Objective:The tyrosine phosphatase SHP2 has a dual role in cancer initiation and progression in a tissue type-dependent manner.Several studies have linked SHP2 to the aggressive behavior of breast cancer cells and poo...Objective:The tyrosine phosphatase SHP2 has a dual role in cancer initiation and progression in a tissue type-dependent manner.Several studies have linked SHP2 to the aggressive behavior of breast cancer cells and poorer outcomes in people with cancer.Nevertheless,the mechanistic details of how SHP2 promotes breast cancer progression remain largely undefined.Methods:The relationship between SHP2 expression and the prognosis of patients with breast cancer was investigated by using the TCGA and GEO databases.The expression of SHP2 in breast cancer tissues was analyzed by immunohistochemistry.CRISPR/Cas9 technology was used to generate SHP2-knockout breast cancer cells.Cell-counting kit-8,colony formation,cell cycle,and EdU incorporation assays,as well as a tumor xenograft model were used to examine the function of SHP2 in breast cancer proliferation.Quantitative RT-PCR,western blotting,immunofluorescence staining,and ubiquitination assays were used to explore the molecular mechanism through which SHP2 regulates breast cancer proliferation.Results:High SHP2 expression is correlated with poor prognosis in patients with breast cancer.SHP2 is required for the proliferation of breast cancer cellsin vitro and tumor growthin vivo through regulation of Cyclin D1 abundance,thereby accelerating cell cycle progression.Notably,SHP2 modulates the ubiquitin–proteasome-dependent degradation of Cyclin D1viathe PI3K/AKT/GSK3βsignaling pathway.SHP2 knockout attenuates the activation of PI3K/AKT signaling and causes the dephosphorylation and resultant activation of GSK3β.GSK3βthen mediates phosphorylation of Cyclin D1 at threonine 286,thereby promoting the translocation of Cyclin D1 from the nucleus to the cytoplasm and facilitating Cyclin D1 degradation through the ubiquitin–proteasome system.Conclusions:Our study uncovered the mechanism through which SHP2 regulates breast cancer proliferation.SHP2 may therefore potentially serve as a therapeutic target for breast cancer.展开更多
Of the few avian influenza viruses that have crossed the species barrier to infect humans, the highly pathogenic influenza A （H5NI） strain has claimed the lives of more than half of the infected patients. With large...Of the few avian influenza viruses that have crossed the species barrier to infect humans, the highly pathogenic influenza A （H5NI） strain has claimed the lives of more than half of the infected patients. With largely unknown mechanism of lung injury by H5N1 infection, acute respiratory distress syndrome （ARDS） is the major cause of death among the victims. Here we present the fact that HSN 1 caused autophagic cell death through suppression of mTOR signaling. Inhibition of autophagy, either by depletion of autophagy gene Beclinl or by autophagy inhibitor 3-methyladenine （3-MA）, significantly reduced H5N1 mediated cell death. We suggest that autophagic cell death may contribute to the development of ARDS in H5N1 influenza patients and inhibition of autophagy could therefore become a novel strategy for the treatment of H5N1 infection.展开更多
Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer ce...Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.展开更多
The effect of a proteolytic starter culture isolated from Nanx Wudl,on microbiological,biochemical and organoleptic attributes of dry fermented sausages was investigated during processing.Based on preliminary screenin...The effect of a proteolytic starter culture isolated from Nanx Wudl,on microbiological,biochemical and organoleptic attributes of dry fermented sausages was investigated during processing.Based on preliminary screening,the combination of Staphylococcus xylosus SX16 and Lactobacillus plantarum CMRC6,showing excellent proteolytic activity in vitro,was selected as the multi-strain starter(starter LS).For comparison,the single-strain starter culture of L.plantarum CMRC6(starter LB)and non-inoculated control were also tested.During fermentation,lactic acid bacteria and staphylococci dominated the microbiota and suppressed the Enterobacteriaceae growth in LS-inoculated sausages.The addition of LS starter accelerated acidification and proteolysis during ripening,improving the contents of total free amino acids and several essential free amino acids(Phe,Ile and Leu).Volatile compounds analysis revealed that LS-fermented sausage showed the highest abundance of 3-methyl-1-butanol,probably due to the inoculated S.xylosus.The inoculation of LS starter improved the sensory properties of sausages,especially the flavor attribute.Therefore,S.xylosus SX16 and L.plantarum CMRC6 are promising candidates for inclusion as multi-strain starters in the manufacture of gourmet fermented dry sausage.展开更多
Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical applicatio...Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.展开更多
Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated de...Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated delayed fluorescence(TADF)materials,it is thus interesting to explore whether weak light-matter coupling can be used to redistribute optical density of states and to change the rate of radiative decay.Here,we demonstrate that the emission distribution of TADF emitters can be reshaped and narrowed in a top-emitting organic light-emitting device(OLED)with a weakly coupled microcavity.The Purcell effect of weak microcavity is found to be different for TADF emitters with different molecular orientations.We demonstrate that radiative rates of the TADF emitters with vertical orientation can be substantial increased in weakly coupled organic microcavity.These observations can enhance external quantum efficiencies,reduce efficiency roll-off,and improve color-purities of TADF OLEDs,especially for emitters without highly horizontal orientation.展开更多
Spermatogenesis is the process by which diploid male germ cells propagate and differentiate into haploid flagellated spermatozoa.This highly complicated process is dependent on testicular somatic cells maturation.Whil...Spermatogenesis is the process by which diploid male germ cells propagate and differentiate into haploid flagellated spermatozoa.This highly complicated process is dependent on testicular somatic cells maturation.While the role of these somatic cells in spermatogenesis is relatively well established,knowledge about their development and maturation,particularly at the molecular level,is limited.In this study,we profiled the testicular single-cell transcriptomes of Guanzhong black pigs at the age of 7,30,60,90,and 150 days.Five types of Sertoli cells,five types of Leydig cells,and four types of peritubular myoid cells were identified.Histological analysis revealed the changes in proliferation levels and marker gene expressions,and the prion-like protein gene(PRND)was identified as a novel marker for Sertoli cells.Additionally,integrated analyses of porcine and human datasets revealed similarities between human and pig testicular somatic cells.Overall,the data obtained in this study contribute to the understanding of testicular development in pigs as a model species.展开更多
The structure importance in Fault Tree Analysis(FTA) reflects how important Basic Events are to Top Event.Attribute at alternative level in Analytic Hierarchy Process(AHP) also reflect its importance to general goal.B...The structure importance in Fault Tree Analysis(FTA) reflects how important Basic Events are to Top Event.Attribute at alternative level in Analytic Hierarchy Process(AHP) also reflect its importance to general goal.Based on the coherence of these two methods,an improved AHP is put forward.Using this improved method,how important the attribute is to the fire safety of public building can be analyzed more credibly because of the reduction of subjective judgment.Olympic venues are very important public buildings in China.The fire safety evaluation of them will be a big issue to engineers.Improved AHP is a useful tool to the safety evaluation to these Olympic venues,and it will guide the evaluation in other areas.展开更多
In order to concentrate the diluted sulfuric acid from the titanium dioxide(TiO2)production of sulphate process,a new concentration process was proposed by coupling chemical dehydration and multi-effect evaporation.Th...In order to concentrate the diluted sulfuric acid from the titanium dioxide(TiO2)production of sulphate process,a new concentration process was proposed by coupling chemical dehydration and multi-effect evaporation.The ferrous sulfate monohydrate(FeSO4·H2O),as the dehydrant,was added to the diluted sulfuric acid to form ferrous sulfate heptahydrate(FeSO4·7H2O)according to the H2SO4-FeSO4-H2O phase diagrams,which partially removes the water.This process was named as Chemical Dehydration Process.The residual water was further removed by two-effect evaporation and finally 70 wt%sulfuric acid was obtained.The FeSO4·H2O can be regenerated through drying and dehydration of FeSO4·7H2O.The results show that FeSO4·H2O is the most suitable dehydrant,the optimal reaction time of chemical dehydration process is 30 min,and low temperature is favorable for the dehydration reaction.45.17%of the entire removed water can be removed by chemical dehydration from the diluted sulfuric acid.This chemical dehydration process is also energy efficient with 24.76%saving compared with the direct evaporation process.Furthermore,51.21%of the FeSO4 dissolved originally in the diluted sulfuric acid are precipitated out during the chemical dehydration,which greatly reduces the solid precipitation and effectively alleviates the scaling in the subsequent multi-effect evaporation process.展开更多
Yeasts play a critical role in the flavor formation of dry-cured ham.In this study,41 yeast isolates from the dry-cured ham at different processing stages were evaluated for their technological properties.Debaryomyces...Yeasts play a critical role in the flavor formation of dry-cured ham.In this study,41 yeast isolates from the dry-cured ham at different processing stages were evaluated for their technological properties.Debaryomyces hansenii was the most dominant yeast and has been detected at each phase of dry-cured ham,followed by Candida zeylanoides which was mainly detected in salting phase.Yarrowia bubula and Yarrowia alimentaria were found at the first two-phase of dry-cured ham.All isolates of yeast showed enzymatic activities against milk protein and tributyrin,while only 4 strains displayed proteolytic activity on meat protein.Yeast strains were grown in a meat model medium and volatile compounds were identified.The result showed that inoculated yeast strains could promote the production of volatiles and there were significant differences among strains.D.hansenii S25 showed the highest production of volatile compounds,followed by the strain C.zeylanoides C4.D.hansenii S25 was the highest producer of alcohols showing the highest production of benzeneethanol and 3-(methylthio)-1-propanol.Based on OAV and PLS analysis,D.hansenii S25 was strongly correlated with overall flavor and key volatile compounds of dry-cured ham,which could be selected as potential starter cultures.展开更多
Hydrothermal alteration of olivine greatly influences geodynamics and the recycling of volatiles(such as water and carbon)in subduction zones.Silica is an important component of geological fluids,and its influence on ...Hydrothermal alteration of olivine greatly influences geodynamics and the recycling of volatiles(such as water and carbon)in subduction zones.Silica is an important component of geological fluids,and its influence on the hydrothermal alteration of olivine remains poorly constrained.In this study,we performed experiments at 300–515℃ and 3.0 kbar(1 bar=10^(5)Pa)by reacting well homogenized mixtures of olivine and silica powders with saline solutions(0.5 mol L^(−1)NaCl).Silica greatly influences the reaction pathways,reaction rates,and molecular hydrogen(H_(2))formation during olivine hydrothermal alteration.In experiments at 300℃ and 3.0 kbar with mixtures of olivine and 10 wt%silica,olivine was replaced by serpentine and talc.The proportions of serpentine and talc were determined according to standard curves based on infrared spectroscopy analyses.Around 6.5%serpentine and 12%talc were produced after an experimental duration of 7 days,which had no change after a longer period(14 days).Compared to the kinetics in silica-free systems,the rates of olivine hydrothermal alteration in experiments with 10 wt%silica are much lower.The overall reaction is:4.5Forsterite+5.5SiO_(2),aq+4H_(2)O=Serpentine+2Talc.With the addition of more silica(20 wt%and 40 wt%),olivine was transformed into talc.The rates of reaction were much faster,e.g.,for experiments with olivine and 20 wt%silica,43%of talc was produced after 14 days,which increased to 77%for experiments with 40 wt%silica over the same period.The overall reaction is:3Forsterite+5SiO_(2),aq+2H_(2)O=2Talc.In experiments at 400–505℃ and 3.0 kbar,the promoting effect of silica on olivine hydrothermal alteration was also observed,which is closely associated with a decrease in Gibbs free energies of olivine hydrothermal alteration.At 300℃ and 3.0 kbar,silica decreased H_(2)formed during olivine hydrothermal alteration by around an order of magnitude,resulting in an increase in oxygen fugacity.Based on measured H_(2),we calibrated oxygen fugacities,ranging from 0.96 展开更多
Aerosol liquid water content(ALWC)plays an important role in secondary aerosol formation.In this study,a whole year field campaign was conducted at Shanxi in north Zhejiang Province during 2021.ALWC estimated by ISORR...Aerosol liquid water content(ALWC)plays an important role in secondary aerosol formation.In this study,a whole year field campaign was conducted at Shanxi in north Zhejiang Province during 2021.ALWC estimated by ISORROPIA-Ⅱ was then investigated to explore its characteristics and relationship with secondary aerosols.ALWC exhibited a highest value in spring(66.38μg/m^(3)),followed by winter(45.08μg/m^(3)),summer(41.64μg/m^(3)),and autumn(35.01μg/m^(3)),respectively.It was supposed that the secondary inorganic aerosols(SIA)were facilitated under higher ALWC conditions(RH>80%),while the secondary organic species tended to form under lower ALWC levels.Higher RH(>80%)promoted the NO_(3)^(-)formation via gas-particle partitioning,while SO_(4)^(2-)was generated at a relative lower RH(>50%).The ALWC was more sensitive to NO_(3)^(-)(R=0.94)than SO_(4)^(2-)(R=0.90).Thus,the self-amplifying processes between the ALWC and SIA enhanced the particle mass growth.The sensitivity of ALWC and OX(NO_(2)+O_(3))to secondary organic carbon(SOC)varied in different seasons at Shanxi,more sensitive to aqueous-phase reactions(daytime R=0.84;nighttime R=0.54)than photochemical oxidation(daytime R=0.23;nighttime R=0.41)in wintertime with a high level of OX(daytime:130-140μg/m^(3);nighttime:100-140μg/m^(3)).The self-amplifying process of ALWC and SIA and the aqueous-phase formation of SOC will enhance aerosol formation,contributing to air pollution and reduction of visibility.展开更多
Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical ...Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical are 1) education, 2) notification of screening opportunities, 3) registration, 4) submission of samples, 5) receiving results with an explanation, and 6) being advised where to receive evaluation and management from qualified healthcare personnel. Methods: Our primary objectives were to create, register, and pilot a website as a public platform for cervical cancer prevention for both city and rural, individual and organizational application. We selected two sites: Shenzhen City in China as the local city (individual participant) site, and Sangzhi County in Hunan Province as the remote (group management) site. The website was reviewable to all of China, but applications for screening and registration were open only to the women from the 2 pilot sites. In the local site, the women would first sign up (obtain a password) to view the website (www.mcareu.com), and then if they desired, they could register for screening using their true name and their state ID. After an offline confirmation of the address, the sampling kit would arrive. Results were available with additional education and guidance for care also on the website. Findings: 120,099 people nationwide visited the website in 27 months by the end of May, 2015, 1148 women from the sites registered at the website and 87.5% enrolled in the pilot trial. 72.3% of those testing positive returned for management. Virtually 100% of the registration/historical information was entered appropriately and 100% of the samples were handled properly. Interpretation: Web-based decision aids help patients through the uncertainties of healthcare. Applied to cervical cancer screening using self-collection, the effectiveness of the model specifically in respect to accessibility, education, registration, data input, and instructions for positive management was clearly d展开更多
Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2...Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.展开更多
Small cell lung cancer(SCLC)is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models.Here,we analyzed formalin-fixed,paraffin-embedded(FFPE)samples of surgical re...Small cell lung cancer(SCLC)is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models.Here,we analyzed formalin-fixed,paraffin-embedded(FFPE)samples of surgical resections by proteomic profiling,and stratified SCLC into three proteomic subtypes(S-I,S-II,and S-III)with distinct clinical outcomes and chemotherapy responses.The proteomic subtyping was an independent prognostic factor and performed better than current tumor–node–metastasis or Veterans Administration Lung Study Group staging methods.The subtyping results could be further validated using FFPE biopsy samples from an independent cohort,extending the analysis to both surgical and biopsy samples.The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy.Differentially overexpressed proteins in S-III,the worst prognostic subtype,allowed us to nominate potential therapeutic targets,indicating that patient selection may bring new hope for previously failed clinical trials.Finally,analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy.Collectively,our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.展开更多
Purpose: To evaluate the effects of surgical treatment on macular epiretinal membranes.Methods: Vitrectomy and membrane removal were undergone for idopathic or secondary macular epiretinal membrane.Results: Fourteen e...Purpose: To evaluate the effects of surgical treatment on macular epiretinal membranes.Methods: Vitrectomy and membrane removal were undergone for idopathic or secondary macular epiretinal membrane.Results: Fourteen eyes of 15 patients (93%) had vision improvement after operation in which 8 eyes (57%) increased 3 or more Senellen lines. Only one case suffered from paracentral scotoma. No other complications were noted. Conclusion: Surgical management of macular epiretinal membrane is safe and effective with good visual outcome and few complications. Eye Science 1996; 12:140 -144.展开更多
Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants.However,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in ...Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants.However,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans(Glycine max).In this study,we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers.Molecular and genetic studies have characterized two antagonistic regulators,the positive activator GmMYBA3 and the negative repressor GmMYBR1,that modulate the gene expression of anthocyanin biosynthesis in soybean flowers.Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a,highlighting the complexity of anthocyanin regulation in different soybean organs.Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes,with GmF3’5’H identified as a crucial determinant of white flower color.This study provides a molecular mechanism underlying soybean flower color determination,paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.展开更多
基金This work was supported by grants from the National Natural S&ence Foundation of China(grant Nos.81372844,81472474,81772804 and 81903092)Tianjin Municipal Science and Technology Commission(grant No.16JCYBJC25400)+1 种基金Changjiang Researchers and Innovative Research Team(grant No.IRT_14R40)Postgraduate Innovation Fund of"13th Five-Year Comprehensive Investment,"Tianjin Medical University(grant No.YJSCX201716).
文摘Objective:The tyrosine phosphatase SHP2 has a dual role in cancer initiation and progression in a tissue type-dependent manner.Several studies have linked SHP2 to the aggressive behavior of breast cancer cells and poorer outcomes in people with cancer.Nevertheless,the mechanistic details of how SHP2 promotes breast cancer progression remain largely undefined.Methods:The relationship between SHP2 expression and the prognosis of patients with breast cancer was investigated by using the TCGA and GEO databases.The expression of SHP2 in breast cancer tissues was analyzed by immunohistochemistry.CRISPR/Cas9 technology was used to generate SHP2-knockout breast cancer cells.Cell-counting kit-8,colony formation,cell cycle,and EdU incorporation assays,as well as a tumor xenograft model were used to examine the function of SHP2 in breast cancer proliferation.Quantitative RT-PCR,western blotting,immunofluorescence staining,and ubiquitination assays were used to explore the molecular mechanism through which SHP2 regulates breast cancer proliferation.Results:High SHP2 expression is correlated with poor prognosis in patients with breast cancer.SHP2 is required for the proliferation of breast cancer cellsin vitro and tumor growthin vivo through regulation of Cyclin D1 abundance,thereby accelerating cell cycle progression.Notably,SHP2 modulates the ubiquitin–proteasome-dependent degradation of Cyclin D1viathe PI3K/AKT/GSK3βsignaling pathway.SHP2 knockout attenuates the activation of PI3K/AKT signaling and causes the dephosphorylation and resultant activation of GSK3β.GSK3βthen mediates phosphorylation of Cyclin D1 at threonine 286,thereby promoting the translocation of Cyclin D1 from the nucleus to the cytoplasm and facilitating Cyclin D1 degradation through the ubiquitin–proteasome system.Conclusions:Our study uncovered the mechanism through which SHP2 regulates breast cancer proliferation.SHP2 may therefore potentially serve as a therapeutic target for breast cancer.
基金supported by the National Natural Science Foundation of China(No.30788004)the National Basic Research Program of China(973 Program)(No. 2009CB522106)Ministry of Education of China(111 Project)(No.B08007)
文摘Of the few avian influenza viruses that have crossed the species barrier to infect humans, the highly pathogenic influenza A （H5NI） strain has claimed the lives of more than half of the infected patients. With largely unknown mechanism of lung injury by H5N1 infection, acute respiratory distress syndrome （ARDS） is the major cause of death among the victims. Here we present the fact that HSN 1 caused autophagic cell death through suppression of mTOR signaling. Inhibition of autophagy, either by depletion of autophagy gene Beclinl or by autophagy inhibitor 3-methyladenine （3-MA）, significantly reduced H5N1 mediated cell death. We suggest that autophagic cell death may contribute to the development of ARDS in H5N1 influenza patients and inhibition of autophagy could therefore become a novel strategy for the treatment of H5N1 infection.
基金supported by the National Natural Science Foundation of China (Grant no. 81001186)the Tianjin Municipal Natural Science Foundation (Grant no. 10JCYBJ C14100,11JCZDJC28000,13JCYBJC21800)
文摘Apigenin （4＇,5,7-trihydroxyflavone） is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-（4,5-dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide （MTT） and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles （AVOs） by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-Ⅱ, the processed form of LC3-Ⅰ, was increased. Treatment with the autophagy inhibitor, 3-methyladenine （3-MA）, significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis- and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.
基金the National Key R&D Program of China(grant no.2018YFD0400404).
文摘The effect of a proteolytic starter culture isolated from Nanx Wudl,on microbiological,biochemical and organoleptic attributes of dry fermented sausages was investigated during processing.Based on preliminary screening,the combination of Staphylococcus xylosus SX16 and Lactobacillus plantarum CMRC6,showing excellent proteolytic activity in vitro,was selected as the multi-strain starter(starter LS).For comparison,the single-strain starter culture of L.plantarum CMRC6(starter LB)and non-inoculated control were also tested.During fermentation,lactic acid bacteria and staphylococci dominated the microbiota and suppressed the Enterobacteriaceae growth in LS-inoculated sausages.The addition of LS starter accelerated acidification and proteolysis during ripening,improving the contents of total free amino acids and several essential free amino acids(Phe,Ile and Leu).Volatile compounds analysis revealed that LS-fermented sausage showed the highest abundance of 3-methyl-1-butanol,probably due to the inoculated S.xylosus.The inoculation of LS starter improved the sensory properties of sausages,especially the flavor attribute.Therefore,S.xylosus SX16 and L.plantarum CMRC6 are promising candidates for inclusion as multi-strain starters in the manufacture of gourmet fermented dry sausage.
基金Acknowledgments This work was supported by the National Basic Research Program of China （2012CB934004）, the National Funds for Distinguished Young Scientists （31325010）, the Key Research Program of the Chinese Academy of Sciences （KGZD-EW-T06） and the National Natural Science Foundation of China （31300822）.
文摘Quercetin （Que） is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing antitumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin （Dox） by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly（ethylene glycol） and poly（D, L-lactide-co-glycolide）, respectively. The antitumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing chemotherapy-induced toxicity on normal nanoparticulate tissues.
基金supported by the National Natural Science Foundation of China(grant nos.61774074 and 61905086)Science and Technology Development Planning of Jilin Province(project nos.20190101024JH and 20200201296JC)+1 种基金the Hong Kong Scholars Program(project no.XJ2020028)grants from the Research Grants Council of the Hong Kong Special Administrative Region,China(project nos.11300418 and 11300419).
文摘Resonance interaction between a molecular transition and a confined electromagnetic field can lead to weak or strong light-matter coupling.Considering the substantial exciton–phonon coupling in thermally activated delayed fluorescence(TADF)materials,it is thus interesting to explore whether weak light-matter coupling can be used to redistribute optical density of states and to change the rate of radiative decay.Here,we demonstrate that the emission distribution of TADF emitters can be reshaped and narrowed in a top-emitting organic light-emitting device(OLED)with a weakly coupled microcavity.The Purcell effect of weak microcavity is found to be different for TADF emitters with different molecular orientations.We demonstrate that radiative rates of the TADF emitters with vertical orientation can be substantial increased in weakly coupled organic microcavity.These observations can enhance external quantum efficiencies,reduce efficiency roll-off,and improve color-purities of TADF OLEDs,especially for emitters without highly horizontal orientation.
基金supported in part by the National Natural Science Foundation of China(31772605)Research Project of Shaanxi Science and Technology Department(2020NY-003)to Tao Zhang。
文摘Spermatogenesis is the process by which diploid male germ cells propagate and differentiate into haploid flagellated spermatozoa.This highly complicated process is dependent on testicular somatic cells maturation.While the role of these somatic cells in spermatogenesis is relatively well established,knowledge about their development and maturation,particularly at the molecular level,is limited.In this study,we profiled the testicular single-cell transcriptomes of Guanzhong black pigs at the age of 7,30,60,90,and 150 days.Five types of Sertoli cells,five types of Leydig cells,and four types of peritubular myoid cells were identified.Histological analysis revealed the changes in proliferation levels and marker gene expressions,and the prion-like protein gene(PRND)was identified as a novel marker for Sertoli cells.Additionally,integrated analyses of porcine and human datasets revealed similarities between human and pig testicular somatic cells.Overall,the data obtained in this study contribute to the understanding of testicular development in pigs as a model species.
基金Support by the National Natural Science Foundation of China (Grant No.50536030)National Project of Scientific and Technical Supporting Programs funded by Ministry of Science & Technology of China (Grant No.2006BAK06B02)China Postdoctoral Science Foundation (Grant No.20070410220)
文摘The structure importance in Fault Tree Analysis(FTA) reflects how important Basic Events are to Top Event.Attribute at alternative level in Analytic Hierarchy Process(AHP) also reflect its importance to general goal.Based on the coherence of these two methods,an improved AHP is put forward.Using this improved method,how important the attribute is to the fire safety of public building can be analyzed more credibly because of the reduction of subjective judgment.Olympic venues are very important public buildings in China.The fire safety evaluation of them will be a big issue to engineers.Improved AHP is a useful tool to the safety evaluation to these Olympic venues,and it will guide the evaluation in other areas.
基金the State Key Laboratory of Vanadium and Titanium Resources Comprehensive Utilization of China for its financial supportthe financial support of National Natural Science Foundation of China(Grant No.21576168)Science and Technology Cooperation Fund of Sichuan University-Panzhihua(No:2018CDPZH-23-SCU)。
文摘In order to concentrate the diluted sulfuric acid from the titanium dioxide(TiO2)production of sulphate process,a new concentration process was proposed by coupling chemical dehydration and multi-effect evaporation.The ferrous sulfate monohydrate(FeSO4·H2O),as the dehydrant,was added to the diluted sulfuric acid to form ferrous sulfate heptahydrate(FeSO4·7H2O)according to the H2SO4-FeSO4-H2O phase diagrams,which partially removes the water.This process was named as Chemical Dehydration Process.The residual water was further removed by two-effect evaporation and finally 70 wt%sulfuric acid was obtained.The FeSO4·H2O can be regenerated through drying and dehydration of FeSO4·7H2O.The results show that FeSO4·H2O is the most suitable dehydrant,the optimal reaction time of chemical dehydration process is 30 min,and low temperature is favorable for the dehydration reaction.45.17%of the entire removed water can be removed by chemical dehydration from the diluted sulfuric acid.This chemical dehydration process is also energy efficient with 24.76%saving compared with the direct evaporation process.Furthermore,51.21%of the FeSO4 dissolved originally in the diluted sulfuric acid are precipitated out during the chemical dehydration,which greatly reduces the solid precipitation and effectively alleviates the scaling in the subsequent multi-effect evaporation process.
基金the financial support of Guizhou Province Science and Technology Plan Project(QKHZC[2020]1Y152)the Guizhou High-level Innovative Talent Training Project(Qianke Cooperation Platform Talent number[2016]5662)Guizhou Science and Technology Innovation Talent Team of Ecological Characteristic Meat Products(QKHPTRC[2020]5004).
文摘Yeasts play a critical role in the flavor formation of dry-cured ham.In this study,41 yeast isolates from the dry-cured ham at different processing stages were evaluated for their technological properties.Debaryomyces hansenii was the most dominant yeast and has been detected at each phase of dry-cured ham,followed by Candida zeylanoides which was mainly detected in salting phase.Yarrowia bubula and Yarrowia alimentaria were found at the first two-phase of dry-cured ham.All isolates of yeast showed enzymatic activities against milk protein and tributyrin,while only 4 strains displayed proteolytic activity on meat protein.Yeast strains were grown in a meat model medium and volatile compounds were identified.The result showed that inoculated yeast strains could promote the production of volatiles and there were significant differences among strains.D.hansenii S25 showed the highest production of volatile compounds,followed by the strain C.zeylanoides C4.D.hansenii S25 was the highest producer of alcohols showing the highest production of benzeneethanol and 3-(methylthio)-1-propanol.Based on OAV and PLS analysis,D.hansenii S25 was strongly correlated with overall flavor and key volatile compounds of dry-cured ham,which could be selected as potential starter cultures.
基金This study was supported by the National Natural Science Foundation of China(Grant No.41873069)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant Nos.XDA22050103,XDB42000000)the Shenzhen Municipal Natural Science Foundation(Grant No.JCYJ20220530113016038).
文摘Hydrothermal alteration of olivine greatly influences geodynamics and the recycling of volatiles(such as water and carbon)in subduction zones.Silica is an important component of geological fluids,and its influence on the hydrothermal alteration of olivine remains poorly constrained.In this study,we performed experiments at 300–515℃ and 3.0 kbar(1 bar=10^(5)Pa)by reacting well homogenized mixtures of olivine and silica powders with saline solutions(0.5 mol L^(−1)NaCl).Silica greatly influences the reaction pathways,reaction rates,and molecular hydrogen(H_(2))formation during olivine hydrothermal alteration.In experiments at 300℃ and 3.0 kbar with mixtures of olivine and 10 wt%silica,olivine was replaced by serpentine and talc.The proportions of serpentine and talc were determined according to standard curves based on infrared spectroscopy analyses.Around 6.5%serpentine and 12%talc were produced after an experimental duration of 7 days,which had no change after a longer period(14 days).Compared to the kinetics in silica-free systems,the rates of olivine hydrothermal alteration in experiments with 10 wt%silica are much lower.The overall reaction is:4.5Forsterite+5.5SiO_(2),aq+4H_(2)O=Serpentine+2Talc.With the addition of more silica(20 wt%and 40 wt%),olivine was transformed into talc.The rates of reaction were much faster,e.g.,for experiments with olivine and 20 wt%silica,43%of talc was produced after 14 days,which increased to 77%for experiments with 40 wt%silica over the same period.The overall reaction is:3Forsterite+5SiO_(2),aq+2H_(2)O=2Talc.In experiments at 400–505℃ and 3.0 kbar,the promoting effect of silica on olivine hydrothermal alteration was also observed,which is closely associated with a decrease in Gibbs free energies of olivine hydrothermal alteration.At 300℃ and 3.0 kbar,silica decreased H_(2)formed during olivine hydrothermal alteration by around an order of magnitude,resulting in an increase in oxygen fugacity.Based on measured H_(2),we calibrated oxygen fugacities,ranging from 0.96
基金supported by the National Natural Science Foundation of China(Nos.91844301 and 42005087)the support from State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex,Shanghai Academy of Environment Sciences(No.CX2020080581)。
文摘Aerosol liquid water content(ALWC)plays an important role in secondary aerosol formation.In this study,a whole year field campaign was conducted at Shanxi in north Zhejiang Province during 2021.ALWC estimated by ISORROPIA-Ⅱ was then investigated to explore its characteristics and relationship with secondary aerosols.ALWC exhibited a highest value in spring(66.38μg/m^(3)),followed by winter(45.08μg/m^(3)),summer(41.64μg/m^(3)),and autumn(35.01μg/m^(3)),respectively.It was supposed that the secondary inorganic aerosols(SIA)were facilitated under higher ALWC conditions(RH>80%),while the secondary organic species tended to form under lower ALWC levels.Higher RH(>80%)promoted the NO_(3)^(-)formation via gas-particle partitioning,while SO_(4)^(2-)was generated at a relative lower RH(>50%).The ALWC was more sensitive to NO_(3)^(-)(R=0.94)than SO_(4)^(2-)(R=0.90).Thus,the self-amplifying processes between the ALWC and SIA enhanced the particle mass growth.The sensitivity of ALWC and OX(NO_(2)+O_(3))to secondary organic carbon(SOC)varied in different seasons at Shanxi,more sensitive to aqueous-phase reactions(daytime R=0.84;nighttime R=0.54)than photochemical oxidation(daytime R=0.23;nighttime R=0.41)in wintertime with a high level of OX(daytime:130-140μg/m^(3);nighttime:100-140μg/m^(3)).The self-amplifying process of ALWC and SIA and the aqueous-phase formation of SOC will enhance aerosol formation,contributing to air pollution and reduction of visibility.
文摘Background: Community based cervical cancer screening models using self-collection can effectively place the identification of who is positive in the hands of the patient. The key areas we have identified as critical are 1) education, 2) notification of screening opportunities, 3) registration, 4) submission of samples, 5) receiving results with an explanation, and 6) being advised where to receive evaluation and management from qualified healthcare personnel. Methods: Our primary objectives were to create, register, and pilot a website as a public platform for cervical cancer prevention for both city and rural, individual and organizational application. We selected two sites: Shenzhen City in China as the local city (individual participant) site, and Sangzhi County in Hunan Province as the remote (group management) site. The website was reviewable to all of China, but applications for screening and registration were open only to the women from the 2 pilot sites. In the local site, the women would first sign up (obtain a password) to view the website (www.mcareu.com), and then if they desired, they could register for screening using their true name and their state ID. After an offline confirmation of the address, the sampling kit would arrive. Results were available with additional education and guidance for care also on the website. Findings: 120,099 people nationwide visited the website in 27 months by the end of May, 2015, 1148 women from the sites registered at the website and 87.5% enrolled in the pilot trial. 72.3% of those testing positive returned for management. Virtually 100% of the registration/historical information was entered appropriately and 100% of the samples were handled properly. Interpretation: Web-based decision aids help patients through the uncertainties of healthcare. Applied to cervical cancer screening using self-collection, the effectiveness of the model specifically in respect to accessibility, education, registration, data input, and instructions for positive management was clearly d
文摘Objective: To investigate the correlation between fundus atherosclerosis and carotid arterial atherosclerosis. Methods: A total of 516 people undergoing physical examination in Deyang People’s Hospital between June 2020 and December 2022 were randomly selected. Fundus atherosclerosis and carotid arterial atherosclerosis were evaluated by fundus photography and carotid artery ultrasonography, respectively. Results: Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). There were 286 cases (55.4%) without carotid atherosclerosis, 201 cases (38.9%) with carotid atherosclerotic plaque, and 33 cases (6.4%) with carotid stenosis. Fundus arteriosclerosis is independently associated with carotid artery intima-media thickness, vulnerable plaques, plaque scores, and carotid artery stenosis (P Conclusion: In summary, there is a close relationship between carotid artery disease and the degree of arteriosclerosis in the eyeground. Fundus photography is a simple, non-invasive, and easily acceptable method of inspection. The results obtained from it are useful in determining the severity of carotid atherosclerosis and guiding early detection and intervention in clinical cases. This can help reduce the incidence of cardiovascular and cerebrovascular diseases.
基金supported by the National Key R&D Program of China(Grant Nos.2018YFA0507503,2017YFA0505102,2017YFA0505103,and 2017YFA0505104)the National Natural Science Foundation of China(Grant Nos.82072597,62131009,31770892,31970725,31870828,81874237,and 81974016)+2 种基金the Beijing Municipal Natural Science Foundation(Grant No.7192199)the State Key Laboratory of Proteomics(Grant No.SKLP-K202002)the Kaifeng Science and Technology Development Plan Project(Grant No.1806005),China.
文摘Small cell lung cancer(SCLC)is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models.Here,we analyzed formalin-fixed,paraffin-embedded(FFPE)samples of surgical resections by proteomic profiling,and stratified SCLC into three proteomic subtypes(S-I,S-II,and S-III)with distinct clinical outcomes and chemotherapy responses.The proteomic subtyping was an independent prognostic factor and performed better than current tumor–node–metastasis or Veterans Administration Lung Study Group staging methods.The subtyping results could be further validated using FFPE biopsy samples from an independent cohort,extending the analysis to both surgical and biopsy samples.The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy.Differentially overexpressed proteins in S-III,the worst prognostic subtype,allowed us to nominate potential therapeutic targets,indicating that patient selection may bring new hope for previously failed clinical trials.Finally,analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy.Collectively,our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.
文摘Purpose: To evaluate the effects of surgical treatment on macular epiretinal membranes.Methods: Vitrectomy and membrane removal were undergone for idopathic or secondary macular epiretinal membrane.Results: Fourteen eyes of 15 patients (93%) had vision improvement after operation in which 8 eyes (57%) increased 3 or more Senellen lines. Only one case suffered from paracentral scotoma. No other complications were noted. Conclusion: Surgical management of macular epiretinal membrane is safe and effective with good visual outcome and few complications. Eye Science 1996; 12:140 -144.
基金supported by the National Natural Science Foundation of China(32201781,32100211)the Department of Science and Technology of Jilin Province(20220508112RC,20210101005JC)+1 种基金the Fundamental Research Fund for the Central Universities(2412023YQ005)China Agriculture Research System(CARS04)。
文摘Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants.However,the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans(Glycine max).In this study,we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers.Molecular and genetic studies have characterized two antagonistic regulators,the positive activator GmMYBA3 and the negative repressor GmMYBR1,that modulate the gene expression of anthocyanin biosynthesis in soybean flowers.Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a,highlighting the complexity of anthocyanin regulation in different soybean organs.Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis-related genes,with GmF3’5’H identified as a crucial determinant of white flower color.This study provides a molecular mechanism underlying soybean flower color determination,paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.
