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Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enterovirus 71 (EV71) that frequently affects children, leading to severe infections in some cases. In general, when infection occurs, the body upregulates inflammatory responses to eliminate pathogenic microorganisms to protect the host from infection. However, EV71 may inhibit host’s innate immunity to promote virus infection. At present, it is not fully understood how EV71 hijack the host cells for its own replication. Toll-like receptor 4 (TLR4), a natural immune receptor, historically associated with bacterial endotoxin-induced inflammatory responses. However, it is still unclear whether and how TLR4 is altered during EV71 infection. In this study, we observed a reduction in both TLR4 protein and gene transcript levels in RD, GES-1, and Vero cells following EV71 infection, as detected by RT-qPCR, immunofluorescence staining and western blot. Furthermore, we observed that the TLR4 downstream molecules of MYD88, p-NF-κB p65, p-TBK1 and related inflammatory cytokines were also reduced, suggesting that antiviral innate immune and inflammatory response were suppressed. To determine the impact of TLR4 changes on EV71 infection, we interfered EV71-infected RD cells with TLR4 agonist or inhibitor and the results showed that activation of TLR4 inhibited EV71 replication, while inhibition of TLR4 promote EV71 replication. Besides, EV71 replication was also promoted in TLR4 siRNA-transfected and EV71-infected RD cells. This suggests that down-regulation the expression of TLR4 by EV71 can inhibit host immune defense to promote EV71 self-replication. This novel mechanism may be a strategy for EV71 to evade host immunity.

Thermogravimetric-differential thermal analysis (TG-DSC) has been used to obtain information on combustion characteristics of bituminous coal and anthracite incorporating Cu(NO3)2, KNO3, ZnO and MnO2, and the apparent kinetic parameters were determined by the first-order Coats & Redfern method based on the TG-DSC results. Experiments were conducted from the 303 K–1172 K at heating rate of 10 K min−1. The ignition index, burning intensity, burnout index and activation energy were used as evaluation indexes. The weight of evaluation indexes was given by relative comparison method, The catalyst activity was evaluated by linear weighted synthesis method. It was indicated that those of bituminous coal and anthracite, the relative active sequence of catalysts to the comprehensive combustion performance of bituminous coal could be described as follows: Cu(NO3)2>KNO3>ZnO > MnO2. The relative active sequence of catalysts to the comprehensive combustion performance of anthracite could be described as follows: Cu(NO3)2>ZnO > MnO2>KNO3.

Background: To investigate the influence of blood pressure (BP) level on short-term prognosis of heart failure (HF), the effect of the BP level on clinical end point events 3 months after discharge was observed. Methods: A retrospective cohort study was performed on 1492 hospitalized HF patients. All patients were divided according to systolic blood pressure (SBP) per 20 mmHg and diastolic blood pressure (DBP) per 10 mmHg. Logistic regression analysis was used to analyze the relationship between BP level and heart failure rehospitalization, cardiac death, all-cause death and a composite end point of heart failure rehospitalization/all-cause death at 3 month follow-up after discharge. Results: After multivariable adjustment, the relationship between SBP and DBP levels and outcomes followed an inverted J curve relationship. Compared with the reference group (110 150 mmHg significantly increased the risk of heart failure rehospitalization (OR 2.67, 95%CI 1.15–6.18, P = 0.022). Compared with.the reference group (65 0.05). Conclusions: There is a significant difference in the short-term prognosis 3 months after discharge in HF patients with different BP levels at discharge. There was an inverted J curve relationship between BP levels and prognosis.

Introduction: In comparison to the audiovisual integration of younger adults, the same process appears more complex and unstable in older adults. Previous research has found that stimulus intensity is one of the most important factors influencing audiovisual integration.Methods: The present study compared differences in audiovisual integration between older and younger adults using dynamic hand-held tool stimuli, such as holding a hammer hitting the floor. Meanwhile, the effects of stimulus intensity on audiovisual integration were compared. The intensity of the visual and auditory stimuli was regulated by modulating the contrast level and sound pressure level.Results: Behavioral results showed that both older and younger adults responded faster and with higher hit rates to audiovisual stimuli than to visual and auditory stimuli. Further results of event-related potentials (ERPs) revealed that during the early stage of 60–100 ms, in the low-intensity condition, audiovisual integration of the anterior brain region was greater in older adults than in younger adults; however, in the high-intensity condition, audiovisual integration of the right hemisphere region was greater in younger adults than in older adults. Moreover, audiovisual integration was greater in the low-intensity condition than in the high-intensity condition in older adults during the 60–100 ms, 120–160 ms, and 220–260 ms periods, showing inverse effectiveness. However, there was no difference in the audiovisual integration of younger adults across different intensity conditions.Discussion: The results suggested that there was an age-related dissociation between high- and low-intensity conditions with audiovisual integration of the dynamic hand-held tool stimulus. Older adults showed greater audiovisual integration in the lower intensity condition, which may be due to the activation of compensatory mechanisms.

As older adults experience degenerations in perceptual ability, it is important to gain perception from audiovisual integration. Due to attending to one or more auditory stimuli, performing other tasks is a common challenge for older adults in everyday life. Therefore, it is necessary to probe the effects of auditory attentional load on audiovisual integration in older adults. The present study used event-related potentials (ERPs) and a dual-task paradigm [Go / No-go task + rapid serial auditory presentation (RSAP) task] to investigate the temporal dynamics of audiovisual integration. Behavioral results showed that both older and younger adults responded faster and with higher accuracy to audiovisual stimuli than to either visual or auditory stimuli alone. ERPs revealed weaker audiovisual integration under the no-attentional auditory load condition at the earlier processing stages and, conversely, stronger integration in the late stages. Moreover, audiovisual integration was greater in older adults than in younger adults at the following time intervals: 60–90, 140–210, and 430–530 ms. Notably, only under the low load condition in the time interval of 140–210 ms, we did find that the audiovisual integration of older adults was significantly greater than that of younger adults. These results delineate the temporal dynamics of the interactions with auditory attentional load and audiovisual integration in aging, suggesting that modulation of auditory attentional load affects audiovisual integration, enhancing it in older adults.

Audiovisual integration is an essential process that influences speech perception in conversation. However, it is still debated whether older individuals benefit more from audiovisual integration than younger individuals. This ambiguity is likely due to stimulus features, such as stimulus intensity. The purpose of the current study was to explore the effect of aging on audiovisual integration, using event-related potentials (ERPs) at different stimulus intensities. The results showed greater audiovisual integration in older adults at 320–360 ms. Conversely, at 460–500 ms, older adults displayed attenuated audiovisual integration in the frontal, fronto-central, central, and centro-parietal regions compared to younger adults. In addition, we found older adults had greater audiovisual integration at 200–230 ms under the low-intensity condition compared to the high-intensity condition, suggesting inverse effectiveness occurred. However, inverse effectiveness was not found in younger adults. Taken together, the results suggested that there was age-related dissociation in audiovisual integration and inverse effectiveness, indicating that the neural mechanisms underlying audiovisual integration differed between older adults and younger adults.

(1) Background: This study investigates whether audiovisual n-back training leads to training effects on working memory and transfer effects on perceptual processing. (2) Methods: Before and after training, the participants were tested using the audiovisual n-back task (1-, 2-, or 3-back), to detect training effects, and the audiovisual discrimination task, to detect transfer effects. (3) Results: For the training effect, the behavioral results show that training leads to greater accuracy and faster response times. Stronger training gains in accuracy and response time using 3- and 2-back tasks, compared to 1-back, were observed in the training group. Event-related potentials (ERPs) data revealed an enhancement of P300 in the frontal and central regions across all working memory levels after training. Training also led to the enhancement of N200 in the central region in the 3-back condition. For the transfer effect, greater audiovisual integration in the frontal and central regions during the post-test rather than pre-test was observed at an early stage (80–120 ms) in the training group. (4) Conclusion: Our findings provide evidence that audiovisual n-back training enhances neural processes underlying a working memory and demonstrate a positive influence of higher cognitive functions on lower cognitive functions.

Abstract Background Many circRNAs have been reported to play important roles in cancer development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in esophageal carcinoma (EC) remains unclear. In the current study, we investigated the potential role of circPVT1 in esophageal carcinoma. Methods Quantitative real-time PCR was performed to detect circPVT1 levels. CircPVT1-specific siRNA or plasmids were used to knock down or overexpression the target RNA. Hoechst Staining was implemented to evaluate the ratio of cell apoptosis. Transwell migration assays were carried out to study the effects of circPVT1 on esophageal squamous cell carcinoma cell invasion. RegRNA 2.0 was used for bioinformatics analysis. The expression levels of Pax-4, Pax-6, PPARα and PPAR-γ were assessed using Western blot. Results In the present study, we demonstrated a significant up-regulation of circPVT1 levels in EC tissues and cancer cell lines. The levels of circPVT1 decreased significantly when the cells were maintained to over-confluence. These results suggested a potential role for circPVT1 in cell proliferation. In addition, overexpressing circPVT1 in TE-10 cell promoted invasive ability of cancer cell. In contrast, siRNA knockdown of circPVT1 inhibited this phenomenon, leading to increased apoptosis levels of TE-10 cell. What’s more, miR-4663 had the effect of inhibiting tumor growth by downregulated Paxs and upregulated PPARs. Whereas, after the addition of circPVT1, this effect no longer worked, suggesting that circPVT1 may affect the malignancy of the tumor by affecting miRNA and regulating the levels of Paxs and PPARs. Conclusions Collectively, our study reveals a critical role for circPVT1 in esophageal carcinoma, which may provide new insights of this circRNA as a biomarker for the diagnosis and treatment target of EC.

Although emotional audiovisual integration has been investigated previously, whether emotional audiovisual integration is affected by the spatial allocation of visual attention is currently unknown. To examine this question, a variant of the exogenous spatial cueing paradigm was adopted, in which stimuli varying by facial expressions and nonverbal affective prosody were used to express six basic emotions (happiness, anger, disgust, sadness, fear, surprise) via a visual, an auditory, or an audiovisual modality. The emotional stimuli were preceded by an unpredictive cue that was used to attract participants’ visual attention. The results showed significantly higher accuracy and quicker response times in response to bimodal audiovisual stimuli than to unimodal visual or auditory stimuli for emotional perception under both valid and invalid cue conditions. The auditory facilitation effect was stronger than the visual facilitation effect under exogenous attention for the six emotions tested. Larger auditory enhancement was induced when the target was presented at the expected location than at the unexpected location. For emotional perception, happiness shared the biggest auditory enhancement among all six emotions. However, the influence of exogenous cueing effect on emotional perception seemed to be absent.

Osteoarthritis (OA) is a common chronic joint disease characterized by articular cartilage degeneration, subchondral sclerosis, synovitis, and osteophyte formation. OA is associated with disability and impaired quality of life, particularly among the elderly. Leptin, a 16-kD non-glycosylated protein encoded by the obese gene, is produced on a systemic and local basis in adipose tissue and the infrapatellar fat pad located in the knee. The metabolic mechanisms employed by leptin in OA development have been widely studied, with attention being paid to aging as a corroborative risk factor for OA. Hence, in this review, we have attempted to establish a potential link between leptin and OA, by focusing on aging-associated mechanisms and proposing leptin as a potential diagnostic and therapeutic target in aging-related mechanisms of OA that may provide fruitful guidance and emphasis for future research.

There has been growing interest in designing and developing polymeric nanoparticles in recent years. The inclusion of nanoparticles can enhance the performances of polymer solutions, including stability, rheology, and shear resistance. Nano-graphene oxide (Nano-GO) has been considered a superior nanoparticle for this purpose because of its robust thermal and mechanical properties. However, systematic studies on the application of graphene oxide nanoparticles in slickwater fracturing fluid have not been reported. Therefore, this study aims to improve the stability of nanoparticles, enhance the rheological properties of polymer nanofluids, and elucidate the synergy between nanoparticles and fracturing fluids through Fourier transform infrared spectroscopy and scanning electron microscopy. By evaluating rheological properties, drag reduction performances, and sand carrying capacity, this study confirms that the slickwater fracturing fluid added with Nano-GO (referred to as DRGO) meets the industrial requirement, and Nano-GO can significantly improve the rheological properties, apparent viscosity, as well as temperature and salt resistance of slickwater fracturing fluid. In terms of microstructure, the polymer molecules inside DRGO are closely overlapped to form a uniform network structure with greatly enhanced molecular chain strength.

Abstract Background Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown. Methods HIGD1A expression was determined in 24 pairs of human HCC samples and para-tumorous tissues. Loss-of-function experiments were conducted both in vivo and in vitro to explore the role of HIGD1A in HCC proliferation and metastasis. Results Increased HIGD1A expression was found in HCC tissues and cell lines, which was induced by hypoxia or low-glucose condition. Moreover, HIGD1A knockdown in HCC cells arrested the cell cycle at the G2/M phase and promoted hypoxia-induced cell apoptosis, resulting in great inhibition of cell proliferation, migration, and invasion, as well as tumor xenograft formation. Interestingly, these anti-tumor effects were not observed in normal hepatocyte cell line L02. Further, HIGD1A knockdown suppressed the expression of ornithine decarboxylase 1 (ODC1), a rate-limiting enzyme of polyamine metabolism under c-Myc regulation. HIGD1A was found to bind with the c-Myc promoter region, and its knockdown decreased the levels of polyamine metabolites. Consistently, the inhibitory effect on HCC phenotype by HIGD1A silencing could be reversed by overexpression of c-Myc or supplementation of polyamines. Conclusions Our results demonstrated that HIGD1A activated c-Myc–ODC1 nexus to regulate polyamine synthesis and to promote HCC survival and malignant phenotype, implying that HIGD1A might represent a novel therapeutic target for HCC.

Abstract Background The Hypoxia inducible gene domain family member 2A (HIGD2A) protein is indispensable for the assembly of the mitochondrial respiratory supercomplex, which has been implicated in cell proliferation and cell survival under hypoxic conditions. Because the liver has a naturally low oxygen microenvironment, the role of HIGD2A in the development of hepatocellular carcinoma (HCC) remains largely unknown. Methods Gene expression data and clinical information were obtained from multiple public databases. A lentivirus-mediated gene knockdown approach was conducted to explore the function and mechanism of HIGD2A activity in HCC cells. In vivo and in vitro assays were performed to investigate the biological roles of HIGD2A. Results HIGD2A was overexpressed in HCC tissues and cell lines and was associated with a worse prognosis. Silencing HIGD2A expression significantly attenuated cell proliferation and migration, caused S-phase cell cycle arrest, and decreased tumor formation in nude mice. Mechanistically, HIGD2A depletion greatly decreased cellular ATP levels by disrupting mitochondrial ATP production. Moreover, HIGD2A knockdown cells displayed impaired mitochondrial function, such as mitochondrial fusion, increased expression of the mitochondrial stress response protein, and decreased oxygen consumption. Furthermore, knockdown of HIGD2A markedly attenuated the activation of the MAPK/ERK pathway. Conclusions HIGD2A promoted liver cancer cell growth by fueling mitochondrial ATP synthesis and activating the MAPK/ERK pathway, suggested that targeting HIGD2A may represent a new strategy for HCC therapy.

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.