Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.

Osteosarcoma is the most common malignant bone tumor. It has a poor prognosis because of a lack of therapeutic targets and strategies. The SET domain-containing lysine-specific methyltransferase, SET7/9, has various functions in different cancer types in tissue-type and signaling context-dependent manners. The role of SET7/9 in osteosarcoma cells is currently controversial and its potential as a therapeutic candidate in osteosarcoma is unknown. In the present study, SET7/9 inhibition or ablation suppressed osteosarcoma cell proliferation by causing G1 arrest. Mechanistically, SET7/9 inhibition disrupted the interaction between cyclin-dependent kinase 4 (CDK4) and cyclin D1, which affected CDK4-cyclin D1 complex function, leading to decreased phosphorylation of retinoblastoma protein. CDK4 was overexpressed in osteosarcoma tissues and was closely related to a poor prognosis in patients with osteosarcoma. We therefore hypothesized that SET7/9 inhibition might increase the sensitivity of osteosarcoma cells to CDK4 inhibitors, potentially decreasing the risk of adverse effects of CDK4 inhibitors. The combination of SET7/9 and CDK4 inhibition enabled dose reductions of both inhibitors and had a synergistic effect against osteosarcoma growth in vivo. Collectively, these findings indicate that SET7/9 plays an oncogenic role in osteosarcoma by regulating CDK4-cyclin D1 complex interaction and function. The combination of SET7/9 and CDK4 inhibition may thus provide a novel effective therapeutic strategy for osteosarcoma with no significant toxicity.

What affects how Chinese patients wish to be involved in health care delivery? Perspectives of the Chinese policy and institutional contexts.

INTRODUCTION: The benefits of involving patients and carers include improving health outcomes and safety, reducing costs and enhancing an open, accountable and equitable relationship between service providers and users. However, the willingness for involvement and participation is largely affected by a range of factors, including those at the micro, meso and macro levels. As the previous studies have given much attention to the factors at the individual level, it is worthwhile to explore the factors at the broader levels of the policy and institutional contexts. The objective of the research is to understand how the policy and institutional contexts in China affect how patients wish to be involved in their health care delivery. METHODS: An abductive research strategy was used to generate emergent hypotheses in the first stage of data construction. In the second stage of fieldwork, hypotheses were tested using the deductive approach. Three local hospitals in Shandong Province, China, were selected. The case study method was designed with qualitative methods of policy documents and interviews. Interviews included health professionals, health board managers, local administrators and service users. Thematic analysis and framework analysis were conducted. RESULTS: Four policy and institutional contexts were identified: insufficient policy support, the current institutional design of involving users, the heterogeneity of organisational autonomy and resources, as well as the demography of the population of service users. CONCLUSIONS: As a policy strategy at the state level, there is a lack of policy support for patient involvement and participation in the Chinese health system. The heterogeneity of the institutional context of health facilities plays a key role in affecting how patients wish to be involved in health care delivery.

Girls Are Better Students but Boys Will Be More Successful at Work: Discordance Between Academic and Career Gender Stereotypes in Middle Childhood.

Despite findings of female advantages at school, men still are higher achieving in the workplace. Only a small amount of research has simultaneously investigated stereotypes of these different domains. We investigated whether stereotypes about academic female superiority and paradoxical stereotypes about workplace male superiority coexist. Participants were 1144 Grades 1-6 students (Mage = 9.66) from Hong Kong. They completed measures of academic gender stereotypes and meta-stereotypes, career gender stereotypes, career-related motivation for school excellence, and school engagement. Teachers provided school exam scores. We examined (1) gender and age differences, (2) the relationship between the stereotypes, and (3) the moderating role of these stereotypes in gender differences in school engagement, exam scores, and career-related motivation. Both boys and girls perceived girls as better students but a belief in female superiority did not translate to the career domain. Although both boys and girls beginning primary school believed their gender was superior in both domains, those at the end of primary school believed that girls do better at school while men are more successful at work. Also, at the end of primary school, these two stereotypes were more discordant on the individual level, i.e., the tendency for children who believed that girls perform better at school to also believe that women perform better at work was weaker in older children. Academic gender stereotypes moderated gender differences in school engagement and exam scores. Understanding why children hold discordant beliefs about success in different arenas and combating both academic and career stereotypes early may help improve gender equality for both genders.

Pseudo-2D Layered Organic-Inorganic Manganese Bromide with a Near-Unity Photoluminescence Quantum Yield for White Light-Emitting Diode and X-Ray Scintillator.

Eco-friendly lead-free organic-inorganic manganese halides (OIMHs) have attracted considerable attention in various optoelectronic applications because of their superior optical properties and flexible solution processibility. Herein, we report a novel pseudo-2D layered OIMH (MTP)2 MnBr4 (MTP: methyltriphenylphosphonium), which exhibits intense green emission under UV/blue or X-ray excitation, with a near-unity photoluminescence quantum yield, high resistance to thermal quenching (I150 °C =84.1 %) and good photochemical stability. These features enable (MTP)2 MnBr4 as an efficient green phosphor for blue-converted white light-emitting diodes, demonstrating a commercial-level luminous efficiency of 101 lm W-1 and a wide color gamut of 116 % NTSC. Moreover, these (MTP)2 MnBr4 crystals showcase outstanding X-ray scintillation properties, delivering a light yield of 67000 photon MeV-1 , a detection limit of 82.4 nGy s-1 , and a competitive spatial resolution of 6.2 lp mm-1 for X-ray imaging. This work presents a new avenue for the exploration of eco-friendly luminescent OIMHs towards multifunctional light-emitting applications.

Duodenal microbiota makes an important impact in functional dyspepsia.

Duodenal microbiota may have impact in Functional Dyspepsia. The aim of this study was to explore the difference of microbiota on duodenal mucosa between patients with Functional Dyspepsia and normal subjects. The duodenal mucosa of the subjects were collected under upper gastrointestinal endoscope and the contents of the descending duodenal intestine were extracted with cell brushes in 20 patients with Functional Dyspepsia and 5 healthy subjects. The microbiome on duodenal was studied by 16SrDNA gene sequencing. The differences of duodenal flora were analyzed and compared by LEfSe, FAPROTAX, SPSS and other software. There were significant differences in ACE index, shannon index and observedspecies index between patients with functional dyspepsia and healthy people (P < 0.05). PCoA analysis of the structure of bacteria between two groups found that the duodenal microbiome showed a separate trend. In further study, Amova analysis showed a significant difference (P < 0.05). We found that the there are obvious differences in the composition of duodenal microbiome in functional dyspepsia and healthy people. At the genus level, there were significant differences in Alloprevotella, Peptostreptococcus,Sutterella, Corynebacteriurn,Catonella, Faecalibacterium,Staphylococcus,Eubacteriumnodatumgro-up, Lachnoclostridiurn and Lautropia between the two groups (P < 0.05). The prediction results of Microflora function from FAPROTAX showed that the urea decomposing (ureolysis) and fumaric acid respiratory (fumaraterespiration) function of duodenal bacteria in patients with functional dyspepsia were significantly different from those in healthy people (P < 0.05). In conclusion, there is a significant difference in mucosal microflora of duodenum between patients with functional dyspepsia and healthy groups. It includes greater microflora diversity, different microflora structure, different microflora composition, specific taxa and specific microbiome function. The disorder of duodenal microecology may be the formation mechanism of functional dyspepsia.

Toward high-power-density laser-driven lighting: enhancing heat dissipation in phosphor-in-glass film by introducing h-BN.

In this work,  hexagonal boron nitride (h-BN) nanocrystals as functional additives in a phosphor-in-glass film are shown to substantially increase the luminous performance driven by a blue laser. Microstructural and spectroscopic studies reveal that h-BN particles distributed over the whole glass matrix build in situ a local heat conductive path which effectively accelerates heat dissipation and so greatly relieves the "thermal run-away effect". The developed composite material with fine thermal manipulation may be a promising phosphor color converter for high-power-density laser-driven lighting.

Visualisation of the vomerovaginal canal during endonasal transpterygoid approaches and CT imaging diagnosis.

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.

Early Gender Differences in Spatial and Social Skills and Their Relations to Play and Parental Socialization in Children from Hong Kong.

Children's play preferences are highly gender-typed. At the same time, much research revolves around spatial and social skills that sometimes show male and female advantages, respectively. There is evidence that play with masculine toys is associated with better spatial skills and emerging evidence suggests that play with feminine toys is associated with better social skills. However, several research gaps limit current knowledge on these aspects of gender development. First, the study of childhood gender development has been largely Eurocentric; second, the link between gender-typed play and social skills development is not well supported. We tested 644 5-year-old Hong Kong Chinese children on five gender-typed skills, play preferences, and parental gender socialization. The pattern of gender differences was remarkably similar to those in the West. Boys preferred masculine toys more than girls and were better at mental transformation and targeting accuracy, while girls preferred feminine (and neutral) toys more than boys and were better at empathy and were less aggressive, although there was no significant gender difference in comforting skill. There was little evidence that these gender differences varied with socioeconomic status (parental income and education). Play correlated with some outcomes in expected ways. This is in contrast to parents' gender socialization, which showed some expected differences by child gender but minimally correlated with children's skills. These findings shed light on the generalizability of current knowledge on early gender differences and may facilitate gender developmental research outside the West. Although the study did not test the direction of effects, they substantiate the growing discourse on gender-typed play as an important learning mechanism.

Expression of Cytosolic Phospholipase A2 (cPLA2)-Arachidonic Acid (AA)-Cyclooxygenase-2 (COX-2) Pathway Factors in Lung Cancer Patients and Its Implication in Lung Cancer Early Detection and Prognosis.

BACKGROUND The aim of this study was to elucidate the involvement of cPLA2-AA-COX-2 pathway factors and their potential role in lung cancer early diagnosis and prognosis. MATERIAL AND METHODS We selected 80 lung cancer patients as the cancer group, and 30 normal patients were selected as the normal group. Serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 were measured, and mRNA levels of COX-2, cPLA2, COX-1, and mPGES in serum were determined. Spearman's P-test was used to analyze the correlation between expression of PGI2 and mPGES in serum and the clinical characteristics of these lung cancer patients. The factors affecting the prognosis lung cancer were analyzed by COX regression model. RESULTS The serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 in the cancer patient group were significantly higher (p<0.05) than in the normal group; after treatment, the serum contents of these factors were significantly decreased (p<0.05). However, distant metastasis had a significant effect on serum contents of mPGES and PGI2 (p<0.05), but not on the other factors. The mRNA levels of COX-2, cPLA2, COX-1, and mPGES in cancer patients were significantly higher than in normal patients. In addition, the 5-year survival rate of patients with high expression of mPGES and/or PGI2 was lower than that of the low expression group. Cox regression analysis showed that the expression of mPGES and PGI2 had statistical significance in predicting the prognosis of lung cancer. CONCLUSIONS The cPLA2-AA-COX-2 pathway is closely associated with lung cancer. These findings are important for clinical diagnosis of lung cancer.

Synthesis, Spectroscopic Study and Radical Scavenging Activity of Kaempferol Derivatives: Enhanced Water Solubility and Antioxidant Activity.

Kaempferol (Kae) is a natural flavonoid with potent antioxidant activity, but its therapeutic use is limited by its low aqueous solubility. Here, a series of Kae derivatives were synthesized to improve Kae dissolution property in water and antioxidant activity. These compounds included sulfonated Kae (Kae-SO3), gallium (Ga) complexes with Kae (Kae-Ga) and Kae-SO3 (Kae-SO3-Ga). The compound structures were characterized by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy and thermal methods (TG/DSC). The results showed that a sulfonic group (-SO3) was successfully tethered on the C3' of Kae to form Kae-SO3. And in the metal complexation, 4-CO and 3-OH of the ligand participated in the coordination with Ga(III). The metal-to-ligand ratio 1:2 was suggested for both complexes. Interestingly, Kae-SO3-Ga was obviously superior to other compounds in terms of overcoming the poor water-solubility of free Kae, and the solubility of Kae-SO3-Ga was about 300-fold higher than that of Kae-Ga. Furthermore, the evaluation of antioxidant activities in vitro was carried out for Kae derivatives by using α,α-diphenyl-ß-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging. The results showed that Kae-SO3-Ga was also optimal for scavenging free radicals in a dose-dependent manner. These data demonstrate that sulfonate kaempferol-gallium complex has a promising future as a potential antioxidant and as a potential therapeutic agent for further biomedical studies.

Emergence of the Asian lineage dengue virus type 3 genotype III in Malaysia.

BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally. RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5-553I/M, NS5-629 T, and NS5-820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013. CONCLUSIONS: Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.

Neuropeptide imaging in rat spinal cord with MALDI-TOF MS: Method development for the application in pain-related disease studies.

Spinal cord as a connection between brain and peripheral nervous system is an essential material for studying neural transmission, especially in pain-related research. This study was the first to investigate pain-related neuropeptide distribution in rat spinal cord using a matrix-assisted laser desorption ionization-time of flight imaging mass spectrometry (MALDI TOF MS) approach. The imaging workflow was evaluated and showed that MALDI TOF MS provides efficient resolution and robustness for neuropeptide imaging in rat spinal cord tissue. The imaging result showed that in naive rat spinal cord the molecular distribution of haeme, phosphatidylcholine, substance P and thymosin beta 4 were well in line with histological features. Three groups of pain-related neuropeptides, which are cleaved from prodynorphin, proenkephalin and protachykinin-1 proteins were detected. All these neuropeptides were found predominantly localized in the dorsal spinal cord and each group had unique distribution pattern. This study set the stage for future MALDI TOF MS application to elucidate signalling mechanism of pain-related diseases in small animal models.

Enzymatic Process Enhances the Flavour Profile and Increases the Proportion of Esters in Citrus Essential Oils.

Citrus essential oils (CEOs) are important flavors in the food and confectionary industries. A lipase process was proposed for enhancing the flavor profiles and increasing the proportions of esters in CEOs. The effects of the enzymatic process were explored by detecting the constituents of the CEOs of American sweet orange oil (ASO) and Brazil mandarin oil (BMO) through GC/MS and sensory evaluation by a trained panel, and positive effects were confirmed by both methods. A further eleven kinds of CEOs were treated via the lipase process and increments of 10 - 1170% were achieved in the proportions of esters, which were mostly ethyl esters. Enhancement in fruity odor, especially the top note, was demonstrated by all CEOs after enzymatic processing. All CEOs were tested for antimicrobial activities, and only ASO displayed fairly ideal antimicrobial activities. Meanwhile, modified ASO showed a certain increase in antimicrobial activities. This methodology might be considered a sustainable route for acquiring 'natural' essential oils with enhanced flavor profiles and simultaneously enhancing the comprehensive utilization of citrus fruits.

Improving the catalytic characteristics of lipase-displaying yeast cells by hydrophobic modification.

Lipase-displaying yeast cells are a promising alternative to the conventional immobilised lipases for organic bioconversions. However, the hydrophilic characteristics of the yeast cell surface may impede efficient immobilisation. Herein, we tested three methods to enhance the hydrophobicity of the surface of Candida antarctica lipase B-displaying Pichia pastoris cells, co-displaying a fungal hydrophobin, coating with ionic liquids, and adding decane as a hydrophobic carbon source during fermentation. Modified cells showed higher surface hydrophobicity and superior esterification of C6-C18 saturated fatty acids in hydrophobic solvents. When used for biodiesel synthesis, modified cells exhibited an improved initial reaction rate and equilibrium fatty acid methyl ester yield. We systematically discuss the influence of cell surface hydrophobicity on the catalytic properties, and the results provide guidance for improving the catalytic efficiency and operational characteristics of lipase-displaying yeast cells for organic bioconversions.

Robust Dehaze Algorithm for Degraded Image of CMOS Image Sensors.

The CMOS (Complementary Metal-Oxide-Semiconductor) is a new type of solid image sensor device widely used in object tracking, object recognition, intelligent navigation fields, and so on. However, images captured by outdoor CMOS sensor devices are usually affected by suspended atmospheric particles (such as haze), causing a reduction in image contrast, color distortion problems, and so on. In view of this, we propose a novel dehazing approach based on a local consistent Markov random field (MRF) framework. The neighboring clique in traditional MRF is extended to the non-neighboring clique, which is defined on local consistent blocks based on two clues, where both the atmospheric light and transmission map satisfy the character of local consistency. In this framework, our model can strengthen the restriction of the whole image while incorporating more sophisticated statistical priors, resulting in more expressive power of modeling, thus, solving inadequate detail recovery effectively and alleviating color distortion. Moreover, the local consistent MRF framework can obtain details while maintaining better results for dehazing, which effectively improves the image quality captured by the CMOS image sensor. Experimental results verified that the method proposed has the combined advantages of detail recovery and color preservation.

Synthesis, characterization and anticancer activity of kaempferol-zinc(II) complex.

According to the previous studies, the anticancer activity of flavonoids could be enhanced when they are coordinated with transition metal ions. In this work, kaempferol-zinc(II) complex (kaempferol-Zn) was synthesized and its chemical properties were characterized by UV-VIS, FT-IR, (1)H NMR, elemental analysis, electrospray mass spectrometry (ES-MS) and fluorescence spectroscopy, which showed that the synthesized complex was coordinated with a Zn(II) ion via the 3-OH and 4-oxo groups. The anticancer effects of kaempferol-Zn and free kaempferol on human oesophageal cancer cell line (EC9706) were compared. MTT results demonstrated that the killing effect of kaempferol-Zn was two times higher than that of free kaempferol. Atomic force microscopy (AFM) showed the morphological and ultrastructural changes of cellular membrane induced by kaempferol-Zn at subcellular or nanometer level. Moreover, flow cytometric analysis indicated that kaempferol-Zn could induce apoptosis in EC9706 cells by regulating intracellular calcium ions. Collectively, all the data showed that kaempferol-Zn might be served as a kind of potential anticancer agent.

[Analysis of Animal Modeling Methods for Functional Dyspepsia].

Functional dyspepsia (FD) is a common disease in clinics. It is necessary to establish suitable animal models for clarifying the pathogenesis of FD. FD belongs to "Piman" (abdominal disten- sion) , "Weiwantong" (epigastric pain) , "Caoza" (epigastric upset) in Chinese medicine (CM). It is inor- ganic disease but functional disease. There is no unified standard for FD animal models. Pi deficiency syndrome model is often used as FD animal model now, but they are not completely the same thing. Au- thors summarized and analyzed common methods for FD modeling.

Imipenem Treatment Induces Expression of Important Genes and Phenotypes in a Resistant Acinetobacter baumannii Isolate.

Acinetobacter baumannii has emerged as a notorious multidrug-resistant pathogen, and development of novel control measures is of the utmost importance. Understanding the factors that play a role in drug resistance may contribute to the identification of novel therapeutic targets. Pili are essential for A. baumannii adherence to and biofilm formation on abiotic surfaces as well as virulence. In the present study, we found that biofilm formation was significantly induced in an imipenem-resistant (Imp(r)) strain treated with a subinhibitory concentration of antibiotic compared to that in an untreated control and an imipenem-susceptible (Imp(s)) isolate. Using microarray and quantitative PCR analyses, we observed that several genes responsible for the synthesis of type IV pili were significantly upregulated in the Imp(r) but not in the Imp(s) isolate. Notably, this finding is corroborated by an increase in the motility of the Imp(r) strain. Our results suggest that the ability to overproduce colonization factors in response to imipenem treatment confers biological advantage to A. baumannii and may contribute to clinical success.

Proteomics of neuropathic pain: proteins and signaling pathways affected in a rat model.

The myriad proteins may be involved in the mechanisms underlying the development and maintenance of neuropathic pain, an extremely disabling condition that originates from pathology of the nervous system. To address the mechanisms, we here analyzed proteins and cellular networks in the dorsal spinal cord mediating pain processing in a well-established rat model of neuropathic pain induced by spinal nerve ligation (SNL). Labeling-based proteomic methods together with high-resolution mass spectrometry for proteome analysis were applied. 38 proteins including synapsin 1 and microtubule-associated protein 2 were identified as differently expressed in the SNL group. Pathway analysis suggests that maladaptive changes in the levels of these proteins may contribute to abnormal synaptic transmission and neuronal intracellular signaling underlying the onset and development of neuropathic pain.

Quantification analysis of yeast-displayed lipase.

We describe a method for quantification of displayed lipase on yeast cell surface. The strategy uses an organophosphonate ester to irreversibly inhibit the active lipase and release a detectable fluorescent group. The amount of displayed lipase can be represented as "g/g cell" or "molecules/cell". The results obtained correlated well with those obtained by existing methods. Therefore, this method is credible and will provide a powerful tool to promote research of lipase yeast surface display.