A cold method was used to prepare coated sand for application in the selective laser sintering(SLS)process.Tensile strength,loss on ignition,gas evolution,and accuracy of the SLS samples were tested and analyzed,and t...A cold method was used to prepare coated sand for application in the selective laser sintering(SLS)process.Tensile strength,loss on ignition,gas evolution,and accuracy of the SLS samples were tested and analyzed,and the baking process was thoroughly investigated.Compared with coated sand prepared by the hot method,the cold method yields a more uniform and complete resin film on the sand's surface,resulting in enhanced tensile strength and accuracy.Additionally,the cold method requires a lower binder content to meet the same strength requirements,thereby minimizing gas evolution,reducing porosity defects,and ultimately improving casting quality.The coated sand samples prepared through the cold method exhibit superior accuracy,with a size error of within±0.4 mm.In contrast,the coated sand samples prepared by the hot method display a lower accuracy,with an average negative error of 2.1993 mm.The highest tensile strength could be attained by controlling the baking temperature within a suitable range(180-190°C),which can effectively reduce the generation of gas,thus contributing to improved overall performance.展开更多
Block copolymers(BCPs) with high Flory-Huggins parameter(χ) and balanced surface energy have aroused tremendous interest for ultra-small nanopatterns processing.However,high χ and balanced surface energy are general...Block copolymers(BCPs) with high Flory-Huggins parameter(χ) and balanced surface energy have aroused tremendous interest for ultra-small nanopatterns processing.However,high χ and balanced surface energy are generally contradicted.The fine tune of chain structure might be a useful way to achieve high χ and balanced surface energy.To realize this,the block copolymer with exactly uniform chain structure,i.e.,defined molecular structure,is highly desirable for accurately evaluating the phase behavior.Herein,two kinds of discrete oligo ester-b-oligo olefin block copolymers with different chemical structures(oligo lactic acid-boligo olefin BCP,oLA_(n)-b-C_(m);oligo phenyl lactic acid-b-oligo olefin BCP,oPL_(n)-b-C_(m)) were modularly synthesized through iterative growth methods.The effect of chain structure on segregation strength and surface properties was quantitatively investigated using the discrete BCPs as precise models.On the one hand,introducing rigid and nonpolar phenyl groups into oligo ester block has a negligible effect on the chemical incompatibility,as confirmed by the identical high χ values of oLA_(n)-b-C_(m) and oPL_(n)-b-C_(m)(χ_(oLA/C)=0.21 and χ_(oPL/C)=0.19).On the other hand,the incorporation of nonpolar phenyl groups creates balanced surface energy,that is,the high χ and balanced surface energy were simultaneously achieved by oPL_(n)-b-C_(m).Therefore,sub-10 nm perpendicular nanopatterns can be easily produced upon brief thermal treatment,demonstrating its potential application in semiconductor manufacturing with ultra-small feature size.The discrete BCP can serve as a quantitative and exquisite model to study the critical contribution of chain structures on phase separation behavior,providing insightful understanding to facilitate the potential application in the chip process.展开更多
Lithium metal anodes are of great interest for advanced high-energy density batteries such as lithiumair, lithium-sulfur and solid-state batteries, due to their low electrode potential and ultra-high theoretical capac...Lithium metal anodes are of great interest for advanced high-energy density batteries such as lithiumair, lithium-sulfur and solid-state batteries, due to their low electrode potential and ultra-high theoretical capacity. There are, however, several challenges limiting their practical applications, which include low coulombic efficiency, the uncontrollable growth of dendrites and poor rate capability. Here, a rational design of 3D structured lithium metal anodes comprising of in-situ growth of cobalt-decorated nitrogen-doped carbon nanotubes on continuous carbon nanofibers is demonstrated via electrospinning.The porous and free-standing scaffold can enhance the tolerance to stresses resulting from the intrinsic volume change during Li plating/stripping, delivering a significant boost in both charge/discharge rates and stable cycling performance. A binary Co-Li alloying phase was generated at the initial discharge process, creating more active sites for the Li nucleation and uniform deposition. Characterization and density functional theory calculations show that the conductive and uniformly distributed cobalt-decorated carbon nanotubes with hierarchical structure can effectively reduce the local current density and more easily absorb Li atoms, leading to more uniform Li nucleation during plating. The current work presents an advance on scalable and cost-effective strategies for novel electrode materials with 3D hierarchical microstructures and mechanical flexibility for lithium metal anodes.展开更多
BACKGROUND Infective endocarditis(IE) is a rare disease with a high mortality rate.Leclercia adecarboxylata(L.adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae,and it can rarely be a pathogen w...BACKGROUND Infective endocarditis(IE) is a rare disease with a high mortality rate.Leclercia adecarboxylata(L.adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae,and it can rarely be a pathogen which often affects immunodeficient patients.There are about three cases of immunocompetent patients with monomicrobial L.adecarboxylata infection.There are only three reported cases of IE caused by L.adecarboxylata in the world.The mitral valve is often affected in IE,and the prognosis for IE with mitral valve lesions is often poor.CASE SUMMARY A 51-year-old man was found to have moderate to severe mitral stenosis on echocardiography.He came to our Cardiothoracic Surgery Department for surgical management.A diastolic murmur was heard on auscultation of the heart in the mitral region.On the second day of hospitalisation,he presented with slurred speech,reduced muscle strength in the left limb,and acute cerebral infarction on cranial computed tomography.Surgical treatment was decided to postpone.On the ninth day of admission,the patient developed a sudden high fever and shock and was transferred to the Cardiac Intensive Care Unit,where echocardiogram revealed an anterior mitral valve leaflet vegetation.After empirical anti-infective treatment with vancomycin(1g q12h),an emergency valve replacement was performed.Bacterial culture identified L.adecarboxylata.Antiinfective treatment with piperacillin-tazobactam(4.5g q8h) was added for 4 wk.Follow-up echocardiography showed normal bioprosthetic valve function after mitral valve replacement.CONCLUSION We report the first case of L.adecarboxylata IE in China,and clinicians should pay attention to this pathogen.展开更多
Two important factors affecting the performance of sand mold/core generated by 3D printing(3DP)are strength and dimensional accuracy,which are not only closely related to the reactivity of furan resin and the phase tr...Two important factors affecting the performance of sand mold/core generated by 3D printing(3DP)are strength and dimensional accuracy,which are not only closely related to the reactivity of furan resin and the phase transition of silica sand,but also the curing agent system of furan resin.This paper studies the influence of gel time on the strength and dimensional accuracy of a 3DP sand mold/core,taking the furan resin system as an example and using a sand specimen generated by a 3DP inkjet molding machine.The experiment demonstrates that the gel time of 3 to 6 min for the sand mixture suits 3DP core-making most under the experimental condition.However,it should be noted that under the same resin condition,the strength of a no-bake sand mold/core is higher than that of a 3DP sand mold/core.The dimensional accuracy of the sand mold/core does not change significantly when the gel time is less than 15 min.Improving the activity of binder and developing ultra-strong acid with low corrosion shall be an effective way to improve the quality of the mold/core by 3D printing.展开更多
Bisulfite(HSO_3) is an important sulfur dioxide(SO_2) derivative, which plays a major role in many physiological processes and is also closely associated with a variety of diseases. Thus the development of highly sele...Bisulfite(HSO_3) is an important sulfur dioxide(SO_2) derivative, which plays a major role in many physiological processes and is also closely associated with a variety of diseases. Thus the development of highly selective and sensitive fluorescent probes is essential to detect HSO_3 in living cells. In this work,we report the synthesis and analysis of a ratiometric fluorescent probe for selective detection of HSO_3 based on the 1,4-nucleophilic addition reaction with the carbazole as an electron donor(D) and aldehyde group as an electron acceptor(A). The addition of HSO_3 and other ions to our probe can be observed by UV vis and fluorescence spectrometry. Our investigation proved that the probe is highly selective and sensitive for HSO_3 and ratiometric changes. Moreover, the probe has good cell permeability and was successfully applied to the detection of exogenous HSO_3 in Hela cells and C. elegans.展开更多
A rhodamine-based sensor(1) has been developed for the detection of chromium ions.Cr-(3+)-induced opening of the rhodamine spirocycle in sensor(1) led to the distinct colorimetric and fluorescence responses.Amo...A rhodamine-based sensor(1) has been developed for the detection of chromium ions.Cr-(3+)-induced opening of the rhodamine spirocycle in sensor(1) led to the distinct colorimetric and fluorescence responses.Among all the tested ions,only Cr-(3+) generated a significant fluorescence enhancement of up to13-fold,which indicated the high selectivity of 1.Sensor(1) was successfully applied in the in vivo fluorescence imaging of Cr-(3+) in C.elegans.The results provided solid evidences for the future estimation of Cr-(3+) in environmental applications and tobacco samples.展开更多
Mitochondrial calcium uniporter(MCU)has an important role in regulating mitochondrial calcium(Ca^(2+))homeostasis.Dysregulation of mitochondrial Ca^(2+)homeostasis has been implicated in various cancers.However,it rem...Mitochondrial calcium uniporter(MCU)has an important role in regulating mitochondrial calcium(Ca^(2+))homeostasis.Dysregulation of mitochondrial Ca^(2+)homeostasis has been implicated in various cancers.However,it remains unclear whether MCU regulates mitochondrial Ca^(2+)uptake to promote cell growth in colorectal cancer(CRC).Therefore,in the present study the expression of MCU in CRC tissues and its clinical significance were examined.Following which,the biological function of MCUmediated mitochondrial Ca^(2+)uptake in CRC cell growth and the underlying mechanisms were systematically evaluated using in in vitro and in vivo assays,which included western blotting,cell viability and apoptosis assays,as well as xenograft nude mice models.Our results demonstrated that MCU was markedly upregulated in CRC tissues at both the mRNA and protein levels.Upregulated MCU was associated with poor prognosis in patients with CRC.Our data reported that upregulation of MCU enhanced the mitochondrial Ca^(2+)uptake to promote mitochondrial biogenesis,which in turn facilitated CRC cell growth in vitro and in vivo.In terms of the underlying mechanism,it was identified that MCU-mediated mitochondrial Ca^(2+)uptake inhibited the phosphorylation of transcription factor A,mitochondrial(TFAM),and thus enhanced its stability to promote mitochondrial biogenesis.Furthermore,our data indicated that increased mitochondrial Ca^(2+)uptake led to increased mitochondrial production of ROS via the upregulation of mitochondrial biogenesis,which subsequently activated NF-κB signaling to accelerate CRC growth.In conclusion,the results indicated that MCU-induced mitochondrial Ca^(2+)uptake promotes mitochondrial biogenesis by suppressing phosphorylation of TFAM,thus contributing to CRC cell growth.Our findings reveal a novel mechanism underlying mitochondrial Ca^(2+)-mediated CRC cell growth and may provide a potential pharmacological target for CRC treatment.展开更多
Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inheri...Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inherited risk component to SCD.Signal transducer and activators of transcription 5 A(STAT5A)is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes.In this study,we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations.Based on the screening results,an insertion/deletion polymorphism(rs3833144)in 3’UTR of STAT5A was selected as the candidate variant.A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations.Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk(odds ratio(OR)=1.54;95%confidence interval(CI)=1.18-2.01;P=0.000955).Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A,and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant.On the other hand,the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144,and eQTL analysis showed the higher expression of both genes in samples with deletion allele.Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription.Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.展开更多
Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this ...Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this study,we developed a six-dye multiplex typing system consisting of 34 autosomal InDels and Amelogenin for forensic application.The contained InDels were specifically selected for Chinese population with the MAF≥0.25 in East Asia,which do not overlap with the markers of Investigator^(■)DIPplex kit.The typing system was named as GoldeneyeTM DNA ID System 35InDel Kit,and a series of developmental validation studies including repeatability/reproducibility,concordance,accuracy,sensitivity,stability,species specificity and population genetics were conducted on this kit.We confirmed that the 35InDel kit is precise,sensitive,species specific and robust for forensic practice.Moreover,the 35InDel kit is capable of typing DNA extracted from forensic routine case-type samples as well as degraded samples and mixture samples.All markers are proved to be highly polymorphic with an average observed heterozygosity(He)of 0.4582.The combined power of discrimination(CPD)is 0.999999999999978 and the combined power of exclusion in duos(CPE_(D))and trios(CPE_(T))are 0.978837 and 0.999573,respectively,which are higher than those of the Investigator^(■)DIPplex kit.Thus,the GoldeneyeTM DNA ID System 35InDel kit is suitable for forensic human identification and could serve as a supplementary typing system for paternity testing.展开更多
Objective: To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments. Methods: The ex vivo study used corpus cavemosum strips pre...Objective: To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments. Methods: The ex vivo study used corpus cavemosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats. Results: Preconstricted with phenylephrine (PE) in isolated endothelium- intact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-l-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]- oxadiazole-[4,3-α ]-quinoxalin-l-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P〈0.01), a nonselective K+ channel blocker, 4-aminopyridine (4-AP, P〈0.01), a voltage-dependent K+ channel blocker, and charybdotoxin (P〈0.01), a large and intermediate conductance Ca2. sensitive-K+ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently. Conclusion: BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2. sensitive-K+ (BK+ and IK+) channels in the corpus cavemosum.展开更多
基金This work was financially supported by the Joint Funds of the National Natural Science Foundation of China(Grant No.U1808216)the Shanxi Provincial Key Research and Development Project(2022ZDYF072).
文摘A cold method was used to prepare coated sand for application in the selective laser sintering(SLS)process.Tensile strength,loss on ignition,gas evolution,and accuracy of the SLS samples were tested and analyzed,and the baking process was thoroughly investigated.Compared with coated sand prepared by the hot method,the cold method yields a more uniform and complete resin film on the sand's surface,resulting in enhanced tensile strength and accuracy.Additionally,the cold method requires a lower binder content to meet the same strength requirements,thereby minimizing gas evolution,reducing porosity defects,and ultimately improving casting quality.The coated sand samples prepared through the cold method exhibit superior accuracy,with a size error of within±0.4 mm.In contrast,the coated sand samples prepared by the hot method display a lower accuracy,with an average negative error of 2.1993 mm.The highest tensile strength could be attained by controlling the baking temperature within a suitable range(180-190°C),which can effectively reduce the generation of gas,thus contributing to improved overall performance.
基金supported by the National Natural Science Foundation of China(21925107,22273026)China Postdoctoral Science Foundation(71st,2022M712306)+1 种基金the Collaborative Innovation Center of Suzhou Nano Science and Technologythe Jiangsu Funding Program for Excellent Postdoctoral Talent。
文摘Block copolymers(BCPs) with high Flory-Huggins parameter(χ) and balanced surface energy have aroused tremendous interest for ultra-small nanopatterns processing.However,high χ and balanced surface energy are generally contradicted.The fine tune of chain structure might be a useful way to achieve high χ and balanced surface energy.To realize this,the block copolymer with exactly uniform chain structure,i.e.,defined molecular structure,is highly desirable for accurately evaluating the phase behavior.Herein,two kinds of discrete oligo ester-b-oligo olefin block copolymers with different chemical structures(oligo lactic acid-boligo olefin BCP,oLA_(n)-b-C_(m);oligo phenyl lactic acid-b-oligo olefin BCP,oPL_(n)-b-C_(m)) were modularly synthesized through iterative growth methods.The effect of chain structure on segregation strength and surface properties was quantitatively investigated using the discrete BCPs as precise models.On the one hand,introducing rigid and nonpolar phenyl groups into oligo ester block has a negligible effect on the chemical incompatibility,as confirmed by the identical high χ values of oLA_(n)-b-C_(m) and oPL_(n)-b-C_(m)(χ_(oLA/C)=0.21 and χ_(oPL/C)=0.19).On the other hand,the incorporation of nonpolar phenyl groups creates balanced surface energy,that is,the high χ and balanced surface energy were simultaneously achieved by oPL_(n)-b-C_(m).Therefore,sub-10 nm perpendicular nanopatterns can be easily produced upon brief thermal treatment,demonstrating its potential application in semiconductor manufacturing with ultra-small feature size.The discrete BCP can serve as a quantitative and exquisite model to study the critical contribution of chain structures on phase separation behavior,providing insightful understanding to facilitate the potential application in the chip process.
基金kindly supported by the National Natural Science Foundation of China (No. U1864213)the EPSRC Joint UK-India Clean Energy center (JUICE) (EP/P003605/1)+2 种基金the EPSRC Multi-Scale Modelling project (EP/S003053/1)the Innovate UK for Advanced Battery Lifetime Extension (ABLE) projectthe EPSRC for funding under EP/S000933/1。
文摘Lithium metal anodes are of great interest for advanced high-energy density batteries such as lithiumair, lithium-sulfur and solid-state batteries, due to their low electrode potential and ultra-high theoretical capacity. There are, however, several challenges limiting their practical applications, which include low coulombic efficiency, the uncontrollable growth of dendrites and poor rate capability. Here, a rational design of 3D structured lithium metal anodes comprising of in-situ growth of cobalt-decorated nitrogen-doped carbon nanotubes on continuous carbon nanofibers is demonstrated via electrospinning.The porous and free-standing scaffold can enhance the tolerance to stresses resulting from the intrinsic volume change during Li plating/stripping, delivering a significant boost in both charge/discharge rates and stable cycling performance. A binary Co-Li alloying phase was generated at the initial discharge process, creating more active sites for the Li nucleation and uniform deposition. Characterization and density functional theory calculations show that the conductive and uniformly distributed cobalt-decorated carbon nanotubes with hierarchical structure can effectively reduce the local current density and more easily absorb Li atoms, leading to more uniform Li nucleation during plating. The current work presents an advance on scalable and cost-effective strategies for novel electrode materials with 3D hierarchical microstructures and mechanical flexibility for lithium metal anodes.
文摘BACKGROUND Infective endocarditis(IE) is a rare disease with a high mortality rate.Leclercia adecarboxylata(L.adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae,and it can rarely be a pathogen which often affects immunodeficient patients.There are about three cases of immunocompetent patients with monomicrobial L.adecarboxylata infection.There are only three reported cases of IE caused by L.adecarboxylata in the world.The mitral valve is often affected in IE,and the prognosis for IE with mitral valve lesions is often poor.CASE SUMMARY A 51-year-old man was found to have moderate to severe mitral stenosis on echocardiography.He came to our Cardiothoracic Surgery Department for surgical management.A diastolic murmur was heard on auscultation of the heart in the mitral region.On the second day of hospitalisation,he presented with slurred speech,reduced muscle strength in the left limb,and acute cerebral infarction on cranial computed tomography.Surgical treatment was decided to postpone.On the ninth day of admission,the patient developed a sudden high fever and shock and was transferred to the Cardiac Intensive Care Unit,where echocardiogram revealed an anterior mitral valve leaflet vegetation.After empirical anti-infective treatment with vancomycin(1g q12h),an emergency valve replacement was performed.Bacterial culture identified L.adecarboxylata.Antiinfective treatment with piperacillin-tazobactam(4.5g q8h) was added for 4 wk.Follow-up echocardiography showed normal bioprosthetic valve function after mitral valve replacement.CONCLUSION We report the first case of L.adecarboxylata IE in China,and clinicians should pay attention to this pathogen.
基金financially supported by the Liaoning Science and Technology Plan Program(2019-ZD-0998)the National Natural Science Foundation of China(Grant No.U1808216)。
文摘Two important factors affecting the performance of sand mold/core generated by 3D printing(3DP)are strength and dimensional accuracy,which are not only closely related to the reactivity of furan resin and the phase transition of silica sand,but also the curing agent system of furan resin.This paper studies the influence of gel time on the strength and dimensional accuracy of a 3DP sand mold/core,taking the furan resin system as an example and using a sand specimen generated by a 3DP inkjet molding machine.The experiment demonstrates that the gel time of 3 to 6 min for the sand mixture suits 3DP core-making most under the experimental condition.However,it should be noted that under the same resin condition,the strength of a no-bake sand mold/core is higher than that of a 3DP sand mold/core.The dimensional accuracy of the sand mold/core does not change significantly when the gel time is less than 15 min.Improving the activity of binder and developing ultra-strong acid with low corrosion shall be an effective way to improve the quality of the mold/core by 3D printing.
基金supported by the National Natural Science Foundation of China(Nos.21262050,21302165,21867019 and 41561108)the Foundation of the Department of Science and Technology of Yunnan Province(Nos.2014HB008,2017HB019)
文摘Bisulfite(HSO_3) is an important sulfur dioxide(SO_2) derivative, which plays a major role in many physiological processes and is also closely associated with a variety of diseases. Thus the development of highly selective and sensitive fluorescent probes is essential to detect HSO_3 in living cells. In this work,we report the synthesis and analysis of a ratiometric fluorescent probe for selective detection of HSO_3 based on the 1,4-nucleophilic addition reaction with the carbazole as an electron donor(D) and aldehyde group as an electron acceptor(A). The addition of HSO_3 and other ions to our probe can be observed by UV vis and fluorescence spectrometry. Our investigation proved that the probe is highly selective and sensitive for HSO_3 and ratiometric changes. Moreover, the probe has good cell permeability and was successfully applied to the detection of exogenous HSO_3 in Hela cells and C. elegans.
基金supported by fund of China Tobacco Yunnan Industrial Co.(No.2015JC05)the Foundation of the Department of Science and Technology of Yunnan Province of China(Nos.2013HB062,2014HB008,2016FB020)the Program for Excellent Youth Talents of Yunnan University(No.XT412003)
文摘A rhodamine-based sensor(1) has been developed for the detection of chromium ions.Cr-(3+)-induced opening of the rhodamine spirocycle in sensor(1) led to the distinct colorimetric and fluorescence responses.Among all the tested ions,only Cr-(3+) generated a significant fluorescence enhancement of up to13-fold,which indicated the high selectivity of 1.Sensor(1) was successfully applied in the in vivo fluorescence imaging of Cr-(3+) in C.elegans.The results provided solid evidences for the future estimation of Cr-(3+) in environmental applications and tobacco samples.
基金supported by the National Natural Science Foundation of China(grants 81872302 and 81902513)Science and Technology Co-ordinate Innovation Project of Shaanxi Province,China(grants 2016TZC-S-18-1).
文摘Mitochondrial calcium uniporter(MCU)has an important role in regulating mitochondrial calcium(Ca^(2+))homeostasis.Dysregulation of mitochondrial Ca^(2+)homeostasis has been implicated in various cancers.However,it remains unclear whether MCU regulates mitochondrial Ca^(2+)uptake to promote cell growth in colorectal cancer(CRC).Therefore,in the present study the expression of MCU in CRC tissues and its clinical significance were examined.Following which,the biological function of MCUmediated mitochondrial Ca^(2+)uptake in CRC cell growth and the underlying mechanisms were systematically evaluated using in in vitro and in vivo assays,which included western blotting,cell viability and apoptosis assays,as well as xenograft nude mice models.Our results demonstrated that MCU was markedly upregulated in CRC tissues at both the mRNA and protein levels.Upregulated MCU was associated with poor prognosis in patients with CRC.Our data reported that upregulation of MCU enhanced the mitochondrial Ca^(2+)uptake to promote mitochondrial biogenesis,which in turn facilitated CRC cell growth in vitro and in vivo.In terms of the underlying mechanism,it was identified that MCU-mediated mitochondrial Ca^(2+)uptake inhibited the phosphorylation of transcription factor A,mitochondrial(TFAM),and thus enhanced its stability to promote mitochondrial biogenesis.Furthermore,our data indicated that increased mitochondrial Ca^(2+)uptake led to increased mitochondrial production of ROS via the upregulation of mitochondrial biogenesis,which subsequently activated NF-κB signaling to accelerate CRC growth.In conclusion,the results indicated that MCU-induced mitochondrial Ca^(2+)uptake promotes mitochondrial biogenesis by suppressing phosphorylation of TFAM,thus contributing to CRC cell growth.Our findings reveal a novel mechanism underlying mitochondrial Ca^(2+)-mediated CRC cell growth and may provide a potential pharmacological target for CRC treatment.
基金This study was funded by National Natural Science Foundation of China[grant numbers 81772029 and 81572767]Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Definitive diagnosis to sudden cardiac death(SCD)is often challenging since the postmortem examination on SCD victims could hardly demonstrate an adequate cause of death.It is therefore important to uncover the inherited risk component to SCD.Signal transducer and activators of transcription 5 A(STAT5A)is a member of the STAT family and a transcription factor that is activated by many cell ligands and associated with various cardiovascular processes.In this study,we performed a systematic variant screening on the STAT5A to filter potential functional genetic variations.Based on the screening results,an insertion/deletion polymorphism(rs3833144)in 3’UTR of STAT5A was selected as the candidate variant.A total of 159 SCD cases and 668 SCD matched healthy controls was enrolled to perform a case-control study and evaluate the association between rs3833144 and SCD susceptibility in Chinese populations.Logistic regression analysis showed that the deletion allele of rs3833144 had significantly increased the SCD risk(odds ratio(OR)=1.54;95%confidence interval(CI)=1.18-2.01;P=0.000955).Further genotype-expression eQTL analysis showed that samples with deletion allele appeared to lower expression of STAT5A,and in silico prediction suggested the local 3 D structure changes of STAT5A mRNA caused by the variant.On the other hand,the bioinformatic analysis presented that promoters of RARA and PTGES3L-AARSD1 could interact with rs3833144,and eQTL analysis showed the higher expression of both genes in samples with deletion allele.Dual-luciferase activity assays also suggested the significant regulatory role of rs3833144 in gene transcription.Our current data thus suggested a possible involvement of rs3833144 to SCD predisposition in Chinese populations and rs3833144 with potential function roles may become a candidate marker for SCD diagnosis and prevention.
基金This study was supported by grants from the National Youth Top-Notch Talent of Ten Thousand Program[grant number WRQB2019]the Youth Science and Technology Innovation Leader of Ten Thousand Program[grant number 2018RA2102],China.
文摘Insertion/deletion polymorphisms(InDels)have been treated as a prospective and helpful genetic marker in the fields of forensic human identification,anthropology and population genetics for the past few years.In this study,we developed a six-dye multiplex typing system consisting of 34 autosomal InDels and Amelogenin for forensic application.The contained InDels were specifically selected for Chinese population with the MAF≥0.25 in East Asia,which do not overlap with the markers of Investigator^(■)DIPplex kit.The typing system was named as GoldeneyeTM DNA ID System 35InDel Kit,and a series of developmental validation studies including repeatability/reproducibility,concordance,accuracy,sensitivity,stability,species specificity and population genetics were conducted on this kit.We confirmed that the 35InDel kit is precise,sensitive,species specific and robust for forensic practice.Moreover,the 35InDel kit is capable of typing DNA extracted from forensic routine case-type samples as well as degraded samples and mixture samples.All markers are proved to be highly polymorphic with an average observed heterozygosity(He)of 0.4582.The combined power of discrimination(CPD)is 0.999999999999978 and the combined power of exclusion in duos(CPE_(D))and trios(CPE_(T))are 0.978837 and 0.999573,respectively,which are higher than those of the Investigator^(■)DIPplex kit.Thus,the GoldeneyeTM DNA ID System 35InDel kit is suitable for forensic human identification and could serve as a supplementary typing system for paternity testing.
基金Supported by the National Research Foundation of Korea(NRF)Grant by Republic of Korea(MSIP,No.2017R1A5A2015805,No.2014R1A2A2A01005101)
文摘Objective: To investigate whether the methanol extract of Berberis amurensis Rupr. (BAR) augments penile erection using in vitro and in vivo experiments. Methods: The ex vivo study used corpus cavemosum strips prepared from adult male New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP), blood pressure, mean arterial pressure (MAP), and increase of peak ICP were continuously monitored during electrical stimulation of Sprague-Dawley rats. Results: Preconstricted with phenylephrine (PE) in isolated endothelium- intact rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3-α]-quinoxalin-l-one, a soluble guanylyl cclase inhibitor. BAR significantly relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited by pretreatment with L-NAME 1H-[1,2,4]- oxadiazole-[4,3-α ]-quinoxalin-l-one. BAR-induced relaxation was significantly attenuated by pretreatment with tetraethylammonium (TEA, P〈0.01), a nonselective K+ channel blocker, 4-aminopyridine (4-AP, P〈0.01), a voltage-dependent K+ channel blocker, and charybdotoxin (P〈0.01), a large and intermediate conductance Ca2. sensitive-K+ channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio and area under the curve dose dependently. Conclusion: BAR augments penile erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2. sensitive-K+ (BK+ and IK+) channels in the corpus cavemosum.