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Abstract Background Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. Method We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. Result Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor’s aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. Conclusion G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Abstract Background Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1. Methods In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2′-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo. Results The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression. Conclusions Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.

Abstract Background Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear. Methods Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2′-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo. Results We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration. Conclusion The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.

Abstract Intercellular communication often relies on exosomes as messengers and is critical for cancer metastasis in hypoxic tumor microenvironment. Some circular RNAs (circRNAs) are enriched in cancer cell‐derived exosomes, but little is known about their ability to regulate intercellular communication and cancer metastasis. Here, by systematically analyzing exosomes secreted by non‐small cell lung cancer (NSCLC) cells, a hypoxia‐induced exosomal circPLEKHM1 is identified that drives NSCLC metastasis through polarizing macrophages toward to M2 type. Mechanistically, exosomal circPLEKHM1 promoted PABPC1‐eIF4G interaction to facilitate the translation of the oncostatin M receptor (OSMR), thereby promoting macrophage polarization for cancer metastasis. Importantly, circPLEKHM1‐targeted therapy significantly reduces NSCLC metastasis in vivo. circPLEKHM1 serves as a prognostic biomarker for metastasis and poor survival in NSCLC patients. This study unveils a new circRNA‐mediated mechanism underlying how cancer cells crosstalk with macrophages within the hypoxic tumor microenvironment to promote metastasis, highlighting the importance of exosomal circPLEKHM1 as a prognostic biomarker and therapeutic target for lung cancer metastasis.

Abstract The type parameter helps in scattering mechanism analysis and scattering centre identification. However, current approximate solution methods based on spectral estimation are noise‐sensitive and exhibit low accuracy. In this letter, a high‐precision approach for the type parameter based on the alternating direction method of multipliers (ADMM) is proposed. Logarithmic transformation is used to separate the type parameter and the amplitude from the coupling term, and initially obtain the closed‐form solution of the type parameter. Then, the regularization term of l2‐norm is used for denoising. Finally, a joint optimization model based on ADMM is constructed to effectively estimate the type parameter. Simulation results confirm the high accuracy of the proposed approach.

A major driving force behind China’s low-carbon, environmentally friendly development of agriculture and the accomplishment of the “dual-carbon” goal is the digital transformation of rural areas. In this study, on the basis of clarifying the degree of rural digitization and agricultural carbon emissions efficiency in China from 2010 to 2021, the degree of coupled coordination and the spatiotemporal pattern characteristics between the two are examined using the coupled coordination model. Then, the influencing factors are analyzed in depth using the spatial Durbin model. Our findings reveal that, first, in terms of the degree of rural digitization, the index increases overall and the spatial imbalance is obvious, with a spatial distribution pattern of “high in the east and low in the west”. Regarding the efficiency of agricultural carbon emissions, there is an overall “N-shaped” change, which is mainly influenced by technological progress in agricultural production, and the regional annual averages are, in descending order, the Western, Eastern, Northeastern, and Central regions, with obvious regional differences. Second, the coupling coordination index shows a fluctuating upward trend, from “extreme disorder” to “high-level coordination”. Furthermore, there are obvious regional characteristics. The regional growth rates are, in descending order, the Western, Eastern, Central, and Northeastern regions. Third, coupling coordination is jointly influenced by a variety of factors, including government input, educational level, industrial structure, energy use, urbanization rate, living standards, driving temporal patterns, and regional differences. This study not only helps to clarify the relationship between the two, offering a reference for the realization of the “dual-carbon” goal, but also broadens the concepts of the low-carbon and environmentally friendly development of agriculture.

Lung cancer is the main cause of cancer-related deaths, and non-small cell lung cancer (NSCLC) is the most common type. Understanding the potential mechanisms, prognosis, and treatment aspects of NSCLC is essential. This study systematically analyzed the correlation between mitophagy and NSCLC. Six mitophagy-related feature genes (SRC, UBB, PINK1, FUNDC1, MAP1LC3B, and CSNK2A1) were selected through machine learning and used to construct a diagnostic model for NSCLC. These feature genes are closely associated with the occurrence and development of NSCLC. Additionally, NSCLC was divided into two subtypes using unsupervised consensus clustering, and their differences in clinical characteristics, immune infiltration, and immunotherapy were systematically analyzed. Furthermore, the interaction between mitophagy-related genes (MRGs) and immune cells was analyzed using single-cell sequencing data. The findings of this study will contribute to the development of potential diagnostic biomarkers for NSCLC and the advancement of personalized treatment strategies.

Abstract Background Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear. Methods Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1. Results Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model. Conclusion Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p–HMGB1 axis and support the development of circ-YES1 probability as a new therapeutic NSCLC target.

Abstract Dysregulation of circular RNAs (circRNAs) has recently been found to play an important role in the progression and development of cancers such as non-small cell lung cancer (NSCLC). Yet the functions of many circRNAs in NSCLC remain unclear. In this study, the circRNA expression profiles in NSCLC tumor tissues and adjacent non-tumorous tissues were detected by high-throughput sequencing. Bioinformatics analyses, the dual-luciferase reporter system, fluorescence in situ hybridization (FISH) and miRNA/mRNA high-throughput sequencing were used to identify circ-EPB41 and its downstream target. The subcutaneous tumor/caudal vein transfer mouse model was used for tumor growth and invasion analysis. The results show that the circ-EPB41 was upregulated in NSCLC tissues and cell lines. Increased circ-EPB41 expression in NSCLC was significantly correlated with malignant characteristics, and positive to post-surgical overall survival of NSCLC patients. Reduced circ-EPB41 expression in NSCLC decreased cell proliferation and invasion in both in vitro and in vivo experiments. The miRNA/mRNA high-throughput sequencing suggested that downregulation of circ-EPB41 promoted microRNA (miR)-486-3p and suppressed eukaryotic translation initiation factor 5A (eIF5A) expression. Luciferase reporter experiments confirmed that miR-486-3p/eIF5A were downstream targets of circ-EPB41. In addition, we also found that downregulation of circ-EPB41 suppressed self-renewal and decreased expression of stemness markers SOX2, OCT-4, Nanog and CD133 by sponging miR-486-3p to enhance eIF5A expression. Taken togeter, these data revealed the important role of circ-EPB41 in regulating NSCLC cell invasion and proliferation by modifying miR-486-3p/eIF5A axis-mediated stemness. We believe our study provides a novel perspective regarding the role of circRNAs in NSCLC progression.

The remote and non-contact monitoring of human respiration and heartbeat based on radars is a safe and convenient practice. However, how to accurately estimate the heart rate is still an open issue, because the heartbeat information in radar signals is affected by respiratory harmonics. In this paper, a maximum likelihood estimation was introduced to extract the heart rate from high-pass-filtered radar heartbeat waveforms where the low-frequency respiratory and heartbeat components were attenuated. The closed-form asymptotic estimation variance of the maximum likelihood estimator was derived to describe its performance in white Gaussian noise with a high signal-to-noise ratio (SNR). The proposed method was verified using two publicly available datasets and demonstrated superior performance compared to other methods. The estimation method and the asymptotic estimation variance here described are also applicable for signal period estimation in other settings with similar conditions.

Emerging studies showed that α-hederin induced autophagic cell death in different cancers via reactive oxygen species. Nevertheless, α-hederin role in non-small-cell lung cancer (NSCLC) remains unknown. So, the aim of this study was to explain whether ferroptosis is a therapeutic strategy to NSCLC, and to explore the effect of α-hederin on NSCLC ferroptosis. Current investigation found that α-hederin inhibited NSCLC cell proliferation, invasion, and migration in vitro and in vivo at toxic doses. The α-hederin treatment also increased NSCLC cell chemosensitivity to cisplatin and promoted ferroptosis and apoptosis at a safe dose. Proteomics, metabolomics, and high-throughput sequencing detection confirmed that α-hederin treatment downregulated glutathione peroxidase 2 (GPX2), and glutathione synthase (GSS) expression suppressed the synthesis of glutathione (GSH), which destroyed the GSH redox system. Eventually, it led to ferroptosis, apoptosis, and membrane permeabilization in NSCLC. Taken together, the study provided molecular data to confirm that α-hederin induced ferroptosis, apoptosis, and membrane permeabilization in NSCLC by destroying the GSS/GSH/GPX2 axis–mediated GSH oxidation-reduction system at a safe and low-toxicity dose.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-020-01697-6.

Corosolic acid is a pentacyclic triterpenoid isolated from Lagerstroemia speciosa, which is known to inhibit cancer cell proliferations. Whereas, the role of this compound on non-small cell lung cancer (NSCLC) cells still largely unclear. So, the aim of this study was to reveal the regulatory mechanism of corosolic acid to NSCLC. Here, we cultured A549 and PC9 cells in increasing corosolic acid concentrations, as well as treated mice with a physiologically relevant concentration of the compound, and used metabolomics analysis and high-throughput sequencing to examine its influences on cell invasion and proliferation, chemoresistance, and metastasis. We found that corosolic acid inhibited cell invasion and proliferation in vivo and in vitro, as well as increase the chemosensitivity of both cell types to cisplatin. Furthermore, we found that corosolic acid destabilized the glutathione peroxidase 2-mediated redox system, which increased mitochondrial and liposomal oxidative stress. Corosolic acid also decreased the targeting protein for TPX2 level, which inhibited PI3K/AKT signaling and induced apoptosis. In addition, the accumulation of reactive oxygen species dissociated the CCNB1/CDK1 complex and induced G2/M cell cycle arrest. Taken collectively, the data indicate that corosolic acid reduces NSCLC cell invasion and proliferation, as well as chemoresistance, by inducing mitochondrial and liposomal oxidative stress.

Background: Lung cancer is among the most dangerous malignant tumors to human health. Lung adenocarcinoma (LUAD) accounts for about 40% of all lung cancers. Accumulating evidence suggests that the tumor microenvironment (TME) is a crucial regulator of carcinogenesis and therapeutic efficacy in LUAD. However, the impact of tumor microenvironment-related signatures (TMERSs) representing the TME characteristics on the prognosis and therapeutic outcome of LUAD patients remains to be further explored. Materials and methods: Gene expression files and clinical information of 1630 LUAD samples and 275 samples with immunotherapy information from different databases such as The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Cancer Research Institute (CRI) iAtlas were downloaded and analyzed. Three hundred tumor microenvironment-related signatures (TMERS) based on a comprehensive collection of marker genes were quantified by single sample gene set enrichment analysis (ssGSEA), and then eight significant signatures were selected to construct the tumor microenvironment-related signature score (TMERSscore) by performing Least Absolute Shrinkage and Selection Operator (LASSO)-Cox analysis. Results: In this study, we constructed a TME-based prognostic stratification model for patients with LUAD and validated it in several external datasets. Furthermore, the TMERSscore was found to be positively correlated with tumor malignancy and a high TMERSscore predicted a poor prognosis. Moreover, the TMERSscore of responders treated with Immune Checkpoint Inhibitor (ICI) therapies was significantly lower than that of non-responders, and the TMERSscore was positively correlated with the tumor immune dysfunction and exclusion (TIDE) score, implying that a low TMERSscore predicts a better response to ICI treatment and may provide independent and incremental predictive value over current biomarkers. Conclusions: Overall, we constructed a TMERSscore that can be used for LUAD patient prognosis stratification as well as ICI therapeutic efficacy evaluation, supportive results from independent external validation sets showed its robustness and effectiveness.

Myasthenia gravis (MG) is a disease involving neuromuscular transmission that causes fatigue of skeletal muscles and fluctuating weakness. It has been shown that impairment of myogenic differentiation and myofiber maturation may be the underlying cause of MG. In this study, we detected the abnormal expression of circular RNA (circRNA) using next-generation sequencing in patients with MG. We then investigated the regulatory mechanism and the relationship among circRNA, microRNA, and messenger RNA using quantitative reverse-transcription polymerase chain reaction, bioinformatics analysis, and luciferase report analysis. The expression of inflammatory cytokines and regulatory T lymphocytes was shown to be increased. Circ-FBL was significantly increased in MG patients. Bioinformatics and luciferase report analyses confirmed that miR-133 and PAX7 were the downstream targets of circ-FBL. Overexpression of circ-FBL promoted myoblast proliferation by regulation of miR-133/PAX7. Taken together, our study showed that upregulation of circ-FBL promoted myogenic proliferation in patients with MG by regulating miR-133/PAX7. [ABSTRACT FROM AUTHOR]

Frost heaving damage of canal lining in cold and dry areas is one of the important causes of canal leakage. In this paper, based on the bending theory of thin plate, a mechanical model of canal lining under the action of frost heaving force is established and solved. Through parametric and engineering case analysis, the following conclusions are drawn: under the action of frost heaving force, the bending moment, shear force, and internal force of the slope plate show a nonuniform distribution, and the maximum values of bending moment Mx and normal stress σx are close to the bottom third of the slope, which is consistent with the existing research and engineering practice. Compared with the theory of beam, the results of the theory of thin plates show that the internal forces and stresses increase at the free boundary (longitudinal expansion joint). The bending moment Mxy and stress τxy are maximum at the four corners of the plate: although the numerical magnitude is lower than that of Mx, it may cause stress concentration to damage the lining plate and thus cause break. The shear force at the longitudinal expansion joint may lead to fracture of the joint material, which needs to be considered in the design process. Due to the uniform distribution of the frost heaving force on the bottom plate lining, its deflection, internal forces, and stresses also show a uniform distribution. The research results can provide scientific reference for the design and operation and maintenance of water transmission canal lining in cold areas.