Down-regulation of kappa opioid receptor promotes ESCC proliferation, invasion and metastasis via the PDK1-AKT signaling pathway.

BACKGROUND: As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism. METHODS: Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway. RESULTS: Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR. CONCLUSION: KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype. Video Abstract.

Adipose induces myoblast differentiation and mediates TNFα-regulated myogenesis.

Skeletal muscle formation is controlled by multiple processes. These processes are tightly regulated by muscle regulatory factors. Genes that are highly and specifically expressed during myogenesis need to be identified. In the present study, the role of an anti-adipogenic gene adipose (Adp) in myogenesis is demonstrated. We discover that the expression of Adp is increased during myoblast differentiation. Overexpression of Adp in mouse myoblast C2C12 cells leads to an increase of myogenesis and up-regulation of MyoG expression. The inhibition effect of tumor necrosis factor α (TNFα) on myogenic differentiation is reversed by Adp-overexpression. Further research showed that TNFα significantly decreases Adp expression at both the mRNA and protein levels. Luciferase reporter assays showed that TNFα can inhibit Adp gene promoter activity and impair gene transcription. KLF15 was found to regulate the transcription of Adp. Furthermore, the expression of KLF15 and its binding to Adp promoter were reduced due to TNFα treatment. The reduced KLF15 expression after TNFα treatment is responsible for the repression of Adp gene promoter activity. KLF15 was also found to participate in Adp-mediated myogenic differentiation. Taken together, these data identify Adp as a positive modulator of myoblast differentiation and provide new insights for Adp function research.

Evaluating the efficacy of Tui Na in treatment of childhood anorexia: a meta-analysis.

CONTEXT: Medical practitioners are now seeing more children younger than 15 y who are developing childhood anorexia. Hua Tuo chiropractic treatments are an ancient and practical massage therapy and are a type of Tui Na therapy, which has been used for curing childhood anorexia for thousands of years in China. Research literature suggests that chiropractic care produces outcomes at least comparable with alternative treatments. OBJECTIVE: The research team intended to perform a systematic review to identify and synthesize evidence on the efficacy of Tui Na for treatment of childhood anorexia. DESIGN: Systematic searches were conducted for studies evaluating Tui Na therapy in electronic databases MEDLINE, EMBASE, PsychINFO, the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, the Midwives Information and Resource Service, the Health Management Information Consortium, the Health Management and Information Service, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature Database (CBM), the Chinese Scientific Journal Database VIP, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Chinese Clinical Trial Register-from inception to November 2011. The research team hand-searched reference lists and journals, extracted data from the papers, and assessed the quality of the research. PARTICIPANTS: Participants of the reviewed studies were infants and children younger than 15 y. RESULTS: Of the 109 papers identified, 3 papers reported on randomized, controlled trials (RCTs) involving 332 patients; 45 covered cohort or quasi-experimental studies; and 61 discussed nonintervention studies. Meta-analysis results from the 3 RCTs showed that Tui Na can improve the curative effect compared with oral medicine that is used for infants and young children with anorexia and can also increase a child's weight. CONCLUSIONS: The level of evidence reported was mixed, but given the available evidence, the research team concluded that Tui Na therapy was a viable intervention that could benefit infants and young children with anorexia. No serious adverse events were reported. Larger randomized, controlled trials are required to explore the effects of Tui Na therapy for treatment of childhood anorexia further.

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates. METHODS: Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points. RESULTS: The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2-E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1-E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point. CONCLUSIONS: Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.

Molecular phylogenetic evidence for paraphyly of Ceratovacuna and Pseudoregma (Hemiptera, Hormaphidinae) reveals late Tertiary radiation.

Ceratovacuna and Pseudoregma are important groups in Cerataphidini (Hemiptera, Hormaphidinae) that not only produce soldier aphids in galls on the primary hosts but also produce horned soldiers on the herbaceous secondary hosts. However, due to sampling bias in previous studies, the phylogenetic relationships of these two genera remain inconclusive. In this study, based on more extensive sampling and examination of both mitochondrial (cytochrome c oxidase subunit I (COI); cytochrome b (Cytb)) and nuclear (elongation factor-1α (EF-1α); long-wavelength opsin (LWO)) genes, we reconstructed the phylogenetic relationships of Ceratovacuna and Pseudoregma. Phylogenetic analyses, along with morphological evidence, suggested that these two genera belong to the paraphyletic groups with species clustered into three main groups. The monophyly of Ceratovacuna and Pseudoregma as a whole was generally supported by all analyses. Monophyly of Pseudoregma was also supported. The estimated divergence times demonstrated that diversification of Ceratovacuna and Pseudoregma occurred approximately at 10 mya. The relatively low resolution for the basal relationships of the three main clades may indicate that these two genera have experienced a rapid radiation along with speciation burst of their secondary hosts during the late Tertiary.

Tetra-aqua-bis-(6-chloro-pyridine-3-carboxyl-ato-κO)nickel(II) tetra-hydrate.

In the title compound, [Ni(C(6)H(3)ClNO(2))(2)(H(2)O)(4)]·4H(2)O, the Ni(II) ion is located on an inversion centre and is octa-hedrally coordinated by four O atoms from four water mol-ecules in the equatorial plane and two O atoms of two 6-chloro-3-carboxyl-ate ligands in axial positions. There are also four lattice water molecules present. The organic ligands are bound to the Ni(II) ion in a monodentate manner through a carboxyl-ate O atom. There is one strong intra-molecular O-H⋯O hydrogen bond and six inter-molecular O-H⋯O and O-H⋯N hydrogen-bonding inter-actions in the packing, resulting in a complex three-dimensional network structure.

Tetra-aqua-bis-(6-chloro-pyridine-3-carboxyl-ato-κO)cobalt(II) tetra-hydrate.

In the title compound, [Co(C(6)H(3)ClNO(2))(2)(H(2)O)(4)]·4H(2)O, the Co(II) cation is located on an inversion center and is coordinated by four water mol-ecules and two 6-chloro-pyridine-3-carboxyl-ate anions in a slightly distorted octa-hedral geometry. In the crystal, complex mol-ecules and lattice water mol-ecules are linked by O-H⋯O and O-H⋯N hydrogen bonds into a three-dimensional network.

catena-Poly[[[diaqua-copper(II)]-µ-quinoline-2,3-dicarboxyl-ato-κ(3)N,O(2):O(3)] monohydrate].

In the title compound, {[Cu(C(11)H(5)NO(4))(H(2)O)(2)]·H(2)O}(n), the Cu(II) ion is five-coordinated by two O atoms and one N atom of two symmetry-related quinoline-2,3-dicarboxyl-ate ligands, and two water mol-ecules. The water mol-ecules occupy basal and apical positions of the square-pyramidal coordination polyhedron. Each quinoline-2,3-dicarboxyl-ate dianion bridges two adjacent Cu(II) ions, forming a polymeric chain along [010]. The chains are further connected via O-H⋯O hydrogen-bonding inter-actions and quinoline ring π-π inter-actions [centroid-centroid distance = 3.725 (4) Å], generating a three-dimensional structure. Lattice water mol-ecules participate in the crystal structure via O-H⋯O hydrogen bonds.

Surgical resection of chemotherapy-insensitive pulmonary metastases in children with hepatoblastoma in China: A single-center experience.

Objective: The objective of this study is to investigate the operation timing, methods, and outcome of pulmonary metastases of hepatoblastoma (HB) in children. Methods: The clinical and follow-up data of 53 children with pulmonary metastases of HB that were admitted to our hospital from January 2012 to December 2018 were retrospectively analyzed. The pediatric patients, 36 male and 17 female, aged 13-124 months with the median age of 41 months, and all underwent routine thoracotomy. Results: In the 53 cases, 77 lung metastatic tumors were resected. Further, 37 patients received only one operation, 10 received two operations, 4 received 3 operations, and 2 received 4 operations. Based on Kaplan-Meier analysis, the accumulative overall survival (OS) rates at 1, 3, and 5 years were 86.8%, 69.0%, and 57.0%, respectively (median OS time: 60 months; 95% CI: 50.675-69.709 months), and accumulative EFS (vent-free survival) rates at 1, 3, and 5 years were 86.8%, 67.0%, and 55.4%, respectively (median EFS time: 59 months; 95% CI: 49.519-68.578 months). According to univariate analysis, OS was significantly altered for patients with no more than 5 nodules (p = 0.023), lung metastases without extrapulmonary metastases (p = 0.000), and laterality (p = 0.029). Gender and age (less than three years) were not significantly related to survival. According to univariate analysis, lung metastases with extrapulmonary metastases could be considered as individual factor contributing to poorer prognosis. Conclusion: In this pediatric group, patients with residual nodules after chemotherapy of HB could benefit from surgical treatment, but the appropriate surgical indication of metastasectomy needs to be further investigated.

Green and Rapid Preparation of Fluorosilicone Rubber Foam Materials with Tunable Chemical Resistance for Efficient Oil-Water Separation.

Polydimethylsiloxane (PDMS) foam materials with lightweight, excellent oil resistance and mechanical flexibility are highly needed for various practical applications in aerospace, transportation, and oil/water separation. However, traditional PDMS foam materials usually present poor chemical resistance and easily swell in various solvents, which greatly limits their potential application. Herein, novel fluorosilicone rubber foam (FSiRF) materials with different contents of trifluoropropyl lateral groups were designed and fabricated by a green (no solvents used) and rapid (<10 min foaming process) foaming/crosslinking approach at ambient temperature. Typically, vinyl-terminated poly(dimethyl-co-methyltrifluoropropyl) siloxanes with different fluorine contents of 0−50 mol% were obtained through ring-opening polymerization to effectively adjust the chemical resistance of the FSiRFs. Notably, the optimized FSiRF samples exhibit lightweight (~0.25 g/cm−3), excellent hydrophobicity/oleophilicity (WCA > 120°), reliable mechanical flexibility (complete recovery ability after stretching of 130% strain or compressing of >60%), and improved chemical resistance and structural stability in various solvents, making them promising candidates for efficient and continuous oil−water separation. This work provides an innovative concept to design and prepare advanced fluorosilicone rubber foam materials with excellent chemical resistance for potential oil−water separation application.

Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations.

Toxoplasmosis, an infectious zoonotic disease caused by the apicomplexan parasite Toxoplasma gondii (T. gondii), is a major worldwide health problem. However, there are currently no effective options (chemotherapeutic drugs or prophylactic vaccines) for treating chronic latent toxoplasmosis infection. Accordingly, seeking more effective and safer chemotherapeutics for combating this disease remains a long-term and challenging objective. In this paper, we summarize possible molecular biotargets, with an emphasis on those that are druggable and promising, including, without limitation, calcium-dependent protein kinase 1, bifunctional thymidylate synthase-dihydrofolate reductase, and farnesyl diphosphate synthase. Meanwhile, as important components of medicinal chemistry, the binding modes and structure-activity relationship profiles of the corresponding inhibitors were also illuminated. We anticipate that this information will be helpful for further identification of more effective chemotherapeutic interventions to prevent and treat zoonotic infections caused by T. gondii.

Ultrafast Flame-Induced Pyrolysis of Poly(dimethylsiloxane) Foam Materials toward Exceptional Superhydrophobic Surfaces and Reliable Mechanical Robustness.

Superhydrophobic surfaces are imperative in flexible polymer foams for diverse applications; however, traditional surface coatings on soft skeletons are often fragile and can hardly endure severe deformation, making them unstable and highly susceptible to cyclic loadings. Therefore, it remains a great challenge to balance their mutual exclusiveness of mechanical robustness and surface water repellency on flexible substrates. Herein, we describe how robust superhydrophobic surfaces on soft poly(dimethylsiloxane) (PDMS) foams can be achieved using an extremely simple, ultrafast, and environmentally friendly flame scanning strategy. The ultrafast flame treatment (1-3 s) of PDMS foams produces microwavy and nanosilica rough structures bonded on the soft skeletons, forming robust superhydrophobic surfaces (i.e., water contact angles (WCAs) > 155° and water sliding angles (WSAs) < 5°). The rough surface can be effectively tailored by simply altering the flame scanning speed (2.5-15.0 cm/s) to adjust the thermal pyrolysis of the PDMS molecules. The optimized surfaces display reliable mechanical robustness and excellent water repellency even after 100 cycles of compression of 60% strain, stretching of 100% strain, and bending of 90° and hostile environmental conditions (including acid/salt/alkali conditions, high/low temperatures, UV aging, and harsh cyclic abrasion). Moreover, such flame-induced superhydrophobic surfaces are easily peeled off from ice and can be healable even after severe abrasion cycles. Clearly, the flame scanning strategy provides a facile and versatile approach for fabricating mechanically robust and surface superhydrophobic PDMS foam materials for applications in complex conditions.

Resistin Activates p65 Pathway and Reduces Glycogen Content through Keratin 8.

Resistin is associated with metabolic syndrome and inflammatory conditions. Many studies have suggested that resistin inhibits the accumulation of glycogen; however, the exact mechanisms of resistin-induced decrease in glycogen content remain unclear. Keratin 8 is a typical epithelial intermediate filament protein, but numerous studies suggest a vital role of K8 in glucose metabolism. However, it is still not known whether K8 participates in the mediation of resistin-induced reduction of cellular glycogen accumulation. In this study, we found that resistin upregulated expression of the p65 subunit of NF-κB, which led to the promotion of K8 transcriptional expression; in turn, the expression of K8 inhibited glycogen accumulation in HepG2 cells.

Temperature-triggered sensitive resistance transition of graphene oxide wide-ribbons wrapped sponge for fire ultrafast detecting and early warning.

Fire prevention and safety of combustible materials is a global challenge. To reduce their high fire risk, traditional smoke detectors are widely used indoor via detecting smoke product after combustion; however, they usually show a long response time and limitation for outdoor use. Herein, we report a temperature-induced electrical resistance transition of graphene oxide wide-ribbon (GOWR) wrapped sponges to reliably monitor fire safety of the combustible materials. Novel rectangle-like GOWR sheets are synthesized from unzipping carbon nanofibers and used to fabricate GOWR wrapped melamine formaldehyde sponges with multi-functionalities, e.g. lightweight, good hydrophobicity, reversible compressibility, excellent acidic/alkaline tolerance and flame resistance. The GOWR sheets on the sponge skeleton can be in-situ thermally reduced once encountering a flame attack or abnormal high temperature, inducing a distinct transition in electrical resistance. Consequently, an ultrafast alarm response of ∼2 s to flame attack is triggered, and rapid fire early warning signals to abnormal high temperatures, e.g. ∼33 s at 300 °C, are achieved below ignition temperature of most combustible materials. This method drives substantial motivation and opportunity to develop advanced fire detection and early warning sensors for reducing the high fire risk of various combustible materials in outdoor applications.

Prevalence of migraine in Han Chinese of Fujian province: An epidemiological study.

Migraine is a relatively common disease that is associated with high disability and reduced quality-of-life. This study aimed to investigate the prevalence, epidemiological characteristics, and risk factors of migraine in Han Chinese from Fujian Province, China.A cross-sectional epidemiological survey study was conducted to evaluate characteristics of migraine in Han Chinese. Demographic and clinical data were collected through a survey administered in face-to-face interviews by trained investigators, and a physical exam and symptom review were performed. Univariate and multivariate regression analyses were performed to assess independent risk factors for migraine.A total of 7860 subjects aged 15 years and older were surveyed, of which 9.1% (n = 717) were diagnosed with migraine. Among these, a higher percentage was female (12.6%) than male (5.3%). Only 114 subjects (15.9%) were diagnosed as having migraine with aura, which was closely associated with family history of migraine. Multivariate regression analysis showed that the odds of migraine were significantly lower in subjects aged ≥50 years compared with those aged <30 years (odds ratio [OR] ranged from 0.40 to 0.64; P ≤.013) and was higher in females compared with males (OR = 2.89, P <.001). The odds of migraine was significantly greater in subjects with a history of alcohol consumption (OR = 1.81, P <.00) and insomnia (OR = 2.77, P <.001).Han Chinese in Fujian province has a relatively high prevalence of migraine, and female gender, <50 years of age, insomnia, and use of alcohol are associated with increased odds of having migraine in this population.

A novel luminescence-functionalized metal-organic framework nanoflowers electrochemiluminesence sensor via "on-off" system.

A novel solid-state electrochemiluminesence (ECL) "on-off" switch system for highly sensitive detection of tryptophan based on the luminescence-functionalized ruthenium metal-organic framework (Ru-MOF) nanoflowers and CdS quantum dots (CdSQDs) was described. Ru-MOF nanoflowers were prepared by a one-step solvothermal method at low temperature and characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared (FTIR) spectra and fluorescence (FL) spectra. For potential applications, the Ru-MOF nanoflowers were used to fabricate an ECL "on-off" switch sensor with CdSQDs for the detection of tryptophan enantiomers by quenching effect. Meanwhile the functionalized fullerene nanoparticles were used to enhance signal intensity. Furthermore, the stepwise modified process was investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The proposed ECL sensor had a wide linear range from 1.0 nM to 1.0mM with a lower detection limit of 0.33nM for tryptophan enantiomers. This method was simple to prepare, fast to operate, with good sensitivity and excellent stability for the development of efficient and practical ECL sensors.

Chiral recognition of penicillamine enantiomers using hemoglobin and gold nanoparticles functionalized graphite-like carbon nitride nanosheets via electrochemiluminescence.

A new stable and stereo-selective electrochemiluminescence (ECL) interface has been designed for specific recognition of penicillamine (Pen) enantiomers by using hemoglobin (Hb) and gold nanoparticles functionalized graphite-like carbon nitride nanosheets composite (Au-g-C3N4 NHs) modified glassy carbon electrodes (Hb/Au-g-C3N4/GCE). The advantages of Hb as chiral selector and Au-g-C3N4 NHs as luminophore were perfectly displayed in this novel interface. The obviously different ECL intensity was exhibited after l-Pen and d-Pen adsorbed on Hb/Au-g-C3N4/GCE, and a larger response was observed on d-Pen/Hb/Au-g-C3N4/GCE. Under the optimum conditions, the developed ECL chiral sensor showed excellent analytical property for detection of Pen enantiomers in a linear range of 1.0×10-4M to 5.0×10-3M, and the detection limits of l-Pen and d-Pen were 3.1×10-5M and 3.3×10-5M (S/N=3) respectively. This work with high selectivity, stability and reproducibility may open a new door based on ECL to discriminate Pen enantiomers.

Design, synthesis, biological evaluation and molecular docking study on peptidomimetic analogues of XK469.

XK469 is identified as a potent quinoxaline antineoplastic agent based on its significant clinical efficacy. It probably exerts its activity via DNA topoisomerase II (topo II) inhibition. To obtain more effective antineoplastic agents, a spectrum of peptidomimetic-type quinoxaline analogues of XK469 was herein designed, synthesized, and evaluated. Few compounds (e.g. 13a and 13b) exhibited obvious cytotoxicity indicated by in vitro anti-proliferative assay. SAR investigation revealed that introducing of hydrophobic tert-butylamine or dodecylamine moiety at the 3-position of quinoxaline core is favorable for achieving a better anti-proliferative potency, while peptidomimetic derivatives only yielded moderate cytotoxicity. Compounds with improved anti-proliferative activities also demonstrated decent anti-metastatic potencies comparable with that of doxorubicin (Doxo) based on in vivo mouse model study. The topo II-mediated kinetoplast DNA (kDNA) decatenation assay as well as molecular docking studies implicated that these compounds tend to be potent topo II inhibitors. Overall, compounds 13a and 13b, 13b in particular, standed out from various assessments and might be promising candidates for further chemical optimization.

Chemometric strategy for automatic chromatographic peak detection and background drift correction in chromatographic data.

Peak detection and background drift correction (BDC) are the key stages in using chemometric methods to analyze chromatographic fingerprints of complex samples. This study developed a novel chemometric strategy for simultaneous automatic chromatographic peak detection and BDC. A robust statistical method was used for intelligent estimation of instrumental noise level coupled with first-order derivative of chromatographic signal to automatically extract chromatographic peaks in the data. A local curve-fitting strategy was then employed for BDC. Simulated and real liquid chromatographic data were designed with various kinds of background drift and degree of overlapped chromatographic peaks to verify the performance of the proposed strategy. The underlying chromatographic peaks can be automatically detected and reasonably integrated by this strategy. Meanwhile, chromatograms with BDC can be precisely obtained. The proposed method was used to analyze a complex gas chromatography dataset that monitored quality changes in plant extracts during storage procedure.