Two-billion-year-old volcanism on the Moon from Chang'e-5 basalts.

The Moon has a magmatic and thermal history that is distinct from that of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by around 2.9-2.8 billion years ago (Ga)2,3, although younger basalts between 3 Ga and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4,5. Here we report a precise lead-lead age of 2,030 ± 4 million years ago for basalt clasts returned by the Chang'e-5 mission, and a 238U/204Pb ratio (µ value)6 of about 680 for a source that evolved through two stages of differentiation. This is the youngest crystallization age reported so far for lunar basalts by radiometric dating, extending the duration of lunar volcanism by approximately 800-900 million years. The µ value of the Chang'e-5 basalt mantle source is within the range of low-titanium and high-titanium basalts from Apollo sites (µ value of about 300-1,000), but notably lower than those of potassium, rare-earth elements and phosphorus (KREEP) and high-aluminium basalts7 (µ value of about 2,600-3,700), indicating that the Chang'e-5 basalts were produced by melting of a KREEP-poor source. This age provides a pivotal calibration point for crater-counting chronology in the inner Solar System and provides insight on the volcanic and thermal history of the Moon.

Nitric Oxide-Releasing Porous Coating with Antibacterial Activity and Blood Compatibility.

Nitric oxide (NO)-releasing coating is promising to enhance the biocompatibility of medical devices. In this study, polyurethane (PU) and S-nitrosated keratin (KSNO) were dissolved with dimethyl sulfoxide (DMSO) and tetrahydrofuran (THF) to prepare a coating solution. This solution is facile to form a porous coating on various substrates based on solvent-evaporation-induced phase separation (SEIPS). The coating could continuously release NO up to 200 h in the presence of ascorbic acid (Asc). In addition, the coating could accelerate endothelialization by promoting the viability of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation of human umbilical artery smooth muscle cells (HUASMCs). Furthermore, the coating had good antibacterial activity and blood compatibility. Taken together, this universal coating provides wider potential applications in the field of cardiovascular implants.

Liraglutide alleviates high-fat diet-induced kidney injury in mice by regulating the CaMKKß/AMPK pathway.

OBJECTIVE: Liraglutide, a glucagon-like peptide-1 receptor agonist, has been shown to regulate blood sugar and control body weight, but its ability to treat obesity-related nephropathy has been poorly studied. Therefore, this study was designed to observe the characteristics and potential mechanism of liraglutide against obesity-related kidney disease. METHODS: Thirty-six C57BL/6J male mice were randomly divided into six groups (n = 6 per group). Obesity-related nephropathy was induced in mice by continuous feeding of high-fat diet (HFD) for 12 weeks. After 12 weeks, liraglutide (0.6 mg/kg) and AMP-activated protein kinase (AMPK) agonists bortezomib (200 µg/kg) were injected for 12 weeks, respectively. Enzyme-linked immunosorbent assay was employed to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, blood urea nitrogen, creatinine in serum, as well as urinary protein in urine. Besides, hematoxylin-eosin staining and periodic acid-Schiff staining were used to observe the pathological changes of kidney tissue; immunohistochemistry, western blot, and real-time quantitative PCR to assess the calmodulin-dependent protein kinase kinase beta (CaMKKß)/AMPK signaling pathway activation. RESULTS: Liraglutide significantly reduced serum lipid loading, improved kidney function, and relieved kidney histopathological damage and glycogen deposition in the mouse model of obesity-related kidney disease induced by HFD. In addition, liraglutide also significantly inhibited the CaMKKß/AMPK signaling pathway in kidney tissue of HFD-induced mice. However, bortezomib partially reversed the therapeutic effect of liraglutide on HDF-induced nephropathy in mice. CONCLUSIONS: Liraglutide has a therapeutic effect on obesity-related kidney disease, and such an effect may be achieved by inhibiting the CaMKKß/AMPK signaling pathway in kidney tissue.

Yolk-Shell and Hollow Zr/Ce-UiO-66 for Manipulating Selectivity in Tandem Reactions and Photoreactions.

One of the hallmarks of multicomponent metal-organic frameworks (MOFs) is to finely tune their active centers to achieve product selectivity. In particular, obtaining bimetallic MOF hollow structures with precisely tailored redox centers under the same topology is still challenging despite a recent surge of such efforts. Herein, we present an engineering strategy named "cluster labilization" to generate hierarchically porous MOF composites with hollow structures and tunable active centers. By partially replacing zirconium with cerium in the hexanuclear clusters of UiO-66, unevenly distributed yolk-shell structures (YSS) were formed. Through acid treatment or annealing of the YSS precursor, single-shell hollow structures (SSHS) or double-shell hollow structures (DSHS) can be obtained, respectively. The active centers in SSHS and DSHS differ in their species, valence, and spatial locations. More importantly, YSS, SSHS, and DSHS with distinct active centers and microenvironments exhibit tunable catalytic activity, reversed selectivity, and high stability in the tandem reaction and the photoreaction.

Multiresponsive Keratin-Polysulfobetaine Conjugate-Based Micelles as Drug Carriers with a Prolonged Circulation Time.

A protein-polymer conjugate combines the chemical properties of a synthetic polymer chain with the biological properties of a protein. In this study, the initiator terminated with furan-protected maleimide was first synthesized through three steps. Then, a series of zwitterionic poly[3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate] (PDMAPS) was synthesized via atom transfer radical polymerization (ATRP) and optimized. Subsequently, well-controlled PDMAPS was conjugated with keratin via thiol-maleimide Michael addition. The keratin-PDMAPS conjugate (KP) could self-assemble in an aqueous solution to form micelles with low critical micelle concentration (CMC) values and good blood compatibility. The drug-loaded micelles exhibited triple responsiveness to pH, glutathione (GSH), and trypsin under tumor microenvironments. In addition, these micelles showed high toxicity against A549 cells while low toxicity on normal cells. Furthermore, these micelles performed prolonged blood circulation.

A Stable Fe-Zn Modified Sludge-Derived Biochar for Diuron Removal: Kinetics, Isotherms, Mechanism, and Practical Research.

To remove typical herbicide diuron effectively, a novel sludge-derived modified biochar (SDMBC600) was prepared using sludge-derived biochar (SDBC600) as raw material and Fe-Zn as an activator and modifier in this study. The physico-chemical properties of SDMBC600 and the adsorption behavior of diuron on the SDMBC600 were studied systematically. The adsorption mechanisms as well as practical applications of SDMBC600 were also investigated and examined. The results showed that the SDMBC600 was chemically loaded with Fe-Zn and SDMBC600 had a larger specific surface area (204 m2/g) and pore volume (0.0985 cm3/g). The adsorption of diuron on SDMBC600 followed pseudo-second-order kinetics and the Langmuir isotherm model, with a maximum diuron adsorption capacity of 17.7 mg/g. The biochar could maintain a good adsorption performance (8.88-12.9 mg/g) under wide water quality conditions, in the pH of 2-10 and with the presence of humic acid and six typical metallic ions of 0-20 mg/L. The adsorption mechanisms of SDMBC600 for diuron were found to include surface complexation, π-π binding, hydrogen bonding, as well as pore filling. Additionally, the SDMBC600 was tested to be very stable with very low Fe and Zn leaching concentration ≤0.203 mg/L in the wide pH range. In addition, the SDMBC600 could maintain a high adsorption capacity (99.6%) after four times of regeneration and therefore, SDMBC600 could have a promising application for diuron removal in water treatment.

"Typhoidal Cells" Appear in a Woman with Hemophagocytic Syndrome Secondary To Brucellosis: A Case Report.

We report a case of hemophagocytic syndrome (HPS) secondary to brucellosis, in which typhoidal cells were found in bone marrow, suggesting typhoidal cells present not only in Salmonella typhi infections but also in other bacterial infections. Typhoidal cells in bone marrow can be used to quickly identify the presence of bacterial infection pending the results of bone marrow and/or blood cultures.

Modeling the Enzyme Specificity by Molecular Cages through Regulating Reactive Oxygen Species Evolution.

Mimicking the active site and the substrate binding cavity of the enzyme to achieve specificity in catalytic reactions is an essential challenge. Herein, porous coordination cages (PCCs) with intrinsic cavities and tunable metal centers have proved the regulation of reactive oxygen species (ROS) generating pathways as evidenced by multiple photo-induced oxidations. Remarkably, in the presence of the Zn4 -µ4 -O center, PCC converted dioxygen molecules from triplet to singlet excitons, whereas the Ni4 -µ4 -O center promoted the efficient dissociation of electrons and holes to conduct electron transfer towards substrates. Accordingly, the distinct ROS generation behavior of PCC-6-Zn and PCC-6-Ni enables the conversion of O2 to 1 O2 and O2 ⋅- , respectively. In contrast, the Co4 -µ4 -O center combined the 1 O2 and O2 ⋅- together to generate carbonyl radicals, which in turn reacted with the oxygen molecules. Harnessing the three oxygen activation pathways, PCC-6-M (M=Zn/Ni/Co) display specific catalytic activities in thioanisole oxidation (PCC-6-Zn), benzylamine coupling (PCC-6-Ni), and aldehyde autoxidation (PCC-6-Co). This work not only provides fundamental insights into the regulation of ROS generation by a supramolecular catalyst but also demonstrates a rare example of achieving reaction specificity through mimicking natural enzymes by PCCs.

Tannic Acid-Assisted Immobilization of Copper(II), Carboxybetaine, and Argatroban on Poly(ethylene terephthalate) Mats for Synergistic Improvement of Blood Compatibility and Endothelialization.

Due to thrombosis and intimal hyperplasia, small-diameter vascular grafts have poor long-term patency. A combination strategy based on nitric oxide (NO) and anticoagulants has the potential to address those issues. In this study, poly(ethylene terephthalate) (PET) mats were prepared by electrospinning and coated with tannic acid (TA)/copper ion complexes. The chelated copper ions endowed the mats with sustained NO generation by catalytic decomposition of endogenous S-nitrosothiol. Subsequently, zwitterionic carboxybetaine acrylate (CBA) and argatroban (AG) were immobilized on the mats. The introduced AG and CBA had synergistic effects on the improvement of blood compatibility, resulting in reduced platelet adhesion and prolonged blood clotting time. The biocomposite mats selectively promoted the proliferation and migration of human umbilical vein endothelial cells while inhibiting the proliferation and migration of human umbilical arterial smooth muscle cells under physiological conditions. In addition, the prepared mats exhibited antibacterial activity against Escherichia coli and Staphylococcus aureus. Collectively, the prepared mats hold great promise as artificial small-diameter vascular grafts.

Contribution of Thrombospondin-1 and -2 to Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.

Thrombospondin (TSP) proteins have been shown to impact T-cell adhesion, migration, differentiation, and apoptosis. Thrombospondin-1 (TSP-1) is specifically upregulated in several inflammatory diseases and can effectively promote lipopolysaccharide- (LPS-) induced inflammation. In contrast, thrombospondin-2 (TSP-2) has been associated with activation of "anti-inflammatory" T-regulatory cells (Tregs). In this study, we investigated the effects of both TSP-1 and TSP-2 overexpression on macrophage polarization and activation in vitro and in vivo. We analyzed the effects of TSP-1 and TSP-2 on inflammation, vascular endothelial permeability, edema, ultrastructural morphology, and apoptosis in lung tissues of an ARDS mouse model and cultured macrophages. Our results demonstrated that TSP-2 overexpression effectively attenuated LPS-induced ARDS in vivo and promoted M2 macrophage phenotype polarization in vitro. Furthermore, TSP-2 played a role in regulating pulmonary vascular barrier leakage by activating the PI3K/Akt pathway. Overall, our findings indicate that TSP-2 can modulate inflammation and could therefore be a potential therapeutic target against LPS-induced ARDS.

Two CRISPR/Cas9 Systems Developed in Thermomyces dupontii and Characterization of Key Gene Functions in Thermolide Biosynthesis and Fungal Adaptation.

Thermomyces dupontii, a widely distributed thermophilic fungus, is an ideal organism for investigating the mechanism of thermophilic fungal adaptation to diverse environments. However, genetic analysis of this fungus is hindered by a lack of available and efficient gene-manipulating tools. In this study, two different Cas9 proteins from mesophilic and thermophilic bacteria, with in vivo expression of a single guide RNA (sgRNA) under the control of tRNAGly, were successfully adapted for genome editing in T. dupontii We demonstrated the feasibility of applying these two gene editing systems to edit one or two genes in T. dupontii The mesophilic CRISPR/Cas9 system displayed higher editing efficiency (50 to 86%) than the thermophilic CRISPR/Cas9 system (40 to 67%). However, the thermophilic CRISPR/Cas9 system was much less time-consuming than the mesophilic CRISPR/Cas9 system. Combining the CRISPR/Cas9 systems with homologous recombination, a constitutive promoter was precisely knocked in to activate a silent polyketide synthase-nonribosomal peptide synthase (PKS-NRPS) biosynthetic gene, leading to the production of extra metabolites that did not exist in the parental strains. Metabolic analysis of the generated biosynthetic gene mutants suggested that a key biosynthetic pathway existed for the biosynthesis of thermolides in T. dupontii, with the last two steps being different from those in the heterologous host Aspergillus Further analysis suggested that these biosynthetic genes might be involved in fungal mycelial growth, conidiation, and spore germination, as well as in fungal adaptation to osmotic, oxidative, and cell wall-perturbing agents.IMPORTANCEThermomyces represents a unique ecological taxon in fungi, but a lack of flexible genetic tools has greatly hampered the study of gene function in this taxon. The biosynthesis of potent nematicidal thermolides in T. dupontii remains largely unknown. In this study, mesophilic and thermophilic CRISPR/Cas9 gene editing systems were successfully established for both disrupting and activating genes in T. dupontii In this study, a usable thermophilic CRISPR/Cas9 gene editing system derived from bacteria was constructed in thermophilic fungi. Chemical analysis of the mutants generated by these two gene editing systems identified the key biosynthetic genes and pathway for the biosynthesis of nematocidal thermolides in T. dupontii Phenotype analysis and chemical stress experiments revealed potential roles of secondary metabolites or their biosynthetic genes in fungal development and adaption to chemical stress conditions. These two genomic editing systems will not only accelerate investigations into the biosynthetic mechanisms of unique natural products and functions of cryptic genes in T. dupontii but also offer an example for setting up CRISPR/Cas9 systems in other thermophilic fungi.

Catalytic Generation of Nitric Oxide from Poly(ε-caprolactone)/Phosphobetainized Keratin Mats for a Vascular Tissue Engineering Scaffold.

Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.

Keratin-Poly(2-methacryloxyethyl phosphatidylcholine) Conjugate-Based Micelles as a Tumor Micro-Environment-Responsive Drug-Delivery System with Long Blood Circulation.

Drug-loaded micelles with long circulation time in blood and stimuli-responsiveness under the tumor micro-environment can significantly enhance therapeutic efficacy. In this report, human hair keratin was extracted with a reduction method and then conjugated with zwitterionic poly(2-methacryloxyethyl phosphatidylcholine, MPC) via thiol chain transfer polymerization (thiol CTP). Subsequently, keratin-polyMPC conjugates (KPC) were prepared into micelles and loaded with doxorubicin (DOX) by self-assembly. These micelles exhibited pH, glutathione (GSH), and enzyme triple-responsiveness as well as charge reversibility under the tumor micro-environment. In addition, these micelles showed high toxicity against A549 cells while low toxicity to normal cells. In vivo anticancer efficacy results revealed that these micelles showed better therapeutic efficiency than free DOX. Furthermore, these carriers exhibited prolonged circulation time, good stability, and no hemolysis in blood. Based on the results, these drug delivery systems of micelles were proper candidates as drug carriers.

Screening of cardioprotective diseases bioactive components from Danshen extracts and LC-MS analysis.

A rapid and efficient analysis and screening method is adopted for cell affinity capture coupled with HPLC-MS (CAC-HPLC-MS) analysis of bioactive components that have possible efficiency against cardiovascular diseases. This method involves affinity capture, concentration, and separation of bioactive components from Danshen library using oxidatively damaged endothelial cells induced by H2 O2 , as well as analysis and identification of targeted compounds with HPLC and MS. It combines the specific interaction between cell membrane receptors and bioactive components with the powerful analysis and identification function of HPLC-MS. The CAC-HPLC-MS method was also used for analysis and screening of bioactive components from crude extracts of Danshen. A total of 19 components were found to be bound to oxidatively damaged endothelial cells with seven of these identified. Existing literature confirms that these seven components have many activities related to cardioprotective diseases. Therefore, the combination of biological affinity capture with HPLC-MS should be regarded as an attractive method with great potential for rapid and efficient screening of bioactive components related to anti-cardiovascular diseases from natural product libraries.

Uniportal thoracoscopic pulmonary lobectomy in the treatment of Lung Cancer.

OBJECTIVE: To investigate the clinical efficacy of uniportal thoracoscopic pulmonary lobectomy in the treatment of lung cancer. METHODS: One hundred and ten patients with lung cancer who were admitted to our hospital from February 2017 to June 2018 were enrolled and they were divided into the control group (55 patients) and observation group (55 patients) according to the random number table method. The patients in the observation group received uniportal thoracoscopic pulmonary lobectomy, and patients in the control group underwent triportal thoracoscopic pulmonary lobectomy. The surgical condition, postoperative pulmonary functions, postoperative complication incidence, and postoperative quality of life were compared between the two groups. RESULTS: The intraoperative blood loss and number of dissected lymph nodes of the observation group were (125.31±12.63) mL and (13.91±2.41) respectively, which were not significantly different with (127.54±13.60) mL and (13.96±2.69) of the control group (P>0.05). The incision length of the observation group was (4.22±0.31) cm, shorter than (6.97±0.42) cm of the control group, the postoperative pain score was (2.87±0.69) points, lower than (4.31±1.09) points of the control group, and the operation time was (195.21±19.42) minutes, longer than (162.68±18.52) min of the control group; the differences were significantly different (P<0.05). The postoperative forced vital capacity (FVC), Maximum Ventilatory Volume (MVV) and Forced Expiratory Volume in 1s (FEV1) in the observation group were (1.90±0.75) L, (54.59±16.03) L/minutes and (1.60±0.53) L respectively, larger than (1.06±0.28) L, (38.41±15.59) L/min and (1.02±0.15) L respectively (P<0.05). The scores of Short Form 36-item Health Survey (SF-36) of patients in the observation group was observed one month after surgery, significantly higher than those in the control group, and the difference was statistically significant (P<0.05). The incidence of complications of the postoperative complication of the observation group was 12.7%, which was not significantly different with 14.5% of the control group (P>0.05). CONCLUSION: Patients who receive uniportal video-assisted thoracoscopic pulmonary lobectomy have milder trauma, which is beneficial to the lung functions and postoperative recovery. Moreover, the number of dissected lymph nodes in uniportal thoracoscopic pulmonary lobectomy is equivalent with that in triportal thoracoscopic pulmonary lobectomy. Hence it is worth clinical promotion.

[Study on molecular of anti-tumor mechanism of Forsythia suspensa based on molecular docking and network pharmacology].

In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.

Harmine suppresses hyper-activated Ras-MAPK pathway by selectively targeting oncogenic mutated Ras/Raf in Caenorhabditis elegans.

BACKGROUND: Mutationally activated Ras proteins are closely linked to a wide variety of human cancers. Hence, there has been an intensive search for anti-Ras therapies for cancer treatment. The sole Ras gene, which encodes LET-60, in Caenorhabditis elegans regulates vulval development. While the loss of let-60 function leads to failure of vulva formation, the let-60(n1046gf) allele, which contains a missense mutation mimicking a Ras codon 13 mutation found in human cancers, results in extra vulval tissue, a phenotype named Muv (multiple vulvas). METHODS: By taking advantage of the easy-to-score Muv phenotype of let-60(n1046gf), we used a step-by-step screening approach (from crude extract to active fraction to active natural compound) to search for inhibitors of oncogenic Ras. Mutants of other key components in the Ras-mitogen-activated protein kinase (MAPK) pathway were used to identify other candidate targets. RESULTS: The natural compound harmine, isolated from the plant Peganum harmala, was found to suppress the Muv phenotype of let-60(n1046gf). In addition, harmine targets the hyper-activation of the Ras/MAPK pathway specifically caused by overexpression or mutated forms of LET-60/Ras and its immediate downstream molecule LIN-45/Raf. Finally, harmine can be absorbed into the worm body and probably functions in its native form, rather than requiring metabolic activation. CONCLUSION: In sum, we have revealed for the first time the anti-Ras activity of harmine in a C. elegans model system. Our results revealed the potential anti-cancer mechanism of harmine, which may be useful for the treatment of specific human cancers that are associated with oncogenic Ras mutations.

Mussel-Inspired Surface Functionalization of PET with Zwitterions and Silver Nanoparticles for the Dual-Enhanced Antifouling and Antibacterial Properties.

Herein, we designed and constructed a dual functional surface with antimicrobial and antifouling abilities to prevent protein and bacterial attachment that are significant challenges in biomedical devices. Primary amino-group-capped sulfobetaine of DMMSA was synthesized and then grafted onto polydopamine pretreated PET sheets via click chemistry. The sheets were subsequently immersed into silver ion solution, in which the absorbed silver ions were reduced to silver nanoparticles (AgNPs) in situ by a polydopamine layer. The antifouling assays demonstrated that the resultant PET/DMMSA/AgNPs sheets exhibited great antifouling performances against bovine serum albumin (BSA), bovine fibrinogen (BFG), platelets, and bacteria, the critical proteins/microorganisms leading to implant failure. The antibacterial data suggested that the sheets had dual functions as inhibitors of bacterial growth and bactericide and could efficiently delay the biofilm formation. This repelling and killing approach is green and simple, with potential biomedical applications.

Are the Same Health Warnings Effective Across Different Countries? An Experimental Study in Seven Countries.

INTRODUCTION: More than 100 countries have implemented pictorial health warnings on cigarette packages. However, few studies have compared how consumers from different geographic and cultural contexts respond to health warning content. The current study compares perceptions of warnings among adult smokers and youth in seven countries, to examine the efficacy of different health warning themes and images. METHODS: Between 2010 and 2012, online and face-to-face surveys were conducted with ~500 adult smokers and ~500 youth (age 16-18) smokers and nonsmokers in each of Mexico, United States, China, Germany, India, Bangladesh, and Republic of Korea (total N = 8182). Respondents were randomized to view and rate sets of 5-7 health warnings (each set for a different health effect); each set included a text-only warning and various types (ie, themes) of pictorial warnings, including graphic health effects, "lived experience," symbolic images, and personal testimonials. Mixed-effects models were utilized to examine perceived effectiveness of warning themes, and between-country differences in responses. RESULTS: Overall, pictorial warnings were rated as more effective than text-only warnings (p < .001). Among pictorial themes, "graphic" health effects were rated as more effective than warnings depicting "lived experience" (p < .001) or "symbolic" images (p < .001). Pictorial warnings with personal testimonials were rated as more effective than the same images with didactic text (p < .001). While the magnitude of differences between warning themes varied across countries, the pattern of findings was generally consistent. CONCLUSIONS: The findings support the efficacy of graphic pictorial warnings across diverse geographic and cultural contexts, and support sharing health warning images across jurisdictions. IMPLICATIONS: Although over 100 countries have implemented pictorial health warnings on cigarette packages, there is little research on the most effective types of message content across geographic and cultural contexts. The current study examined perceived effectiveness of text and pictorial health warnings featuring different message content-graphic health effects, "lived experience," personal testimonials, and symbolic imagery-among more than 8000 adults and youth in Mexico, United States, China, Germany, India, Bangladesh, and Korea. Across countries, "graphic" pictorial messages were rated as most effective. Consistencies across countries in rating message content suggests there may be "globally effective" themes and styles for designing effective health warnings.

[Curcumin inhibits proliferation,migration and invasion of gastric cancer cells via Wnt3a/ß-catenin/EMT signaling pathway].

The aim of this paper was to investigate the effects of curcumin on the proliferation,migration,invasion and apoptosis of human gastric cancer cells and to explore the potential mechanisms. SGC7901,MKN45 and NCI N87 cells lines were cultured under different concentrations of curcumin( 2. 5,5,10,20,40,80 and 160 µmol·L~(-1)) at different time points( 12,24,48 and 72 h),and the effect of curcumin on cell proliferation was detected by CCK-8 assay. The migration and invasiveness of cells were determined by wound healing and Transwell assays,the apoptosis rate was assessed by flow cytometry,the expression of N-cadherin,E-cadherin,snail1,Wnt3 a,p-ß-catenin,p-LRP6,Bcl-2 and Bax were detected by Western blot,and the enzymatic activity of caspase-3,caspase-8 and caspase-9 was evaluated via caspase kit. RESULTS:: indicated that the proliferation of MKN45 cells was significantly inhibited by curcumin in a dose-and time-dependent manner( IC50= 21. 93 µmol·L~(-1)). Moreover,curcumin could inhibit the migration and invasion of MKN45 cells,downregulate the expression of N-cadherin,snail1,Wnt3 a,p-ß-catenin,p-LRP6 and Bcl-2,and upregulate the expression of E-cadherin and Bax,it could increase the activity of caspase-3,caspase-8,caspase-9 and induce apoptosis as well. The potential mechanism is through inhibiting the Wnt3 a/ß-catenin/EMT pathway,regulating Bcl-2 signaling and caspase pathway,which might provide new potential strategies for gastric cancer treatment.