BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
The western Ordos Basin(WOB), situated in a tectonic transition zone in the North China Craton, acts as an excellent example for studying the Mesozoic intraplate sedimentation and deformation in Asia. In this study, U...The western Ordos Basin(WOB), situated in a tectonic transition zone in the North China Craton, acts as an excellent example for studying the Mesozoic intraplate sedimentation and deformation in Asia. In this study, U-Pb ages for 1203 detrital zircons of 14 sandstone samples collected from 11 sections are presented to unravel the sediment source locations and paleogeographic environments of the Early-Middle Jurassic coal-bearing Yan'an Formation in the WOB. Data show that there are five prominent age groups in the detrital zircons of the Yan'an Formation, peaking at ca. 282 Ma, 426 Ma, 924 Ma, 1847 Ma, and2468 Ma. Samples from the northern, middle, and southern parts of the WOB contain these five age categories in various proportions. In the northern region, the Yan'an Formation exclusively contains Early Permian detrital zircons with a single age group peaking at 282 Ma, matching well with the crystallizing ages of the widespread Early Permian granites in the Yinshan Belt to the north and the Alxa Block to the northwest. While in the southern region, the Yan'an Formation mainly contains three groups of detrital zircons, with age peaks at 213 Ma, 426 Ma, and 924 Ma. These zircon ages resemble those of the igneous rocks in the Qilian-Qinling Orogenic Belt to the south-southwest. Samples in the middle region, characterized by a mixture age spectrum with peaks at 282 Ma, 426 Ma, 924 Ma, 1847 Ma and 2468 Ma, are previously thought to have mixed derivations from surrounding ranges. However, by referring to the detrital-zircon age compositions of the pre-Jurassic sedimentary successions and combining with paleontological and petrographic analysis, we firstly propose that the sediments of the Yan'an Formation in the middle region were partly recycled from the Triassic and Paleozoic sedimentary strata in the WOB.The occurrence of recycled sedimentation suggests that the Late Triassic-Early Jurassic intraplate compressional deformation was very intense in the WOB, especially for regions in front of the Qilian Orogenic Belt.展开更多
CsgA protein monomers consist of aβ-helix of five repeat units possessing several conservative residues and thus,inherently fibrillate.CsgA protein monomers could self-assemble into hierarchical nanofiber structure c...CsgA protein monomers consist of aβ-helix of five repeat units possessing several conservative residues and thus,inherently fibrillate.CsgA protein monomers could self-assemble into hierarchical nanofiber structure cross multiple scales after expression and secretion by E.Coli cells.Previous researches show that CsgA nanofibers could provide adhesion,stiffness,and mechanical homogeneity for the biofilms,host cells’fibronectin binding for internalization,or protection against phage attack.CsgA nanofibers have obtained various applications in material science and synthetic biology.To illustrate,CsgA nanofibers have characteristics of intrinsic hierarchical structures across multiple scales,robustness in harsh environments and programmable functionality via biological tools.Studying the force spectrum or mechanical properties of the nanofiber can provide fundamental information of self-assembly process and ultra-stability in extreme conditions.Single molecule techniques such as atomic force microscopy,optical tweezers,and magnetic tweezers have been widely applied to study proteins.In these studies,proteins are usually chemically conjugated or genetically constructed to have a tag such as histidine,cysteine or biotin.Genetic engineering requires modification of the plasmids encoding the specific protein,and also involve special protein expression and purification.Such study needs collaboration from multi-disciplinary.It normally studies one protein at a time which gives out clear signal but lacks throughput and efficiency.Here we have established a simple method to measure all kinds of proteins without labels.The carboxyl terminus of a protein is attached to the amine group on a magnetic bead,and the amine terminus of the protein is attached to glutaraldehyde on the glass slide.Then we used magnetic tweezers to manipulate and stretched the bead and protein.Extension versus rotation relation was used to identify a single protein or protein fibril.The fiber under tension is also observed by Scanning Electronic Microcopy which convinces that single CsgA-His fibril is linked to a microbead.The peak of diameter distribution is around 15 nm.The fracture of fibers was observed in real time on SEM.Force-extension curves of single fibers are obtained in real time.The force-extension curves generally agree with the worm like chain model.The persistence lengths from the fitting are from 0.9 to 49.8 nm.The elongation ratio increases gradually with force until reaches a plateau.The maximum elongation ratio of 78 nanofibers were made into an elongation ratio distribution diagram,more than half of CsgA-His nanofibers has an elongation ratio from 0 to 2,some are distributed in 2~10,and a few are distributed in 10~18.The maximum elongation ratio of CsgA-His nanofibers is 17.1,indicating that the fibril’s flexibility is much higher than DNA or silk fiber.For forces less than 20 pN,the extension was reversible.With a 42.1 pN holding force,the extension jumped in steps of from 30 to 365 nm and was irreversible.At the scale tested,the jumps corresponded to the unfolding of multiple beta sheets in the fiber.Work for CsgA-His nanofibers during stretching increase with the normalized strain fractions.The experimental data agree with a theoretical prediction for a single CsgA protein from a SMD calculation.Therefore,our results provide key information for the understandings of CsgA protein nanofiber assembly and biofilm robustness.展开更多
DNA is an attractive biomaterial for constructing nanomachines and nanomaterials owing to their self-recognition and self-assembly properties.In addition to the well-known double helical structures,DNA molecules can a...DNA is an attractive biomaterial for constructing nanomachines and nanomaterials owing to their self-recognition and self-assembly properties.In addition to the well-known double helical structures,DNA molecules can also form a variety of unusual structures like hairpins,triplexes and quadruplexes.These unusual DNAs sometimes have advantages over double helical DNAs in constructing nanomachines such as enhanced thermodynamic stability and higher sensitivity to external stimuli,which made them as promising motifs in recenttwo decades.Regardless of how complicated DNA-based nanomachines are,the fundamental concept in these nanomachines is based on a proper design and usage of DNA molecular switch.Among the reported DNA molecular switches,pH-controlled systems show great potentials in drug delivery and cellular pH sensing.Up to now,most of the reported pH-controlled molecular switches used i-motif or triplex DNAs.However,owing to the relatively long sequence requirement for the formation of i-motif and triplex DNAs,an invading DNA strand needs to be added to activate the molecular switch,and thus DNA wastes will be generated into the system and a full structural conversion will usually take a relatively long time of minutes to hours.To overcome the disadvantages of DNA waste generation and slow kinetics,molecular switches using smaller-size,thermodynamically stable and pH-sensible unusual DNA structures will have the advantages of easier manipulation and faster kinetics.Recently,we discovered a new type of unusual DNA structure called the minidumbbell(MDB)which is formed by a single-strand 8-nucleotide sequence.The MDB is composed of two type II tetraloops in which the first and fourth loop residues form loop-closing base pairs,the second loop residues fold into the minor groove to form base-base stacking or mispairing interactions,and the third loop residues stack on their nearby loop-closing base pairs.In particular,the MDB formed by a sequence containing two CCTG repeats has a relatively low melting temperature(Tm)of^22℃at pH 7.0,whereas its Tm can be significantly increased to^46℃at pH 5.0 due to the formation of a three hydrogen bond hemiprotonated C+·C mispair in the minor groove.This MDB,when combined with its complementary sequence,shows instant and complete structural conversions when the pH switches between 5.0 and 7.0 without using an invading DNA strand,serving as a simple and efficient pH-controlled molecular switch.In order to allow the incorporation of fluorophores to the two termini of the MDB,we aim to design a thermodynamically more stable MDB structure in this study.Through a rational design by introducing hydrophobic interactions to the MDB formed by the sequence containing two CCTG repeats at pH 5.0,we obtained an MDB structure with a record-high Tm of^62℃.Furthermore,this MDB was found to exist stably in the presence of 5’and 3’-overhanging residues,revealing its capability of being attached with fluorophores or other functional groups,and thus making it potentially a versatile pH-controlled molecular switch for designing nanomachines and nanomaterials.展开更多
Yunnan plateau characteristic agriculture is an essential force for increasing farmers' income and promoting prosperity of rural economy. The fundamental position of agriculture should be kept all the time. This p...Yunnan plateau characteristic agriculture is an essential force for increasing farmers' income and promoting prosperity of rural economy. The fundamental position of agriculture should be kept all the time. This paper analyzed practical basis and existing problems in development of Yunnan plateau characteristic agriculture. In line with these problems,it present ideas,main points and objectives of Yunnan plateau characteristic agriculture,and finally came up with recommendations for accelerating development of Yunnan plateau characteristic agriculture.展开更多
To the Editor:Cardiovascular disease(CVD)remains a leading cause of morbidity and mortality globally,with coronary heart disease(CHD)exhibiting the highest mortality rate.Obesity is an important risk factor for cardio...To the Editor:Cardiovascular disease(CVD)remains a leading cause of morbidity and mortality globally,with coronary heart disease(CHD)exhibiting the highest mortality rate.Obesity is an important risk factor for cardiometabolic complication and CVD.Visceral adipose(VA)and subcutaneous adipose(SA)tissues exert differential and possibly opposing effects on cardiometabolic outcomes.展开更多
China’s Tiangong space station has been completed in 2022 to support large-scale multidisciplinary space science research and technology experiments.With a large payload capacity and long operating time,Tiangong spac...China’s Tiangong space station has been completed in 2022 to support large-scale multidisciplinary space science research and technology experiments.With a large payload capacity and long operating time,Tiangong space station has many irreplaceable advantages over other spacecraft,such as space transportation,global tracking,on-orbit care for astronauts,and the ability to replace and upgrade experiment equipment.The resources available to the space station and its affiliated spacecraft provide an excellent open verification platform for experimental programs.The modular design of the intravehicular experiment rack can support different combinations of normal payloads for experiment,and an extravehicular exposed platform is planned to support different sizes of normal payloads for experiment.This paper firstly discusses the mission objectives of China’s Tiangong space station and the development of new space systems.Secondly,it sorts out the conditions for China’s Tiangong space station to conduct experiments for space technology.On this basis,a systematic layout for the missions of space technology experiments on China’s Tiangong space station is made.Five research topics are proposed,i.e.,robotics and autonomous system technology,on-orbit assembly and construction technology for spacecraft,environmental control and life support system technology,new energy and propulsion technology,and new generic technology for spacecraft.Centering on the key technologies that restrict the development of China’s future space missions and systems,this study gives an outlook on the on-orbit space technology experiment and verification project for China’s Tiangong space station.Finally,development strategy and suggestions are put forward for China’s space technology.展开更多
Background: Some depressed patients receive acupuncture as an adjunct to their conventional medications.Objective: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness ...Background: Some depressed patients receive acupuncture as an adjunct to their conventional medications.Objective: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.Search strategy: English and Chinese databases were searched for randomized controlled trials(RCTs)published until December 1, 2021.Inclusion criteria: RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.Data extraction and analysis: Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose.The Grading of Recommendations Assessment, Development and Evaluation(GRADE) framework was used to evaluate the overall quality of evidence in the included studies.Results: This review included 16 studies(with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17(HAMD-17) scores(standard mean difference [SMD]-0.44, 95% confidence interval [CI]-0.55 to-0.33, P < 0.01;I^(2)= 14%), Self-rating Depression Scale(SDS) scores(SMD-0.53, 95% CI-0.84 to-0.23, P < 0.01;I^(2)= 79%), and the Side Effect Rating Scale(SERS) scores(SMD-1.11, 95% CI-1.56 to-0.66, P < 0.01;I^(2)= 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores(SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01;I^(2)= 15%), decreased the number of participants who increased their antidepressant dosages(relative risk[RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01;I^(2)= 0%), and resulted in significantly higher remission rates(RR1.52, 95% CI 1.26 to 1.83, P < 0.01;I^(2)= 0%) and treatment responses(RR 1.35, 95% CI 1.24 to 1.47, P < 0.01;I^(2)= 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.Conclusion: Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.Systematic review registration: INPLASY202150008.展开更多
The Bohai Bay and Hehuai(southern North China) rift basins in the eastern part of the North China Craton are southnorth-adjacent. They have shown synchronous evolutionary processes, and possess generally identical sup...The Bohai Bay and Hehuai(southern North China) rift basins in the eastern part of the North China Craton are southnorth-adjacent. They have shown synchronous evolutionary processes, and possess generally identical superficial and shallow structural characteristics as well as similar basin areas. However, there is a large difference in the richness of oil resources between the two basins. The Bohai Bay Basin has extremely abundant oil reserves, while commercial oil reserves have not been found in the Hehuai Basin. The deep tectonic structures, magmatic activities, and modern and paleo-geothermal fields of the two basins are significantly different. Compared with the Hehuai Basin, the Bohai Bay Basin has a thinner crust and more complex structure with multiple low-velocity layers. It is also characterized by intense magmatic activity, high modern and paleogeothermal fields, frequent seismic activity, and active deep interactions, small effective elastic thickness of the isotropic lithosphere, and shorter balanced transformation wavelength of the lithosphere with a high likelihood of local compensation. The Hehuai Basin has a simple deep structure and homogeneous crustal composition, with a high likelihood of regional compensation. The characteristics of the deep structures mentioned above are generally similar to those of the southern part of the stable Ordos Basin, except for the smaller crust thickness. This indicates the presence of differences in Mesozoic destruction between the southern and northern zones in the eastern part of the North China Craton. The northern zone was subjected to significant destruction, while the southern zone was subjected to modifications, primarily in the form of local changes in the structures and/or properties of the crust or lithospheric mantle, with the overall structure and stability of the craton kept intact. The formation of high-quality source rock is primarily influenced by the abnormal flourishment of organisms in water bodies during the syndepositional period, and is also strongly associated with the high geothermal setting of basins and nutrients from hydrothermal solutions and volcanoes. In other words, it is mainly controlled by deep processes and deep-major fault activity. The differences in the deep structures and modern and paleo geothermal fields of the two basins correspond to the difference in richness of oil resources, suggesting that there is an important internal or causal relationship between the two aspects. This viewpoint coincides with the conditions and environments required for the development of high-quality source rock in hydrocarbon-rich basins(sags)in China and other countries, and is evidenced by the modern lake basin of the East African Rift. A new hydrocarbon generation model is proposed in this work: petroleum is a comprehensive product of the integration of bioenergy, thermal energy, and other related energies(such as chemical and kinetic energy) and their interactions; the degree of richness of petroleum is generally controlled by the regional tectonic structure, thermal environment, and deep processes; nonmarine basins or depressions with abundant resources are closely related to active deep processes, intense exchange of material between the deep and shallow layers, participation of external hydrocarbons, and energy integration and conversion.展开更多
Single-layer YBa2Cu3O7-δ(YBCO) films with the thickness of over 600 nm were fabricated by modified metal organic deposition using trifluoroacetate metal organic deposition(TFA-MOD) method on LaAlO3(LAO) substra...Single-layer YBa2Cu3O7-δ(YBCO) films with the thickness of over 600 nm were fabricated by modified metal organic deposition using trifluoroacetate metal organic deposition(TFA-MOD) method on LaAlO3(LAO) substrates. Polyvinylbutyral(PVB) was added into the precursor solution to enhance the thickness of the single layer. The pyrolysis process was shortened to about 3 h due to the reduction of the fluorine content in the precursor solution.The effects of heating rate during the crystallization process on the microstructure and Jcvalues of YBCO films were investigated. The α-axis-oriented YBCO crystals dominate when the heating rate is lower than 20 °C·min^-1, while faster heating rate of 43 °C·min^-1 results in pure c-axis epitaxial growth. The Jcvalues of YBCO films increase linearly with heating rate increasing due to the increase of c-axis YBCO growth, and the critical current(Ic) value of 100 A·cm^-1 within a single-layer YBCO film is achieved.展开更多
Using the firsthand materials collected during on-site fieldworks and in-depth interviews,this paper examines the dimensions,especially the motives,for driving Chinese firms to invest in agriculture overseas from the ...Using the firsthand materials collected during on-site fieldworks and in-depth interviews,this paper examines the dimensions,especially the motives,for driving Chinese firms to invest in agriculture overseas from the macro(or government’s)-and micro(or firms’)-perspectives,as well as the impact of Chinese firms’agricultural outward foreign direct investment(OFDI)from the multistakeholder perspective.From the perspective of China’s central government,the goal of encouraging domestic enterprises’overseas investment in agriculture is not to ensure national grain security,but to stabilise the domestic supply of strategic agricultural products.From the micro-perspective,the impetuses for driving Chinese firms to invest in agriculture overseas are diverse and land exploitation is just one of them.They may wish to compete with local producers and some of the enterprises do not have a strong awareness of environmental protection and social responsibility.This is not the whole story.Chinese enterprises’agricultural OFDI increases agricultural investment and reduces poverty in the host countries,and expands the supply of agricultural products of the local markets.In the long run,the growing presence of Chinese firms with advanced technology will yield the benefits of competition:an expansion of local supplies while providing cheap technology that can be duplicated by local farmers.Only a very small proportion of the agricultural products grown abroad is sold back to China,while a large part is sold domestically or exported to a third market.Therefore,Chinese firms’agricultural OFDI has offered little direct,but some indirect,help in guaranteeing China’s food security.Perhaps,China’s diplomatic and political benefits obtained through agricultural OFDI outweigh the benefits of ensuring food security.Chinese enterprises’agricultural OFDI is a win-win situation for the host countries and for China.展开更多
This study compares the efficacy,toxicity,hematopoietic recovery,and cost of stem-cell mobilization using intermediate-dose cyclophosphamide(IDCy)plus granulocyte colony-stimulating factor(G-CSF)compared with etoposid...This study compares the efficacy,toxicity,hematopoietic recovery,and cost of stem-cell mobilization using intermediate-dose cyclophosphamide(IDCy)plus granulocyte colony-stimulating factor(G-CSF)compared with etoposide(VP-16)plus pegylated granulocyte colony-stimulating factor(PEG-rhG-CSF)in multiple myeloma(MM)patients.Two hundred forty-four consecutive patients undergoing mobilization with IDCy(3-3.5g/m^(2))plus G-CSF(n=155)were compared with patients receiving VP-16 plus PEG-rhG-CSF(n=89),including oral etoposide(n=65)and intravenous etoposide(n=24).Compared with IDCy,VP-16 use was associated with significantly higher median peak peripheral blood CD34+cell count(8.20[range:1.84-84]×10^(6)/kg vs 4.58[range:0.1-27.9]×10^(6)/kg,P=.000),and ideal CD34+cell yield of more than 6×10^(6)/kg(56.8%vs 35.1%,P=.001),notably with a higher efficacy in oral VP-16 use compared with IDCy use(CD 34+cell counts:median peak peripheral blood 5.87 vs 4.58?106/kg and≥6×10^(6)/kg[48.4%vs 35.1%]).The median number of apheresis courses was reduced from two in the IDCy group to one in the VP-16 group(P=.000).IDCy use was associated with significantly more frequent episodes of neutropenia(70.2%vs 35.2%;P=.000),intravenous antibiotic use(13.2%vs 11.4%;P=.672),and hospitalization(P=.000).The recoveries of neutrophils and platelets after autologous stem-cell transplantation were significantly faster in the VP-16 group compared with the IDCy group(P=.000).Our data indicate robust stem-cell mobilization in MM patients with VP-16 delivered either orally or intravenously.When compared with intravenous VP-16,oral VP-16 mobilization was associated with significantly more convenient,lower average total costs,and especially decreased the risk of hospital visits and exposure.展开更多
CCTG repeat expansions in intron 1 of the cellular nucleic acid-binding protein gene are associated with myotonic dystrophy type 2.Recently,we have reported a novel mini-dumbbell(MDB)structure formed by two CCTG or TT...CCTG repeat expansions in intron 1 of the cellular nucleic acid-binding protein gene are associated with myotonic dystrophy type 2.Recently,we have reported a novel mini-dumbbell(MDB)structure formed by two CCTG or TTTA repeats,which potentially has a critical role in repeat expansions.Here we present a mechanism,called the competing MDB mechanism,to explain how the formation of MDB can lead to efficient mismatch repair(MMR)escape and thus CCTG repeat expansions during DNA replication.In a long tract of CCTG repeats,two competing MDBs can be formed in any segment of three repeats.Fast exchange between these MDBs will make the commonly occupied repeat behave like a mini-loop.Further participations of the 5′-or 3′-flanking repeat in forming competing MDBs will make the mini-loop shift in the 5′-or 3′-direction,thereby providing a pathway for the mini-loop to escape from MMR.To avoid the complications due to the formation of hairpin conformers in longer CCTG repeats,we made use of TTTA repeats as model sequences to demonstrate the formation of competing MDBs and shifting of mini-loop in a long tract of repeating sequence.展开更多
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
基金funded by the National Natural Science Foundation of China(No.41330315)the Northwest University Doctorate Dissertation of Excellence Funds(No.YYB17024)the China Geological Survey(Nos.12120113039900 and 12120114009201)
文摘The western Ordos Basin(WOB), situated in a tectonic transition zone in the North China Craton, acts as an excellent example for studying the Mesozoic intraplate sedimentation and deformation in Asia. In this study, U-Pb ages for 1203 detrital zircons of 14 sandstone samples collected from 11 sections are presented to unravel the sediment source locations and paleogeographic environments of the Early-Middle Jurassic coal-bearing Yan'an Formation in the WOB. Data show that there are five prominent age groups in the detrital zircons of the Yan'an Formation, peaking at ca. 282 Ma, 426 Ma, 924 Ma, 1847 Ma, and2468 Ma. Samples from the northern, middle, and southern parts of the WOB contain these five age categories in various proportions. In the northern region, the Yan'an Formation exclusively contains Early Permian detrital zircons with a single age group peaking at 282 Ma, matching well with the crystallizing ages of the widespread Early Permian granites in the Yinshan Belt to the north and the Alxa Block to the northwest. While in the southern region, the Yan'an Formation mainly contains three groups of detrital zircons, with age peaks at 213 Ma, 426 Ma, and 924 Ma. These zircon ages resemble those of the igneous rocks in the Qilian-Qinling Orogenic Belt to the south-southwest. Samples in the middle region, characterized by a mixture age spectrum with peaks at 282 Ma, 426 Ma, 924 Ma, 1847 Ma and 2468 Ma, are previously thought to have mixed derivations from surrounding ranges. However, by referring to the detrital-zircon age compositions of the pre-Jurassic sedimentary successions and combining with paleontological and petrographic analysis, we firstly propose that the sediments of the Yan'an Formation in the middle region were partly recycled from the Triassic and Paleozoic sedimentary strata in the WOB.The occurrence of recycled sedimentation suggests that the Late Triassic-Early Jurassic intraplate compressional deformation was very intense in the WOB, especially for regions in front of the Qilian Orogenic Belt.
基金supported by the National Science Foundation of China ( 11772133, 11372116)
文摘CsgA protein monomers consist of aβ-helix of five repeat units possessing several conservative residues and thus,inherently fibrillate.CsgA protein monomers could self-assemble into hierarchical nanofiber structure cross multiple scales after expression and secretion by E.Coli cells.Previous researches show that CsgA nanofibers could provide adhesion,stiffness,and mechanical homogeneity for the biofilms,host cells’fibronectin binding for internalization,or protection against phage attack.CsgA nanofibers have obtained various applications in material science and synthetic biology.To illustrate,CsgA nanofibers have characteristics of intrinsic hierarchical structures across multiple scales,robustness in harsh environments and programmable functionality via biological tools.Studying the force spectrum or mechanical properties of the nanofiber can provide fundamental information of self-assembly process and ultra-stability in extreme conditions.Single molecule techniques such as atomic force microscopy,optical tweezers,and magnetic tweezers have been widely applied to study proteins.In these studies,proteins are usually chemically conjugated or genetically constructed to have a tag such as histidine,cysteine or biotin.Genetic engineering requires modification of the plasmids encoding the specific protein,and also involve special protein expression and purification.Such study needs collaboration from multi-disciplinary.It normally studies one protein at a time which gives out clear signal but lacks throughput and efficiency.Here we have established a simple method to measure all kinds of proteins without labels.The carboxyl terminus of a protein is attached to the amine group on a magnetic bead,and the amine terminus of the protein is attached to glutaraldehyde on the glass slide.Then we used magnetic tweezers to manipulate and stretched the bead and protein.Extension versus rotation relation was used to identify a single protein or protein fibril.The fiber under tension is also observed by Scanning Electronic Microcopy which convinces that single CsgA-His fibril is linked to a microbead.The peak of diameter distribution is around 15 nm.The fracture of fibers was observed in real time on SEM.Force-extension curves of single fibers are obtained in real time.The force-extension curves generally agree with the worm like chain model.The persistence lengths from the fitting are from 0.9 to 49.8 nm.The elongation ratio increases gradually with force until reaches a plateau.The maximum elongation ratio of 78 nanofibers were made into an elongation ratio distribution diagram,more than half of CsgA-His nanofibers has an elongation ratio from 0 to 2,some are distributed in 2~10,and a few are distributed in 10~18.The maximum elongation ratio of CsgA-His nanofibers is 17.1,indicating that the fibril’s flexibility is much higher than DNA or silk fiber.For forces less than 20 pN,the extension was reversible.With a 42.1 pN holding force,the extension jumped in steps of from 30 to 365 nm and was irreversible.At the scale tested,the jumps corresponded to the unfolding of multiple beta sheets in the fiber.Work for CsgA-His nanofibers during stretching increase with the normalized strain fractions.The experimental data agree with a theoretical prediction for a single CsgA protein from a SMD calculation.Therefore,our results provide key information for the understandings of CsgA protein nanofiber assembly and biofilm robustness.
基金supported by General Research Fund ( CUHK14302915) from the Research Grants Council of the Hong Kong Special Administrative RegionDirect Grant ( 4053270) from the Faculty of Science of The Chinese University of Hong Kong
文摘DNA is an attractive biomaterial for constructing nanomachines and nanomaterials owing to their self-recognition and self-assembly properties.In addition to the well-known double helical structures,DNA molecules can also form a variety of unusual structures like hairpins,triplexes and quadruplexes.These unusual DNAs sometimes have advantages over double helical DNAs in constructing nanomachines such as enhanced thermodynamic stability and higher sensitivity to external stimuli,which made them as promising motifs in recenttwo decades.Regardless of how complicated DNA-based nanomachines are,the fundamental concept in these nanomachines is based on a proper design and usage of DNA molecular switch.Among the reported DNA molecular switches,pH-controlled systems show great potentials in drug delivery and cellular pH sensing.Up to now,most of the reported pH-controlled molecular switches used i-motif or triplex DNAs.However,owing to the relatively long sequence requirement for the formation of i-motif and triplex DNAs,an invading DNA strand needs to be added to activate the molecular switch,and thus DNA wastes will be generated into the system and a full structural conversion will usually take a relatively long time of minutes to hours.To overcome the disadvantages of DNA waste generation and slow kinetics,molecular switches using smaller-size,thermodynamically stable and pH-sensible unusual DNA structures will have the advantages of easier manipulation and faster kinetics.Recently,we discovered a new type of unusual DNA structure called the minidumbbell(MDB)which is formed by a single-strand 8-nucleotide sequence.The MDB is composed of two type II tetraloops in which the first and fourth loop residues form loop-closing base pairs,the second loop residues fold into the minor groove to form base-base stacking or mispairing interactions,and the third loop residues stack on their nearby loop-closing base pairs.In particular,the MDB formed by a sequence containing two CCTG repeats has a relatively low melting temperature(Tm)of^22℃at pH 7.0,whereas its Tm can be significantly increased to^46℃at pH 5.0 due to the formation of a three hydrogen bond hemiprotonated C+·C mispair in the minor groove.This MDB,when combined with its complementary sequence,shows instant and complete structural conversions when the pH switches between 5.0 and 7.0 without using an invading DNA strand,serving as a simple and efficient pH-controlled molecular switch.In order to allow the incorporation of fluorophores to the two termini of the MDB,we aim to design a thermodynamically more stable MDB structure in this study.Through a rational design by introducing hydrophobic interactions to the MDB formed by the sequence containing two CCTG repeats at pH 5.0,we obtained an MDB structure with a record-high Tm of^62℃.Furthermore,this MDB was found to exist stably in the presence of 5’and 3’-overhanging residues,revealing its capability of being attached with fluorophores or other functional groups,and thus making it potentially a versatile pH-controlled molecular switch for designing nanomachines and nanomaterials.
基金Supported by Key Development and Research Project of Yunnan Provincial Development and Reform Commission(2012)
文摘Yunnan plateau characteristic agriculture is an essential force for increasing farmers' income and promoting prosperity of rural economy. The fundamental position of agriculture should be kept all the time. This paper analyzed practical basis and existing problems in development of Yunnan plateau characteristic agriculture. In line with these problems,it present ideas,main points and objectives of Yunnan plateau characteristic agriculture,and finally came up with recommendations for accelerating development of Yunnan plateau characteristic agriculture.
基金supported by a grant from the Key Research and Development Program(No.2016YFC0900604)from the Ministry of Science and Technology of China
文摘To the Editor:Cardiovascular disease(CVD)remains a leading cause of morbidity and mortality globally,with coronary heart disease(CHD)exhibiting the highest mortality rate.Obesity is an important risk factor for cardiometabolic complication and CVD.Visceral adipose(VA)and subcutaneous adipose(SA)tissues exert differential and possibly opposing effects on cardiometabolic outcomes.
基金supported by China Manned Space Engineering Office and Development research projects of the Science and Technology Commission of the China Academy of Space Technology(CAST)(FZYJ-2022-11).
文摘China’s Tiangong space station has been completed in 2022 to support large-scale multidisciplinary space science research and technology experiments.With a large payload capacity and long operating time,Tiangong space station has many irreplaceable advantages over other spacecraft,such as space transportation,global tracking,on-orbit care for astronauts,and the ability to replace and upgrade experiment equipment.The resources available to the space station and its affiliated spacecraft provide an excellent open verification platform for experimental programs.The modular design of the intravehicular experiment rack can support different combinations of normal payloads for experiment,and an extravehicular exposed platform is planned to support different sizes of normal payloads for experiment.This paper firstly discusses the mission objectives of China’s Tiangong space station and the development of new space systems.Secondly,it sorts out the conditions for China’s Tiangong space station to conduct experiments for space technology.On this basis,a systematic layout for the missions of space technology experiments on China’s Tiangong space station is made.Five research topics are proposed,i.e.,robotics and autonomous system technology,on-orbit assembly and construction technology for spacecraft,environmental control and life support system technology,new energy and propulsion technology,and new generic technology for spacecraft.Centering on the key technologies that restrict the development of China’s future space missions and systems,this study gives an outlook on the on-orbit space technology experiment and verification project for China’s Tiangong space station.Finally,development strategy and suggestions are put forward for China’s space technology.
基金supported by a grant from National Natural Science Foundation of China (grant number 82104983)Scientific Research Program by Traditional Chinese Medicine Bureau of Guangdong Province,China (grant number 20201103)Fundamental Research Funds for the Central Universities,China (grant number 21620362)。
文摘Background: Some depressed patients receive acupuncture as an adjunct to their conventional medications.Objective: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.Search strategy: English and Chinese databases were searched for randomized controlled trials(RCTs)published until December 1, 2021.Inclusion criteria: RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.Data extraction and analysis: Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose.The Grading of Recommendations Assessment, Development and Evaluation(GRADE) framework was used to evaluate the overall quality of evidence in the included studies.Results: This review included 16 studies(with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17(HAMD-17) scores(standard mean difference [SMD]-0.44, 95% confidence interval [CI]-0.55 to-0.33, P < 0.01;I^(2)= 14%), Self-rating Depression Scale(SDS) scores(SMD-0.53, 95% CI-0.84 to-0.23, P < 0.01;I^(2)= 79%), and the Side Effect Rating Scale(SERS) scores(SMD-1.11, 95% CI-1.56 to-0.66, P < 0.01;I^(2)= 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores(SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01;I^(2)= 15%), decreased the number of participants who increased their antidepressant dosages(relative risk[RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01;I^(2)= 0%), and resulted in significantly higher remission rates(RR1.52, 95% CI 1.26 to 1.83, P < 0.01;I^(2)= 0%) and treatment responses(RR 1.35, 95% CI 1.24 to 1.47, P < 0.01;I^(2)= 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.Conclusion: Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.Systematic review registration: INPLASY202150008.
基金supported by the National Natural Science Foundation of China (Grant Nos. 41330315, 91214301, 90814005)the Special Fund of the State Key Laboratory of Continental Dynamics (Northwest University).
文摘The Bohai Bay and Hehuai(southern North China) rift basins in the eastern part of the North China Craton are southnorth-adjacent. They have shown synchronous evolutionary processes, and possess generally identical superficial and shallow structural characteristics as well as similar basin areas. However, there is a large difference in the richness of oil resources between the two basins. The Bohai Bay Basin has extremely abundant oil reserves, while commercial oil reserves have not been found in the Hehuai Basin. The deep tectonic structures, magmatic activities, and modern and paleo-geothermal fields of the two basins are significantly different. Compared with the Hehuai Basin, the Bohai Bay Basin has a thinner crust and more complex structure with multiple low-velocity layers. It is also characterized by intense magmatic activity, high modern and paleogeothermal fields, frequent seismic activity, and active deep interactions, small effective elastic thickness of the isotropic lithosphere, and shorter balanced transformation wavelength of the lithosphere with a high likelihood of local compensation. The Hehuai Basin has a simple deep structure and homogeneous crustal composition, with a high likelihood of regional compensation. The characteristics of the deep structures mentioned above are generally similar to those of the southern part of the stable Ordos Basin, except for the smaller crust thickness. This indicates the presence of differences in Mesozoic destruction between the southern and northern zones in the eastern part of the North China Craton. The northern zone was subjected to significant destruction, while the southern zone was subjected to modifications, primarily in the form of local changes in the structures and/or properties of the crust or lithospheric mantle, with the overall structure and stability of the craton kept intact. The formation of high-quality source rock is primarily influenced by the abnormal flourishment of organisms in water bodies during the syndepositional period, and is also strongly associated with the high geothermal setting of basins and nutrients from hydrothermal solutions and volcanoes. In other words, it is mainly controlled by deep processes and deep-major fault activity. The differences in the deep structures and modern and paleo geothermal fields of the two basins correspond to the difference in richness of oil resources, suggesting that there is an important internal or causal relationship between the two aspects. This viewpoint coincides with the conditions and environments required for the development of high-quality source rock in hydrocarbon-rich basins(sags)in China and other countries, and is evidenced by the modern lake basin of the East African Rift. A new hydrocarbon generation model is proposed in this work: petroleum is a comprehensive product of the integration of bioenergy, thermal energy, and other related energies(such as chemical and kinetic energy) and their interactions; the degree of richness of petroleum is generally controlled by the regional tectonic structure, thermal environment, and deep processes; nonmarine basins or depressions with abundant resources are closely related to active deep processes, intense exchange of material between the deep and shallow layers, participation of external hydrocarbons, and energy integration and conversion.
基金financially supported by the National Natural Science Foundation of China (No.51002024)the Sichuan Youth Science and Technology Innovation Research Team (No.2011JTD0006)+1 种基金the Program for Cooperation of Industry, Education and Academy of Guangdong Province, China (No. 2012B091100298)the Fundamental Research Funds for the Central Universities (Nos.ZYGX2012J039, ZYGX2011Z002, and ZYGX2012J035)
文摘Single-layer YBa2Cu3O7-δ(YBCO) films with the thickness of over 600 nm were fabricated by modified metal organic deposition using trifluoroacetate metal organic deposition(TFA-MOD) method on LaAlO3(LAO) substrates. Polyvinylbutyral(PVB) was added into the precursor solution to enhance the thickness of the single layer. The pyrolysis process was shortened to about 3 h due to the reduction of the fluorine content in the precursor solution.The effects of heating rate during the crystallization process on the microstructure and Jcvalues of YBCO films were investigated. The α-axis-oriented YBCO crystals dominate when the heating rate is lower than 20 °C·min^-1, while faster heating rate of 43 °C·min^-1 results in pure c-axis epitaxial growth. The Jcvalues of YBCO films increase linearly with heating rate increasing due to the increase of c-axis YBCO growth, and the critical current(Ic) value of 100 A·cm^-1 within a single-layer YBCO film is achieved.
文摘Using the firsthand materials collected during on-site fieldworks and in-depth interviews,this paper examines the dimensions,especially the motives,for driving Chinese firms to invest in agriculture overseas from the macro(or government’s)-and micro(or firms’)-perspectives,as well as the impact of Chinese firms’agricultural outward foreign direct investment(OFDI)from the multistakeholder perspective.From the perspective of China’s central government,the goal of encouraging domestic enterprises’overseas investment in agriculture is not to ensure national grain security,but to stabilise the domestic supply of strategic agricultural products.From the micro-perspective,the impetuses for driving Chinese firms to invest in agriculture overseas are diverse and land exploitation is just one of them.They may wish to compete with local producers and some of the enterprises do not have a strong awareness of environmental protection and social responsibility.This is not the whole story.Chinese enterprises’agricultural OFDI increases agricultural investment and reduces poverty in the host countries,and expands the supply of agricultural products of the local markets.In the long run,the growing presence of Chinese firms with advanced technology will yield the benefits of competition:an expansion of local supplies while providing cheap technology that can be duplicated by local farmers.Only a very small proportion of the agricultural products grown abroad is sold back to China,while a large part is sold domestically or exported to a third market.Therefore,Chinese firms’agricultural OFDI has offered little direct,but some indirect,help in guaranteeing China’s food security.Perhaps,China’s diplomatic and political benefits obtained through agricultural OFDI outweigh the benefits of ensuring food security.Chinese enterprises’agricultural OFDI is a win-win situation for the host countries and for China.
基金This work was supported in part by the National Natural Science Foundation of China(NFSC 81372543,NFSC 81870164).
文摘This study compares the efficacy,toxicity,hematopoietic recovery,and cost of stem-cell mobilization using intermediate-dose cyclophosphamide(IDCy)plus granulocyte colony-stimulating factor(G-CSF)compared with etoposide(VP-16)plus pegylated granulocyte colony-stimulating factor(PEG-rhG-CSF)in multiple myeloma(MM)patients.Two hundred forty-four consecutive patients undergoing mobilization with IDCy(3-3.5g/m^(2))plus G-CSF(n=155)were compared with patients receiving VP-16 plus PEG-rhG-CSF(n=89),including oral etoposide(n=65)and intravenous etoposide(n=24).Compared with IDCy,VP-16 use was associated with significantly higher median peak peripheral blood CD34+cell count(8.20[range:1.84-84]×10^(6)/kg vs 4.58[range:0.1-27.9]×10^(6)/kg,P=.000),and ideal CD34+cell yield of more than 6×10^(6)/kg(56.8%vs 35.1%,P=.001),notably with a higher efficacy in oral VP-16 use compared with IDCy use(CD 34+cell counts:median peak peripheral blood 5.87 vs 4.58?106/kg and≥6×10^(6)/kg[48.4%vs 35.1%]).The median number of apheresis courses was reduced from two in the IDCy group to one in the VP-16 group(P=.000).IDCy use was associated with significantly more frequent episodes of neutropenia(70.2%vs 35.2%;P=.000),intravenous antibiotic use(13.2%vs 11.4%;P=.672),and hospitalization(P=.000).The recoveries of neutrophils and platelets after autologous stem-cell transplantation were significantly faster in the VP-16 group compared with the IDCy group(P=.000).Our data indicate robust stem-cell mobilization in MM patients with VP-16 delivered either orally or intravenously.When compared with intravenous VP-16,oral VP-16 mobilization was associated with significantly more convenient,lower average total costs,and especially decreased the risk of hospital visits and exposure.
基金The work described in this paper was supported by General Research Fund(project no.CUHK14302114)from the Research Grants Council of the Hong Kong Special Administrative Region and a direct grant(project ID:3132671)from the Faculty of Science of The Chinese University of Hong Kong.
文摘CCTG repeat expansions in intron 1 of the cellular nucleic acid-binding protein gene are associated with myotonic dystrophy type 2.Recently,we have reported a novel mini-dumbbell(MDB)structure formed by two CCTG or TTTA repeats,which potentially has a critical role in repeat expansions.Here we present a mechanism,called the competing MDB mechanism,to explain how the formation of MDB can lead to efficient mismatch repair(MMR)escape and thus CCTG repeat expansions during DNA replication.In a long tract of CCTG repeats,two competing MDBs can be formed in any segment of three repeats.Fast exchange between these MDBs will make the commonly occupied repeat behave like a mini-loop.Further participations of the 5′-or 3′-flanking repeat in forming competing MDBs will make the mini-loop shift in the 5′-or 3′-direction,thereby providing a pathway for the mini-loop to escape from MMR.To avoid the complications due to the formation of hairpin conformers in longer CCTG repeats,we made use of TTTA repeats as model sequences to demonstrate the formation of competing MDBs and shifting of mini-loop in a long tract of repeating sequence.