis Two researchers independently reviewed the studies and extracted the data. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with the “metan” and “glst” commands in Stata 14.0.Main outcomes and measures Prostate cancer was the main outcome. It was classified as localised prostate cancer which included localised or non-aggressive cancers; advanced prostate cancer which included advanced or aggressive cancers; or fatal prostate cancer which included fatal/lethal cancers or prostate cancer-specific deaths.Results Sixteen prospective cohort studies were finally included, with 57 732 cases of prostate cancer and 1 081 586 total cohort members. Higher coffee consumption was significantly associated with a lower risk of prostate cancer. Compared with the lowest category of coffee consumption, the pooled relative risk (RR) was 0.91 (95% CI 0.84 to 0.98), I2= 53.2%) for the highest category of coffee consumption. There was a significant linear trend for the association (p=0.006 for linear trend), with a pooled RR of 0.988 (95% CI 0.981 to 0.995) for each increment of one cup of coffee per day. For localised, advanced and fatal prostate cancer, the pooled RRs were 0.93 (95% CI 0.87 to 0.99), 0.88 (95% CI 0.71 to 1.09) and 0.84 (95% CI 0.66 to 1.08), respectively. No evidence of publication bias was indicated in this meta-analysis.Conclusions This study suggests that a higher intake of coffee may be associated with a lower risk of prostate cancer.

Background The purpose of this study was to determine the key microRNAs (miRNAs) and their regulatory networks in clear cell renal cell carcinoma (ccRCC). Methods Five mRNA and three microRNA microarray datasets were downloaded from the Gene Expression Omnibus database and used to screen the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed with Metascape. A miRNA-mRNA network was mapped with the Cytoscape tool. The results were validated with data from The Cancer Genome Atlas (TCGA) and qRT-PCR. A nomogram model based on independent prognostic key DEMs, stage and grade was constructed for further investigation. Results A total of 26 key DEMs and 307 DEGs were identified. Dysregulation of four key DEMs (miR-21-5p, miR-142-3p, miR-155-5p and miR-342-5p) was identified to correlate with overall survival. The results were validated with TCGA data and qRT-PCR. The nomogram model showed high accuracy in predicting the prognosis of patients with ccRCC. Conclusion We identified 26 DEMs that may play vital roles in the regulatory networks of ccRCC. Four miRNAs (miR-21-5p, miR-142-3p, miR-155-5p and miR-342-5p) were considered as potential biomarkers in the prognosis of ccRCC, among which only miR-21-5p was found to be an independent prognostic factor. A nomogram model was then created on the basis of independent factors for better prediction of prognosis for patients with ccRCC. Our results suggest a need for further experimental validation studies.

Metabolic alterations play crucial roles in carcinogenesis, tumor progression, and prognosis in clear cell renal cell carcinoma (ccRCC). A risk score (RS) model for ccRCC consisting of disease-associated metabolic genes remains unidentified. Here, we utilized gene set enrichment analysis to analyze expression data from normal and tumor groups from the cancer genome atlas. Out of 70 KEGG metabolic pathways, we found seven and two pathways to be significantly enriched in our normal and tumor groups, respectively. We identified 113 genes enriched in these nine pathways. We further filtered 47 prognostic-related metabolic genes and used Least absolute shrinkage and selection operator (LASSO) analysis to construct a three-metabolic-genes RS model composed of ALDH3A2, B3GAT3, and CPT2. We further tested the RS by mapping Kaplan-Meier plots and receiver operating characteristic curves, the results were promising. Additionally, multivariate Cox analysis revealed the RS to be an independent prognostic factor. Thereafter, we considered all the independent factors and constructed a nomogram model, which manifested in better prediction capability. We validated our results using a dataset from ArrayExpress and through qRT-PCR. In summary, our study provided a metabolic gene-based RS model that can be used as a prognostic predictor for patients with ccRCC.

N6-methyladenosine (m6A) modifications can be found in eukaryotic messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA). Several studies have demonstrated a close relationship between m6A modifications and cancer cells. Methyltransferase-like enzyme 3 (METTL3) and methyltransferase-like enzyme 14 (METTL14) are two major enzymes involved in m6A modifications that play vital roles in various cancers. However, the roles and regulatory mechanisms of METTL3 and METTL14 in urological cancers are largely unknown. In this review, we summarize the current research results for METTL3 and METTL14 and identify potential pathways involving these enzymes in kidney, bladder, prostate, and testicular cancer. We found that METTL3 and METTL14 have different expression patterns in four types of urological cancers. METTL3 is highly expressed in bladder and prostate cancer and plays an oncogenic role on cancer cells; however, its expression and role are opposite in kidney cancer. METTL14 is expressed at low levels in kidney and bladder cancer, where it has a tumor suppressive role. Low METTL3 or METTL14 expression in cancer cells negatively regulates cell growth-related pathways (e.g., mTOR, EMT, and P2XR6) but positively regulates cell death-related pathways (e.g., P53, PTEN, and Notch1). When METTL3 is highly expressed, it positively regulates the NF-kB and SHH-GL1pathways but negatively regulates PTEN. These results suggest that although METTL3 and METTL14 have different expression levels and regulatory mechanisms in urological cancers, they control cancer cell fate via cell growth- and cell death-related pathways. These findings suggest that m6A modification may be a potential new therapeutic target in urological cancer.

Campylobacter is a zoonotic pathogen that causes foodborne diarrheal illness globally. To better understand health risks in Southeastern China, Campylobacter spp. were surveyed in humans and representative poultry products over 3 years. One hundred and ninety-five representative isolates (n = 148, Campylobacter jejuni; n = 45, Campylobacter coli; n = 2 Campylobacter hyointestinalis) were examined for genetic relatedness and antimicrobial susceptibility. Nearly all Campylobacter isolates (99.0%, 193/195) were resistant to at least one class of antimicrobials, and 45.6% (89/195) of the isolates exhibited multidrug resistance. Genotypic analysis revealed high diversity among tested strains. Multilocus sequence typing (MLST) displayed 120 sequence types (STs) including 42 novel STs being added to the PubMLST international database. Sixty-two STs belonged to 16 previously characterized clonal complexes (CCs), of which CC-21, CC-45, CC-464, CC-574, CC-353, and CC-828 were most frequently identified. In addition, pulsed-field gel electrophoresis (PFGE) fingerprinting resulted in 66 PFGE SmaI patterns among the 125 isolates, with eight patterns shared between human and poultry sources. Subtyping data did not correlate with antimicrobial resistance phenotypes. Taken together, this large-scale surveillance study highlights high antimicrobial resistance and molecular features of Campylobacter isolates in Southeastern China.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, which ranks the third leading cause of cancer-related death worldwide. The screening of anti-HCC drug with high efficiency and low toxicity from traditional Chinese medicine (TCM) has attracted more and more attention. As a TCM, Chinese dragon’s blood has been used for the treatment of cardiovascular illness, gynecological illness, skin disorder, otorhinolaryngological illness, and diabetes mellitus complications for many years. However, the anti-tumor effect and underlying mechanisms of Chinese dragon’s blood remain ill-defined. Herein we have revealed that Chinese dragon’s blood EtOAc extract (CDBEE) obviously suppressed the growth of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, CDBEE inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, CDBEE displayed good in vitro anti-angiogenic activity. Importantly, CDBEE treatment significantly blunted the oncogenic capability of HepG2 cells in nude mice. Mechanistically, CDBEE inhibited Smad3 expression in human hepatoma cells and tumor tissues from nude mice. Using RNA interference, we demonstrated that CDBEE exerted anti-hepatoma activity partially through down-regulation of Smad3, one of major members in TGF-β/Smad signaling pathway. Therefore, CDBEE may be a promising candidate drug for HCC treatment, especially for liver cancer with aberrant TGF-β/Smad signaling pathway.

Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, N6-methyladenosine (m6A) has been shown to play important roles in regulating gene expression and phenotypes in both health and disease. Here, our purpose is to construct a m6A-regulrator-based risk score (RS) for prediction of the prognosis of ccRCC. Methods We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage. Validation of this RS was then engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset. Finally, we used quantitative real-time PCR to analyze the expression profile of genes consists of the RS. Results A three-gene RS including METTL3, METTL14 and HNRNPA2B1 which can predict overall survival (OS) of ccRCC patients from TCGA. After applying this RS into the validation cohort from Arrayexpress, we found that it successfully reproduced the result; furthermore, the results of PCR validation were in line with our analysis. Conclusion To sum up, our study has identified an RS composed of m6A related genes that may predict the prognosis of ccRCC patients, which might be helpful for future therapeutic strategies. Our results call for further experimental studies for validations.

ObjectiveThis study aims to explore the mechanism of the miR-424-5p/E2F7 axis in hepatocellular carcinoma (HCC) and provide new ideas for targeted therapy of HCC.MethodsBioinformatics analysis was used to identify the target differentially expressed miRNA in HCC and predict its target gene. qRT-PCR was employed to verify the expression of miR-424-5p and E2F7 mRNA in HCC cells. Western blot was performed to detect the effect of miR-424-5p ectopic expression on the protein expression of E2F7. CCK-8 was used to detect proliferative activity of HCC cells and flow cytometry was carried out for analyzing cell cycle distribution. Dual luciferase reporter assay was conducted to verify the direct targeting relationship between miR-424-5p and E2F7.ResultsWe observed that miR-424-5p was down-regulated in HCC cells. CCK-8 showed that overexpression of miR-424-5p inhibited cell proliferation, and flow cytometry showed that miR-424-5p could block cells in G0/G1 phase. E2F7 was up-regulated in HCC cells, and E2F7 overexpression could facilitate the proliferative ability of HCC cells and promote the cell cycle progressing from G0/G1 to S phase. Furthermore, dual-luciferase reporter assay indicated that miR-424-5p could directly down-regulate E2F7 expression. Analysis on cell function demonstrated that miR-424-5p inhibited the proliferation of HCC cells and blocked cell cycle at G0/G1 phase by targeting E2F7.ConclusionOur results proved that E2F7 was a direct target of miR-424-5p, and miR-424-5p could regulate cell cycle and further inhibit the proliferation of HCC cells by targeting E2F7.

Stereocomplex-type polylactide (SC-PLA) created by alternate packing of poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA) chains in a crystalline state has emerged as a growingly popular engineering bioplastic that possesses excellent hydrolytic stability and thermomechanical properties. However, it is extremely difficult to acquire high-performance SC-PLA products via melt-processing of high-molecular-weight PLLA/PDLA blends because both SC crystallites and homocrystallites (HCs) are competitively formed in the melt-crystallization. Herein, a facile yet powerful way was employed to boost SC formation by introducing trace amounts of some epoxy-functionalized small-molecule modifiers into the enantiomeric blends during reactive melt-blending. The results show that the SC formation is considerably enhanced with the in situ generation of multi-arm stereo-block PLA copolymers, based on the reaction between epoxy groups of the modifiers and hydroxyl end groups of PLAs. More impressively, it is intriguing to find that the introduction of only 0.5 wt% modifiers can induce exclusive SC formation in the blends upon isothermal and non-isothermal melt-crystallizations. The outstanding SC crystallizability might be attributed to the suppressing effect of such unique copolymers on the separation of the alternately arranged PLLA/PDLA chain segments in molten state as a compatibilizer. Furthermore, the generation of these copolymers does not result in a significant increase in melt viscosity of the blends. These findings suggest new opportunities for the high-throughput processing of SC-PLA materials into useful products.

Background: Bladder urothelial cancer (BLCA) treatment using immune checkpoint inhibitors (IMCIs) can result in long-lasting clinical benefits. However, only a fraction of patients respond to such treatment. In this study, we aimed to identify the relationships between immune cell infiltration levels (ICILs) and IMCIs and identify markers for ICILs.Methods: ICILs were estimated based on single-sample gene set enrichment analysis. The response rates of different ICILs to IMCIs were calculated by combining the ICILs of molecular subtypes in BLCA with the response rates of different molecular subtypes of IMvigor 210 trials to a programmed cell death ligand-1 inhibitor. Weighted gene co-expression network analysis was used to identify modules of interest with ICILs. Functional enrichment analysis was performed to functionally annotate the modules. Screening of key genes and unsupervised clustering were used to identify candidate biomarkers. Tumor IMmune Estimation Resource was used to validate the relationships between the biomarkers and ICILs. Finally, we verified the expression of key genes in molecular subtypes of different response rates for IMCIs.Findings: The basal squamous subtype and luminal infiltrated subtype, which showed low response rates for IMCIs, had the highest levels of immune infiltration. The neuronal subtypes, which showed the highest response rates to IMCIs, had low ICILs. The modules of interest and key genes were determined based on topological overlap measurement, clustering results, and inclusion criteria. Modules highly correlated with ICILs were mainly enriched in immune responses and epithelial–mesenchymal transition. After screening the key genes in the modules, five candidate biomarkers (CD48, SEPT1, ACAP1, PPP1R16B, and IL16) were selected by unsupervised clustering. The key genes were inversely associated with tumor purity and were mostly expressed in the basal squamous subtype and luminal infiltrated subtypes.Interpretation: Patients with high ICILs may benefit the least from treatment with IMCIs. Five key genes could predict ICILs in BLCA, and their high expression suggested that the response rate to IMCIs may decrease.

Background: Stem cells characterized by self-renewal and therapeutic resistance play crucial roles in bladder cancer (BLCA). However, the genes modulating the maintenance and proliferation of BLCA stem cells are still unclear. In this study, we aimed to characterize the expression of stem cell-related genes in BLCA.Methods: The mRNA expression-based stemness index (mRNAsi) of The Cancer Genome Atlas (TCGA) was evaluated and corrected by tumor purity. Corrected mRNAsi were further analyzed with regard to muscle-invasive bladder cancer molecular subtypes, survival analysis, pathological staging characteristics, and outcomes after primary treatment. Next, weighted gene co-expression network analysis was used to find modules of interest and key genes. Functional enrichment analysis was performed to functionally annotate the modules and key genes. The expression levels of key genes in all cancers were validated using Oncomine and Gene Expression Omnibus (GEO) database containing molecular subtypes in BLCA. Protein interaction networks were used to identify upstream genes, and the relationships between genes were analyzed at the protein and transcription levels.Findings: mRNAsi was significantly upregulated in cancer tissues. Corrected mRNAsi in BLCA increased as tumor stage increased, with T3 having the highest stem cell characteristics. Lower corrected mRNAsi scores had better overall survival and treatment outcome. The modules of interest and key genes were determined based on topological overlap measurement clustering results and the inclusion criteria. For 13 key genes (AURKA, BUB1B, CDCA5, CDCA8, KIF11, KIF18B, KIF2C, KIFC1, KPNA2, NCAPG, NEK2, NUSAP1, and RACGAP1), enriched gene ontology terms related to cell proliferation (e.g., mitotic nuclear division, spindle, and microtubule binding) were determined. Their expression did not differ according to the pathological stages of BLCA, and these genes were clearly overexpressed in many types of cancers. In GEO database, the expression levels of 13 key genes were higher in basal subtype with the highest stem cell characteristics than in luminal and its subtypes. AURKB and PLK1 may be regulated upstream of other key genes, and the key genes were found to be strongly correlated with each other and with upstream genes.Interpretation: The 13 key genes identified in this study were found to play important roles in the maintenance of BLCA stem cells. Controlling the upstream genes AURKB and PLK1 may have applications in the treatment of BLCA. These genes may act as therapeutic targets for inhibiting the stemness characteristics of BLCA.

Abstract Background Human DNA polymerase β (polβ) is a small monomeric protein that is essential for short-patch base excision repair. It plays an important role in regulating the sensitivity of tumor cells to chemotherapy. Methods We evaluated the mutation of polβ in a larger cohort of esophageal cancer (EC) patients by RT-PCR and sequencing analysis. The function of the mutation was evaluated by CCK-8, in vivo tumor growth, and flow cytometry assays. Results There are 229 patients with the polβ mutation, 18 patients with A613T mutation, 12 patients with G462T mutation among 538 ECs. Analysis results of survival time showed that EC patients with A613T, G462T mutation had a shorter survival than the others (P