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Abstract Background Ageing results in diminished adaptability, as well as declines in physiological and psychological functions and resilience. The epigenetic clock ‘Phenotypic Age’ (PhenoAge) represents ‘preclinical ageing’. Phenotypic Age Acceleration (PhenoAgeAccel) is defined as the residual from a linear regression model predicting PhenoAge on the basis of chronological age. Abdominal subcutaneous adipose tissue, visceral adipose tissue, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and high-density lipoprotein cholesterol (HDL-C) have all been shown to correlate with ageing; however, the connections between these factors and PhenoAge are still insufficiently investigated. Methods Data for this study were sourced from the National Health and Nutrition Examination Survey (2015–2018), comprising 2580 participants. Complex survey designs were considered. To examine the association between body fat area and PhenoAgeAccel, logistic regression was applied. Additionally, subgroup analysis was used to identify variations in population characteristics. The dose‒response relationship between body fat area and PhenoAgeAccel was determined via restricted cubic spline analysis. Mediation and interaction analyses were further employed to investigate the roles of the HOMA-IR and HDL-C in this association. Results In nonelderly adults, the relationships between body fat area and PhenoAgeAccel differed chronological age. For abdominal subcutaneous fat area (SFA), this relationship was nonlinear in individuals aged 18–44 years and 45–59 years, with thresholds of 2.969 m² and 3.394 m², respectively. In contrast, a nonlinear relationship of visceral fat area (VFA) with PhenoAgeAccel was observed in individuals aged 18–44 years, while this relationship was linear in individuals aged 45–59 years, with thresholds of 0.769 m² and 1.220 m², respectively. Mediation effect analysis revealed that the HOMA-IR had a more pronounced mediation effect in individuals aged 18–44 years, accounting for 13.4% of the relationship between VFA and PhenoAgeAccel and 6.9% of the relationship between SFA and PhenoAgeAccel. Conversely, HDL-C had a greater mediating effect in individuals aged 45–59 years, accounting for 21.7% of the relationship between VFA and PhenoAgeAccel and 11.6% of the relationship between abdominal SFA and PhenoAgeAccel. HOMA-IR ≥ 2.73 or VFA > 0.925 m², as well as HOMA-IR ≥ 2.73 or abdominal SFA > 3.137 m², accelerated PhenoAge, whereas 1.60

Context Tabersonine has been investigated for its role in modulating inflammation-associated pathways in various diseases. However, its regulatory effects on triple-negative breast cancer (TNBC) have not yet been fully elucidated.Objective This study uncovers the anticancer properties of tabersonine in TNBC cells, elucidating its role in enhancing chemosensitivity to cisplatin (CDDP).Materials and methods After tabersonine (10 μM) and/or CDDP (10 μM) treatment for 48 h in BT549 and MDA-MB-231 cells, cell proliferation was evaluated using the cell counting kit-8 and colony formation assays. Quantitative proteomics, online prediction tools and molecular docking analyses were used to identify potential downstream targets of tabersonine. Transwell and wound-healing assays and Western blot analysis were used to assess epithelial–mesenchymal transition (EMT) phenotypes.Results Tabersonine demonstrated inhibitory effects on TNBC cells, with IC50 values at 48 h being 18.1 μM for BT549 and 27.0 μM for MDA-MB-231. The combined treatment of CDDP and tabersonine synergistically suppressed cell proliferation in BT549 and MDA-MB-231 cells. Enrichment analysis revealed that the proteins differentially regulated by tabersonine were involved in EMT-related signalling pathways. This combination treatment also effectively restricted EMT-related phenotypes. Through the integration of online target prediction and proteomic analysis, Aurora kinase A (AURKA) was identified as a potential downstream target of tabersonine. AURKA expression was reduced in TNBC cells post-treatment with tabersonine.Discussion and conclusions Tabersonine significantly enhances the chemosensitivity of CDDP in TNBC cells, underscoring its potential as a promising therapeutic agent for TNBC treatment.

Abstract Pumped storage plants (PSPs) play an important role in renewable energy consumption in power systems. Variable‐speed technology is a new and critical direction for the development of PSPs. In pump mode, variable‐speed pumped storage units (VSPSUs) have wider power regulation ranges and more flexible power responses than fixed‐speed pumped storage units (FSPSUs); however, the corresponding quantification study of VSPSUs is rare. Therefore, this study aims to quantify the static and dynamic power regulation characteristics of VSPSU in pump mode. First, the modeling of the fast speed control strategy of VSPSU in pump mode is improved. Then, the power regulation range of the VSPSU is explored. The factors (i.e., power command, governor, and converter) affecting the power response rapidity are quantified through the engineering case of a variable‐speed PSP adopting the doubly fed induction machine. Accordingly, suggestions on the settings of the parameters are provided. Quantification results show that parameter tuning based on this study effectively solves the problem of low regulation rate caused by great power fluctuations under typical power regulation cases in pump mode. This VSPSU has the fastest regulation rate of 13.75%/s when adjusting 40% power. This study could provide technical support to the practical operation of VSPSU.

Abstract Temozolomide (TMZ) represents a standard-of-care chemotherapeutic agent in glioblastoma (GBM). However, the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma. Although specific innovative approaches, such as immunotherapy, have shown favorable clinical outcomes, the inherent invasiveness of most gliomas continues to make them challenging to treat. Consequently, there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug development. This investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors. A total of 648 proteins exhibiting significant differential expression were identified. Gene Set Enrichment Analysis (GSEA) unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent groups. Validation through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate (IP3) kinase B (ITPKB) in the recurrence group, correlating with poor survival in glioma patients. In TMZ-resistant cells, the depletion of ITPKB led to an increase in reactive oxygen species (ROS) related to NADPH oxidase (NOX) activity and restored cell sensitivity to TMZ. Mechanistically, the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ubiquitination. This, in turn, elevated ITPKB stability and impaired ROS production. Furthermore, ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse model. These findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target for TMZ-resistant GBM.

The microstructure and texture features of the dissimilar inertia friction welded (IFW) joint of Ti65 titanium alloy to TC25G titanium alloy were characterized. The β textures in dynamic recrystallization zone (DRZ) produced by severe hot shear deformation were dominated by the bcc D2 (11-2)[111] shear texture for both the Ti65 and the TC25G alloys. The variant selection occurred during the β α phase transformation at the final cooling stage, in which higher fraction of α variants with misorientation of [−10 5 5 3]/63.26° formed. The triangular configuration structures were frequently observed in the interior of the β grains in DRZ, which was resulted from the variant selection occurring in microregion. The formation of triangular configurations was also favored naturally by the bcc β fiber texture.

Objective To investigate the clinical effect of external diaphragmatic pacing(EDP) combined with Hu Xi Jian Fei Gong in the treatment of pulmonary dysfunction in stroke patients. Methods From July 2020 to July 2022, 162 stroke patients in Shanghai Tongren Hospital and Yueyang Hospital of Integrated Traditional Chinese and Western Medicine were randomly divided into a control group and an observation group, with 81 patients in each group.Both group received conventional rehabilitation and EDP, and the observation group additionally received Hu Xi Jian Fei Gong.Forced vital capacity(FVC), forced expiratory volume in 1 second(FEV1), peak expiratory flow(PEF), diaphragmatic mobility, end-expiratory diaphragmatic thickness, and end-inspiratory diaphragmatic thickness were compared between the two groups before treatment and after 4 weeks of treatment.The activity of daily living(ADL) of 72 patients admitted to Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine were compared before treatment, after 4 weeks of treatment and 12 weeks after the end of treatment. Results After treatment, FVC, FEV1, PEF, end-expiratory diaphragmatic thickness and end-inspiratory diaphragmatic thickness in the two groups were higher than those before treatment(P

Abstract The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.

Abstract Gliomas are the most prevalent primary tumor in the central nervous system, with an abysmal 5-year survival rate and alarming mortality. The current standard management of glioma is maximum resection of tumors followed by postoperative chemotherapy with temozolomide (TMZ) or radiotherapy. Low chemosensitivity of TMZ in glioma treatment eventuates limited therapeutic efficacy or treatment failure. Hence, overcoming the resistance of glioma to TMZ is a pressing question. Our research centered on identifying the drug metabolism-related genes potentially involved in TMZ-treated resistance of glioma through several bioinformatics datasets and cell experiments. One efflux transporter, ATP-binding cassette transporter subfamily A1 (ABCA1), was discovered with an upregulated expression level and signaled poor clinical outcomes for glioma patients. The transcript level of ABCA1 significantly elevated across the TMZ-resistant glioma cells in contrast with non-resistant cells. Over-expressed ABCA1 restrained the drug activity of TMZ, and ABCA1 knockdown improved the treatment efficacy. Meanwhile, the results of molecular docking between ABCA1 protein and TMZ showed a high binding affinity. Additionally, co-expression and immunological analysis revealed that ABCA1 facilitates the immune infiltration of M2 macrophages in glioma, thereby stimulating tumor growth and aggravating the poor survival of patients. Altogether, we discovered that the ABCA1 transporter was involved in TMZ chemoresistance and the immune infiltration of M2 macrophages in glioma. Treatment with TMZ after ABCA1 knockdown enhances the chemosensitivity, suggesting that inhibition of ABCA1 may be a potential strategy for improving the therapeutic efficacy of gliomas.

Abstract Staging lymph nodes (LN) is crucial in diagnosing and treating cancer metastasis. Biotechnologies for the specific localization of metastatic lymph nodes (MLNs) have attracted significant attention to efficiently define tumor metastases. Bioimaging modalities, particularly magnetic nanoparticles (MNPs) such as iron oxide nanoparticles, have emerged as promising tools in cancer bioimaging, with great potential for use in the preoperative and intraoperative tracking of MLNs. As radiation-free magnetic resonance imaging (MRI) probes, MNPs can serve as alternative MRI contrast agents, offering improved accuracy and biological safety for nodal staging in cancer patients. Although MNPs’ application is still in its initial stages, exploring their underlying mechanisms can enhance the sensitivity and multifunctionality of lymph node mapping. This review focuses on the feasibility and current application status of MNPs for imaging metastatic nodules in preclinical and clinical development. Furthermore, exploring novel and promising MNP-based strategies with controllable characteristics could lead to a more precise treatment of metastatic cancer patients.

The abnormal expression of tumor associated genes in pan-cancer is closely related to the clinicopathological features of distinct cancer types. Thus, identifying the role of specific genes in pan-cancer is needed for developing effective anti-cancer strategies. However, the function of CD244 in pan-cancer has not been fully understood. In this study, we explored the CD244 expression profile across 33 tumor types based on The Cancer Genome Atlas project, the Gene Expression Omnibus database, and other bioinformatics tools. We found down-regulated expression levels in seven tumor types and up-regulated expression levels in two tumor types. We subsequently explored the relationship between survival rate and CD244 expression, and found the positive relationship in patients with adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), skin cutaneous melanoma (SKCM), and uterine corpus endometrial carcinoma (UCEC). We further investigated the association between CD244 expression and tumor-infiltrating immune cells, and discovered their positive correlation in different tumors. We found that CD244 expression level was higher in normal samples than in UCEC samples, and was positively associated with CD8+ T cells infiltrating. The mutation status, promoter methylation, CD244-related molecules and signaling pathways were also employed to study the potential function of CD244 in tumor initiation and progression. Our study offers a comprehensive overview of CD244 in human tumors, revealing CD244 as a potential prognostic biomarker and immunotherapeutic target in cancers.

Abstract Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

Study region: Middle and lower reaches of Tarim River, southwestern of Xinjiang Province, China. Study focus: Ecological water conveyance is an important measure to protect the fragile ecosystem of inland rivers in arid areas. This paper attempted to present a integrated model for optimal ecological water conveyance scheme (EWCS). In this model, the impact of the duration of water conveyance and the water allocation of each channel on the groundwater level was considered. The optimized ecological water conveyance scheme can simultaneously maximize groundwater level rise value (GLRV) and minimize ecological water conveyance volume (EWCV). New hydrological insights for the region: An simulation-optimization model was proposed based on MODFLOW model, Kriging surrogate model and NSGA-II. The study obtained the Pareto frontiers of EWCS in three typical years (dry, normal and wet), and made decisions using the TOPISIS-Entropy method. The scenario comparison results indicated that the optimized EWCS requires less EWCV than the existing one when achieving the same GLRV, proving that the optimized EWCS has higher water resource utilization efficiency. This simulation-optimization model fills the research gap of EWCS in arid inland river basins and provides scientific guidance for government management.

To realize the all-around assessment of teaching quality in the context of engineering education accreditation, this study proposes a single-valued neutrosophic information entropy and a novel assessment method of teaching effectiveness. In this proposed assessment model, an optimization model is structured based on the minimum information entropy value of single-valued neutrosophic sets (SvNSs). In this study, the primary innovation is that by using the structured model, the attribute weights are extracted from the given deterministic information. The main work of this study is summarized as follows. Firstly, aiming at the engineering certification problem, this study proposes an improved single-value neutrosophic information entropy formula to enhance the effectiveness of the engineering certification results. Secondly, this paper establishes an optimization model based on the minimum information entropy value and provides a method for assigning weight values. Thirdly, this study proposes an improved evaluation method for teaching effect, which provides a novel idea for engineering certification. Thereafter, a case study is presented to demonstrate the effectiveness and practicality of the proposed model.

Abstract Background The past few years have witnessed a significant increase in research related to plant-derived extracellular vesicles (PDEVs) in biological and medical applications. Using biochemical technologies, multiple independent groups have demonstrated the important roles of PDEVs as potential mediators involved in cell-cell communication and the exchange of bio-information between species. Recently, several contents have been well identified in PDEVs, including nucleic acids, proteins, lipids, and other active substances. These cargoes carried by PDEVs could be transferred into recipient cells and remarkably influence their biological behaviors associated with human diseases, such as cancers and inflammatory diseases. Main body of the abstract This review summarizes the latest updates regarding PDEVs and focuses on its important role in nanomedicine applications, as well as the potential of PDEVs as drug delivery strategies to develop diagnostic and therapeutic agents for the clinical management of diseases, especially like cancers. Conclusion Considering its unique advantages, especially high stability, intrinsic bioactivity and easy absorption, further elaboration on molecular mechanisms and biological factors driving the function of PDEVs will provide new horizons for the treatment of human disease.

Sensors are a key component in industrial automation systems. A fault or malfunction in sensors may degrade control system performance. An engineering system model is usually disturbed by input uncertainties, which brings a challenge for monitoring, diagnosis, and control. In this study, a novel estimation technique, called adaptive unknown-input observer, is proposed to simultaneously reconstruct sensor faults as well as system states. Specifically, the unknown input observer is used to decouple partial disturbances, the un-decoupled disturbances are attenuated by the optimization using linear matrix inequalities, and the adaptive technique is explored to track sensor faults. As a result, a robust reconstruction of the sensor fault as well as system states is then achieved. Furthermore, the proposed robustly adaptive fault reconstruction technique is extended to Lipschitz nonlinear systems subjected to sensor faults and unknown input uncertainties. Finally, the effectiveness of the algorithms is demonstrated using an aircraft system model and robotic arm and comparison studies.

Immunogenic cell death (ICD) is a novel cell death mechanism that activates and regulates the immune system against cancer. However, its prognostic value in liver cancer remains unclear. Here, several algorithms such as correlation analysis, Cox regression analysis, and Lasso regression analysis were carried out to evaluate the prognostic value of ICD-related genes in patients with liver cancer. Three ICD-related prognostic genes, the prion protein gene (PRNP), dynamin 1-like gene (DNM1L), and caspase-8 (CASP8), were identified and used to construct a risk signature. Patients with liver cancer were categorized into high- and low-risk groups using the ICD-related signature. Subsequently, a multivariate regression analysis revealed that the signature was an independent risk factor in liver cancer [hazard ratio (HR) = 6.839; 95% confidence interval (CI) = 1.625–78.785]. Patient survival was also predicted using the risk model, with area under the curve values of 0.75, 0.70, and 0.69 for 1-, 3-, and 5-year survival, respectively. Finally, a prognostic nomogram containing the clinical characteristics and risk scores of patients was constructed. The constructed ICD-related signature could serve as a prognostic and immunotherapeutic biomarker in liver cancer.

Natural compounds are widely used to prevent and treat various diseases due to their antioxidant and anti-inflammatory effects. As a kind of promising natural compound, plant-derived exosome-like nanoparticles (PELNs) are extracted from multivesicular bodies of various edible plants, including vegetables, foods, and fruits, and mainly regulate the cellular immune response to pathogen attacks. Moreover, PELNs could remarkably interfere with the dynamic imbalance between pro-inflammatory and anti-inflammatory effects, facilitating to maintain the homeostasis of cellular immune microenvironment. PELNs may serve as a better alternative to animal-derived exosomes (ADEs) owing to their widespread sources, cost-effectiveness, and easy accessibility. PELNs can mediate interspecies communication by transferring various cargoes such as proteins, lipids, and nucleic acids from plant cells to mammalian cells. This review summarizes the biogenesis, composition, and classification of exosomes; the common separation, purification, and characterization methods of PELNs, the potential advantages of PELNs over ADEs; and the anti-inflammatory and immunomodulatory functions of PELNs in various diseases including colitis, cancer, and inflammation-associated metabolic diseases. Additionally, the future perspectives of PELNs and the challenges associated with their clinical application are discussed.

Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients.

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell–cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.

Pyruvate dehydrogenase E1 subunit beta (PDHB) is located in mitochondria and catalyzes the conversion of glucose-derived acetyl-CoA. The detailed roles of PDHB in human cancers is unclear. Here, through comprehensive bioinformatics analysis, we found that PDHB was aberrantly expressed in multiple human cancers and is associated with patients' clinical stage. The abnormal expression of PDHB was related to the prognostic values of cancers, such as kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). The Wanderer database with clinical data from Cancer Genome Atlas (TCGA) showed a significant correlation between PDHB expression and the pathologic stage of KIRP patients. We also evaluated the mutation profiles of PDHB in pan-cancer, and showed its roles on the patients’ prognosis. At last, from several immunity algorithms, we demonstrated that the expression of PDHB was correlated with the infiltration of various immune cells in pan-cancer. Moreover, the aberrant PDHB had effects on the response to immune checkpoint inhibitors in cancer patients, such as anti-PD-1. Taken together, our study demonstrated the prognostic values of PDHB in pan-cancers. PDHB may be a potential molecular marker to predicting the immune response in cancer patients.

In recent years, electric vehicles powered by lithium-ion batteries have developed rapidly, and the safety and reliability of lithium-ion batteries have been a paramount issue. Battery management systems are highly dependent on sensor measurements to ensure the proper functioning of lithium-ion batteries. Therefore, it is imperative to develop a suitable fault diagnosis scheme for battery sensors, to realize a diagnosis at an early stage. The main objective of this paper is to establish validated electrical and thermal models for batteries, and address a model-based fault diagnosis scheme for battery sensors. Descriptor proportional and derivate observer systems are applied for sensor diagnosis, based on electrical and thermal models of lithium-ion batteries, which can realize the real-time estimation of voltage sensor fault, current sensor fault, and temperature sensor fault. To verify the estimation effect of the proposed scheme, various types of faults are utilized for simulation experiments. Battery experimental data are used for battery modeling and observer-based fault diagnosis in battery sensors.

Since most hepatocellular carcinoma (HCC) patients are diagnosed at advanced stages, there is no effective treatment to improve patient survival. Ferroptosis, a regulated cell death driven by iron accumulation and lipid peroxidation, has been reported to play an important role in tumorigenesis. However, the detailed mechanism and biological function of ferroptosis are still incompletely understood in HCC patients. In this study, we analyzed genomic profiles of three HCC datasets, GSE6764, GSE14520, and GSE14323. Venn diagrams were implemented to visualize the overlapping genes between differentially expressed genes and ferroptosis-related gene set. Then, one up-regulated gene, ACSL4, and five down-regulated genes, STEAP3, MT1G, GCH1, HAMP, and CXCL2, were screened. Based on the survival analysis performed by Kaplan-Meier plotter database, ferroptosis-related gene CXCL2 was demonstrated positively-correlated with the patients’ prognosis. Moreover, CXCL2 overexpression significantly inhibited cell growth and improved cellular ROS, Fe2+ and MDA levels in HCC cells Huh7 and MHCC97H, suggesting the roles of CXCL2 in inducing ferroptotic cell death. In addition, aberrantly expressed CXCL2 was negatively associated with malignancy clinical features, such as nodal metastasis and higher grades. The ssGSEA enrichment analysis revealed that CXCL2 co-expressed molecules were mainly involved in inflammation and immune-related pathways, such as acute inflammatory response, humoral immune response, adaptive immune response. TISIDB algorithm indicated the positive correlation between CXCL2 expression and tumor-infiltrating immune cells, including neutrophils and macrophages. Additionally, we also found that CXCL2 was positively correlated with immune infiltration score, and HCC patients with higher score harbored better prognosis. Together, these findings suggested that CXCL2 may enhance ferroptosis sensitivity and regulate immune microenvironment in HCC, and serve as a promising prognosis biomarker for HCC patients.

The primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovarian cancer, glioma, and non-small-cell lung carcinoma, respectively, were collected for the screening process, and two genes were found. A-kinase anchor protein 12 (AKAP12), one of these two genes, correlates with tumorigenesis of some cancers. However, the role of AKAP12 in pan-cancer remains poorly defined. The present study first systematically analyzed the association of AKAP12 with anti-VEGF inhibitors’ sensitivity, clinical prognosis, DNA methylation, protein phosphorylation, and immune cell infiltration across various cancers via bioinformatic tools. We found that AKAP12 was upregulated in anti-VEGF therapy-resistant cancers, including ovarian cancer (OV), glioblastoma (GBM), lung cancer, and colorectal cancer (CRC). A high AKAP12 expression revealed dismal prognoses in OV, GBM, and CRC patients receiving anti-VEGF inhibitors. Moreover, AKAP12 expression was negatively correlated with cancer sensitivity towards anti-VEGF therapy. Clinical prognosis analysis showed that AKAP12 expression predicted worse prognoses of various cancer types encompassing colon adenocarcinoma (COAD), OV, GBM, and lung squamous cell carcinoma (LUSC). Gene mutation status may be a critical cause for the involvement of AKAP12 in resistance. Furthermore, lower expression of AKAP12 was detected in nearly all cancer types, and hypermethylation may explain its decreased expression. A decreased phosphorylation of T1760 was observed in breast cancer, clear-cell renal cell carcinoma, and lung adenocarcinoma. For the immunologic significance, AKAP12 was positively related to the abundance of pro-tumor cancer-associated fibroblasts (CAFs) in various types of cancer. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that “cell junction organization” and “MAPK pathway” participated in the effect of AKAP12. Importantly, we discovered that AKAP12 expression was greatly associated with metastasis of lung adenocarcinoma as well as differential and angiogenesis of retinoblastoma through investigating the single-cell sequencing data. Our study showed that the dual role of AKAP12 in various cancers and AKAP12 could serve as a biomarker of anti-VEGF resistance in OV, GBM, LUSC, and COAD.

BackgroundWith promotion of COVID-19 vaccinations, there has been a corresponding vaccine hesitancy, of which older adolescents and young adults represent groups of particular concern. In this report, we investigated the prevalence and reasons for vaccine hesitancy, as well as potential risk factors, within older adolescents and young adults in China.MethodsTo assess these issues, an online survey was administered over the period from March 14 to April 15, 2021. Older adolescents (16–17 years old) and young adults (18–21 years old) were recruited nationwide from Wechat groups and results from a total of 2,414 respondents were analyzed. Socio-demographic variables, vaccine hesitancy, psychological distress, abnormal illness behavior, global well-being and social support were analyzed in this report.ResultsCompared to young adults (n = 1,405), older adolescents (n = 1,009) showed higher prevalence rates of COVID-19 vaccine hesitancy (16.5 vs. 7.9%, p < 0.001). History of physical diseases (p = 0.007) and abnormal illness behavior (p = 0.001) were risk factors for vaccine hesitancy among older adolescents, while only a good self-reported health status (p = 0.048) was a risk factor for young adults. Concerns over COVID-19 vaccine side effects (67.1%) and beliefs of invulnerability regarding infection risk (41.9%) were the most prevalent reasons for vaccine hesitancy. Providing evidence on the vaccine reduction of COVID-19 infection risk (67.5%), ensuring vaccine safety (56.7%) and the low risk of side effects (52.7%) were the most effective persuasions for promoting vaccinations.ConclusionIn China, older adolescents showed a higher prevalence for vaccine hesitancy than that of young adults. Abnormal illness behavior and history of physical diseases were risk factors for vaccine hesitancy among these older adolescents, while social support represents an important factor which could help to alleviate this hesitancy.

Understanding the distribution of natural and artificial oases is essential for effective management of desert oases and water resources in arid regions. In order to explore characterization of Oases, we developed an ensemble method for the identification of factors influencing the distribution of oases in the upper reaches of the Tarim River Basin (TRB), China. To determine the affected elements of artificial and natural oases in arid lands through multi-function choices from 1990 to 2020, the Oases Integrated Analysis Model (OIAM) was used. The following input data was included in the OIAM: meteorological conditions, salinity, depth of groundwater, time sequence of Landsat images, and environmental chemicals such as calcium, bicarbonate, potassium, sodium, sulfate, and fluoride ions. Several functional methods were used to assess the efficiency of the OIAM. The results indicated that the OIAM consistently outperformed stable Wi (spatial contribution rate to Oases’ indicators). Moreover, the results from OIAM indicated that salinity and meteorological indicators influenced the spatial distribution of artificial and natural oases. For environmental chemical, Na and Mg ions were strongly associated with the distribution of artificial and natural oases, respectively. This indicates that the OIAM model effectively identifies factors influencing the distribution of artificial and natural oases in arid regions, and thus can be applied to other similar regions.

Low-valency titanium species, generated in situ by using Ti(OiPr)4/2 c-C5H9MgCl reagent, react with imines to give a titanium-imine complex that can couple with terminal alkynes to provide azatitanacyclopentenes with excellent regioselectivity. Stereodefined allylic amines are obtained in good yields after hydrolysis or iodonolysis of the corresponding azatitanacyclopentenes. When ethynylcyclopropane is used as the coupling partner to react with imines in this reaction, the initially generated allylic amine undergoes an unexpected 1,3-amino migration on silica gel during the column chromatography.

This article investigates the networked finite-time control problem for a class of continuous-time linear systems. A novel event-driven data transmission scheme is invoked to reduce the network loads. Moreover, the non-uniform sampling triggered by sampling jitter or the fault of hold circuits is taken into account. By employing an input-delay approach, the underlying system is first reformulated to linear system with time-varying delays. Based on the Lyapunov–Krasovskii functional method, the stabilizing controller is then designed in the finite-time control sense, such that the closed-loop system is finite-time bounded. Potential and advantage of the developed techniques are demonstrated by a numerical example and an application to damping boring bar system.

Whole-genome shotgun (WGS) sequencing has become a routine method in genome research over the past decade. However, the assembly of highly polymorphic regions in WGS projects remains a challenge, especially for large genomes. Employing BAC library constructing, PCR screening and Sanger sequencing, traditional strategy is laborious and expensive, which hampers research on polymorphic genomic regions. As one of the most highly polymorphic regions, the major histocompatibility complex (MHC) plays a central role in the adaptive immunity of all jawed vertebrates. In this study, we introduced an efficient procedure based on recombination screening and short-reads assembly. With this procedure, we constructed a high quality 488-kb region of crested ibis MHC that consists of 3 superscaffolds and contains 50 genes. Our sequence showed comparable quality (97.29% identity) to traditional Sanger assembly, while the workload was reduced almost 7 times. Comparative study revealed distinctive features of crested ibis by exhibiting the COL11A2-BLA-BLB-BRD2 cluster and presenting both ADPRH and odorant receptor (OR) gene in the MHC region. Furthermore, the conservation of the BF-TAP1-TAP2 structure in crested ibis and other vertebrate lineages is interesting in light of the hypothesis that coevolution of functionally related genes in the primordial MHC is responsible for the appearance of the antigen presentation pathways at the birth of the adaptive immune system.

Dimension reduction is an important tool for feature extraction and has been widely used in many fields including image processing, discrete-time systems, and fault diagnosis. As a key parameter of the dimension reduction, intrinsic dimension represents the smallest number of variables which is used to describe a complete dataset. Among all the dimension estimation methods, correlation dimension (CD) method is one of the most popular ones, which always assumes that the effect of every point on the intrinsic dimension estimation is identical. However, it is different when the distribution of a dataset is nonuniform. Intrinsic dimension estimated by the high density area is more reliable than the ones estimated by the low density or boundary area. In this paper, a novel weighted correlation dimension (WCD) approach is proposed. The vertex degree of an undirected graph is invoked to measure the contribution of each point to the intrinsic dimension estimation. In order to improve the adaptability of WCD estimation, k-means clustering algorithm is adopted to adaptively select the linear portion of the log-log sequence (log⁡δk,log⁡C(n,δk)). Various factors that affect the performance of WCD are studied. Experiments on synthetic and real datasets show the validity and the advantages of the development of technique.