Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during t...Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during the electrochemical reaction causes its electrochemical cycling stability to be undesirable.In this work,heterointerface engineering-induced oxygen defects are introduced into heterostructure MnO_(2)(δa-MnO_(2))by in situ electrochemical activation to inhibit manganese dissolution for aqueous zinc ion batteries.Meanwhile,the heterointerface between the disordered amorphous and the crystalline MnO_(2)ofδa-MnO_(2)is decisive for the formation of oxygen defects.And the experimental results indicate that the manganese dissolution ofδa-MnO_(2)is considerably inhibited during the charge/discharge cycle.Theoretical analysis indicates that the oxygen defect regulates the electronic and band structure and the Mn-O bonding state of the electrode material,thereby promoting electron transport kinetics as well as inhibiting Mn dissolution.Consequently,the capacity ofδa-MnO_(2)does not degrade after 100 cycles at a current density of 0.5 Ag^(-1)and also 91%capacity retention after 500cycles at 1 Ag^(-1).This study provides a promising insight into the development of high-performance manganese-based cathode materials through a facile and low-cost strategy.展开更多
Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s...Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.展开更多
Nitrification,a central process in the marine nitrogen cycle,produces regenerated nitrate in the euphotic zone and emits N_(2)O,a potent greenhouse gas as a by-product.The regulatory mechanisms of nitrification in the...Nitrification,a central process in the marine nitrogen cycle,produces regenerated nitrate in the euphotic zone and emits N_(2)O,a potent greenhouse gas as a by-product.The regulatory mechanisms of nitrification in the Southern Ocean,which is a critical region for CO_(2)sequestration and radiative benefits,remain poorly understood.Here,we investigated the in situ and dark nitrification rates in the upper 500 m and conducted substrate kinetics experiments across the Indian Sector in the Cosmonaut and Cooperation seas in the late austral summer.Our findings indicate that light inhibition of nitrification decreases exponentially with depth,exhibiting a light threshold of 0.53%photosynthetically active radiation.A positive relationship between dark nitrification and apparent oxygen utilization suggests a dependence on substrate availability from primary production.Importantly,an increased NH_(4)^(+) supply can act as a buffer against photo-inhibitory damage.Globally,substrate affinity(α)increases with depth and transitions from light to dark,decreases with increasing ambient NH_(4)^(+)and exhibits a latitudinal distribution,reflecting substrate utilization strategies.We also reveal that upwelling in Circumpolar Deep Water(CDW)stimulates nitrification through the introduction of potentially higher iron and deep diverse nitrifying microorganisms with higherα.We conclude that although light is the primary limiting factor for nitrification in summer,coupling between substrate availability and CDW upwelling can overcome this limitation,thereby alleviating photoinhibition by up to 45%±5.3%.展开更多
Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active mate...Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active material Zn.However,the Zn anode also leads to many challenges,including dendrite growth,deformation,and hydrogen precipitation self-corrosion.In this context,Zn dendrite growth has a greater impact on the cycle lives.In this dissertation,a dendrite growth model for a Zn-air battery was established based on electrochemical phase field theory,and the effects of the charging time,anisotropy strength,and electrolyte temperature on the morphology and growth height of Zn dendrites were studied.A series of experiments was designed with different gradient influencing factors in subsequent experiments to verify the theoretical simulations,including elevated electrolyte temperatures,flowing electrolytes,and pulsed charging.The simulation results show that the growth of Zn dendrites is controlled mainly by diffusion and mass transfer processes,whereas the electrolyte temperature,flow rate,and interfacial energy anisotropy intensity are the main factors.The experimental results show that an optimal electrolyte temperature of 343.15 K,an optimal electrolyte flow rate of 40 ml·min^(-1),and an effective pulse charging mode.展开更多
[Objectives]To fully understand the quality of commercial enzyme inhibition-colorimetric pesticide residue rapid detection kits,so that they can play a greater role in the detection and supervision of agricultural pro...[Objectives]To fully understand the quality of commercial enzyme inhibition-colorimetric pesticide residue rapid detection kits,so that they can play a greater role in the detection and supervision of agricultural products.[Methods]The sensitivity of 28 kinds of pesticides was determined by using the commercially available enzyme inhibition colorimetric rapid detection kit with Hendu brand.[Results]There was a significant difference in the sensitivity of the kit to each pesticide,and the kit was more sensitive to dichlorvos among the 28 pesticides tested.The sensitivity to methyl isosalifos,dimethoate,isocarbophos,fenthion and phorate was poor,and the sensitivity to quinalphos was different between 3.0 and 2.5 mL.[Conclusions]The large difference of the sensitivity of the enzyme inhibition-colorimetric rapid detection kit for pesticide residues to different kits is a reason for the false positive and false negative test results of the kit,which needs to be considered by relevant personnel.展开更多
Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are inv...Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.展开更多
Honey has long been considered a wound treatment used to keep cuts and other epidermal injuries clean. This study tested that claim by comparing manuka honey used in medicine today, local unprocessed honey taken strai...Honey has long been considered a wound treatment used to keep cuts and other epidermal injuries clean. This study tested that claim by comparing manuka honey used in medicine today, local unprocessed honey taken straight from a hive, and pasteurized honey found at a store, on strains of E. coli and S. epidermidis. The study evaluated the effects these honeys had on bacterial growth to determine which had the greatest inhibition of bacterial growth. To determine this, plates streaked with strains of E. coli or S. epidermidis bacteria and agar wells filled with one of the honeys were incubated and subsequently the diameter of the zone of inhibition was measured. After 20 trials using each honey and bacteria type, manuka and unprocessed were shown to have a statistically significant advantage over the pasteurized honey at inhibiting the growth of E. coli and S. epidermidis, though it was variable whether manuka had an advantage over the unprocessed honey.展开更多
Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylas...Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylase activity.Therefore,sweet buckwheat produced in Inner Mongolia was used as the research object,and buckwheat fl avonoids were extracted by ultrasonic-assisted extraction method.Total fl avonoids content was determined by ultraviolet-visible spectrophotometry.With acarbose as the positive control,the inhibition test ofα-amylase was carried out by DNS colorimetry to study the inhibition behavior of fl avonoids onα-amylase activity.The results showed that the extraction process of flavonoids was stable and reliable,and the established method for the determination of flavonoids was simple,accurate and reproducible.The total flavonoids content of buckwheat samples was 2.706 mg/g,buckwheat total fl avonoids extraction solution had an inhibitory eff ect onα-amylase,and its median inhibition concentration(IC_(50))was 38.53 mg/mL.The results of this experiment provide a technical reference for the development and utilization of fl avonoids in Inner Mongolia sweet buckwheat,and provide a theoretical reference for the development and application of flavonoid-rich hypoglycemic food.展开更多
Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were s...Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.展开更多
Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor a...Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.展开更多
The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in hig...The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.展开更多
Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avo...Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avoiding hydrogen explosion risks,we try to use a combination of chitosan(CS)and sodium phosphate(SP)to inhibit the hydrogen evolution reaction between magnesium alloy waste dust and water.The hydrogen evolution curves and chemical kinetics modeling for ten different mixing ratios demonstrate that 0.4wt%CS+0.1wt%SP yields the best inhibition efficiency with hydrogen generation rate of almost zero.SEM and EDS analyses indicate that this composite inhibitor can create a uniform,smooth,tight protective film over the surface of the alloy dust particles.FTIR and XRD analysis of the chemical composition of the surface film show that this protective film contains CS and SP chemically adsorbed on the surface of ZK60 but no detectable Mg(OH)_(2),suggesting that magnesium-water reaction was totally blocked.Our new method offers a thorough solution to hydrogen explosion by inhibiting the hydrogen generation of magnesium alloy waste dust in a wet dust removal system.展开更多
α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in var...α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.展开更多
Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious ...Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.展开更多
Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine dril...Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine drillingfluids also exhibit problems such as easy decomposition and poor inhibition performances.In order to mitigate these issues,additives can be used,such as polyamine inhibitors and the synthesis of nanometerfiltrate reducers.Tests conducted in the frame of this study with a polyamine drillingfluid and such additives show that thisfluid has the same inhibitory,plugging,lubricating,and wellbore-stability performances as oil-based drillingfluids.However,it has long-term anti-wear performances even better than those of oil-based drillingfluids.The out-comes of a series of comparisons with other sample cases(other wells)are reported and the advantages related to the proposedfluid discussed in detail.展开更多
By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by memb...By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.展开更多
The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, ag...The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, against Escherichia coli and Salmonella typhi bacteria in aquatic microcosms. Phytochemical screening was performed as described by Pareck. The results obtained show that the hydro-ethanolic and aqueous extracts of Albizia zygia trunk bark recorded higher extraction yields (26.71% and 33.2% respectively) compared to the aqueous and hydro-ethanolic extracts of leaves of the same plant. Secondary metabolites with antibacterial activities such as anthraquinones, anthocyanins, flavonoids, polyphenols, tannins and saponins were found in both types of extracts. Flavonoids and anthocyanins were relatively more abundant than the other chemical constituents. The highest cellular inhibition rate of Escherichia coli was 99.88%, obtained after 9 hours of exposure in the hydro-ethanolic extract solution of trunk bark at the concentration 1.5 g/L. The Salmonella typhi rate was 99.95% after 9 hours of exposure of bacterial cells to the hydro-ethanol extract of the bark of the trunk at the concentration 1.5 g/L. This rate increased proportionally with the bacterial-extract contact time. The temperature of the medium did not significantly influence bacterial inhibition (P > 0.05). The obtained results justify the use of the plant Albizia zygia in the reduction of the flow of bacterio-pollutants contained in water intended for consumption.展开更多
Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biologica...Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biological behavior of human hepatocellular carcinoma Huh7 cells.Methods:The experiment was divided into four groups:Huh7 cells control group,DMDD group,sorafenib group and DMDD and sorafenib combination group.The CCK-8 assay was used to measure the viability of Huh7 cells,and the Kim's formula was used to determine the synergistic effect.The plate cloning experiment was conducted to test colony formation ability of Huh7 cells.The scratch and Transwell experiments were performed to evaluate the migration ability and the invasion ability of Huh7 cells.The cell cycle of Huh7 cells was detected by flow cytometry.RT-qPCR and Western blot were used to measure the mRNA transcription level and protein expression level of PHGDH in the serine synthesis pathway.Results:The plate cloning experiment,scratch experiment,and Transwell migration experiment showed that the combined application of DMDD and Sorafenib significantly enhanced the inhibitory effect on the proliferation,migration,and invasion ability of Huh7 cells compared to the control group,DMDD group,and Sorafenib group(P<0.05).According to the Kim's formula,the combination of DMDD(final concentrations of 2,4,8μmol/L)and Sorafenib(final concentrations of 1,2,4μmol/L)had a synergistic inhibitory effect on the proliferation of Huh7 cells(Q>1.15).6,10μmol/L DMDD combined with 3,5μmol/L Sorafenib showed additive effect.The cell cycle of Huh7 cells was detected by flow cytometry,and the results showed that after 48 hours of drug intervention,the proportion of G2/M phase cells in the control group,DMDD group,Sorafenib group,and combination group were(10.63±0.32)%,(35.77±1.22)%,(30.03±2.22)%,and(38.97±0.60)%,respectively.Compared with the control group,the proportion of G2/M phase cells in the three groups significantly increased(P<0.0001).Compared with the Sorafenib group,the proportion of G2/M phase cells in the combination group significantly increased(P<0.0001).RT-qPCR and Western blot results showed that the combined application of DMDD and Sorafenib significantly inhibited the mRNA transcription level and protein expression level of PHGDH(P<0.05).Conclusion:The combined application of DMDD and Sorafenib has a synergistic effect that can enhance the inhibitory effect on the proliferation,invasion,and migration ability of Huh7 cells.The mechanism of this effect is related to the synergistic inhibition of the gene transcription and protein expression of PHGDH in the serine synthesis pathway.展开更多
Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH r...Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH represents a spectrum of disease that may lead to hepatic fibrosis and eventual cirrhosis,with the risk of cirrhosis decompensation,and hepatocellular carcinoma.New therapies are desperately needed for NASH,especially for later stages of fibrosis and cirrhosis.Galectin-3 inhibition is being explored as a new liver antifibrotic therapy.This concise review will outline the state of the art of this new therapeutic target.展开更多
With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE)...With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).展开更多
基金funds from the National Natural Science Foundation of China(51772082 and 51804106)the Natural Science Foundation of Hunan Province(2023JJ10005)
文摘Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during the electrochemical reaction causes its electrochemical cycling stability to be undesirable.In this work,heterointerface engineering-induced oxygen defects are introduced into heterostructure MnO_(2)(δa-MnO_(2))by in situ electrochemical activation to inhibit manganese dissolution for aqueous zinc ion batteries.Meanwhile,the heterointerface between the disordered amorphous and the crystalline MnO_(2)ofδa-MnO_(2)is decisive for the formation of oxygen defects.And the experimental results indicate that the manganese dissolution ofδa-MnO_(2)is considerably inhibited during the charge/discharge cycle.Theoretical analysis indicates that the oxygen defect regulates the electronic and band structure and the Mn-O bonding state of the electrode material,thereby promoting electron transport kinetics as well as inhibiting Mn dissolution.Consequently,the capacity ofδa-MnO_(2)does not degrade after 100 cycles at a current density of 0.5 Ag^(-1)and also 91%capacity retention after 500cycles at 1 Ag^(-1).This study provides a promising insight into the development of high-performance manganese-based cathode materials through a facile and low-cost strategy.
基金supported by the National Natural Science Foundation of China (31901462 and 31671613).
文摘Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.
基金The National Natural Science Foundation of China under contract No.41721005the Fund of the Ministry of Natural Resources of the People’s Republic of China under contract Nos IRASCC 02-01-01 and 01-01-02C.
文摘Nitrification,a central process in the marine nitrogen cycle,produces regenerated nitrate in the euphotic zone and emits N_(2)O,a potent greenhouse gas as a by-product.The regulatory mechanisms of nitrification in the Southern Ocean,which is a critical region for CO_(2)sequestration and radiative benefits,remain poorly understood.Here,we investigated the in situ and dark nitrification rates in the upper 500 m and conducted substrate kinetics experiments across the Indian Sector in the Cosmonaut and Cooperation seas in the late austral summer.Our findings indicate that light inhibition of nitrification decreases exponentially with depth,exhibiting a light threshold of 0.53%photosynthetically active radiation.A positive relationship between dark nitrification and apparent oxygen utilization suggests a dependence on substrate availability from primary production.Importantly,an increased NH_(4)^(+) supply can act as a buffer against photo-inhibitory damage.Globally,substrate affinity(α)increases with depth and transitions from light to dark,decreases with increasing ambient NH_(4)^(+)and exhibits a latitudinal distribution,reflecting substrate utilization strategies.We also reveal that upwelling in Circumpolar Deep Water(CDW)stimulates nitrification through the introduction of potentially higher iron and deep diverse nitrifying microorganisms with higherα.We conclude that although light is the primary limiting factor for nitrification in summer,coupling between substrate availability and CDW upwelling can overcome this limitation,thereby alleviating photoinhibition by up to 45%±5.3%.
基金financially supported by the National Natural Science Foundation of China(22168019 and 52074141)the Major Science and Technology Projects in Yunnan Province(202202AB080014)+1 种基金The authors are grateful to the National Natural Science Foundation of Chinathe Major Science and Technology Projects in Yunnan Province for their support.
文摘Zinc(Zn)-air batteries are widely used in secondary battery research owing to their high theoretical energy density,good electrochemical reversibility,stable discharge performance,and low cost of the anode active material Zn.However,the Zn anode also leads to many challenges,including dendrite growth,deformation,and hydrogen precipitation self-corrosion.In this context,Zn dendrite growth has a greater impact on the cycle lives.In this dissertation,a dendrite growth model for a Zn-air battery was established based on electrochemical phase field theory,and the effects of the charging time,anisotropy strength,and electrolyte temperature on the morphology and growth height of Zn dendrites were studied.A series of experiments was designed with different gradient influencing factors in subsequent experiments to verify the theoretical simulations,including elevated electrolyte temperatures,flowing electrolytes,and pulsed charging.The simulation results show that the growth of Zn dendrites is controlled mainly by diffusion and mass transfer processes,whereas the electrolyte temperature,flow rate,and interfacial energy anisotropy intensity are the main factors.The experimental results show that an optimal electrolyte temperature of 343.15 K,an optimal electrolyte flow rate of 40 ml·min^(-1),and an effective pulse charging mode.
文摘[Objectives]To fully understand the quality of commercial enzyme inhibition-colorimetric pesticide residue rapid detection kits,so that they can play a greater role in the detection and supervision of agricultural products.[Methods]The sensitivity of 28 kinds of pesticides was determined by using the commercially available enzyme inhibition colorimetric rapid detection kit with Hendu brand.[Results]There was a significant difference in the sensitivity of the kit to each pesticide,and the kit was more sensitive to dichlorvos among the 28 pesticides tested.The sensitivity to methyl isosalifos,dimethoate,isocarbophos,fenthion and phorate was poor,and the sensitivity to quinalphos was different between 3.0 and 2.5 mL.[Conclusions]The large difference of the sensitivity of the enzyme inhibition-colorimetric rapid detection kit for pesticide residues to different kits is a reason for the false positive and false negative test results of the kit,which needs to be considered by relevant personnel.
基金supported by the Ministerio de Economía,Industria y Competitividad(Agencia Estatal de Investigación,AEI,to CGF and MP)Fondo Europeo de Desarrollo Regional(MINECO-FEDER)(PID2022-139016OA-I00,PDC2022-133441-I00,to CGF and MP),Generalitat de Catalunya(2021 SGR 00357+3 种基金to CGF and MP)co-financed by Secretaria d’Universitats i Recerca del Departament d’Empresai Coneixement de la Generalitat de Catalunya 2021(Llavor 00086,to CGF)the recipient of an Alzheimer’s Association Research Fellowship(AARF-21-848511)the Agència de Gestiód’Ajuts Universitaris i de Recerca(AGAUR)for her FI-SDUR fellowship(2021FISDU 00182).
文摘Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.
文摘Honey has long been considered a wound treatment used to keep cuts and other epidermal injuries clean. This study tested that claim by comparing manuka honey used in medicine today, local unprocessed honey taken straight from a hive, and pasteurized honey found at a store, on strains of E. coli and S. epidermidis. The study evaluated the effects these honeys had on bacterial growth to determine which had the greatest inhibition of bacterial growth. To determine this, plates streaked with strains of E. coli or S. epidermidis bacteria and agar wells filled with one of the honeys were incubated and subsequently the diameter of the zone of inhibition was measured. After 20 trials using each honey and bacteria type, manuka and unprocessed were shown to have a statistically significant advantage over the pasteurized honey at inhibiting the growth of E. coli and S. epidermidis, though it was variable whether manuka had an advantage over the unprocessed honey.
文摘Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylase activity.Therefore,sweet buckwheat produced in Inner Mongolia was used as the research object,and buckwheat fl avonoids were extracted by ultrasonic-assisted extraction method.Total fl avonoids content was determined by ultraviolet-visible spectrophotometry.With acarbose as the positive control,the inhibition test ofα-amylase was carried out by DNS colorimetry to study the inhibition behavior of fl avonoids onα-amylase activity.The results showed that the extraction process of flavonoids was stable and reliable,and the established method for the determination of flavonoids was simple,accurate and reproducible.The total flavonoids content of buckwheat samples was 2.706 mg/g,buckwheat total fl avonoids extraction solution had an inhibitory eff ect onα-amylase,and its median inhibition concentration(IC_(50))was 38.53 mg/mL.The results of this experiment provide a technical reference for the development and utilization of fl avonoids in Inner Mongolia sweet buckwheat,and provide a theoretical reference for the development and application of flavonoid-rich hypoglycemic food.
文摘Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.
基金National Key R&D Program of China(2022YFA1103200,2017YFA0106400,2021YFA1100900)Ministry of Science and Technology of China(2020YFC2002804)+3 种基金National Natural Science Foundation of China(91749124,81772389,82070108)Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004)Fundamental Research Funds for the Central Universities(22120190149 and kx0200020173386)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai。
文摘Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.
基金This work was supported by Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project:HZQB-KCZYB-2020030the National Natural Science Foundation of China(No.91860131and No.52074157)+2 种基金Guangdong Provincial Department of Science and Technology,Key-Area Research and Development Program of Guangdong Province(No.2020B090923002)the National Key Research and Development Program of China(No.2017YFB0702901)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20170817111811303,No.KQTD20170328154443162and No.ZDSYS201703031748354).
文摘The additive manufacturing(AM)of Ni-based superalloys has attracted extensive interest from both academia and industry due to its unique capabilities to fabricate complex and high-performance components for use in high-end industrial systems.However,the intense temperature gradient induced by the rapid heating and cooling processes of AM can generate high levels of residual stress and metastable chemical and structural states,inevitably leading to severe metallurgical defects in Ni-based superalloys.Cracks are the greatest threat to these materials’integrity as they can rapidly propagate and thereby cause sudden and non-predictable failure.Consequently,there is a need for a deeper understanding of residual stress and cracking mechanisms in additively manufactured Ni-based superalloys and ways to potentially prevent cracking,as this knowledge will enable the wider application of these unique materials.To this end,this paper comprehensively reviews the residual stress and the various mechanisms of crack formation in Ni-based superalloys during AM.In addition,several common methods for inhibiting crack formation are presented to assist the research community to develop methods for the fabrication of crack-free additively manufactured components.
基金This work was supported by the National Natural Science Foundation of China(52074066).
文摘Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avoiding hydrogen explosion risks,we try to use a combination of chitosan(CS)and sodium phosphate(SP)to inhibit the hydrogen evolution reaction between magnesium alloy waste dust and water.The hydrogen evolution curves and chemical kinetics modeling for ten different mixing ratios demonstrate that 0.4wt%CS+0.1wt%SP yields the best inhibition efficiency with hydrogen generation rate of almost zero.SEM and EDS analyses indicate that this composite inhibitor can create a uniform,smooth,tight protective film over the surface of the alloy dust particles.FTIR and XRD analysis of the chemical composition of the surface film show that this protective film contains CS and SP chemically adsorbed on the surface of ZK60 but no detectable Mg(OH)_(2),suggesting that magnesium-water reaction was totally blocked.Our new method offers a thorough solution to hydrogen explosion by inhibiting the hydrogen generation of magnesium alloy waste dust in a wet dust removal system.
基金supported by the General Research Fund of Hong Kong (14105820)。
文摘α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.
基金supported by National Natural Science Foundation of China(52170074).
文摘Air nanobubbles(A-NBs)were used to inhibit the brass corrosion in circulating cooling water for the first time in the study.The results of mass loss method and electrochemical method showed that A-NBs had the obvious corrosion inhibition effect.The inhibition rate reached 52%at 35℃.The impedance and surface characterization results of corrosion samples indicated that the corrosion inhibition mechanisms of A-NBs mainly included adsorption of corrosion ions,promoting the formation of the passivation film on metal surface and the formation of the bubble layer and scale film on metal surface.A-NBs are potential excellent corrosion inhibitors.
文摘Drilling technologies based on oil-based drillingfluids and strong inhibitory saltwaterfluids are affected by draw-backs such as downhole accidents where sticking and wellbore instabilities occur.Existing polyamine drillingfluids also exhibit problems such as easy decomposition and poor inhibition performances.In order to mitigate these issues,additives can be used,such as polyamine inhibitors and the synthesis of nanometerfiltrate reducers.Tests conducted in the frame of this study with a polyamine drillingfluid and such additives show that thisfluid has the same inhibitory,plugging,lubricating,and wellbore-stability performances as oil-based drillingfluids.However,it has long-term anti-wear performances even better than those of oil-based drillingfluids.The out-comes of a series of comparisons with other sample cases(other wells)are reported and the advantages related to the proposedfluid discussed in detail.
基金Supported by the National Natural Science Foundation of China(5215000105)Huo Yingdong Education Foundation(171043).
文摘By analyzing the corrosion of phosphate completion fluid on the P110 steel at 170 °C, the high-temperature corrosion mechanism of phosphate completion fluid was revealed, and a corrosion inhibition method by membrane transformation was proposed and an efficient membrane-forming agent was selected. Scanning electron microscope (SEM) images, X-ray energy spectrum and X-ray diffraction results were used to characterize the microscopic morphology, elemental composition and phase composition of the precipitation membrane on the surface of the test piece. The effect and mechanism of corrosion inhibition by membrane transformation were clarified. The phosphate completion fluid eroded the test piece by high-temperature water vapor and its hydrolyzed products to form a membrane of iron phosphate corrosion product. By changing the corrosion reaction path, the Zn2+ membrane-forming agent could generate KZnPO4 precipitation membrane with high temperature resistance, uniform thickness and tight crystal packing on the surface of the test piece, which could inhibit the corrosion of the test piece, with efficiency up to 69.63%. The Cu2+ membrane-forming agent electrochemically reacted with Fe to precipitate trace elemental Cu on the surface of the test piece, thus forming a protective membrane, which could inhibit metal corrosion, with efficiency up to 96.64%, but the wear resistance was poor. After combining 0.05% Cu2+ and 0.25% Zn2+, a composite protective membrane of KZnPO4 crystal and elemental Cu was formed on the surface of the test piece. The corrosion inhibition efficiency reached 93.03%, which ensured the high corrosion inhibition efficiency and generated a precipitation membrane resistant to temperature and wear.
文摘The objective of this study is the phytochemical analysis and the determination of the antibacterial activity of aqueous and hydro-ethanolic extracts obtained from the leaves and bark of the trunk of Albizia zygia, against Escherichia coli and Salmonella typhi bacteria in aquatic microcosms. Phytochemical screening was performed as described by Pareck. The results obtained show that the hydro-ethanolic and aqueous extracts of Albizia zygia trunk bark recorded higher extraction yields (26.71% and 33.2% respectively) compared to the aqueous and hydro-ethanolic extracts of leaves of the same plant. Secondary metabolites with antibacterial activities such as anthraquinones, anthocyanins, flavonoids, polyphenols, tannins and saponins were found in both types of extracts. Flavonoids and anthocyanins were relatively more abundant than the other chemical constituents. The highest cellular inhibition rate of Escherichia coli was 99.88%, obtained after 9 hours of exposure in the hydro-ethanolic extract solution of trunk bark at the concentration 1.5 g/L. The Salmonella typhi rate was 99.95% after 9 hours of exposure of bacterial cells to the hydro-ethanol extract of the bark of the trunk at the concentration 1.5 g/L. This rate increased proportionally with the bacterial-extract contact time. The temperature of the medium did not significantly influence bacterial inhibition (P > 0.05). The obtained results justify the use of the plant Albizia zygia in the reduction of the flow of bacterio-pollutants contained in water intended for consumption.
基金This study was supported by National Natural Foundation Project of China(81860504)。
文摘Objective:To investigate the effects and possible mechanisms of the combination of DMDD(2-dodecyl-6-methoxycyclohexa-2-5-diene-1-4-dione),a traditional Chinese medicine monomer,and sorafenib on the malignant biological behavior of human hepatocellular carcinoma Huh7 cells.Methods:The experiment was divided into four groups:Huh7 cells control group,DMDD group,sorafenib group and DMDD and sorafenib combination group.The CCK-8 assay was used to measure the viability of Huh7 cells,and the Kim's formula was used to determine the synergistic effect.The plate cloning experiment was conducted to test colony formation ability of Huh7 cells.The scratch and Transwell experiments were performed to evaluate the migration ability and the invasion ability of Huh7 cells.The cell cycle of Huh7 cells was detected by flow cytometry.RT-qPCR and Western blot were used to measure the mRNA transcription level and protein expression level of PHGDH in the serine synthesis pathway.Results:The plate cloning experiment,scratch experiment,and Transwell migration experiment showed that the combined application of DMDD and Sorafenib significantly enhanced the inhibitory effect on the proliferation,migration,and invasion ability of Huh7 cells compared to the control group,DMDD group,and Sorafenib group(P<0.05).According to the Kim's formula,the combination of DMDD(final concentrations of 2,4,8μmol/L)and Sorafenib(final concentrations of 1,2,4μmol/L)had a synergistic inhibitory effect on the proliferation of Huh7 cells(Q>1.15).6,10μmol/L DMDD combined with 3,5μmol/L Sorafenib showed additive effect.The cell cycle of Huh7 cells was detected by flow cytometry,and the results showed that after 48 hours of drug intervention,the proportion of G2/M phase cells in the control group,DMDD group,Sorafenib group,and combination group were(10.63±0.32)%,(35.77±1.22)%,(30.03±2.22)%,and(38.97±0.60)%,respectively.Compared with the control group,the proportion of G2/M phase cells in the three groups significantly increased(P<0.0001).Compared with the Sorafenib group,the proportion of G2/M phase cells in the combination group significantly increased(P<0.0001).RT-qPCR and Western blot results showed that the combined application of DMDD and Sorafenib significantly inhibited the mRNA transcription level and protein expression level of PHGDH(P<0.05).Conclusion:The combined application of DMDD and Sorafenib has a synergistic effect that can enhance the inhibitory effect on the proliferation,invasion,and migration ability of Huh7 cells.The mechanism of this effect is related to the synergistic inhibition of the gene transcription and protein expression of PHGDH in the serine synthesis pathway.
基金The author acknowledges Dr.Pol Boudes for reviewing this manuscript and Dr.Zachary Goodman for providing the galectin-3 antibody histological images.
文摘Nonalcoholic fatty liver disease continues to be one of the major health challenges facing the world,with estimates of non-alcoholic steatohepatitis(NASH)prevalence in over 25 percent of the world’s population.NASH represents a spectrum of disease that may lead to hepatic fibrosis and eventual cirrhosis,with the risk of cirrhosis decompensation,and hepatocellular carcinoma.New therapies are desperately needed for NASH,especially for later stages of fibrosis and cirrhosis.Galectin-3 inhibition is being explored as a new liver antifibrotic therapy.This concise review will outline the state of the art of this new therapeutic target.
文摘With the help of model experiments, we are able to offer a detailed proposal for the inhibition of DNA duplication and no inhibition of RNA viral infectivity. As a backbone, we introduced methyl phosphotriester (MPTE). Duplex formation according to the traditional Watson and Crick base-pairing: [(MPTE)<sub>n−1</sub> DNA] * DNA and [(MPTE)<sub>n−1</sub> DNA] * RNA, where n = number of DNA and RNA bases. However, in the latter case, inhibition is obtained by reduction of the number of MPTE linkages, as is confirmed with model experiments and under biological conditions with micro (mi)RNA substrates. The latter results have recently been published. One or more single MPTEs are disseminated over different places of DNA without neighbour MPTEs (Prof. Wen-Yih Chen and his group, Taiwan).
