The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved ...The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.展开更多
The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower sp...To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,展开更多
How the tubular network of the endoplasmic reticulum (ER) is generated is not well understood, but a class of membrane proteins, the reticulons and DP1/Yop1p, are known
The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide （LPS） and interferon-γ （IFN-γ）. However, M1 can be found under physiological conditions without any pathological stimu...The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide （LPS） and interferon-γ （IFN-γ）. However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages （BMDMs） were activated with LPS＋IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction （RT-qPCR） and fluorescence-activated cell sorting （FACS）. Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive （iNOS＋） cells in vivo, suggesting an association between RANKL expression and iNOS＋ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger Ml-like macrophages with properties that were different from those of LPS＋IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.展开更多
Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studie...Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than展开更多
Dear Editor Despite remarkable advances in our understanding of brain functions,the neural substrates and correlates of consciousness remain unclear[1].It has been argued that classical physics is intrinsically incapa...Dear Editor Despite remarkable advances in our understanding of brain functions,the neural substrates and correlates of consciousness remain unclear[1].It has been argued that classical physics is intrinsically incapable of explaining the holistic aspects of consciousness.展开更多
Quality function deployment (QFD),which can translate efficiently customer requirement (CRs) into technical attributes (TAs),is widely used in new product development (NPD) as an efficient customer-driven approach. Af...Quality function deployment (QFD),which can translate efficiently customer requirement (CRs) into technical attributes (TAs),is widely used in new product development (NPD) as an efficient customer-driven approach. After lots of QFD application is applied in manufacturing fields,it was proved that without considering suppliers involved,it is difficult to get precise and satisfying results in each process of QFD,particularly part deployment. The paper will address the issues of a model of optional parts selection in suppliers involved in part deployment process. Further,it has been applied to an ERP system reconstruction and updating problem as an illustration.展开更多
Background:With the popularization of lung cancer screening,more early-stage lung cancers are being detected.This study aims to compare three types of N classifications,including location-based N classification(pathol...Background:With the popularization of lung cancer screening,more early-stage lung cancers are being detected.This study aims to compare three types of N classifications,including location-based N classification(pathologic nodal classification[pN]),the number of lymph node stations(nS)-based N classification(nS classification),and the combined approach proposed by the International Association for the Study of Lung Cancer(IASLC)which incorporates both pN and nS classification to determine if the nS classification is more appropriate for early-stage lung cancer.Methods:We retrospectively reviewed the clinical data of lung cancer patients treated at the Cancer Hospital,Chinese Academy of Medical Sciences between 2005 and 2018.Inclusion criteria was clinical stage IA lung adenocarcinoma patients who underwent resection during this period.Sub-analyses were performed for the three types of N classifications.The optimal cutoffvalues for nS classification were determined with X-tile software.Kaplan‒Meier and multivariate Cox analyses were performed to assess the prognostic significance of the different N classifications.The prediction performance among the three types of N classifications was compared using the concordance index(C-index)and decision curve analysis(DCA).Results:Of the 669 patients evaluated,534 had pathological stage N0 disease(79.8%),82 had N1 disease(12.3%)and 53 had N2 disease(7.9%).Multivariate Cox analysis indicated that all three types of N classifications were independent prognostic factors for prognosis(all P<0.001).However,the prognosis overlaps between pN(N1 and N2,P=0.052)and IASLC-proposed N classification(N1b and N2a1[P=0.407],N2a1 and N2a2[P=0.364],and N2a2 and N2b[P=0.779]),except for nS classification subgroups(nS0 and nS1[P<0.001]and nS1 and nS>1[P=0.006]).There was no significant difference in the C-index values between the three N classifications(P=0.370).The DCA results demonstrated that the nS classification provided greater clinical utility.Conclusion:The nS classification might be a better choice for nodal classification in clinical stage IA lung adeno-carcinoma.展开更多
We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcri...We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.展开更多
AIM： To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation （SMP）, for the treatment of non-center involved diabetic macular edema （non-CI DME）. METHODS： Prospective,...AIM： To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation （SMP）, for the treatment of non-center involved diabetic macular edema （non-CI DME）. METHODS： Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity （BCVA） of 0.30 logMAR or better. Each eye was randomized into three groups： group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness （CST）, macular area of greater thickness （MAGT） and total macular volume （TMV）. Results were analyzed after 3mo. RESULTS： A total of 32 eyes were included. Group 3 improved in BCVA （0.19±0.16 to 0.12±0.14 logMAR; P=0.041） and in TMV （7.90±0.57 to 7.65±0.73 mm3; P=0.025）. Group 1 improved in MAGT （325±26.26 to 298.20±44.85 μm; P=0.022） and TMV （7.79±0.57 to 7.50±0.56 mm3, P=0.047）. Group 2 didn’t show significant improvement of any variable. CONCLUSION： The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.展开更多
Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets an...Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular mechanism.However,its regulating signaling pathways remain to be elucidated.We investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of F-Hst1.We performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of Hst1.We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1.Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1.The inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity.Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1.We further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important role.Overall,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular targeting.The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.展开更多
Transcription of human immunodeficiency virus (HIV-1) is activated by viral Tat protein which regulates HIV-long terminal reapaet (LTR) transcription and elongation.
Verticillium dahliae Kleb.is a necrotrophic plant pathogen which causes serious soil borne vascular disease in cotton.The molecular basis the defense response of cotton to this pathogen is
A cDNA subtractive library enriched for dark-induced up-regulated ESTs was constructed by suppression subtractive hybridization(SSH) from leaf tissues of soybean cultivar DongNong L13 treated with short-day(8-h light/...A cDNA subtractive library enriched for dark-induced up-regulated ESTs was constructed by suppression subtractive hybridization(SSH) from leaf tissues of soybean cultivar DongNong L13 treated with short-day(8-h light/16-h dark) and long-day(16-h light/8-h dark) conditions.A total of 148 clones were sequenced,representing 76 unique ESTs which corresponded to about 20% of 738 clones from the cDNA library and showed a significant up-regulation of at least three fold verified by dot blot hybridization.The putative functions of ESTs were predicted by Blastn and Blastx.The 43 differentially expressed genes identified by subtractions were classified according to their putative functions generated by Blast analysis.Genetic functional analysis indicated that putative proteins encoded by these genes were related to diverse functions during organism development,which include biological regulation pathways such as transcription,signal transduction and programmed cell death,protein,nucleic acid and carbohydrate macromolecule degradation,the cell wall modification,primary and secondary metabolism and stress response.Two soybean transcription factors enhanced in SD conditions,GAMYB-binding protein and DNA binding protein RAV cDNAs that may be involved in SD soybean photoperiod response,had been isolated using 5'-and 3'-rapid amplification of cDNA ends(RACE)(Genbank Accession numbers DQ112540 and DQ147914).展开更多
<p align="justify"> <span style="font-family:Verdana;">Background:<span style="font-family:Verdana;"> Indigent selected for their health care is complex and poses enormo...<p align="justify"> <span style="font-family:Verdana;">Background:<span style="font-family:Verdana;"> Indigent selected for their health care is complex and poses enormous challenges. The actors involved have an influence on health actions and their perception is decisive for better care for the indigent. Little evidence exists on these perceptions and this paper has captured this. <span style="font-family:Verdana;">Methods:<span style="font-family:Verdana;"> A case study involved 163 participants with a questionnaire and an interview guide. The quantitative responses were classified according to a measurement scale, proportions and overall indices of perception (Ip) and satisfaction (CSAT) were calculated. The relationship between variables was investigated using chi-square. Thematic analysis was used with qualitative data. The study met ethical requirements. <span style="font-family:Verdana;">Results: <span style="font-family:Verdana;">The participants had a positive perception of the selection: Ip = 0.77, but a minority (1/5) were dissatisfied with the selection. The perception of selection did not differ significantly depending on the experience of the actors. For the vast majority, the definition of indigent was satisfactory (CSAT = 91.4). The selection was done in a top down fashion and steps such as setting up committees, informing stakeholders, had shortcomings which negatively impacted the effectiveness of the selection. The needs of the participants included transparency in the indigent select process, matching the tools for selecting the indigent to the context, strengthening of local action, deconstruction of prejudices in terms of the indigent, power of actors to act, and importance for health services to reach out to the indigent. <span style="font-family:Verdana;">Conclusion: <span style="font-family:Verdana;">Considering the perception of the actors as well as their needs will improve the selection for effective care of the indigent.展开更多
Background: Sentinel node (SLN) status is the most important prognostic factor for early-stage melanoma patients. It will influence follow-up and may change therapy. Positive SLNs present different degrees of involvem...Background: Sentinel node (SLN) status is the most important prognostic factor for early-stage melanoma patients. It will influence follow-up and may change therapy. Positive SLNs present different degrees of involvement so that subgroups of patients may have minimal SLN invasion. The aim of this study was to evaluate survival in subgroups with minimally involved SLNs and to compare them to negative SLN patients. Method: SLN biopsy was performed in 499 consecutive clinically N0 patients between 1997 and 2008. Following updated recommendations from the Melanoma Group of the European Organization of Research and Treatment of Cancer, degrees of SLN involvement were fully reassessed for two anatomopathological parameters: tumour burden according to Rotterdam criteria (1.0 mm) and microanatomic location according to Dewar (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive). Minimally involved SLNs were defined as those with tumor burden <0.1 mm and/or subcapsular metastasis location. Kaplan-Meier and multivariable logistic regression analyses were performed. Results: Out of 499 clinically N0 patients, positive SLNs were found in 123 patients (24.7 percent). With a median follow-up of 52 months (range: 9 - 146), five-year disease-free (DFS), disease-specific survival (DSS) and overall survival (OS) were 88.1, 93.9 and 89.9 percent for negative SLN patients, respectively. In minimally involved SLNs, there were 21 with tumour burden <0.1 mm, and 52 with subcapsular metastasis. Five-year DFS, DSS and OS in these sub-groups were 79.6, 86.6 and 86.6 percent, then 57.3, 69.8 and 67.8 percent respectively. DFS univariable analysis of these sub-groups compared to negative SLNs showed: (HR1.89, 95 percent CI 0.75 - 4.79;p 0.175) and (HR 3.92, 95 percent CI 2.29 - 6.71;p < 0.0001) respectively. Minimally involved sub-groups were not predictive for NSLN negativity. Conclusion: Rotterdam’s tumour burden stratification is an easy and useful prognostic factor of melanoma survival. There was a trend showing that patients with SLN tumour burden <0.1 mm have a lower survival compared to SLN negative patients. One might suggest that patients with minimally involved SLNs may not be managed similarly to negative SLN patients. Subcapsular metastasis subgroup according to the microanatomic location has statistically significant worst survival.展开更多
Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
基金supported by grants from the National Natural Science Foundation of China(8120223181273116+2 种基金81430079)the Science and Technology Program of Guangdong Bureau of Science and TechnologyChina(2013B021800069)
文摘The molecular mechanism of DNA damage induced by hydroquinone （HQ） remains unclear. Poly（ADP-ribose） polymerase-1 （PARP-1） usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor （AATF）, PARP-1, and phosphorylated H2AX （v-H2AX） were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-l-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, y-H2AX expression increased to 265%. Co-immunoprecipitation （co-IP） assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly（ADP-ribosyl）ation {PARylation） regulated AATF expression, in conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.
文摘The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
文摘To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,
文摘How the tubular network of the endoplasmic reticulum (ER) is generated is not well understood, but a class of membrane proteins, the reticulons and DP1/Yop1p, are known
基金supported by the CSC (China Scholarship Council)-QUT (Queensland University of Technology) PhD Scholarship awarded to Ms Rong Huangthe Institute of Health and Biomedical Innovation Early Career Researcher Scheme Funding awarded to Dr Yinghong Zhou
文摘The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide （LPS） and interferon-γ （IFN-γ）. However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages （BMDMs） were activated with LPS＋IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction （RT-qPCR） and fluorescence-activated cell sorting （FACS）. Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive （iNOS＋） cells in vivo, suggesting an association between RANKL expression and iNOS＋ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger Ml-like macrophages with properties that were different from those of LPS＋IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.
基金supported by the National Natural Science Foundation of China[81202231 to LLH]the Medical Scientific Research Funding of Guangdong Province,China[A2018225 to LLH]+1 种基金the College Students Cultivate Special Science and Technology Innovation from Education Department of Guangdong Province,China[pdjh2016a0212]the Project for Creative Talent of Guangdong Education Department[2014KQNCX102]
文摘Particulate matter （PM）, which is a great environmental concern, has been classified as a Group 1 human carcinogen by the International Agency for Research on Cancer （IARC）;.Epidemiological and experimental studies have indicated that chronic exposure to PM, especially PM;(particles with an aerodynamic diameter less than
基金supported by the National Natural Science Foundation of China (31640034)the Sci-Tech Support Plan of Hubei Province, China (2014BEC086)the Research Team Fund of the South-Central University for Nationalities, China (XTZ15014)
文摘Dear Editor Despite remarkable advances in our understanding of brain functions,the neural substrates and correlates of consciousness remain unclear[1].It has been argued that classical physics is intrinsically incapable of explaining the holistic aspects of consciousness.
基金Funded by Natural Science Foundation of China (70471028) ,and the Excellent Youth Teacher Program of Ministry of Education of China .
文摘Quality function deployment (QFD),which can translate efficiently customer requirement (CRs) into technical attributes (TAs),is widely used in new product development (NPD) as an efficient customer-driven approach. After lots of QFD application is applied in manufacturing fields,it was proved that without considering suppliers involved,it is difficult to get precise and satisfying results in each process of QFD,particularly part deployment. The paper will address the issues of a model of optional parts selection in suppliers involved in part deployment process. Further,it has been applied to an ERP system reconstruction and updating problem as an illustration.
基金supported by CAMS Innovation Fund for Med-ical Sciences(grant number:2021-I2M-C&T-B-061)Beijing Hope Run Special Fund of Cancer Foundation of China(grant number:LC2022A22)+1 种基金Beijing Municipal Natural Science Foundation(grant num-ber:7184238)National Natural Science Foundation of China(grant number:81701692).
文摘Background:With the popularization of lung cancer screening,more early-stage lung cancers are being detected.This study aims to compare three types of N classifications,including location-based N classification(pathologic nodal classification[pN]),the number of lymph node stations(nS)-based N classification(nS classification),and the combined approach proposed by the International Association for the Study of Lung Cancer(IASLC)which incorporates both pN and nS classification to determine if the nS classification is more appropriate for early-stage lung cancer.Methods:We retrospectively reviewed the clinical data of lung cancer patients treated at the Cancer Hospital,Chinese Academy of Medical Sciences between 2005 and 2018.Inclusion criteria was clinical stage IA lung adenocarcinoma patients who underwent resection during this period.Sub-analyses were performed for the three types of N classifications.The optimal cutoffvalues for nS classification were determined with X-tile software.Kaplan‒Meier and multivariate Cox analyses were performed to assess the prognostic significance of the different N classifications.The prediction performance among the three types of N classifications was compared using the concordance index(C-index)and decision curve analysis(DCA).Results:Of the 669 patients evaluated,534 had pathological stage N0 disease(79.8%),82 had N1 disease(12.3%)and 53 had N2 disease(7.9%).Multivariate Cox analysis indicated that all three types of N classifications were independent prognostic factors for prognosis(all P<0.001).However,the prognosis overlaps between pN(N1 and N2,P=0.052)and IASLC-proposed N classification(N1b and N2a1[P=0.407],N2a1 and N2a2[P=0.364],and N2a2 and N2b[P=0.779]),except for nS classification subgroups(nS0 and nS1[P<0.001]and nS1 and nS>1[P=0.006]).There was no significant difference in the C-index values between the three N classifications(P=0.370).The DCA results demonstrated that the nS classification provided greater clinical utility.Conclusion:The nS classification might be a better choice for nodal classification in clinical stage IA lung adeno-carcinoma.
文摘We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase Ⅱ. The cyclin L2 protein contains an N-terminal "cyclin box" and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase Ⅱ and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.
文摘AIM： To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation （SMP）, for the treatment of non-center involved diabetic macular edema （non-CI DME）. METHODS： Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity （BCVA） of 0.30 logMAR or better. Each eye was randomized into three groups： group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness （CST）, macular area of greater thickness （MAGT） and total macular volume （TMV）. Results were analyzed after 3mo. RESULTS： A total of 32 eyes were included. Group 3 improved in BCVA （0.19±0.16 to 0.12±0.14 logMAR; P=0.041） and in TMV （7.90±0.57 to 7.65±0.73 mm3; P=0.025）. Group 1 improved in MAGT （325±26.26 to 298.20±44.85 μm; P=0.022） and TMV （7.79±0.57 to 7.50±0.56 mm3, P=0.047）. Group 2 didn’t show significant improvement of any variable. CONCLUSION： The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.
基金funded by Eurostars project,grant number E!12764。
文摘Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular mechanism.However,its regulating signaling pathways remain to be elucidated.We investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of F-Hst1.We performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of Hst1.We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1.Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1.The inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity.Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1.We further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important role.Overall,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular targeting.The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.
基金Funded by National Natural Sciences Foundation of China (No. 30800580Beijing Nova Program (No. 2007B014)+3 种基金Beijing Natural Science Foundation (No. 5093025)Beijing Talents Foundation (No. 20071D0501500213)BJUT Science Foundation for Youths (No. 97015999200702)BJUT Scientific Research Starting Foundation for Doctor (No. 52015999200703)
文摘Transcription of human immunodeficiency virus (HIV-1) is activated by viral Tat protein which regulates HIV-long terminal reapaet (LTR) transcription and elongation.
文摘Verticillium dahliae Kleb.is a necrotrophic plant pathogen which causes serious soil borne vascular disease in cotton.The molecular basis the defense response of cotton to this pathogen is
文摘A cDNA subtractive library enriched for dark-induced up-regulated ESTs was constructed by suppression subtractive hybridization(SSH) from leaf tissues of soybean cultivar DongNong L13 treated with short-day(8-h light/16-h dark) and long-day(16-h light/8-h dark) conditions.A total of 148 clones were sequenced,representing 76 unique ESTs which corresponded to about 20% of 738 clones from the cDNA library and showed a significant up-regulation of at least three fold verified by dot blot hybridization.The putative functions of ESTs were predicted by Blastn and Blastx.The 43 differentially expressed genes identified by subtractions were classified according to their putative functions generated by Blast analysis.Genetic functional analysis indicated that putative proteins encoded by these genes were related to diverse functions during organism development,which include biological regulation pathways such as transcription,signal transduction and programmed cell death,protein,nucleic acid and carbohydrate macromolecule degradation,the cell wall modification,primary and secondary metabolism and stress response.Two soybean transcription factors enhanced in SD conditions,GAMYB-binding protein and DNA binding protein RAV cDNAs that may be involved in SD soybean photoperiod response,had been isolated using 5'-and 3'-rapid amplification of cDNA ends(RACE)(Genbank Accession numbers DQ112540 and DQ147914).
文摘<p align="justify"> <span style="font-family:Verdana;">Background:<span style="font-family:Verdana;"> Indigent selected for their health care is complex and poses enormous challenges. The actors involved have an influence on health actions and their perception is decisive for better care for the indigent. Little evidence exists on these perceptions and this paper has captured this. <span style="font-family:Verdana;">Methods:<span style="font-family:Verdana;"> A case study involved 163 participants with a questionnaire and an interview guide. The quantitative responses were classified according to a measurement scale, proportions and overall indices of perception (Ip) and satisfaction (CSAT) were calculated. The relationship between variables was investigated using chi-square. Thematic analysis was used with qualitative data. The study met ethical requirements. <span style="font-family:Verdana;">Results: <span style="font-family:Verdana;">The participants had a positive perception of the selection: Ip = 0.77, but a minority (1/5) were dissatisfied with the selection. The perception of selection did not differ significantly depending on the experience of the actors. For the vast majority, the definition of indigent was satisfactory (CSAT = 91.4). The selection was done in a top down fashion and steps such as setting up committees, informing stakeholders, had shortcomings which negatively impacted the effectiveness of the selection. The needs of the participants included transparency in the indigent select process, matching the tools for selecting the indigent to the context, strengthening of local action, deconstruction of prejudices in terms of the indigent, power of actors to act, and importance for health services to reach out to the indigent. <span style="font-family:Verdana;">Conclusion: <span style="font-family:Verdana;">Considering the perception of the actors as well as their needs will improve the selection for effective care of the indigent.
文摘Background: Sentinel node (SLN) status is the most important prognostic factor for early-stage melanoma patients. It will influence follow-up and may change therapy. Positive SLNs present different degrees of involvement so that subgroups of patients may have minimal SLN invasion. The aim of this study was to evaluate survival in subgroups with minimally involved SLNs and to compare them to negative SLN patients. Method: SLN biopsy was performed in 499 consecutive clinically N0 patients between 1997 and 2008. Following updated recommendations from the Melanoma Group of the European Organization of Research and Treatment of Cancer, degrees of SLN involvement were fully reassessed for two anatomopathological parameters: tumour burden according to Rotterdam criteria (1.0 mm) and microanatomic location according to Dewar (subcapsular, combined subcapsular and parenchymal, parenchymal, multifocal, or extensive). Minimally involved SLNs were defined as those with tumor burden <0.1 mm and/or subcapsular metastasis location. Kaplan-Meier and multivariable logistic regression analyses were performed. Results: Out of 499 clinically N0 patients, positive SLNs were found in 123 patients (24.7 percent). With a median follow-up of 52 months (range: 9 - 146), five-year disease-free (DFS), disease-specific survival (DSS) and overall survival (OS) were 88.1, 93.9 and 89.9 percent for negative SLN patients, respectively. In minimally involved SLNs, there were 21 with tumour burden <0.1 mm, and 52 with subcapsular metastasis. Five-year DFS, DSS and OS in these sub-groups were 79.6, 86.6 and 86.6 percent, then 57.3, 69.8 and 67.8 percent respectively. DFS univariable analysis of these sub-groups compared to negative SLNs showed: (HR1.89, 95 percent CI 0.75 - 4.79;p 0.175) and (HR 3.92, 95 percent CI 2.29 - 6.71;p < 0.0001) respectively. Minimally involved sub-groups were not predictive for NSLN negativity. Conclusion: Rotterdam’s tumour burden stratification is an easy and useful prognostic factor of melanoma survival. There was a trend showing that patients with SLN tumour burden <0.1 mm have a lower survival compared to SLN negative patients. One might suggest that patients with minimally involved SLNs may not be managed similarly to negative SLN patients. Subcapsular metastasis subgroup according to the microanatomic location has statistically significant worst survival.
基金This work was supported by the National Natural Science Foundation of China (No 30370904and No 30671258)the National High Technology Research and Development Program(863 project)of China (No 2006AA10Z121)the Program for New Century Excellent Talents in University(No NCET-07-0712)
文摘Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
