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Pomegranate (Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate 'Hongbaoshi' and a purple-red-skinned cultivar 'Moshiliu', by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of 'Hongbaoshi' but high Dp in late stages of 'Moshiliu' were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of 'Moshiliu'. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in 'Moshiliu' compared with 'Hongbaoshi'. Alao, ANR was specially expressed in 'Hongbaoshi', with extremely low expression levels in 'Moshiliu'. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYBs and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin 'Moshiliu'. SG4 MYBs exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in 'Moshiliu' pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate.
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Antocianinas , Frutas , Regulación de la Expresión Génica de las Plantas , Granada (Fruta) , Transcriptoma , Frutas/genética , Frutas/metabolismo , Antocianinas/metabolismo , Antocianinas/genética , Granada (Fruta)/genética , Granada (Fruta)/metabolismo , Pigmentación/genética , Perfilación de la Expresión Génica , Color , Metabolómica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Activating industrially important aromatic hydrocarbons by installing halogen atoms is extremely important in organic synthesis and often improves the pharmacological properties of drug molecules. To this end, tryptophan halogenase enzymes are potentially valuable tools for regioselective halogenation of arenes, including various industrially important indole derivatives and similar scaffolds. Although endogenous enzymes show reasonable substrate scope towards indole compounds, their efficacy can often be improved by engineering. Using a structure-guided semi-rational mutagenesis approach, we have developed two RebH variants with expanded biocatalytic repertoires that can efficiently halogenate several novel indole substrates and produce important pharmaceutical intermediates. Interestingly, the engineered enzymes are completely inactive towards their natural substrate tryptophan in spite of their high tolerance to various functional groups in the indole ring. Computational modelling and molecular dynamics simulations provide mechanistic insights into the role of gatekeeper residues in the substrate binding site and the dramatic switch in substrate specificity when these are mutated.
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Proteínas Bacterianas/metabolismo , Indoles/química , Oxidorreductasas/metabolismo , Triptófano/metabolismo , Actinobacteria/enzimología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Biocatálisis , Halogenación , Indoles/metabolismo , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Oxidorreductasas/química , Oxidorreductasas/genética , Especificidad por Sustrato , Triptófano/químicaRESUMEN
The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , China , Control de Enfermedades Transmisibles , Monitoreo del Ambiente , Humanos , Oxígeno , Material Particulado/análisis , SARS-CoV-2RESUMEN
At present, lung cancer ranks second and first respectively in the incidence and the mortality among malignant tumors. It is urgent to find new effective anti-lung cancer drugs with less side effects and relatively defined mechanisms. Endoplasmic reticulum stress (ERS)-mediated apoptosis pathway is an effective way to promote tumor cell apoptosis; diterpenoid tanshinone (DT), an effective part separated from Salviae Miltiorrhizae Radix et Rhizoma, was found to have an anti-lung cancer effect in previous studies via ERS-induced PERK-EIF2α pathway. In this paper, human lung adenocarcinoma PC9 cell line and nude mouse transplantation tumor model were applied to verify the anti-lung cancer effect of DT in vivo and in vitro, and illuminate the potential mechanism via ERS induced IRE1α/caspase 12 apoptosis pathway. The results showed that in vivo, DT could promote PC9 cell apoptosis in a concentration-dependent manner, up-regulate Bip, IRE1 and TRAF2 protein expressions in tumor tissue, reduce tumor weight and alleviate bodyweight loss. In vitro, DT inhibited the proliferation of PC9 cell line in a concentration-dependent manner, and destroyed the structure of mitochondria in PC9 cell, promoted Bax, IRE1α, Bip, TRAF2 and caspase 12 protein expressions, lower Bcl-2 protein expression in a time-dependent manner. DT shows a good effect on anti-lung cancer both in vivo and in vitro. The mechanism is related to the activation of ERS-induced IRE1α/caspase 12 apoptosis pathway and the promotion of cell apoptosis. ERS-mediated apoptosis pathway may be an important target of DT on anti-lung cancer.
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Estrés del Retículo Endoplásmico , Neoplasias Pulmonares , Abietanos , Animales , Apoptosis , Línea Celular Tumoral , Humanos , Ratones , Transducción de SeñalRESUMEN
OBJECTIVE: To observe the expression of phospholipid scramblase 1 (PLSCR1) in matrine (MAT) induced differentiation of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) cells, and to explore its correlation to cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal pathway. METHODS: NB4 (an APL cell line sensitive to ATRA) and NB4-R1 (a resistant strain of ATRA) were observed as subjects in this study. Effects of combined treatment of 0.1 mmol/L MAT and 1 [mol/L ATRA on the differentiation of two cell lines were detected using nitroblue tetrazolium (NBT) reduction test and flow cytometry (CD11b). Expressions of PML/RARot and PLSCR1 protein/gene were detected using Western blot and Real-time fluorescence quantitative PCR assay. Meanwhile, H89, PKA antagonist, was used to observe cell differentiation antigen and changes of aforesaid proteins and genes. RESULTS: MAT combined ATRA could significantly elevate positive rates of NBT and CD11 b in NB4-R1 cells, and significantly down-regulate the expression of PML/RARapha-fusion protein/gene (P < 0.05, P < 0.01). ATRA used alone could obviously enhance the expression of PLSCRI in NB4 cells at protein and mRNA levels (P < 0.01). But the expression of PLSCR1 was up-regulated in NB4-R1 cells, but with statistical.difference only at the protein level (P <0. 01). In combination of MAT, PLSCR1 protein expression was further elevated in the two cell lines (P < 0.01). Besides, there was statistical difference in mRNA expressions in NB4-R1 cells (P < 0.05). All these actions could be reversed by treatment of 10 micromol/L H89 (P < 0.05, P < 0.01). CONCLUSION: MAT combined ATRA could significantly induce the differentiation of NB4-R1 cells, and inhibit the expression of PML/RARalpha fusion gene/protein, which might be associated with up-regulating PLSCR1 expression.
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Diferenciación Celular , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Transferencia de Fosfolípidos/metabolismo , Alcaloides , Antineoplásicos , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Quinolizinas , ARN Mensajero , Transducción de Señal , Tretinoina , Células Tumorales Cultivadas , Regulación hacia Arriba , MatrinasRESUMEN
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) provide an in vitro system to identify the impact of cell behavior on the earliest stages of cell fate specification during human development. Here, we developed an hiPSC-based model to study the effect of collective cell migration in meso-endodermal lineage segregation and cell fate decisions through the control of space confinement using a detachable ring culture system. RESULTS: The actomyosin organization of cells at the edge of undifferentiated colonies formed in a ring barrier differed from that of the cells in the center of the colony. In addition, even in the absence of exogenous supplements, ectoderm, mesoderm, endoderm, and extraembryonic cells differentiated following the induction of collective cell migration at the colony edge by removing the ring-barrier. However, when collective cell migration was inhibited by blocking E-cadherin function, this fate decision within an hiPSC colony was altered to an ectodermal fate. Furthermore, the induction of collective cell migration at the colony edge using an endodermal induction media enhanced endodermal differentiation efficiency in association with cadherin switching, which is involved in the epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that collective cell migration can be an effective way to drive the segregation of mesoderm and endoderm lineages, and cell fate decisions of hiPSCs.
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AIMS: Immunotherapy has shown remarkable effects on several malignancies; however, its impact on gastric cancers has been limited. Therefore, a novel strategy to overcome resistance to immunotherapy is required. In this study, we compared the gene expression profiles of two murine GC cell lines that exhibited different effects on tumor immunity. The functions of specific genes related to negative tumor immunity and the impact of a specific inhibitor were evaluated in syngeneic GC mouse models. MATERIALS AND METHODS: RT-PCR and Western blotting validated Gas6 and AXL expression in murine cell lines. RT-PCR compared YTN16 and YTN3 GC cell's impact on T cell activation. AXL, the receptor for GAS6 in YTN16, was validated by western blotting. Gas6 was inhibited in YTN16 cells using shRNA, and then the gene expression pattern, effects to T cell activation, and tumor growth were assessed. YTN16 cells were injected into mice and treated with CCB-3233, anti-PD-1 antibody, or both. Immunohistochemistry and flow cytometry evaluated tumor-infiltrating immune cells. KEY FINDINGS: YTN16 cells expressed more Gas6 and had reduced T cell activation compared to YTN3 cells. AXL activation was higher in YTN16. CCB-3233 reduced AXL phosphorylation. Knocking down Gas6 in YTN16 reduced immunosuppression-related genes and increased tumor-infiltrating T cells. Combined CCB-3233 and anti-PD-1 treatment reduced tumor growth and increased T-cell infiltration. Human GC data revealed a negative correlation between GAS6 and immune activation-related genes. SIGNIFICANCE: The GAS6/AXL pathway contributes to immunotherapy resistance in GC. Targeting this pathway may be a novel therapeutic strategy.
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Proteínas Tirosina Quinasas Receptoras , Neoplasias Gástricas , Humanos , Ratones , Animales , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Tirosina Quinasa del Receptor Axl , Neoplasias Gástricas/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Microambiente Tumoral , InmunoterapiaRESUMEN
Halogenation of bioactive peptides via incorporation of non-natural amino acid derivatives during chemical synthesis is a common strategy to enhance functionality. Bacterial tyrptophan halogenases efficiently catalyze regiospecific halogenation of the free amino acid tryptophan, both in vitro and in vivo. Expansion of their substrate scope to peptides and proteins would facilitate highly-regulated post-synthesis/expression halogenation. Here, we demonstrate novel in vitro halogenation (chlorination and bromination) of peptides by select halogenase enzymes and identify the C-terminal (G/S)GW motif as a preferred substrate. In a first proof-of-principle experiment, we also demonstrate chemo-catalyzed derivatization of an enzymatically chlorinated peptide, albeit with low efficiency. We further rationally derive PyrH halogenase mutants showing improved halogenation of the (G/S)GW motif, both as a free peptide and when genetically fused to model proteins with efficiencies up to 90%.
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Halogenación , Oxidorreductasas , Oxidorreductasas/metabolismo , Proteínas Bacterianas/metabolismo , Péptidos/metabolismo , Aminoácidos/metabolismoRESUMEN
Biocatalytic C-H halogenation is becoming increasingly attractive due to excellent catalyst-controlled selectivity and environmentally benign reaction conditions. Significant efforts have been made on enzymatic halogenation of industrial arenes in a cost-effective manner. Here we report an unprecedented enzymatic halogenation of a panel of industrially important indole, azaindole and anthranilamide derivatives using a thermostable RebH variant without addition of any external flavin reductase enzyme. The reactions were catalyzed by the RebH variant 3-LSR enzyme with the help of a co-purified E. coli reductase identified as alkyl hydroperoxide reductase F (AhpF).
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Introduction: A contactless multiscale cardiac motion measurement method is proposed using impulse radio ultra-wideband (IR-UWB) radar at a center frequency of 7.29 GHz. Motivation: Electrocardiograph (ECG), heart sound, and ultrasound are traditional state-of-the-art heartbeat signal measurement methods. These methods suffer from defects in contact and the existence of a blind information segment during the cardiogram measurement. Methods: Experiments and analyses were conducted using coarse-to-fine scale. Anteroposterior and along-the-arc measurements were taken from five healthy male subjects (aged 25-43) when lying down or prone. In every measurement, 10 seconds of breath-holding data were recorded with a radar 55 cm away from the body surface, while the ECG was monitored simultaneously as a reference. Results: Cardiac motion detection from the front was superior to that from the back in amplitude. In terms of radar detection angles, the best cardiac motion information was observed at a detection angle of 120°. Finally, in terms of cardiac motion cycles, all the ECG information, as well as short segments of cardiac motion details named blind ECGs segments, were detected. Significance: A contactless and multiscale cardiac motion detection method is proposed with no blind detection of segments during the entire cardiac cycle. This paves the way for a potentially significant method of fast and accurate cardiac disease assessment and diagnosis that exhibits promising application prospects in contactless online cardiac monitoring and in-home healthcare.
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a-FABP is indespensible in inflammation and may serve as a new potential drug target for inflammation related diseases. We have successfully designed and synthesized a series of aromatic substituted pyrazoles as new human a-FABP inhibitors. The compounds strongly bound to the hydrophobic binding pocket of a-FABP, while showed significantly lower binding affinities to the closely related homologue protein h-FABP. The most potent and selective compound 5 g bound to a-FABP with an apparent K(i) value below 1.0 nM, while did not inhibit h-FABP at 50 µM and thus represents one of the most potent and selective a-FABP inhibitors to date. The strong binding capacity of these inhibitors was further validated by their effective blockade of inflammatory responses as determined by the production of pro-inflammatory cytokines upon LPS stimulation. Compound 5 g may serve as a lead compound for developing new effective therapeutic agent for prevention and treatment of atherosclerosis, type 2 diabetes and other inflammatory and metabolic related diseases.
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Adipocitos/efectos de los fármacos , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Proteínas de Unión a Ácidos Grasos/antagonistas & inhibidores , Pirazoles/síntesis química , Pirazoles/farmacología , Antiinflamatorios/química , Diseño de Fármacos , Humanos , Modelos Moleculares , Estructura Molecular , Unión Proteica/efectos de los fármacos , Pirazoles/químicaRESUMEN
OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.
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Medicamentos Herbarios Chinos/uso terapéutico , Qi , Trombocitopenia/tratamiento farmacológico , Deficiencia Yin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/uso terapéutico , Recuento de Plaquetas , Trombocitopenia/sangre , Deficiencia Yin/sangre , Adulto JovenRESUMEN
Here, we compare two different transparent conducting oxides (TCOs), namely indium tin oxide (ITO) and indium zinc tin oxide (IZTO), fabricated as transparent conducting films using processes that require different temperatures. ITO and IZTO films were prepared at 230 °C and at room temperature, respectively, on glass and polyethylene terephthalate (PET) substrates using reactive magnetron sputtering. Electrochromic WO3 films deposited on ITO-based and IZTO-based ECDs using vacuum cathodic arc plasma (CAP) were investigated. IZTO-based ECDs have higher optical transmittance modulation, ΔT = 63% [from Tbleaching (90.01%) to Tcoloration (28.51%)], than ITO-based ECDs, ΔT = 59%. ECDs consisted of a working electrochromic electrode (WO3/IZTO/PET) and a counter-electrode (Pt mesh) in a 0.2 M LiClO4/perchlorate (LiClO4/PC) liquid electrolyte solution with an active area of 3 cm × 4 cm a calculated bleaching time tc of 21.01 s and a coloration time tb of 4.7 s with varying potential from -1.3 V (coloration potential, Vc) to 0.3 V (bleaching potential, Vb).
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Oxygenated volatile organic compounds (OVOCs) are important intermediates in the troposphere and the most important sources of ozone. Proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) was used to measure VOCs in the Chengdu Plain, Southwestern China. The diurnal variations, photochemical reactivity, O3 formation potential, and sources were also investigated. The mixing ratios of ten kinds of VOCs (acetaldehyde, acetone, isoprene, Methyl ethyl ketone, Methyl vinyl ketone and Methacrolein, benzene, toluene, styrene, C8 aromatics, and C9 aromatics) were (10.97±4.69)×10-9. The concentrations of OVOCs, aromatic hydrocarbons, and biogenic VOCs were (8.54±3.44)×10-9, (1.53±0.93)×10-9, and (0.90±0.32)×10-9, respectively. Isoprene, acetaldehyde, and m-xylene were the top three photochemically active species with the greatest O3 formation potentials. The dominant three OVOCs species (acetaldehyde, acetone, and MEK) were mainly derived from local biogenic sources and anthropogenic secondary sources, and acetone had a strong regional background level, indicating that pollution in this area is significantly affected by regional transmission. This study deepens the understanding of regional O3 formation mechanisms in southwest China and provides a basis for the scientifically informed control of O3 pollution.
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Nanoporous structures have proven as an effective way for enhanced electrochromic performance by providing a large surface area can get fast ion/electron transfer path, leading to larger optical modulation and fast response time. Herein, for the first time, application of vacuum cathodic arc plasma (CAP) deposition technology to the synthesis of WO3/NiO electrode films on ITO glass for use in fabricating complementary electrochromic devices (ECDs) with a ITO/WO3/LiClO4-Perchlorate solution/NiO/ITO structure. Our objective was to optimize electrochromic performance through the creation of electrodes with a nanoporous structure. We also examined the influence of WO3 film thickness on the electrochemical and optical characteristics in terms of surface charge capacity and diffusion coefficients. The resulting 200-nm-thick WO3 films achieved ion diffusion coefficients of (7.35 × 10-10 (oxidation) and 4.92 × 10-10 cm2/s (reduction)). The complementary charge capacity ratio of WO3 (200 nm thickness)/NiO (60 nm thickness) has impressive reversibility of 98%. A demonstration ECD device (3 × 4 cm2) achieved optical modulation (ΔT) of 46% and switching times of 3.1 sec (coloration) and 4.6 sec (bleaching) at a wavelength of 633 nm. In terms of durability, the proposed ECD achieved ΔT of 43% after 2500 cycles; i.e., 93% of the initial device.
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OBJECTIVE: To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. METHODS: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and ß -galactosidase (ß -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. RESULTS: Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced ß -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01). CONCLUSION: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.
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Médula Ósea/efectos de los fármacos , Senescencia Celular/efectos de los fármacos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Ciclofosfamida/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Animales , Antineoplásicos Alquilantes/efectos adversos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , RatonesRESUMEN
To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (nâ=â1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3âkm of living residence (odds ratio [OR]â=â8.73, 95% CI: 1.42-53.74, Pâ=â.019), living in a newly decorated house/apartment (ORâ=â25.37, 95% CI: 4.44-144.81, Pâ<â.001), vegetarian diet (ORâ=â131.60, 95% CI: 3.45-5020.16, Pâ=â.009), preference of sugar (ORâ=â89.38, 95% CI: 7.22-1106.44, Pâ<â.001), preference of oily food (ORâ=â55.68, 95% CI: 5.12-605.26, Pâ=â.001), drinking lake water or pond water (ORâ=â58.05, 95% CI: 3.21-1049.81, Pâ<â.001), habit of staying up late (ORâ=â11.87, 95% CI: 3.43-41.02, Pâ<â.001), infection history (ORâ=â10.08, 95% CI: 2.75-36.93, Pâ<â.001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.
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Anemia Aplásica/etiología , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Anemia Aplásica/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , China/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Conductas Relacionadas con la Salud/etnología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Objective:To evaluate the relationship between mitochondrial calcium uniporter protein (MCU)-mediated mitochondrial dynamics and intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four wild-type adult male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (IIR group), sham operation+ MCU inhibitor Ru360 group (S+ Ru360 group) and intestinal I/R + Ru360 group (IIR+ Ru360 group). The mouse model of intestinal I/R injury was prepared by clamping the root of the superior mesenteric artery for 45 min followed by 2 h of reperfusion in anesthetized animals. Small intestinal tissues were obtained at the end of reperfusion for examination of the intestinal mucosal injury which was scored according to Chiu and for determination of the content of malondialdehyde (MDA) (TBA method), activity of superoxide dismutase (SOD) (WST-8 method), content of lactic dehydrogenase (LDH) (colorimetric method), and expression of MCU, dynamin-related protein 1 (Drp1), recombinant human mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1) and Mfn2 (by Western blot). Results:Compared with S and S+ Ru360 groups, the Chiu′s score and contents of MDA and LDH were significantly increased, the activity of SOD was decreased, the expression of MCU, Drp1 and Fis1 was up-regulated, and the expression of Mfn1 and Mfn2 was down-regulated in IIR and IIR+ Ru360 groups ( P<0.05). Compared with IIR group, the Chiu′s score and contents of MDA and LDH were significantly decreased, the activity of SOD was increased, the expression of MCU, Drp1 and Fis1 was down-regulated, and the expression of Mfn1 and Mfn2 was up-regulated in IIR+ Ru360 group ( P<0.05). Conclusions:The mechanism underlying intestinal I/R injury may be related to MCU-induced promotion of mitochondrial fission, reduction of mitochondrial fusion and mediation of imbalance in mitochondrial dynamics in mice.
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This paper reports on the fabrication of indium-zinc-tin-oxide (IZTO) transparent conductive film deposited by direct current (DC) reactive magnetron sputtering. The electrical, structural, and optical properties of IZTO film were investigated by Hall measurement, X-ray diffraction (XRD), and optical transmission spectroscopy with various sputtering powers. The IZTO film prepared used power at 100 W showed the lowest resistivity of 5.2 × 10-4 Ω cm. To accomplish rapid switching and high optical modulation, we have fabricated an electrochromic device (ECD) consisting of an working electrode (WO3 electrode film deposited on IZTO/ITO/glass) and a counter-electrode (Pt mesh) in 0.2 M LiClO4/PC liquid solution. The device demonstrated an optical contrast of 44% and switching times of 4.6 s and 8.1 s for the coloring and bleaching state, respectively, at the wavelength of 550 nm.
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Objective: To analyze the prevalence and the trend of the disease burden of chronic respiratory diseases and relevant risk factors in Jiangsu province from 1990 to 2019 and provide evidence for the prevention and treatment of chronic respiratory diseases. Methods: The data from the 2019 Global Burden of Disease Study (GBD2019) were used to calculate the prevalence rate, mortality rate and disability-adjusted life year (DALY) rate. Software Joinpoint was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of the standardized prevalence rate, standardized mortality rate and standardized DALY rate. The population attributable fractions (PAF) were used to estimate the proportion of chronic respiratory disease caused by different risk factors. Results: In 1990 and 2019, the prevalence rates of chronic respiratory diseases were 4.83% and 5.45%. The mortality rates were 134.91/100 000 and 80.99/100 000 respectively, and the DALY rates were 2 678.52/100 000 and 1 534.31/100 000 respectively. From 1990 to 2019, the age-standardized prevalence rate, mortality rate and DALY rate in Jiangsu showed a significant downward trend (AAPC values were -0.90%, -5.28% and -4.70% respectively, P<0.05). Tobacco use was the leading cause of chronic respiratory diseases, followed by air pollution, occupational exposure, suboptimal temperature and high BMI. Compared with 1990, the proportion of DALYs of chronic respiratory diseases attributable to tobacco use and high BMI increased in 2019. Conclusion: The overall burden of chronic respiratory diseases in Jiangsu shows a downward trend. Prevention and health education should be focused on the population with a smoking history and high BMI. At the same time, environmental management, attention to suboptimal temperature and control of occupational exposure factors should also be adopted as important means to prevent and control chronic respiratory diseases.