Screening for the presence of aberrantly expressed ACTR2 in osteosarcoma and analyzing its mechanism of action through an online database.

Osteosarcoma (OS) represents the most prevalent malignant bone tumor clinically, significantly impacting the health and safety of patients. The exploration of molecular pathogenic mechanisms is deemed a breakthrough for OS diagnosis and treatment. Within the GSE16088 dataset, a total of 1,948 differentially expressed genes (DEGs) were identified, comprising 1,697 down-regulated and 251 up-regulated genes. Notably, only two DEGs were associated with the response to trichostatin A: ARP2 actin-related protein 2 homolog (ACTR2) and MEF2C; ACTR2 garnered particular interest. Subsequently, 57 OS patients (research group) and 50 healthy controls from the same period (control group) were selected for analysis. The expression of ACTR2 in peripheral blood in both groups, as well as its levels in cancerous tissues and adjacent counterparts of OS patients, were evaluated, ascertaining the correlation between ACTR2 and OS. OS cases exhibited lower levels of ACTR2 compared to controls (P<0.05), with ACTR2 expression demonstrating a robust diagnostic capability for OS. Similarly, ACTR2 expression was diminished in cancer tissues (P<0.05). A three-year prognostic follow-up was conducted to assess the prognostic value of ACTR2 in OS patients. The follow-up findings revealed a significantly lower survival rate among patients with low ACTR2 expression in contrast to those with high expression (P<0.05). In vitro studies involved the construction of abnormal expression vectors for ACTR2 and miR-374a-5p, which were transfected into human OS cells (U2OS, SAOS). The outcomes indicated that elevating ACTR2 or suppressing miR-374a-5p attenuated the proliferative, invasive, and migratory capacities as well as the epithelial-mesenchymal transition (EMT) of OS cells while enhancing their apoptosis. Conversely, upregulation of miR-374a-5p yielded opposing effects (P<0.05). The dual-luciferase reporter (DLR) assay demonstrated that the fluorescence activity of ACTR2-WT was significantly inhibited by the miR-374a-5p mimic sequence (P<0.05), confirming the presence of a targeted regulatory relationship between ACTR2 and miR-374a-5p. These findings offer novel insights for future research directions in the diagnosis and treatment of OS.

Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release.

Cancer is a significant health concern, increasingly showing insensitivity to traditional treatments, highlighting the urgent need for safer and more practical treatment options. Ribonucleic acid (RNA) gene therapy drugs have demonstrated promising potential in preclinical and clinical trials for antitumor therapy by regulating tumor-related gene expression. However, RNA's poor membrane permeability and stability restrict its effectiveness in entering and being utilized in cells. An appropriate delivery system is crucial for achieving targeted tumor effects. The tumor microenvironment (TME), characterized by acidity, hypoxia, enzyme overexpression, elevated glutathione (GSH) concentration, and excessive reactive oxygen species (ROS), is essential for tumor survival. Furthermore, these distinctive features can also be harnessed to develop intelligent drug delivery systems. Various nanocarriers that respond to the TME have been designed for RNA drug delivery, showing the advantages of tumor targeting and low toxicity. This Review discusses the abnormal changes of components in TME, therapeutic RNAs' roles, underlying mechanisms, and the latest developments in utilizing vectors that respond to microenvironments for treating tumors. We hope it provides insight into creating and optimizing RNA delivery vectors to improve their effectiveness.

Antitumor activity of Polygonatum sibiricum polysaccharides.

Cancer is a global public health problem. Natural polysaccharides have been shown to enhance the effectiveness of cancer treatments. Polygonatum sibiricum (PS) has been used for millennia to treat diverse diseases. PS comprises numerous active constituents, including saponins, peptides, volatile oils, polysaccharides, and lectins. Many studies have highlighted the crucial role of polysaccharides in PS. Modern studies have shown that Polygonatum sibiricum polysaccharide (PSP) exhibits diverse pharmacological activities, including immunomodulatory, antitumor, antioxidant, and anti-aging effects. However, further study of the antitumor mechanisms is difficult because the activities of PSP are closely associated with its complex structural features and the different molecular weights of its components. Therefore, this review focuses on the research background and the extraction and purification of PSP. Studies related to the mechanism of the antitumor effects of PSP constituents of different molecular weights are also summarized, and perspectives on PSP research are presented.

GAPVD1 Promotes the Proliferation of Triple-Negative Breast Cancer Cells by Regulating the ERK/MAPK Signaling Pathway.

BACKGROUND: Triple-Negative Breast Cancer (TNBC) accounts for 15-20% of all breast cancers and approximately 50% of breast cancer deaths. Chemotherapy remains the mainstay of systemic treatment due to the lack of effective therapy targets. Thus, more studies are urgently needed to identify new therapeutic targets in TNBC patients. METHODS: GAPVD1 expression and prognosis value in breast cancer samples were explored in The Cancer Genome Atlas database (TCGA). GAPVD1 knockdown and overexpression TNBC cell lines were constructed. CCK-8 and colony formation assays were performed to detect cell viability. Flow cytometry analysis was performed to detect cell cycle variation. Western blotting was conducted to determine the levels of target genes. Finally, an enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. RESULTS: GAPVD1 is overexpressed in breast cancer tissues and predicts poor prognosis. In vitro experiments demonstrated that GAPVD1 is correlated with cell proliferation and the cell cycle of TNBC cells. Mechanistically, alteration in GAPVD1 expression was found to be associated with cell cycle-related proteins PCNA, Cyclin A, and the activity of the ERK/MAPK signaling pathway. Consistent with these findings, enrichment analysis of GAPVD1-involving partners and signaling pathways revealed that the cellular biosynthetic process, macromolecule biosynthetic process, and cell cycle signaling are related to GAPVD1. In vivo experiment demonstrated that GAPVD1 inhibition impedes tumor growth and expression of cell cyclerelated proteins. CONCLUSION: Taken together, our results indicate that GAPVD1 may participate in TNBC cell growth by regulating the cell cycle and ERK/MAPK signaling pathway.

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.

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.

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.

Application of anesthesia management plan based on ERAS concept in thoracoscopic surgery / 中国内镜杂志

Objective To investigate the application of anesthesia management plan based on the concept of enhanced recovery after surgery(ERAS)in thoracoscopic surgery.Methods From December 2021 to December 2022,100 patients underwent thoracoscopic surgery were randomly divided into control group and observation group with 50 patients in each.The control group received routine anesthesia management,and the observation group received anesthesia management based on ERAS concept.The two groups were compared in terms of clinical indicators,the degree of incision pain on day 1,3,5 and 7 after surgery,the levels of inflammatory factors on day 1 and 3 after surgery.The incidence rates of pulmonary complications,nausea and vomiting,and respiratory depression in the two groups were calculated.Results Awakening and extubation time and hospital stay of observation group were shorter than those of control group,the treatment costs of observation group was less than that of control group,the visual analogue scale(VAS)of observation group at each time point after surgery were lower than those of control group,the levels of C-reactive protein(CRP)and tumor necrosis factor-α(TNF-α)of observation group on day 1 and 3 after surgery were lower than those of control group,the differences were statistically significant(P<0.05).The total incidence of pulmonary complications of observation group was lower than that of control group(6.00%vs 22.22%),the difference was statistically significant(P<0.05).The incidence rates of respiratory depression and nausea and vomiting in the observation group were 0.00%and 2.00%,respectively,while the incidence rates of respiratory depression and nausea and vomiting in the control group were 4.00%and 6.00%,respectively.There was no statistically significant difference in the total incidence rates of other complications between the two groups of patients(P>0.05).Conclusion Applying the anesthesia management plan based on ERAS concept in thoracoscopic surgery can promote postoperative recovery,reduce pain and pulmonary complications,and save treatment costs.It is worthy of clinical application.

Application value of fumarate hydratase and 2-succinocysteine in primary screening of fumarate hydratase-deficient uterine leiomyoma / 临床与实验病理学杂志

Purpose To investigate the expression of fuma-rate hydratase(FH)and 2-succinocysteine(2SC)in leiomyoma with singular nuclear features,and to analyze the diagnostic val-ue of these two proteins in fumarase hydratase-deficient(FH-d)uterine leiomyomas.Methods Sixty-seven cases of leiomyoma with singular nuclear features were collected.The expression was detected by immunohistochemical EnVision method,and the relationship between the expression of FH,2SC and the morpho-logical characteristics of FH-d uterine leiomyomas was analyzed,and the relevant literature was reviewed.Results There were 67 patients of leiomyoma with singular nuclear features,among which 27 had FH-d leiomyoma.The positive rate of FH was(2/27,7.41％),significantly lower than that of leiomyomas without FH-d(31/40,77.50％).The positive rate of 2SC(26/27,96.30％)was significantly higher than that of leiomyo-mas without FH-d(11/40,27.50％).The statistical results showed that there was a correlation between the expression of FH and 2SC(P＜0.05);positive expression of FH and 2SC was associated with significant eosinophilic nucleoli,perinucleolar vacuoles,eosinophilic inclusions and antler vessels(P＜0.05).The sensitivity and specificity of FH immunohistochemi-cal identification of FH defective leiomyoma were 92.59％and 77.50％,respectively.The sensitivity and specificity of 2SC immunohistochemical were 96.30％and 72.50％for FH defec-tive leiomyomas,respectively.Conclusion In most leiomyomas with FH-d morphology,FH expression is negative and 2SC ex-pression is positive.The combined detection of FH and 2SC can significantly improve the diagnosis of FH defective leiomyoma.

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.

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.

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.

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).

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.

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.