Effects of continuous and transgenerational rearing in peanut leaves on the performance and enzyme activity of Spodoptera frugiperda (Lepidoptera: Noctuidae).

The invasive fall armyworm (FAW), Spodoptera frugiperda, is a polyphagous pest that significantly threatens crops worldwide. FAW may undergo adaptation, enhancing its ability to infect specific plant hosts. However, there is limited knowledge on this topic. After 8 generations of constant rearing on peanut leaves, the performance and enzyme activities of FAW were investigated in this study. Compared to FAW fed on the peanut cultivars 'Fuhua 8' and 'Quanhonghua 1' for 2 generations, those grown on leaves for 5 to 8 generations had significantly shorter pre-adult development times and total preoviposition periods. Fecundity also increased significantly, resulting in an overall improvement in population fitness as measured by demographic parameters. However, the F2 generation of FAW fed on corn leaves outperformed the F8 generation of FAW fed on peanut leaves. In the F2 generation, the FAW peanut population exhibited 30-55% supernumerary larval molts, which decreased substantially in the F5 and F8 generations. Notably, supernumerary larval molts displayed pupation and emergence rates comparable to normal larvae, regardless of the peanut cultivar or rearing generation. The activities of lipase and acetylcholinesterase increased significantly from the F2 to F8 generations, showing substantial negative and positive correlations with larval development time and fecundity, respectively. In conclusion, FAW demonstrated inferior performance on peanut leaves compared to corn leaves, despite its performance was significantly improved after 5 to 8 generations of acclimation. These results suggest that corn will continue to be the primary target crop for FAW in China.

Predicting vulnerable carotid plaques by detecting wall shear stress based on ultrasonic vector flow imaging.

OBJECTIVE: Carotid plaque vulnerability is a significant factor in the risk of cardiocerebrovascular events, with intraplaque neovascularization (IPN) being a crucial characteristic of plaque vulnerability. This study investigates the value of ultrasound vector flow imaging (V-flow) for measuring carotid plaque wall shear stress (WSS) in predicting the extent of IPN. METHODS: We enrolled 140 patients into three groups: 53 in the plaque group (72 plaques), 23 in the stenosis group (27 plaques), and 64 in the control group. V-flow was used to measure WSS parameters, including the average WSS (WSS mean) and the maximum WSS (WSS max), across three plaque locations: mid-upstream, maximum thickness, and mid-downstream. Contrast-enhanced ultrasound examination was used in 76 patients to analyze IPN and its correlation with WSS parameters. RESULTS: WSS max in the stenosis group was significantly higher than that in the control and plaque groups at the maximum thickness part (P < .05) and WSS mean in the stenosis group was significantly lower than that in the control group at the mid-upstream and mid-downstream segments (P < .05). WSS mean in the plaque group was significantly lower than that of the control group at all three locations (P < .05). Contrast-enhanced ultrasound examination revealed that plaques with neovascularization enhancement exhibited significantly higher WSS values (P < .05), with a positive correlation between WSS parameters and IPN enhancement grades, particularly WSS max at the thickest part (r = 0.508). Receiver operating characteristic curve analysis of WSS parameters for evaluating IPN showed that the efficacy of WSS max in evaluating IPN was better than that of WSS mean (P < .05), with an area under the curve of 0.7762 and 0.6973 (95% confidence intervals, 0.725-0.822 and 0.642-0.749, respectively). The cut-offs were 4.57 Pa and 1.12 Pa, sensitivities were 74.03% and 63.64%, and specificities were 75.00% and 68.18%. CONCLUSIONS: V-flow effectively measures WSS in carotid plaques. WSS max provides a promising metric for assessing IPN, offering potential insights into plaque characteristics and showing some potential in predicting plaque vulnerability.

Comprehensive bioinformatics analytics and in vivo validation reveal SLC31A1 as an emerging diagnostic biomarker for acute myocardial infarction.

BACKGROUND: Globally, Acute Myocardial Infarction (AMI) is a common cause of heart failure (HF), which has been a leading cause of mortality resulting from non-communicable diseases. On the other hand, increasing evidence suggests that the role of energy production within the mitochondria strongly links to the development and progression of heart diseases, while Cuproptosis, a newly identified cell death mechanism, has not yet been comprehensively analyzed from the aspect of cardiovascular medicine. MATERIALS AND METHODS: 8 transcriptome profiles curated from the GEO database were integrated, from which a diagnostic model based on the Stacking algorithm was established. The efficacy of the model was evaluated in a multifaced manner (i.e., by Precision-Recall curve, Receiver Operative Characteristic curve, etc.). We also sequenced our animal models at the bulk RNA level and conducted qPCR and immunohistochemical staining, with which we further validated the expression of the key contributor gene to the model. Finally, we explored the immune implications of the key contributor gene. RESULTS: A merged machine learning model containing 4 Cuproptosis-related genes (i.e., PDHB, CDKN2A, GLS, and SLC31A1) for robust AMI diagnosis was developed, in which SLC31A1 served as the key contributor. Through in vivo modeling, we validated the aberrant overexpression of SLC31A1 in AMI. Besides, further transcriptome analysis revealed that its high expression was correlated with significant potential immunological implications in the infiltration of many immune cell types, especially monocyte. CONCLUSIONS: We constructed an AMI diagnostic model based on Cuproptosis-related genes and validated the key contributor gene in animal modeling. We also analyzed the effects on the immune system for its overexpression in AMI.

Interplay of Sphingolipid Metabolism in Predicting Prognosis of GBM Patients: Towards Precision Immunotherapy.

Background: In spite of numerous existing bio-surveillance systems for predicting glioma (GBM) prognosis, enhancing the efficacy of immunotherapy remains an ongoing conundrum. The continual scrutiny of the dynamic interplay between the sphingolipid metabolic pathway and tumor immunophenotypes has unveiled potential implications. However, the intricate orchestration of functional and regulatory mechanisms by long non-coding RNAs (lncRNAs) in GBM, particularly in the context of sphingolipid metabolism, remains cryptic. Methods: We harnessed established R packages to intersect gene expression profiles of GBM patients within the The Cancer Genome Atlas (TCGA) database with the compilation of sphingolipid metabolism genes from GeneCards. This enabled us to discern markedly distinct lncRNAs, which were subsequently deployed to construct a robust prognostic model utilizing Lasso-Cox regression analysis. We then scrutinized the immune microenvironment across various risk strata using the ssGSEA and CIBERSORT algorithms. To evaluate mutation patterns and drug resistance profiles within patient subgroups, we devised the "Prophytic" and "Maftools" packages, respectively. Results: Our investigation scrutinized lncRNAs linked to sphingolipid metabolism, utilizing glioma specimens from TCGA. We meticulously curated 1224 sphingolipid-associated genes gleaned from GeneCards and pinpointed 272 differentially expressed mRNAs via transcriptomic analysis. Enrichment analyses underscored their significance in sphingolipid processes. A prognostic model founded on 17 meticulously selected lncRNAs was systematically constructed and validated. This model adeptly stratified GBM patients into high- and low-risk categories, yielding highly precise prognostic insights. We also discerned correlations between immune cell infiltration and genetic mutation discrepancies, along with distinct therapeutic responses through drug sensitivity analysis. Notably, computational findings were corroborated through experimental validation by RT-PCR. Conclusion: In summation, our exhaustive inquiry underscores the multifaceted utility of the sphingolipid metabolic pathway as an autonomous diagnostic and prognostic indicator for glioma patients. Furthermore, we amalgamate a profusion of substantiated evidence concerning immune infiltration and gene mutations, thereby reinforcing the proposition that sphingolipid metabolism may function as a pivotal determinant in the panorama of immunotherapeutic interventions.

Circadian gene Per3 promotes astroblastoma progression through the P53/BCL2/BAX signalling pathway.

The key circadian genes, Period1(Per1), Period2(Per2), and Period3(Per3), constitute the mammalian Period gene family. The abnormal expression of Per1 and Per2 is closely related to tumor development, but there are few reports on Per3 and tumorigenesis. This study was conducted to determine whether the abnormal expression of Per3 could influence the progression of astroblastoma. The results indicated that the expression level of Per3 was increased in astroblastoma cells, and the high expression of Per3 was correlated with the poor overall survival time of glioma patients. The role of Per3 in astroblastoma cells was then investigated using two approaches: interference and overexpression. The interference of Per3 inhibited astroblastoma cell proliferation by inducing the cell cycle at the S phase. The interference of Per3 inhibited the migration and invasion of astroblastoma cells, while promoted the astroblastoma cell apoptosis and the expression of the apoptosis genes Cleaved-CASP3, P53, and BAX. The overexpression of Per3 promoted proliferation by affecting the S phase distribution of the astroblastoma cell cycle. The overexpression of Per3 promoted the migration and invasion of astroblastoma cells, while inhibited the astroblastoma cell apoptosis and the expression of apoptosis genes Cleaved-CASP3, P53, and BAX. RNA-seq analysis showed that the interference of Per3 in astrocytoma cells resulted in significant changes in the expression levels of 764 genes. Among the differentially expressed genes enriched in apoptosis-related pathways, the interference of Per3 resulted in significant upregulation of MARCKSL1 expression, in contrast to significant downregulation of SFRP4, EPB41L3, and GPC5 expression. Taken together, our results suggest that Per3 appears to be a pro-cancer gene by altering the proliferation, migration, invasion, and apoptosis of astroblastoma cells. As a result, the Per3 gene may be a promising therapeutic target in the treatment of astroblastoma.

Capsaicin alleviates doxorubicin-induced acute myocardial injury by regulating iron homeostasis and PI3K-Akt signaling pathway.

BACKGROUND: Capsaicin (CAP), a frequently occurring alkaloid component found in spicy peppers, has demonstrated therapeutic potential against tumors, metabolic disease, and cardiovascular disorders. Doxorubicin (DOX), a widely used anthracycline drug in chemotherapy, is notorious for its cardiotoxicity. This study aimed to investigate the potential of CAP in mitigating DOX toxicity in mouse hearts and H9C2 cells, as well as to explore the underlying mechanisms. METHODS: In our study, we conducted experiments on both mice and H9C2 cells. The mice were divided into four groups and treated with different substances: normal saline, CAP, DOX and CAP+DOX. We evaluated the induction of ferroptosis by DOX and the remission of ferroptosis by CAP using various methods, including echocardiography, Hematoxylin and Eosin (H&E) staining, Masson's trichrome staining, and determination of ferroptosis metabolites, genes and proteins. Additionally, we employed RNA-seq to identify the inhibitory effect of CAP on DOX-induced myocardial apoptosis, which was further confirmed through western blotting. Similar approaches were applied to H9C2 cells, yielding reliable results. RESULTS: Our study demonstrated that treatment with CAP improved the survival rate of DOX-treated mice and reduced myocardial injury. Mechanistically, CAP downregulated transferrin (Trf) and upregulated solute carrier family 40 member 1 (SLC40A1), which helped maintain iron levels in the cells and prevent ferroptosis. Furthermore, CAP inhibited DOX-induced apoptosis by modulating the phosphoinositide 3-kinase (PI3K)- protein kinase B (Akt) signaling pathway. Specifically, CAP activated the PI3K-Akt pathway and regulated downstream BCL2 and BAX to mitigate DOX-induced apoptosis. Therefore, our results suggest that CAP effectively alleviates acute myocardial injury induced by DOX. CONCLUSION: Our findings demonstrate that CAP has the potential to alleviate DOX-induced ferroptosis by regulating iron homeostasis. Additionally, it can inhibit DOX-induced apoptosis by activating PI3K-Akt signaling pathway.

Novel bone cement based on calcium phosphate composited CNT curcumin with improved strength and antitumor properties.

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.

GLS as a diagnostic biomarker in breast cancer: in-silico, in-situ, and in-vitro insights.

Background: Recently, a novel programmed cell death mechanism, Cuproptosis, has been discovered and found to play an important role in the development and progression of diverse tumors. In the present study, we comprehensively investigated the core gene of this mechanism, GLS, in breast cancer. Materials and methods: Bulk RNA sequencing data were curated from the TCGA repository to investigate the aberrant expression of GLS over diverse cancer types. Then, we examined its efficacy as a diagnostic biomarker in breast cancer by Area Under Curve (AUC) of the Receiver Operative Characteristic (ROC) curve. Furthermore, by applying siRNA technique, we knocked down the GLS expression level in cancerous cell lines, measuring the corresponding effects on cell proliferation and metastasis. Afterward, we explored the potential implications of GLS expression in the tumor immune microenvironment quantitatively by using several R packages and algorithms, including ESTIMATE, CIBERSORT, etc. Results: Pan-cancer analysis suggested that GLS was aberrantly over-expressed in many cancer types, with breast cancer being typical. More in-depth analyses revealed the expression of GLS exerted a high ROC-AUC value in breast cancer diagnosis. Through the knock-down of GLS expression, it was found that GLS expression was strongly relevant to the growth and metastasis of tumor. Furthermore, it was also found to be correlated with the immune tumor microenvironment. Conclusion: We highlighted that GLS expression might be applicable as a diagnostic biomarker in breast cancer and possess significant implications in the growth and metastasis of tumor and the immune tumor microenvironment, sharing new insights into ontological and personalized medicine.

Establishment of a novel lysosomal signature for the diagnosis of gastric cancer with in-vitro and in-situ validation.

Background: Gastric cancer (GC) represents a malignancy with a multi-factorial combination of genetic, environmental, and microbial factors. Targeting lysosomes presents significant potential in the treatment of numerous diseases, while lysosome-related genetic markers for early GC detection have not yet been established, despite implementing this process by assembling artificial intelligence algorithms would greatly break through its value in translational medicine, particularly for immunotherapy. Methods: To this end, this study, by utilizing the transcriptomic as well as single cell data and integrating 20 mainstream machine-learning (ML) algorithms. We optimized an AI-based predictor for GC diagnosis. Then, the reliability of the model was initially confirmed by the results of enrichment analyses currently in use. And the immunological implications of the genes comprising the predictor was explored and response of GC patients were evaluated to immunotherapy and chemotherapy. Further, we performed systematic laboratory work to evaluate the build-up of the central genes, both at the expression stage and at the functional aspect, by which we could also demonstrate the reliability of the model to guide cancer immunotherapy. Results: Eight lysosomal-related genes were selected for predictive model construction based on the inclusion of RMSE as a reference standard and RF algorithm for ranking, namely ADRB2, KCNE2, MYO7A, IFI30, LAMP3, TPP1, HPS4, and NEU4. Taking into account accuracy, precision, recall, and F1 measurements, a preliminary determination of our study was carried out by means of applying the extra tree and random forest algorithms, incorporating the ROC-AUC value as a consideration, the Extra Tree model seems to be the optimal option with the AUC value of 0.92. The superiority of diagnostic signature is also reflected in the analysis of immune features. Conclusion: In summary, this study is the first to integrate around 20 mainstream ML algorithms to construct an AI-based diagnostic predictor for gastric cancer based on lysosomal-related genes. This model will facilitate the accurate prediction of early gastric cancer incidence and the subsequent risk assessment or precise individualized immunotherapy, thus improving the survival prognosis of GC patients.

Lactate in the tumor microenvironment: A rising star for targeted tumor therapy.

Metabolic reprogramming is one of fourteen hallmarks of tumor cells, among which aerobic glycolysis, often known as the "Warburg effect," is essential to the fast proliferation and aggressive metastasis of tumor cells. Lactate, on the other hand, as a ubiquitous molecule in the tumor microenvironment (TME), is generated primarily by tumor cells undergoing glycolysis. To prevent intracellular acidification, malignant cells often remove lactate along with H+, yet the acidification of TME is inevitable. Not only does the highly concentrated lactate within the TME serve as a substrate to supply energy to the malignant cells, but it also works as a signal to activate multiple pathways that enhance tumor metastasis and invasion, intratumoral angiogenesis, as well as immune escape. In this review, we aim to discuss the latest findings on lactate metabolism in tumor cells, particularly the capacity of extracellular lactate to influence cells in the tumor microenvironment. In addition, we examine current treatment techniques employing existing medications that target and interfere with lactate generation and transport in cancer therapy. New research shows that targeting lactate metabolism, lactate-regulated cells, and lactate action pathways are viable cancer therapy strategies.

NCAPG2 could be an immunological and prognostic biomarker: From pan-cancer analysis to pancreatic cancer validation.

More recently, NCAPG2 has emerged as an intrinsically essential participant of the condensin II complex involved in the process of chromosome cohesion and stabilization in mitosis, and its position in particular tumours is now being highlighted. Simultaneously, the genetic properties of NCAPG2 hint that it might have enormous potential to interpret the malignant progression of tumors in a broader perspective, that is, in pan-cancer. Yet, at present, this recognition remains merely superficial and there is a lack of more detailed studies to explore the underlying pathogenesis. To meet this need, the current study was undertaken to comprehensively elucidate the potential functions of NCAPG2 in pan-cancer, based on a combination of existing databases like TCGA and GTEx. NCAPG2 was identified to be overexpressed in almost every tumor and to exhibit significant prognostic and diagnostic efficacy. Furthermore, the correlation between NCAPG2 and selected immune features, namely immune cell infiltration, immune checkpoint genes, TMB, MSI, etc. also indicates that NCAPG2 could potentially be applied in guidance of immunotherapy. Subsequently, in pancreatic cancer, this study further clarified the utility of NCAPG2 that downregulation of its expression could result in reduced proliferation, invasion and metastasis of pancreatic cancer cells, among such phenotypical changes, the epithelial-mesenchymal transition disruption could be at least one of the possible mechanisms raising or enhancing tumorigenesis. Taken above, NCAPG2, as a member of pan-oncogenes, would serve as a biomarker and potential therapeutic target for a range of malignancies, sharing new insights into precision medicine.

IL1RN and PRRX1 as a Prognostic Biomarker Correlated with Immune Infiltrates in Colorectal Cancer: Evidence from Bioinformatic Analysis.

The extensive morbidity of colorectal cancer (CRC) and the inferior prognosis of terminal CRC urgently call for reliable prognostic biomarkers. For this, we identified 704 differentially expressed genes (DEGs) by intersecting three datasets, GSE41328, GSE37364, and GSE15960 from Gene Expression Omnibus database, to maximize the accuracy of the results. Preliminary analysis of the DEGs was then performed using online gene analysis datasets, such as DAVID, UCSC Cancer Genome Browser, CBioPortal, STRING, and UCSC Cancer Genome Browser. Cytoscape was utilized to visualize the protein perception interaction network of DEGs, and the bubble map of GO and KEGG enrichment function was demonstrated using the R package. The Molecular Complex Detection (MCODE), Biological Network Gene Oncology (BiNGO) plug-in in Cytoscape, was applied to further screen the DEGs to obtain 15 seed genes, which were IL1RN, GALNT12, ADH6, SCN7A, CXCL1, FGF18, SOX9, ACACB, PRRX1, MZB1, SLC22A3, CNNM4, LY6E, IFITM2, and GDPD3. Among them, IL1RN, ADH6, SCN7A, ACACB, MZB1, and GDPD3 exhibited statistically significant survival differences, whereas limited studies were conducted in CRC. Based on the enrichment results of the "Gene Ontology"(GO) and "Kyoto Encyclopedia of Genes and genomes "(KEGG) as well as documented findings of key genes, we further emphasized the potential of IL1RN and PRRX1 as markers of immune infiltrates in CRC and confirmed our hypothesis by compiling data from the UALCAN, Tumor Immune Estimation Resource, and TISIDB databases for these two genes. The above-mentioned genes might offer a valuable insight into the diagnosis, immunotherapeutic targets, and prognosis of CRC.

A Novel Immune-Related Gene Prognostic Index (IRGPI) in Pancreatic Adenocarcinoma (PAAD) and Its Implications in the Tumor Microenvironment.

PURPOSE: Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies, with less than 10% of patients surviving more than 5 years. Existing biomarkers for reliable survival rate prediction need to be enhanced. As a result, the objective of this study was to create a novel immune-related gene prognostic index (IRGPI) for estimating overall survival (OS) and to analyze the molecular subtypes based on this index. Materials and procedures: RNA sequencing and clinical data were retrieved from publicly available sources and analyzed using several R software packages. A unique IRGPI and optimum risk model were developed using a machine learning algorithm. The prediction capability of our model was then compared to that of previously proposed models. A correlation study was also conducted between the immunological tumor microenvironment, risk groups, and IRGPI genes. Furthermore, we classified PAAD into different molecular subtypes based on the expression of IRGPI genes and investigated their features in tumor immunology using the K-means clustering technique. RESULTS: A 12-gene IRGPI (FYN, MET, LRSAM1, PSPN, ERAP2, S100A1, IL20RB, MAP3K14, SEMA6C, PRKCG, CXCL11, and GH1) was established, and verified along with a risk model. OS prediction by our model outperformed previous gene signatures. According to the findings of our correlation studies, different risk groups and IRGPI genes were found to be tightly related to tumor microenvironments, and PAAD could be further subdivided into immunologically distinct molecular subtypes based on the expression of IRGPI genes. CONCLUSION: The current study constructed and verified a unique IRGPI. Furthermore, our findings revealed a connection between the IRGPI and the immunological microenvironment of tumors. PAAD was differentiated into several molecular subtypes that might react differently to immunotherapy. These findings could provide new insights for precision and translational medicine for more innovative immunotherapy strategies.

Cuproptosis-related gene index: A predictor for pancreatic cancer prognosis, immunotherapy efficacy, and chemosensitivity.

Aim: The term "Cuproptosis" was coined to describe a novel type of cell death triggered by intracellular copper buildup that is fundamentally distinct from other recognized types such as autophagy, ferroptosis, and pyroptosis in recent days. As the underlying mechanism was newly identified, its potential connection to pancreatic adenocarcinoma (PAAD) is still an open issue. Methods: A set of machine learning algorithms was used to develop a Cuproptosis-related gene index (CRGI). Its immunological characteristics were studied by exploring its implications on the expression of the immunological checkpoints, prospective immunotherapy responses, etc. Moreover, the sensitivity to chemotherapeutic drugs was predicted. Unsupervised consensus clustering was performed to more precisely identify different CRGI-based molecular subtypes and investigate the immunotherapy and chemotherapy efficacy. The expression of DLAT, LIPT1 and LIAS were also investigated, through real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunofluorescence staining (IFS). Results: A novel CRGI was identified and validated. Additionally, correlation analysis revealed major changes in tumor immunology across the high- and low-CRGI groups. Through an in-depth study of each medication, it was determined that the predictive chemotherapeutic efficacy of 32 regularly used anticancer drugs differed between high- and low-CRGI groups. The results of the molecular subtyping provided more support for such theories. Expressional assays performed at transcriptomic and proteomic levels suggested that the aforementioned Cuproptosis-related genes might serve as reliable diagnostic biomarkers in PAAD. Significance: This is, to the best of our knowledge, the first study to examine prognostic prediction in PAAD from the standpoint of Cuproptosis. These findings may benefit future immunotherapy and chemotherapeutic therapies.

Network Pharmacology-Based Approach Combined with Bioinformatic Analytics to Elucidate the Potential of Curcumol against Hepatocellular Carcinoma.

PURPOSE: Modern, open-source databases provide an unprecedented wealth of information to help drug development. By combining data available in these databases with the proper bioinformatical tools, we can elucidate the molecular targets of natural compounds. One such molecule is curcumol, a guaiane-type sesquiterpenoid hemiketal isolated from Rhizoma Curcumae, which is used for a broad range of diseases in traditional Chinese and Indian medicine. It has been reported to exert anti-tumor activity, but the intrinsic molecular mechanism in hepatocellular carcinoma (HCC) is unclear. Therefore, the present study was designed to reveal the predictive targets and biological mechanisms of curcumol against HCC via a network pharmacology-based approach combined with bioinformatic analytics and to provide proof of concept for further similar investigations. METHODS: Data available from open-source databases (Traditional Chinese Medicine Systems Pharmacology, Comparative Toxicogenomic Database, The Cancer Genome Atlas, the Human Protein Atlas project) was processed with the help of a variety of open-source tools (SwissADME, SwissTargetPrediction, JVenn, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, GeneMANIA, Cytoscape). RESULTS: In the present study, the potential of curcumol against HCC was unraveled by network pharmacology-based elucidation. It suggests that curcumol shows exciting druggability with 44 potent homo sapiens biotargets against HCC. The GO terms and KEGG pathways enrichment analyses, curcumol-targets-pathways-HCC network, PPI network, and corresponding in-depth topological analyses, as well as survival analysis, molecular docking simulation indicate that the potential mechanism of curcumol against HCC is complicated, as it may act in various ways, mainly by inducing apoptosis and modulating the inflammatory response, increasing presentation of HCC-specific protein. CONCLUSION: The present study highlights the potential of curcumol against HCC, giving reference to further experimental study. It also presents a roadmap that can be followed to conduct in silico prescreening of other compounds of interest.

Lung protective ventilation strategy to reduce postoperative pulmonary complications (PPCs) in patients undergoing robot-assisted laparoscopic radical cystectomy for bladder cancer: A randomized double blinded clinical trial.

STUDY OBJECTIVE: To evaluate the effects of ventilation with low tidal volume and positive end-expiratory pressure (PEEP) on postoperative pulmonary complications in patients undergoing robot-assisted laparoscopic radical cystectomy (RARC) for bladder cancer. DESIGN: A prospective randomized double-blinded study. SETTING: A single center trial in a comprehensive tertiary hospital from January 2017 to January 2019. PATIENTS: A total of 258 patients undergoing RARC for bladder cancer. INTERVENTIONS: Patients were randomly assigned to receive either lung-protective ventilation (LPV group) [tidal volume 6 ml/ kg predicated body weight (PBW) + PEEP 7 cmH2O] or nonprotective ventilation (control group) (tidal volume 9 ml/ kg PBW without PEEP) during anesthesia. MEASUREMENTS: The primary outcome was the occurrence of postoperative pulmonary complications (PPCs) during the first 90 days after surgery. The secondary outcomes were extubation time, oxygenation index (OI) after extubation and at postoperative day 1 in blood gas. MAIN RESULTS: The incidence of PPCs at postoperative day1, 2 and 3 were lower in LPV group [26.8% vs. 47.2%, odds ratio (OR) 0.41, 95% confidence interval (CI), 0.24-0.69, P = 0.0007, 21.3% vs. 43.3%, OR 0.36, 95% CI, 0.20-0.61, P = 0.0002, 14.2% vs. 27.5%, OR0.43, 95%CI, 0.23-0.82, P = 0.0087, respectively], while no differences were observed at day 7 and 28 (3.9% vs. 9.4%, P = 0.0788, 0% vs. 1.6%, P = 0.4980, respectively). No PPCs were observed at postoperative day 90 in both groups. Furthermore, immediately after extubating and at postoperative day 1, OI was significantly higher in LPV group compared with control group [390(337-467) vs. 343(303-420), P = 0.0005, 406.7(73.0) vs. 425.5(74.7), P = 0.0440, respectively]. Patients in LPV group had a significant shorter extubation time after operation compared with control group [38(33-54) vs. 35(25-46), P = 0.0012]. CONCLUSION: LPV combining low tidal volume and PEEP during anesthesia for RARC may decrease the incidence of postoperative pulmonary complications.

National survey on sedation for gastrointestinal endoscopy in 2758 Chinese hospitals.

BACKGROUND: Although sedation during gastrointestinal endoscopy is widely used in China, the characteristics of sedation use, including regional distribution, personnel composition, equipment used, and drug selection, remain unclear. The present study aimed to provide insights into the current practice and regional distribution of sedation for gastrointestinal endoscopy in China. METHODS: A questionnaire consisting of 19 items was distributed to directors of anaesthesiology departments and anaesthesiologists in charge of endoscopic sedation units in mainland China through WeChat. RESULTS: The results from 2758 participating hospitals (36.7% of the total) showed that 9 808 182 gastroscopies (69.3%) and 4 353 950 colonoscopies (30.7%), with a gastroscopy-to-colonoscopy ratio of 2.3, were conducted from January to December 2016. Sedation was used with 4 696 648 gastroscopies (47.9%) and 2 148 316 colonoscopies (49.3%), for a ratio of 2.2. The most commonly used sedative was propofol (61.0% for gastroscopies and 60.4% for colonoscopies). Haemoglobin oxygen saturation (SpO2) was monitored in most patients (96.1%). Supplemental oxygen was routinely administered, but the availability of other equipment was variable (anaesthesia machine in 64.9%, physiological monitor in 84.4%, suction device in 72.3%, airway equipment in 75.5%, defibrillator in 32.7%, emergency kit in 57.0%, and difficult airway kit in 20.8% of centres responding). CONCLUSIONS: The sedation rate for gastrointestinal endoscopy is much lower in China than in the USA and in Europe. The most commonly used combination of sedatives was propofol plus an opioid (either fentanyl or sufentanil). Emergency support devices, such as difficult airway devices and defibrillators, were not usually available.

Novel Span-PEG Multifunctional Ultrasound Contrast Agent Based on CNTs as a Magnetic Targeting Factor and a Drug Carrier.

Based on the targeting of ferroferric oxide (Fe3O4) and the drug-loading property of carbon nanotubes (CNTs), a novel Span-PEG-composited Fe3O4-CNTs-DOX multifunctional ultrasound contrast agent was designed and applied to tumor lesions. In situ liquid phase synthesis was employed to prepare the Fe3O4-CNTs magnetic targeting complex, and the physical method was used to obtain the Fe3O4-CNTs-DOX complex by loading doxorubicin (DOX) onto Fe3O4-CNTs. The targeted drug-loading complex Fe3O4-CNTs-DOX was combined with the membrane material of Span-PEG by the acoustic vibration cavitation method. The maximum tolerance for Span-PEG-composited Fe3O4-CNTs-DOX microbubbles was 450 times higher, which has good safety. The loading rate of DOX in the obtained composite microbubbles was 17.02%. The proliferation inhibition rate of Span-PEG-composited Fe3O4-CNTs-DOX microbubbles on liver cancer SMMC-7721 cells reached 48.3%. Span-PEG-composited Fe3O4-CNTs-DOX microbubbles could significantly enhance ultrasonic imaging and enrich at a specific location under an external magnetic field, and the extended imaging time could ensure the effective observation and diagnosis of lesions.

New Polylactic Acid Multifunctional Ultrasound Contrast Agent Based on Graphene Oxide as the Carrier of Targeted Factor and Drug Delivery.

In recent years, the development of ultrasound contrast agents has encouraged their use as a drug system for diagnosis and therapy. In this paper, polylactic acid (PLA) composite microbubbles (FA/DOX/GO/DOX/PLA) were prepared with graphene oxide (GO) as a carrier of the targeted factor folic acid (FA) and doxorubicin (DOX) by the multiple emulsification-solvent evaporating process. Appearance, particle size, and zeta potential of PLA composite microbubbles were characterized by using a nanoparticle size analyzer and transmission electron microscopy. Breast cancer cells MCF-7 were used to evaluate the antitumor activity of PLA composite microbubbles in vitro by using the CCK-8 and acridine orange staining method. The ultrasonic imaging effect of PLA composite microbubbles was investigated in New Zealand white rabbits by the Doppler color ultrasound imaging system. With Kunming mice as the research model, the acute toxicity of PLA composite microbubbles was examined. The experimental results showed that the prepared PLA composite microbubbles presented a hollow and spherical shape with a particle size of 600 nm or so and a zeta potential of -37.5 ± 10.0 mV. They had a good effect of the enhancing imaging, and clear ultrasound imaging can be obtained. PLA composite microbubbles showed a significant proliferation inhibition effect on breast cancer cells MCF-7 in a dose-dependent manner. After PLA composite microbubbles were modified by FA, they were good for targeting FA receptors on the surface of MCF-7 cells, which increased the inhibition rate of the tumor cells. LD50 of PLA composite microbubbles was 87.529 mg·kg-1; the mice did not show the acute toxicity when the dose of composite microbubbles was lower than this value.

Enhanced ultrasound imaging and anti-tumor in vivo properties of Span-polyethylene glycol with folic acid-carbon nanotube-paclitaxel multifunctional microbubbles.

With Span and polyethylene glycol (PEG) as the membrane material, the as-prepared folate-carbon nanotube-paclitaxel (FA-CNT-PTX) complex was added to the reaction system under sound vibration cavitation and Span-PEG with FA-CNT-PTX microbubbles was obtained. The maximum tolerating dose of the obtained composite microbubbles on Kunming mice was determined by acute toxicity test. Utilizing the breast cancer tumor model in the nude mice to assess the anti-tumor activity in vivo, the inhibition effect of the composite microbubbles on tumor growth was analyzed by recording the weight and tumor volume of the nude mice. HE staining observations, the immunohistochemistry method, and TUNEL were, respectively, used to examine the inhibition effect of the composite microbubbles on breast cancer tumors in the nude mice. The ultrasound imaging effects and the changes in the peak intensities of the composite microbubbles were inspected using a Doppler color ultrasound imaging system. The experimental results showed that the maximum tolerated dose of the composite microbubbles was 3500 mg kg-1, indicating that the composite microbubbles had low toxicity and good biocompatibility. The composite microbubbles could reach the breast cancer tumor via a targeting factor, and then hindered the tumor growth by inhibiting the proliferation of tumor cells and inducing apoptosis of the tumor cells. The composite microbubbles contributed toward enhancing the ultrasound signal and improved the resolution of the ultrasound images and extended the imaging time. Also, the addition of CNTs in the composite microbubbles could enhance the ultrasound contrast. Simultaneously, the peak intensity at the tumor was significantly reduced after the treatment.