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Sitravatinib, also called MGCD516 or MG-516, is a broad-spectrum tyrosine kinase inhibitor (TKI) under phase III clinical evaluation. Herein, we explored the activity of sitravatinib toward multidrug resistance (MDR) by emphasizing its inhibitory effect on ATP-binding cassette super-family G member 2 (ABCG2). ABCG2 is a member of ATP-binding cassette (ABC) transporter family and plays a critical role in mediating MDR. Sitravatinb received an outstanding docking score for binding to the human ABCG2 model (PDB code: 6ETI) among thirty screened TKIs. Also, an MTT assay indicated that sitravatinib at 3 μM had the ability to restore the antineoplastic effect of various ABCG2 substrates in both drug-selected and gene-transfected ABCG2-overexpressing cell lines. In further tritium-labeled mitoxantrone transportation study, sitravatinib at 3 μM blocked the efflux function mediated by ABCG2 and as a result, increased the intracellular concentration of anticancer drugs. Interestingly, sitravatinib at 3 μM altered neither protein expression nor subcellular localization of ABCG2. An ATPase assay demonstrated that ATPase activity of ABCG2 was inhibited in a concentration-dependent manner with sitravatinib; thus, the energy source to pump out compounds was interfered. Collectively, the results of this study open new avenues for sitravatinib working as an ABCG2 inhibitor which restores the antineoplastic activity of anticancer drugs known to be ABCG2 substrates.

Supplemental Digital Content is available in the text, To study the effects of Tui Na therapy on patients with mammary gland hyperplasia. A total of 68 female patients with mammary gland hyperplasia were included in this retrospective study from May 2016 to May 2017 and assigned into control group (N = 34) treated with Rupixiao only (a proprietary Chinese medicine) or Tui Na group (N = 34) treated with Tui Na (Chinese massage) combined with Rupixiao. The pain intensity (visual analogous scale, VAS) and serum levels of luteinizing hormone (LH), estradiol (E2), prolactin (PRL), and progesterone (P) were examined before and after the treatment. The efficacies were 94.1% (32/34) in the Tui Na group and 76.5% (26/34) in the control group (P = .04). After treatment, VAS in Tui Na groups was significantly lower than that in control group (2.1 ± 1.1 vs 3.1 ± 1.1, P

The clinical outcome of oral squamous cell carcinoma (OSCC) has not improved in recent years, mainly due to the limited effective targeted therapy that has been applied. Recently, a transcriptional coactivator, YAP, has been shown to have a key regulatory role in malignant progression in multiple cancers, including OSCC. But pharmacologically targeting YAP or the Hippo pathway, which is the main signaling pathway regulating YAP, has been proven to be challenging. Therefore, uncovering YAP upstream regulators in cancer would identify novel therapeutic targets for treatment of YAP-sustained cancers. Here, we showed that YAP was overactivated in OSCC and that high YAP activity in patients with OSCC was associated with malignant progression and poor survival. We uncovered that GPR39 (a G protein–coupled receptor) was overexpressed in OSCC, that the expression level of GPR39 was correlated with the activity level of YAP, and that the high GPR39 expression was associated with malignant progression and poor survival in patients with OSCC. Moreover, we found that GPR39 regulated YAP through a Gαq/11-RhoA–dependent signaling pathway. Importantly, inhibition of GPR39 resulted in YAP-sustained OSCC growth inhibition. Our findings suggest that GPR39 is a potential therapeutic target for OSCC treatment with itself as a biomarker.

BackgroundExtraovarian Brenner tumors (EOBTs) are extremely rare and can be observed incidentally in both female and male patients, raising concerns regarding the origin of Brenner tumors.Case presentationA 53-year-old postmenopausal woman presented with a nodular lesion in the left side of the corpus uteri, which was found at a routine health check. Macroscopically, the lesion appeared as a solid nodule with a yellowish-gray cut surface, approximately 6 cm in greatest diameter. Microscopically, the lesion consisted of well-defined epithelial nests and spindled stromal cells. Parenchymal cells expressed CK7, GATA3, CK5/6, 34βE12, and p63. A single layer of cavity-lined cells with umbrella-like shape showed apical Uroplakin III positivity. Stromal cells were positive for SMA, ER, and PR. The final diagnosis was EOBT and the patient was followed for 2 months with no recurrence.ConclusionsWe report here the third case of EOBTs in the uterus. The combination of morphologic and immunohistochemical results supported the involvement of urothelial metaplasia in the development of EOBTs. The similarities between EOBTs and Walthard nests made Müllerian epithelium an attractive candidate as the cellular origin. Changes of tissue structure or sex hormones imbalance may lead to the translocation of Müllerian remnants to distant organs, explaining the pathogenesis of EOBTs.

Until now, comparative studies on proton conductivity between organic ligands and related metal–organic frameworks (MOFs) have been very limited. Herein, a stable 2D Zn(II) MOF, [Zn(L)Cl]n (1), has...

Objectives To investigate the underlying mechanism between diabetic periodontitis and NLR family pyrin domain containing 3 (NLRP3) inflammasome associated pyroptosis. Design Experimental models of diabetes-associated periodontitis were implemented in db/db mice. We detected NLRP3 inflammasome related cytokines and gasdermin D (GSDMD) both in vitro and in vivo. We performed bioinformatics predictions based on microarray analysis using bone marrow derived macrophages (BMDMs). Results Diabetes-associated periodontitis mice exhibited the worst fasting glucose and alveolar bone destruction. GSDMD positive cells and NLRP3 inflammasome expression were augmented in gingival tissue, which were partly reversed by metformin. In vitro data suggested NLRP3 inflammasomes stimuli induced cell pyroptotic death and deletion of NLRP3 decreased GSDMD expression. We found a profile of differential lncRNAs expression and three co-expressed lncRNAs of nlrp3 and gsdmd in BMDMs. Conclusions Our data show that NLRP3 mediated pyroptosis has a significant role in diabetes-associated periodontitis. The pyroptotic cell death may be the pivot reason of the deteriorated inflammation in this disease, which is ameliorated by metformin treatment. Moreover, the role of both NLRP3 and GSDMD may be regulated by lncRNA_1810058I24Rik, lncRNA_Gm12474 and lncRNA_Gm41514.

Previous studies have shown that small-molecule BCL-2 inhibitors can have a synergistic interaction with ABCG2 substrates in chemotherapy. Venetoclax is a potent and selective BCL-2 inhibitor, approved by the FDA in 2016 for the treatment of patients with chronic lymphocytic leukemia (CLL). This study showed that, at a non-toxic concentration, venetoclax at 10 &micro, M significantly reversed multidrug resistance (MDR) mediated by wild-type ABCG2, without significantly affecting MDR mediated by mutated ABCG2 (R482G and R482T) and ABCB1, while moderate or no reversal effects were observed at lower concentrations (0.5 to 1 &micro, M). The results showed that venetoclax increased the intracellular accumulation of chemotherapeutic agents, which was the result of directly blocking the wild-type ABCG2 efflux function and inhibiting the ATPase activity of ABCG2. Our study demonstrated that venetoclax potentiates the efficacy of wild-type ABCG2 substrate drugs. These findings may provide useful guidance in combination therapy against wild-type ABCG2-mediated MDR cancer in clinical practice.

One of the major limitations in the production of genetically engineered RNA from Escherichia coli (E. coli) is contamination by endotoxin. Here we report the first method that is capable of removing endotoxin from genetically engineered RNA. As a proof of concept, we transformed E. coli with a plasmid containing a tandem short interspersed nuclear elements from the mouse genome (SINE B1 elements). We then evaluated several extraction methods (SDS-NaCl centrifugation, SDS-NaCl filtration, TRIzol and SDS hot-phenol) and refinements thereof, and measured the resulting RNA yield, RNA purity, RNA integrity and endotoxin content. SDS-NaCl filtration with 2 mol/L NaCl, incorporating DEPC as an RNA protective agent, effectively removed endotoxin and resulted in a good RNA yield. Triton X-114 phase separation further reduced the endotoxin content of SDS-NaCl filtration-extracted RNA. RNA extracted by SDS-NaCl filtration with Triton X-114 phase separation did not cause adverse reactions in BALB/c mice and did not induce fever in rabbits when injected into these animals. The RNA met the requirements of nucleic acid reagents for in vivo experiments on animals.

Objective: This study aimed to explore the association between monoaminergic genetic variants and emotional lability (EL) symptoms in children with ADHD. In addition, genetic effects on prefrontal cortex (PFC)–amygdala functional connectivity (FC) were investigated. Method: Children with ADHD and controls were genotyped for five monoaminergic genetic variants and were evaluated for EL symptoms. Imaging genetic exploration was conducted with previously reported aberrant PFC–amygdala resting-state functional connectivities (RSFCs) as target features. Results: A genotypic effect on EL symptoms was only found for NET1-rs3785143, indicating higher EL symptoms in TT genotype carriers than in C-allele carriers. Imaging genetic analyses indicated a marginal effect of NET1-rs3785143 on ADHD-altered FC between the superficial amygdala (SFA) and middle frontal gyrus (MFG). Mediation analysis suggested potential effects of NET1-rs3785143 via RSFC (SFA–MFG) on EL. Conclusion: NET1 variants might participate in the pathogenesis of EL in children with ADHD by influencing the function of the PFC–amygdala circuit.

The purpose of this study was to investigate the association between refined grains intake and obesity in China. Refined grain intake was considered in relation to energy intake and at varied levels of macronutrient distribution. A cross-sectional study of 6913 participants was conducted using internet-based dietary questionnaire for Chinese (IDQC). The associations and dose–response relationships between refined grains intake and obesity were investigated using multivariable logistic regression analyses and restricted cubic spline (RCS) models. There was a positive association between refined grains intake and abdominal obesity for all participants (forth quartile OR, 1.313; 95% CI, 1.103–1.760; p

Taking advantage of V-shaped ligands, a Zn

Symbiotic fungi are required to provide nutrients for orchid seed germination and seedling development, underpinning the long-term conservation and reintroduction of species. Cremastra appendiculata is a terrestrial orchid whose asymbiotic seed germination has been studied to some extent, but the role of symbiotic fungi in seed germination is still unclear. We isolated a number of strains of mycorrhizal fungi from the roots of C. appendiculata and used them for in vitro experiments to investigate the role of mycorrhizal fungi in seed germination and seedling establishment. Molecular analysis showed that the seven isolated strains belonged to the genera Candida (DJF-01), Mucor (DJF-06), Coprinellus (DJF-10), Gongronella (DJF-11), Barnettozyma (DJF-13), Penicillium (DJF-15), and Trichoderma (DJF-17). The isolated strain Coprinellus disseminatus DJF-10 was chosen for further experiments because it formed pelotons inside protocorms and promoted seed germination (up to 71.61 ± 0.92% seeds germinated) after 30 days co-cultivation; moreover, some protocorms grew up to seedlings with one leaf and roots after about 6 months. This is the first report that C. disseminatus can promote seed germination and seedling development of C. appendiculata; these findings provide new knowledge to support species conservation.

Three Co(II) metal-organic frameworks, namely, {[Co(L)(dpyb)0.5(H2O)2]·3H2O}n (1), {[Co(L)(dpyb)0.5]·CH3CN}n (2), and {[Co2(L)2(dpyp)1.5(H2O)]}n (3) have been hydrothermally synthesized based on a substituted thiophene carboxylic acid 3,3′-(thiophene-2,5-diyl)dibenzoic acid (H2L) and auxiliary N-donor co-ligands 1,4-di(pyridin-4-yl)benzene (dpyb) and 1,3-di(4-pyridyl)propane (dpyp). 1 possesses a 1D double chains structure, which is further extended into a 3D supramolecular framework via O–H···O hydrogen bonds and π···π interactions. 2 shows a novel 2D + 2D→ 2D network with unusual polyrotaxane entanglements of (4, 4)-sql subnets. The two sets of adjacent such networks are further extended via C–H···π interactions into a 3D supramolecular framework. 3 displays a non-interpenetrated 2D sheet with the point symbol {44.62} sql net topology and further extends via π···π interactions into a 3D supramolecular framework. The three MOFs were characterized by IR spectra, elemental analysis, thermal analysis and single crystal X-ray diffraction. In addition, solid-state UV–vis spectra experiments show that 1, 2, and 3 exhibit semiconductive properties with band gap of 2.23, 2.95, and 3.12 eV.

Although transition-metal oxides offer the potential for intimate coupling of energy storage application and environmental sustainability, how to find the suitable relationship between materials structures and properties is still a problem to explore further applications. In this work, Jahn-Teller effects proved by Crystal Field Theory (CFT) and Density Functional Theory (DFT) are used to predict the electronic structures of MoO3 and MoO2 reasonably, such results guided us to design two more reasonable applications. On account of the metallicity tendency of MoO2 with a stronger electron mobility from band structure, MoO2/rGO/g-C3N4 composite was performed as a high-performance electrode in asymmetric supercapacitors (SCs). MoO2 with the assistance of mesoporous graphitic carbon nitride and high conductivity graphene shows an enhanced capacity at 1700 F g−1 at 1 A g−1 and cycling retention at 84% retention after 3000 cycles for supercapacitors, the corresponding assemble asymmetric devices shows a maximum power density of 6.25 kW kg−1 at an energy density of 16.0 W h kg−1. Furthermore, the proper band structure of MoO3 predicted by DFT calculation has guided MoO3/rGO composite as a photocatalyst to degrade tetracycline, which shows a high elimination efficiency of 90.6% within 2 h illumination of simulated solar light.

Type 2 diabetic mellitus is manifested by metabolic impairments with high prevalence worldwide, of which periodontitis represents a typical oral complication (also called diabetic periodontitis). Oral epithelia bear the brunt of periodontal damage from microscopic intruders; thus the defense function of epithelial cells is of vital significance. We have previously proved that 25-hydroxyvitamin D3 (25-OHD3) altered the expression of cathelicidin antimicrobial peptide in oral epithelial cells in vitro. Herein, we discovered that 25-OHD3 intraperitoneal injection attenuated periodontal inflammation by promoting cathelicidin production in gingival epithelia and reducing fasting glucose of diabetic mice. Dotblotting of serum showed cathelicidin secretion was consistent with 25-OHD3 treatment. Immunochemistry exhibited enhanced expression of cathelicidin and vitamin D receptors along with reduced expression of TLR4 in diabetic mice. Stereomicroscope showed less alveolar bone loss when injected with 25-OHD3.These results showed 25-OHD3 can promote cathelicidin and ameliorate the severity of diabetic periodontitis. Our study complemented the mechanism of cathelicidin and extended knowledge of 25-OHD3's role in diabetic periodontitis.

Two coordination polymers, namely [Mn(L)2(H2O)2]n (1) and [Cd2(L)4(H2O)4]n (2) {HL = (benzotriazol-1-yloxy)-acetic acid}, have been synthesized and characterized by single-crystal X-ray diffraction as well as with infrared spectroscopy and elemental analysis. The results reveal that CP1 has 1D double chain structure, while CP2 features a 1D infinite chain structure. Additionally, there both exist O–H···O and O–H···N hydrogen bonds in CP1 and CP2, forming 3D supramolecular structures, respectively. UV-vis absorption spectra of CP1, and photoluminescence property of CP2, have been examined in solid state at room temperature. The result on optical energy gap of 2.80 eV indicates that CP1 is a potential semiconductive material.

Several DNA copy number amplifications (CNAs) have been reported in papillary thyroid cancer (PTC). However, the functional role of CNAs in PTC remains very unclear. And whether there is a correlation between long noncoding RNA (lncRNA) and CNA requires to be explored. Here, we identified a novel lncRNA LINC01061. The genomic copy number of LINC01061 is amplified, which leads to its elevated expression level in PTC tissues. Moreover, increased level of LINC01061 was correlated with aggressive clinicopathological characteristics. Functional study indicated that LINC01061 silence significantly inhibited the proliferation, cell-cycle and invasion of PTC cells in vitro and tumor growth in vivo. Mechanistically, we showed that LINC01061 interacted with miR-4316 to promote E2F6 expression. The expression of miR-4316 was downregulated in PTC tissues while that of E2F6 was upregulated. Through rescue assay, we demonstrated that LINC01061 promoted PTC cell proliferation, cell-cycle progression and invasion by regulating miR-4316/E2F6 signaling pathway. In conclusion, our research indicated that LINC01061 might be a target for PTC therapy.

We explore the effects of different passivating agents on livestock manure treatment by using chicken manure and straw as raw materials and thermophilic rapid fermentation. We investigate the effects of sepiolite (SE), calcium magnesium phosphate fertilizer (NP), biochar (BI), compounds of sepiolite plus calcium magnesium phosphate fertilizer (S+N), sepiolite plus biochar (S+B), calcium magnesium phosphate fertilizer plus biochar (N+B), and sepiolite plus calcium magnesium phosphate fertilizer and biochar (SNB) on the physical and chemical characteristics, heavy metal fraction and distribution, and organic matter content in chicken manure compost. The results showed that the addition of different passivating agents significantly increased the pH in chicken manure organic fertilizer (

PA28γ promotes tumor development and progression and is suggested to play a role in tumor angiogenesis, but the molecular mechanisms have not been investigated. Here, we found that PA28γ enhanced the ability of OSCC cells to promote the migration, invasion, and tube formation of HUVECs and promoted tumor-induced angiogenesis in xenograft mice models in vivo. Then, a mechanism study revealed that the expression and secretion of IL-6 and CCL2 were dependent on PA28γ expression. Furthermore, blocking IL-6 or CCL2 or the transcription factor NF-κB induced the inhibition of tube formation in HUVECs co-cultured with PA28γ-overexpression OSCC cell supernatants. Moreover, we revealed that p-STAT3 and p-AKT, which are downstream of the IL-6 and CCL2 signaling axis, were downregulated in HUVECs co-cultured with the PA28γ-silenced supernatant and were upregulated with the PA28γ-overexpressing supernatant. In addition, IL-6, CCL2 and PA28γ expressions were correlated in a clinical OSCC cohort. Collectively, our study indicates that PA28γ contributes to tumor angiogenesis by regulating IL-6 and CCL2. PA28γ may be a novel therapeutic target as a dual regulator of IL-6 and CCL2 for treating PA28γ-positive OSCC.

Two new isomorphous zinc(II) and nickel(II) supramolecular complexes, [Zn(L)2(H2O)2]n, (1), and [Ni(L)2(H2O)2]n (2) {HL = (benzotriazol-1-yloxy)-acetic acid} have been synthesized under ambient conditions by the self-assembly of HL with Zn(Ac)2·2H2O or Ni(Ac)2·4H2O in the presence of triethylamine. The two complexes have been characterized by single-crystal X-ray diffraction, elemental analysis, and IR spectroscopy. Single-crystal X-ray diffraction shows that the two complexes are isostructural and crystallize in monoclinic crystal system P21/c with similar unit-cell parameters and exhibit one-dimensional infinite chain structures. Adjacent chains are linked by O–H⋯O hydrogen bonds, giving rise to a two-dimensional network and these networks are further extended by weak π⋯π stacking interactions among adjacent aromatic cycles of HL ligands into a three-dimensional framework. In addition, the luminescent property of 1 and UV–Visible absorbance of 2 were also investigated and discussed. Density functional theory (DFT) calculations of the structures, stabilities, orbital energies, and composition characteristics of some frontier molecular orbitals of the two complexes were performed by means of Gaussian 09W package and taking B3LYP basis set.

In this paper, the vibration control for a flexible satellite subject to input constraint and external disturbance is considered. The symmetrical flexible solar panels are described as symmetrical Euler–Bernoulli beams modelled as partial differential equations (PDEs). By using the backstepping method, a vibration control scheme is designed to regulate the satellite's vibration. An auxiliary system based on a smooth hyperbolic function and a Nussbaum function is designed to satisfy the constrained input. In order to overcome external disturbance, a robust item is introduced. It is proved that the vibration, the constrained input and external disturbance can be handled simultaneously. Simulations results are demonstrated for illustration.

AFF4, an essential core of SEC, was overexpressed in HNSCC tissue and cell lines. AFF4 promoted the proliferation, migration, invasion and tumor-initiation capacity by regulating SOX2 in HNSCC cells, indicating AFF4 may serve as a potential therapeutic target of HNSCC., Super elongation complex (SEC) controls gene transcription by releasing Pol II from pausing. Previous studies have shown that dysfunction of SEC was associated with multiple human cancers, such as leukemia and breast cancer. However, the role of SEC in head and neck squamous cell carcinoma (HNSCC) development remains largely unknown. In this study, we found expression of AF4/FMR2 family member 4 (AFF4), the core component of SEC, was upregulated dramatically in HNSCC cell lines and tumor tissues. By using siRNA-mediated depletion and overexpression of AFF4, we demonstrated AFF4 promoted proliferation, migration and invasion of HNSCC cells. Moreover, we found AFF4 enhanced the aldehyde dehydrogenase (ALDH) activity and sphere formatting activity and was required for the tumor-initiation capacity of stem-like cells in HNSCC cell lines. Mechanistically, we found the role of AFF4 in regulation of HNSCC cell behaviors was mainly mediated by sex-determining region Y box2 (SOX2), a critical regulator involved in development of several human cancers. SOX2 expression changed in parallel with AFF4 expression in response to depletion and overexpression of AFF4, respectively. More importantly, overexpression of SOX2 rescued the inhibited proliferation, migration, invasion and ALDH activity induced by knockdown of AFF4 in HNSCC cells, at least in part. Collectively, our findings indicate AFF4 may serve as a biomarker and a potential target of therapies for patients with HNSCC.

Objective We aimed to investigate the mechanism of paraventricular nucleus (PVN) and ventral tegmental area (VTA) circuit in the pathogenesis of visceral pain-depression with a rat model induced by neonatal and adult colorectal distension (CRD). Methods Neonate male Sprague-Dayley (SD) rats underwent CRD on postnatal days 8, 10, and 12, and when matured, were tested for adult abdominal withdrawal reflex (AWR) scores to assess visceral hypersensitivity. The forced swimming test was employed to evaluate depression-like behaviors. The rats exhibiting visceral pain-depressive behaviors underwent lidocaine injection in the VTA to explore the relationship between VTA and visceral pain. Moreover, double immunofluorescence was employed to evaluate the qualitative and quantitative expression of dopamine/ c-Fos in CRD rats. After verifying the existed fiber projection from PVN to VTA, the intra-PVN microinjection of CRH-RNAi lentivirus to inhibit corticotropin-releasing hormone (CRH) expression, behavioral changes were assessed by AWR score and FST. Thereafter, with the sacrifice of the rats, the variations of TH protein in rats were evaluated by immunofluorescence and Western blot. Results Intra-VTA microinjection of lidocaine increased the pain threshold of CRD group. After intra-VTA microinjection of green retrograde tracer, immunofluorescence photomicrographs visualized the PVN with a typical green retrograde tracer. Intra-PVN microinjection of CRH-RNAi lentivirus alleviated the visceral pain-depression behaviors and decreased the TH protein expression in the VTA. Conclusion These data demonstrated that the VTA played a functional role in chronic visceral pain and depression, and the CRH-containing neurons in hypothalamic PVN may be implicated in the onset and maintenance of the chronic visceral pain and depression via the activation of dopamine in the VTA.

Background and Objective Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D3 (25VD3) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD3/vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis. Material and Methods Porphyromonas gingivalis-infected db/db mice were treated with 25VD3. Their fasting blood glucose and body weight were monitored every other week, and the levels of alveolar bone loss and serum inflammatory cytokines (tumor necrosis factor-α, interferon-γ and interleukin-6) were determined at the time of killing. The effect of PTPN2 on human OKF6-TERT2 oral keratinocytes was examined through the knockout of PTPN2 using the CRISPR/Cas9 knockout plasmid. The expression levels of the PTPN2, vitamin D receptor and JAK1/STAT3 signaling proteins in the gingival epithelium and OKF6-TERT2 cells were determined through western blot and immunohistochemical analyses. Results After 25VD3 treatment, db/db mice exhibited alleviated serum inflammatory cytokines and alveolar bone loss, and 25VD3-enhanced PTPN2 expression decreased the expression of the JAK1/STAT3 signaling proteins in the gingival epithelium. Analyses of human oral keratinocytes showed that 25VD3 increased the expression of PTPN2, which dephosphorylates protein substrates in the JAK1/STAT3 signaling pathway. Conclusion PTPN2 contributed to a decrease in periodontal inflammation in type 2 diabetes mellitus via dephosphorylate protein substrates in the JAK1/STAT3 signaling pathway after 25VD3 treatment in human oral keratinocytes and a mouse model of type 2 diabetes mellitus. A thorough understanding of PTPN2 and its involvement in inhibiting inflammation might provide alternative therapeutic approaches for the pathogenesis and treatment of diabetes mellitus-associated periodontitis.

In this paper, the vibration control problem for the nonlinear three-dimensional Euler–Bernoulli beam with input magnitude and rate constraints is addressed. By using the backstepping method with smooth hyperbolic tangent function, a boundary control scheme is designed to suppress vibration of the nonlinear three-dimensional Euler–Bernoulli beam and to satisfy the input magnitude and rate constraints. It is proved that the proposed control scheme can handle the vibration and input magnitude and rate constraints simultaneously. Finally, numerical simulations illustrate the effectiveness of the proposed control.

The design and synthesis of coordination polymers with a self-penetrating architecture has attracted much interest not only due to their interesting structures but also due to their potential applications. 5,5′-Bis(pyridin-4-yl)-2,2′-bithiophene (bpbp), as a conjugated bithiophene ligand, can exhibit trans and cis conformations and this can lead to the construction of a self-penetrating architecture. In addition, the semi-rigid ancillary ligand 4,4′-oxybis(benzoic acid) (H2oba) can adopt different coordination modes, resulting in coordination polymers with high-dimensional skeletons. A new CdII coordination polymer based on mixed ligands, namely poly[diaquapentakis[μ-5,5′-bis(pyridin-4-yl)-2,2′-bithiophene-κ2 N:N′]bis(nitrato-κ2 O,O′)tetrakis(μ3-4,4′-oxydibenzoato)-κ10 O:O,O′:O′′,O′′′;κ6 O:O′:O′′-pentacadmium(II)], [Cd5(C14H14O5)4(NO3)2(C18H12N2S2)5(H2O)2] n , (I), has been synthesized under solvothermal conditions and characterized by single-crystal X-ray diffraction, IR spectroscopy and elemental analysis. Single-crystal X-ray diffraction indicates that there are three crystallographically independent CdII cations, three bpbp ligands, two deprotonated oba2− ligands, one nitrate ligand and one coordinated water molecule in the asymmetric unit. One CdII centre is seven-coordinated, exhibiting a distorted {CdN2O5} pentagonal bipyramidal geometry, while the other two Cd centres are both six-coordinated, showing slightly distorted {CdN2O4} octahedral geometries. The most interesting feature is the co-existence of trans and cis conformations in a single net, allowing structural interpenetration via self-threading and yet the expected self-penetrating structure was obtained. Topological analysis shows that the whole three-dimensional framework can be classified as a 3-nodal (4,6,6)-c net with Schläfli symbol {613.82}2{66}, which is a new topology. Furthermore, the luminescence properties of (I) were examined in the solid state at room temperature.

Objectives This study aims to verify that RACK1 is an organ-specific prognostic predictor in patients with oral squamous cell carcinoma (OSCC). Experimental design The RACK1 expression level was assessed by immunohistochemistry (IHC) in a total of 342 OSCC patients from 3 independent cohorts. The multivariate hazard ratios for Overall Survival (OS) was determined by Cox proportional hazards regression model. OS was analyzed in 460 Head Neck Squamous Cell Carcinoma (HNSCC) patients from TCGA data set. The expression level of RACK1 was analyzed in 60 cases multiple organ tissue microarrays representing both normal and cancer tissues by IHC, and in TCGA database of mRNA abundance in cancers and paired normal tissues. Results The median follow-up times of patients in the study was 74, 52, and 78 months. High expression of RACK1 was identified in tumors from 103 of 151 patients (68.2%), 51 of 83 patients (61.4%), and 59 of 108 patients (54.6%). Compared with low expression, high expression of RACK1 was strongly associated with worse OS, with HR of 0.5995 (95% CI, 0.3929 to 0.9147; P = 0.0176), 0.4402 (95% CI, 0.2321 to 0.8348; P = 0.0120), and 0.5010 (95% CI, 0.2886 to 0.8699; P = 0.0141). This finding is consistent with TCGA HNSCC data (P = 0.0276). Tissue microarrays analyses showed different protein expression level of RACK1 in multiple human carcinomas and this finding is consistent with the TCGA database analysis of RACK1 mRNA abundance. Conclusion Our findings demonstrated that RACK1 is a good independent organ-specific predictor of the risk of death in OSCC.

The combination of π-conjugated fluorophores within a hybrid system gives rise to a triphenylamine-functionalized material [Zn(bpba)(NO3)] (1) (Hbpba = 4-(bis(4-(pyridin-4-yl)phenyl)amino)benzoic acid). Compound 1 features a 2D + 2D → 2D parallel polycatenation structure with 63-hcb net. Photophysical studies revealed that the title phase showed superior sensitivity towards p-nitroaniline (p-NA) with a low detection limit (down to ∼0.10 ppm). Specifically, following a new detection route, vapor-sensing experiments using a saturated ethanol solution of nitroaromatic isomers have been established for the first time. Highly sensitive and selective detection of p-NA by the proposed material with a rapid response time (t = 30 s, QE > 90.0%) as compared to that via the control isomers (t = 60s, QE < 6.0%) demonstrates an attractive feasible route and a promising luminescent sensor for nitroaromatic detection.

The photon router plays an essential role in the optical quantum network. However, conventional routers generally couple photons chirally into waveguides to achieve complete transmission from the input port to the required port. Here, we use non-chiral photon-atom interactions for targeted routing. The system consists of two V-type three-level atoms and two parallel waveguides. In addition, the two atoms are driven by external coherent fields, respectively. With a real-space Hamiltonian, the probability of photon transmitted to four ports can be obtained. The study shows that a single photon input from the left port of the waveguide-a can be deterministically transferred to any of the four ports of the two waveguides by adjusting the detuning of the atom and the driving field on the atom, as well as the distance between the two atoms.

Background Central aortic pressure (CAP) as the major load on the left heart is of great importance in the diagnosis of cardiovascular disease. Studies have pointed out that CAP has a higher predictive value for cardiovascular disease than peripheral artery pressure (PAP) measured by means of traditional sphygmomanometry. However, direct measurement of the CAP waveform is invasive and expensive, so there remains a need for a reliable and well validated non-invasive approach. Methods In this study, a multi-channel Newton (MCN) blind system identification algorithm was employed to noninvasively reconstruct the CAP waveform from two PAP waveforms. In simulation experiments, CAP waveforms were recorded in a previous study, on 25 patients and the PAP waveforms (radial and femoral artery pressure) were generated by FIR models. To analyse the noise-tolerance of the MCN method, variable amounts of noise were added to the peripheral signals, to give a range of signal-to-noise ratios. In animal experiments, central aortic, brachial and femoral pressure waveforms were simultaneously recorded from 2 Sprague-Dawley rats. The performance of the proposed MCN algorithm was compared with the previously reported cross-relation and canonical correlation analysis methods. Results The results showed that the root mean square error of the measured and reconstructed CAP waveforms and less noise-sensitive using the MCN algorithm was smaller than those of the cross-relation and canonical correlation analysis approaches. Conclusion The MCN method can be exploited to reconstruct the CAP waveform. Reliable estimation of the CAP waveform from non-invasive measurements may aid in early diagnosis of cardiovascular disease.

// Ruixue Ai 1 , Yan Tao 1 , Yilong Hao 1 , Lu Jiang 1 , Hongxia Dan 1 , Ning Ji 1 , Xin Zeng 1 , Yu Zhou 1 and Qianming Chen 1 1 State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral Medicine of West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China Correspondence to: Yu Zhou, email: zhouyu19830306@sina.com Qianming Chen, email: qmchen@scu.edu.cn Keywords: immunity, premalignant condition, microenvironment, oral potentially malignant disorder, therapeutics Received: May 24, 2017 Accepted: August 04, 2017 Published: August 17, 2017 ABSTRACT Oral potentially malignant disorders (OPMD) develop in a complex tissue microenvironment where they grow sustainably, acquiring oral squamous cell carcinoma (OSCC) characteristics. The malignant tumor depends on interactions with the surrounding microenvironment to achieve loco-regional invasion and distant metastases. Unlike abnormal cells, the multiple cell types in the tissue microenvironment are relatively stable at the genomic level and, thus, become therapeutic targets with lower risk of resistance, decreasing the risk of OPMD acquiring cancer characteristics and carcinoma recurrence. However, deciding how to disrupt the OPMD and OSCC microenvironments is itself a daunting challenge, since their microenvironments present opposite capacities, resulting in diverse consequences. Furthermore, recent studies revealed that tumor-associated immune cells also participate in the process of differentiation from OPMD to OSCC, suggesting that reeducating stromal cells may be a new strategy to prevent OPMD from acquiring OSCC characteristics and to treat OSCC. In this review, we discuss the characteristics of the microenvironment of OPMD and OSCC as well as new therapeutic strategies.

In this paper, the vibration control problem for the payload at the end of a three-dimensional Euler–Bernoulli beam in the presence of input constraints and input disturbances is addressed. Disturbance observers are designed to estimate the disturbances on the tip payload. Based on the disturbance observers, a boundary control scheme is designed to suppress elastic vibration for the payload at the end of the beam. The smooth hyperbolic function is applied for the proposed control scheme, which can satisfy physical conditions and input constraints. It is proved that the proposed control scheme can be guaranteed in handling input constraints and disturbances. Finally, numerical simulations illustrate the effectiveness of the results.

This work considered a tripartite cooperation-competition game model for the convergence product market, whose products are compounds of two base products or services. An early convergence product firm monopoly in this market and two potential entrants from the base products decide to cooperate with another to compete with the monopolist. We analyzed factors that affect existence and local stability of the Nash equilibrium. Rich nonlinear dynamic behaviors like bifurcation, chaos, and attractors are presented to explain the complex relationships between the three players. Results showed that the pulling effect on profit for the united R&D activity can significantly enlarge the stable region. Too frequently adjusted price strategy will bring the system into chaos. A parameter feedback control method is given to control the chaotic system and we numerically verified its effectiveness. This study has significant values to understand the fluctuations in related convergence product market.

Background: Accumulating evidence indicates that attention deficit hyperactivity disorder (ADHD) is associated with core deficits in executive function (EF) which predicts poorer academic and occupational functioning. This makes early intervention targeting EF impairments important to prevent long-term negative outcomes. Cognitive training is a potential ADHD treatment target. The present study aimed to explore the efficacy, feasibility, and acceptability of a cognitive training program (targeting child's multiple EF components and involving parent support in daily life), as a nonpharmacological intervention for children with ADHD. Methods: Forty-four school -age children with ADHD and their parents participated in 12 sessions of EF training (last for 12 weeks) and 88 health controls (HC) were also recruited. Training effects were explored using both neuropsychological tests (Stroop color-word test, Rey-Osterrieth complex figure test, trail making test, tower of Hanoi, and false-belief task) and reports of daily life (ADHD rating scale-IV, Conners' parent rating scale, and behavior rating inventory of executive function [BRIEF]) by analysis of paired sample t-test and Wilcoxon signed-rank test. The differences on EF performances between children with ADHD after training and HC were explored using multivariate analysis. Results: The results (before vs. after EF training) showed that after intervention, the children with ADHD presented better performances of EF both in neuropsychological tests (word interference of Stroop: 36.1 ± 14.6 vs. 27.1 ± 11.1, t = 4.731, P < 0.001; shift time of TMT: 194.9 ± 115.4 vs. 124.8 ± 72.4, Z = –4.639, P < 0.001; false-belief task: χ2 = 6.932, P = 0.008) and reports of daily life (global executive composite of BRIEF: 148.9 ± 17.5 vs. 127.8 ± 17.5, t = 6.433, P < 0.001). The performances on EF tasks for children with ADHD after EF training could match with the level of HC children. The ADHD symptoms (ADHD rating scale total score: 32.4 ± 8.9 vs. 22.9 ± 8.2, t = 6.331, P < 0.001) and behavioral problems of the children as reported by parents also reduced significantly after the intervention. Participants reported that the EF training program was feasible to administer and acceptable. Conclusions: The EF training program was feasible and acceptable to children with ADHD and parents. Although replication with a larger sample and an active control group are needed, EF training program with multiple EF focus and parent involving in real-life activities could be a potentially promising intervention associated with significant EF (near transfer) and ADHD symptoms improvement (far transfer).