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
BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the i...BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.展开更多
While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is ac...While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.展开更多
Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants.In this study,we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative s...Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants.In this study,we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat[Fortunella margarita(Lour.)Swingle]contributes to its freezing tolerance by minimizing protein degradation.Firstly,we found that only cold-acclimated kumquat plants,despite extensive leaf cellular damage during freezing,were able to resume their normal growth upon stress relief.To dissect the impact of cold acclimation on this anti-freezing performance,we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation(4◦C),freezing treatment(−10◦C)and post-freezing recovery(25◦C).FmASP(Against Serine Protease)and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment.FmASP was further characterized as a robust inhibitor of multiple proteases.In addition,heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance.Finally,we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation,therebymaintaining essential cellular function for post-freezing recovery.These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.展开更多
In the process of exploration and development of oil and gas fields, the acidic environment of oil reservoir, production and transport processes cause corrosion of pipelines and equipment, resulting in huge economic l...In the process of exploration and development of oil and gas fields, the acidic environment of oil reservoir, production and transport processes cause corrosion of pipelines and equipment, resulting in huge economic losses and production safety risks. Corrosion inhibitors were widely used in oil industry because of simple operation process and economical. In this study, three environmentally friendly corrosion inhibitors were synthesized based on the natural polysaccharide chitosan. Corrosion inhibition of three dendritic chitosan derivatives (We name them BH, CH and DH) on mild steel in 1 mol/L HCl solution with natural ventilation system was evaluated by weight loss experiment, electrochemical analysis and surface morphology characterization. The experimental results showed that when the three dendritic chitosan derivatives added in the corrosive medium were 500 mg L^(−1), the corrosion inhibition efficiencies were all more than 80%. Based on quantum chemical calculation, inhibition mechanisms of three dendritic chitosan derivatives were investigated according to molecular structures. The results showed that the benzene ring, Schiff base and N atom contained in the molecule were the active centers of electron exchange, which were more likely to form a film on the carbon steel surface, thereby slowing or inhibiting corrosion. The results also predicted the corrosion inhibition effect BH > DH > CH, which was consistent with the experimental conclusion.展开更多
Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanor...Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.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
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
Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulat...Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.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
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
The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood ...The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood circulation and immune systems.However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs(m BMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted m BMSCs was restored at both the molecular and phenotypic levels.Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.展开更多
Melatonin has been shown to alleviate the effects of abiotic stress and to regulate plant development.Copper,a common heavy metal and soil pollutant,can suppress plant growth and development.In this work,we explored t...Melatonin has been shown to alleviate the effects of abiotic stress and to regulate plant development.Copper,a common heavy metal and soil pollutant,can suppress plant growth and development.In this work,we explored the protective effects of exogenous melatonin on lateral root formation in response to copper stress using melon seeds subjected to three germination treatments:CK1(control),CK2(300μmol/L CuSO4),and MT3(300μmol/L melatonin+300μmol/L CuSO4).Melatonin pretreatment increased the antioxidant enzyme activities and root vigor,and decreased the proline and malondialdehyde(MDA)contents in the roots of copper-stressed melon seedlings.We then used transcriptomic and metabolomic analyses to explore the mechanisms by which exogenous melatonin protects against copper stress.There were 70 significant differentially expressed genes(DEGs)(28 upregulated,42 downregulated)and 318 significantly differentially expressed metabolites(DEMs)(168 upregulated,150 downregulated)between the MT3 and CK2 treatments.Melatonin pretreatment altered the expression of genes related to redox and cell wall formation processes.In addition,we found that members of the AP2/ERF,BBR/BPC,GRAS,and HD-ZIP transcription factor families may have vital roles in lateral root development.Melatonin also increased the level of Glutathione(GSH),which chelates excess Cu^(2+).The combined transcriptomic and metabolomic analysis revealed DEGs and DEMs involved in jasmonic acid(JA)biosynthesis,including four lipoxygenase-related genes and two metabolites(linoleic acid and lecithin)related to melatonin’s alleviation effect on copper toxicity.This research elucidated the molecular mechanisms of melatonin’s protective effects in copper-stressed melon.展开更多
Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes ...Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.展开更多
Human dental pulp stem cells(DPSCs)have emerged as an important source of stem cells in the tissue engineering,and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration...Human dental pulp stem cells(DPSCs)have emerged as an important source of stem cells in the tissue engineering,and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration.Nevertheless,little is known about the complicated molecular mechanisms.In this study,we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition.Hypoxia was induced in DPSCs by Cobalt chloride(CoCl_(2))treatment.The osteo/dentinogenic differentiation capacity of DPSCs was assessed by alkaline phosphatase(ALP)activity,Alizarin Red S staining and main osteo/dentinogenic markers.A luciferase reporter gene assay was performed to verify the downstream target gene of miR-140-3p.This research exhibited that miR-140-3p promoted osteo/dentinogenic differentiation of DPSCs under normoxia environment.Furthermore,miR-140-3p rescued the CoCl_(2)-induced decreased osteo/odontogenic differentiation potentials in DPSCs.Besides,we investigated that miR-140-3p directly targeted lysine methyltransferase 5B(KMT5B).Surprisingly,we found inhibition of KMT5B obviously enhanced osteo/dentinogenic differentiation of DPSCs both under normoxia and hypoxia conditions.In conclusion,our study revealed the role and mechanism of miR-140-3p for regulating osteo/dentinogenic differentiation of DPSCs under hypoxia,and discovered that miR-140-3p and KMT5B might be important targets for DPSC-mediated tooth or bone tissue regeneration.展开更多
Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell ...Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.展开更多
Leaf size and flatness directly affect photosynthesis and are closely related to agricultural yield.The final leaf size and shape are coordinately determined by cell proliferation,differentiation,and expansion during ...Leaf size and flatness directly affect photosynthesis and are closely related to agricultural yield.The final leaf size and shape are coordinately determined by cell proliferation,differentiation,and expansion during leaf development.Lettuce(Lactuca sativa L.)is one of the most important leafy vegetables worldwide,and lettuce leaves vary in shape and size.However,the molecular mechanisms of leaf development in lettuce are largely unknown.In this study,we showed that the lettuce APETALA2(LsAP2)gene regulates leaf morphology.LsAP2 encodes a transcriptional repressor that contains the conserved EAR motif,which mediates interactions with the TOPLESS/TOPLESS-RELATED(JPL/TPR)corepressors.Overexpression of LsAP2 led to small and crinkly leaves,and many bulges were seen on the surface of the leaf blade.LsAP2 physically interacted with the CINCINNATA(CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR(TCP)transcription factors and inhibited their transcriptional activation activity.RNA sequencing analysis showed that LsAP2 affected the expression of auxin-and polarity-related genes.In addition,LsAP2 directly repressed the abaxial identity gene KANAD12(LsKAN2).Together,these results indicate that LsAP2 regulates leaf morphology by inhibiting CIN-like TCP transcription factors and repressing LsKAN2,and our work provides insights into the regulatory mechanisms of leaf development in lettuce.展开更多
In this study,the role of(NH_(4))_(2)SO_(4)during the sulfurization of azurite and its response to flotation were investigated.The flotation results showed that adding(NH_(4))_(2)SO_(4)prior to sulfurization decreased...In this study,the role of(NH_(4))_(2)SO_(4)during the sulfurization of azurite and its response to flotation were investigated.The flotation results showed that adding(NH_(4))_(2)SO_(4)prior to sulfurization decreased the formation of colloid in flotation pulp,and the floatability of the suppressed azurite caused by excess sodium sulfide was restored.After adding(NH_(4))_(2)SO_(4)prior to sulfurization,the formation of Cu(NH_(3))_(n) ^(2+)intermediate products changed the path of the sulfurization reaction,which slowed the direct impact of HSon the azurite surface.The nucleation rate was reduced,and the growth of copper sulfide crystal was improved.Covellite(syn,CuS)with larger crystal grains was formed on the azurite surface,thereby enhancing the mechanical stability of copper sulfide products onto the mineral surface.Therefore,the generated copper sulfide colloid significantly reduced,ultimately promoting the effective adsorption of xanthate on the azurite surface.展开更多
The mitigation of the CO inhibition effect in palladium membranes is necessary due to its significance in the efficiency of membrane reactors and hydrogen production systems. In this work, the hydrogen separation perf...The mitigation of the CO inhibition effect in palladium membranes is necessary due to its significance in the efficiency of membrane reactors and hydrogen production systems. In this work, the hydrogen separation performance of a Pd and Pd/Ag membrane both of thickness 2 μm is investigated using a mixed gas with composition (H2 = 50%, CO = 28%, CO2 = 10%, CH4 = 8%, N2 = 4%) at temperature 623 - 873 K and pressure (0.05 - 0.4 bar) was investigated. The component gases CO and CO2 were observed to inhibit hydrogen permeation through the membrane and lead to deviations from Sievert’s law for n values 0.55 and 0.62 for the Pd membrane and unity for the Pd/Ag membrane. For the Pd/Ag membrane, the concentration of CO in the permeate stream was reduced as a result of the addition of Ag. The effect of the component gases to hydrogen permeation was observed to be lower for the Pd/Ag membrane. Annealing the membrane in hydrogen at high temperature decreased the inhibition effect and enhanced hydrogen permeation through the membrane.展开更多
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 as follows:National Natural Science Foundation of China(81970379)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3712)Medical Innovation Team Project of Jiangsu Province(CXTDA2017010).
文摘BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.
基金supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (C) 20K08399 (to Yasuhiro Maejima)KAKENHI 19K18985,Grant-in-Aid for JSPS Fellows+1 种基金MSD Life Science FoundationPublic Interest Incorporated Foundation (to Yuka Shiheido-Watanabe)
文摘While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
基金sponsored by the National Natural Science Foundation of China(No.31200963)the Key Project of Hunan Provincial Education Department(No.18A091).
文摘Cold acclimation is a complex biological process leading to the development of freezing tolerance in plants.In this study,we demonstrated that cold-induced expression of protease inhibitor FmASP in a Citrus-relative species kumquat[Fortunella margarita(Lour.)Swingle]contributes to its freezing tolerance by minimizing protein degradation.Firstly,we found that only cold-acclimated kumquat plants,despite extensive leaf cellular damage during freezing,were able to resume their normal growth upon stress relief.To dissect the impact of cold acclimation on this anti-freezing performance,we conducted protein abundance assays and quantitative proteomic analysis of kumquat leaves subjected to cold acclimation(4◦C),freezing treatment(−10◦C)and post-freezing recovery(25◦C).FmASP(Against Serine Protease)and several non-specific proteases were identified as differentially expressed proteins induced by cold acclimation and associated with stable protein abundance throughout the course of low-temperature treatment.FmASP was further characterized as a robust inhibitor of multiple proteases.In addition,heterogeneous expression of FmASP in Arabidopsis confirmed its positive role in freezing tolerance.Finally,we proposed a working model of FmASP and illustrated how this extracellular-localized protease inhibitor protects proteins from degradation,therebymaintaining essential cellular function for post-freezing recovery.These findings revealed the important role of protease inhibition in freezing response and provide insights on how this role may help develop new strategies to enhance plant freezing tolerance.
文摘In the process of exploration and development of oil and gas fields, the acidic environment of oil reservoir, production and transport processes cause corrosion of pipelines and equipment, resulting in huge economic losses and production safety risks. Corrosion inhibitors were widely used in oil industry because of simple operation process and economical. In this study, three environmentally friendly corrosion inhibitors were synthesized based on the natural polysaccharide chitosan. Corrosion inhibition of three dendritic chitosan derivatives (We name them BH, CH and DH) on mild steel in 1 mol/L HCl solution with natural ventilation system was evaluated by weight loss experiment, electrochemical analysis and surface morphology characterization. The experimental results showed that when the three dendritic chitosan derivatives added in the corrosive medium were 500 mg L^(−1), the corrosion inhibition efficiencies were all more than 80%. Based on quantum chemical calculation, inhibition mechanisms of three dendritic chitosan derivatives were investigated according to molecular structures. The results showed that the benzene ring, Schiff base and N atom contained in the molecule were the active centers of electron exchange, which were more likely to form a film on the carbon steel surface, thereby slowing or inhibiting corrosion. The results also predicted the corrosion inhibition effect BH > DH > CH, which was consistent with the experimental conclusion.
基金supported by the Natural Science Foundation of Hebei Province (H2020206226)Hebei Province Science and Technology Support Program (18277756D)+1 种基金the Science and Technology Research Project of Hebei Higher Education Institutions (ZD2022010)High-level Talent Funding Project of Hebei (C20231141) to W.W。
文摘Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing.However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.
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 National Natural Science Foundation of China(Grant No.U23A20591,52203201,52173149,and 81971174)the Youth Talents Promotion Project of Jilin Province(Grant No.202019)+1 种基金the Science and Technology Development Program of Jilin Province(Grant No.20210101114JC)Research Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin University(Grant No.KYXZ2022JC04).
文摘Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
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supported by the Foundation of the National Natural Science Foundation of China (No. 81671024, 81371171, 81571009, and 81600877)the China Postdoctoral Science Foundation (2016M600745)。
文摘The lineage specification of mesenchymal stem/stromal cells(MSCs) is tightly regulated by a wide range of factors. Recently, the versatile functions of ZBP1(also known as DAI or DLM-1) have been reported in the blood circulation and immune systems.However, the biological function of ZBP1 during the lineage specification of MSCs is still unknown. In the present study, we found that ZBP1 was upregulated during osteogenesis but downregulated during adipogenesis in mouse bone marrow-derived MSCs(m BMSCs). ZBP1 was highly expressed in osteoblasts but expressed at a relatively low level in marrow adipocytes. Knockdown of ZBP1 inhibited alkaline phosphataseactivity, extracellular matrix mineralization, and osteogenesis-related gene expression in vitro and reduced ectopic bone formation in vivo. Knockdown of ZBP1 also promoted adipogenesis in MSCs in vitro. Conversely, the overexpression of ZBP1 increased the osteogenesis but suppressed the adipogenesis of MSCs. When the expression of ZBP1 was rescued, the osteogenic capacity of ZBP1-depleted m BMSCs was restored at both the molecular and phenotypic levels.Furthermore, we demonstrated that ZBP1, a newly identified target of Wnt/β-catenin signaling, was required for β-catenin translocation into nuclei. Collectively, our results indicate that ZBP1 is a novel regulator of bone and fat transdifferentiation via Wnt/β-catenin signaling.
基金supported by the National Key R&D Program of China(2018YFD0100705)the China Agriculture Research System of Watermelon and Melon(CARS-25)the Innovation Engineering Project of the Chinese Academy of Agricultural Sciences,and the Central Public-Interest Scientific Institution Basal Research Fund(1610102016026,IVF-BRF2018011).
文摘Melatonin has been shown to alleviate the effects of abiotic stress and to regulate plant development.Copper,a common heavy metal and soil pollutant,can suppress plant growth and development.In this work,we explored the protective effects of exogenous melatonin on lateral root formation in response to copper stress using melon seeds subjected to three germination treatments:CK1(control),CK2(300μmol/L CuSO4),and MT3(300μmol/L melatonin+300μmol/L CuSO4).Melatonin pretreatment increased the antioxidant enzyme activities and root vigor,and decreased the proline and malondialdehyde(MDA)contents in the roots of copper-stressed melon seedlings.We then used transcriptomic and metabolomic analyses to explore the mechanisms by which exogenous melatonin protects against copper stress.There were 70 significant differentially expressed genes(DEGs)(28 upregulated,42 downregulated)and 318 significantly differentially expressed metabolites(DEMs)(168 upregulated,150 downregulated)between the MT3 and CK2 treatments.Melatonin pretreatment altered the expression of genes related to redox and cell wall formation processes.In addition,we found that members of the AP2/ERF,BBR/BPC,GRAS,and HD-ZIP transcription factor families may have vital roles in lateral root development.Melatonin also increased the level of Glutathione(GSH),which chelates excess Cu^(2+).The combined transcriptomic and metabolomic analysis revealed DEGs and DEMs involved in jasmonic acid(JA)biosynthesis,including four lipoxygenase-related genes and two metabolites(linoleic acid and lecithin)related to melatonin’s alleviation effect on copper toxicity.This research elucidated the molecular mechanisms of melatonin’s protective effects in copper-stressed melon.
基金supported by the National Natural Science Foundation of China(82170947)the Applied Basic Research Project of Science and Technology Department of Sichuan Province(2020YJ0296)the Innovation and Collaborative Project of Science and Technology Department of Sichuan Province(2019YFH0025)。
文摘Glucosyltransferases(Gtfs)play critical roles in the etiology and pathogenesis of Streptococcus mutans(S.mutans)-mediated dental caries including early childhood caries.Gtfs enhance the biofilm formation and promotes colonization of cariogenic bacteria by generating biofilm extracellular polysaccharides(EPSs),the key virulence property in the cariogenic process.Therefore,Gtfs have become an appealing target for effective therapeutic interventions that inhibit cariogenic biofilms.Importantly,targeting Gtfs selectively impairs the S.mutans virulence without affecting S.mutans existence or the existence of other species in the oral cavity.Over the past decade,numerous Gtfs inhibitory molecules have been identified,mainly including natural and synthetic compounds and their derivatives,antibodies,and metal ions.These therapeutic agents exert their inhibitory role in inhibiting the expression gtf genes and the activities and secretion of Gtfs enzymes with a wide range of sensitivity and effectiveness.Understanding molecular mechanisms of inhibiting Gtfs will contribute to instructing drug combination strategies,which is more effective for inhibiting Gtfs than one drug or class of drugs.This review highlights our current understanding of Gtfs activities and their potential utility,and discusses challenges and opportunities for future exploration of Gtfs as a therapeutic target.
基金This work was supported by grants from the National Natural Science Foundation of China(81625005 to Z.P.F.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-031 to Z.P.F.)+1 种基金the Program for“Hundred-Thousand-Ten Thousand”Talents in Beijing(2018A16 to Z.P.F.)Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction(KFKT2019012 to L.L).
文摘Human dental pulp stem cells(DPSCs)have emerged as an important source of stem cells in the tissue engineering,and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration.Nevertheless,little is known about the complicated molecular mechanisms.In this study,we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition.Hypoxia was induced in DPSCs by Cobalt chloride(CoCl_(2))treatment.The osteo/dentinogenic differentiation capacity of DPSCs was assessed by alkaline phosphatase(ALP)activity,Alizarin Red S staining and main osteo/dentinogenic markers.A luciferase reporter gene assay was performed to verify the downstream target gene of miR-140-3p.This research exhibited that miR-140-3p promoted osteo/dentinogenic differentiation of DPSCs under normoxia environment.Furthermore,miR-140-3p rescued the CoCl_(2)-induced decreased osteo/odontogenic differentiation potentials in DPSCs.Besides,we investigated that miR-140-3p directly targeted lysine methyltransferase 5B(KMT5B).Surprisingly,we found inhibition of KMT5B obviously enhanced osteo/dentinogenic differentiation of DPSCs both under normoxia and hypoxia conditions.In conclusion,our study revealed the role and mechanism of miR-140-3p for regulating osteo/dentinogenic differentiation of DPSCs under hypoxia,and discovered that miR-140-3p and KMT5B might be important targets for DPSC-mediated tooth or bone tissue regeneration.
基金supported by grants from the National Natural Science Foundation of China(81625005 to Z.P.F.)the Program for“Hundred-Thousand-Ten thousand”Talents in Beijing(2018A16 to Z.P.F.)。
文摘Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.
基金This work was supported by the Beijing Leafy Vegetables Innovation Team of Modern Agro-industry Technology Research System(BAIC07-2020)The Construction of Beijing Science and Technology Innovation and Service Capacity in Top Subjects(CEFF-PXM2019_014207_000032).
文摘Leaf size and flatness directly affect photosynthesis and are closely related to agricultural yield.The final leaf size and shape are coordinately determined by cell proliferation,differentiation,and expansion during leaf development.Lettuce(Lactuca sativa L.)is one of the most important leafy vegetables worldwide,and lettuce leaves vary in shape and size.However,the molecular mechanisms of leaf development in lettuce are largely unknown.In this study,we showed that the lettuce APETALA2(LsAP2)gene regulates leaf morphology.LsAP2 encodes a transcriptional repressor that contains the conserved EAR motif,which mediates interactions with the TOPLESS/TOPLESS-RELATED(JPL/TPR)corepressors.Overexpression of LsAP2 led to small and crinkly leaves,and many bulges were seen on the surface of the leaf blade.LsAP2 physically interacted with the CINCINNATA(CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR(TCP)transcription factors and inhibited their transcriptional activation activity.RNA sequencing analysis showed that LsAP2 affected the expression of auxin-and polarity-related genes.In addition,LsAP2 directly repressed the abaxial identity gene KANAD12(LsKAN2).Together,these results indicate that LsAP2 regulates leaf morphology by inhibiting CIN-like TCP transcription factors and repressing LsKAN2,and our work provides insights into the regulatory mechanisms of leaf development in lettuce.
基金This research project was supported by the National Natural Science Foundation of China(No.52074138)Basic research project of Yunnan Province(No.202001AS070030)Open Foundation of State Key Laboratory of Mineral Processing(No.BGRIMM-KJSKL-2020-03).
文摘In this study,the role of(NH_(4))_(2)SO_(4)during the sulfurization of azurite and its response to flotation were investigated.The flotation results showed that adding(NH_(4))_(2)SO_(4)prior to sulfurization decreased the formation of colloid in flotation pulp,and the floatability of the suppressed azurite caused by excess sodium sulfide was restored.After adding(NH_(4))_(2)SO_(4)prior to sulfurization,the formation of Cu(NH_(3))_(n) ^(2+)intermediate products changed the path of the sulfurization reaction,which slowed the direct impact of HSon the azurite surface.The nucleation rate was reduced,and the growth of copper sulfide crystal was improved.Covellite(syn,CuS)with larger crystal grains was formed on the azurite surface,thereby enhancing the mechanical stability of copper sulfide products onto the mineral surface.Therefore,the generated copper sulfide colloid significantly reduced,ultimately promoting the effective adsorption of xanthate on the azurite surface.
文摘The mitigation of the CO inhibition effect in palladium membranes is necessary due to its significance in the efficiency of membrane reactors and hydrogen production systems. In this work, the hydrogen separation performance of a Pd and Pd/Ag membrane both of thickness 2 μm is investigated using a mixed gas with composition (H2 = 50%, CO = 28%, CO2 = 10%, CH4 = 8%, N2 = 4%) at temperature 623 - 873 K and pressure (0.05 - 0.4 bar) was investigated. The component gases CO and CO2 were observed to inhibit hydrogen permeation through the membrane and lead to deviations from Sievert’s law for n values 0.55 and 0.62 for the Pd membrane and unity for the Pd/Ag membrane. For the Pd/Ag membrane, the concentration of CO in the permeate stream was reduced as a result of the addition of Ag. The effect of the component gases to hydrogen permeation was observed to be lower for the Pd/Ag membrane. Annealing the membrane in hydrogen at high temperature decreased the inhibition effect and enhanced hydrogen permeation through the membrane.