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Isodeoxyelephantopin (IDET), a sesquiterpene lactone compound isolated from the Asteraceae plant Inula helenium, has been demonstrated to possess excellent antimicrobial, antidiabetic, hepatoprotective, wound healing, anti-inflammatory, and anticancer activities. However, the underlying mechanisms of IDET's anti-inflammatory properties remain unclear. In this study, we investigated the anti-inflammatory effects and mechanisms of IDET using both in vitro and in vivo models. Our findings revealed that IDET dose-dependently inhibited the upregulation of inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-inflammatory chemokines (MCP-1, CCL20) induced by Lipopolysaccharide (LPS). IDET suppressed the activation of cyclooxygenase-2 (COX-2) and the NLRP3 inflammasome. Subsequent mechanistic investigations demonstrated that IDET inhibited the mRNA and protein levels of Txnip, FOXO1, and EFhd2 in THP-1 cells in a time- and concentration-dependent manner. Furthermore, in an LPS-induced acute peritonitis mouse model, IDET effectively ameliorated symptoms, preserved ileal tissue integrity, attenuated immune cell infiltration, and reduced the expression of inflammatory cytokines in mouse serum. Notably, IDET exhibited an improvement in acute peritonitis by inhibiting the activation of NLRP3 inflammasome. Overall, our study highlights the significant anti-inflammatory activity of IDET, providing valuable insights into its therapeutic potential for acute peritonitis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

SMARCA2 and SMARCA4 are the mutually exclusive catalytic subunits of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, and have recently been considered as attractive synthetic lethal targets for PROTAC-based cancer therapy. However, the potential off-tissue toxicity towards normal tissues remains a concern. Here, we optimize a GSH-inducible SMARCA2/4-based PROTAC precursor with selective antitumor activity towards lung cancer cells and negligible cytotoxicity towards normal cells in both in vitro and in vivo studies. The precursor is not bioactive or cytotoxic, but preferentially responds to endogenous GSH in GSH-rich lung cancer cells, releasing active PROTAC to degrade SMARCA2/4 via PROTAC-mediated proteasome pathway. Subsequent xenograft model study reveals that selective SMARCA2/4 degradation in lung tumors triggers DNA damage and apoptosis, which significantly inhibits lung cancer cell proliferation without obvious adverse events towards normal tissues. This study exemplifies the targeted degradation of SMARCA2/4 in lung cancer cells by the GSH-responsive PROTAC precursor, highlighting its potential as an encouraging cancer therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Polyphenol oxidase (PPO) activity drives walnut fruit browning, but the roles of its only two-family genes, JrPPO1 and JrPPO2, remain unclear. This study explores the spatiotemporal expression and enzymatic characteristics of JrPPO1 and JrPPO2 in walnut. Treatment with the PPO activator CuSO 4 and H 2 O 2 accelerated fruit browning and up-regulated JrPPO1/2 expression, whereas treatment with the PPO inhibitor ascorbic acid delayed browning, down-regulating JrPPO1 and up-regulating JrPPO2 expression. Compared to mJrPPO1, mJrPPO2 can exhibited better enzyme activity at higher temperatures (47 °C) and in more acidic environments (pH 4.25). mJrPPO2 exhibited a higher substrate specificity over mJrPPO1, and the preferred substrates are catechol, chlorogenic acid, and epicatechin. Additionally, mJrPPO2 adapted better to low concentration of oxygen (as low as 1.0% O 2 ) and slightly elevated CO 2 levels compared to mJrPPO1. Subcellular localization and spatiotemporal expression patterns showed that JrPPO1 is only expressed in green tissues and located in chloroplasts, while JrPPO2 is also located in chloroplasts, partly associated with membranes, and is expressed in both green and non-green tissues. Silencing JrPPO1/2 with virus-induced gene silencing (VIGS) reduced fruit browning, maintained higher total phenols, and decreased MDA production. Notably, silencing JrPPO1 had a greater impact on browning than JrPPO2, indicating JrPPO1's greater contribution to PPO activity and fruit browning in walnut fruits. Consequently, JrPPO1 can be effectively regulated both at the molecular level and by manipulating environmental conditions, to achieve the objective of controlling fruit browning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Esophageal cancer (EC), a common type of malignant tumor, ranks as the sixth highest contributor to cancer-related mortality worldwide. Due to the condition that most patients with EC are diagnosed at advanced or metastatic status, the efficacy of conventional treatments including surgery, chemotherapy and radiotherapy is limited, resulting in a dismal 5-year overall survival rate. In recent years, the application of immune checkpoint inhibitors (ICIs) has presented a novel therapeutic avenue for EC patients. Both ICIs monotherapy and immunotherapy combined with chemotherapy or chemoradiotherapy (CRT) have demonstrated marked benefits for patients with advanced EC. Adjuvant or neoadjuvant therapy incorporating immunotherapy has also demonstrated promising prospects in the context of perioperative treatment. Nonetheless, due to the variable response observed among patients undergoing immunotherapy, it is of vital importance to identify predictive biomarkers for patient stratification, to facilitate identification of subgroups who may derive greater benefits from immunotherapy. In this review, we summarize validated or potential biomarkers for immunotherapy in EC in three dimensions: tumor-cell-associated biomarkers, tumor-immune microenvironment (TIME)-associated factors, and host-associated biomarkers, so as to provide a theoretical foundation to inform tailored therapy for individuals diagnosed with EC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tong, Jin, Wang, Zhang, Yin and Shen.)

The incidence of germinal center B-cell-like type diffuse large B-cell lymphoma (GCB DLBCL) is steadily increasing, with a known hereditary component. Although some molecular mechanisms in GCB DLBCL have been elucidated, understanding remains incomplete, limiting the effectiveness of targeted therapies. In GCB DLBCL patients, abnormally high expression of zeste homologs 2 (EZH2) is noted, and the compensatory effect of EZH1 following EZH2 inhibition contributes to poor prognosis. This highlights the potential of dual targeting of EZH1/2 as a promising strategy. In this study, we developed a novel inhibitor, EZH-1-P2, targeting EZH1/2 and evaluated its antitumor effects on DLBCL cells. Mechanistically, inhibition of EZH1/2 affects the epigenetic regulation of gene expression related to p53, impacting cell cycle progression and GCB DLBCL cell growth. Additionally, while EZH1/2 inhibition impacts NOTCH signaling, the precise mechanism by which it affects M2-type tumor-associated macrophage polarization and germinal center expansion requires further investigation. Our research introduces EZH-1-P2 as a novel inhibitor with potential as a candidate for GCB DLBCL therapy, although further studies are needed to fully elucidate its mechanisms., Competing Interests: Conflicts of interest The authors declare no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of tumor-related deaths in China. Circ_0050444 has been revealed to be downregulated in ESCC tissues, however, its function and molecular mechanism underlying ESCC progression is unknown. Therefore, we attempted to clarify the functional role and molecular mechanism of circ_0050444 underlying ESCC progression. RT-qPCR and RNase R digestion assays were used to evaluate circ_0050444 expression and stability characteristics in ESCC cells. Gain-of-function assays were conducted to clarify circ_0050444 role in ESCC cell malignant behaviors. Bioinformatics and mechanism experiments were performed to assess the relationship between circ_0050444 or C10orf91 and miR-486-3p in ESCC cells. Rescue assays were conducted to evaluate the regulatory function of the circ_0050444-miR-486-3p-C10orf91 axis in ESCC cellular processes. Circ_0050444 expression was found to be downregulated both in ESCC patient tissues and cell lines. Functionally, circ_0050444 overexpression repressed ESCC cell proliferative, migratory, and invasive capabilities in cultured cells. Mechanistically, circ_0050444 was found to be competitively bound with miR-486-3p to upregulate C10orf91 in ESCC cells. Moreover, the impact of circ_0050444 elevation on ESCC cell proliferation, migration, and invasion was countervailed by C10orf91 silencing. Circ_0050444 presents downregulation and functions as a tumor suppressor in ESCC progression. Circ_0050444 suppresses ESCC proliferation, migration, and invasion through sponging miR-486-3p to upregulate C10orf91, providing a potential new direction for seeking therapeutic plans for ESCC.

In this study, a novel iron 1,3,5-benzene tricarboxylate loaded on biochar (BC-FeBTC) was developed and applied to kitchen waste composting. The results demonstrated that the emissions of NH 3 and N 2 O were significantly reduced by 57.2% and 37.8%, respectively, compared with those in control group (CK). Microbiological analysis indicated that BC-FeBTC addition altered the diversity and abundance of community structure as well as key functional genes. The nitrification genes of ammonia-oxidizing bacteria were enhanced, thereby promoting nitrification and reducing the emission of NH 3 . The typical denitrifying bacterium, Pseudomonas, and critical functional genes (nirS, nirK, and nosZ) were significantly inhibited, contributing to reduced N 2 O emissions. Network analysis further revealed the important influence of BC-FeBTC in nitrogen transformation driven by functional microbes. These findings offer crucial scientific foundation and guidance for the application of novel materials aimed at mitigating nitrogen loss and environmental pollution during composting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Additives are important for accelerating humification during aerobic composting. The impacts of porous additives biochar and volcanic rock on the physicochemical parameters, maturity indicators, microbial communities, and bacterial functional metabolism during the aerobic composting of cow manure were investigated in this study. The results showed that the biochar addition decreased the E4/E6 value by 10.42% and increased the abundance of Geobacillus (1.69 times), and volcanic rock addition decreased the E4/E6 value by 11.31% and increased the abundance of Thermobacillus (1.29 times) and Paenibacillus (1.72 times). The network analysis demonstrated that biochar promoted maturity by reducing the abundance of Pseudomonas and increasing the abundance of genes related to the metabolism of other amino acids, while volcanic rock promoted maturity by reducing the abundance of genes related to nucleotide metabolism. These results provided data and theoretical justification for the selection of porous additives for composting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Fresh-eating walnuts are perishable and become mildewed during shelf life, limiting their sales span. The effects of chlorine dioxide (ClO 2 ) alone and its combination with walnut green husk extract (WGHE) on shelf stored fresh walnuts were investigated to develop a pollution-free preservative for the produce. The initial development of mildew incidence was delayed by both treatments under 25 °C, whereas, WGHE + ClO 2 acted more effectively than ClO 2 under 5 °C. The WGHE + ClO 2 treatment presented superior effects on improving moisture, soluble sugar and total phenol content, alleviating loss of oil and unsaturated fatty acid and delaying peroxide value increase of walnut kernels at both temperatures. Both treatments inhibited the activities of three lipolytic enzymes and two oxidases at 25 °C and 5 °C, WGHE + ClO 2 acted more effectively at 5 °C. The results guide the combined application of WGHE with ClO 2 on shelf preservation of fresh walnut., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Clear cell renal cell carcinoma (ccRCC) is identified as a malignant tumor in the urinary tract. The research was an attempt to probe the biological function and molecular mechanism of lncRNA LINC00667 in ccRCC development., Methods: qRT-PCR monitored LINC00667, miR-143-3p, and ZEB1 levels. The models of LINC00667, miR-143-3p, and ZEB1 overexpression or knockdown were constructed in ccRCC cells. Cell proliferation, apoptosis, migration, and invasion of the cells were detected. The levels of apoptosis-associated proteins and epithelial-mesenchymal transition (EMT)-related proteins, and ZEB1 were detected by WB. Dual-luciferase reporter assay and RNA pull-down assay identified the binding association between LINC00667 and miR-143-3p, miR-143-3p and ZEB1. Moreover, a xenograft tumor model in nude mice was used for evaluating tumor growth in vivo ., Results: LINC00667 and ZEB1 displayed high expression in ccRCC tissues and cells. miR-143-3p was lowly expressed in ccRCC tissues and cells. LINC00667 targeted and repressed miR-143-3p, which inhibited ZEB1 expression in a targeted manner. Overexpression of LINC00667 facilitated ccRCC cell proliferation, migration, invasion and EMT and retarded apoptosis, whereas LINC00667 knockdown or miR-143-3p overexpression exerted reverse effects. The rescue experiments indicated that overexpressing miR-143-3p dampened LINC00667-mediated oncogenic effects. Overexpressing ZEB1 diminished miR-143-3p-mediated tumor-suppressive effects. In-vivo experiments displayed that overexpression of LINC00667 contributed to the tumor growth of ccRCC cells, in contrast to miR-143-3p overexpression, which restrained the tumor growth., Conclusions: LINC00667 is up-regulated in ccRCC and enhances the ZEB1 expression by targeting miR-143-3p, which in turn accelerates ccRCC progression and induces chemoresistance.

Background: Glioma is the most common extracranial solid tumor of children. The malignant (cancer) cells form in neural crest cell of the adrenal gland. In this study we investigate the expressions of myogenin and OCT4 in Glioma which might be used as prognostic makers for this deteriorated disease., Methods: We used Quantitative Fluorescence PCR (QF-PCR), Enzyme-linked immunosorbent assay (ELISA), and Western-blotting to measure the expression level of myogenin and OCT4 in surgical removed glioma from 41 patients in our hospital., Results: Compared to the healthy children the expression of myogenin and OCT4 was significantly increased in both mRNA and protein level in Glioma tumor cells. In addition, these expressions increased as glioma deterioration., Conclusions: These findings suggesting the expression of myogenin and Oct4 may be useful indicators for predicting the prognosis of children with glioma.

The signaling pathways are highly conserved between Drosophila and mammals concerning intestinal development, regeneration, and disease. The powerful genetic tools of Drosophila make it a valuable and convenient alternative to answer basic biological questions that can not be addressed using mammalian models. In this review, we discuss recent advances in how we use fly midgut to answer the following key questions: (1) How intestine stem cell niches are established; (2) which factors control asymmetric division of stem cells; (3) how intestinal cells interact with environmental factors, such as tissue damage, microbiota, and diet; (4) how to screen aging/cancer-related factors or drugs by fly intestine stem cells., (© 2022 International Federation for Cell Biology.)

Ammonia (NH 3 ) emissions during agricultural production can cause serious consequences on animal and human health, and it is quite vital to develop high-efficiency adsorbents for NH 3 removal from emission sources or air. Porous metal-organic frameworks (MOFs), as the most promising candidates for the capture of NH 3 , offer a unique solid adsorbent design platform. In this work, a series of MOFs with different metal centers, ZnBTC, FeBTC and CuBTC, were proposed for NH 3 adsorption. The metal centers of the three MOFs are coordinated in a different manner and can be attacked by NH 3 with different strengths, resulting in different adsorption capacities of 11.33, 9.5, and 23.88 mmol/g, respectively. In addition, theoretical calculations, powder XRD patterns, FTIR, and BET for the three materials before and after absorption of ammonia were investigated to elucidate their distinctively different ammonia absorption mechanisms. Overall, the study will absolutely provide an important step in designing promising MOFs with appropriate central metals for the capture of NH 3 .

Background: Tumor diameter (TD)/original lesion area has been reported to have a certain predictive effect on lymph node metastasis (LNM) and recurrence of endometrial cancer (EC) patients, but there is still controversy about their relationship. Therefore, we conducted a meta-analysis to provide reference for clinical management and follow-up studies of patients with EC., Methods: The databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang were searched, from inception to 27 October 2022, for studies regarding the association of TD with LNM risk and recurrence rate in EC. The search strategy was developed using a combination of free terms and medical subject headings (MeSH). Stata 15.0 was used to conduct the statistical analysis. Odds ratio (OR) with the 95% confidence interval (CI) were calculated to evaluate the association of TD and the risk of LNM and recurrence in EC patients. The OR value obtained from the multivariate analysis is first extracted; the results of univariate analysis were extracted for articles without the results of multivariate analysis. Newcastle-Ottawa Scale (NOS) assessed the quality of the included articles, publication bias was evaluated by Egger's test with funnel plots., Results: There was a total of 69 studies 123,383 EC patients included. Meta-analysis showed higher LNM risk in EC patients with the TD >2 cm, which was 2.88 times higher than that in those with ≤2 cm, and the difference was statistically significant (OR =2.88; 95% CI: 2.12-3.89; P<0.001), publication bias had no effect on the results. The risk of recurrence in EC patients with a TD >2 cm was 2.45 times higher than that in those with ≤2 cm (OR =2.45; 95% CI: 1.73-3.48; P<0.001), publication bias exerted influence over the results., Conclusions: TD is associated with LNM and recurrence in patients with EC. Therefore, TD should be considered in the scope of surgery and adjuvant therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2595/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Ammonia (NH 3 ) is a common pollutant mostly derived from pig manure composting under humid conditions, and it is absolutely necessary to develop materials for ammonia removal with high stability and efficiency. To this end, metal-organic frameworks (MOFs) have received special attention because of their high selectivity of harmful gases in the air, resulting from their large surface area and high density of active sites, which can be tailored by appropriate modifications. Herein, two synthetic metal-organic frameworks (MOFs), 2-methylimidazole zinc salt (ZIF-8) and zinc-trimesic acid (ZnBTC), were selected for ammonia removal under humid conditions during composting. The two MOFs, with different organic linkers, exhibit fairly distinctive ammonia absorption behaviors under the same conditions. For the ZnBTC framework, the ammonia intake is 11.37 mmol/g at 298 K, nine times higher than that of the ZIF-8 framework (1.26 mmol/g). In combination with theoretical calculations, powder XRD patterns, FTIR, and BET surface area tests were conducted to reveal the absorption mechanisms of ammonia for the two materials. The adsorption of ammonia on the ZnBTC framework can be attributed to both physical and chemical adsorption. A strong coordination interaction exists between the nitrogen atom from the ammonia molecule and the zinc atom in the ZnBTC framework. In contrast, the absorption of ammonia in the ZIF-8 framework is mainly physical. The weak interaction between the ammonia molecule and the ZIF-8 framework mainly results from the inherent severely steric hindrance, which is related to the coordination mode of the imidazole ligands and the zinc atom of this framework. Therefore, this study provides a method for designing promising MOFs with appropriate organic linkers for the selective capture of ammonia during manure composting.

Backgrounds: Special AT-rich sequence-binding protein 1 (SATB1) belongs to the chromatin-remodeling protein which regulates different genes expression. High expression of SATB1 was found to be associated with the development of certain carcinomas. However, the functions of SATB1 in colon adenocarcinoma (CAC) remains unclear yet. Our study aims to investigate the potential role of SATB1 in CAC and whether it is associated with the unfavorable symptoms of CAC patients., Methods: The expression pattern of SATB1 was measured in CAC samples and adjacent noncancerous samples through quantitative real-time polymerase chain reaction and immunohistochemistry staining. We performed univariate and multivariate analyses to evaluate the clinical role of SATB1 in enrolled patients. The Kaplan-Meier analyses and log-rank tests were carried out to assess the clinicopathologic characteristics. The effect of SATB1 in human colon cancer cells was examined through cellular experiments., Results: The expression level of SATB1 in CAC tissues was significantly elevated compared with adjacent control tissues. High expression of SATB1 in tumor tissue was found to be associated with lymph node metastasis and advanced TNM stage. Higher SATB1 level in CAC patients indicated a worse 5-year survival time. Moreover, high SATB1 was defined as an independent poor prognostic factor. Cellular experiments showed that inhibition of the SATB1 protein level in human colon cells could suppress the migration and invasion capabilities., Conclusions: Our findings revealed that high expression of SATB1 was significantly correlated with the poor clinical features and prognosis of CAC patients. It indicated that SATB1 might serve as a potential prognostic predictor and novel drug target for CAC treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To observe the relationship between Tumor Necrosis Factor-alpha (TNF-α) and Neuropeptide Y (NPY) expression and neurological function score in epileptic children., Methods: Fifty-four epileptic children diagnosed and treated in Xuzhou Children's Hospital, China from Feb 2017 to Mar 2018 were collected and included in a research group (RG), while 30 healthy children who underwent physical examination at the same time were included in the control group (CG). ELISA was used to detect the expression of TNF-α and NPY in the serum of children in the two groups, and those before treatment were compared. The National Institute of Health stroke scale (NIHSS) and Hamilton Anxiety (HAMA) scores before and after treatment were observed, and Pearson correlation was used to analyze the relationship between the expression levels of TNF-α and NPY in the serum as well as NIHSS and HAMA scores., Results: The expression levels of TNF-α and NPY in the serum of children in the RG were significantly higher than those in the CG ( P <0.001). The expression level of TNF-α was positively correlated with the NIHSS and HAMA scores (r=0.748, P <0.001) (r=0.772, P <0.001). The expression level of NPY was positively correlated with the NIHSS and HAMA scores (r=0.768, P <0.001) (r=0.643, P <0.001)., Conclusion: TNF-α and NPY are highly expressed in epileptic children and are positively correlated with neurological function score., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2021 Qiu et al. Published by Tehran University of Medical Sciences.)

Pancreatic cancer is one of the deadliest diseases, due to the lack of early symptoms and resistance to current therapies, including radiotherapy. However, the mechanisms of radioresistance in pancreatic cancer remain unknown. The present study explored the role of microRNA-153 (miR-153) in radioresistance of pancreatic cancer. It was observed that miR-153 was downregulated in pancreatic cancer and positively correlated with patient survival time. Using stably-infected pancreatic cancer cells that overexpressed miR-153 or miR-153 inhibitor, it was found that miR-153 overexpression sensitized pancreatic cancer cells to radiotherapy by inducing increased cell death and decreased colony formation, while cells transfected with the miR-153 inhibitor promoted radioresistance. Further investigation demonstrated that miR-153 promoted radiosensitivity by directly targeting jagged canonical Notch ligand 1 (JAG1). The addition of recombinant JAG1 protein in the cell cultures reversed the therapeutic effect of miR-153. The present study revealed a novel mechanism of radioresistance in pancreatic cancer and indicated that miR-153 may serve as a potential therapeutic target for radioresistance., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Zhao et al.)

Glioma is the most common primary intracranial tumor, in which glioblastoma (GBM) is the most malignant and lethal. However, the current chemotherapy drugs are still unsatisfactory for GBM therapy. As the natural products mainly extracted from Eucalyptus species, phloroglucinol-terpene adducts have the potential to be anti-cancer lead compounds that attracted increasing attention. In order to discover the new lead compounds with the anti-GBM ability, we isolated Eucalyptal A with a phloroglucinol-terpene skeleton from the fruit of E. globulus and investigated its anti-GBM activity in vitro and in vivo. Functionally, we verified that Eucalyptal A could inhibit the proliferation, growth and invasiveness of GBM cells in vitro. Moreover, Eucalyptal A had the same anti-GBM activity in tumor-bearing mice as in vitro and prolonged the overall survival time by maintaining mice body weight. Further mechanism research revealed that Eucalyptal A downregulated SRSF1 expression and rectified SRSF1-guided abnormal alternative splicing of MYO1B mRNA, which led to anti-GBM activity through the PDK1/AKT/c-Myc and PAK/Cofilin axes. Taken together, we identified Eucalyptal A as an important anti-GBM lead compound, which represents a novel direction for glioma therapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Calycosin, a functional phytoestrogen isoflavone isolated from Radix astragali, has been shown to possess multiple pharmacological properties including anti-cancer activity. However, up to now, the anti-cancer effect and the related mechanism of calycosin on cervical cancer (CC) cells have not been explored. It has been demonstrated that tumor suppressor miR-375 was downregulated in CC and calycosin upregulated miR-375 expression in cerebral ischemia/reperfusion. Thus we supposed that calycosin exerted anti-cancer effect by upregulating miR-375 expression in CC cells. Effects of calycosin or combined with miR-375 on cell viability and lactate dehydrogenase (LDH) release were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetra zoliumromide (MTT) and LDH release assay. Apoptosis, caspase-3 activity, and cell invasion were determined by flow cytometry, caspase-3 activity assay, and Transwell assay, respectively. miR-375 expression was detected by quantitative real-time PCR (qRT-PCR). Our results showed that Calycosin dose-dependently inhibited cell viability and increased LDH release in CC cells, suggesting the cytotoxic effect of calycosin on CC cells. Calycosin enhanced the apoptotic rate and caspase-3 activity and decreased the number of invaded cells in CC cells. In addition, we found that miR-375 expression was decreased in CC cells but was upregulated in response to calycosin. Mechanistically, knockdown of miR-375 significantly reversed the anti-cancer effect of calycosin on CC cells. In conclusion, calycosin inhibited viability, induced apoptosis, and suppressed invasion of CC cells by upregulating tumor suppressor miR-375., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Efficacy and safety of sodium valproate (SV) and lamotrigine (LTG) in treating refractory epilepsy (RE) in children and the predictive value of serum neuron-specific enolase (NSE) and central nervous system specific S100β protein (S100β) on efficacy assessment were explored. A total of 110 RE children admitted to Xuzhou Children's Hospital, Xuzhou Medical University were enrolled. Patients treated with SV alone served as the control group (n=51), and those treated with SV plus LTG as the study group (n=59). Serum NSE and S100β expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The efficacy, seizure frequency, adverse reactions, concentration of serum brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), and expression of serum NSE and S100β were observed and compared. The total effective rate in the study group was significantly higher than that in the control group, and the seizure frequency and incidence of adverse reactions were significantly lower than that in the control group. The study group showed remarkably higher BDNF and NGF than the control group after treatment. The expression of serum NSE and S100β in effectively treated children were significantly lower than that in ineffectively treated children. The area under the curve (AUC) of serum NSE and S100β were 0.828 and 0.814 respectively. SV combined with LTG is better and safer than SV alone in the treatment of RE in children. Serum NSE and S100β are of high value in predicting the efficacy., (Copyright: © Zhang et al.)

Chronic HCV infection can lead to cirrhosis and is associated with increased mortality. Interleukin (IL)-10-producing B cells (B10 cells) are regulatory cells that suppress cellular immune responses. Here, we aimed to determine whether HCV induces B10 cells and assess the roles of the B10 cells during HCV infection. HCV-induced B10 cells were enriched in CD19 hi and CD1d hi CD5 + cell populations. HCV predominantly triggered the TLR2-MyD88-NF-κB and AP-1 signaling pathways to drive IL-10 production by B cells. In a humanized murine model of persistent HCV infection, to neutralize IL-10 produced by B10 cells, mice were treated with pcCD19scFv-IL-10R, which contains the genes coding the anti-CD19 single-chain variable fragment (CD19scFv) and the extracellular domain of IL-10 receptor alpha chain (sIL-10Ra). This treatment resulted in significant reduction of B10 cells in spleen and liver, increase of cytotoxic CD8 + T-cell responses against HCV, and low viral loads in infected humanized mice. Our results indicate that targeting B10 cells via neutralization of IL-10 may offer a novel strategy to enhance anti-HCV immunotherapy., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Efficacy of levetiracetam (LEV) combined with sodium valproate (SV) on pediatric epilepsy and its effect on serum miR-106b in children were investigated. One hundred and twenty children with epilepsy in Xuzhou Children's Hospital from July 2015 to July 2017 were enrolled, and divided into control group (n=60) and observation group (n=60) according to random sampling. Additionally, 100 children undergoing normal physical examination were collected as normal group. Patients in the control group were treated with SV, and patients in the observation group were treated with SV and LEV. RT-qPCR was used for detecting the relative expression of serum miR-106b in children. The clinical efficacy was evaluated. After treatment, the relative expression of serum miR-106b in the control group was significantly higher than that in the observation group (P<0.05). The difference in the control group was smaller than that in the observation group (P<0.05). According to the ROC curve analysis, when the cut-off value was 1.442, the sensitivity, specificity and area under curve (AUC) of miR-106b in the diagnosis of pediatric epilepsy were 94.00, 64.17 and 0.833 respectively. The clinical efficacy in the observation group was significantly better than that in the control group (P<0.05). Spearman's test showed that the expression of miR-106b gradually decreased with the continuous improvement of the clinical efficacy (P<0.05). The AUC of miR-106b was 0.833, 95% CI: 0.779 to 0.887, the cut-off was 1.442. LEV combined with SV is effective in the treatment of children with epilepsy, and does not increase the clinical ADR. The expression of serum miR-106b in children can be used as a clinical prognostic indicator and a potential diagnostic indicator., (Copyright: © Zhao et al.)

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo . However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro , which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application., Competing Interests: The authors declare no conflict of interest., (© 2019 Chongqing Medical University. Production and hosting by Elsevier B.V.)

Background: Infant colic is a common benign disease during early infancy. Migraine and tension-type headache (TTH) are the most common primary headache forms among pediatric population. Several studies have investigated the incidence of infant colic in patients with migraine and TTH. The meta-analysis was to assess the relationship between infant colic and migraine as well as TTH., Methods: PubMed, Web of Science, and Cochrane Library were searched until August 16, 2018, for potential studies. Data were extracted by two independent authors and analyzed using RevMan 5.2 software. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine the association between infant colic and migraine as well as TTH, respectively., Results: A total of 148 studies were found, and 7 studies were finally included. A higher incidence of colic during infancy was revealed in migraine patients than controls ( P =0.05, OR: 2.51, 95% CI: 1.32-4.77) and TTH subjects ( P =0.02, OR: 0.33, 95% CI: 0.13-0.86), respectively. And no significances were found between TTHs with controls ( P =0.51, OR: 1.17, 95% CI: 0.73-1.89)., Conclusion: This meta-analysis indicated that migraine was associated with increased incidence of infantile colic history, but TTH incidence was not relevant with the incidence of infantile colic history.

Recently, chronic osteomyelitis is still a challenging surgical problem. Unfortunately, the traditional clinical method using bone cement loaded antibiotics is restricted due to its non-biodegradability and limited release of antibiotics. Hydroxyapatite is a good adsorbent with good biocompatibility, an ideal bone repair material, and can avert the requirement for the secondary surgical procedure of removal. In this study, nano-hydroxyapatite combined with a polyurethane containing 3% silver (Ag/n-HA/PU) was synthesized, and investigated for its efficacy of treating chronic bone infection with bone defects. To clarify its silver ions release characteristics, the concentration of the Ag + in the elution was analyzed every day after in vitro deionized water immersion. A chronic osteomyelitis of tibia in rabbit model was established, and 70 New Zealand rabbits were divided into 4 groups, including the blank control group, nano-hydroxyapatite combined with polyurethane (n-HA/PU) implant group, 3% Ag/n-HA/PU group and 10% Ag/n-HA/PU group after debridement. Routine blood tests, radiography, Micro-CT, and histological staining were conducted at 4 days, 3, 6 and 12 weeks post-treatment. The results showed that the released silver from the 3% Ag/n-HA/PU and 10% Ag/n-HA/PU exhibited an initial burst release and followed by a slow controlled release up to 39 days and 42 days respectively. A good repair of bone defects, an appropriate rate of degradation of scaffolds and no significant toxicity were observed in the 3% Ag/n-HA/PU group, indicating the advantages of this novel synthetic scaffold to be a potential option for the treatment of chronic osteomyelitis. A novel nano-composite, nano-hydroxyapatite combined with a polyurethane containing 3% silver (Ag/n-HA/PU) provide controlled release of Ag + , illustrated by its abilities of biodegradation, antimicrobial activity, and favorable repair of bone defects in the treatment of chronic osteomyelitis.

Background: The present study aimed to explore the potential effects of brain electronic biofeedback training in combination with psycho-behavior intervention during non-medical treatment of children with attention deficit hyperactivity disorder (ADHD)., Methods: The children with ADHD admitted to our department from January 2015 to January 2016 were selected as the study subjects. All the cases met the standard of Chinese classification of mental disorders criterion and were divided into two groups, the control group and the observation group, with 15 cases in each group. Medical treatment and brain electronic biofeedback training were provided for the children in the control group; while medical treatment and brain electronic biofeedback training in combination with psycho-behavior intervention were provided to children in the observation group. For both groups, one course lasted for three months, after which questionnaires were distribute in order to evaluate the application effects., Results: The symptoms of the children in the two groups were improved after the treatment. However, the improvement in observation group was significantly higher that of the children in the control group., Conclusions: Brain electronic biofeedback training in combination with psycho-behavior intervention is significantly better treatment option for children affected with ADHD.

Objective: To evaluate the bone repair efficacy of the new nano-hydroxyapatite (n-HA)/polyurethane (PU) composite scaffold in the treatment of chronic osteomyelitis in tibia., Methods: A novel levofloxacin@mesoporous silica microspheres (Lev@MSNs)/n-HA/PU was successfully synthesized. Its surface structure was observed by scanning electron microscopy (SEM). Fifty adult female New Zealand rabbits were randomly selected, and osteomyelitis was induced in the right tibia of the rabbit by injecting bacterial suspension ( Staphylococcus aureus ; 3×10 7 CFU/mL), which of the method was described by Norden. A total of 45 animals with the evidence of osteomyelitis were randomly divided into 4 groups, and the right medullary cavity of each animal was exposed. Animals in the blank control group (group A, n =9) were treated with exhaustive debridement only. The remaining animals were first treated by exhaustive debridement, and received implantations of 5 mg Lev@PMMA (group B, n =12), 1 mg Lev@MSNs/n-HA/PU (group C, n =12), and 5 mg Lev@MSNs/n-HA/PU (group D, n =12), respectively. At 12 weeks postoperatively, the right tibia of rabbits were observed by X-ray film, and then gross observation, methylene blue/acid fuchsin staining, and SEM observation of implant-bone interface, as well as biomechanical test (measuring the maximal compression force) were performed., Results: X-ray films showed that the infection were severer than those of preoperation in group A, while the control of inflammation and bone healing of rabbits in group D were obviously better than those at preoperation. The gross observation showed extensive bone destruction in group A, a significant gap between bone tissue and the material in groups B and C, and close combination between bone tissue and the material in group D. The histology of the resected specimens showed that there was no obvious new bone formation around the materials in groups B and C, and there was abundant new bone formation around the periphery and along the voids of the materials and active bone remodeling in group D. The SEM observation of the bone-implant interface demonstrated that no new bone formation was observed at the bone-implant interface in groups B and C. However, bony connections and blurred boundaries were observed between the material and host bone tissue in group D. The biomechanical test showed the maximal compression force of groups B and D were significantly higher than that of groups A and C ( P <0.05), but there was no significant difference between groups B and D ( P >0.05)., Conclusion: The novel synthetic composite Lev@MSNs/n-HA/PU exhibit good antibacterial activities, osteoconductivity, and biomechanical properties, and show great potential in the treatment of chronic osteomyelitis of rabbits.

Acetylated nanofibrillated cellulose (ANFC) with different degrees of substitution (DS) was prepared from corn-stalk microcrystalline cellulose (MCC) using chemical-mechanical combined processes. The physicochemical properties of nanofibrillated cellulose (NFC) and ANFC were investigated together with the influence of added nanoparticles on the mechanical properties of starch films. The acetylation reaction was monitored by Fourier transform infrared (FT-IR) and titration. Particle size and morphological of NFC and ANFC were studied by atomic force microscope (AFM). The results suggested that NFC had nano-order-unit web-like network with mean diameter of ~24 nm. The thermostability of all samples was found to decrease as the modification extent rose, and mechanical disposal revealed no significant influence on the DS and crystalline structure of cellulose. The ANFC with the DS value of 0.35 demonstrated the best enhancement effect on starch films, with increased tension strength (TS) by 201%. The tensile tests confirmed that the web-like network structure of NFC was more conducive to strength, and proper chemical modification could improve the uniform dispersion of nano-fillers in starch to result in higher strength performances., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The molecular bases of behavior problems in young infants are related to genetic and epigenetic determinants of children's behavior. It has been estimated that 7% of preschoolers and 13-20% of school-aged children and adolescents suffer from internalizing and/or externalizing problems. Researchers in the field are involved in the search for specific epigenetic patterns related to the prenatal environment using cutting-edge approaches like the candidate gene, the genome-wide, and epigenome-wide approaches. The present review article will discuss all these latest innovations in order to better understand molecular bases of behavior problems in young infants that shall definitely result in better treatment planning.

Sensitive and selective detection of Pb 2+ is a very worthwhile endeavor in terms of both human health and environmental protection, as the heavy metal is fairly ubiquitous and highly toxic. In this study, we designed phthalocyanine-porphyrin (Pc-Por) heterodyads, namely, H 2 Pc-α-ZnPor (1) and H 2 Pc-β-ZnPor (2), by connecting a zinc(II) porphyrin moiety to the nonperipheral (α) or peripheral (β) position of a metal-free phthalocyanine moiety. Upon excitation at the porphyrin Soret region (420 nm), both of the dyads exhibited not only a porphyrin emission (605 nm) but also a phthalocyanine emission (ca. 700 nm), indicating the occurrence of intramolecular fluorescence resonance energy transfer (FRET) processes from the porphyrin donor to the phthalocyanine acceptor. The dyads can selectively bind Pb 2+ in the phthalocyanine core leading to a red shift of the phthalocyanine absorption and thus a decrease of spectral overlap between the porphyrin emission and phthalocyanine absorption, which in turn suppresses the intramolecular FRET. In addition, the binding of Pb 2+ can highly quench the emission of phthalocyanine by heavy-metal ion effects. The synergistic coupled functions endow the dyads with remarkable ratiometric fluorescent responses at two distinct wavelengths (F 605 /F 703 for 1 and F 605 /F 700 for 2). The emission intensity ratio increased as a linear function to the concentration of Pb 2+ in the range of 0-4.0 μM, whereas the detection limits were determined to be 3.4 × 10 -9 and 2.2 × 10 -8 M for 1 and 2, respectively. Furthermore, by comparative study of 1 and 2, the effects of distance and relative orientation between Pc and ZnPor fluorophores on the FRET efficiency and sensing performance were highlighted, which is helpful for further optimizing such FRET systems.

The diagnosis of debilitating psychiatric disorders like autism spectrum disorder (ASD) and schizophrenia (SCHZ) is on the rise. These are severe conditions that lead to social isolation and require lifelong professional care. Improved diagnosis of ASD and SCHZ provides early access to medication and therapy, but the reality is that the mechanisms and the cellular pathology underlying these conditions are mostly unknown at this time. Although both ASD and SCHZ have strong inherited components, genetic risk seems to be distributed in hundreds of variants, each conferring low risk. The poor understanding of the genetics of ASD and SCHZ is a significant hurdle to developing effective treatments for these costly conditions. The recent implementation of next-generation sequencing technologies and the creation of large consortia have started to reveal the genetic bases of ASD and SCHZ. Alterations in gene expression regulation, synaptic architecture and activity and immunity seem to be the main cellular mechanisms contributing to both ASD and SCHZ, a surprising overlap given the distinct phenotypes and onset of these conditions. These diverse pathways seem to converge in aberrant synaptic plasticity and remodelling, which leads to altered connectivity between relevant brain regions. Continuous efforts to understand the genetic basis of ASD and SCHZ will soon lead to significant progress in the mechanistic understanding of these prominent psychiatric disorders and enable the development of disease-modifying therapies for these devastating conditions., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim of this study was to analyze the concentration changes of nuclear factor-κB (NF-κB) and the related inflammatory factors of pre-treatment and post-treatment in children with viral encephalitis, to examine the mechanism of NF-κB in the pathogenesis of child viral encephalitis. Twenty-two children with severe viral encephalitis, 13 children with mild viral encephalitis and 12 normal children, who were treated in our hospital, were randomly selected. Before and after treatment, the concentrations of inflammation-related factors in serum including interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α) were detected by ELISA and comparative analysis were performed. The expression of NF-κB in peripheral blood and cerebrospinal fluid (CSF) before and after treatment was detected by RT-PCR and western blotting, while the difference of NF-κB expressions between viral encephalitis children and normal children was analyzed. The concentrations of inflammation-related factors in serum of children with viral encephalitis, including IL-1, IL-6 and TNF-α were significantly higher than those of normal children (P<0.01), and after treatment, the concentrations of IL-1, IL-6 and TNF-α were distinctly lower than those of pre-treatment (P<0.01). The concentrations of NF-κB in peripheral blood and CSF of children with viral encephalitis in the mild group and severe group were evidently increased compared to those of pre-treatment, while the degree of increase in the severe group was higher than that in mild group, which was higher than that in the control group (P<0.01). After treatment, the concentrations of serum NF-κB of children in the severe and mild groups were distinctly lower than those of pre-treatment (P<0.01), with statistically significant difference. In conclusion, the NF-κB level in serum and CSF of children with viral encephalitis was positively related to the severity of the disease. The higher the concentration of pre-treatment was, the more serious the disease would be. Our results indicate that NF-κB plays an important role in the occurrence and development of viral encephalitis in children.

Astrocytomas (gliomas) are the most common primary brain tumors among adults and second most frequent neoplasm among children. New ideas and novel approaches are being explored world over with aim to devise better management strategeies for this deadly pathological state. We searched the electronic database PubMed for pre-clinical as well as clinical controlled trials reporting importance of various therapeutic drugs against gliomas. It was observed clearly that this approach of using therapeutic drugs is clearly evolving and has been observed to be promising future therapeutic avenue against gliomas. The searched literature on whole revealed that although gliomas are treated aggressively with surgery, chemotherapy and radiation, treatment resistance, drug toxicity and poor response rates among pediatric glioma patients, continue to drive the need to discover new and more effective chemotherapeutic agents. The present review is focused on the latest updates in therapeutic drugs against gliomas in pediatric patients. The important chemo-therapeutics discussed in this review included alkylating agents like temoxolomide, derivatives of platinum, nitrosoureas, topoisomerases, angiogenesis inhibitors and cytomegalovirus as therapeutic agents.

Childhood epilepsy affects ~0.5-1% in the general population worldwide. Early-onset epileptic encephalopathies are considered to be severe neurological disorders, which lead to impaired motor, cognitive, and sensory development due to recurrence of seizures. Many of the observed epilepsy phenotypes are associated with specific chromosomal imbalances and thus display gene dosage effects, and also specific mutations of a variety of genes ranging from ion channels to transcription factors. High throughput sequencing technologies and whole exome sequencing have led to the recognition of several new candidate genes with a possible role in the pathogenesis of epileptic encephalopathies. The mutations causing channelopathies can be either a gain or a loss of ion channel function and contribute to the pathogenesis of epilepsy syndrome. Nearly 300 mutations of SCN1A gene coding for the Nav1.1 channel protein have been identified that contribute to the pathology of epilepsy. Besides Na, potassium and calcium channels are also implicated in epileptic encephalopathies. Therapeutic management of epileptic encephalopathies has been challenging as the majority of the medications are not efficient and often have many undesirable side effects. A better understanding of the molecular nature of epilepsy in an individual is important to design a personalized medication, considering the number of possible genetic mutations that can contribute to epileptic encephalopathies.

Chronic osteomyelitis is a prolonged persistent disease accompanied by bone destruction and sequestrum formation, it is very difficult to treat. Antibiotic loaded polymethyl methacrylate (PMMA) has been used in clinical. However, when PMMA was implanted in the body, the deficiencies is that it is non-biodegradable and a second operation is needed. Here, we synthesize a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffolds, and evaluated the therapeutic effect in treating chronic osteomyelitis with bone defects in rabbit model compared with bulk PMMA. X-ray, Micro CT, gross pathology as well as immunohistochemical staining were performed at predesignated time points (1, 3, 6 and 12 weeks). Our results demonstrated that the efficiency of mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffolds loaded with 5 mg levofloxacin was much better at treating bone defects than the other groups. This novel synthetic scaffold may provide a solution for the treatment of chronic osteomyelitis., Competing Interests: The authors declare no competing financial interests.

Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are playing critical roles in tumorgenesis. LncRNA ANRIL has been reported to promote tumor progression in types of cancers. However, the expression and function of ANRIL in cervical cancer are still largely unclear. We measured the expression of ANRIL in cervical cancer tissues and cell lines and analyzed its association with clinicopathological features and prognosis. Loss-of-function experiments were used to identify the biological function of ANRIL. Our results showed that the expression of lncRNA ANRIL was significantly increased both in cervical cancer tissues and cell lines. Patients with high ANRIL expression had advanced FIGO stage, lymph node metastasis and poor overall survival than those with low ANRIL expression. Multivariable Cox proportional hazards regression analysis suggested that high ANRIL expression was an independent prognostic factor of prognosis. Loss-of-function experiments showed that decreased expression of ANRIL inhibited cell proliferation, migration and invasion of cervical cancer. Finally, western blot indicated that the PI3K/Akt pathway was found to be inactivated in cervical cancer cells after ANRIL inhibition. These results indicated that lncRNA ANRIL might play an important role in cervical cancer progression and could serve as a novel prognostic biomarker and therapeutic target in cervical cancer., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The aim was to study the frequencies of common deafness-related mutations and their contribution to hearing loss in different regions of Inner Mongolia. A total of 738 deaf children were recruited from five different ethnic groups of Inner Mongolia, including Han Chinese (n=486), Mongolian (n=216), Manchurian (n=24), Hui (n=6) and Daur (n=6). Nine common mutations in four genes (GJB2, SLC26A4, GJB3 and mitochondrial MT-RNR1 gene) were detected by allele-specific PCR and universal array. At least one mutated allele was detected in 282 patients. Pathogenic mutations were detected in 168 patients: 114 were homozygotes and 54 were compound heterozygotes. The 114 patients were carriers of only one mutated allele. The frequency of GJB2 variants in Han Chinese (21.0%) was higher than that in Mongolians (16.7%), but not significantly different. On the other hand, the frequency of SLC26A4 variants in Han Chinese (14.8%) was lower than that in Mongolians (19.4%), but also not significantly different. The frequency of patients with pathogenic mutations was different in Ulanqab (21.4%), Xilingol (40.0%), Chifeng (40.0%), Hulunbeier (30.0%), Hohhot (26.3%), and in Baotou (0%). In conclusion, the frequency of mutated alleles in deafness-related genes did not differ between Han Chinese and Mongolians. However, differences in the distribution of common deafness-related mutations were found among the investigated areas of Inner Mongolia.

Objectives: This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis., Methods: Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene., Results: MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3'UTR to regulate the expression of SOX6., Conclusion: MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis.

The urinary metabolic marker compounds, namely phenylpyruvic acid (PPA), 2-hydroxyphenylacetic acid (oOPAA), 4-hydroxyphenylacetic acid (pOPAA), phenyllactic acid (PLA) and phenylacetic acid (PAA) of phenylketonuric individuals were detected by a novel method of micellar electrokinetic capillary chromatography with capacitively coupled contactless conductivity detection and amperometric detection (MECC-C(4)D/AD). Electrophoretic runs were performed in a 35 mmol L(-1) SDS/60 mmol L(-1) H(3)BO(3)-Na(2)B(4)O(7) running buffer (pH 8.2) at a separation voltage of 16 kV, and five marker compounds and the major coexisting compound uric acid (UA) could be well separated within 23 min. Highly linear response was obtained for five marker compounds over three orders of magnitude with detection limits ranging from 6.6×10(-6) to 6.4×10(-8) g mL(-1) (S/N=3). The proposed method has been used to detect the marker compounds simultaneously in urine samples with the advantages of obtaining more information about target analytes and avoiding redundant measurements and high assay cost. Urinary patterns in phenylketonuric babies were distinct and easily distinguished from those of healthy newborns. The proposed MECC-C(4)D/AD method could find clinical application in early noninvasive diagnosis of phenylketonuria (PKU), as significant differences could be found in the urinary content of five marker compounds among the phenylketonuric babies without or with dietotherapy and the healthy babies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Two non-electroactive biomarkers methylglyoxal (MGo) and glyoxal (Go) in urine and environmental water samples were determined for the first time by capillary electrophoresis with amperometric detection (CE-AD) after derivatizing with an electroactive compound 2-thiobarbituric acid. Experimental conditions of derivatization and CE-AD detection were optimized. Highly linear response was obtained for these two biomarkers over three orders of magnitude with good correlation (r(2)>0.999). The limits of detection (LODs) and limits of quantitation (LOQs) of MGo and Go were 0.2microgL(-1) and 1.0microgL(-1), 0.5microgL(-1) and 2.0microgL(-1), respectively. The average recovery and relative standard deviation (RSD) were within the range of 90.9-101.3% and 0.7-2.2%, respectively. The proposed CE-AD method provides a reliable and sensitive quantitative evaluation of MGo and Go in real sample matrices by employing relatively simple and inexpensive instrument.

It has been reported that conditional double knockout of presenilin-1 and presenilin-2 in forebrain of mice (dKO mice) induce symptoms most analogous to that of neurodegenerative diseases, especially Alzheimer's disease, however, there is no deposition of extra amyloid-beta (Abeta(40) or Abeta(42)) in dKO brain. In the present study, we thoroughly measured the inflammatory response in dKO mice, which is another global symptom in neurodegenerative diseases. We demonstrated that glial cells were dramatically activated from early age (3 months) in dKO brain when compared with control mice. In addition, complement C1qalpha and C4, the key components in the classical complement pathway, were also stimulated in dKO mice brain. Antibody array and ELISA analysis indicated that cytokine and chemokine levels were also significantly increased in dKO brain. Moreover, we found that leukocytes were elevated beginning at 6 months of age, and multiple inflammatory mediators changed in dKO mice serum at 9 months, showing that the inflammatory responses gradually expanded to systemic tissue. These findings confirm that presenilins double knockout results in robust inflammatory response both in brain and in periphery and suggest that dKO mice may be useful to further understand the effects of inflammation on the pathological processes of neurodegenerative diseases.

A rapid and simple analytical method was developed for the simultaneous and quantitative determination and separation of hydrophilic imidazolium ionic liquids (ILs) (1-butyl-3-methylimidazolium chloride, [C(4)mim]Cl; 1-hexyl-3-methylimidazolium chloride, [C(6)mim]Cl; 1-octyl-3-methylimidazolium chloride, [C(8)mim]Cl; 1-allyl-3-methylimidazolium chloride, [Amim]Cl; or 1-allyl-3-methylimidazolium bromide, [Amim]Br) with miscible ethyl acetate and EtOH and their mixtures using reverse phase liquid chromatography coupled with refractive index detection (RPLC-RI). The influence of 60 to 100% (volume percentage) methanol in the mobile phase on the IL systems ([C(4)mim]Cl, [C(6)mim]Cl, [C(8)mim]Cl, [Amim]Br, or [Amim]Cl)-ethyl acetate-EtOH was investigated. The optimum mobile phase for the system [C(8)mim]Cl-ethyl acetate-EtOH, [C(4)mim]Cl-ethyl acetate-EtOH, [Amim]Br-ethyl acetate-EtOH and [Amim]Cl-ethyl acetate-EtOH was methanol/water (60:40, v/v), and methanol/water (70:30, v/v) for [C(6)mim]Cl-ethyl acetate-EtOH. Under optimum mobile phase conditions for each system, the RSD of the retention time ranged from 0.02 to 0.04%, and the RSDs of the peak area percent ranged from 0.23 to 1.85%, which showed good reproducibility of the RPLC-RI method. The RPLC-RI method can determine IL, ethyl acetate, and EtOH simultaneously in 5 min, and the analytes, especially IL, can be eluted completely. The results show that the RPLC-RI method can be used to separate and determine ILs in mixtures with organic compounds simultaneously and quantitatively.