Endocytosis triggers V-ATPase-SYK-mediated priming of cGAS activation and innate immune response.

The current view of nucleic acid-mediated innate immunity is that binding of intracellular sensors to nucleic acids is sufficient for their activation. Here, we report that endocytosis of virus or foreign DNA initiates a priming signal for the DNA sensor cyclic GMP-AMP synthase (cGAS)-mediated innate immune response. Mechanistically, viral infection or foreign DNA transfection triggers recruitment of the spleen tyrosine kinase (SYK) and cGAS to the endosomal vacuolar H+ pump (V-ATPase), where SYK is activated and then phosphorylates human cGASY214/215 (mouse cGasY200/201) to prime its activation. Upon binding to DNA, the primed cGAS initiates robust cGAMP production and mediator of IRF3 activation/stimulator of interferon genes-dependent innate immune response. Consistently, blocking the V-ATPase-SYK axis impairs DNA virus- and transfected DNA-induced cGAMP production and expression of antiviral genes. Our findings reveal that V-ATPase-SYK-mediated tyrosine phosphorylation of cGAS following endocytosis of virus or other cargos serves as a priming signal for cGAS activation and innate immune response.

Molecular subtypes predict therapeutic responses and identifying and validating diagnostic signatures based on machine learning in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological tumor derived from hematopoietic stem cells. The aim of this study is to analyze the biological characteristics and identify the diagnostic markers of CML. We obtained the expression profiles from the Gene Expression Omnibus (GEO) database and identified 210 differentially expressed genes (DEGs) between CML and normal samples. These DEGs are mainly enriched in immune-related pathways such as Th1 and Th2 cell differentiation, primary immunodeficiency, T cell receptor signaling pathway, antigen processing and presentation pathways. Based on these DEGs, we identified two molecular subtypes using a consensus clustering algorithm. Cluster A was an immunosuppressive phenotype with reduced immune cell infiltration and significant activation of metabolism-related pathways such as reactive oxygen species, glycolysis and mTORC1; Cluster B was an immune activating phenotype with increased infiltration of CD4 + and CD8 + T cells and NK cells, and increased activation of signaling pathways such as interferon gamma (IFN-γ) response, IL6-JAK-STAT3 and inflammatory response. Drug prediction results showed that patients in Cluster B had a higher therapeutic response to anti-PD-1 and anti-CTLA4 and were more sensitive to imatinib, nilotinib and dasatinib. Support Vector Machine Recursive Feature Elimination (SVM-RFE), Least Absolute Shrinkage Selection Operator (LASSO) and Random Forest (RF) algorithms identified 4 CML diagnostic genes (HDC, SMPDL3A, IRF4 and AQP3), and the risk score model constructed by these genes improved the diagnostic accuracy. We further validated the diagnostic value of the 4 genes and the risk score model in a clinical cohort, and the risk score can be used in the differential diagnosis of CML and other hematological malignancies. The risk score can also be used to identify molecular subtypes and predict response to imatinib treatment. These results reveal the characteristics of immunosuppression and metabolic reprogramming in CML patients, and the identification of molecular subtypes and biomarkers provides new ideas and insights for the clinical diagnosis and treatment.

Effect of the Early Application of Evolocumab on Blood Lipid Profile and Cardiovascular Prognosis in Patients with Extremely High-Risk Acute Coronary Syndrome.

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors significantly reduce low-density lipoprotein cholesterol (LDL-C) and improve the prognosis of patients with acute coronary syndrome (ACS). However, the feasibility and safety of early application of PCSK9 inhibitors on the basis of statins combined with ezetimibe to strengthen lipid lowering in extremely high-risk coronary heart disease populations are still unknown.This study was a prospective, randomized controlled study. A total of 136 patients with extremely high-risk ACS with LDL-C ≥ 3.0 mmol/L after percutaneous coronary intervention (PCI) treatment were randomly assigned 1:1 to the control group (atorvastatin 40 mg/day and ezetimibe 10 mg/day) or the evolocumab group (evolocumab 140 mg every 2 weeks combined with atorvastatin 40 mg/day and ezetimibe 10 mg/day). We compared the blood lipid profiles, major adverse cardiovascular events (MACEs), and adverse reactions. MACEs included cardiogenic death, nonfatal myocardial infarction, nonfatal stroke, and readmission due to angina. Adverse reactions included allergies, myalgia, poor blood glucose control, and liver damage.Within 1 month, the average level of LDL-C in the evolocumab group decreased from 3.54 to 0.57 mmol/L and that in the control group decreased from 3.52 to 1.26 mmol/L. The LDL-C compliance (< 1.0 mmol/L) rate was significantly increased in the evolocumab group compared with the control group (82.35% versus 22.06%, P < 0.01). The average level of lipoprotein (a) (Lp (a) ) in the control group increased by 9.94 ± 51.93% from baseline after treatment, but evolocumab reduced the Lp (a) level (-38.84 ± 32.40%). Additionally, evolocumab further reduced the levels of apolipoprotein B/A1 (-70.56 ± 22.38% versus -51.29 ± 18.14%), cholesterol (-54.76 ± 18.10% versus -41.16 ± 18.14%), and apolipoprotein B (-66.47 ± 26.89% versus -46.78 ± 24.12%) compared with those in the control group, all P < 0.01. The blood lipid levels of both control and evolocumab groups stabilized after 1 month. During the 3-month follow-up, the incidence of MACEs after PCI was lower in the evolocumab group than in the control group (8.82% versus 24.59%, P = 0.015), and evolocumab combined with statins and ezetimibe did not increase the occurrence of adverse reactions (13.24% versus 11.48%, P = 0.762).In patients with extremely high-risk ACS with high levels of LDL-C, adding evolocumab to their treatment regimen as early as possible may enhance lipid lowering, increase the patient's LDL-C compliance rate in the short term, and improve cardiovascular prognosis but will not increase adverse reactions.

Verbascoside inhibits the epithelial-mesenchymal transition of prostate cancer cells through high-mobility group box 1/receptor for advanced glycation end-products/TGF-ß pathway.

INTRODUCTION: Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. MATERIALS AND METHODS: The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 µM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-ß)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. RESULTS: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-ß pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-ß receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-ß signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. CONCLUSION: Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-ß-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

Angiotensin-converting enzyme inhibitors attenuated advanced glycation end products-induced renal tubular hypertrophy via enhancing nitric oxide signaling.

Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3',5'-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1 , and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway.

A Dual Associated-Functional Fluorescent Switch: From Alternate Detection Cycle for Fe(III) and pH to Molecular Logic Operations.

With the expansion and deepening of scientific research, dual-functional or multifunctional materials are urgently needed to replace those for single application. Herein, a fluorescence sensing system based on an In(III)-organic complex with in situ Lewis acid sites has been constructed, exhibiting high sensitivity for the detection of Fe(III) ions with a low detection limit of 3.95 µM and a short response time of within 10 s. It is noteworthy that the quenched fluorescence of the Fe(III)-incorporated sample could be reopened linearly with an increase of alkalinity, followed by the reactivation of its functionality to identify Fe(III) ions, forming an alternate detection cycle for Fe(III) and pH with off-on-off fluorescent switch characteristics. Considering its unique molecular recognition capability, an advanced three-input (Fe(III), EDTA, and OH-) and two-output (B440 and G489) Boolean logic operation comprising BUFF, NOT, OR, and AND logic gates was integrated, possessing potential applications in intelligent multianalyte sensing systems.

Antifibrotic role of PGC-1α-siRNA against TGF-ß1-induced renal interstitial fibrosis.

Peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1α) is a transcriptional coactivator that regulates energy metabolism and mitochondrial biogenesis. Recently, mitochondrial dysfunction has been indicated as an established risk factor for the development of renal fibrosis. However, whether PGC-1α is involved in the pathogenesis of renal fibrosis is unknown. In this study, we treated NRK-49F (normal rat kidney fibroblast) cells with transforming growth factor-beta 1 (TGF-ß1) for 24 h to establish an in vitro fibrosis model. TGF-ß1 induced the upregulation of type I collagen, fibronectin, TGF-ß receptor I (TGFß-RI), TGFß-RII, Smad4, and pSmad2/3, as well as PGC-1α. NRK-49F cells transfected with pcDNA-PGC-1α showed significantly increased expression of fibronectin and type I collagen, as revealed by western blot assay. Interestingly, transfection with PGC-1α-siRNA caused a stark reversal of TGF-ß1-induced cellular fibrosis, with concomitant suppression of fibronectin and type I collagen, as revealed by western blot and immunofluorescence assays. Moreover, SB431542 (TGFß-RI), LY294002 (PI3K/Akt), and SB203580 (p38 MAPK), inhibitors of TGF-ß-associated pathways, markedly suppressed TGF-ß1-induced PGC-1α upregulation. These results implicate a role of PGC-1α in renal interstitial fibrosis mediated via the TGFß-RI, PI3K/Akt, and p38 MAPK pathways. Our findings that PGC-1α-siRNA downregulates fibronectin and type I collagen suggest that it can be used as a novel molecular treatment for renal fibrosis.

Serum Procalcitonin as a Potential Early Predictor of Short-Term Outcomes in Acute Severe Ulcerative Colitis.

BACKGROUND: Delayed colectomy can be life-threatening for patients with acute severe ulcerative colitis (ASUC). However, few biomarkers can predict the outcomes of ASUC patients before treatment. Serum procalcitonin (PCT) has been observed to be increased in ASUC patients. AIM: The aim of this study was to estimate the association between serum PCT and short-term outcomes in patients with ASUC. METHODS: A single-center observational study was conducted at a referral hospital from January 2012 to January 2018. Hospitalized ASUC patients, who were administered intravenous corticosteroids (IVCS), were enrolled and followed up for 6 months. The primary outcome was IVCS failure; the secondary outcome was colectomy. Relationships between indicators and clinical outcomes were assessed. RESULTS: Of 152 ASUC patients enrolled in this study, 81 responded to IVCS and 71 failed (62 required short-term colectomy and 9 responded to second-line rescue therapy). Serum PCT on admission was significantly higher in IVCS-failure cases and surgical cases than in medical responders. Serum PCT ≥ 0.10 µg/L (OR = 4.134, p = 0.001) predicted IVCS failure with specificity of 0.741, and the combined measurement with fecal calprotectin (FC) ≥ 1500 µg/g improved the sensitivity. Serum PCT correlated significantly with the Ulcerative Colitis Endoscopic Index of Severity (r = 0.416, p < 0.001) and FC (r = 0.384, p < 0.001). CONCLUSION: Serum PCT on admission could be a potential early non-invasive predictive biomarker for IVCS failure in ASUC patients, and a combination of PCT and FC could improve the predictive value.

Four new monoterpenoids from the whole plants of Valeriana stenoptera.

Four new monoterpenoids, including two new acyclic monoterpenoids (2R, 6R)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (1) and (2S, 6S)-2, 6-dimethyl-8-isovaleroxyoctan-1-ol (2), as well as two new iridoids stenopterins F-G (3 and 4), together with fifteen known compounds (5-19), were isolated from whole dried material of Valeriana stenoptera. Stenopterin F was the first reported iridoids with n-butoxyl in the Valerianaceae family. The structures of new compounds were established on the basis of extensive spectroscopic analysis.

Meta-analysis of antiviral protection of white spot syndrome virus vaccine to the shrimp.

Currently, white spot syndrome virus (WSSV) is one of the most serious pathogens that impacts shrimp farming around the world. A WSSV vaccine provides a significant protective benefit to the host shrimp. Although various types of vaccines against WSSV have emerged, the immune effects among them were not compared, and it remains unclear which type of vaccine has the strongest protective effect. Meanwhile, due to the lack of effective routes of administration and immunization programs, WSSV vaccines have been greatly limited in the actual shrimp farming. To answer these questions, this study conducted a comprehensive meta-analysis over dozens of studies and compared all types WSSV vaccines, which include sub-unit protein vaccines, whole virus inactivated vaccines, DNA vaccines and RNA-based vaccines. The results showed that the RNA-based vaccine had the highest protection rate over the other three types of vaccines. Among the various sub-unit protein vaccines, VP26 vaccine had the best protective effects than other sub-unit protein vaccines. Moreover, this study demonstrated that vaccines expressed in eukaryotic hosts had higher protection rates than that of prokaryotic systems. Among the three immunization modes (oral administration, immersion and injection) used in monovalent protein vaccines, oral administration had the highest protection rate. In natural conditions, shrimp are mostly infected by the virus orally. These results provide a guide for exploration of a novel WSSV vaccine and help facilitate the application of WSSV vaccines in shrimp farming.

Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis.

BACKGROUND: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. MATERIALS AND METHODS: In vitro fibrosis model was established by treatment with transforming growth factor-ß1 (TGF-ß1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). RESULTS: Under renal fibrosis conditions, TGF-ß1 (5ng/ml) increased ROS. Simultaneously, TGF-ß1-induced extracellular fibronectin by ELISA assay. In addition, TGF-ß1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2µg/ml) expression vector dramatically reverse TGF-ß1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2µg/ml) significantly increased the expression of fibronectin of both intercellular and extracellular origins in NRK-49F cells. DISCUSSION: These finding suggest that NRF-1 plays a pivotal role on renal cellular fibrosis. Moreover, NRF-1 might act as a novel renal fibrosis antagonist by down-regulating fibrosis signaling in renal fibroblast cells.

Treatment with cytokine thymic stromal lymphopoietin short hairpin RNA substantially reduces TGF-ß1-induced interstitial cellular fibrosis.

Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-ß1 (TGF-ß1), after which the levels of various fibrogenic markers (e.g., fibronectin) and downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also, TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F cells was dose- and time-dependently increased by the administration of exogenous TSLP (P<0.05). TSLP also significantly increased the level of fibrosis signaling, in addition to inducing a marked decrease in the down-regulation of Smad7. Interestingly, the application of TSLP shRNA caused a stark reversal of the TGF-ß1-induced cellular fibrosis while simultaneously leading to the suppression of fibronectin and fibrogenic signal proteins. Taken together, these observations provide insights into how extracellular matrices develop and could thus lead to potential therapeutic interventions for the suppression of renal fibrosis.

Thermally-induced single-crystal-to-single-crystal transformations from a 2D two-fold interpenetrating square lattice layer to a 3D four-fold interpenetrating diamond framework and its application in dye-sensitized solar cells.

In this work, a rare 2D → 3D single-crystal-to-single-crystal transformation (SCSC) is observed in metal-organic coordination complexes, which is triggered by thermal treatment. The 2D two-fold interpenetrating square lattice layer [Cd(IBA)2]n (1) is irreversibly converted into a 3D four-fold interpenetrating diamond framework {[Cd(IBA)2(H2O)]·2.5H2O}n (2) (HIBA = 4-(1H-imidazol-1-yl)benzoic acid). Consideration is given to these two complexes with different interpenetrating structures and dimensionality, and their influence on photovoltaic properties are studied. Encouraged by the UV-visible absorption and HOMO-LUMO energy states matched for sensitizing TiO2, the two complexes are employed in combination with N719 in dye-sensitized solar cells (DSSCs) to compensate absorption in the ultraviolet and blue-violet region, offset competitive visible light absorption of I3(-) and reducing charge the recombination of injected electrons. After co-sensitization with 1 and 2, the device co-sensitized by 1/N719 and 2/N719 to yield overall efficiencies of 7.82% and 8.39%, which are 19.94% and 28.68% higher than that of the device sensitized only by N719 (6.52%). Consequently, high dimensional interpenetrating complexes could serve as excellent co-sensitizers and have application in DSSCs.

HONH3Cl optimized CH3NH3PbI3 films for improving performance of planar heterojunction perovskite solar cells via a one-step route.

Planar heterojunction perovskite solar cells (PHJ-PSCs) constructed with one-step precursor solution spin-coating deposition (OPSSD) usually give an extremely low performance mainly due to the poor morphology and low crystallinity of the perovskite films. In this work, by incorporating a suitable HONH3Cl additive in the perovskite precursor solution, a high quality perovskite film with improved morphology and crystallinity was obtained. The UV-vis measurement of the CH3NH3I solutions without and with HONH3Cl demonstrates that the improved quality of the perovskite film can be easily attributed to a combined effect of N2, I2, H2O and CH3NH3Cl originating from the oxidation of CH3NH3I triggered by the HONH3Cl additive, which can manipulate the crystallization process of the perovskite. Accordingly, the improved performance for the HONH3Cl-induced PHJ-PSCs can also be demonstrated. At the optimized molar ratio of 1 : 1 : 0.1 for PbI2 : CH3NH3I : HONH3Cl, the PHJ-PSCs exhibit an average power conversion efficiency (PCE) of 10.61 ± 0.51%, which is much higher than that of pristine 1 : 1 : 0 based cells without additive (7.21 ± 0.61%), and the best performing HONH3Cl-induced device can yield a PCE as high as 11.12% with a Jsc of 18.42 mA cm-2, Voc of 0.95 V and FF of 0.63. Introducing suitable HONH3Cl as an additive into the perovskite precursor solution is really an effective route to enhance the performance of the PHJ-PSCs via OPSSD.

[Study on the Structure and Photoluminescent Properties of Mono-Zn(â ¡) and Di-Cu(â ) Complexes Constructed from Nitrogen Heterocyclic Ring Ligand].

The mononuclear Zn(Ⅱ) complex [Zn(2,6-PDA)(phen)H2O]·H2O (1) and binuclear Cu(Ⅰ) complex{[Cu(µ-Ⅰ)(phen)H2O]·H2O}2 (2) (2,6-H2PDA=2,6- pyridinedicarboxylic acid，phen=1,10- phenanthroline monohydrate) have been prepared with hydro-thermal synthesis method. These complexes have been characterized with single-crystal X-ray, elemental analysis, and IR spectroscopy. The fluorescence spectra of 1 and 2 are studied in solid-state and dimethyl sulfoxide (DMSO) solution. The maximum absorption peak of 1 and 2 are at 253 nm and 242 nm respectively, which are red shift to that of the phen ligand with inceased intensity. It may be assigned to the intraligand π→π* transition of the phen ligand that is modified by the Zn(Ⅱ) or Cu(Ⅰ) ions. On the basis of the coordination, the absorption of organic ligands in the ultraviolet region is increased, which is better for the energy absorption of the ligand. 1 and 2 all showed blue light emission. The emission peak of 1 and 2 have experienced a red shift (ca. 55 and 23 nm) in the solid state (λem = 407, 434, 467 nm for 1, 442, 469, 501 nm for 2) compared to in DMSO solution (λem = 361, 379, 392 nm for 1, 422, 443, 461 nm for 2). The red shift phenomenon can be attributed to the π-stacking of the aromatic rings and other intermolecular Interactions in these molecules in the solid state. Especially, the strong Cu(Ⅰ)…Cu(Ⅰ) interaction of 2 can decrease the HOMO­LUMO energy gap with the red-shifted emission wavelength.

Survey on the Implementation of Preconception Care in Shanghai, China.

BACKGROUND: Recently, the Chinese government has promoted preconception care (PCC) to prevent birth defects. The objective of this study was to evaluate the implementation of PCC in Shanghai, China, following a 3-year municipal project providing 'Free Pre-pregnancy Health Evaluation Services' to 20 000 residents. METHODS: A retrospective questionnaire survey was undertaken among 12 309 pregnant women and 8997 of their partners during their initial prenatal visit in six hospitals with the most births in Shanghai. RESULTS: A total of 90% (n = 11 113) of the women and 87% (n = 7856) of the men were aware of PCC, and 40% (n = 4890) of the women and 35% (n = 3185) of the men had previously participated in PCC. Logistic regression showed that PCC participants were more likely to have a planned pregnancy, receive support from their partner for PCC services, were older, and have higher educational attainment and higher household incomes. Regardless of gender, there were significant differences between the participating and non-participating groups in terms of prepregnancy changes in lifestyle and behaviour, such as folic acid supplementation, smoking cessation (for men only), avoiding passive smoking, abstaining from alcohol/drugs, and rubella/hepatitis B immunity. CONCLUSIONS: The government-led efforts proved to be effective in promoting PCC participation and positive lifestyle and behavioural changes in couples of childbearing age. Future efforts should target couples who are young, poorly educated, and/or from low-income families. Strategies must ensure that the couples' knowledge of and positive attitudes toward PCC are translated into their practical participation in PCC.

Tunable Luminescence and Application in Dye-Sensitized Solar Cells of Zn(II)/Hg(II) Complexes: Methyl Substitution-Induced Supramolecular Structures Based on (E)-N-(6-Methoxypyridin-2-ylmethylene)arylamine Derivatives.

Using Schiff-base ligands (E)-N-(6-methoxypyridin-2-yl)(CH═NAr) (where Ar = C6H5, L1; 2-MeC6H4, L2; 2,4,6-Me3C6H2, L3), six Zn(II)/Hg(II) complexes, namely, [ZnL1Cl2] (Zn1), [HgL1Cl2] (Hg1), [ZnL2Cl2] (Zn2), [HgL2Cl2] (Hg2), [ZnL3Cl2] (Zn3), and [HgL3Cl2] (Hg3) have been synthesized under solvothermal conditions. The structures of six complexes have been established by X-ray single-crystal analysis and further physically characterized by EA, FT-IR, (1)H NMR, and ESI-MS. The crystal structures of these complexes indicate that noncovalent interactions, such as hydrogen bonds, C-H···Cl, and π···π stacking, play essential roles in constructing the resulting supramolecular structures (1D for Hg3; 2D for Zn2, Hg2; 3D for Zn1, Hg1, and Zn3). Upon irradiation with UV light, the emission of complexes Zn1-Zn3 and Hg1-Hg3 could be finely tuned from green (480-540 nm) in the solid state to blue (402-425 nm) in acetonitrile solution. It showed that the ligand and metal cation can influence the structures and luminescence properties of complexes such as emission intensities and maximum wavelengths. Since these ligands and complexes could compensate for the absorption of N719 in the low-wavelength region of the visible spectrum and reduce charge recombination of the injected electron, the ligands L1-L3 and complexes Zn3/Hg3 were employed to prepare cosensitized dye-sensitized solar cells devices for investigating the influences of the electron-donating group and coordination on the DSSCs performance. Compared to DSSCs only being sensitized by N719, these prepared ligands and complexes chosen to cosensitize N719 in solar cell do enhanced its performance by 11-41%. In particular, a DSSC using L3 as cosensitizer displays better photovoltaic performance with a short circuit current density of 18.18 mA cm(-2), corresponding to a conversion efficiency of 7.25%. It is much higher than that for DSSCs only sensitized by N719 (5.14%).

The effects of diosgenin in the regulation of renal proximal tubular fibrosis.

Fibrosis is the important pathway for end-stage renal failure. Glucose has been demonstrated to be the most important fibrogenesis-inducing agent according to previous studies. Despite diosgenin has been demonstrated to be anti-inflammatory, the possible role in fibrosis regulation of diosgenin remain to be investigated. In this study, renal proximal tubular epithelial cells (designated as HK-2) were treated with high concentration of glucose (HG, 27.5mM) to determine whether diosgenin (0.1, 1 and 10 µM) has the effects to regulate renal cellular fibrosis. We found that 10 µM of diosgenin exert optimal inhibitory effects on high glucose-induced fibronectin expression in HK-2 cells. In addition, diosgenin markedly inhibited HG-induced increase in α-smooth muscle actin (α-SMA) and HG-induced decrease in E-cadherin. In addition, diosgenin antagonizes high glucose-induced epithelial-to-mesenchymal transition (EMT) signals partly by enhancing the catabolism of Snail in renal cells. Collectively, these data suggest that diosgenin has the potential to inhibit high glucose-induced renal tubular fibrosis possibly through EMT pathway.

[A purple-emitting luminescence complex [Cd(bpdc)(phen)2(H2O)] . 6H2O: synthesis, structure and spectral properties].

A supramolecular Cd(II) complex[Cd(bpdc) (phen)2 (H2O)] . 6H20 (1) was synthesized with 2, 4'-biphenyldicarboxylic acid (H2bpdc) and 1, 10-phenanthroline (phen) under hydrothermal conditions and characterized by single-crystal X-ray diffraction elemental analysis, and IR spectrum. Single-crystal X-ray analysis reveals complex 1 crystalizes in the triclinic P 1 space group, the metal center Cd(II) ion is six-coordinated and exhibits a distorted octahedron geometry arrangement. 3D supramolecular structure could be formed taking into account two kinds of hydrogen bonds and π--π interactions. At the same time, we discussed the luminescent properties of complex 1 in the solid-state as well as in the solvents at different temperatures. When excited at 350 nm, in the solid state at 298 K, 1 has purple luminescence with emission band at 390 nm; in the solid state at 77 K, 1 displays two emission bands at 380 and 520 nm. Because the vibration structure is more defined at low temperature, at 298 K, 1 also has purple luminescence in DMSO and CH3OH solutions with emission bands at 380 and 375 nm, which are blue-shifted compared with solid-state maximum emission band. These all can be attribute to the π*-->π transition based on the coordinate ligands. The fluorescence decay curves of complex 1 indicate that the processes of decay consist of two components. At 298 K, the lifetime of 1 is longer in DMSO solution (τ1 =1. 73 µs and τ2 =14. 07 µs) than that in CH3OH solution (τ1 =1. 21 µs and τ2 = 12. 44 µs). Moreover, the-lifetime of 1 is longer at 77 K (τ1 =1. 96 µs and τ2= 16. 11 µs) than that at 298 K in the solid state (τ1= 1. 20 µs and τ2 =11. 34 µs). The results might be caused by the increase in radiative rate and decrease in non-radiative rate at low temperature.

ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia.

BACKGROUND: In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold­inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). METHODS: CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. RESULTS: Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)­like population. Moreover, hyperthermia substantially improved the sensitivity of radiation­resistant NPC cells and CSC­like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti­tumor­killing activity of hyperthermia against NPC cells and CSC­like cells, whereas ectopic expression of Cirbp compromised tumor­killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC­like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. CONCLUSION: Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.