Search

Abstract Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

Abstract Objective The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. Methods This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut‐off value. The Kaplan–Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). Results The best cut‐off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional‐hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. Conclusion We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.

Abstract Background Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. Methods Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. Results Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. Conclusions We developed a DLAT-based model to predict patients’ clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy.

Mimicking the functional traits of the muscle system evolves the development of the neuromorphic prosthetic limbs. Herein, a bioinspired neuromuscular system was constructed by connecting an information processor that uses a flexible electro-optical synaptic transistor (FNST) to an effector that uses artificial muscle fibers. In this system, the response of artificial muscle fibers, which imitate the movement of biological muscle fibers, is manipulated by neuromorphic synaptic devices. The FNST is regulated by light pulses and electrical spikes to emulate biological synaptic functions, and thereby applied in secure communication. The feasibility of n-type organic nanowires acting as the channels for neuromorphic devices was demonstrated. Attributing to the flexibility of the n-type organic semiconductor N2200 nanowires, the current of the FNST retains >85% of its initial value after the 5000 bending cycles to radius = 1 cm. The tolerance of bending of the FNST implies its potential applications in wearable electronics. This work offers an approach to potentially advancing electronic skin, neuro-controlled robots, and neuromorphic prosthetic limbs.

5-Aminolevulinic acid hydrochloride (ALA)-mediated sonodynamic therapy (SDT) had anti-tumour effect on pancreatic cancer cells. Hence, ALA loaded lipid/poly(lactic-co-glycolic acid) (PLGA) microbubbles (MBs)-mediated SDT for pancreatic cancer has great potential. The average size of ALA-lipid MBs and ALA-PLGA MBs was about 3.0 µm. The two kinds of MBs had good biocompatibility to normal HPDE6-C7 cells and were not toxic to pancreatic cancer cells. Compared with ALA-induced SDT, a statistically significant decrease in cell viability was observed in ALA lipid/PLGA MBs combined with ultrasound groups in AsPC-1 and BxPC-3 cells (p

Abstract In this study, the corrosion behavior of N80 and TP125V steels was delved firstly into produced water from shale gas fields containing CO2-O2. Moreover, the localized corrosion of these steels was investigated to elucidate the effects of aerobic and anoxic on steel corrosion. The results indicated that the corrosion rates of N80 and TP125V steels under aerobic conditions were lower compared to those in the presence of CO2-O2. Specifically, at temperature of 100 °C and with dissolved oxygen (DO) concentration of 4 mg/L in the CO2-O2 environment, the N80 and TP125V steels exhibited the highest corrosion rate, with values of 0.13 mm/y and 0.16 mm/y, respectively, as determined by specific weight loss measurements. Conversely, these rates decreased to 0.022 mm/y and 0.049 mm/y under aerobic conditions. Furthermore, severe localized corrosion of N80 and TP125V steels with a DO concentration of 4 mg/L was also observed in the CO2-O2 environment. Finally, it was evident that pitting corrosion is the predominant type of corrosion affecting N80 and TP125V steels in the produced water from shale gas fields.

Abstract Structural modification based on existing drugs, which ensures the safety of marketed drugs, is an essential approach in developing new drugs. In this study, we modified the structure of cabotegravir by introducing the front alkyne on the core structure through chemical reaction, resulting in the synthesis of 9 compounds resembling 1,2,3‐triazoles. The potential of these new cabotegravir derivatives as tumor suppressors in gastrointestinal tumors was investigated. Based on the MTT experiment, most compounds showed a reduction in the viability of KYSE30 and HCT116 cells. Notably, derivatives 5b and 5h exhibited the most significant inhibitory effects. To further explore the effects of derivatives 5b and 5h on gastrointestinal tumors, KYSE30 cells were chosen as a representative cell line. Both derivatives can effectively curtail the migration and invasion capabilities of KYSE30 cells and induce apoptosis in a dose‐dependent manner. We further demonstrated these derivatives induce cell apoptosis in KYSE30 cells by inhibiting the expression of Stat3 protein and Smad2/3 protein. Based on the above results, we suggest they show promise in developing drugs for esophageal squamous cell carcinoma.

The optimal RRT in elliptic space sampling (Informed-RRT*) is an extension of RRT that provides asymptotic optimality, however, it experiences gradual progress and close to obstacles. In the paper, we propose a novel path planning algorithm guided bidirectional Informed-RRT* (BI-RRT*), that introduces extension range, dual-direction exploration, and refinement in trajectory design. The growth range refers to maintaining an additional area from the obstacle to enhance the dependability of the path through preventing impacts. Bidirectional search is a search strategy using both start and target points for a initial solution. Smoothing improves path robustness by using cubic spline. Furthermore, simulation tests for the BI-RRT* algorithm are executed, and the efficacy of the suggested algorithm is confirmed through its application in a robot operating system (ROS). Simulations and experimental tests verify that the proposed algorithm improves the path planning capability. We emphasize the importance of safety, privacy, and reliability in the deployment of AI systems. Our algorithm ensures that the planned paths maintain a safe distance from obstacles, reducing the risk of collisions. Additionally, we prioritize privacy by adhering to data protection regulations and implementing secure communication protocols within the AI system. Moreover, we have applied rigorous testing and validation processes to enhance the reliability of our algorithm, ensuring consistent and accurate path planning outcomes.

ObjectiveThe female reproductive tract is a significant microecological region, and its micro-environment can directly affect women’s cervical health. This research aimed to investigate the effect of vaginal microecology on human papillomavirus (HPV) infection and cervical intraepithelial neoplasia(CIN).MethodsA retrospective cohort study enrolling 2,147 women who underwent a colposcopic examination between August 2021 and August 2022 was conducted. The relationship between vaginal microecology and HPV infection as well as cervical lesions were assessed using the chi-square test, univariate and multivariate logistic regression analyses, and Cochran-Armitage trend test.ResultsHPV infection was linked to the imbalance of vaginal microecology [odds ratio (OR)=3.00, 95% confidence interval (CI)=1.66–5.43; P 0.05), the proportions of abnormal PH value (OR=2.6, 95% CI=1.63–10.42; P=0.001) and abnormal vaginal cleanliness (OR=2.6, 95% CI=1.36–4.0; P= 0.004) increased as the histological stage progressed.ConclusionVaginal microecology associates with HPV infection and the progression of cervical lesions. Detection of vaginal secretion may contribute to the development of targets for micro-environmental modulation with probiotics and the reduction of the incidence of cervical cancer.

Abstract This article presents a novel 3‐D shape reconstruction strategy for small solar system bodies using spaceborne radar which is applied in flyby trajectories to characterize multiple targets in one mission to save time and cost. In this study, we establish a measurement geometry for rapidly spinning small solar system bodies that combines the motion properties of synthetic aperture radar and circular synthetic aperture radar techniques. We also propose a modified imaging algorithm, which is processed using Cardano's formula and the modified polar format algorithm, to improve the imaging quality. Finally, we present simulated results of point‐scattering and 3D shape models. Our analysis shows that the shape reconstruction errors of the algorithm are less than 1.5 m as indicated by the standard deviation.

Satellites with amateur radio communication capabilities have not been operated in lunar orbit before. Here, the authors present the design and performance of a VHF/UHF software-defined radio developed for and tested on lunar microsatellites.

This study investigated the effects of Cordyceps militaris (CM) on intestinal barrier function and gut microbiota in a pig model. A total of 160 pigs were randomly allocated to either a control group (fed the basal diet) or a CM group (fed the basal diet supplemented with 300 mg/kg CM). CM improved intestinal morphology and increased the numbers of goblet cells and intraepithelial lymphocytes. CM also elevated the expression of zona occluden-1, claudin-1, mucin-2 and secretory immunoglobulin A. Furthermore, the mucosal levels of pro-inflammatory cytokines were downregulated while the levels of anti-inflammatory cytokines were upregulated in the CM group. Mechanistically, CM downregulated the expression of key proteins of the TLR4/MyD88/NF-κB signaling pathway. Moreover, CM altered the colonic microbial composition and increased the concentrations of acetate and butyrate. In conclusion, CM can modulate the intestinal barrier function and gut microbiota, which may provide a new strategy for improving intestinal health.

The aim of this study was to determine the effect of excessive back-fat (BF) of sows on placental oxidative stress, ATP generation, mitochondrial alterations in content and structure, and mitochondrial function in isolated trophoblasts. Placental tissue was collected by vaginal delivery from BFI (15−20 mm, n = 10) and BFII (21−27 mm, n = 10) sows formed according to BF at mating. Our results demonstrated that excessive back-fat contributed to augmented oxidative stress in term placenta, as evidenced by excessive production of ROS, elevated protein carbonylation, and reduced SOD, GSH-PX, and CAT activities (p < 0.05). Indicative of mitochondrial dysfunction, reduced mitochondrial respiration in cultured trophoblasts was linked to decreased ATP generation, lower mitochondrial Complex I activity and reduced expression of electron transport chain subunits in placenta of BFII sows (p < 0.05). Meanwhile, we observed negative alterations in mitochondrial biogenesis and structure in the placenta from BFII group (p < 0.05). Finally, our in vitro studies showed lipid-induced ROS production resulted in mitochondrial alterations in trophoblasts, and these effects were blocked by antioxidant treatment. Together, these data reveal that excessive back-fat aggravates mitochondrial injury induced by increased oxidative stress in pig term placenta, which may have detrimental consequences on placental function and therefore impaired fetal growth and development.

In order to explore the effect of controlled atmosphere (CA) storage on alleviating chilling injury (CI) in peach fruit and the possible underlying mechanism, the effect of CA treatment (5% O2 + 10% CO2) on internal browning index (IB), firmness, ethylene release rate, reactive oxygen species (ROS) content, malondialdehyde (MDA) content, compounds and key enzyme activities related to the ascorbic acid-glutathione (AsA-GSH) cycle and volatile contents in yellow-fleshed peach fruit (cv. Jinxiu) during low temperature ((0 ± 2) ℃) storage and shelf (20 ℃, 3 d) was investigated. The results showed that CA alleviated CI significantly relative to the control group; on the third day of the shelf life after 30-day cold storage (30dS3), IB was lower than 10%, fruit firmness decreased to below 10 N, and ethylene release rate was 1.7-fold as high as in the control. During the late period of cold storage, the contents of total ROS, MDA, and hydrogen peroxide (H2O2) were significantly lower and scavenging capacities against 1,1-diphenyl-lpicrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation free radicals were significantly higher in the CA-treated fruit than the control group (P < 0.05 or P < 0.01). Meanwhile, in the CA-treated peach fruit, the activity of superoxide dismutase (SOD) was increased by 36% on 30dS3, while the activities of AsA-GSH cycle-related key enzymes such as ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR) and monodehydroascorbate reductase (MDHAR) were enhanced, and the conversion of reduced ascorbic acid to dehydroascorbic acid was significantly inhibited. Moreover, CA treatment accumulated higher amounts of C6 alcohols, esters, and lactones compared with the control group at the end of the shelf life; on 30dS3, the contents of γ-hexalactone, γ-decalactone, and δ-decalactone were increased by 3.0, 2.6 and 5.0 folds compared with the control group, respectively. In addition, higher contents of sucrose and sorbitol and lower contents of glucose and fructose were observed in the CA-treated fruit. Therefore, CA treatment (5% O2 + 10% CO2) can alleviate CI and maintain aroma quality by activating the AsA-GSH cycle and SOD, and enhancing ROS scavenging capacity in peach fruit.