Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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.

Heterointerface Engineering-Induced Oxygen Defects for the Manganese Dissolution Inhibition in Aqueous Zinc Ion Batteries

Manganese-based material is a prospective cathode material for aqueous zinc ion batteries(ZIBs)by virtue of its high theoretical capacity,high operating voltage,and low price.However,the manganese dissolution during the electrochemical reaction causes its electrochemical cycling stability to be undesirable.In this work,heterointerface engineering-induced oxygen defects are introduced into heterostructure MnO_(2)(δa-MnO_(2))by in situ electrochemical activation to inhibit manganese dissolution for aqueous zinc ion batteries.Meanwhile,the heterointerface between the disordered amorphous and the crystalline MnO_(2)ofδa-MnO_(2)is decisive for the formation of oxygen defects.And the experimental results indicate that the manganese dissolution ofδa-MnO_(2)is considerably inhibited during the charge/discharge cycle.Theoretical analysis indicates that the oxygen defect regulates the electronic and band structure and the Mn-O bonding state of the electrode material,thereby promoting electron transport kinetics as well as inhibiting Mn dissolution.Consequently,the capacity ofδa-MnO_(2)does not degrade after 100 cycles at a current density of 0.5 Ag^(-1)and also 91%capacity retention after 500cycles at 1 Ag^(-1).This study provides a promising insight into the development of high-performance manganese-based cathode materials through a facile and low-cost strategy.

Inhibition of protein degradation increases the Bt protein concentration in Bt cotton

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.

Alleviated photoinhibition on nitrification in the Indian Sector of the Southern Ocean

Nitrification,a central process in the marine nitrogen cycle,produces regenerated nitrate in the euphotic zone and emits N_(2)O,a potent greenhouse gas as a by-product.The regulatory mechanisms of nitrification in the Southern Ocean,which is a critical region for CO_(2)sequestration and radiative benefits,remain poorly understood.Here,we investigated the in situ and dark nitrification rates in the upper 500 m and conducted substrate kinetics experiments across the Indian Sector in the Cosmonaut and Cooperation seas in the late austral summer.Our findings indicate that light inhibition of nitrification decreases exponentially with depth,exhibiting a light threshold of 0.53%photosynthetically active radiation.A positive relationship between dark nitrification and apparent oxygen utilization suggests a dependence on substrate availability from primary production.Importantly,an increased NH_(4)^(+) supply can act as a buffer against photo-inhibitory damage.Globally,substrate affinity(α)increases with depth and transitions from light to dark,decreases with increasing ambient NH_(4)^(+)and exhibits a latitudinal distribution,reflecting substrate utilization strategies.We also reveal that upwelling in Circumpolar Deep Water(CDW)stimulates nitrification through the introduction of potentially higher iron and deep diverse nitrifying microorganisms with higherα.We conclude that although light is the primary limiting factor for nitrification in summer,coupling between substrate availability and CDW upwelling can overcome this limitation,thereby alleviating photoinhibition by up to 45%±5.3%.

Inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.on human carboxylesterases

OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester⁃ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi⁃azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultrahigh performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100μmol·L^(-1)).Kinetics analysis,involving half inhibitory concentra⁃tion(IC_(50)),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con⁃stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC_(50)was 9.95 and 4.02 mol·L^(-1),respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55μmol·L^(-1)for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.

Growth and inhibition of zinc anode dendrites in Zn-air batteries:Model and experiment

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.

Sensitivity of Commercial Enzyme Inhibition Colorimetric Pesticide Residue Rapid Test Kit to a Variety of Pesticides

[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.

Enhancing Li-S battery performance via functional polymer binders for polysulfide inhibition

The commercialization of lithium-sulfur(Li-S)batteries faces several challenges,including poor conductivity,unexpected volume expansion,and continuous sulfur loss from the cathode due to redox shuttling.In this study,we introduce a novel polymer via a simple cross-linking between poly(ether-thioureas)(PETU)and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)(PEDOT:PSS)as a bifunctio nal binder for Li-S batteries(devotes as"PPTU").Compared to polyvinylidene fluoride(PVDF),as-prepared PPTU exhibits significantly higher electrical conductivity,facilitating electrochemical reactions.Additionally,PPTU demonstrates effective adsorption of lithium polysulfides,leading to improved cycling stability by suppressing the shuttling effect.We investigate this behavior by monitoring morphological changes at the cell interface using synchrotron X-ray tomography.Cells with PPTU binders exhibit remarkable rate performance,desired reversibility,and excellent cycling stability even under stringent bending and twisting conditions.Our work represents promising progress in functional polymer binder development for Li-S batteries.

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

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.

Inhibitory effect of procyanidin B2 and tannin acid on cholesterol esterase and their synergistic effect with orlistat

This study was aimed to analyze the effect of procyanidin B2(PC)and tannin acid(TA)on the activities of cholesterol esterase(CEase)and the inhibitory mechanisms of enzymatic activity.The interaction mechanisms were investigated by enzymatic kinetics,multi-spectroscopy methods,thermodynamics analysis,molecular docking,and dynamic simulations.PC and TA could bind with CEase and inhibit the activity of enzyme in a mixed-competitive manner and non-competitive manner,which was verified by molecular docking simulations and dynamics simulations.Also,PC and TA showed the synergistic inhibition with orlistat.Fluorescence,UVvis and the thermodynamic analysis revealed that the complexes were formed from CEase and inhibitors by noncovalent interaction.As revealed by the circular dichroism results,both PC and TA decreased enzymatic activities by altering the conformations of CEase.The inhibition of PC and TA on CEase might be one mechanism for its cholesterol-lowering effect.

Growth Inhibition of Escherichia coli and Staphylococcus epidermidis from Various Types of Honey

Honey has long been considered a wound treatment used to keep cuts and other epidermal injuries clean. This study tested that claim by comparing manuka honey used in medicine today, local unprocessed honey taken straight from a hive, and pasteurized honey found at a store, on strains of E. coli and S. epidermidis. The study evaluated the effects these honeys had on bacterial growth to determine which had the greatest inhibition of bacterial growth. To determine this, plates streaked with strains of E. coli or S. epidermidis bacteria and agar wells filled with one of the honeys were incubated and subsequently the diameter of the zone of inhibition was measured. After 20 trials using each honey and bacteria type, manuka and unprocessed were shown to have a statistically significant advantage over the pasteurized honey at inhibiting the growth of E. coli and S. epidermidis, though it was variable whether manuka had an advantage over the unprocessed honey.

Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

Determination of total flavonoids content in buckwheat and inhibition of α-amylase activity

Diabetes is one of the most difficult chronic diseases to cure in the world,which seriously affects people’s health and quality of life.Flavonoids in buckwheat can regulate blood glucose levels by inhibitingα-amylase activity.Therefore,sweet buckwheat produced in Inner Mongolia was used as the research object,and buckwheat fl avonoids were extracted by ultrasonic-assisted extraction method.Total fl avonoids content was determined by ultraviolet-visible spectrophotometry.With acarbose as the positive control,the inhibition test ofα-amylase was carried out by DNS colorimetry to study the inhibition behavior of fl avonoids onα-amylase activity.The results showed that the extraction process of flavonoids was stable and reliable,and the established method for the determination of flavonoids was simple,accurate and reproducible.The total flavonoids content of buckwheat samples was 2.706 mg/g,buckwheat total fl avonoids extraction solution had an inhibitory eff ect onα-amylase,and its median inhibition concentration(IC_(50))was 38.53 mg/mL.The results of this experiment provide a technical reference for the development and utilization of fl avonoids in Inner Mongolia sweet buckwheat,and provide a theoretical reference for the development and application of flavonoid-rich hypoglycemic food.

Hydrogen inhibition effect of chitosan and sodium phosphate on ZK60 waste dust in a wet dust removal system:A feasible way to control hydrogen explosion

Wet dust removal systems used to control dust in the polishing or grinding process of Mg alloy products are frequently associated with potential hydrogen explosion caused by magnesium-water reaction.For purpose of avoiding hydrogen explosion risks,we try to use a combination of chitosan(CS)and sodium phosphate(SP)to inhibit the hydrogen evolution reaction between magnesium alloy waste dust and water.The hydrogen evolution curves and chemical kinetics modeling for ten different mixing ratios demonstrate that 0.4wt%CS+0.1wt%SP yields the best inhibition efficiency with hydrogen generation rate of almost zero.SEM and EDS analyses indicate that this composite inhibitor can create a uniform,smooth,tight protective film over the surface of the alloy dust particles.FTIR and XRD analysis of the chemical composition of the surface film show that this protective film contains CS and SP chemically adsorbed on the surface of ZK60 but no detectable Mg(OH)_(2),suggesting that magnesium-water reaction was totally blocked.Our new method offers a thorough solution to hydrogen explosion by inhibiting the hydrogen generation of magnesium alloy waste dust in a wet dust removal system.

Chemical Constituents of Pu-erh Tea and Its Inhibition Effect on α-amylase in vitro

[Objective]The aim was to clarify the chemical substance basis of hypoglycemic and lipid-lowering effects of Pu-erh Tea. [Method]Pu-erh Tea was extracted with 95% ethanol,followed by petroleum ether,chloroform,ethyl acetate and n-butanol extraction,after the further purification and through the NKA-9 macroporous resin and many times of Sephadex column chromatography,two compounds were isolated,in the same time,the effect of Uracil and Gallic acid on α-amylase was studied. [Result]The Uracil and Gallic acid were isolated and identified respectively from Pu-erh Tea and the Uracil was firstly isolated from Pu-erh Tea; Gallic acid had strong inhibition on α-amylase. [Conclusion]It could provide some theories on the hypoglycemic and lipid-lowering effects of Pu-erh Tea.

Effect of water content on corrosion inhibition behavior of self-assembled TDPA on aluminum alloy surface

Self assembled monolayers （SAMs） of 1-tetradecylphosphonic acids （TDPA, CH3（CH2）13P（O）（OH）2 ） were formed on the 2024 aluminum alloy surface in TDPA-containing ethanol-water solutions with different water content. The adsorption and corrosion protection properties of the SAMs for 2024 alloy in 0.1 mol/L H2SO4 solution were examined and characterized by potentiodynamic polarization, electrochemical impedance spectrum （EIS）, Fourier transformed infrared spectroscopy （FTIR）, Auger electron spectra （AES） and atomic force microscopy （AFM）. FTIR and AES results show that the TDPA molecules were successfully adsorbed on the 2024 aluminum alloy surface, and the density of the SAMs increased with the increasing water content in the assembly solution. The results of electrochemical studies and corrosion morphologies observed by AFM show that a 4 h modification resulted in maximal inhibition efficiency, and the higher the water content in the assembly solution is, the better the inhibition performance of the SAMs can be achieved. The effect of water content in TDPA solutions on the performance of the SAMs is related to the hydration reaction of the metal surface.

Influence Factors in the Inhibition Effect of Pyrazosulfuron-ethyl against Sagittaria pygmaea in Paddy Soils

[Objective] The aim was to explore the factors affecting the herbicidal activity of pyrazosulfuron-ethyl against Sagittaria pygmaea in paddy soil.[Method] The bioassay method was carried out under greenhouse conditions.[Result] The reduction of more than 80% in fresh weight was observed in S.pygmaea treated with 45 g/hm2 of pyrazosulfuron-ethyl for 7 d or more.Application of 60 g/hm2 at the sprouting stage of S.pygmaea suppressed completely the growth in fresh weight irrespective of tuber size.However,at 6 g/hm2 growth of the weed sustained less reduction with increasing tuber size.Differences in flooding water depth and temperature had no appreciable influence on the herbicidal activity.Growth inhibition of S.pygmaea by pre-emergence or 1.5-leaf stage applications under non-leaching conditions was significantly higher than that under water leaching conditions.Under non-leaching condition,there was no remarkable difference in this inhibition between preemergence and 1.5-leaf stage applications,while under water leaching conditions the growth reduction with the latter application was significantly larger.Growth inhibition of S.pygmaea planted at a depth of 2 cm was significantly higher than that planted deeper （5 cm） with the pre-emergence applications.[Conclusion] This study had provide basis for the further study on the inhibition effect of pyrazosulfuron-ethyl.

Inhibition Effect of Antagonistic Fungal Strain BOS-013 against the Pathogen of Rice Blast (Pyricularia oryzae)

[ ObjeeUve ] To search for the beneficial microorganisms and their metabolic products with control effect against rice Mast, the paper studied the inhibi- tion effect of the fermentation broth of actinomycetes BOS-013 strain against the pathogen of rice blast （Pyricularia oryzae）. [ Method ] With P. oryzae as the target indicator fungus, the inhibition effect of the fermentation broth of BOS-013 strain and its extracts from different solvents against the pathogen were determined using cylinder plate method and filter paper method. [ Result] The results showed that the inhibition rate of the fermentation broth of BOS-013 strain with fungus amount of 4×10^8 cfu/ml against P. oryzae was 92.0% ±0.5% ; the fermentation broth still had inhibition effect against P. oryaae after inactivation under high temperature and high pressure, and the inhibition rate was 60.0%±0.5%. After absorbed by non-polar CAD-45 type macroperous adsorption resin and eluted by 60% etha- nol, the antifungal activity of the fermentation broth was still high, and the diameter of inhibition zone reached 33.0 mm. [ Conclusion] The fermentation broth of BOS-O13 strain had significant inhibition effect against P. oryzae. The results would provide foundation for further clarification of inhibition mechanism of BOS-013 strain fermentation broth against P. oryzae and its practical application.

Inhibition Effect of Biocontrol Strain BS-315 against Alternaria mali

[Objective] The study aimed to study the antifungal activity of biocontrol strains against Alternaria mali,colonization ability in apple leaves and the impact of some chemical fungicides on biocontrol strains were also studied.[Method] Healthy leaves of Matsumotokin were collected to conduct vitro leaf test,colonization test and influence test of different fungicides on biocontrol strains.[Result] Vitro leaf test showed that B.subtilis BS-315 had strong inhibition effect on A.mali,when biocontrol strain was daubed on leaves,and pathogen was inoculated after 1 d,the inhibition effect of BS-315 against A.mali was over 90% after 3 d.BS-315 could colonize in leaves of Matsumotokin,colonization volume reached the maximum after inoculation for 3 d.Azoxystrobin and polyoxin had certain promoting effect on the growth of BS-315,while carbendazim and propiconazole completely inhibited the growth of BS-315.[Conclusion] This study would provide theoretical basis for development and rational utilization of biocontrol preparations.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.