Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pecti...Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pectin.PGIPs,also known as leucine-rich repeat pathogenesis-related(PR)proteins,activate the host’s defense response upon interaction with PG,thereby reinforcing the host defense against plant pathogens attacks.In Egyptian or extra-long staple cotton(Gossypium barbadense),the interaction between PGIP and PG is one of the crucial steps in the defense mechanism against major pathogens such as Xanthomonas citri pv.malvacearum and Alternaria mac-rospora,which are responsible for bacterial leaf blight and leaf spot diseases,respectively.Results To unravel the molecular mechanisms underlying these PR proteins,we conducted a comprehensive study involving molecular modeling,protein-protein docking,site-specific double mutation(E169G and F242K),and molec-ular dynamics simulations.Both wild-type and mutated cotton PGIPs were examined in the interaction with the PG enzyme of a bacterial and fungal pathogen.Our findings revealed that changes in conformations of double-mutated residues in the active site of PGIP lead to the inhibition of PG binding.The molecular dynamics simulation studies provide insights into the dynamic behaviour and stability of the PGIP-PG complexes,shedding light on the intricate details of the inhibitory and exhibitory mechanism against the major fungal and bacterial pathogens of G.barbadense,respectively.Conclusions The findings of this study not only enhance our understanding of the molecular interactions between PGs of Xanthomonas citri pv.malvacearum and Alternaria macrospora and PGIP of G.barbadense but also pre-sent a potential strategy for developing the disease-resistant cotton varieties.By variations in the binding affinities of PGs through specific mutations in PGIP,this research offers promising avenues for the development of enhanced resistance to cotton plants against bacterial leaf blight and leaf spot diseases.展开更多
The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14...The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions...P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions that occur at high voltage severely limit their practical application.Herein,a novel high-valence tungsten doped P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)cathode material was prepared using the sol–gel method.Through diffusion kinetics analysis and in situ X-ray diffraction(in situ XRD),it has been proven that W^(6+)not only enhances the Na^(+)diffusion coefficient but also reduces the P2–O2 phase transition.The optimized NNMO-W1%delivers a high discharge specific capacity of 163 mAh·g^(-1)at 0.1C,and the capacity retention rate is as high as 77.6%after 1000 cycles at 10C.This is mainly due to that W^(6+)enters the lattice,optimizing the arrangement of primary particles.This work sheds light on the design and construction of high-performance layered oxides cathode materials.展开更多
Over the past two decades,superhydrophobic surfaces that are easily created have aroused considerable attention for their superior performances in various applications at room temperature.Nowadays,there is a growing d...Over the past two decades,superhydrophobic surfaces that are easily created have aroused considerable attention for their superior performances in various applications at room temperature.Nowadays,there is a growing demand in special fields for the development of surfaces that can resist wetting by high-temperature molten droplets(>1200°C)using facile design and fabrication strategies.Herein,bioinspired directional structures(BDSs)were prepared on Y2O3-stabilized ZrO2(YSZ)surfaces using femtosecond laser ablation.Benefiting from the anisotropic energy barriers,the BDSs featured with no additional modifiers showed a remarkable increase from 9.2°to 60°in the contact angle of CaO–MgO–Al2O3–SiO2(CMAS)melt and a 70.1%reduction in the spreading area of CMAS at 1250°C,compared with polished super-CMAS-melt-philic YSZ surfaces.Moreover,the BDSs demonstrated exceptional wetting inhibition even at 1400°C,with an increase from 3.3°to 31.3°in contact angle and a 67.9%decrease in spreading area.This work provides valuable insight and a facile preparation strategy for effectively inhibiting the wetting of molten droplets on super-melt-philic surfaces at extremely high temperatures.展开更多
Osteoarthritis(OA)is an age-related cartilage-degenerating joint disease.Mitochondrial dysfunction has been reported to promote the development of OA.Poly(ADP-ribose)polymerase family member 12(PARP12)is a key regulat...Osteoarthritis(OA)is an age-related cartilage-degenerating joint disease.Mitochondrial dysfunction has been reported to promote the development of OA.Poly(ADP-ribose)polymerase family member 12(PARP12)is a key regulator of mitochondrial function,protein translation,and inflammation.However,the role of PARP12 in OA-based cartilage degradation and the underlying mechanisms are relatively unknown.Here,we first demonstrated that PARP12 inhibits mitophagy and promotes OA progression in human OA cartilage and a monosodium iodoacetate-induced rat OA model.Using mass spectrometry and co-immunoprecipitation assay,PARP12 was shown to interact with ISG15,upregulate mitofusin 1 and 2(MFN1/2)ISGylation,which downregulated MFN1/2 ubiquitination and SUMOylation,thereby inhibiting PINK1/Parkin-dependent chondrocyte mitophagy and promoting cartilage degradation.Moreover,inflammatory cytokine-induced interferon regulatory factor 1(IRF1)activation was required for the upregulation of PARP12 expression,and it directly bound to the PARP12 promoter to activate transcription.XAV-939 inhibited PARP12 expression and suppressed OA pathogenesis in vitro and in vivo.Clinically,PARP12 can be used to predict the severity of OA;thus,it represents a new target for the study of mitophagy and OA progression.In brief,the IRF1-mediated upregulation of PARP12 promoted cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy via ISG15-based attenuation of MFN1/2 ubiquitylation and SUMOylation.Our data provide new insights into the molecular mechanisms underlying PARP12-based regulation of mitophagy and can facilitate the development of therapeutic strategies for the treatment of OA.展开更多
Soil acidification is a major threat to agricultural sustainability in tropical and subtropical regions.Biodegradable and environmentally friendly materials,such as calcium lignosulfonate(CaLS),calcium poly(aspartic a...Soil acidification is a major threat to agricultural sustainability in tropical and subtropical regions.Biodegradable and environmentally friendly materials,such as calcium lignosulfonate(CaLS),calcium poly(aspartic acid)(PASP-Ca),and calcium polyγ-glutamic acid(γ-PGA-Ca),are known to effectively ameliorate soil acidity.However,their effectiveness in inhibiting soil acidification has not been studied.This study aimed to evaluate the effect of CaLS,PASP-Ca,andγ-PGA-Ca on the resistance of soil toward acidification as directly and indirectly(i.e.,via nitrification)caused by the application of HNO_(3)and urea,respectively.For comparison,Ca(OH)_(2)and lignin were used as the inorganic and organic controls,respectively.Among the materials,γ-PGA-Ca drove the substantial improvements in the pH buffering capacity(pHBC)of the soil and exhibited the greatest potential in inhibiting HNO_(3)-induced soil acidification via protonation of carboxyl,complexing with Al~(3+),and cation exchange processes.Under acidification induced by urea,CaLS was the optimal one in inhibiting acidification and increasing exchangeable acidity during incubation.Furthermore,the sharp reduction in the population sizes of ammonia-oxidizing bacteria(AOB)and ammonia-oxidizing archaea(AOA)confirmed the inhibition of nitrification via CaLS application.Therefore,compared to improving soil pHBC,CaLS may play a more important role in suppressing indirect acidification.Overall,γ-PGA-Ca was superior to PASP-Ca and CaLS in enhancing the soil pHBC and the its resistance to acidification induced by HNO_(3) addition,whereas CaLS was the best at suppressing urea-driven soil acidification by inhibiting nitrification.In conclusion,these results provide a reference for inhibiting soil re-acidification in intensive agricultural systems.展开更多
In the context of building a country with a strong transportation network,railway container transportation(RCT)is an important means of reducing costs,increasing efficiency,and adjusting transportation structures.Thus...In the context of building a country with a strong transportation network,railway container transportation(RCT)is an important means of reducing costs,increasing efficiency,and adjusting transportation structures.Thus,its impact on regional economic development is important.Based on data from railway container-handling stations and spatial econometric models,this study discusses the differences in the development of RCT and their impact on regional economic development at different leves.This study has three main findings:first,there are significant regional differences in the development of the RCT.The intra-regional differences between the eastern and central regions of China(which do not include Hong Kong,Macao and Taiwan)are gradually narrowing,while the regional differences in the western region are widening.Meanwhile,the intra-regional differences in important economic zones such as Pearl River Delta Economic Zone(PRDEZ),Chengdu-Chongqing Economic Zone(CYEZ),Bohai Rim Economic Zone(BHEZ),and Yangtze River Delta Economic Zone(YRDEZ)are narrowing daily.Second,the development differences of RCT in regional level and important economic regions level show different trends.The unbalanced features of large regions are increasingly evident,whereas the differences in economic regions are decreasing.However,the problem of overlapping RCT remains prominent.Third,the transformation of RCT development mode and fierce competition among transportation modes cause RCT to have a restraining effect on the regional economy at three levels.Rational allocation of resources and other means must be used to guide the transformation from inhibition to promotion,and by formulating targeted policies that will promote the development of RCT,which will improve the transportation structure and help construct a country with a strong transportation 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
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
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
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
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
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
The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and ch...The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and characterizing a peptide with angiotensin-? converting enzyme(ACE-I) inhibiting activity from Venerupis philippinarum hydrolysate. Firstly, ethanol supernatant of V. philippinarum hydrolysate was separated into active fractions with chromatographic methods such as ion-exchange chromatography and high performance liquid chromatography in combination. Then seven peptides from active fraction were identified according to the searching result of the MS/MS spectra against protein databases. Peptides were synthesized and subjected to ACE-Iinhibition assay. The peptide NTLTLIDTGIGMTK showed the highest potency with an IC_(50) of 5.75 μmol L^(-1). The molecular docking analysis showed that the ACE-I inhibiting peptide NTLTLIDTGIGMTK bond with residues Glu123, Glu403, Arg522, Glu376, Gln281 and Asn285 of ACE-I. Therefore, active peptides could be identified with the present method rather than the traditional purification and identification strategies. It may also be feasible to identify other food-derived peptides which target other enzymes and receptors with the method developed in this study.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
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
The article by Lan et al.[1],published on 30 October 2021 in Hepatology,showed the relationship between the natural flavonoid compound breviscapine and nonalcoholic steatohepatitis(NASH).The researchers demonstrated t...The article by Lan et al.[1],published on 30 October 2021 in Hepatology,showed the relationship between the natural flavonoid compound breviscapine and nonalcoholic steatohepatitis(NASH).The researchers demonstrated that breviscapine might be a novel therapeutic candidate for the treatment of NASH.It can be proven that breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of the TGF-β-activated Kinase 1(TAK1)signaling pathway.展开更多
Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus(HCV)for a few years.New researches support that sofosbuvir might he useful for the management of Zika virus infection.Ba...Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus(HCV)for a few years.New researches support that sofosbuvir might he useful for the management of Zika virus infection.Based on the pharmacological activity,inhibiting the HCV RNA-dependent RNA polymerase(RdRp or NS5 protein).sofosbuvir is proposed for its effectiveness against Zika virus infection.Here,the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection.Based on the modeling study,if sofosbuvir is assigned for management of Zika virus.infection,doubled dosage of the present dosage for hepatitis C management is recommended.展开更多
The aim of this study was to investigate the inhibitory effect of heparin/fibronectin （Hep/Fn） complexes on neointimal hyperplasia following endovascular intervention. Hep/Fn complexes were immobilized onto titanium...The aim of this study was to investigate the inhibitory effect of heparin/fibronectin （Hep/Fn） complexes on neointimal hyperplasia following endovascular intervention. Hep/Fn complexes were immobilized onto titanium （Ti） surfaces, with subsequent X-ray photoelectron spectroscopy （XPS）, Toluidine Blue 0 （TBO） and immunohistochemistry methods were used to characterize surface properties. Smooth muscle cell （SMC） cultures were used to evaluate the effect of Hep/Fn complexes on SMC proliferation. Results showed that Hep/Fn complexes successfully immobilized onto Ti surfaces and resulted in an inhibition of SMC proliferation. This study suggests that Hep/Fn surface-immobilized biomaterials develop as a new generation of biomaterials to prevent neointimal hyperplasia, particularly for use in cardiovascular implants.展开更多
基金CABin grant(F.no.Agril.Edn.4-1/2013-A&P)Indian Council of Agricul-tural Research,Ministry of Agriculture and Farmers’Welfare,Govt.of India and Department of Biotechnology,Govt.of India for BIC project grant(BT/PR40161/BTIS/137/32/2021)。
文摘Background Polygalacturonase inhibiting proteins(PGIPs)play a pivotal role in plant defense against plant patho-gens by inhibiting polygalacturonase(PG),an enzyme produced by pathogens to degrade plant cell wall pectin.PGIPs,also known as leucine-rich repeat pathogenesis-related(PR)proteins,activate the host’s defense response upon interaction with PG,thereby reinforcing the host defense against plant pathogens attacks.In Egyptian or extra-long staple cotton(Gossypium barbadense),the interaction between PGIP and PG is one of the crucial steps in the defense mechanism against major pathogens such as Xanthomonas citri pv.malvacearum and Alternaria mac-rospora,which are responsible for bacterial leaf blight and leaf spot diseases,respectively.Results To unravel the molecular mechanisms underlying these PR proteins,we conducted a comprehensive study involving molecular modeling,protein-protein docking,site-specific double mutation(E169G and F242K),and molec-ular dynamics simulations.Both wild-type and mutated cotton PGIPs were examined in the interaction with the PG enzyme of a bacterial and fungal pathogen.Our findings revealed that changes in conformations of double-mutated residues in the active site of PGIP lead to the inhibition of PG binding.The molecular dynamics simulation studies provide insights into the dynamic behaviour and stability of the PGIP-PG complexes,shedding light on the intricate details of the inhibitory and exhibitory mechanism against the major fungal and bacterial pathogens of G.barbadense,respectively.Conclusions The findings of this study not only enhance our understanding of the molecular interactions between PGs of Xanthomonas citri pv.malvacearum and Alternaria macrospora and PGIP of G.barbadense but also pre-sent a potential strategy for developing the disease-resistant cotton varieties.By variations in the binding affinities of PGs through specific mutations in PGIP,this research offers promising avenues for the development of enhanced resistance to cotton plants against bacterial leaf blight and leaf spot diseases.
文摘The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金supported by the National Natural Science Foundation of China Key Program(No.U22A20420)Changzhou Leading Innovative Talents Introduction and Cultivation Project(No.CQ20230109)the Key Project of Jiangsu Provincial Basic Research Program(No.BK20243032)。
文摘P2-type layered oxide cathode materials have attracted extensive attention due to their simple preparation,high specific capacity,adjustable voltage range,and high packing density.However,the harmful phase transitions that occur at high voltage severely limit their practical application.Herein,a novel high-valence tungsten doped P2-Na_(0.67)Ni_(0.33)Mn_(0.67)O_(2)cathode material was prepared using the sol–gel method.Through diffusion kinetics analysis and in situ X-ray diffraction(in situ XRD),it has been proven that W^(6+)not only enhances the Na^(+)diffusion coefficient but also reduces the P2–O2 phase transition.The optimized NNMO-W1%delivers a high discharge specific capacity of 163 mAh·g^(-1)at 0.1C,and the capacity retention rate is as high as 77.6%after 1000 cycles at 10C.This is mainly due to that W^(6+)enters the lattice,optimizing the arrangement of primary particles.This work sheds light on the design and construction of high-performance layered oxides cathode materials.
基金This work was supported by National Natural Science Foundation of China(No.52105212)Sichuan Science and Technology Program(No.2023NSFSC0863)China Postdoctoral Science Foundation(No.2021M702712).
文摘Over the past two decades,superhydrophobic surfaces that are easily created have aroused considerable attention for their superior performances in various applications at room temperature.Nowadays,there is a growing demand in special fields for the development of surfaces that can resist wetting by high-temperature molten droplets(>1200°C)using facile design and fabrication strategies.Herein,bioinspired directional structures(BDSs)were prepared on Y2O3-stabilized ZrO2(YSZ)surfaces using femtosecond laser ablation.Benefiting from the anisotropic energy barriers,the BDSs featured with no additional modifiers showed a remarkable increase from 9.2°to 60°in the contact angle of CaO–MgO–Al2O3–SiO2(CMAS)melt and a 70.1%reduction in the spreading area of CMAS at 1250°C,compared with polished super-CMAS-melt-philic YSZ surfaces.Moreover,the BDSs demonstrated exceptional wetting inhibition even at 1400°C,with an increase from 3.3°to 31.3°in contact angle and a 67.9%decrease in spreading area.This work provides valuable insight and a facile preparation strategy for effectively inhibiting the wetting of molten droplets on super-melt-philic surfaces at extremely high temperatures.
基金supported by the National Natural Science Foundation of China (82202739)Guangdong Basic and Applied Basic Research Foundation Natural Science Fund Project-Youth Promotion Project (2024A1515030260)+1 种基金China Statefunded Postdoctoral Researchers Program (GZC20233265)National Natural Science Foundation of China (81972051)。
文摘Osteoarthritis(OA)is an age-related cartilage-degenerating joint disease.Mitochondrial dysfunction has been reported to promote the development of OA.Poly(ADP-ribose)polymerase family member 12(PARP12)is a key regulator of mitochondrial function,protein translation,and inflammation.However,the role of PARP12 in OA-based cartilage degradation and the underlying mechanisms are relatively unknown.Here,we first demonstrated that PARP12 inhibits mitophagy and promotes OA progression in human OA cartilage and a monosodium iodoacetate-induced rat OA model.Using mass spectrometry and co-immunoprecipitation assay,PARP12 was shown to interact with ISG15,upregulate mitofusin 1 and 2(MFN1/2)ISGylation,which downregulated MFN1/2 ubiquitination and SUMOylation,thereby inhibiting PINK1/Parkin-dependent chondrocyte mitophagy and promoting cartilage degradation.Moreover,inflammatory cytokine-induced interferon regulatory factor 1(IRF1)activation was required for the upregulation of PARP12 expression,and it directly bound to the PARP12 promoter to activate transcription.XAV-939 inhibited PARP12 expression and suppressed OA pathogenesis in vitro and in vivo.Clinically,PARP12 can be used to predict the severity of OA;thus,it represents a new target for the study of mitophagy and OA progression.In brief,the IRF1-mediated upregulation of PARP12 promoted cartilage degradation by inhibiting PINK1/Parkin-dependent mitophagy via ISG15-based attenuation of MFN1/2 ubiquitylation and SUMOylation.Our data provide new insights into the molecular mechanisms underlying PARP12-based regulation of mitophagy and can facilitate the development of therapeutic strategies for the treatment of OA.
基金supported by the Major project of Ministry of Agriculture and Rural Affairs of the People’s Republic of China(No.NK2022180401)the major project of Ministry of Agriculture and Rural Affairs of the People’s Republic of China(No.NK2022180404)。
文摘Soil acidification is a major threat to agricultural sustainability in tropical and subtropical regions.Biodegradable and environmentally friendly materials,such as calcium lignosulfonate(CaLS),calcium poly(aspartic acid)(PASP-Ca),and calcium polyγ-glutamic acid(γ-PGA-Ca),are known to effectively ameliorate soil acidity.However,their effectiveness in inhibiting soil acidification has not been studied.This study aimed to evaluate the effect of CaLS,PASP-Ca,andγ-PGA-Ca on the resistance of soil toward acidification as directly and indirectly(i.e.,via nitrification)caused by the application of HNO_(3)and urea,respectively.For comparison,Ca(OH)_(2)and lignin were used as the inorganic and organic controls,respectively.Among the materials,γ-PGA-Ca drove the substantial improvements in the pH buffering capacity(pHBC)of the soil and exhibited the greatest potential in inhibiting HNO_(3)-induced soil acidification via protonation of carboxyl,complexing with Al~(3+),and cation exchange processes.Under acidification induced by urea,CaLS was the optimal one in inhibiting acidification and increasing exchangeable acidity during incubation.Furthermore,the sharp reduction in the population sizes of ammonia-oxidizing bacteria(AOB)and ammonia-oxidizing archaea(AOA)confirmed the inhibition of nitrification via CaLS application.Therefore,compared to improving soil pHBC,CaLS may play a more important role in suppressing indirect acidification.Overall,γ-PGA-Ca was superior to PASP-Ca and CaLS in enhancing the soil pHBC and the its resistance to acidification induced by HNO_(3) addition,whereas CaLS was the best at suppressing urea-driven soil acidification by inhibiting nitrification.In conclusion,these results provide a reference for inhibiting soil re-acidification in intensive agricultural systems.
基金Under the auspices of National Key Research and Development Program of China(No.2023YFB4302200)National Natural Science Foundation of China(No.71831002,72174053)+1 种基金Liaoning Province Xingliao Talent Plan(No.XLYC2008030)Talent Planning in Dalian(No.2022RG05)。
文摘In the context of building a country with a strong transportation network,railway container transportation(RCT)is an important means of reducing costs,increasing efficiency,and adjusting transportation structures.Thus,its impact on regional economic development is important.Based on data from railway container-handling stations and spatial econometric models,this study discusses the differences in the development of RCT and their impact on regional economic development at different leves.This study has three main findings:first,there are significant regional differences in the development of the RCT.The intra-regional differences between the eastern and central regions of China(which do not include Hong Kong,Macao and Taiwan)are gradually narrowing,while the regional differences in the western region are widening.Meanwhile,the intra-regional differences in important economic zones such as Pearl River Delta Economic Zone(PRDEZ),Chengdu-Chongqing Economic Zone(CYEZ),Bohai Rim Economic Zone(BHEZ),and Yangtze River Delta Economic Zone(YRDEZ)are narrowing daily.Second,the development differences of RCT in regional level and important economic regions level show different trends.The unbalanced features of large regions are increasingly evident,whereas the differences in economic regions are decreasing.However,the problem of overlapping RCT remains prominent.Third,the transformation of RCT development mode and fierce competition among transportation modes cause RCT to have a restraining effect on the regional economy at three levels.Rational allocation of resources and other means must be used to guide the transformation from inhibition to promotion,and by formulating targeted policies that will promote the development of RCT,which will improve the transportation structure and help construct a country with a strong transportation 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 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 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 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supported by the Public Science and Technology Research Funds (Projects of Ocean)State Ocean Administration of P. R. China (Nos. 201305007 and 201405017)+3 种基金National High Technology Research and Development Program of China (No. 2013AA093003)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)Jiangsu Qinglan ProjectJiangsu 333 Project
文摘The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and characterizing a peptide with angiotensin-? converting enzyme(ACE-I) inhibiting activity from Venerupis philippinarum hydrolysate. Firstly, ethanol supernatant of V. philippinarum hydrolysate was separated into active fractions with chromatographic methods such as ion-exchange chromatography and high performance liquid chromatography in combination. Then seven peptides from active fraction were identified according to the searching result of the MS/MS spectra against protein databases. Peptides were synthesized and subjected to ACE-Iinhibition assay. The peptide NTLTLIDTGIGMTK showed the highest potency with an IC_(50) of 5.75 μmol L^(-1). The molecular docking analysis showed that the ACE-I inhibiting peptide NTLTLIDTGIGMTK bond with residues Glu123, Glu403, Arg522, Glu376, Gln281 and Asn285 of ACE-I. Therefore, active peptides could be identified with the present method rather than the traditional purification and identification strategies. It may also be feasible to identify other food-derived peptides which target other enzymes and receptors with the method developed in this study.
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the National Natural Science Foundation of China(nos.32072309)Tianjin Municipal Science and Technology Committee(19JCYBJC27800).
文摘The article by Lan et al.[1],published on 30 October 2021 in Hepatology,showed the relationship between the natural flavonoid compound breviscapine and nonalcoholic steatohepatitis(NASH).The researchers demonstrated that breviscapine might be a novel therapeutic candidate for the treatment of NASH.It can be proven that breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of the TGF-β-activated Kinase 1(TAK1)signaling pathway.
文摘Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus(HCV)for a few years.New researches support that sofosbuvir might he useful for the management of Zika virus infection.Based on the pharmacological activity,inhibiting the HCV RNA-dependent RNA polymerase(RdRp or NS5 protein).sofosbuvir is proposed for its effectiveness against Zika virus infection.Here,the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection.Based on the modeling study,if sofosbuvir is assigned for management of Zika virus.infection,doubled dosage of the present dosage for hepatitis C management is recommended.
基金supported by the financial support of Natural Science Research Program of Jiangsu Education Department(No.13KJB310014)Natural Science Foundation of Jiangsu Province(BK20140429)the Natural Science Foundation of Nantong University(No.14ZY015,No.13R23)
文摘The aim of this study was to investigate the inhibitory effect of heparin/fibronectin （Hep/Fn） complexes on neointimal hyperplasia following endovascular intervention. Hep/Fn complexes were immobilized onto titanium （Ti） surfaces, with subsequent X-ray photoelectron spectroscopy （XPS）, Toluidine Blue 0 （TBO） and immunohistochemistry methods were used to characterize surface properties. Smooth muscle cell （SMC） cultures were used to evaluate the effect of Hep/Fn complexes on SMC proliferation. Results showed that Hep/Fn complexes successfully immobilized onto Ti surfaces and resulted in an inhibition of SMC proliferation. This study suggests that Hep/Fn surface-immobilized biomaterials develop as a new generation of biomaterials to prevent neointimal hyperplasia, particularly for use in cardiovascular implants.
