Metformin suppresses NFE2L1 pathway activation to inhibit gap junction beta protein expression in NSCLC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) is a deadly form of cancer that exhibits extensive intercellular communication which contributed to chemoradiotherapy resistance. Recent evidence suggests that arrange of key proteins are involved in lung cancer progression, including gap junction proteins (GJPs). METHODS AND RESULTS: In this study, we examined the expression patterns of GJPs in NSCLC, uncovering that both gap junction protein, beta 2 (GJB2) and gap junction protein, beta 2 (GJB3) are increased in LUAD and LUSC. We observed a correlation between the upregulation of GJB2, GJB3 in clinical samples and a worse prognosis in patients with NSCLC. By examining the mechanics, we additionally discovered that nuclear factor erythroid-2-related factor 1 (NFE2L1) had the capability to enhance the expression of connexin26 and connexin 31 in the NSCLC cell line A549. In addition, the use of metformin was discovered to cause significant downregulation of gap junction protein, betas (GJBs) by limiting the presence of NFE2L1 in the cytoplasm. CONCLUSION: This emphasizes the potential of targeting GJBs as a viable treatment approach for NSCLC patients receiving metformin.

VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.

Triple-negative breast cancer (TNBC) has long been considered a major clinical challenge due to its aggressive behavior and poor prognosis. Cancer stem cells (CSCs) are known as the main cells responsible for tumor origination, progression, recurrence and metastasis. Here, we report that M2-type tumor-associated macrophages (TAMs) contribute to cancer stemness in TNBC cells via the secretion of VEGFA. Reciprocally, elevated VEGFA expression by TAM-educated TNBC cells acts as a regulator of macrophage polarization, therefore constitute a feed-back loop between TNBC cells and TAMs. Mechanistically, VEGFA facilitates the CSC phenotype via the NRP-1 receptor and downstream GAPVD1/Wnt/ß-catenin signaling pathway in TNBC cells. Our study underscores the crosstalk between TNBC cells and TAMs mediated by VEGFA and further clarifies the role and underlying mechanisms of the VEGFA/NRP-1/GAPVD1 axis in regulating cancer stemness. We also document an immunosuppressive function of VEGFA in the tumor microenvironment (TME). Therefore, the present study indicates crosstalk between TNBC cells and TAMs induced by VEGFA and provides a potential implication for the combination of immunotherapy and VEGFA-targeted agents in TNBC therapy.

Factors affecting patient activation among patients with systemic lupus erythematosus.

There are limited published studies on patient activation among patients with systemic lupus erythematosus (SLE) in China. Disease activity can significantly influence a patient's perception of their condition, subsequently impacting patient activation. However, the mechanisms through which disease activity influences patient activation remain poorly understood. This study aimed to investigate patient activation among patients with SLE in China and explore the influencing factors. We conducted a cross-sectional study from June to December 2021 at a rheumatology and immunology department of a tertiary hospital in Chengdu, China. Data were collected by questionnaire, including general information, disease activity, quality of chronic illness care, health literacy, self-efficacy, motivation, social support, and patient activation. A patient activation model was constructed based on the conceptual framework derived from the individual and family self-management theory. To evaluate the moderating effect of disease activity on patient activation model, participants were divided into two subgroups (low disease activity group and high disease activity group). 426 SLE patients were included. The mean score of patient activation among SLE patients was 63.28 ± 11.82, indicating that most SLE patients lacked skills and confidence to stick with health-promoting behaviors. Health literacy, social support, and self-efficacy had the greatest effect on patient activation. In the multi-group analysis, social support and health literacy contributed more to patient activation in SLE patients with high and low disease activity, respectively. Patient activation among SLE patients in China was at the third level. Healthcare professionals should help them adhere to health-promoting behaviors. Health literacy, social support, and self-efficacy are vital factors for patient activation. These factors should be prioritized based on disease activity when developing individually tailored interventions for patient activation.

Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque / 神经科学通报·英文版

Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

Targeting ENPP1 for cancer immunotherapy: Killing two birds with one stone.

Cancer immunotherapy, particularly with immune checkpoint inhibitors, has revolutionized the paradigm of cancer treatment. Nevertheless, the efficacy of cancer immunotherapy remains limited in most clinical settings due to the lack of a preexisting antitumor T-cell response in tumors. Therefore, the clinical outcomes of cancer immunotherapy must be improved crucially. With increased awareness of the importance of the innate immune response in the recruitment of T cells, as well as the onset and maintenance of the T cell response, great interest has been shown in activating the cGAS-STING signaling pathway to awaken the innate immune response, thereby orchestrating both innate and adaptive immune responses to induce tumor clearance. However, tumor cells have evolved to overexpress ectonucleotide pyrophosphate phosphodiesterase 1 (ENPP1), which degrades the immunotransmitter 2',3'-cGAMP and promotes the production of immune-suppressing adenosine, resulting in inhibition of the anticancer immune response in the tumor microenvironment. Clinically, ENPP1 overexpression is closely associated with poor prognosis in patients with cancer. Conversely, depleting or inhibiting ENPP1 has been verified to elevate extracellular 2',3'-cGAMP levels and inhibit the generation of adenosine, thereby reinvigorating the anticancer immune response for tumor elimination. A variety of ENPP1 inhibitors have recently been developed and have demonstrated significant promise for cancer immunotherapy. In this review, we provide an overview of ENPP1, dissect its immunosuppressive mechanisms, and discuss the development of ENPP1 inhibitors with the potential to further improve the efficacy of cancer immunotherapy.

Bioaccumulation, biomagnification, and ecological risk of trace metals in the ecosystem around oilfield production area: A case study in Shengli Oilfield.

The production for crude oil usually leads to contamination of the soil with trace metals and organic contaminants from spilled petroleum. Organic contaminants were generally paid more attention than trace metals in the oilfield pollution. Many studies have investigated the impacts of some petroleum hydrocarbon pollutants, however, the impacts and risk assessment of trace metals remain largely unexplored. Moreover, under some circumstances, the risks associated with trace metals are not necessarily lower than those associated with organic contaminants. This study aimed to investigate methods to evaluate the possible risks associated with 11 trace metals (Ti, Ba, Sr, Rb, V, Li, Mo, Co, Cs, Bi, and Tl) in soil and biota samples from the Shengli Oilfield using ICP-MS. The results showed that 11 trace metals in the surface soils exceeded the local background levels. The geo-accumulation index (Igeo) indicated that the soils had light-moderate to moderate contamination levels, with higher Igeo value of Ba, V, Li, Mo, Co, and Cs. The individual potential ecological risk indices ([Formula: see text]) demonstrated moderate Bi and Tl pollution in soils. Comparatively, the [Formula: see text] is recommended for the risk assessment of trace metals on the ecosystem around the oilfield area. Mo, Bi, and Sr easily accumulate in plants, as reflected by their bioaccumulation factor. Ti, Ba, V, Li, Co, Cs, Bi, and Tl exhibited considerable biomagnification, particularly in birds. In this study, trace metals showed considerable bioaccumulation and biomagnification, and the risks of these trace metals on the ecosystem around oilfield production area need more attention.

Can new urbanization and ecological environment achieve synergistic development? Empirical evidence from 63 counties in Zhejiang, China.

As China's urbanization accelerates, ecological environmental issues have become increasingly prominent, and how to achieve the synergistic development of urbanization and ecological environment is worth exploring. The paper uses the Super-SBM model and the improved entropy method to calculate the ecological efficiency and the new urbanization in 63 counties in Zhejiang Province from 2000 to 2019. Furthermore, the coupling coordination degree between new urbanization and ecological efficiency is discussed with the coupling degree model, Markov chain, and spatial correlation methods, and its influencing factors are explored by the geographic detector. The results show that: (1) The development trends of new urbanization and ecological efficiency in Zhejiang Province counties both present a "U" shape. Their inflection points appeared in 2005 and 2006, respectively. The gap between counties is gradually narrowing. (2) The coupling coordination degree between new urbanization and ecological efficiency in Zhejiang Province counties also develops in a "U" shape with the minimum value appearing in 2006. Its temporal evolution is dominated by advancement towards a higher level and maintenance of the original type, with most countries advancing from General Disorder to Preliminary Coordination. There is a good positive correlation in the spatial distribution, showing significant High-High and Low-Low agglomeration. (3) In detecting the driving factors, the explanatory power of economic development, natural conditions and social conditions diminishes sequentially. The interaction groups mostly are nonlinear enhancements, and the rest are all two-factor enhancements. Social factors are the main interaction objects. (4) The empirical analysis verified the efficacy of the "Two Mountains" theory and the importance of government investment in the regional coordinated development.

PLK3 promotes the proneural-mesenchymal transition in glioblastoma via transcriptional regulation of C5AR1.

BACKGROUND: Accumulating evidence suggests that polo-like kinase 3 (PLK3) plays an essential role in tumor cells and induces cell proliferation and may have implications for the prognosis of various cancers. We sought to define the role of PLK3-dependent proneural-mesenchymal transition (PMT) in the glioblastoma (GBM) therapy. METHODS AND RESULTS: We analyzed the expression data for PLK3 by using the TCGA database. PLK3 expression in GBM cell lines was determined by qRT-PCR and Western blotting. PLK3 levels were modulated using Lentivirus infection, and the effects on symptoms, tumor volume, and survival in mice intracranial xenograft models were determined. Irradiation (IR) was performed to induce PMT. PLK3 expression was significantly elevated in mesenchymal subtype GBM and promoted tumor proliferation in GBM. Additionally enriched PLK3 expression could be associated with poor prognosis in GBM patients compared with those who have lower PLK3 expression. Mechanically, PLK3-dependent PMT induced radioresistance in GBM cells via transcriptional regulation of complement C5a receptor 1 (C5AR1). In therapeutic experiments conducted in vitro, targeting PLK3 by using small molecule inhibitor decreased tumor growth and radioresistance of GBM cells both in vitro and in vivo. CONCLUSIONS: PLK3-C5AR1 axis induced PMT thus enhanced radioresistance in GBM and could become a novel potential therapeutic target for GBM.

Use of Tandem Mass Spectrometry Quantitative Proteomics to Identify Potential Biomarkers to Follow the Effects of Cold and Frozen Storage of Muscle Tissue of Litopenaeus vannamei.

L. vannamei has become one of the most productive species. However, it is susceptible to microbial contamination during fishing, transportation, and storage, which can lead to spoilage and quality deterioration. This study investigates the relationship between changes in the proteome of Litopenaeus vannamei (L. vannamei) muscle and quality characteristics during low-temperature storage using the tandem mass spectrometry technology of quantitative proteomics strategy. The differential expression of proteins under cold storage (4 °C, CS), partial slight freezing (-3 °C, PFS), and frozen storage (-18 °C, FS) conditions was compared with the fresh group (CK), resulting in 1572 proteins identified as differentially expressed. The purpose of this research is to identify potential biochemical markers by analyzing quality changes and relative differential proteins through searches in the UniProt database, Gene Ontology database, and Genome Encyclopedia. Correlation analysis revealed that seven DEPs were significantly related to physical and chemical indicators. Bioinformatics analysis demonstrated that most DEPs are involved in binding proteins, metabolic enzymes, and protein turnover. Additionally, some DEPs were identified as potential biomarkers for muscle decline. These findings contribute to understanding the mechanism of freshness decline in L. vannamei under low-temperature storage and the changes in muscle proteome.

The First-Night Effect on the Instability of Stage N2: Evidence from the Activity of the Central and Autonomic Nervous Systems.

A series of studies have suggested that stage N2 is vulnerable and strongly affected by the first-night effect (FNE). However, the neurophysiological mechanism underlying the vulnerability of stage N2 of the FNE has not been well examined. A total of 17 healthy adults (11 women and 6 men, mean age: 21.59 ± 2.12) underwent two nights of polysomnogram recordings in the sleep laboratory. We analyzed sleep structure and central and autonomic nervous system activity during stage N2 and applied the electroencephalographic (EEG) activation index (beta/delta power ratio) and heart rate variability to reflect changes in central and autonomic nervous system activity caused by the FNE. Correlation analyses were performed between EEG activation and heart rate variability. The results showed that EEG activation and high-frequency heart rate variability increased on the adaptation night (Night 1). Importantly, EEG activation was significantly associated with the percentage of stage N1, and the correlation between EEG activation and high-frequency heart rate variability decreased due to the FNE. These findings indicate that the FNE affects the instability of stage N2 by increasing central nervous system activity and uncoupling the activity between the central and autonomic nervous systems.

Dual gatekeepers-modified mesoporous organic silica nanoparticles for synergistic photothermal-chemotherapy of breast cancer.

HYPOTHESIS: Construction of dual gatekeepers-functionalized mesoporous organic silica nanoparticles (MONs) with both physical and chemical mechanisms for modulated drug delivery properties provides one solution to the extracellular stability vs. intracellular high therapeutic efficiency of MONs that hold great potential for clinical translations. EXPERIMENTS: We reported herein facile construction of diselenium-bridged MONs decorated with dual gatekeepers, i.e., azobenzene (Azo)/polydopamine (PDA) for both physical and chemical modulated drug delivery properties. Specifically, Azo can act as a physical barrier to block DOX in the mesoporous structure of MONs for extracellular safe encapsulation. The PDA outer corona serves not only as a chemical barrier with acidic pH-modulated permeability for double insurance of minimized DOX leakage in the extracellular blood circulation but also for inducing a PTT effect for synergistic PTT and chemotherapy of breast cancer. FINDINGS: An optimized formulation, DOX@(MONs-Azo3)@PDA resulted in approximately 1.5 and 2.4 fold lower IC50 values than DOX@(MONs-Azo3) and (MONs-Azo3)@PDA controls in MCF-7 cells, respectively, and further mediated complete tumor eradication in 4T1 tumor-bearing BALB/c mice with insignificant systematic toxicity due to the synergistic PTT and chemotherapy with enhanced therapeutic efficiency.

Ambient fine particulate matter and allergic symptoms in the middle-aged and elderly population: results from the PIFCOPD study.

BACKGROUND: The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. METHODS: Participants (n = 10,142; age = 40-75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0-7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. RESULTS: A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0-7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. CONCLUSIONS: Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. TRIAL REGISTRATION: Clinical trial ID: NCT03532893 (29 Mar 2018).

Synchronization of Switched Neural Networks via Attacked Mode-Dependent Event-Triggered Control and Its Application in Image Encryption.

It is challenging to synchronize switched time-delay systems when some modes are uncontrolled and the dwell time (DT) of controlled mode is very small. Therefore, in this article, global exponential synchronization almost surely (GES a.s.) in a cluster of switched neural networks (NNs) with hybrid delays (time-varying delay and infinite-time distributed delay) is investigated, where transition probability (TP)-based random mode-dependent average DT (MDADT) switching is considered. A novel mode-dependent pinning event-triggered controller with nonidentical deception attacks is proposed to save the communication resource and derive less conservative results. The two necessary and restrictive conditions in existing papers that the value of the Lyapunov-Krasovskii functional (LKF) before switching instants should be smaller than that after corresponding instant and the DT of each switching mode is restricted by the sampling intervals of the event trigger are moved. Sufficient conditions in terms of linear matrix inequalities (LMIs) are given to guarantee the GES a.s., even though both synchronizing and nonsynchronizing modes coexist and maybe the minimum DT of synchronizing modes is very small. Numerical examples, including image encryption, are provided to demonstrate the merits of the new technique.

Comprehensive Analysis of the Expression and Prognosis of chromobox Family Members in Breast Cancer.

BACKGROUND: Chromobox proteins are canonical components of the Polycomb group family and play pivotal roles in several cancers. However, little is known about the function, prognostic value and drug sensitivity of CBX family members in breast cancer. METHODS: In this study we investigated the expression, prognosis value and drug sensitivity of CBX family in breast cancer using the ONCOMINE, GEPIA, Human Protein Atlas and Kaplan-Meier Plotter databases, etc. and preliminary verified the expression of CBX family in breast cancer cell lines by RT-qPCR. RESULTS: We found that the expression levels of CBX1/2/3/4/8 members were elevated in breast cancer tissues compared to adjacent normal breast tissues, while the expression levels of CBX6/7 genes were reduced in breast cancer tissue. In vitro qRT-PCR validated the expression differences of CBX1/2/3/4/8 in breast cancer cell lines. Further analysis showed expression of CBX family members was remarkably correlated with cancer subgroups. As nodal metastasis status increased, the mRNA expression of CBX1/2/3/4/8 members tended to be higher, while CBX6/7 tended to be lower. The expression of CBX1/2/3 was higher in patients with TP53 mutation and CBX6/7 expression tended to be lower in patients with TP53 mutation groups. High transcription levels of CBX2/3 were significantly associated with shorter overall survival in breast cancer patients, while lower expression of CBX4/5/6/7 members was associated with unfavorable overall survival. Moreover, a high mutation rate of CBX gene members (43%) was observed in breast cancer patients, and genetic alterations in CBX genes was associated with poor prognosis. CONCLUSION: Taken together, our results indicated that CBX2/3/6/7/8 could be considered prognostic and therapeutic biomarkers of breast cancer and are worthy of further study.

One night of 10-h sleep restores vigilance after total sleep deprivation: the role of delta and theta power during recovery sleep.

A series of studies have demonstrated that impaired vigilance performance caused by total sleep deprivation could restore to baseline when recovery sleep is longer than the habitual sleep. However, it is unclear which factors on the recovery night affected the restoration of vigilance performance impaired by sleep deprivation. 22 participant's sleep electroencephalograms were recorded with polysomnography in 8-h baseline sleep and one-night 10-h recovery sleep following 36-h sleep deprivation. Participants completed a 10-min psychomotor vigilance task and subjective ratings after baseline and recovery sleep the following day. Objective vigilance and subjective ratings were impaired by sleep deprivation and recovered to baseline after one-night 10-h recovery sleep. Compared with baseline sleep, sleep depth increased with enhanced delta and theta power density, and sleep duration was also prolonged during recovery sleep. The vigilance performance difference between recovery and baseline sleep was taken as a behavioral index of the restoration of vigilance. The restoration of vigilance was correlated with the delta and theta power density of stage N3 in the frontal and central region during the recovery sleep. These findings indicated that one-night 10-h recovery sleep could restore the impaired objective vigilance and subjective ratings caused by sleep deprivation. The recuperative effect of vigilance relies on individual differences in sleep intensity. Individuals with higher sleep intensity in recovery sleep obtained better vigilance recovery.

Interaction of aging and Immunosenescence: New therapeutic targets of aging.

Aging is a natural physiological process, but aging can increase the prevalence and mortality of chronic diseases in the elderly. It involves multiple organs and systems, and an essential aspect of aging is immunosenescence. With the increase of age, the immune system has undergone a series of changes and disorders. These changes have led to a decline in the resistance of the elderly to infection, reduced immunity to vaccines, increased incidence of cancer and autoimmune diseases, and an increased structural prevalence of low-grade inflammation. Moreover, affecting the aging process to a certain extent. This review introduces the changes in the immune system during aging and discusses the consequences and effects of these changes. And its effect on the aging process and the methods and ways of anti-aging were discussed.

A yes-associated protein 1- Notch1 receptor positive feedback loop promotes breast cancer lung metastasis by attenuating the bone morphogenetic protein 4-SMAD family member 1/5 signaling.

The Notch1 (Notch1 receptor) and yes-associated protein 1 (YAP1) signaling can regulate breast cancer metastasis. This study aimed at investigating whether and how these two signal pathways crosstalk to promote breast cancer lung metastasis. Here, we show that YAP1 expression was positively correlated with Notch1 in breast cancer according to bioinformatics and experimental validation. Mechanistically, YAP1 with TEA domain transcription factors (TEADs) enhanced Jagged1(JAG1)-Notch1 signaling. Meanwhile, Notch1 promoted YAP1 stability in breast cancer cells by inhibiting the ß-TrCP-mediated degradation, thereby, forming a YAP1- JAG1/Notch1 positive feedback loop in breast cancer. Furthermore, YAP1 enhanced the mammosphere formation and stemness of MDA-MB-231 cells by attenuating the inhibition of the BMP4-SMAD1/5 signaling. In vivo, the YAP1- JAG1/Notch1 positive feedback loop promoted the lung colonization of MDA-MB-231 cells. Our data for the first time indicate that the YAP1-Notch1 positive feedback loop promotes lung metastasis of breast cancer by modulating self-renewal and inhibiting the BMP4-SMAD1/5 signaling.

Targeting STING for cancer immunotherapy: From mechanisms to translation.

Cancer immunotherapy with immune checkpoint inhibitors has achieved unprecedented success in cancer treatment; However, only a subset of patients achieved clinical benefit from this treatment, underscoring the urgent need to identify new strategies to enhance the clinical efficacy of immune checkpoint inhibitors. Given the essential role of innate immunity in cancer immune surveillance, tremendous effort has been focused on the innate immune pathways that can be pharmacologically modulated to improve the clinical outcome of checkpoint inhibitors. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway plays essential roles in host defense against cancers. Activation of the cGAS-STING signaling pathway induces the expression of type I interferons and proinflammatory cytokines, culminating in promotion of a robust adaptive antitumor immunity. As part of this innate immune signaling pathway, STING is ubiquitously expressed in immune and nonimmune cells. STING activation has been demonstrated to propagate the cancer immunity cycle, remodel the tumor microenvironment, and ultimately eliminate tumor cells. The immunomodulatory roles of STING enable it to be an appealing target for cancer immunotherapy. As such, STING agonists that are capable of triggering antitumor immune responses have been developed in recent years, and several of them have advanced into clinical trials. In this review, we first give an overview on the STING signaling pathway, then dissect the roles of STING activation in different steps of the cancer immunity cycle and finally discuss the development of STING agonists as well as challenges with STING activation, with the potential to make cancer immunotherapy with STING agonists more effective.

The formation mechanism and homeostasis of extrachromosomal DNA.

Extrachromosomal DNA, referred to as extrachromosomal DNA (ecDNA), was found in most cancers and nearly absent in normal cells. The properties of ecDNA enable tumor cells to be more responsive to various environments. The non-Mendelian genetic mechanism of ecDNA could arouse increasing tumor heterogeneity. Besides, ecDNA would promote tumor invasiveness and provide resistance mechanisms associated with poorer survival consequences. Furthermore, ecDNA could profoundly impact oncogene activation, genome instability, tumor heterogeneity, etc. Consequently, they may offer potential possibilities for tumor diagnosis and therapeutics. We primarily reviewed the classification, several primary formation mechanisms, homeostasis maintenance and frontier progress of ecDNA and late emphasized its fundamental roles in tumorigenesis and put forward some new insights.

MiR-26a-5p regulates proliferation, apoptosis, migration and invasion via inhibiting hydroxysteroid dehydrogenase like-2 in cervical cancer cell.

BACKGROUND: Evidences have indicated that miR-26a-5p regulates the malignant properties of various tumor cells. However, the influences of miR-26a-5p on proliferation, apoptosis and invasion are still vague in the cervical cancer (CC) cells. METHODS: The miRNA microarray and real-time quantitative PCR (RT-qPCR) analysis were utilized to detect the expression of miR-26a-5p in the patients with CC. Kaplan-Meier plotter was performed to evaluate the overall survival (OS) of the patients with CC. The CCK-8, flow cytometry, transwell and wound healing analyses were respectively used to analyze proliferation, migration and invasion in the CC cells. RT-qPCR, western blot and IHC analysis were executed to measure the expression of hydroxysteroid dehydrogenase like-2 (HSDL2) in the patients with CC. Bioinformatics and luciferase reporter assay were carried out to verify the relationship of miR-26a-5p and HSDL2. RESULTS: The expression of miR-26a-5p was downregulated and low expression of miR-26a-5p indicated a poor OS in patients with CC. Overexpression of miR-26a-5p significantly inhibited proliferation, migration and invasion, accelerated apoptosis in the Hela and C33A cells. The expression of HSDL2 was upregulated, and negatively correlated with miR-26a-5p in the patients with CC. HSDL2 was directly targeted by miR-26a-5p and rescue experiments displayed that HSDL2 partially abolished proliferation, apoptosis, migration, and invasion induced by miR-26a-5p in CC cells. CONCLUSIONS: MiR-26a-5p alleviated progression of CC by suppressing proliferation, migration and invasion, promoting apoptosis through downregulating HSDL2.