BACKGROUND Aberrant expression of stanniocalcin 2(STC2)is implicated in colon adenocarcinoma(COAD).A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers,but the role ...BACKGROUND Aberrant expression of stanniocalcin 2(STC2)is implicated in colon adenocarcinoma(COAD).A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers,but the role of its overexpression in the development of COAD remains unclear.AIM To evaluate the regulation mechanism of STC2 overexpression in COAD.METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO(GSE50760).Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform,and the correlation between STC2 expression and survival rate was investigated with TCGA COAD.Transcription binding site prediction was conducted by TRANSFAC and LASAGNA,and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines,including HEK293T,NCM460,HT29,SW480,and HCT116.Western blotting was performed to evaluate the role of Sp1 on the expression of STC2.RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis.Importantly,the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2.A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2,and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2.Furthermore,inhibition of Sp1 remarkably decreased protein levels of STC2.CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity.Taken together,our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.展开更多
The ACE(angiotensin converting enzyme)inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases,but also potentially therapeutic agents in dementia.Based on the findings that the ACE inhibitors ...The ACE(angiotensin converting enzyme)inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases,but also potentially therapeutic agents in dementia.Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity,we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons.The three reporter vectors,pACEpro(0-SEAP,p-I-ACEpro-SEAP,and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells.Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%.Additionally,we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%,but adversely reduced that of the D-form vector by 16.8%,as compared with the respective control without the lisinopril treatment.Firstly,our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons,which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD(Alzheimer's disease)patients.展开更多
The 5＇ fragment （1 647 bp） of the cotton glucuronosyltransferase gene （GhGlcAT1） was transcriptionally fused to the β-glucuronidase （GUS） gene, and functionally analyzed for important regulatory regions contro...The 5＇ fragment （1 647 bp） of the cotton glucuronosyltransferase gene （GhGlcAT1） was transcriptionally fused to the β-glucuronidase （GUS） gene, and functionally analyzed for important regulatory regions controlling gene expression in transgenic tobacco plants. GUS activity analysis revealed that the full-length promoter drives efficient expression of the GUS gene in the root cap, seed coat, pollen grains and trichomes. Exposure of the transgenic tobacco to various abiotic stresses showed that the promoter was mainly responsive to the sugars （glucose and sucrose） as well as gibberellic acid. Progressive upstream deletion analyses of the promoter showed that the region from -281 to ＋30 bp is sufficient to drive strong GUS expression in the trichomes of shoot, suggesting that the 311 bp region contains all cis-elements needed for trichome-specific expression. Furthermore, deletion analysis also revealed that the essential cis-element（s） for sucrose induction might be located between -635 and -281 bp. In addition, sequence analysis of the regulatory region indicated several conserved motifs among which some were shared with previously reported seed-specific elements and sugarresponsive elements, while others were related with trichome expression. These findings indicate that a 1 647-bp fragment of the cotton GhGIcAT1 promoter contains specific transcription regulatory elements, and provide clues about the roles of GhGIcAT 1 in cotton fiber development. Further analyses of these elements will help to elucidate the molecular mechanisms regulating the expression of the GhGlcAT1 gene during fiber elongation.展开更多
Graphene films(GFs) and graphene-reinforced nanocomposite coatings(GNCs) have received unprecedented attention for corrosion protection because graphene possesses a remarkable chemical inertness and is completely impe...Graphene films(GFs) and graphene-reinforced nanocomposite coatings(GNCs) have received unprecedented attention for corrosion protection because graphene possesses a remarkable chemical inertness and is completely impermeable to aggressive chemicals. However, the high electric conductivity and positive potential of graphene make graphene-based metal protectors tend to exhibit an undesirable high corrosion-promotion activity(CPA), which is widely known as the phenomenon that graphene connecting with metal accelerates the corrosion of metal substrate by inducing micro-galvanic corrosion at the defect sites of GFs or GNCs in aggressive environments. Therefore, inhibiting the CPA of graphene is currently a key focus for the application of graphene in the field of corrosion protection. In this review, the mechanisms, influencing factors, and inhibition strategies of the CPA of GFs and GNCs are highlighted from the point of view of corrosion science to address the bottlenecks and challenges for future research and potential applications of graphene for corrosion protection.展开更多
Physical inactivity has been identified as one of the leading causes of many chronic diseases such as cardiovascular disease,type 2 diabetes,and obesity.Technology such as video games plays a complicated role in physi...Physical inactivity has been identified as one of the leading causes of many chronic diseases such as cardiovascular disease,type 2 diabetes,and obesity.Technology such as video games plays a complicated role in physical inactivity—much like a double-edged sword.Traditionally,video games have contributed to the epidemic of physical inactivity and have展开更多
Objective： To examine factors of the youth physical activity promotion （YPAP） model that are associated with Chinese international students＇ meeting PA recommendations （MPAR）. Methods： A total of 649 （females ...Objective： To examine factors of the youth physical activity promotion （YPAP） model that are associated with Chinese international students＇ meeting PA recommendations （MPAR）. Methods： A total of 649 （females = 320, males = 329） Chinese international college students participated in the study. This study was conducted in the United States （US.） between June and August in 2011. Participants completed an online survey regarding their demographic, PA, predisposing, enabling, and reinforcing factors. Results： Logistic nested-regression analysis suggested that being male, having a higher body mass index, perceived competence, self-efficacy, attitude, and enjoyment all increased （p 〈 0.001） the participants＇ odds of MPAR. Except language barriers, all of the enabling and reinforcing factors predicted MPAR indirectly through the predisposing factors （p 〈 0.001）. Conclusion： Understanding factors that influence PA among Chinese international students is an important step in the process of promoting their long-term health and wellbeing. Designing program that address the identified key factors may help colleges and universities achieve this goal.展开更多
Due to the overuse and misuse of antibiotic,an increase in antibiotic resistance of pathogenic bacteria is evolving.Attention should be focused on natural alternatives to antibiotics,like propolis,royal jelly(R J)and ...Due to the overuse and misuse of antibiotic,an increase in antibiotic resistance of pathogenic bacteria is evolving.Attention should be focused on natural alternatives to antibiotics,like propolis,royal jelly(R J)and honeys.They all have strong antibacterial properties due to the active substances they contain.This study investigated the effect of combination of water soluble propolis(WSP)Greitl20 or fresh royal jelly(F-RJ)(MiZigoj)and Forest honeys as antibacterial against Escherichia coli,Pseudomonas aeruginosa,Proteus mirabilis,Acinetobacter baumanii,Staphylococcus aureus,methicillin resistant Staphylococcus aureus(MRSA),Streptococcus pyogenes,Streptococcus agalactiae and Candida albicans.These substances are also cell growth promoters for human macrophage(TLT)cell line.WSP Greitl20,F-RJ(M)and different Forest honeys were prepared in saline as 10%solutions.The antimicrobial activity was expressed as the minimal inhibitory concentration(MIC)in mg/mL.The growth promotion activity was measured at optical density(OD)595 nm.The combination ofWSP Greitl20 with different Forest honeys is better than F-RJ(M)in same combination with different Forest honeys.The best antibacterial/antifungal activity was found with the combination of 10%WSP Greit 120 in the Forest honey(1:10)from Italy or Spain.When measuring the growth promoting activity of TLT cell line,the best activity was detected at the combination of 10%WSP Greitl20 in the Forest honey from Italy(GI3=0.796±0.014 and GI5=1.133±0.022).Antimicrobial and growth promoting activities are correlated and WSP-dependent.展开更多
This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immu...This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.展开更多
BMP2 plays crucial roles in vertebrate developmental process and acts as a bone inducer during osteogenesis. We present here the molecular cloning of bmp2 cDNA from the marine flatfish Cynoglossus semilaevis, and the ...BMP2 plays crucial roles in vertebrate developmental process and acts as a bone inducer during osteogenesis. We present here the molecular cloning of bmp2 cDNA from the marine flatfish Cynoglossus semilaevis, and the analysis of bmp2 expression profiling and promoter function. The full length of bmp2 cDNA sequence is 2 048 bp,which encodes a protein of 422 amino acids. Tissue expression distribution of bmp2 was examined in 14 tissues of mature individuals by quantitative real time PCR（qRT-PCR）. The results revealed that bmp2 was expressed ubiquitously, and the highest expression level was detected in the spinal cord. Moreover, bmp2 expression levels were detected at 15 sampling time points of early developmental stages（egg, larva, juvenile and fingerling stages）.The highest expression level of bmp2 was observed at the gastrula stage, which was about ten times higher than those at the other three embryo stages. Whole-mount in situ hybridization showed that the bmp2 signal was strongly detected at the location of the crown-like larval fin, heart and liver, and slightly expressed in the notochord at one day post hatch（dph）; then the expression of bmp2 started to be concentrated in notochord at three dph. Subsequently, we characterized the 5′-flanking region of bmp2 by testing the promoter activity by Luciferase reporter assays. Positive regulatory region was detected at the location of –179 to ＋109. The predicted transcription factor binding sites（E-box binding factors, zinc finger transcription factor, etc.） in this region might participate in the transcriptional regulation of the bmp2 gene.展开更多
Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.Howe...Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.However,achieving high efficiency and selectivity in NitRR is fundamentally challenged by the complex lifecycle management of active hydrogen derived from water splitting.This review provides a timely and comprehensive analysis centered on the pivotal role and meticulous regulation of active hydrogen throughout the NitRR process.We first elucidate the distinct functions and characteristics of various hydrogen species,followed by a survey of advanced characterization techniques crucial for monitoring the dynamics of active hydrogen.Critically,three core strategies were systematically dissected to modulate the active hydrogen lifecycle:accelerating water activation and dissociation,enhancing the directional transport of hydrogen species,and precisely tuning active hydrogen coupling pathways while suppressing parasitic hydrogen evolution.By consolidating current understanding from both catalyst design and reaction mechanism perspectives,this review offers a hydrogen-centric roadmap and highlights emerging opportunities for rationally engineering advanced NitRR systems.展开更多
Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implicat...Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implications remain unclear.In this study,we demonstrated that in oral cancer,a typical hypoxic tumor,hypoxia can induce chronic but constitutive phosphorylation of wild-type EGFR in the absence of ligands.Oral cancer cell lines exhibit different EGFR phosphorylation responses to hypoxia.In hypoxic HN4 and HN6 cells,ubiquitination-mediated endocytosis,lysosomal sorting,and degradation lead to low levels of EGFR phosphorylation.However,in CAL-27 and HN30 cells,a novel HIF-1α-induced long noncoding RNA(lnc RNA),EUDAL,can compete with the E3 ligase/adaptor complex c-Cbl/Grb2 for binding to EGFR,stabilizing phosphorylated EGFR(p EGFR)and resulting in sustained activation of EGFR and its downstream STAT3/BNIP3 signaling.STAT3/BNIP3-mediated autophagy leads to antitumor drug resistance.A high EUDAL/EGFR/STAT3/autophagy pathway activation predicts poor response to chemotherapy in oral cancer patients.Collectively,hypoxia can induce noncanonical ligand-independent EGFR phosphorylation.High EUDAL expression facilitates sustained EGFR phosphorylation in hypoxic tumor cells and leads to autophagy-related drug resistance.展开更多
The CD80 （B7-1） costimulatory molecule is expressed on the surface of B cells and its expression is transcriptionally upregulated upon stimuli. To identify the region of murine CD80 promoter that direct cell type sp...The CD80 （B7-1） costimulatory molecule is expressed on the surface of B cells and its expression is transcriptionally upregulated upon stimuli. To identify the region of murine CD80 promoter that direct cell type specific gene expression, four promoters construct of CD80 gene were generated with DNA fragments fused to the GFP reporter gene. In the present study, significant promoter activity was detected with all four promoter constructs only in the murine B lymphocyte. Further, the CD80 promoter region extending from -3,005 bp to ＋273 bp in relation to the previously reported transcription start site, was identified as tissue specific region. Interestingly, the shortest 700 bp （-427/＋273） of promoter fragment was sufficient to direct the CD80 gene expression. The level of CD80 expression was also found to be modulated by exogenous stimuli in B lymphocyte. Additionally, it was demonstrated that the CD80 gene expression is regulated at the level of transcription where the inducible CD80 gene transcript was detected in B lymphocyte with increasing time.展开更多
The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this ene...The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function.展开更多
Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstru...Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.展开更多
A Chinese delegation of 24 persons headed by Mr. Luan Enjie, Vice Administrator of China National Space Administration (CNSA) attended the Second Asia-Pacific Conference on Multilateral Cooperation in Space Technology...A Chinese delegation of 24 persons headed by Mr. Luan Enjie, Vice Administrator of China National Space Administration (CNSA) attended the Second Asia-Pacific Conference on Multilateral Cooperation in Space Technology and Applications held at Islamabad, the Capital of Pakistan from April 22 to 26, 1995. Following the First AsiaPacific Workshop held in Beijing in December, 1992, and the First Asia-Pacific Conference on Multilateral Cooperation in展开更多
Respect for human rights and protection of human rights are significant rules in the Constitution of the People’s Republic of China.In 2015,judicial administration departments at all levels legally exercised their du...Respect for human rights and protection of human rights are significant rules in the Constitution of the People’s Republic of China.In 2015,judicial administration departments at all levels legally exercised their duties,implemented the principles and rules in constitution,and kept strengthening propagation of human rights through creation of contents and methods which had acquired great effects.What they have done contributes significantly toward the development of human rights in China.展开更多
Promoters are critical elements to control gene expression but could behave differently under various growth conditions. Here we report the construction of a genome-wide promoter library, in which each native promoter...Promoters are critical elements to control gene expression but could behave differently under various growth conditions. Here we report the construction of a genome-wide promoter library, in which each native promoter in Saccharomyces cerevisiae was cloned upstream of a yellow fluorescent protein （YFP） reporter gene. Nine libraries were arbitrarily defined and assembled in bacteria. The resulting pools of promoters could be prepared and transformed into a yeast strain either as centromeric plasmids or integrated into a genomic locus upon enzymatic treatment. Using fluorescence activated cell sorting, we classified the yeast strains based on YFP fluorescence intensity and arbitrarily divided the entire library into 12 bins, representing weak to strong promoters. Several strong promoters were identified from the most active bins and their activities were assayed under different growth conditions. Finally, these promoters were applied to drive the expression of genes in xylose utilization to improve fermentation efficiency. Together, this library could provide a quick solution to identify and utilize desired promoters under user-defined growth conditions.展开更多
Background The CREG is an important lysosomal protein involved in a variety of cellular functions including promoting cell differentiation,sustaining mature homeostasis,and antagonizing apoptosis.Deficiency of CREG in...Background The CREG is an important lysosomal protein involved in a variety of cellular functions including promoting cell differentiation,sustaining mature homeostasis,and antagonizing apoptosis.Deficiency of CREG in cell and tissue results in a pathologic apoptosis.The present study aimed to elucidate the mechanism of CREG regulation apoptosis.Methods We firstly generated stable NIH3T3 fibroblasts by transfection of pDS_shCREGs vectors.Furthermore,PI-Annexin V and TUNEL staining were used to identify that CREG knockdown promoted the cell apoptosis in NIH3T3 fibroblasts.Western blotting and immunofluorescence staining was used to identify the expression and localization of M6P/IGF2R and cathepsin L in cytoplasm.Results pDS_shCREGs vector transfection produced an approximately 80%decrease in CREG levels both in the lysate and in the media.The expression and localization of M6P/IGF2R and cathepsin L in cytoplasma changed obviously associated with down-regulated of CREG.In addition,the retention and secretion of cathepsin L enhanced significantly.Using the specific inhibitor or siRNA to block cathepsin L activation attenuated the apoptosis mediated by CREG downregulation.Conclusions Our findings indicated that inhibition of CREG expression in NIH3T3 fibroblasts leads to impaired cathepsin L sorting function mediated by M6P/IGF2R and subsequently promotes pathological cell apoptosis.展开更多
Spinal cord injury(SCI)is a severe neurological condition with limited regenerative capacity and no effective curative treatments.Interleukin-13(IL-13),an immunomodulatory cytokine,has shown therapeutic potential by p...Spinal cord injury(SCI)is a severe neurological condition with limited regenerative capacity and no effective curative treatments.Interleukin-13(IL-13),an immunomodulatory cytokine,has shown therapeutic potential by promoting alternative immune activation and improving recovery after SCI in mice.However,cellbased IL-13 delivery is hindered by poor graft survival and limited localisation at the injury site.Here,we developed an injectable hydrogel-based delivery system(HGIL13)composed of IL-13-loaded poly(lactic-co-glycolic acid)(PLGA)microparticles embedded in a photocrosslinkable gelatin methacrylate(GelMA)matrix,enabling sustained and localised IL-13 release.HGIL13 achieved IL-13 release for up to six weeks and significantly reduced lipopolysaccharide(LPS)-induced inflammation in BV2 microglia in vitro.In a mouse contusion SCI model,HGIL13 enhanced functional recovery,reduced lesion volume,and decreased demyelinated area.Using the Hexbtd^(Tomato)mouse we show that HGIL13 modulated the neuroimmune response by decreasing resident microglia density,downregulating CD86 expression,and upregulating Arginase-1 in both microglia and infiltrating monocyte-derived macrophages.RT-qPCR and RNA-seq analyses confirmed sustained immunomodulation over 28 days and indicated early reduction of activated microglia at 7 days post-injury as a key therapeutic mechanism.This study presents a safe,effective,and translatable strategy for localised cytokine delivery,demonstrating strong potential for immunomodulation and improved functional recovery following SCI.展开更多
The molecular basis for increasing of the glucoamylase (GLA) production of an Aspergillus niger mutant T21 was investigated . Northern blot analysis showed that the amount of glaA specific mRNA of A . niger T21 was ab...The molecular basis for increasing of the glucoamylase (GLA) production of an Aspergillus niger mutant T21 was investigated . Northern blot analysis showed that the amount of glaA specific mRNA of A . niger T21 was about 20 times higher than that of its start strain A . niger AS 3.795. The two glaA promoter fusions (PglaA)-uidAs were respectively introduced into A . niger. Analysis of GUS activity of the transformants revealed that the PglaA activity of the strain T21 is about 3 times stronger than that of the strain AS 3.795. It is considered to be one of the reasons for the increase of glaA transcriptional level in the strain T21. However, comparing with the 20 times increase in the amount of glaA mRNA the alteration of trans regulation should be the most important reason for that. The results of deletion analysis of 5′-cis region of A . niger T21 glaA gene indicated that the region from - 408 to - 513 bp upstream of ATG is responsible for the high level expression of glaA.展开更多
基金the Natural Science Foundation of Liaoning Province,China,No.20180550769
文摘BACKGROUND Aberrant expression of stanniocalcin 2(STC2)is implicated in colon adenocarcinoma(COAD).A previous study identified that STC2 functions as a tumor promoter to drive development of some cancers,but the role of its overexpression in the development of COAD remains unclear.AIM To evaluate the regulation mechanism of STC2 overexpression in COAD.METHODS The expression of STC2 in COAD was assessed by TCGA COAD database and GEO(GSE50760).Methylation level of the STC2 promoter was evaluated with beta value in UALCAN platform,and the correlation between STC2 expression and survival rate was investigated with TCGA COAD.Transcription binding site prediction was conducted by TRANSFAC and LASAGNA,and a luciferase reporter system was used to identify STC2 promoter activity in several cell lines,including HEK293T,NCM460,HT29,SW480,and HCT116.Western blotting was performed to evaluate the role of Sp1 on the expression of STC2.RESULTS The central finding of this work is that STC2 is overexpressed in COAD tissues and positively correlated with poor prognosis.Importantly,the binding site of the transcription factor Sp1 is widely located in the promoter region of STC2.A luciferase reporter system was successfully constructed to analyze the transcription activity of STC2,and knocking down the expression of Sp1 significantly inhibited the transcription activity of STC2.Furthermore,inhibition of Sp1 remarkably decreased protein levels of STC2.CONCLUSION Our data provide evidence that the transcription factor Sp1 is essential for the overexpression of STC2 in COAD through activation of promoter activity.Taken together,our finding provides new insights into the mechanism of oncogenic function of COAD by STC2.
文摘The ACE(angiotensin converting enzyme)inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases,but also potentially therapeutic agents in dementia.Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity,we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons.The three reporter vectors,pACEpro(0-SEAP,p-I-ACEpro-SEAP,and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells.Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%.Additionally,we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%,but adversely reduced that of the D-form vector by 16.8%,as compared with the respective control without the lisinopril treatment.Firstly,our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons,which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD(Alzheimer's disease)patients.
文摘The 5＇ fragment （1 647 bp） of the cotton glucuronosyltransferase gene （GhGlcAT1） was transcriptionally fused to the β-glucuronidase （GUS） gene, and functionally analyzed for important regulatory regions controlling gene expression in transgenic tobacco plants. GUS activity analysis revealed that the full-length promoter drives efficient expression of the GUS gene in the root cap, seed coat, pollen grains and trichomes. Exposure of the transgenic tobacco to various abiotic stresses showed that the promoter was mainly responsive to the sugars （glucose and sucrose） as well as gibberellic acid. Progressive upstream deletion analyses of the promoter showed that the region from -281 to ＋30 bp is sufficient to drive strong GUS expression in the trichomes of shoot, suggesting that the 311 bp region contains all cis-elements needed for trichome-specific expression. Furthermore, deletion analysis also revealed that the essential cis-element（s） for sucrose induction might be located between -635 and -281 bp. In addition, sequence analysis of the regulatory region indicated several conserved motifs among which some were shared with previously reported seed-specific elements and sugarresponsive elements, while others were related with trichome expression. These findings indicate that a 1 647-bp fragment of the cotton GhGIcAT1 promoter contains specific transcription regulatory elements, and provide clues about the roles of GhGIcAT 1 in cotton fiber development. Further analyses of these elements will help to elucidate the molecular mechanisms regulating the expression of the GhGlcAT1 gene during fiber elongation.
基金supported by the National Natural Science Foundation of China (Nos. 21703026, 51671047, and 21978036)the General Financial Grant from the China Postdoctoral Science Foundation (Nos. 2017M610177 and 2018T011222)+2 种基金the Doctoral Startup Foundation of Liaoning Province (No. 2019-BS-046)the Research Fund of Open Studio for Marine Corrosion and Protection,Pilot National Laboratory for Marine Science and Technology (Qingdao, No. HYFSKF-201804)the Fundamental Research Funds for the Central Universities (No. DUT19RC(4)003)。
文摘Graphene films(GFs) and graphene-reinforced nanocomposite coatings(GNCs) have received unprecedented attention for corrosion protection because graphene possesses a remarkable chemical inertness and is completely impermeable to aggressive chemicals. However, the high electric conductivity and positive potential of graphene make graphene-based metal protectors tend to exhibit an undesirable high corrosion-promotion activity(CPA), which is widely known as the phenomenon that graphene connecting with metal accelerates the corrosion of metal substrate by inducing micro-galvanic corrosion at the defect sites of GFs or GNCs in aggressive environments. Therefore, inhibiting the CPA of graphene is currently a key focus for the application of graphene in the field of corrosion protection. In this review, the mechanisms, influencing factors, and inhibition strategies of the CPA of GFs and GNCs are highlighted from the point of view of corrosion science to address the bottlenecks and challenges for future research and potential applications of graphene for corrosion protection.
文摘Physical inactivity has been identified as one of the leading causes of many chronic diseases such as cardiovascular disease,type 2 diabetes,and obesity.Technology such as video games plays a complicated role in physical inactivity—much like a double-edged sword.Traditionally,video games have contributed to the epidemic of physical inactivity and have
文摘Objective： To examine factors of the youth physical activity promotion （YPAP） model that are associated with Chinese international students＇ meeting PA recommendations （MPAR）. Methods： A total of 649 （females = 320, males = 329） Chinese international college students participated in the study. This study was conducted in the United States （US.） between June and August in 2011. Participants completed an online survey regarding their demographic, PA, predisposing, enabling, and reinforcing factors. Results： Logistic nested-regression analysis suggested that being male, having a higher body mass index, perceived competence, self-efficacy, attitude, and enjoyment all increased （p 〈 0.001） the participants＇ odds of MPAR. Except language barriers, all of the enabling and reinforcing factors predicted MPAR indirectly through the predisposing factors （p 〈 0.001）. Conclusion： Understanding factors that influence PA among Chinese international students is an important step in the process of promoting their long-term health and wellbeing. Designing program that address the identified key factors may help colleges and universities achieve this goal.
文摘Due to the overuse and misuse of antibiotic,an increase in antibiotic resistance of pathogenic bacteria is evolving.Attention should be focused on natural alternatives to antibiotics,like propolis,royal jelly(R J)and honeys.They all have strong antibacterial properties due to the active substances they contain.This study investigated the effect of combination of water soluble propolis(WSP)Greitl20 or fresh royal jelly(F-RJ)(MiZigoj)and Forest honeys as antibacterial against Escherichia coli,Pseudomonas aeruginosa,Proteus mirabilis,Acinetobacter baumanii,Staphylococcus aureus,methicillin resistant Staphylococcus aureus(MRSA),Streptococcus pyogenes,Streptococcus agalactiae and Candida albicans.These substances are also cell growth promoters for human macrophage(TLT)cell line.WSP Greitl20,F-RJ(M)and different Forest honeys were prepared in saline as 10%solutions.The antimicrobial activity was expressed as the minimal inhibitory concentration(MIC)in mg/mL.The growth promotion activity was measured at optical density(OD)595 nm.The combination ofWSP Greitl20 with different Forest honeys is better than F-RJ(M)in same combination with different Forest honeys.The best antibacterial/antifungal activity was found with the combination of 10%WSP Greit 120 in the Forest honey(1:10)from Italy or Spain.When measuring the growth promoting activity of TLT cell line,the best activity was detected at the combination of 10%WSP Greitl20 in the Forest honey from Italy(GI3=0.796±0.014 and GI5=1.133±0.022).Antimicrobial and growth promoting activities are correlated and WSP-dependent.
基金supported by grants from the National Key Research and Development Projects(2019YFE0103800)Scientific Research Project of Sichuan Provincial Health Department(No.18PJ586)Research and Innovation Team Project of Chengdu Medical College(No.CYTD16-04)。
文摘This study was to explore the immunity-promoting activity of porcine placenta as a potential raw material for functional foods.Porcine placenta was subjected to the analysis for its bioactive substances,and their immunity-promoting activity was determined in mice supplemented with porcine placenta extract(PPE)and freeze-dried porcine placenta powder at high(PPH)and low(PPL)dosage.Results showed that porcine placenta contained placental peptides and 15 free amino acids,and the amounts of estrogen and progesterone in products developed from porcine placenta were within the limit of national standard.Mice model experiment revealed that compared with the control,the PPH treatment significantly improved the spleen index(P<0.05)by increasing the phagocytic rate of macrophages from 20%to 60%and the conversion rate of T lymphocytes from 8%to 60%.The q PCR analysis disclosed that the porcine placenta powder enhanced mice immunity via promoting the expression of Th1 cytokines of interleukin-2(IL-2)and IFN-γ,especially the former,by almost 8 times in the spleens of male mice,while inhibited Th2 cytokines of IL-4 and IL-10.This investigation has provided a reference for the development of porcine placenta as a raw material applied in functional foods to improve human immunity.
基金The Special Scientific Research Funds for Central Non-profit Institutes,Chinese Academy of Fishery Sciences under contract No.2016RC-LX02the National Natural Science Foundation of China under contract No.31201981
文摘BMP2 plays crucial roles in vertebrate developmental process and acts as a bone inducer during osteogenesis. We present here the molecular cloning of bmp2 cDNA from the marine flatfish Cynoglossus semilaevis, and the analysis of bmp2 expression profiling and promoter function. The full length of bmp2 cDNA sequence is 2 048 bp,which encodes a protein of 422 amino acids. Tissue expression distribution of bmp2 was examined in 14 tissues of mature individuals by quantitative real time PCR（qRT-PCR）. The results revealed that bmp2 was expressed ubiquitously, and the highest expression level was detected in the spinal cord. Moreover, bmp2 expression levels were detected at 15 sampling time points of early developmental stages（egg, larva, juvenile and fingerling stages）.The highest expression level of bmp2 was observed at the gastrula stage, which was about ten times higher than those at the other three embryo stages. Whole-mount in situ hybridization showed that the bmp2 signal was strongly detected at the location of the crown-like larval fin, heart and liver, and slightly expressed in the notochord at one day post hatch（dph）; then the expression of bmp2 started to be concentrated in notochord at three dph. Subsequently, we characterized the 5′-flanking region of bmp2 by testing the promoter activity by Luciferase reporter assays. Positive regulatory region was detected at the location of –179 to ＋109. The predicted transcription factor binding sites（E-box binding factors, zinc finger transcription factor, etc.） in this region might participate in the transcriptional regulation of the bmp2 gene.
基金financially supported by the National Natural Science Foundation of China(22179035)the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022B001)the Fundamental Research Funds for the Universities of Heilongjiang Province of China(2023-KYYWF1440)。
文摘Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.However,achieving high efficiency and selectivity in NitRR is fundamentally challenged by the complex lifecycle management of active hydrogen derived from water splitting.This review provides a timely and comprehensive analysis centered on the pivotal role and meticulous regulation of active hydrogen throughout the NitRR process.We first elucidate the distinct functions and characteristics of various hydrogen species,followed by a survey of advanced characterization techniques crucial for monitoring the dynamics of active hydrogen.Critically,three core strategies were systematically dissected to modulate the active hydrogen lifecycle:accelerating water activation and dissociation,enhancing the directional transport of hydrogen species,and precisely tuning active hydrogen coupling pathways while suppressing parasitic hydrogen evolution.By consolidating current understanding from both catalyst design and reaction mechanism perspectives,this review offers a hydrogen-centric roadmap and highlights emerging opportunities for rationally engineering advanced NitRR systems.
基金supported by the National Natural Science Foundation of China(82273095,82203614)the Shanghai Sailing Program(22YF1421600)。
文摘Hypoxia and aberrant activation of epidermal growth factor receptor(EGFR)are considered important features of various malignancies.However,whether hypoxia can directly trigger EGFR activation and its clinical implications remain unclear.In this study,we demonstrated that in oral cancer,a typical hypoxic tumor,hypoxia can induce chronic but constitutive phosphorylation of wild-type EGFR in the absence of ligands.Oral cancer cell lines exhibit different EGFR phosphorylation responses to hypoxia.In hypoxic HN4 and HN6 cells,ubiquitination-mediated endocytosis,lysosomal sorting,and degradation lead to low levels of EGFR phosphorylation.However,in CAL-27 and HN30 cells,a novel HIF-1α-induced long noncoding RNA(lnc RNA),EUDAL,can compete with the E3 ligase/adaptor complex c-Cbl/Grb2 for binding to EGFR,stabilizing phosphorylated EGFR(p EGFR)and resulting in sustained activation of EGFR and its downstream STAT3/BNIP3 signaling.STAT3/BNIP3-mediated autophagy leads to antitumor drug resistance.A high EUDAL/EGFR/STAT3/autophagy pathway activation predicts poor response to chemotherapy in oral cancer patients.Collectively,hypoxia can induce noncanonical ligand-independent EGFR phosphorylation.High EUDAL expression facilitates sustained EGFR phosphorylation in hypoxic tumor cells and leads to autophagy-related drug resistance.
文摘The CD80 （B7-1） costimulatory molecule is expressed on the surface of B cells and its expression is transcriptionally upregulated upon stimuli. To identify the region of murine CD80 promoter that direct cell type specific gene expression, four promoters construct of CD80 gene were generated with DNA fragments fused to the GFP reporter gene. In the present study, significant promoter activity was detected with all four promoter constructs only in the murine B lymphocyte. Further, the CD80 promoter region extending from -3,005 bp to ＋273 bp in relation to the previously reported transcription start site, was identified as tissue specific region. Interestingly, the shortest 700 bp （-427/＋273） of promoter fragment was sufficient to direct the CD80 gene expression. The level of CD80 expression was also found to be modulated by exogenous stimuli in B lymphocyte. Additionally, it was demonstrated that the CD80 gene expression is regulated at the level of transcription where the inducible CD80 gene transcript was detected in B lymphocyte with increasing time.
基金supported in part by National Institutes of Health Grants NS-091201(to MY)and NS-079331(to MY)VA MERIT Award IO1BX003441(to MY)
文摘The central nervous system has a very high energy requirement. Accord- ingly, despite representing only 2% of the body＇s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function.
基金supported by the JSPSKAKENHI Grant-in-Aid for Scientific Research(B),Grant Numbers24700572 and 30614276
文摘Stroke causes long-term disability, and rehabilitative training is commonly used to improve the consecutive functional recovery. Following brain damage, surviving neurons undergo morphological alterations to reconstruct the remaining neural network. In the motor system, such neural network remodeling is observed as a motor map reorganization. Because of its significant correlation with functional recovery, motor map reorganization has been regarded as a key phenomenon for functional recovery after stroke. Although the mechanism underlying motor map reorganization remains unclear, increasing evidence has shown a critical role for axonal remodeling in the corticospinal tract. In this study, we review previous studies investigating axonal remodeling in the corticospinal tract after stroke and discuss which mechanisms may underlie the stimulatory effect of rehabilitative training. Axonal remodeling in the corticospinal tract can be classified into three types based on the location and the original targets of corticospinal neurons, and it seems that all the surviving corticospinal neurons in both ipsilesional and contralesional hemisphere can participate in axonal remodeling and motor map reorganization. Through axonal remodeling, corticospinal neurons alter their output selectivity from a single to multiple areas to compensate for the lost function. The remodeling of the corticospinal axon is influenced by the extent of tissue destruction and promoted by various therapeutic interventions, including rehabilitative training. Although the precise molecular mechanism underlying rehabilitation-promoted axonal remodeling remains elusive, previous data suggest that rehabilitative training promotes axonal remodeling by upregulating growth-promoting and downregulating growth-inhibiting signals.
文摘A Chinese delegation of 24 persons headed by Mr. Luan Enjie, Vice Administrator of China National Space Administration (CNSA) attended the Second Asia-Pacific Conference on Multilateral Cooperation in Space Technology and Applications held at Islamabad, the Capital of Pakistan from April 22 to 26, 1995. Following the First AsiaPacific Workshop held in Beijing in December, 1992, and the First Asia-Pacific Conference on Multilateral Cooperation in
文摘Respect for human rights and protection of human rights are significant rules in the Constitution of the People’s Republic of China.In 2015,judicial administration departments at all levels legally exercised their duties,implemented the principles and rules in constitution,and kept strengthening propagation of human rights through creation of contents and methods which had acquired great effects.What they have done contributes significantly toward the development of human rights in China.
基金We thank Jianhuo Fang at DNA sequencing facility in Tsinghua University for providing the sequencing service. This work was supported by the National Natural Science Foundation of China （Grant No. 31471254）, Chinese Ministry of Science and Technology grant 2012CB725201 and Tsinghua University Initiative grant 20161080088.
文摘Promoters are critical elements to control gene expression but could behave differently under various growth conditions. Here we report the construction of a genome-wide promoter library, in which each native promoter in Saccharomyces cerevisiae was cloned upstream of a yellow fluorescent protein （YFP） reporter gene. Nine libraries were arbitrarily defined and assembled in bacteria. The resulting pools of promoters could be prepared and transformed into a yeast strain either as centromeric plasmids or integrated into a genomic locus upon enzymatic treatment. Using fluorescence activated cell sorting, we classified the yeast strains based on YFP fluorescence intensity and arbitrarily divided the entire library into 12 bins, representing weak to strong promoters. Several strong promoters were identified from the most active bins and their activities were assayed under different growth conditions. Finally, these promoters were applied to drive the expression of genes in xylose utilization to improve fermentation efficiency. Together, this library could provide a quick solution to identify and utilize desired promoters under user-defined growth conditions.
文摘Background The CREG is an important lysosomal protein involved in a variety of cellular functions including promoting cell differentiation,sustaining mature homeostasis,and antagonizing apoptosis.Deficiency of CREG in cell and tissue results in a pathologic apoptosis.The present study aimed to elucidate the mechanism of CREG regulation apoptosis.Methods We firstly generated stable NIH3T3 fibroblasts by transfection of pDS_shCREGs vectors.Furthermore,PI-Annexin V and TUNEL staining were used to identify that CREG knockdown promoted the cell apoptosis in NIH3T3 fibroblasts.Western blotting and immunofluorescence staining was used to identify the expression and localization of M6P/IGF2R and cathepsin L in cytoplasm.Results pDS_shCREGs vector transfection produced an approximately 80%decrease in CREG levels both in the lysate and in the media.The expression and localization of M6P/IGF2R and cathepsin L in cytoplasma changed obviously associated with down-regulated of CREG.In addition,the retention and secretion of cathepsin L enhanced significantly.Using the specific inhibitor or siRNA to block cathepsin L activation attenuated the apoptosis mediated by CREG downregulation.Conclusions Our findings indicated that inhibition of CREG expression in NIH3T3 fibroblasts leads to impaired cathepsin L sorting function mediated by M6P/IGF2R and subsequently promotes pathological cell apoptosis.
基金supported by University College Dublin and Taighde ireann-Research Ireland(19/FFP/6642 to DD,16/IA/4584 to DB,and GOIPG/2021/304 to CW)supported by the Medical Research Center Initiative for High Depth Omics,and CURE:JPMXP1323015486 for MIB,and AMRC,Kyushu University+1 种基金by AMED JP23gm1910004,JP23jf0126004,24zf0127012,JSPS KAKENHIJP25H01009Ono Pharmaceutical Foundation for Oncology,Immunology and Neurology,and the Takeda Science Foundation.
文摘Spinal cord injury(SCI)is a severe neurological condition with limited regenerative capacity and no effective curative treatments.Interleukin-13(IL-13),an immunomodulatory cytokine,has shown therapeutic potential by promoting alternative immune activation and improving recovery after SCI in mice.However,cellbased IL-13 delivery is hindered by poor graft survival and limited localisation at the injury site.Here,we developed an injectable hydrogel-based delivery system(HGIL13)composed of IL-13-loaded poly(lactic-co-glycolic acid)(PLGA)microparticles embedded in a photocrosslinkable gelatin methacrylate(GelMA)matrix,enabling sustained and localised IL-13 release.HGIL13 achieved IL-13 release for up to six weeks and significantly reduced lipopolysaccharide(LPS)-induced inflammation in BV2 microglia in vitro.In a mouse contusion SCI model,HGIL13 enhanced functional recovery,reduced lesion volume,and decreased demyelinated area.Using the Hexbtd^(Tomato)mouse we show that HGIL13 modulated the neuroimmune response by decreasing resident microglia density,downregulating CD86 expression,and upregulating Arginase-1 in both microglia and infiltrating monocyte-derived macrophages.RT-qPCR and RNA-seq analyses confirmed sustained immunomodulation over 28 days and indicated early reduction of activated microglia at 7 days post-injury as a key therapeutic mechanism.This study presents a safe,effective,and translatable strategy for localised cytokine delivery,demonstrating strong potential for immunomodulation and improved functional recovery following SCI.
基金the National Natural Science Foundation of China (GrantNo.39870015).
文摘The molecular basis for increasing of the glucoamylase (GLA) production of an Aspergillus niger mutant T21 was investigated . Northern blot analysis showed that the amount of glaA specific mRNA of A . niger T21 was about 20 times higher than that of its start strain A . niger AS 3.795. The two glaA promoter fusions (PglaA)-uidAs were respectively introduced into A . niger. Analysis of GUS activity of the transformants revealed that the PglaA activity of the strain T21 is about 3 times stronger than that of the strain AS 3.795. It is considered to be one of the reasons for the increase of glaA transcriptional level in the strain T21. However, comparing with the 20 times increase in the amount of glaA mRNA the alteration of trans regulation should be the most important reason for that. The results of deletion analysis of 5′-cis region of A . niger T21 glaA gene indicated that the region from - 408 to - 513 bp upstream of ATG is responsible for the high level expression of glaA.
