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Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats. Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats. [ABSTRACT FROM AUTHOR]

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection. [ABSTRACT FROM AUTHOR]

Purpose: The skin and mucous membrane of cancer patients can be directly or indirectly impaired during the treatment of cancers, bringing about not physical but also psychological damages to cancer patients. A practical guideline is of great significance to improve the quality of life for patients suffered from cutaneous adverse events. Methods: This guideline was generated based on up-to-date evidence and the consensus of experts specialized in dermatology. Results: The current guideline include the baseline screening of skin and mucosal membranes, the manifestations of injuries on skin, mucosa and appendages, along with the treatment of them. The causal anti-tumor management include chemotherapy, radiotherapy, immune therapy and surgery. Conclusion: This guideline can be helpful to reduce the risk of cutaneous adverse events during anti-cancer treatment and improve the quality of life of patients suffered from these adverse events. [ABSTRACT FROM AUTHOR]

The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl–tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention. [ABSTRACT FROM AUTHOR]

The interdependence of various energy forms and flexible cooperative operation between different units in an integrated energy system (IES) are essential for carbon emission reduction. To address the planning problem of an electric–thermal integrated energy system under low-carbon conditions and to fully consider the low carbon and construction sequence of the integrated energy system, a low-carbon-oriented capacity optimization method for the electric–thermal integrated energy system that considers construction time sequence (CTS) and uncertainty is proposed. A calculation model for the carbon transaction cost under the ladder carbon trading mechanism was constructed, and a multi-stage planning model of the integrated energy system was established with the minimum life cycle cost, considering carbon transaction cost as the objective function, to make the optimal decision on equipment configuration in each planning stage. Finally, a case study was considered to verify the advantages of the proposed capacity optimization method in terms of economy and environmental friendliness through a comparative analysis of different planning cases. Simulation results show that, compared with the scenario of completing planning at the beginning of the life cycle at one time, the proposed low-carbon-oriented capacity optimization method that considers construction time sequence and uncertainty can not only reduce the cost of the integrated energy system, but also help to enhance renewable energy utilization and reduce the system's carbon emissions; the total cost of phased planning is reduced by 11.91% compared to the total cost of one-time planning at the beginning of the year. [ABSTRACT FROM AUTHOR]

This paper explores whether the assessment of local government officials affects firm participation in targeted poverty alleviation. Using a sample of Chinese A‐share listed companies in the Midwest from 2016 to 2019, the results show that the greater the importance of officials' poverty alleviation assessment, the higher the participation of firms in precise poverty alleviation. State‐owned enterprises (SOEs) contribute more to the reduction of destitution than private enterprises. We further find that local SOEs' participation in precision poverty alleviation enhances the likelihood of executive promotion, while private enterprises' participation in precision poverty alleviation increases government subsidies and reduces the cost of debt financing. These findings imply that the evaluation mechanisms of Chinese officials can effectively promote enterprises fulfilling social responsibilities. [ABSTRACT FROM AUTHOR]

Three-dimensional porous NiO/CNT microspheres are constructed by the facile spray-drying method and subsequent annealing treatment under N2 atmosphere, which are subsequently wrapped by graphene oxide (GO) to form the porous NiO/CNT/GO microspheres. Benefiting from abundant pores distributed between NiO nanoparticles and CNT, porous NiO/CNT/GO microspheres exhibit a good cycling stability (333.6 mA h g−1 after 1000 cycles at 2000 mA g−1). Thanks to CNTs distributed inside the microspheres and GO that provides support for microspheres, porous NiO/CNT/GO microspheres show a high rate performance (445.1 mA h g−1 at 5000 mA g−1). This work provides an approach for the synthesis of high-performance lithium-ion battery anode materials, and the synthesis of porous NiO/CNT/GO microspheres plays a very important role in promoting applied physics, which has brought vitality to physics. [ABSTRACT FROM AUTHOR]

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. Methods and results: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co‐expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis‐related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four‐gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. Conclusion: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment. [ABSTRACT FROM AUTHOR]

Background: Cell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells. Methods: In this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18–27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily. Results: From October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months. Conclusions: Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended. Trial registration: ClinicalTrials.gov, NCT04074564. [ABSTRACT FROM AUTHOR]

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7–positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers. Wnt signaling is transmitted via ten homologous Frizzled receptors (FZD1-10) in humans, complicating the therapeutic use of inhibitors due to side-effects. This study shows that a bacterial toxin fragment can be used as a tool to specifically inhibit Wnt signaling mediated by a subset of Frizzed receptors (FZD1, 2, 7), with potential for cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is the most prevalent malignancy in women. With the improvement of medical treatment, breast cancer has become one of the solid tumors with the best curative effect. However, triple-negative breast cancer is not sensitive to conventional treatment due to its high invasiveness, resulting in a poorer prognosis than other types. The antibodies of programmed death receptor 1 and its ligands represent a new option as immunotherapy for patients with triple negative breast cancer. However, some recent clinical data suggest that a large proportion of patients exhibit primary or acquired resistance to treatment with programmed death receptor antibodies. In this review, we discuss the mechanisms that lead to resistance and also summarize potential strategies to overcome the resistance, improving the therapeutic efficacy of programmed death receptor 1 and its ligand-based antibodies in triple negative breast cancer. Triple-negative breast cancer (TNBC) is characterized by a high rate of systemic metastasis, insensitivity to conventional treatment and susceptibility to drug resistance, resulting in a poor patient prognosis. The immune checkpoint inhibitors (ICIs) represented by antibodies of programmed death receptor 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have provided new therapeutic options for TNBC. However, the efficacy of PD-1/PD-L1 blockade monotherapy is suboptimal immune response, which may be caused by reduced antigen presentation, immunosuppressive tumor microenvironment, interplay with other immune checkpoints and aberrant activation of oncological signaling in tumor cells. Therefore, to improve the sensitivity of TNBC to ICIs, suitable patients are selected based on reliable predictive markers and treated with a combination of ICIs with other therapies such as chemotherapy, radiotherapy, targeted therapy, oncologic virus and neoantigen-based therapies. This review discusses the current mechanisms underlying the resistance of TNBC to PD-1/PD-L1 inhibitors, the potential biomarkers for predicting the efficacy of anti-PD-1/PD-L1 immunotherapy and recent advances in the combination therapies to increase response rates, the depth of remission and the durability of the benefit of TNBC to ICIs. [ABSTRACT FROM AUTHOR]

Background: Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods: We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer's disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results: We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions: Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development. [ABSTRACT FROM AUTHOR]

Fault diagnosis of rolling bearings under variable speed is a common issue in engineering practice, but it lacks an effective diagnosis algorithm, while approaches developed for steady speed cannot be directly applied. Therefore, for effectively identifying bearing faults under variable speed, this paper proposed a multiscale fractional dimensionless indicator (MSFDI) and put forward a fault diagnosis method with random forest (RF). It can overcome the feature space aliasing problem of traditional dimensionless indicators, which will lead to increased diagnosis uncertainty. The multiorder fractional Fourier transform is carried out on bearing signals to get a series of fractional Fourier domain components, which will be used to construct the original MSFDI feature set. Moreover, reliefF selects the sensitive MSFDIs as the input of the RF algorithm to determine the health condition. The effectiveness of the proposed method is verified by experiments and case studies. [ABSTRACT FROM AUTHOR]

Purpose: The options for the second-line treatment of metastatic osteosarcoma are still limited. Anlotinib is a multi-kinase inhibitor which has shown promising efficacy and good tolerability in various cancer types. This retrospective study was conducted to evaluate the efficacy and safety of anlotinib combined with gemcitabine/docetaxel (GD) in patients with metastatic osteosarcoma who have failed first-line chemotherapy. Patients and Methods: The data of patients who received anlotinib combined with GD or GD were collected. The primary endpoint was progression-free survival. Secondary endpoints included objective response rate and safety. Results: From July 2013 to November 2020, a total of 32 patients were enrolled, 13 received anlotinib combined with GD and 19 received GD. Median PFS was 9.0 months (95% CI 6.7– 39.1) in the combination group and 5.0 months (95% CI 1.2– 6.7) in the chemotherapy group. ORR were 38.4% and 15.8%, DCR were 69.2% and 38.1% in the combination and chemotherapy group, respectively. The most common adverse events included fatigue (78.9% in the combination group vs 69.2% in the chemotherapy group), hypertension (46.2% vs 10.5%), diarrhea (38.5% vs 21.1%), hypothyroidism (38.5% vs 15.8%), neutropenia (23.1% vs 36.8%) and AST elevation (30.8% vs 21.1%). The most common grade 3 or worse adverse events included hand-foot reaction (7.7% vs 5.3%), hypothyroidism (15.4% vs 0), neutropenia (0 vs 10.5%). Conclusion: The combination of anlotinib and GD showed favorable efficacy with manageable toxicities compared with GD in the second-line treatment for metastatic osteosarcoma. This combination therapy deserves further investigations in patients with osteosarcoma. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV), a herpesvirus family member, is a large, complex enveloped virus. The activation of liver X receptor (LXR) can significantly inhibit the replication of HCMV and weaken the virulence of progeny virus (unpublished data). Our results showed activated LXR affected some important viral protein expression and reduced cholesterol content in HCMV infected cells and virus particles. To further clarify the influence of activated LXR on HCMV replication, HCMV assembly and maturation processes were studied by transmission electron microscopy (TEM) in HCMV infected foreskin fibroblasts treated with LXR agonist GW3965. Results showed that activated LXR could reduce the envelope integrity of maturating virions. The functional stage of activated LXR on viral envelope integrity was mainly at virus assembly compartment (VAC) mediated envelopment but not structurally complete virus nucleocapsid formation and the egress of nucleocapsid from the nucleus to the cytoplasm mediated by nuclear egress complex. Reduced cholesterol synthesis and viral protein expression might interfere with the VAC-mediated envelopment. The nucleocapsid and tegument proteins enter the VAC area for the secondary envelope, which was interfered with and resulted in the defective particle, thereby affecting the amount and infectivity of the mature virus. The results indicate that inhibition of HCMV maturation is one mechanism of activated LXR inhibiting virus replication in infected cells. [ABSTRACT FROM AUTHOR]

Purpose: There are two opposite views about whether the Antitrust Law is conducive to the development of the economy. One view is that the Antitrust Law can restrain monopoly, maintain market competition and benefit economic growth. The other view is that the Antitrust Law inhibits innovation by monopolistic firms and fosters rent-seeking, which is bad for economic growth. To provide a possible perspective for clarifying the controversy, this paper aims to answer the following two questions: first, will the Antitrust Law inhibit corporate innovation? Second, does the antitrust enforcement agency discriminate against private enterprises? Design/methodology/approach: Based on the samples of A-share listed companies from 2003 to 2013, the authors use the implementation of China's Antitrust Law in 2008 as a policy shock, take the monopoly enterprises in each industry as the treatment group and competitive enterprises as the control group, using the difference-in-differences method to test the impact of the implementation of the Antitrust Law on corporate innovation activities. Findings: The results show that compared with competitive enterprises, the patent output of monopolistic enterprises was significantly reduced after the implementation of the Antitrust Law, which indicates that the Antitrust Law does inhibit the innovation activities of monopolistic enterprises. Further research finds that the innovation suppression effect of the Antitrust Law is more prominent in state-owned enterprises, which means that the government does not have "selective law enforcement" against private enterprises in the process of law enforcement. Therefore, the results provide evidence for the idea that government intervention is neutral. Originality/value: First, the paper enriches and expands the research on the factors affecting corporate innovation from the perspective of market structure. Second, it enriches and expands relevant research on the consequences of implementing the Antitrust Law from the perspective of corporate innovation. Third, it not only provides the relevant empirical evidence for clarifying the dispute about the Antitrust Law but also is helpful to clarify whether the Chinese Government has "selective law enforcement" against private enterprises. [ABSTRACT FROM AUTHOR]

Cognitive abilities are impaired in patients with pituitary adenoma. However, studies on attention processing impairment in preoperative patients and attention processing recovery after transsphenoidal adenomectomy are lacking. The study aims to identify the electrophysiological change that relates to attention processing in pituitary patients before and after treatment. Twenty five preoperative pituitary patients and 25 follow-up postoperative patients were recruited. 27 healthy controls (HCs) were matched to the patients with age, gender, and education. Event-related potentials were used to investigate the attention processing in the preoperative patients, postoperative patients, and HCs. Across three groups, all emotional stimuli evoked P200 components. Compared with the HCs or postoperative patients, the amplitudes of P200 in the preoperative patients were higher. Moreover, The amplitudes of P200 decreased in the postoperative patients, which were similar to that in the HCs. The attention processing was improved after surgery, but no significant differences were detected between the postoperative patients and HCs. Abnormal hormone levels may be relevant to the factor that impair attention processing. Compared with that of the HCs and postoperative patients, the P200 component elicited by negative stimuli is higher in preoperative patients, which may illustrate compensatory activity after attention impairments. Furthermore, these data indicate that improvements in attention processing may be attributed to the amelioration of endocrine disorders. This study shows that the P200 component may be used to diagnose attention processing in preoperative pituitary patients and prove the improvement of attention processing in postoperative patients. [ABSTRACT FROM AUTHOR]

In this study, the complete mitochondrial genome (mitogenome) of Sinularia humilis van Ofwegen, 2008 was determined using next-generation sequencing (NGS) method. The mitogenome of S. humilis is 18,743 bp in length, containing 14 protein-coding genes (PCGs), two ribosomal RNAs (rRNA) and one tRNA (tRNA-Met), which has same gene order with other species of Sinularia. ATG was determined as start codon in all 14 PCGs. Eight TAG, five TAA, and one incomplete codons (T-) were found as stop codon. Phylogenetic analysis of the small number of available mitogenomes showed that S. humilis is closely related to Sinularia ceramensis and Sinularia peculiaris. [ABSTRACT FROM AUTHOR]

To expand the knowledge on the tempo-spatial patterns of zooplankton and the key modulated factors in urban aquatic ecosystem, we investigated zooplankton and water quality from April 2018 to January 2019 in the hinterland of the Three Gorges Reservoir area, Wanzhou City of China. The results indicated that water quality indicated by the trophic state index (TSI) reached a state of mesotrophication to light eutrophication in the Yangtze River, and a state of moderate- to hyper- eutrophication in its tributaries. Based on the biomass of zooplanktons, Asplanchna priodonta was the most common specie in April; Encentrum sp., Filinia cornuta and Epiphanes senta were the most noticeable species in summer; Cyclopoida Copepodid, Sinocalanus dorrii and Philodina erythrophthalma became the dominant species in winter. Generally, rotifers prevailed in April and August, and copepods became the most popular in January. According to canonical correspondence analysis, nitrate, temperature (T), ammonia, water level and permanganate index (CODMn) significantly influenced the community structure of zooplankton (p < 0.05). The dominant species shifts of zooplankton were partly associated with nutrient level (nitrate and ammonia) under periodic water level fluctuations. Rotifers and protozoans were characterized as high T adapted and CODMn-tolerant species comparing with cladocerans and copepods. The ratio of microzooplankton to mesozooplankton (Pmicro/meso) has presented a strongly positive relationship with T (p < 0.001), as well as Pmicro/meso and CODMn (p < 0.001). It implied that zooplankton tended to miniaturize individual size via species shift under high T and/or CODMn conditions induced by global warming and human activities. The information hints us that climate change and human activities are likely to produce fundamental changes in urban aquatic ecosystem by reorganizing biomass structure of the food web in future. [ABSTRACT FROM AUTHOR]

In recent years, large usage of wireless networks puts forward challenge to the utilization of spectrum resources, and it is significant to improve the spectrum utilization and the system sum data rates in the premise of fairness. However, the existing algorithms have drawbacks in efficiency to maximize the sum data rates of orthogonal frequency division multiple access (OFDMA) systems in the premise of fairness threshold. To address the issue, a novel artificial bee colony algorithm with update quantities of nectar sources is proposed for OFDMA resource allocation in this paper. Firstly, the population of nectar sources is divided into several groups, and a different update quantity of nectar sources is set for each group. Secondly, based on the update quantities of nectar sources set for these groups, nectar sources are initialized by a greedy subcarrier allocation method. Thirdly, neighborhood searches and updates are performed on dimensions of nectar sources corresponding to the preset update quantities. The proposed algorithm can not only make the initialized nectar sources maintain high levels of fairness through the greedy subcarrier allocation but also use the preset update quantities to reduce dimensions of the nectar sources to be optimized by the artificial bee colony algorithm, thereby making full use of both the local optimization of the greedy method and the global optimization of the artificial bee colony algorithm. The simulation results show that, just in the equal-power subcarrier allocation stage, the proposed algorithm can achieve the required fairness threshold and effectively improve the system sum data rates. [ABSTRACT FROM AUTHOR]

Rotating machinery usually runs at time-varying speeds, which often brings failures, especially compound faults. However, currently, there is still a lack of satisfactory coupled fault diagnosis methods at variable speeds. Several methods have been developed, which try to eliminate rotational speed influences by converting nonstationary fault characteristic frequencies into stationary ones. But it brings new problems of computational efficiency and accuracy, and requires an auxiliary tachometer to measure the rotational speed. Time-frequency analysis can solve the problems, and extract time-frequency curves for fault diagnosis through time-frequency representation (TFR). However, for signals containing multiple faults at variable speeds, uninterested components will be generated when extracting multiple time-frequency curve (MTFC), which makes it difficult for compound fault diagnosis. To solve these problems, a novel MTFC classification method for tacho-less and resampling-less compound bearing fault detection under time-varying speed conditions is proposed in this paper. Here the TFR characteristics of a multi-fault vibration signal is analyzed, and a compound fault diagnosis strategy based on MTFC classification is developed. Firstly, MTFC is extracted by a local peak search method. Then, according to the relationship between instantaneous shaft rotational frequency, instantaneous fault characteristics frequency and their respective harmonics, two classification criteria for curves are proposed and MTFC is classified into interested curves and uninterested curves. Finally, the average ratios between interested curves are matched to theoretical fault characteristic coefficients to determine the fault type. Case studies on rolling bearing experiments verified the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study explored the clinical value of the plasma D-dimer level in osteosarcoma. Materials and Methods: We measured the plasma D-dimer level before neoadjuvant chemotherapy (D0) and the plasma D-dimer level after four courses of neoadjuvant chemotherapy (D1) in 103 patients with stage-IIB high-grade osteosarcoma of the limb. The change in the D-dimer level (ΔD) was defined as D1 minus D0. The chi-square test was used to compare categorical variables. Analyses of receiver operating characteristic (ROC) curves were undertaken to determine the optimal cutoff points for D0, D1, and ΔD. The area under the ROC (AUC) of D0, D1, and ΔD was calculated to evaluate their discriminatory abilities in monitoring the response to neoadjuvant chemotherapy (tumor necrosis). Survival curves were generated according to Kaplan–Meier analyses and compared using the Log rank test. Univariate analyses and multivariate analyses were carried out to determine independent prognostic factors. Results: Kaplan–Meier curves showed that a high D-dimer level at D0 and tumor diameter ≥ 8 cm were associated significantly with worse overall survival (OS) (P< 0.05). Multivariate Cox regression analyses revealed a high D-dimer level at D0 (hazard ratio, 3.92; 95% confidence interval, 1.756– 5.804; P=0.000) was an independent unfavorable prognostic factor. The chi-square test showed ΔD to be associated significantly with tumor necrosis. Analyses of ROC curves showed the D-dimer level at D0 and ΔD had better ability compared to that at D1 to discriminate the response to neoadjuvant chemotherapy. Conclusion: The D-dimer level was correlated with the prognosis and response to chemotherapy in patients with stage-IIB high-grade osteosarcoma of the limb. The D-dimer level may serve as a risk factor of the response to chemotherapy and prognosis of localized osteosarcoma. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4+ macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3+ T cells with high proportion of TIGIT+ cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma. Osteosarcomas are difficult to treat and have a limited response to immunotherapy. Here, the authors analyse osteosarcomas at the single-cell level, and identify both the transdifferentiation of malignant cells and an array of immune cells that could have implications for metastasis and immunotherapy. [ABSTRACT FROM AUTHOR]

As rolling bearings are the key components in rotating machinery, bearing performance degradation directly affects machine running status. A tendency prognosis for bearing performance degradation is thus required to ensure the stability of operation. This paper proposes a novel strategy for bearing performance degradation trend prognosis, including health indicator construction techniques and a performance degradation trend prediction method. To more accurately represent the degradation trend, the multiscale deep bottleneck health indicator is proposed as a new synthesized health indicator to remove high-frequency detail signals from features, which can reduce possible fluctuations in conventional synthetic health indicators. A suitable method for selecting the statistical characteristics required for fusion is also presented to solve the problem of information redundancy that affects trend representation. In addition, a stacked autoencoder network is used for deep feature extraction of selected statistical features. A bidirectional long short-term memory network prediction model is also proposed for the prediction of degradation trend, which can make full use of historical and future information to improve prediction accuracy. Finally, experiments are carried out to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the most common primary bone malignancy with high rates of recurrence and metastasis. OS often spreads to lungs, an optimized model for studying lung metastatic OS cells may help develop potential therapies for patients with lung metastasis. Here we firstly report an organoid culture system for lung metastatic OS tissues. We provided a fully described formula that was required for establishing lung metastatic OS organoids (OSOs). Using this protocol, the lung OSOs were able to be maintained and serially propagated for at least six months; the OSOs can also be generated from cryopreserved patient samples without damaging the morphology. The patient-derived lung OSOs retained the cellular morphology and expression of OS markers (Vimentin and Sox9) that recapitulate the histological features of the human OS. The microenvironment of primary lung metastatic OSOs preserved a similar T cell distribution with the human lung OS lesions; this provided a possible condition to explore how OS cells may react to immunotherapy. OSOs established from this protocol can be further utilized for studying various aspects of OS biology (e.g., tumorigenesis and drug screen/discovery) for precision medicine. [ABSTRACT FROM AUTHOR]

Mechanical fault diagnosis under varying speed conditions has gradually become an important issue in rotating machinery monitoring, especially the research on compound fault diagnosis is still rare. Order analysis is one of the most effective and widely used methods to eliminate the effects of speed fluctuations; however, it is difficult to extract compound fault features directly. Moreover, there are often many restrictions on the number and locations of sensors to be installed in practice, which also brings great challenges to compound fault diagnosis under varying speed conditions. In this article, a novel compound fault detection method with virtual multichannel signals in the angle domain is proposed to solve these problems for rolling bearing monitoring under varying speed conditions. First, we aim to use only a vibration acceleration sensor and a noncontact rotational speed sensor to adapt to limitations on sensor installation in practical applications. However, this may result in an underdetermined problem when trying to detect a compound fault with only a single-channel vibration signal. Then we make it up through constructing virtual multichannel signals based on variational mode decomposition theory, before which the nonstationary vibration signal is converted from the time domain into a stationary signal in the angle domain with computed order tracking to eliminate speed fluctuations. Finally, these virtual signals can be easily taken as input to a normal independent component analysis, and different faults can be detected in the order spectrum of each independent component. Case studies on rolling bearing experiments verified the advantages of the proposed method in compound fault detection under varying speed conditions. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia–reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen–glucose deprivation and reoxygenation (OGD/R)-induced cell injury. Results: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor. Conclusions: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV)–encoded microRNAs (miRNAs) are involved in posttranscriptional regulation of gene expression. Extracellular vesicles (EVs) can incorporate miRNAs. Relationship between HCMV infection and miRNAs in EVs remains unknown. EVs were isolated from supernatants of human embryonic lung fibroblasts (HELF) cells. Profiles of miRNAs in EVs were analyzed by deep sequencing. Dynamics of candidate viral miRNAs transportation via EVs was investigated using TaqMan PCR. Levels of candidate viral miRNAs in serum EVs from infants with HCMV active infection were detected and analyzed with their clinical index levels. A total of 16 HCMV miRNAs were found in EVs from infected HELF. Levels of miR-US25-1-5p and miR-UL112-3p in EVs increased at 6 h post-infection and were correlated with those in cells (for miR-US25-1-5p: r2 = 0.9375, p value < 0.05; for miR-UL112-3p: r2 = 0.7557, p value < 0.05). Viral miRNAs were transported into recipient cells at 2 h post-incubation. Moreover, levels of miR-US25-1-5p in serum EVs showed positive correlations with serum levels of γ-glutamyl transpeptidase, direct bilirubin, and total bile acid. Levels of miR-UL112-3p in serum EVs showed a positive correlation with serum levels of direct bilirubin. HCMV miRNAs could be transported to uninfected cells via EVs. Levels of miR-US25-1-5p and miR-UL112-3p in serum EVs from infants with HCMV active infection were significantly correlated with liver damage. [ABSTRACT FROM AUTHOR]

Acceptability judgments have been an important tool in language research. By asking a native speaker whether a linguistic token is acceptable, linguists and psycholinguists can collect negative evidence and directly test predictions by linguistic and psycholinguistic theories, which provide important insight into the human language capacity. In this paper, we first give a brief overview of this method including: (1) the linking hypothesis for this method, (2) the controversy about the test, and (3) limitations of the current analysis of the results. Then, we propose a new way of analyzing the data: Signal Detection Theory. Signal Detection Theory has been used in many other psychological research areas such as recognition memory and clinical assessments. In this paper, using two examples, we show how Signal Detection Theory can be applied to judgment data. The benefits of this approach are that it can: (1) show how well participants can differentiate the acceptable sentences from unacceptable ones and (2) describe the participant's bias in the judgment. We conclude with a discussion of remaining questions and future directions. [ABSTRACT FROM AUTHOR]

Background: Our previous study found that consumption of very low mineral drinking water may retard height development in schoolchildren; however, its association with bone modeling remained unknown.Objectives: The aim of this study was to investigate the influence of very low mineral water on biomarkers of bone modeling in children.Methods: A retrospective cohort study was conducted among 2 groups of 10-13-y-old children who had consumed drinking water with normal mineral contents (conductivity 345 μs/cm, the NW group including 119 boys and 110 girls) or very low mineral contents (conductivity 40.0 μs/cm, the VLW group including 223 boys and 208 girls) in school for 4 y. Differences in daily total mineral intakes, developmental parameters, serum biomarkers of osteoblast activity, and bone formation and resorption between the 2 groups were analyzed with independent t test and chi-square test. Associations of developmental parameters and serum biomarkers with Ca intake from drinking water were analyzed with multiple linear regression and binary logistic regression.Results: Compared with the NW group, the VLW group had lower daily Ca intake, height increase, bone mineral content (BMC), osteoblast activity [serum bone alkaline phosphatase (BALP)] (means ± SDs: 433 ± 131 mg, 16.6 ± 8.27 cm, 1.92 ± 0.431 kg, and 9.28 ± 1.42 μg/L compared with 497 ± 155 mg, 22.3 ± 8.45 cm, 2.14 ± 0.354 kg, and 11.0 ± 0.823 μg/L, respectively, P < 0.001), and higher bone resorption [serum crosslinked C-telopeptide of type I collagen (CTX), mean ± SD: 142 ± 46.9 nmol/L compared with 130 ± 40.6 nmol/L, P = 0.001). Ca intake from drinking water was positively associated with height increase, BMC, and BALP (β: 0.0667, 95% CI: 0.0540, 0.0793; β: 3.22, 95% CI: 2.37, 4.08; and β: 23.9, 95% CI: 20.6, 27.2), respectively, P < 0.001), and was negatively associated with CTX (β: -0.206, 95% CI:-0.321, -0.0904, P < 0.001).Conclusions: These changes suggested that consumption of very low mineral water may be associated with osteoblast inhibition, bone resorption activation, bone mineral reduction, and height development retardation. The health risk of consuming very low mineral water should be considered in children. [ABSTRACT FROM AUTHOR]

With the reformation of energy market and the development of energy intelligent technology, regional integrated energy system, as an important direction of energy system development, is tending to play an important role in the field of energy supply and demand response program. This paper presents an optimal operation model of an integrated energy system considering the response of energy price. In this paper, the typical structure of the integrated energy system and the model of each system module are first introduced in detail, and the system model presented includes three subsystems: power supply, heating, and cooling. Second, a complete scheduling scheme is built based on the energy consumption characteristics and system operation characteristic of the integrated energy system. The model presented could reduce the cost of system without causing a significant amount of environmental pollutions, and improve the energy efficiency of the system efficiently. Besides, the scheduling strategy proposed could also provide support for the operation strategy of the integrated energy system under the energy development. [ABSTRACT FROM AUTHOR]

Recently, a wealth of information has emerged connecting the activation of the NLRP3 (NOD-like receptor family pyrin domain-containing 3) inflammasome to stroke pathogenesis, although the exact influence of the NLRP3 inflammasome on stroke is still in the stage of preliminary study and is awaiting further confirmation. In this paper, we will review the structure, assembly and activation of the NLRP3 inflammasome and its expression in the neurovascular units and will speculate on its possible roles in neurovascular injury post-stroke. Evidence on this topic suggests that targeting NLRP3-mediated inflammation at multiple levels may provide a new therapeutic strategy to prevent the deterioration of neurovascular units after stroke. However, many aspects of the biological link between the NLRP3 inflammasome and stroke remain ill-defined or even completely unknown. As fresh insights come to light regarding the NLRP3 inflammasome, the opportunities to develop new therapeutic strategies for stroke patients are expected to improve accordingly. [ABSTRACT FROM AUTHOR]

To determine the function of miR-206 in epilepsy. Epileptic rat model was established by intra-amygdala injection of kainic acid (KA). Expression levels of miR-206, C–C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) in hippocampus tissues was measured by reverse transcription-quantitative PCR (RT-qPCR) and western blot. Dual luciferase reporter assay was performed to determine the binding of miR-206 to 3′ untranslated region (UTR) of CCL2. Finally, brain waves were recorded and Hematoxylin and eosin (HE) staining and Nissl's staining were performed on the epileptic rat injected with LPS, miR-206 agomir, adeno-associated virus (AAV) expressed CCL2 alone or in combination. Expression of miR-206 was specially decreased in hippocampus tissues compared to cortex in response to KA induced pathologic brain activity. Enforced expression of miR-206 by injection miR-206 agomir not only decreased seizure activity, but also protected KA-induced neuronal loss. And enforced expression of miR-206 suppressed increase of C–C Motif Chemokine Ligand 2 (CCL2) and interleukin-1β (Il-1β) which were induced by injection of KA or KA combined with lipopolysaccharide (LPS). Further more, results of dual luciferase reporter assay confirmed CCL2 was a target of miR-206. Finally, co-injection adeno-associated virus (AAV) expressed CCL2 with miR-206 agomir abolished the function of miR-206 agomir. Taken together, our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2. Our results showed that expression of miR-206 could inhibit seizure-induced brain injury by targeting CCL2. [ABSTRACT FROM AUTHOR]

The digital preservation of intangible cultural heritage has become a major emphasis and challenge in China. This study investigated the state of the field by examining the activities of the local Intangible Cultural Heritage Protection Centers at Nanyang, Kaifeng, Xianning, Chibi, Sanming and Jingdezhen, using semi-structured interviews to document the status of digital preservation of intangible cultural heritage in China. This study found that the digital preservation system of Chinese cultural heritage has a clear structure and pluralistic components. The centers are rich in digital resources, but disordered in their storage, and are supported by policies, but weak in the area of management. It is necessary to further clarify these institutions' rights and responsibilities, formulate storage standards, build shared platforms, and strengthen digital preservation management. [ABSTRACT FROM AUTHOR]

The effect of information sentiment on popularity is meaningful to understand the information content on social media. The present research examined whether emotion values of information could predict the potential of popularity in two psychoinformatic experiments. A prime task was used with popular/unpopular information as prime and high/low sentiment stimuli as targets. In Experiment 1, we observed that unpopular information survived better than popular information. In Experiment 2, the electrophysiological priming effect was observed for unpopular and popular information. According to the findings, sentiment of information on social media plays a key role in information popularity. [ABSTRACT FROM AUTHOR]

Objectives: Neuropathic pain (NP) is one of the main challenges towards NP syndrome treatment. miR-340-5p exhibit different expression levels in NP models. Its effects on NP remained unclear. The objective of this study was to explore the potential regulation mechanisms of miR-340-5p in NP. Methods: Rat model of chronic constriction injury (CCI) was established to induce NP in vivo. NP levels were assessed using mechanical withdrawal threshold (MWT). The inflammation response in CCI rats were determined by HE staining and ELISA assay. The target genes of miR-340-5p were verified by luciferase report assays. Results: In CCI rats, level of miR-340-5p was down-regulated both in spinal cord tissues and isolated microglial cells. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were decreased in CCI rats, which were restored upon miR-340-5p overexpression. miR-340-5p overexpression also decreased inflammation as well as expression levels of COX-2, IL-1β, TNF-α and IL-6 in CCI rats. Luciferase report assays revealed Rap1A was a target gene of miR-340-5p in the experimental model. Elevated miR-340-5p decreased Rap1A expression level in vitro and in vivo. Overexpression of Rap1A protein restored expression levels of COX-2, IL-1β, TNF-α and IL-6, reduced the PWT and PWL and increased inflammation response in CCI rats. Conclusion: miR-340-5p alleviated CCI-induced NP by targeting Rap1A. miR-340-5p and Rap1A may be the potential treatment targets for NP therapeutics. [ABSTRACT FROM AUTHOR]

To investigate the correlation between the air phthalate acid ester (PAE) exposure and serum PAE concentration and the effects of PAE exposure on reproductive health among Chongqing traffic-patrol policemen. In 2013, 32 traffic-patrol policemen working in an area with poor air quality in Chongqing and 28 traffic-patrol policemen working in an area with good air quality were selected. Their blood levels of 14 PAEs and six reproductive hormones were determined. Air samples were collected from four traffic-patrol platforms. The concentrations of 14 PAEs in the air samples were evaluated. All 14 PAEs were detected in the blood samples. The concentrations of seven PAEs in the total suspended particulate, namely, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, bis (2-ethox-yethyl) phthalate, dihexyl phthalate, benzyl butyl phthalate, and bis (2-n-butoxyethyl) phthalate, were positively and significantly associated with the blood levels of these PAEs in the participants. All the sex hormone levels measured here were significantly different between the participants from the two areas. The PAE concentrations in the blood samples were correlated with the reproductive hormone levels in the participants. Air PAE pollution may be a major source of PAE exposure in the traffic-patrol policemen of Chongqing. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to determine the effect of curcumin on osteosarcoma (OS) cells due to inactivation of the p-JAK2/p-STAT3 pathway and evaluate the prognostic value of this pathway in OS. Materials and methods: We exposed a human OS cell line (MG-63) to different concentrations of curcumin. Then, we characterized the effects on MG-63 cells using assays (cell viability, colony formation, cell cycle, wound healing, invasion), flow cytometry, Western blot, immunohistochemical analyses, and tumor xenograft. Results: The half-maximal inhibitory of curcumin for MG-63 cells at 24 hours was 27.6 µM. The number of colonies of MG-63 cells was decreased obviously upon curcumin (10 and 20 µM) treatment. We also found increased accumulation of MG-63 cells in the G2/M phase upon curcumin (10 and 20 µM) treatment. Apoptosis was increased in 10 and 20 µM curcumin-treated MG-63 cells. After incubation of physically wounded cells for 24 hours, the percentage wound width increased upon curcumin exposure. Curcumin obviously decreased the expression of pJAK-2 and pSTAT-3 in MG-63 cells in a dose-dependent manner. Curcumin dose-dependently inhibited the proliferation, migration, and invasion of MG-63 cells and induced arrest of the G0/G1 phase and apoptosis by inhibiting the p-JAK2/p-STAT3 pathway. The linear correlativity between expression of p-JAK2 and STAT3 was very prominent, and both were closely associated with lung metastasis. In vivo study suggested that curcumin suppressed tumor growth through JAK2/STAT3 signaling. Conclusion: Curcumin-mediated inhibition of the proliferation and migration of MG-63 cells was associated with inactivation of JAK/STAT signaling. [ABSTRACT FROM AUTHOR]

Objective: Atherosclerosis is closely associated with ischemic stroke, and long noncoding RNA-H19 (lncRNA-H19) might be a potential target for treating atherosclerosis. The present study aimed to investigate the function of lncRNA-H19 in atherosclerosis and to explore a novel therapeutic strategy for ischemic stroke. Methods: Differentially expressed genes (DEGs) in atherosclerosis were screened by searching public database. In combination with the lncRNA-H19-knockout database, potential lncRNA-H19-mediated gene was retrieved and their relationship was identified. In order to assess the detailed regulatory mechanism of lncRNA-H19, we used a lentivirus packaging system to upregulate Acp5 (Acid phosphatase 5) expression in vascular smooth muscle cells (VSMC) and human umbilical vein endothelial cells (HUVECs). The expression of ACP5 was determined by Western Blot, and evaluations of cell proliferation and apoptosis were detected. An ischemic stroke mouse model was established. Atherosclerosis was measured by using plaque area size. The effects H19 on the expression of ACP5 were explored by the overexpression or silence of H19. Results: H19 and ACP5 were associated with Acute Stroke Treatment (TOAST) subtypes of atherosclerotic patients. The target prediction program and dual-luciferase reporter confirmed ACP5 as a direct target of H19. Lentivirus-mediated H19-forced expression upregulated ACP5 protein levels, promoted cell proliferation and suppressed the apoptosis. The plaque area size was larger in ischemic models than controls. The overexpression or silence of H19 increased or reduced the plaque size. The overexpression or silence of H19 resulted in the expression or inhibition of ACP5. Conclusion: IncRNA-H19 promoting ACP5 protein expression contributed to atherosclerosis and increased the risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose Delivering messages and information to potentially interested users is one of the distinguishing applications of online enterprise social network (ESN). The purpose of this paper is to provide insights to better understand the repost preferences of users and provide personalized information service in enterprise social media marketing.Design/methodology/approach It is accomplished by constructing a target audience identification framework. Repost preference latent Dirichlet allocation (RPLDA) topic model topic model is proposed to understand the mass user online repost preferences toward different contents. A topic-oriented preference metric is proposed to measure the preference degree of individual users. And the function of reposting forecasting is formulated to identify target audience.Findings The empirical research shows the following: a total of 20 percent of the repost users in ESN represent the key active users who are particularly interested in the latent topic of messages in ESN and fits Pareto distribution; and the target audience identification framework can successfully identify different target key users for messages with different latent topics.Practical implications The findings should motivate marketing managers to improve enterprise brand by identifying key target audience in ESN and marketing in a way that truthfully reflects personalized preferences.Originality/value This study runs counter to most current business practices, which tend to use simple popularity to seek important users. Adaptively and dynamically identifying target audience appears to have considerable potential, especially in the rapidly growing area of enterprise social media information service. [ABSTRACT FROM AUTHOR]

Neurodegenerative dementia often has multiple types of underlying pathology, for example, beta-amyloid, misfolded tau, chronic neuroinflammation and neurodegeneration may coexist in Alzheimer's disease. However, the relationship between them is often unclear, in other words, whether one pathology is upstream or downstream of others can be very difficult to investigate directly. This is partly because the underlying pathology in dementia may precede detectable symptoms by several years if not decades. The time scale associated with disease progression in dementia generally exceeds that in conventional longitudinal imaging studies in humans, so it is difficult to directly observe the temporal ordering of different pathologies. Also, animal studies are not always transferable to patients due to obvious differences between the two systems. To investigate the disease progression and relationships among underlying pathological changes, we propose a novel computational modeling approach for multimodal MRI and PET inspired by reaction rate equation in chemical kinetics. We also discuss the possibility and prerequisites to use cross-sectional data to generate preliminary hypothesis for future longitudinal studies. It has been shown that the rate of change in some biomarkers can be approximated by the average trajectory across patients at different stages of disease severity in cross-sectional studies. The relationship modeled in our approach is akin to that in the control theory, and can be assessed by demonstrating that the presence of one disease related biomarker predicts dynamics in another. We argue that the proposed framework has important implications for trials targeting different pathologies in dementia. [ABSTRACT FROM AUTHOR]

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With the application of distributed generation and the development of smart grid technology, micro-grid, an economic and stable power grid, tends to play an important role in the demand side management. Because micro-grid technology and demand response have been widely applied, what Demand Response actions can realize the economic operation of micro-grid has become an important issue for utilities. In this proposed work, operation optimization modeling for micro-grid is done considering distributed generation, environmental factors and demand response. The main contribution of this model is to optimize the cost in the context of considering demand response and system operation. The presented optimization model can reduce the operation cost of micro-grid without bringing discomfort to the users, thus increasing the consumption of clean energy effectively. Then, to solve this operational optimization problem, genetic algorithm is used to implement objective function and DR scheduling strategy. In addition, to validate the proposed model, it is employed on a smart micro-grid from Tianjin. The obtained numerical results clearly indicate the impact of demand response on economic operation of micro-grid and development of distributed generation. Besides, a sensitivity analysis on the natural gas price is implemented according to the situation of China, and the result shows that the natural gas price has a great influence on the operation cost of the micro-grid and effect of demand response. [ABSTRACT FROM AUTHOR]

Endocrine disrupting chemicals may disrupt developing neuroendocrine systems, especially when the exposure occurs during a critical period. This study aimed to investigate whether prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a major component of plasticizers used worldwide, disrupted the development of a network of genes important for neuroendocrine function in male rats. Pregnant rats were treated with corn oil (vehicle control), 2, 10 or 50 mg/kg DEHP by gavage from gestational day 14 to 19. The neuroendocrine gene expressions were quantified using a 48-gene Taqman qPCR array in the whole hypothalamus of neonatal rats (postnatal day 1) and in the anteroventral periventricular nucleus (AVPV), medial preoptic nucleus (MPN) and arcuate nucleus (ARC) of adult rats (postnatal day 70). Immunofluorescent signals of ERα and CYP19 were detected using the confocal microscopy in adult AVPV, MPN and ARC. The results showed that prenatal DEHP exposure perturbed somatic and reproductive development of offspring. Eleven genes were down-regulated in neonatal hypothalamus and showed non-monotonic dose-response relationships, that the 10 mg/kg DEHP dosage was associated with the greatest number of gene expression changes. Different from this, 14 genes were altered in adult AVPV, MPN and ARC and most of alterations were found in the 50 mg/kg DEHP group. Also, 50 mg/kg DEHP reduced ERα expression in the ARC, but no alterations were observed in CYP19 expression. These results indicated that prenatal DEHP exposure may perturb hypothalamic gene programming and the influences are permanent. The effects showed dependence on developmental stages and nuclei region. [ABSTRACT FROM AUTHOR]