Predicting prostate cancer recurrence: Introducing PCRPS, an advanced online web server.

Background: Prostate cancer (PCa) is one of the leading causes of cancer death in men. About 30% of PCa will develop a biochemical recurrence (BCR) following initial treatment, which significantly contributes to prostate cancer-related deaths. In clinical practice, accurate prediction of PCa recurrence is crucial for making informed treatment decisions. However, the development of reliable models and biomarkers for predicting PCa recurrence remains a challenge. In this study, the aim is to establish an effective and reliable tool for predicting the recurrence of PCa. Methods: We systematically screened and analyzed potential datasets to predict PCa recurrence. Through quality control analysis, low-quality datasets were removed. Using meta-analysis, differential expression analysis, and feature selection, we identified key genes associated with recurrence. We also evaluated 22 previously published signatures for PCa recurrence prediction. To assess prediction performance, we employed nine machine learning algorithms. We compared the predictive capabilities of models constructed using clinical variables, expression data, and their combinations. Subsequently, we implemented these machine learning models into a user-friendly web server freely accessible to all researchers. Results: Based on transcriptomic data derived from eight multicenter studies consisting of 733 PCa patients, we screened 23 highly influential genes for predicting prostate cancer recurrence. These genes were used to construct the Prostate Cancer Recurrence Prediction Signature (PCRPS). By comparing with 22 published signatures and four important clinicopathological features, the PCRPS exhibited a robust and significantly improved predictive capability. Among the tested algorithms, Random Forest demonstrated the highest AUC value of 0.72 in predicting PCa recurrence in the testing dataset. To facilitate access and usage of these machine learning models by all researchers and clinicians, we also developed an online web server (https://urology1926.shinyapps.io/PCRPS/) where the PCRPS model can be freely utilized. The tool can also be used to (1) predict the PCa recurrence by clinical information or expression data with high accuracy. (2) provide the possibility of PCa recurrence by nine machine learning algorithms. Furthermore, using the PCRPS scores, we predicted the sensitivity of 22 drugs from GDSC2 and 95 drugs from CTRP2 to the samples. These predictions provide valuable insights into potential drug sensitivities related to the PCRPS score groups. Conclusion: Overall, our study provides an attractive tool to further guide the clinical management and individualized treatment for PCa.

Mesothelin CAR-T cells expressing tumor-targeted immunocytokine IL-12 yield durable efficacy and fewer side effects.

Chimeric antigen receptor (CAR)-modified T cell therapy has achieved remarkable efficacy in treating hematological malignancies, but it confronts many challenges in treating solid tumors, such as the immunosuppressive microenvironment of the solid tumors. These factors reduce the antitumor activity of CAR-T cells in clinical trials. Therefore, we used the immunocytokine interleukin-12(IL-12) to enhance the efficacy of CAR-T cell therapy. In this study, we engineered CAR-IL12R54 T cells that targeted mesothelin (MSLN) and secreted a single-chain IL-12 fused to a scFv fragment R54 that recognized a different epitope on mesothelin. The evaluation of the anti-tumor activity of the CAR-IL12R54 T cells alone or in combination with anti-PD-1 antibody in vitro and in vivo was followed by the exploration of the functional mechanism by which the immunocytokine IL-12 enhanced the antitumor activity. CAR-IL12R54 T cells had potency to lyse mesothelin positive tumor cells in vitro. In vivo studies demonstrated that CAR-IL12R54 T cells were effective in controlling the growth of established tumors in a xenograft mouse model with fewer side effects than CAR-T cells that secreted naked IL-12. Furthermore, combination of PD-1 blockade antibody with CAR-IL12R54 T cells elicited durable anti-tumor responses. Mechanistic studies showed that IL12R54 enhanced Interferon-γ (IFN-γ) production and dampened the activity of regulatory T cells (Tregs). IL12R54 also upregulated CXCR6 expression in the T cells through the NF-κB pathway, which facilitated T cell infiltration and persistence in the tumor tissues. In summary, the studies provide a good therapeutic option for the clinical treatment of solid tumors.

Cardiovascular Risk Factors in China.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. This section dissects cardiovascular risk factors in China which including hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease, metabolic syndrome and air pollution. Hypertension prevalence has steadily increased in China, with efforts to control it facing challenges in achieving optimal rates, especially in rural areas. Interventions like salt substitutes and intensive blood pressure control show promise but need improvement. Abnormal lipid levels, indicative of dyslipidemia, have risen significantly, posing a risk for cardiovascular diseases. Despite efforts, many patients struggle to achieve target lipid levels, necessitating improved treatment strategies. Both type 1 and type 2 diabetes mellitus affect millions of adults in China, with long-term complications adding to the disease burden. Early intervention and effective management are crucial to mitigate its impact. Prevalent among older adults, chronic kidney disease is associated with diabetes mellitus, hypertension, and cardiovascular diseases, necessitating comprehensive management approaches. The prevalence of metabolic syndrome, characterized by a cluster of risk factors, has increased in both adults and adolescents, calling for lifestyle modifications and public health interventions. Ambient and household air pollution remain significant environmental risk factors, despite some improvements in air quality. Continued efforts to reduce emissions are essential for mitigating associated health risks. Addressing these risk factors requires a multifaceted approach, including public health initiatives, policy interventions, and individual-level strategies to promote healthy lifestyles and reduce environmental exposures. Surveillance and research efforts are crucial for monitoring trends and developing effective strategies to lessen the burden of cardiovascular diseases in China.

KN046, a bispecific antibody against PD-L1 and CTLA-4, plus chemotherapy as first-line treatment for metastatic NSCLC: A multicenter phase 2 trial.

KN046, a bispecific antibody targeting PD-L1 and CTLA-4, presents a promising therapeutic option for metastatic non-small cell lung cancer (NSCLC). In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. Following four cycles, maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC. The objective response rate is 46.0%, and the median duration of response is 8.1 months. The median progression-free and overall survival are 5.8 and 26.6 months, respectively. The common adverse events include anemia (87.4%), loss of appetite (72.4%), and neutropenia (70.1%). The most prevalent immune-related adverse event is pruritus (28.7%). These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531).

Ginsenoside Rd enhances blood-brain barrier integrity after cerebral ischemia/reperfusion by alleviating endothelial cells ferroptosis via activation of NRG1/ErbB4-mediated PI3K/Akt/mTOR signaling pathway.

The incidence of ischemic stroke is increasing year by year and showing a younger trend. Impaired blood-brain barrier (BBB) is one of the pathological manifestations caused by cerebral ischemia, leading to poor prognosis of patients. Accumulating evidence indicates that ferroptosis is involved in cerebral ischemia/reperfusion injury (CIRI). We have previously demonstrated that Ginsenoside Rd (G-Rd) protects against CIRI-induced neuronal injury. However, whether G-Rd can attenuate CIRI-induced disruption of the BBB remains unclear. In this study, we found that G-Rd could upregulate the levels of ZO-1, occludin, and claudin-5 in ipsilateral cerebral microvessels and bEnd.3 cells, reduce endothelial cells (ECs) loss and Evans blue (EB) leakage, and ultimately improve BBB integrity after CIRI. Interestingly, the expressions of ACSL4 and COX2 were upregulated, the expressions of GPX4 and xCT were downregulated, the levels of GSH was decreased, and the levels of MDA and Fe2+ were increased in ischemic tissues and bEnd.3 cells after CIRI, suggesting that ECs ferroptosis occurred after CIRI. However, G-Rd can alleviate CIRI-induced BBB disruption by inhibiting ECs ferroptosis. Mechanistically, G-Rd prevented tight junction loss and BBB leakage by upregulating NRG1, activating its tyrosine kinase ErbB4 receptor, and then activating downstream PI3K/Akt/mTOR signaling, thereby inhibiting CIRI-induced ferroptosis in ECs. Taken together, these data provides data support for G-Rd as a promising therapeutic drug for cerebral ischemia.

A multi-constituent model for assessing the effect of impeller shroud on the thrombosis potential of a centrifugal blood pump.

Centrifugal blood pumps can be used for treating heart failure patients. However, pump thrombosis has remained one of the complications that trouble clinical treatment. This study analyzed the effect of impeller shroud on the thrombosis risk of the blood pump, and predicted areas prone to thrombosis. Multi-constituent transport equations were presented, considering mechanical activation and biochemical activation. It was found that activated platelets concentration can increase with shear stress and adenosine diphosphate(ADP) concentration increasing, and the highest risk of thrombosis inside the blood pump was under extracorporeal membrane oxygenation (ECMO) mode. Under the same condition, ADP concentration and thrombosis index of semi-shroud impeller can increase by 7.3% and 7.2% compared to the closed-shroud impeller. The main reason for the increase in thrombosis risk was owing to elevated scalar shear stress and more coagulation promoting factor-ADP released. The regions with higher thrombosis potential were in the center hole, top and bottom clearance. As a novelty, the findings revealed that impeller shroud can influence mechanical and biochemical activation factors. It is useful for identifying potential risk regions of thrombus formation based on relative comparisons.

Clinical study of electroacupuncture on the recovery of gastrointestinal dysfunction after laparoscopic surgery for gastrointestinal cancer - study protocol for a randomized controlled trial.

BACKGROUND: Gastrointestinal dysfunction is one of the common complaints for patient post-surgery. Acupuncture has been employed to improve gastrointestinal function and sleeping quality and has confirmed clinical efficacy for emotional problems. This study aims to evaluate the clinical effect of electroacupuncture for postoperative rapid recovery. METHODS: This study design is a two-arm, parallel, double-blinded randomized controlled trial. 104 subjects, aged from 40 to 89 years old, diagnosed with gastrointestinal cancer undergoing laparoscopic surgery, will be divided into Interventional Group and Control Group. Patients of both groups receive perioperative care under the guidance of ERAS guidance. The Interventional Group receives electroacupuncture treatment starting from the first day post-surgery for a consecutive 5 days, whereas the Control Group receives placebo electroacupuncture treatment. The primary outcome will be the first flatus time whereas the secondary outcomes will be the first sign of borborygmus, recovery of defecation, laboratory tests and questionnaires including Self-rating anxiety scale, Ford Insomnia Response to Stress Test, TCM rating scale of Gastrointestinal symptoms and Gastrointestinal Symptoms Rating Scales. DISCUSSION: This study aims to provide timely intervention for post-laparoscopic patients with gastrointestinal tumour using the ERAS concept combined with electroacupuncture, observe the efficacy of this therapy in treating PGID, and contribute reliable scientific evidence for postoperative rapid recovery. TRIAL REGISTRATION: Chictr.org.cn Identifier: ChiCTR2300078710. Registered on 15th December 2023.

Accurate network pharmacology and novel ingredients formula of herbal targeting estrogen signaling for psoriasis intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: As a common chronic inflammatory skin disease, psoriasis is incompletely understood and brings a lot of distress to patients. The estrogen signaling pathway has been implicated in its pathogenesis, making it a potential therapeutic target. Si Cao Formula (SCF) has demonstrated promise in treating psoriasis clinically. However, its molecular mechanisms concerning psoriasis remain largely unexplored. AIM OF THE STUDY: To elucidate the underlying mechanisms of the action of SCF on psoriasis. MATERIALS AND METHODS: Active ingredients were identified by LC-MS/MS. After the treatment with SCF, the exploration of differentially expressed proteins (DEPs) were conducted using tandem mass tag (TMT)-based quantitative proteomics analysis. By GO/KEGG, WikiPathways and network pharmacology, core signaling pathway and protein targets were explored. Consequently, major signaling pathway and protein targets were validated by RT-qPCR, immunoblotting and immunofluorescence. Based on Lipinski's Rule of Five rules and molecular docking, 8 active compounds were identified that acted on the core targets. RESULTS: 41 compounds of SCF and 848 specific targets of these compounds were identified. There were 570 DEPs between IMQ (Imiquimod) and IMQ + SCF group, including 279 up-regulated and 304 down-regulated proteins. GO/KEGG, WikiPathways and network pharmacology revealed estrogen signaling pathway as the paramount pathways, through which SCF functioned on psoriasis. We further show novel ingredients formula of SCF contributes to estrogen signaling intervention, including liquiritin, parvisoflavone B, glycycoumarin, 8-prenylluteone, licochalcone A, licochalcone B, oxymatrine, and 13-Hydroxylupanine, where targeting MAP2K1, ILK, HDAC1 and PRKACA, respectively. Molecular docking proves that they have good binding properties. CONCLUSION: Our results provide an in-depth view of psoriasis pathogenesis and herbal intervention, which expands our understanding of the systemic pharmacology to reveal the multiple ingredients and multiple targets of SCF and focus on one pathway (estrogen signaling pathway) may be a novel therapeutic strategy for psoriasis treatment of herbal medicine.

Influencing Factors on Cardiovascular Health in China.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. This is the first section of the report, which dissects influential factors across diverse domains. The investigation identifies tobacco use as a paramount concern, portraying China as the global epicenter of tobacco consumption. Cigarette smoking, exacerbated by second-hand smoke exposure, emerges as a critical and preventable risk factor, contributing to a surge in attributable deaths over the past three decades. In the realm of dietary nutrition, the study discerns an overall improvement, yet discerns worrisome deviations, notably an escalating fat intake surpassing recommended guidelines. The shifting dietary structure reveals diminished consumption of cereals and vegetables juxtaposed with an uptick in animal foods, while excessive intake of cooking oil and salt persists, straying substantially from endorsed levels. The exploration of physical activity patterns unfolds a nuanced narrative. Varied trends are observed among students, with concerns arising from sedentary behaviors and inadequate adherence to recommended guidelines. The analysis spans a trajectory of declining physical activity in Chinese adults, coupled with an alarming surge in sedentary leisure time, ultimately linking these factors to heightened risks of cardiovascular diseases and increased adiposity. An examination of overweight and obesity trends uncovers a relentless upward trajectory, projecting substantial prevalence by 2030. Noteworthy prevalence rates underscore the imperative for targeted interventions to curtail this burgeoning health crisis, with the anticipated prevalence extending to nearly two-thirds of the adult population. Psychological factors, notably depression, constitute an integral facet of cardiovascular health. Prevalence rates among patients with coronary artery disease and acute myocardial infarction underscore the intricate interplay between mental health and cardiovascular outcomes. Additionally, persistent depressive symptoms are shown to significantly elevate the risk of cardiovascular diseases and mortality. This first section underscores the multifaceted challenges facing cardiovascular health in China, emphasizing the imperative for tailored interventions across tobacco control, dietary habits, physical activity, obesity management, and psychological well-being to mitigate the escalating burden of cardiovascular diseases in the population.

Intelligent diagnosis of lung nodule images based on machine learning in the context of lung teaching.

The vast majority of intelligent diagnosis models have widespread problems, which seriously affect the medical staff judgment of patients' injuries. So depending on the situation, you need to use different algorithms, The study suggests a model for intelligent diagnosis of lung nodule images based on machine learning, and a support vector machine-based machine learning algorithm is selected. In order to improve the diagnostic accuracy of intelligent diagnosis of lung nodule images as well as the diagnostic model of lung nodule images. The objectives are broken down into algorithm determination and model construction, and the proposed optimized model is solved using machine learning techniques in order to achieve the original algorithm selected for intelligent diagnosis of lung nodule photos. The validation findings demonstrated that dimensionality reduction of the features produced 17 × 1120 and 17 × 2980 non-node matrices with 1216 nodes and 3407 non-nodes in 17 features. The support vector machine classification method has more benefits in terms of accuracy, sensitivity, and specificity when compared to other classification methods. Since there were some anomalies among both benign and malignant tumors and no discernible difference between them, the distribution of median values revealed that the data was symmetrical in terms of texture and gray scale. Non-small nodules can be identified from benign nodules, but more training is needed to separate them from the other 2 types. Pulmonary nodules are a common disease. MN are distinct from the other 2 types, non-small nodules and benign small nodules, which require further training to differentiate. This has great practical value in teaching practice. Therefore, building a machine learning-based intelligent diagnostic model for pulmonary nodules is of significant importance in helping to solve medical imaging diagnostic problems.

Study on Linewidth and Phase Noise Characteristics of a Narrow Linewidth External Cavity Diode Laser.

In the field of inter-satellite laser communication, achieving high-quality communication and compensating for the Doppler frequency shift caused by relative motion necessitate lasers with narrow linewidths, low phase noise, and the ability to achieve mode-hop-free tuning within a specific range. To this end, this paper investigates a novel external cavity diode laser (ECDL) with a frequency-selective F-P etalon structure, leveraging the external cavity F-P etalon structure in conjunction with an auxiliary filter to achieve single longitudinal mode selection. The laser undergoes linewidth testing using a delayed self-heterodyne beating method, followed by the testing of its phase noise and frequency noise characteristics using a noise analyzer, yielding beat spectra and noise power spectral density profiles. Furthermore, the paper introduces an innovative bidirectional temperature-scanning laser method to achieve optimal laser-operating point selection and mode-hop-free tuning. The experimental results showcase that the single longitudinal mode spectral side-mode suppression ratio (SMSR) is around 70 dB, and the output power exceeds 10 mW. Enhancing the precision of the F-P etalon leads to a more pronounced suppression of low-frequency phase noise, reducing the Lorentzian linewidth from the initial 10 kHz level to a remarkable 5 kHz level. The bidirectional temperature-scanning laser method not only allows for the selection of the optimal operating point but also enables mode-hop-free tuning within 160 pm.

First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial.

BACKGROUND: The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial. METHODS: Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile. RESULTS: Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1-49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator. CONCLUSION: Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT04346381.

The volatile organic compounds generated from the Maillard reaction between l-ascorbic acid and l-cysteine in hot compressed water.

BACKGROUND: Hot compressed water (HCW), also known as subcritical water (SCW), refers to high-temperature compressed water in a special physical and chemical state. It is an emerging technology for natural product extraction. The volatile organic compounds (VOCs) generated from the Maillard reaction between l-ascorbic acid (ASA) and l-cysteine (Cys) have attracted significant interest in the flavor and fragrance industry. This study aimed to explore the formation mechanism of VOCs from ASA and Cys and examine the effects of reaction parameters such as temperature, time, and pH in HCW. RESULTS: The identified VOCs were predominantly thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The findings indicated that thiophene derivatives were formed under various pH conditions, with polysulfide formation favored under acidic conditions and pyrazine derivative formation preferred under weak alkaline conditions, specifically at pH 8.0. CONCLUSION: The Maillard reaction between ASA and Cys mainly produced thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The generation mechanism was significantly dependent on the surrounding pH conditions. © 2024 Society of Chemical Industry.

PPT1 Promotes Growth and Inhibits Ferroptosis of Oral Squamous Cell Carcinoma Cells.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. OBJECTIVE: To explore the role of palmitoyl protein thioesterase 1 (PPT1) in OSCC. METHODS: Differentially Expressed Genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments, including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate the gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. RESULTS: A total of 555 DEGs were obtained, and topological analysis revealed that the PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibiting the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). CONCLUSION: PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.

Association Between Serum Uric Acid and Abdominal Aortic Calcification in Adults Aged 40 to 80 years: A Retrospective Cross-Sectional Study.

There are numerous causes of abdominal aortic calcification (AAC), among which the relationship between serum uric acid and AAC still needs to be investigated further. The aim of this research was to ascertain whether serum uric acid is correlated with AAC. Our study included 3007 participants. We described the study population characteristics and utilized univariate analysis, stratified analysis, multiple equation regression analysis, smoothed curve fitting, and threshold effects analysis. AAC Total 24 score is used to reflect the range of aortic calcification at each vertebral level. As serum uric acid increased, the AAC Total 24 score first decreased and then increased. The fold point is located when serum uric is at 3.5 mg/dL. After adjusting for 16 covariates, the beta values for the groups with moderate and high serum uric acid levels were 0.34 and 0.53, respectively, compared with the low serum uric acid tertile group (P < .05). Our research indicates a negative correlation between serum acid level and AAC when serum uric acid <3.5 mg/dl, but it is positively correlated with the formation of AAC when serum uric acid >3.5 mg/dl.

MiRNA-766-3p inhibits gastric cancer via targeting COL1A1 and regulating PI3K/AKT signaling pathway.

Objective MiRNA-766-3p has been shown to be associated with a variety of cancers. However, few studies have been done in gastric cancer (GC). This study explores the mechanism of miR-766-3p in GC. Methods The potential targets of microRNA (miRNA) were predicted using Tarbase and Targetscan databases. The results are intersected with differential genes (DEGs) (fold change > 1.5, P < 0.05) in gastric cancer to obtain potential core targets. The hub targets screened by constructing PPI networks (degree > 5, expression > 0.5). Validating the differential expression and expression in immunohistochemistry of these targets through the database. And the binding sites between miRNAs and mRNAs were verified using dual-luciferase Assay. Finally, qRT-PCR and Western Blot experiments were conducted to validate the hub targets and signal pathways. Results The potential hub targets from the PPI network were THBS2, COL1A1, FGG, FGB, and PLAU. Combining database, luciferase Assay and experimental validation, miR-766-3p can sponge COL1A1 and it plays the most important role in gastric cancer progression. In GC, COL1A1 was upregulated and the enrichment analysis revealed that COL1A1 regulates PI3K/AKT signal pathway, and AKT is also highly expressed in gastric cancer. Conclusion The miR-766-3p can inhibit the progression of gastric cancer by targeting COL1A1 and regulating the PI3K/AKT signal pathway. It could be a potential therapy option for the GC.

Anomaly Detection Method for Lithium-Ion Battery Cells Based on Time Series Decomposition and Improved Manhattan Distance Algorithm.

Abnormalities in individual lithium-ion batteries can cause the entire battery pack to fail, thereby the operation of electric vehicles is affected and safety accidents even occur in severe cases. Therefore, timely and accurate detection of abnormal monomers can prevent safety accidents and reduce property losses. In this paper, a battery cell anomaly detection method is proposed based on time series decomposition and an improved Manhattan distance algorithm for actual operating data of electric vehicles. First, time series decomposition is performed on the voltage data of all battery cells in the battery pack to obtain the voltage trend component of each cell. Then, the improved Manhattan distance algorithm is utilized to calculate and compare the Manhattan distance values between adjacent cell trend components, to determine the abnormal cells inside the battery pack. Furthermore, the Manhattan distance values at the same sampling moment are calculated within the data sequence to detect the specific time when the abnormal cells malfunction. The data analysis and experimental verification results based on actual vehicle operating conditions indicate that this method can accurately identify an abnormal cell within the battery pack and diagnose the specific moment of abnormality in the battery cell at an early stage of failure, with good robustness.

The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions.

CREB3 subfamily belongs to the bZIP transcription factor family and comprises five members. Normally they are located on the endoplasmic reticulum (ER) membranes and proteolytically activated through RIP (regulated intramembrane proteolysis) on Golgi apparatus to liberate the N-terminus to serve as transcription factors. CREB3L1 acting as one of them transcriptionally regulates the expressions of target genes and exhibits distinct functions from the other members of CREB3 family in eukaryotes. Physiologically, CREB3L1 involves in the regulation of bone morphogenesis, neurogenesis, neuroendocrine, secretory cell differentiation, and angiogenesis. Pathologically, CREB3L1 implicates in the modulation of osteogenesis imperfecta, low grade fibro myxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), glioma, breast cancer, thyroid cancer, and tissue fibrosis. This review summarizes the upstream and downstream regulatory network of CREB3L1 and thoroughly presents our current understanding of CREB3L1 research progress in both physiological and pathological conditions with special focus on the novel findings of CREB3L1 in cancers.

Se-(Methyl)-selenocysteine ameliorates blood-brain barrier disruption of focal cerebral ischemia mice via ferroptosis inhibition and tight junction upregulation in an Akt/GSK3ß-dependent manner.

BACKGROUND: Ischemic stroke still ranks as the most fatal disease worldwide. Blood-brain barrier (BBB) is a promising therapeutic target for protection. Brain microvascular endothelial cell is a core component of BBB, the barrier function maintenance of which can ameliorate ischemic injury and improve neurological deficit. Se-methyl L-selenocysteine (SeMC) has been shown to exert cardiovascular protection. However, the protection of SeMC against ischemic stroke remains to be elucidated. This research was designed to explore the protection of SeMC from the perspective of BBB protection. METHODS: To simulate cerebral ischemic injury, C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R), and bEnd.3 was exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). After the intervention of SeMC, the barrier function and the expression of tight junction and ferroptosis-associated proteins were determined. For mechanism exploration, LY294002 (Akt inhibitor) was introduced both in vivo and in vitro. RESULTS: SeMC lessened the brain infarct volume and attenuated the leakage of BBB in mice. In vitro, SeMC improved cell viability and maintained the barrier function of bEnd.3 cells. The protection of SeMC was accompanied with ferroptosis inhibition and tight junction protein upregulation. Mechanism studies revealed that the effect of SeMC was reversed by LY294002, indicating that the protection of SeMC against ischemic stroke was mediated by the Akt signal pathway. CONCLUSION: These results suggested that SeMC exerted protection against ischemic stroke, which might be attributed to activating the Akt/GSK3ß signaling pathway and increasing the nuclear translocation of Nrf2 and ß-catenin, subsequently maintaining the integrity of BBB.