A well designed coating for polyetheretherketone(PEEK)implants can provide enough support to overcome crucial medical challenges,which are insufficient osseointegration and high rate of infection.Herein,we utilize the...A well designed coating for polyetheretherketone(PEEK)implants can provide enough support to overcome crucial medical challenges,which are insufficient osseointegration and high rate of infection.Herein,we utilize the co-deposition of polydopamine(PDA)and copper-citrate nanoclusters to construct a p H-responsive coating on porous PEEK for synergistic bone regeneration,vascular formation and anti-infection.Specifically,this PDA coating released high dose of copper and citrate at lower p H value,which increased intracellular copper content,boosted production of reactive oxygen species and severe damage of protein,leading to killing of 93%planktonic bacterial and eradication of adherent bacteria.At p H of 7.4,the release of copper and citrate were in a slow and sustained behavior,synergistically enhanced vascular formation potential and osteodiffereration of Ad-MSC in vitro.After implanted in rabbit tibia for 6 and 12 weeks,the micro-CT evaluation and histological analysis consistently highlighted the ability of this PDA coating to increase new bone formation adjacent to coated PEEK implant and enhance bone-implant interfacial integration.These results were proven to be related to the synergistic effect that citrate facilitated a 2-fold influx of copper into cells,which not only enhanced the bacteria-killing ability but also encouraged bone regeneration of implants.This present work provides an effective method to control infections while promoting osseointegration simultaneously,which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.展开更多
Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogrammi...Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.展开更多
The performance of gas-drilling(drilling oil and gas wells with air, nitrogen, or natural gas) is very unpredictable in many areas due to lack of proper design of drilling parameters because of limited understanding o...The performance of gas-drilling(drilling oil and gas wells with air, nitrogen, or natural gas) is very unpredictable in many areas due to lack of proper design of drilling parameters because of limited understanding of gas–rock interaction which requires knowledge of heat transfer in the well system. Complete analysis of rock failure requires an accurate mathematical model to predict gas temperature at the bottom hole. The currently available mathematical models are unsuitable for use for the purpose because they do not consider the effects of formation fluid influx, Joule–Thomson cooling, and entrained drill cuttings. A new analytical solution for predicting gas temperature profiles inside the drill string and in the annulus was derived in this study for gas-drilling, considering all these three effects. Results of sensitivity analyses show that formation fluid influx can significantly increase the temperature profiles in both the drill string and the annulus.The Joule–Thomson cooling effect lowers the temperature in the annulus only in a short interval near the bottom hole.The drill cuttings entrained at the bottom hole can slightly increase the temperature profile in the annulus.展开更多
Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asex...Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asexual life cycle are largely unknown. Here, factors involved in the regulation of production and discharge of asexual spores, so-called monospores, are identified in the marine red macroalga Porphyra yezoensis. First, enhanced discharge of monospores was found by incubation of gametophytes in ASPMT1, a modified version of the previously established synthetic medium ASP12. Comparison of the compositions of ASPMT1 and our standard medium, ESL, indicated that the Ca2+ concentration in ASPMT1 was three times lower than that in ESL medium. Thus, we modified ASPMT1 by increasing its Ca2+ concentration, resulting in reduction of monospore discharge. These findings demonstrate the role of reduced Ca2+ concentrations in enhancing monospore production and release. Moreover, it was also observed that initiation of asexual life cycle required illumination, was repressed by DCMU, and was induced by a Ca2+ ionophore in the dark. Taken together, these results indicate that photosynthesis-dependent Ca2+ influx triggers the asexual life cycle by promoting the production and discharge of monospores in P. yezoensis.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component ...Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.展开更多
Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was...Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was applied to evaluate the effects of 4 variables by UAPE on cAMP yield.The results showed that the optimal cAMP yield(783.0μg/g)was derived at ratio of liquid to solid 5 mL/g,ratio of pectinase to raw material 1.5%,time 60 min and temperature 40℃.Moreover,the effect of cAMP on the anti-allergic function of action induced by immunoglobulin E(IgE)and its meschanism was investigated through establishing the sensitized cell model in rat basophilic leukemia(RBL-2 H3)cells using dinitrophenylated(DNP)-bovine serum albumin(BSA)-IgE.The results showed that cAMP interfered with sensitized cells,effectively inhibited the occurrence of basophil degranulation in dose dependence,and significantly reduced the activity ofβ-hexosamindase(β-hex),at the optimal concentration of 50μg/mL.The level of anti-inflammatory factor interleukin-10(IL-10)was promoted and the content of pro-inflammatory factor tumor necrosis factor-α(TNF-α)was suppressed by cAMP.In addition,influx of intracellular Ca^(2+) was repressed effectively.Our results demonstrate that jujube cAMP regulated the cytokine balance in the allergy pathway through blocking the influx of extracellular Ca^(2+),with the prevention of allergy symptoms.展开更多
This study analyzes the sample influx (samples per case file) into forensic science laboratory (FSL) and the corresponding analysis costs and uses arbitrary re-sampling plans to establish the minimum cost function. Th...This study analyzes the sample influx (samples per case file) into forensic science laboratory (FSL) and the corresponding analysis costs and uses arbitrary re-sampling plans to establish the minimum cost function. The demand for forensic analysis increased for all disciplines, especially biology/DNA between 2014 and 2015. While the average distribution of case files was about 42.5%, 40.6% and 17% for the three disciplines, the distribution of samples was rather different being 12%, 82.5% and 5.5% for samples requiring forensic biology, chemistry and toxicology analysis, respectively. Results show that most of the analysis workload was on forensic chemistry analysis. The cost of analysis for case files and the corresponding sample influx varied in the ratio of 35:6:1 and 28:12:1 for forensic chemistry, biology/DNA and toxicology for year 2014 for 2015, respectively. In the two consecutive years, the cost for forensic chemistry analysis was comparatively very high, necessitating re-sampling. The time series of sample influx in all disciplines are strongly stochastic, with higher magnitude for chemistry, biology/DNA and toxicology, in this order. The PDFs of sample influx data are highly skewed to the right, especially forensic toxicology and biology/DNA with peaks at 1 and 3 samples per case file. The arbitrary re-sampling plans were best suited to forensic chemistry case files (where re-sampling conditions apply). The locus of arbitrary number of samples to take from the submitted forensic samples was used to establish the minimum and scientifically acceptable samples by applying minimization function developed in this paper. The cost minimization function was also developed based on the average cost per sample and choice of re-sampling plans depending on the range of sample influx, from which the savings were determined and maximized. Thus, the study gives a forensic scientist a business model and scientific decision making tool on minimum number of samples to analyze focusing on savings on analysis cost.展开更多
The spectra of HeI（587.6 nm）,Hα（656.28 nm） and Dα（656.1 nm） of the helium discharges as well as the normal deuterium discharges have been measured with two optical spectroscopic multi-channel analysis（OMA） s...The spectra of HeI（587.6 nm）,Hα（656.28 nm） and Dα（656.1 nm） of the helium discharges as well as the normal deuterium discharges have been measured with two optical spectroscopic multi-channel analysis（OMA） systems on the experimental advanced superconducting tokamak（EAST）.The influx ratio of the sum of H and D to He spectral lines and the influx ratio of H to D are given.In this way the ratio of hydrogen/deuterium ion（S/X B）H/D to（S/X B）He as well as（S/X B）H/D is not very sensitive to the variation in the edge density and temperature. The low-density helium discharges are operated in order to reduce the recycling hydrogen fluxes; however,the effect is not obvious.The possible reason is that the number of helium discharges is not enough and the content of hydrogen in the wall is still very abundant,which is caused by frequent wall conditionings and the vacuum leakage.The H/（H＋D） ratio decreases quickly after one lithium coating and reduces to less than 10%using several accumulated lithium wall conditioning.It is found that the deposited He atoms on the carbon wall will remain at a low level after several D2 discharges.展开更多
Objective:To study the effect of crude methanol and n-hexane extracts of Hypericum connatum(H.connatum) and Hypericum caprifoliatum on trophoblast-like cells.Methods:BeWo and JEG-3 trophoblast-like cells were submitte...Objective:To study the effect of crude methanol and n-hexane extracts of Hypericum connatum(H.connatum) and Hypericum caprifoliatum on trophoblast-like cells.Methods:BeWo and JEG-3 trophoblast-like cells were submitted to different extract concentrations(1.5,10 and 15 μg/mL) and evaluated in relation to cell viability and in titro trophoblast differentiation and function.Cell viability was evaluated using WST-1 reagent.Differentiation was measured by luciferase production,hCG production/release,and mitogenactivated protein kinase signaling pathway activation.The function of the trophoblast-like cells was measured by^(25)Ca^(2*) influx evaluation.Results:The results showed a decrease in cell viability/proliferation.Both plants and different extracts induced a significant decrease in hCG production/release and luciferase production.H.connatum did not cause mitogen-activated protein kinase signaling pathway disturbance;however,Hypericum caprifoliatum n-hexane extract at 15 μg/mL inhibited extracellular signalregulated kinase 1/2 activation.The significant increase in Ca^(2+) influx by JEG-3 cells was seen after short and long incubation times with H.connatum methanolie extract at 15 μg/mL.Conclusions:The results indicated that these two Hypericum species extracts can interfere on trophoblast differentiation and Ca^(2+)influx,according to their molecular diversity.Although in vivo experiments are necessary to establish their action on placental formation and function,this study suggests that attention must be paid to the potential toxic effect of these plants.展开更多
This paper presents two methods for easy determination of water influx in reservoirs based on the material balance theory of reservoirs,i.e.,the Net Production Volume Curve,and the Production Index Curve.These methods...This paper presents two methods for easy determination of water influx in reservoirs based on the material balance theory of reservoirs,i.e.,the Net Production Volume Curve,and the Production Index Curve.These methods can be used for esti-ma tion of water influx in reservoirs without any assumption of aquifer shape and size by applying the production performance data.Hence the tedium of the c onventional trial-and-error calculations and obvious uncertainty could be over come in ap plication of the easy and practical new methods.展开更多
Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibo...Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.展开更多
Nodulin 26-like intrinsic proteins(NIPs) are a family of channel-forming transmembrane proteins that function in the transport of water and other small molecules.Some NIPs can mediate silicon transport across plasma m...Nodulin 26-like intrinsic proteins(NIPs) are a family of channel-forming transmembrane proteins that function in the transport of water and other small molecules.Some NIPs can mediate silicon transport across plasma membranes and lead to silicon accumulation in plants,which is beneficial for the growth and development of plants.Cucumber is one of the most widely consumed vegetables;however,the functions of NIPs in this crop are still largely unknown.Here,we report the functional characteristics of Cs NIP2;2.It was found that Cs NIP2;2 is a tandem repeat of Cs NIP2;1,which had been demonstrated to be a silicon influx transporter gene.Cs NIP2;2 has a selectivity filter composed of cysteine,serine,glycine and arginine(CSGR),which is different from all previously characterized silicon influx transporters in higher plants at the second helix position.Xenopus laevis oocytes injected with Cs NIP2;2 c RNA demonstrated a higher uptake of silicon than the control,and the uptake remained unchanged under low temperature.Cs NIP2;2 was found to be expressed in the root,stem,lamina and petiole,and exogenous silicon treatment decreased its expression in the stem but not in other tissues.Transient expression of Cs NIP2;2-e GFP fusion sequence in onion epidermal cells showed that Cs NIP2;2 was localized to the cell nucleus,plasma membrane and an unknown structure inside the cell.The results suggest that Cs NIP2;2 is a silicon influx transporter in cucumber,and its subcellular localization and the selectivity filter are different from those of the previously characterized silicon influx transporters in other plants.These findings may be helpful for understanding the functions of NIPs in cucumber plants.展开更多
The effect of verapamil on Ca2+ influx across the myocardial plasma membrane and coxsackie virus B3 ( CVB3)-RNA replication in cultured neonatal rat heart cells infected with CVB3 was investigated. It was found that t...The effect of verapamil on Ca2+ influx across the myocardial plasma membrane and coxsackie virus B3 ( CVB3)-RNA replication in cultured neonatal rat heart cells infected with CVB3 was investigated. It was found that the Ca2+ influx could be inhibited significantly (P<O. 01) by verapamil (1 μmol/L) after infection of heart cells for 48h. However, when the cultured heart cells infected with CVB3 and treated with verapamil (Iμmol/L and 10 nmo/L) at the same time for 48h, the amounts of CVB3-RNA in myocytes were significantly higher than that in infected control group (P<O. 05). These phenomena suggest that the increase of Ca2+ influx of cultured heart cells infected with CVB3 could be inhibited by some calcium antagonists, e. g. verapamil at the early stage. On the other hand, verapamil might accelerate viral replication in myocardium. Thus, although verapamil could be beneficial for decreasing the secondary Ca2+ damages and improve the myocardial electric activity, it isn’t a sensible choice for therapy in early stage of virus infection with cardiac symptoms.展开更多
This paper analyzes the effect of subgroup size on the x-bar chart characteristics using sample influx (SIF) into forensic science laboratory (FSL). The characteristics studied include changes in out-or-control points...This paper analyzes the effect of subgroup size on the x-bar chart characteristics using sample influx (SIF) into forensic science laboratory (FSL). The characteristics studied include changes in out-or-control points (OCP), upper control limit UCLx, and zonal demarcations. Multi-rules were used to identify the number of out-of-control-points, Nocp as violations using five control chart rules applied separately. A sensitivity analysis on the Nocp was applied for subgroup size, k, and number of sigma above the mean value to determine the upper control limit, UCLx. A computer code was implemented using a FORTRAN code to create x-bar control-charts and capture OCP and other control-chart characteristics with increasing k from 2 to 25. For each value of k, a complete series of average values, Q(p), of specific length, Nsg, was created from which statistical analysis was conducted and compared to the original SIF data, S(t). The variation of number of out-of-control points or violations, Nocp, for different control-charts rules with increasing k was determined to follow a decaying exponential function, Nocp = Ae–α, for which, the goodness of fit was established, and the R2 value approached unity for Rule #4 and #5 only. The goodness of fit was established to be the new criteria for rational subgroup-size range, for Rules #5 and #4 only, which involve a count of 6 consecutive points decreasing and 8 consecutive points above the selected control limit (σ/3 above the grand mean), respectively. Using this criterion, the rational subgroup range was established to be 4 ≤ k ≤ 20 for the two x-bar control chart rules.展开更多
As we all know, cyclic gas injection is one of the most effective development methods to improve condensate oil recovery. When dealing with the calculation of the reserves, the injection-production differences and wat...As we all know, cyclic gas injection is one of the most effective development methods to improve condensate oil recovery. When dealing with the calculation of the reserves, the injection-production differences and water influx create great influence on the accuracy. Based on the existing research, we proposed a new material balance equation which considered the differences of composition between produced and injected fluids and the effect of water influx, and a solution was provided in this paper. The results of the method are closer to the actual situation because they are built on the law of conservation of mass, and the using of curve fitting method can not only avoid the use of water influx coefficient but also obtain the water influx rate and reserves at the same time. The YH-23 gas condensate reservoir is taking as a typical subject to do the research, which has been exploited by cycle gas injection for 14 years. Three different methods are used to calculate the reserves, and the results show that the method proposed in this paper has minimum error of 2.96%.展开更多
Because of the diversity of geological characteristics and the complexity of percolation rules,many problems are found ineffective water influx control in gas reservoir development.The problems mainly focus on how to ...Because of the diversity of geological characteristics and the complexity of percolation rules,many problems are found ineffective water influx control in gas reservoir development.The problems mainly focus on how to understand water influx rules,to establish appropriate countermeasures,and to ensure the effectiveness of technical measures.It is hard to obtain a complete applicable understanding through the isolated analysis of an individual gas reservoir due to many factors such as actual gas reservoir development phase,research work,pertinence and timeliness of measures,and so on.Over the past four decades,the exploration,practicing and tracking research have been conducted on water control in gas reservoir development in the Sichuan Basin,and a series of comprehensive water control technologies were developed integrating advanced concepts,successful experiences,specific theories and mature technologies.Though the development of most water-drive gas reservoirs was significantly improved,water control effects were quite different.Based on this background,from the perspective of the earlyphase requirements of water influx control,the influencing factors of a water influx activity,the dynamic analysis method of water influx performance,the optimizing strategy of a water control,and the water control experience of typical gas reservoirs,this paper analyzed the key problems of water control,evaluated the influencing factors of water control effect,explored the practical water control strategies,and proposed that it should be inappropriate to apply the previous water control technological model to actual work but the pertinence should be improved according to actual circumstances.The research results in the paper provide technical reference for the optimization of water-invasion gas reservoir development.展开更多
Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats andseeded intO culture plates. 1OOTCID50 of coxsackie virus B3 (CVB3) (Nancy strain )was added as the infectedgroup. The...Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats andseeded intO culture plates. 1OOTCID50 of coxsackie virus B3 (CVB3) (Nancy strain )was added as the infectedgroup. The dynamics of taurine transport across membrane of normal heart cells and changes after infectionwere examined by using radioactive isotope tracing techniques. The results demonstrated that: (1)two uptake systems of taurine with different affinities and capacities were present in the Plasma membrane of cul-tured rat cardiOmyocytes,the K. of high and low affinity were 9. 5 X 10-5mol/l, and l. 3 X 1 O 2 mol/l,,respectively; (2)taurine transport across membrane was sodium-dependent with a positive linear relationshipbetween amount of taurine influx and extracellular concentration of sOdium;in addition,it was alsO regulat-ed by osmOlarity; (3) fyalanine,a carboxylic analog of taurine,could inhibit the uptake of taurine in dosedependently; (4)taurine influx was decreased in cultured rat cardiomyocytes after infected with CVB3. (5)the lnhibition ratio of taurine transport was enhanced as the infected time prolonged. This experiment pro-vides a basis fOr further investigation of kinetic test of taurine transport and more study should be carriedout to learn the effect of taurine in viral myocarditis.展开更多
基金financially supported by the National Key Research and Development Project(2018YFC1106600)National Natural Science Foundation of China(No.31670974,No.31370954,No.51901003)。
文摘A well designed coating for polyetheretherketone(PEEK)implants can provide enough support to overcome crucial medical challenges,which are insufficient osseointegration and high rate of infection.Herein,we utilize the co-deposition of polydopamine(PDA)and copper-citrate nanoclusters to construct a p H-responsive coating on porous PEEK for synergistic bone regeneration,vascular formation and anti-infection.Specifically,this PDA coating released high dose of copper and citrate at lower p H value,which increased intracellular copper content,boosted production of reactive oxygen species and severe damage of protein,leading to killing of 93%planktonic bacterial and eradication of adherent bacteria.At p H of 7.4,the release of copper and citrate were in a slow and sustained behavior,synergistically enhanced vascular formation potential and osteodiffereration of Ad-MSC in vitro.After implanted in rabbit tibia for 6 and 12 weeks,the micro-CT evaluation and histological analysis consistently highlighted the ability of this PDA coating to increase new bone formation adjacent to coated PEEK implant and enhance bone-implant interfacial integration.These results were proven to be related to the synergistic effect that citrate facilitated a 2-fold influx of copper into cells,which not only enhanced the bacteria-killing ability but also encouraged bone regeneration of implants.This present work provides an effective method to control infections while promoting osseointegration simultaneously,which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant No.81902616 to F.W.)Science and Technology Support Project in the field of biomedicine of Shanghai Science and Technology Action Plan(Grant No.19441909200,F.W.)+6 种基金Clinical Research Project of Shanghai Municipal Commission of Health and Family Planning(Grant No.20184Y0130,F.W.)Precision Medicine Program of Second Military Medical University(Grant No.2017JZ35,F.W.)Youth Startup Program of the Second Military Medical University(Grant No.2016QN12,F.W.)Jiangsu Provincial Medical Youth Talent(Grant No.QNRC2016739,X.W.)Shanghai Sailing Program(Grant No.21YF1423300,H.X.)Natural Science Foundation of Shanghai(Grant No.21ZR1437800,H.X.)Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicine(Grant No.YG2021QN75,H.X.).
文摘Objective:This study aimed to evaluate the effects of mitochondrial pyruvate carrier(MPC)blockade on the sensitivity of detection and radiotherapy of prostate cancer(PCa).Methods:We investigated glycolysis reprogramming and MPC changes in patients with PCa by using metabolic profiling,RNASeq,and tissue microarrays.Transient blockade of pyruvate influx into mitochondria was observed in cellular studies to detect its different effects on prostate carcinoma cells and benign prostate cells.Xenograft mouse models were injected with an MPC inhibitor to evaluate the sensitivity of 18F-fluorodeoxyglucose positron emission tomography with computed tomography and radiotherapy of PCa.Furthermore,the molecular mechanism of this different effect of transient blockage towards benign prostate cells and prostate cancer cells was studied in vitro.Results:MPC was elevated in PCa tissue compared with benign prostate tissue,but decreased during cancer progression.The transient blockade increased PCa cell proliferation while decreasing benign prostate cell proliferation,thus increasing the sensitivity of PCa cells to 18F-PET/CT(SUVavg,P=0.016;SUVmax,P=0.03)and radiotherapy(P<0.01).This differential effect of MPC on PCa and benign prostate cells was dependent on regulation by a VDAC1-MPC-mitochondrial homeostasis-glycolysis pathway.Conclusions:Blockade of pyruvate influx into mitochondria increased glycolysis levels in PCa but not in non-carcinoma prostate tissue.This transient blockage sensitized PCa to both detection and radiotherapy,thus indicating that glycolytic potential is a novel mechanism underlying PCa progression.The change in the mitochondrial pyruvate influx caused by transient MPC blockade provides a critical target for PCa diagnosis and treatment.
基金supported by the China National Natural Science Foundation Funding No.51134004
文摘The performance of gas-drilling(drilling oil and gas wells with air, nitrogen, or natural gas) is very unpredictable in many areas due to lack of proper design of drilling parameters because of limited understanding of gas–rock interaction which requires knowledge of heat transfer in the well system. Complete analysis of rock failure requires an accurate mathematical model to predict gas temperature at the bottom hole. The currently available mathematical models are unsuitable for use for the purpose because they do not consider the effects of formation fluid influx, Joule–Thomson cooling, and entrained drill cuttings. A new analytical solution for predicting gas temperature profiles inside the drill string and in the annulus was derived in this study for gas-drilling, considering all these three effects. Results of sensitivity analyses show that formation fluid influx can significantly increase the temperature profiles in both the drill string and the annulus.The Joule–Thomson cooling effect lowers the temperature in the annulus only in a short interval near the bottom hole.The drill cuttings entrained at the bottom hole can slightly increase the temperature profile in the annulus.
文摘Asexual propagation to increase the number of gametophytic clones via the growth of asexual haploid spores is a unique survival strategy found in marine multicellular algae. However, the mechanisms regulating the asexual life cycle are largely unknown. Here, factors involved in the regulation of production and discharge of asexual spores, so-called monospores, are identified in the marine red macroalga Porphyra yezoensis. First, enhanced discharge of monospores was found by incubation of gametophytes in ASPMT1, a modified version of the previously established synthetic medium ASP12. Comparison of the compositions of ASPMT1 and our standard medium, ESL, indicated that the Ca2+ concentration in ASPMT1 was three times lower than that in ESL medium. Thus, we modified ASPMT1 by increasing its Ca2+ concentration, resulting in reduction of monospore discharge. These findings demonstrate the role of reduced Ca2+ concentrations in enhancing monospore production and release. Moreover, it was also observed that initiation of asexual life cycle required illumination, was repressed by DCMU, and was induced by a Ca2+ ionophore in the dark. Taken together, these results indicate that photosynthesis-dependent Ca2+ influx triggers the asexual life cycle by promoting the production and discharge of monospores in P. yezoensis.
基金financially supported by grants from the National Natural Science Foundation of China(8217087381871095)+1 种基金the National Key R&D Program of China(2018YFC2000304)the Tsinghua University Spring Breeze Fund(20211080005).
文摘Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.
基金supported by grant from the National Key Research and Development Program of China(2018YFC1602201)the Open Research Fund Program of Beijing Key Lab of Plant Resource Research and Development,Beijing Technology and Business University(PRRD-2021-YB8)+1 种基金the National Natural Science Fund(31601395)the Key Program for Shaanxi Science and Technology(2020NY-146)。
文摘Jujube contains abundant cyclic adenosine monophosphate(cAMP)and the ultrasonic-assisted pectinase extraction(UAPE)conditions for obtaining the maximum cAMP yield from jujube were optimized.Orthogonal array design was applied to evaluate the effects of 4 variables by UAPE on cAMP yield.The results showed that the optimal cAMP yield(783.0μg/g)was derived at ratio of liquid to solid 5 mL/g,ratio of pectinase to raw material 1.5%,time 60 min and temperature 40℃.Moreover,the effect of cAMP on the anti-allergic function of action induced by immunoglobulin E(IgE)and its meschanism was investigated through establishing the sensitized cell model in rat basophilic leukemia(RBL-2 H3)cells using dinitrophenylated(DNP)-bovine serum albumin(BSA)-IgE.The results showed that cAMP interfered with sensitized cells,effectively inhibited the occurrence of basophil degranulation in dose dependence,and significantly reduced the activity ofβ-hexosamindase(β-hex),at the optimal concentration of 50μg/mL.The level of anti-inflammatory factor interleukin-10(IL-10)was promoted and the content of pro-inflammatory factor tumor necrosis factor-α(TNF-α)was suppressed by cAMP.In addition,influx of intracellular Ca^(2+) was repressed effectively.Our results demonstrate that jujube cAMP regulated the cytokine balance in the allergy pathway through blocking the influx of extracellular Ca^(2+),with the prevention of allergy symptoms.
文摘This study analyzes the sample influx (samples per case file) into forensic science laboratory (FSL) and the corresponding analysis costs and uses arbitrary re-sampling plans to establish the minimum cost function. The demand for forensic analysis increased for all disciplines, especially biology/DNA between 2014 and 2015. While the average distribution of case files was about 42.5%, 40.6% and 17% for the three disciplines, the distribution of samples was rather different being 12%, 82.5% and 5.5% for samples requiring forensic biology, chemistry and toxicology analysis, respectively. Results show that most of the analysis workload was on forensic chemistry analysis. The cost of analysis for case files and the corresponding sample influx varied in the ratio of 35:6:1 and 28:12:1 for forensic chemistry, biology/DNA and toxicology for year 2014 for 2015, respectively. In the two consecutive years, the cost for forensic chemistry analysis was comparatively very high, necessitating re-sampling. The time series of sample influx in all disciplines are strongly stochastic, with higher magnitude for chemistry, biology/DNA and toxicology, in this order. The PDFs of sample influx data are highly skewed to the right, especially forensic toxicology and biology/DNA with peaks at 1 and 3 samples per case file. The arbitrary re-sampling plans were best suited to forensic chemistry case files (where re-sampling conditions apply). The locus of arbitrary number of samples to take from the submitted forensic samples was used to establish the minimum and scientifically acceptable samples by applying minimization function developed in this paper. The cost minimization function was also developed based on the average cost per sample and choice of re-sampling plans depending on the range of sample influx, from which the savings were determined and maximized. Thus, the study gives a forensic scientist a business model and scientific decision making tool on minimum number of samples to analyze focusing on savings on analysis cost.
基金supported by National Natural Science Foundation of China(Nos.10975155,11175208,10990212)National Magnetic Confinement Fusion Science Program of China(Nos.2012GB101000,2011GB101000,2011GB107000,2009GB104003)
文摘The spectra of HeI（587.6 nm）,Hα（656.28 nm） and Dα（656.1 nm） of the helium discharges as well as the normal deuterium discharges have been measured with two optical spectroscopic multi-channel analysis（OMA） systems on the experimental advanced superconducting tokamak（EAST）.The influx ratio of the sum of H and D to He spectral lines and the influx ratio of H to D are given.In this way the ratio of hydrogen/deuterium ion（S/X B）H/D to（S/X B）He as well as（S/X B）H/D is not very sensitive to the variation in the edge density and temperature. The low-density helium discharges are operated in order to reduce the recycling hydrogen fluxes; however,the effect is not obvious.The possible reason is that the number of helium discharges is not enough and the content of hydrogen in the wall is still very abundant,which is caused by frequent wall conditionings and the vacuum leakage.The H/（H＋D） ratio decreases quickly after one lithium coating and reduces to less than 10%using several accumulated lithium wall conditioning.It is found that the deposited He atoms on the carbon wall will remain at a low level after several D2 discharges.
基金Supported by Canadian Institutes of Health Research(CIHRNET 54002)
文摘Objective:To study the effect of crude methanol and n-hexane extracts of Hypericum connatum(H.connatum) and Hypericum caprifoliatum on trophoblast-like cells.Methods:BeWo and JEG-3 trophoblast-like cells were submitted to different extract concentrations(1.5,10 and 15 μg/mL) and evaluated in relation to cell viability and in titro trophoblast differentiation and function.Cell viability was evaluated using WST-1 reagent.Differentiation was measured by luciferase production,hCG production/release,and mitogenactivated protein kinase signaling pathway activation.The function of the trophoblast-like cells was measured by^(25)Ca^(2*) influx evaluation.Results:The results showed a decrease in cell viability/proliferation.Both plants and different extracts induced a significant decrease in hCG production/release and luciferase production.H.connatum did not cause mitogen-activated protein kinase signaling pathway disturbance;however,Hypericum caprifoliatum n-hexane extract at 15 μg/mL inhibited extracellular signalregulated kinase 1/2 activation.The significant increase in Ca^(2+) influx by JEG-3 cells was seen after short and long incubation times with H.connatum methanolie extract at 15 μg/mL.Conclusions:The results indicated that these two Hypericum species extracts can interfere on trophoblast differentiation and Ca^(2+)influx,according to their molecular diversity.Although in vivo experiments are necessary to establish their action on placental formation and function,this study suggests that attention must be paid to the potential toxic effect of these plants.
文摘This paper presents two methods for easy determination of water influx in reservoirs based on the material balance theory of reservoirs,i.e.,the Net Production Volume Curve,and the Production Index Curve.These methods can be used for esti-ma tion of water influx in reservoirs without any assumption of aquifer shape and size by applying the production performance data.Hence the tedium of the c onventional trial-and-error calculations and obvious uncertainty could be over come in ap plication of the easy and practical new methods.
文摘Autoantibody against neuronal nicotinic acetylcholine receptor (nAChR) α3 subunit is implicated in severe autonomic dysfunction in the patients with autoimmune autonomic ganglionopathy (AAG). Although this autoantibody has been revealed to impair fast excitatory synaptic transmission in autonomic ganglia, its precise mechanism remains unknown. Here, we show that antibody-induced reduction of cell-surface α3 subunits result in impairment of nicotine-evoked Ca2+ influx in stably transfected human embryonic kidney cells. These effects of the antibody were remarkably inhibited by interfering with the endocytic machinery at low-temperature. We conclude that reduction of nAChR in autonomic ganglia can be mediated by the endocytosis of α3 subunits, and resulted in autonomic failure in AAG patients.
基金supported by the National Key Research and Development Program of China (2018YFD1000800)the National Natural Science Foundation of China (32072561 and 31772290)。
文摘Nodulin 26-like intrinsic proteins(NIPs) are a family of channel-forming transmembrane proteins that function in the transport of water and other small molecules.Some NIPs can mediate silicon transport across plasma membranes and lead to silicon accumulation in plants,which is beneficial for the growth and development of plants.Cucumber is one of the most widely consumed vegetables;however,the functions of NIPs in this crop are still largely unknown.Here,we report the functional characteristics of Cs NIP2;2.It was found that Cs NIP2;2 is a tandem repeat of Cs NIP2;1,which had been demonstrated to be a silicon influx transporter gene.Cs NIP2;2 has a selectivity filter composed of cysteine,serine,glycine and arginine(CSGR),which is different from all previously characterized silicon influx transporters in higher plants at the second helix position.Xenopus laevis oocytes injected with Cs NIP2;2 c RNA demonstrated a higher uptake of silicon than the control,and the uptake remained unchanged under low temperature.Cs NIP2;2 was found to be expressed in the root,stem,lamina and petiole,and exogenous silicon treatment decreased its expression in the stem but not in other tissues.Transient expression of Cs NIP2;2-e GFP fusion sequence in onion epidermal cells showed that Cs NIP2;2 was localized to the cell nucleus,plasma membrane and an unknown structure inside the cell.The results suggest that Cs NIP2;2 is a silicon influx transporter in cucumber,and its subcellular localization and the selectivity filter are different from those of the previously characterized silicon influx transporters in other plants.These findings may be helpful for understanding the functions of NIPs in cucumber plants.
文摘The effect of verapamil on Ca2+ influx across the myocardial plasma membrane and coxsackie virus B3 ( CVB3)-RNA replication in cultured neonatal rat heart cells infected with CVB3 was investigated. It was found that the Ca2+ influx could be inhibited significantly (P<O. 01) by verapamil (1 μmol/L) after infection of heart cells for 48h. However, when the cultured heart cells infected with CVB3 and treated with verapamil (Iμmol/L and 10 nmo/L) at the same time for 48h, the amounts of CVB3-RNA in myocytes were significantly higher than that in infected control group (P<O. 05). These phenomena suggest that the increase of Ca2+ influx of cultured heart cells infected with CVB3 could be inhibited by some calcium antagonists, e. g. verapamil at the early stage. On the other hand, verapamil might accelerate viral replication in myocardium. Thus, although verapamil could be beneficial for decreasing the secondary Ca2+ damages and improve the myocardial electric activity, it isn’t a sensible choice for therapy in early stage of virus infection with cardiac symptoms.
文摘This paper analyzes the effect of subgroup size on the x-bar chart characteristics using sample influx (SIF) into forensic science laboratory (FSL). The characteristics studied include changes in out-or-control points (OCP), upper control limit UCLx, and zonal demarcations. Multi-rules were used to identify the number of out-of-control-points, Nocp as violations using five control chart rules applied separately. A sensitivity analysis on the Nocp was applied for subgroup size, k, and number of sigma above the mean value to determine the upper control limit, UCLx. A computer code was implemented using a FORTRAN code to create x-bar control-charts and capture OCP and other control-chart characteristics with increasing k from 2 to 25. For each value of k, a complete series of average values, Q(p), of specific length, Nsg, was created from which statistical analysis was conducted and compared to the original SIF data, S(t). The variation of number of out-of-control points or violations, Nocp, for different control-charts rules with increasing k was determined to follow a decaying exponential function, Nocp = Ae–α, for which, the goodness of fit was established, and the R2 value approached unity for Rule #4 and #5 only. The goodness of fit was established to be the new criteria for rational subgroup-size range, for Rules #5 and #4 only, which involve a count of 6 consecutive points decreasing and 8 consecutive points above the selected control limit (σ/3 above the grand mean), respectively. Using this criterion, the rational subgroup range was established to be 4 ≤ k ≤ 20 for the two x-bar control chart rules.
文摘As we all know, cyclic gas injection is one of the most effective development methods to improve condensate oil recovery. When dealing with the calculation of the reserves, the injection-production differences and water influx create great influence on the accuracy. Based on the existing research, we proposed a new material balance equation which considered the differences of composition between produced and injected fluids and the effect of water influx, and a solution was provided in this paper. The results of the method are closer to the actual situation because they are built on the law of conservation of mass, and the using of curve fitting method can not only avoid the use of water influx coefficient but also obtain the water influx rate and reserves at the same time. The YH-23 gas condensate reservoir is taking as a typical subject to do the research, which has been exploited by cycle gas injection for 14 years. Three different methods are used to calculate the reserves, and the results show that the method proposed in this paper has minimum error of 2.96%.
文摘Because of the diversity of geological characteristics and the complexity of percolation rules,many problems are found ineffective water influx control in gas reservoir development.The problems mainly focus on how to understand water influx rules,to establish appropriate countermeasures,and to ensure the effectiveness of technical measures.It is hard to obtain a complete applicable understanding through the isolated analysis of an individual gas reservoir due to many factors such as actual gas reservoir development phase,research work,pertinence and timeliness of measures,and so on.Over the past four decades,the exploration,practicing and tracking research have been conducted on water control in gas reservoir development in the Sichuan Basin,and a series of comprehensive water control technologies were developed integrating advanced concepts,successful experiences,specific theories and mature technologies.Though the development of most water-drive gas reservoirs was significantly improved,water control effects were quite different.Based on this background,from the perspective of the earlyphase requirements of water influx control,the influencing factors of a water influx activity,the dynamic analysis method of water influx performance,the optimizing strategy of a water control,and the water control experience of typical gas reservoirs,this paper analyzed the key problems of water control,evaluated the influencing factors of water control effect,explored the practical water control strategies,and proposed that it should be inappropriate to apply the previous water control technological model to actual work but the pertinence should be improved according to actual circumstances.The research results in the paper provide technical reference for the optimization of water-invasion gas reservoir development.
文摘Monolayer culture of spontaneously contracting rat heart cells was obtained from newborn SD rats andseeded intO culture plates. 1OOTCID50 of coxsackie virus B3 (CVB3) (Nancy strain )was added as the infectedgroup. The dynamics of taurine transport across membrane of normal heart cells and changes after infectionwere examined by using radioactive isotope tracing techniques. The results demonstrated that: (1)two uptake systems of taurine with different affinities and capacities were present in the Plasma membrane of cul-tured rat cardiOmyocytes,the K. of high and low affinity were 9. 5 X 10-5mol/l, and l. 3 X 1 O 2 mol/l,,respectively; (2)taurine transport across membrane was sodium-dependent with a positive linear relationshipbetween amount of taurine influx and extracellular concentration of sOdium;in addition,it was alsO regulat-ed by osmOlarity; (3) fyalanine,a carboxylic analog of taurine,could inhibit the uptake of taurine in dosedependently; (4)taurine influx was decreased in cultured rat cardiomyocytes after infected with CVB3. (5)the lnhibition ratio of taurine transport was enhanced as the infected time prolonged. This experiment pro-vides a basis fOr further investigation of kinetic test of taurine transport and more study should be carriedout to learn the effect of taurine in viral myocarditis.
