The thesis summarizes bell hooks' stand and viewpoints as expressed in her book Outlaw Culture:Resisting Representations.In this collection,hooks argues that the outlaw culture,a culture of the marginalized groups...The thesis summarizes bell hooks' stand and viewpoints as expressed in her book Outlaw Culture:Resisting Representations.In this collection,hooks argues that the outlaw culture,a culture of the marginalized groups including black people and women,is either distorted or misinterpreted by the mainstream culture which is a white supremacist patriarchal one.Therefore,she calls for a resistance against the mainstream culture's misrepresentations of the outlaw culture.展开更多
Although there exist a few good schemes to protect the kernel hooks of operating systems, attackers are still able to circumvent existing defense mechanisms with spurious context infonmtion. To address this challenge,...Although there exist a few good schemes to protect the kernel hooks of operating systems, attackers are still able to circumvent existing defense mechanisms with spurious context infonmtion. To address this challenge, this paper proposes a framework, called HooklMA, to detect compromised kernel hooks by using hardware debugging features. The key contribution of the work is that context information is captured from hardware instead of from relatively vulnerable kernel data. Using commodity hardware, a proof-of-concept pro- totype system of HooklMA has been developed. This prototype handles 3 082 dynamic control-flow transfers with related hooks in the kernel space. Experiments show that HooklMA is capable of detecting compomised kernel hooks caused by kernel rootkits. Performance evaluations with UnixBench indicate that runtirre overhead introduced by HooklMA is about 21.5%.展开更多
Kernel hooks are very important con- trol data in OS kernel. Once these data are com- promised by attackers, they can change the control flow of OS kemel＇s execution. Previ- ous solutions suffer from limitations in t...Kernel hooks are very important con- trol data in OS kernel. Once these data are com- promised by attackers, they can change the control flow of OS kemel＇s execution. Previ- ous solutions suffer from limitations in that： 1） some methods require modifying the source code of OS kernel and kernel modules, which is less practical for wide deployment; 2） other methods cannot well protect the kernel hooks and function return addresses inside kernel mo- dules whose memory locations cannot be pre- determined. To address these problems, we propose OPKH, an on-the-fly hook protection system based on the virtualization technology. Compared with previous solutions, OPKH off- ers the protected OS a fully transparent envi- ronment and an easy deployment. In general, the working procedure of OPKH can be di- vided into two steps. First, we utilise the me- mory virtualization for offiine profiling so that the dynamic hooks can be identified. Second, we exploit the online patching technique to in- strument the hooks for run-time protection. The experiments show that our system can pro- tect the dynamic hooks effectively with mini- mal performance overhead.展开更多
BACKGROUND Hook of hamate fractures occur either due to repetitive stress from gripping sports(e.g.,golf,tennis,and baseball),leading to fatigue fracture,or as a result of trauma from falls or other injuries.The recom...BACKGROUND Hook of hamate fractures occur either due to repetitive stress from gripping sports(e.g.,golf,tennis,and baseball),leading to fatigue fracture,or as a result of trauma from falls or other injuries.The recommended treatment involves the excision of bone fragments to facilitate athletes’early return to sports;excision surgery is also performed in trauma cases.However,some patients prefer nonsurgical treatment options,and conservative treatment should be considered.AIM To present a case series of 16 patients conservatively treated for hook of hamate fractures.METHODS This study included 16(11 males and 5 females;right side,6 cases;left side,10)patients who desired conservative treatment and could be followed-up until bone union was achieved.The average age of the patients was 49.6(range:24-72)years.The average time from injury to consultation was 4.3(range:0.2-21.4)weeks.The treatment involved 4 weeks of casting from the forearm to the metacarpophalangeal joint,followed by 8 weeks of splint fixation of the wrist.Follow-up computed tomography scans were performed every 4 weeks.RESULTS Bone union was achieved in all patients.The average duration of casting was 3.7(range:0-5)weeks and that of splint fixation thereafter was 8.6(range:0-28)weeks.The patients did not exhibit joint contractures or range of motion restrictions due to prolonged immobilization.CONCLUSION Conservative treatment with external fixation may be an option for hook of hamate fractures.展开更多
BACKGROUND Clavicle fractures are a common type of fracture that often occurs after high-energy trauma.The treatment methods for clavicle fractures remain controversial.Both locking compression and hook plates are rec...BACKGROUND Clavicle fractures are a common type of fracture that often occurs after high-energy trauma.The treatment methods for clavicle fractures remain controversial.Both locking compression and hook plates are recommended.CASE SUMMARY A 44-year-old male suffered an injury during skiing.Radiography revealed a right-sided distal clavicular fracture.The fracture was treated using a hook plate due to its small size.During the surgical procedure,Kirschner wires were used to drill holes in the acromion.The end of the hook plate was inserted into the hole rather than below the edge of the acromion.CONCLUSION One year later,imaging revealed complete healing of the fracture,and the hook plate was removed.The patient was satisfied with the course and treatment results.Additionally,a new classification system was proposed based on the degree of injury to the distal clavicle joint surface.The incidence of postoperative complications associated with the use of hook plates for clavicular fracture treatment is relatively high.Complications can be reduced by changing the hook plate placement.展开更多
This editorial critically evaluates the landmark study by Tanaka and Yoshii,which demonstrated a 100%union rate with conservative management of hamate hook fractures,challenging the historical preference for surgical ...This editorial critically evaluates the landmark study by Tanaka and Yoshii,which demonstrated a 100%union rate with conservative management of hamate hook fractures,challenging the historical preference for surgical intervention.In contrast to Scheufle et al’s report of 90%-100%failure rates with early surgical approaches,Tanaka and Yoshii’s protocol achieved universal healing despite delayed diagnoses in 25%of cases.Central to this success is the systematic inte-gration of high-resolution computed tomography for early diagnosis and dynamic monitoring of trabecular bone regeneration,significantly reducing missed dia-gnoses and guiding personalized immobilization timelines.The patient-centered strategy—allowing temporary splint removal during low-risk activities—balanced fracture stability with joint mobility preservation,avoiding post-treatment stiff-ness.However,limitations such as small sample size(n=16),selection bias,and insufficient long-term functional data(e.g.,grip strength,return-to-sport metrics)underscore the need for comparative trials.Emerging trends,including adjunct therapies like low-intensity pulsed ultrasound and biologics(e.g.,teriparatide),are proposed to accelerate healing while minimizing immobilization risks.This work redefines conservative fracture management paradigms,emphasizing in-novation without compromising efficacy.Overall,this assessment deepens our understanding of the conservative management of hook fractures and provides evidence-based insights for improved clinical decision-making.展开更多
The hook formation mechanism in continuously cast slabs of ultra-low carbon steel was analyzed in detail through numerical calculations and experimental observations using optical microscopy,and its distribution chara...The hook formation mechanism in continuously cast slabs of ultra-low carbon steel was analyzed in detail through numerical calculations and experimental observations using optical microscopy,and its distribution characteristics were determined.Numerical simulations confirmed that the freezing–overflow mechanism is the primary cause of hook formation.They also revealed that the freezing event occurs unpredictably,while the overflow event takes place during the positive strip time.The average pitch of oscillation marks(OMs)on the slab surface was 8.693 mm,while the theoretical pitch was 8.889 mm,with a difference of approximately 2%.This discrepancy primarily results from varying degrees of overflow,which affects the morphology of the OMs and the positions of their deepest points.Notably,this result further confirmed that the freezing and overflow in the meniscus were indeed caused by the periodic oscillation of the mold.Higher superheat hindered hook formation,leading to a negative correlation between the hook depth distribution around the slab and the temperature distribution within the mold.Therefore,the depth of the corner hook was greater than that of other positions,which was caused by the intensified cooling effect of the corner.Moreover,key factors influencing hook development were analyzed,providing insights into transient fluid flow and heat transfer characteristics within the mold.Transient fluid flow and heat transfer contributed to the randomness and tendency of hook formation.This randomness was reflected in the varying angles of the hooks,whereas the tendency was evident in the negative correlation between superheat and hook length.Based on the randomness and tendency of hook formation and its profile characteristics,a new method for controlling hook depth based on“sine law”is proposed.展开更多
During the continuous casting process of low carbon steel,the solidified hook formed in the mold has great effects on the surface quality of the cast slab.Some factory experiments have been conducted to investigate th...During the continuous casting process of low carbon steel,the solidified hook formed in the mold has great effects on the surface quality of the cast slab.Some factory experiments have been conducted to investigate the microscopic characteristics and reveal the influence of process parameters on solidified hooks.The depth of the hooks showed a positive correlation with the deflection angle,length,and oscillation mark(OM)depth,which indicates that the OM depth can serve as an approximate indicator for evaluating the depth of the solidified hooks.On the wide and narrow faces of the cast slab,the depth of the solidified hooks and the temperature distribution in the mold show opposite trends,with lower depths of solidified hooks at positions with higher temperatures.In addition,the influence of process parameters on solidified hooks was analyzed.With the increase in superheat,not only the depth of solidified hooks gradually decreases,but also the ratio of depression-typed marks increases.Increasing casting speed and decreasing immersion depth of the submerged entry nozzle will both lead to a decrease in the depth of the solidified hook.展开更多
According to the boot process of modern computer systems,whoever boots first will gain control first.Taking advantage of this feature,a malicious code called bootkit can hijack the control before the OS bootloader and...According to the boot process of modern computer systems,whoever boots first will gain control first.Taking advantage of this feature,a malicious code called bootkit can hijack the control before the OS bootloader and bypass security mechanisms in boot process.That makes bootkits difficult to detect or clean up thoroughly.With the improvement of security mechanisms and the emergence of UEFI,the attack and defense techniques for bootkits have constantly been evolving.We first introduce two boot modes of modern computer systems and present an attack model of bootkits by some sophistical samples.Then we discuss some classic attack techniques used by bootkits from their initial appearance to the present on two axes,including boot mode axis and attack phase axis.Next,we evaluate the race to the bottom of the system and the evolution process between bootkits and security mechanisms.At last,we present the possible future direction for bootkits in the context of continuous improvement of OS and firmware security mechanisms.展开更多
Soft grippers have great potential applications in daily life,since they can compliantly grasp soft and delicate objects.However,the highly elastic fingers of most soft grippers are prone to separate from each other w...Soft grippers have great potential applications in daily life,since they can compliantly grasp soft and delicate objects.However,the highly elastic fingers of most soft grippers are prone to separate from each other while grasping objects due to their low stiffness,thus reducing the grasping stability and load-bearing capacity.To tackle this problem,inspired from the venus flytrap plant,this work proposes a mutual-hook mechanism to restrain the separation and improve the grasping performance of soft fingers.The novel soft gripper design consists of three modules,a soft finger-cot,two Soft Hook Actuators(SHAs)and two sliding mechanisms.Here,the soft finger-cot covers on the soft finger,increasing the contact area with the target object,two SHAs are fixed to the left and right sides of the finger-cot,and the sliding mechanisms are designed to make SHAs stretch flexibly.Experiments demonstrate that the proposed design can restrain the separation of soft fingers substantially,and the soft fingers with the finger-cots can grasp objects three times heavier than the soft fingers without the proposed design.The proposed design can provide invaluable insights for soft fingers to restrain the separation while grasping,thus improving the grasping stability and the load-bearing capacity.展开更多
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 detect...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.展开更多
文摘The thesis summarizes bell hooks' stand and viewpoints as expressed in her book Outlaw Culture:Resisting Representations.In this collection,hooks argues that the outlaw culture,a culture of the marginalized groups including black people and women,is either distorted or misinterpreted by the mainstream culture which is a white supremacist patriarchal one.Therefore,she calls for a resistance against the mainstream culture's misrepresentations of the outlaw culture.
基金The authors would like to thank the anonymous reviewers for their insightful corrnlents that have helped improve the presentation of this paper. The work was supported partially by the National Natural Science Foundation of China under Grants No. 61070192, No.91018008, No. 61170240 the National High-Tech Research Development Program of China under Grant No. 2007AA01ZA14 the Natural Science Foundation of Beijing un- der Grant No. 4122041.
文摘Although there exist a few good schemes to protect the kernel hooks of operating systems, attackers are still able to circumvent existing defense mechanisms with spurious context infonmtion. To address this challenge, this paper proposes a framework, called HooklMA, to detect compromised kernel hooks by using hardware debugging features. The key contribution of the work is that context information is captured from hardware instead of from relatively vulnerable kernel data. Using commodity hardware, a proof-of-concept pro- totype system of HooklMA has been developed. This prototype handles 3 082 dynamic control-flow transfers with related hooks in the kernel space. Experiments show that HooklMA is capable of detecting compomised kernel hooks caused by kernel rootkits. Performance evaluations with UnixBench indicate that runtirre overhead introduced by HooklMA is about 21.5%.
基金supported in part by the National High Technology Research and Development Program of China(863 Program)under Grant No.2009AA01Z433the Project of National Ministry under Grant No.A21201-10006the Open Foundation of State Key Laboratory of Information Security(Institute of Information Engineering,Chinese Academy of Sciences)under Grant No.2013-4-1
文摘Kernel hooks are very important con- trol data in OS kernel. Once these data are com- promised by attackers, they can change the control flow of OS kemel＇s execution. Previ- ous solutions suffer from limitations in that： 1） some methods require modifying the source code of OS kernel and kernel modules, which is less practical for wide deployment; 2） other methods cannot well protect the kernel hooks and function return addresses inside kernel mo- dules whose memory locations cannot be pre- determined. To address these problems, we propose OPKH, an on-the-fly hook protection system based on the virtualization technology. Compared with previous solutions, OPKH off- ers the protected OS a fully transparent envi- ronment and an easy deployment. In general, the working procedure of OPKH can be di- vided into two steps. First, we utilise the me- mory virtualization for offiine profiling so that the dynamic hooks can be identified. Second, we exploit the online patching technique to in- strument the hooks for run-time protection. The experiments show that our system can pro- tect the dynamic hooks effectively with mini- mal performance overhead.
文摘BACKGROUND Hook of hamate fractures occur either due to repetitive stress from gripping sports(e.g.,golf,tennis,and baseball),leading to fatigue fracture,or as a result of trauma from falls or other injuries.The recommended treatment involves the excision of bone fragments to facilitate athletes’early return to sports;excision surgery is also performed in trauma cases.However,some patients prefer nonsurgical treatment options,and conservative treatment should be considered.AIM To present a case series of 16 patients conservatively treated for hook of hamate fractures.METHODS This study included 16(11 males and 5 females;right side,6 cases;left side,10)patients who desired conservative treatment and could be followed-up until bone union was achieved.The average age of the patients was 49.6(range:24-72)years.The average time from injury to consultation was 4.3(range:0.2-21.4)weeks.The treatment involved 4 weeks of casting from the forearm to the metacarpophalangeal joint,followed by 8 weeks of splint fixation of the wrist.Follow-up computed tomography scans were performed every 4 weeks.RESULTS Bone union was achieved in all patients.The average duration of casting was 3.7(range:0-5)weeks and that of splint fixation thereafter was 8.6(range:0-28)weeks.The patients did not exhibit joint contractures or range of motion restrictions due to prolonged immobilization.CONCLUSION Conservative treatment with external fixation may be an option for hook of hamate fractures.
文摘BACKGROUND Clavicle fractures are a common type of fracture that often occurs after high-energy trauma.The treatment methods for clavicle fractures remain controversial.Both locking compression and hook plates are recommended.CASE SUMMARY A 44-year-old male suffered an injury during skiing.Radiography revealed a right-sided distal clavicular fracture.The fracture was treated using a hook plate due to its small size.During the surgical procedure,Kirschner wires were used to drill holes in the acromion.The end of the hook plate was inserted into the hole rather than below the edge of the acromion.CONCLUSION One year later,imaging revealed complete healing of the fracture,and the hook plate was removed.The patient was satisfied with the course and treatment results.Additionally,a new classification system was proposed based on the degree of injury to the distal clavicle joint surface.The incidence of postoperative complications associated with the use of hook plates for clavicular fracture treatment is relatively high.Complications can be reduced by changing the hook plate placement.
文摘This editorial critically evaluates the landmark study by Tanaka and Yoshii,which demonstrated a 100%union rate with conservative management of hamate hook fractures,challenging the historical preference for surgical intervention.In contrast to Scheufle et al’s report of 90%-100%failure rates with early surgical approaches,Tanaka and Yoshii’s protocol achieved universal healing despite delayed diagnoses in 25%of cases.Central to this success is the systematic inte-gration of high-resolution computed tomography for early diagnosis and dynamic monitoring of trabecular bone regeneration,significantly reducing missed dia-gnoses and guiding personalized immobilization timelines.The patient-centered strategy—allowing temporary splint removal during low-risk activities—balanced fracture stability with joint mobility preservation,avoiding post-treatment stiff-ness.However,limitations such as small sample size(n=16),selection bias,and insufficient long-term functional data(e.g.,grip strength,return-to-sport metrics)underscore the need for comparative trials.Emerging trends,including adjunct therapies like low-intensity pulsed ultrasound and biologics(e.g.,teriparatide),are proposed to accelerate healing while minimizing immobilization risks.This work redefines conservative fracture management paradigms,emphasizing in-novation without compromising efficacy.Overall,this assessment deepens our understanding of the conservative management of hook fractures and provides evidence-based insights for improved clinical decision-making.
基金financially supported by the National Natural Science Foundation of China(No.52174306)the Fundamental Research Funds for the Central Universities(Nos.N2225023 and N2425006)the Basic Research Projects of Liaoning Provincial Department of Education(No.LJ212410148027)。
文摘The hook formation mechanism in continuously cast slabs of ultra-low carbon steel was analyzed in detail through numerical calculations and experimental observations using optical microscopy,and its distribution characteristics were determined.Numerical simulations confirmed that the freezing–overflow mechanism is the primary cause of hook formation.They also revealed that the freezing event occurs unpredictably,while the overflow event takes place during the positive strip time.The average pitch of oscillation marks(OMs)on the slab surface was 8.693 mm,while the theoretical pitch was 8.889 mm,with a difference of approximately 2%.This discrepancy primarily results from varying degrees of overflow,which affects the morphology of the OMs and the positions of their deepest points.Notably,this result further confirmed that the freezing and overflow in the meniscus were indeed caused by the periodic oscillation of the mold.Higher superheat hindered hook formation,leading to a negative correlation between the hook depth distribution around the slab and the temperature distribution within the mold.Therefore,the depth of the corner hook was greater than that of other positions,which was caused by the intensified cooling effect of the corner.Moreover,key factors influencing hook development were analyzed,providing insights into transient fluid flow and heat transfer characteristics within the mold.Transient fluid flow and heat transfer contributed to the randomness and tendency of hook formation.This randomness was reflected in the varying angles of the hooks,whereas the tendency was evident in the negative correlation between superheat and hook length.Based on the randomness and tendency of hook formation and its profile characteristics,a new method for controlling hook depth based on“sine law”is proposed.
基金the financial support of National Key Research and Development Plan(No.2021YFB3702000)National Natural Science of China(Nos.52074076,52174306 and U20A20272)Fundamental Research Funds for the Central Universities(Nos.N2225023 and N2425006).Author information。
文摘During the continuous casting process of low carbon steel,the solidified hook formed in the mold has great effects on the surface quality of the cast slab.Some factory experiments have been conducted to investigate the microscopic characteristics and reveal the influence of process parameters on solidified hooks.The depth of the hooks showed a positive correlation with the deflection angle,length,and oscillation mark(OM)depth,which indicates that the OM depth can serve as an approximate indicator for evaluating the depth of the solidified hooks.On the wide and narrow faces of the cast slab,the depth of the solidified hooks and the temperature distribution in the mold show opposite trends,with lower depths of solidified hooks at positions with higher temperatures.In addition,the influence of process parameters on solidified hooks was analyzed.With the increase in superheat,not only the depth of solidified hooks gradually decreases,but also the ratio of depression-typed marks increases.Increasing casting speed and decreasing immersion depth of the submerged entry nozzle will both lead to a decrease in the depth of the solidified hook.
基金supported by NSFC under Grant 62172308,Grant U1626107,Grant 61972297 and Grant 62172144。
文摘According to the boot process of modern computer systems,whoever boots first will gain control first.Taking advantage of this feature,a malicious code called bootkit can hijack the control before the OS bootloader and bypass security mechanisms in boot process.That makes bootkits difficult to detect or clean up thoroughly.With the improvement of security mechanisms and the emergence of UEFI,the attack and defense techniques for bootkits have constantly been evolving.We first introduce two boot modes of modern computer systems and present an attack model of bootkits by some sophistical samples.Then we discuss some classic attack techniques used by bootkits from their initial appearance to the present on two axes,including boot mode axis and attack phase axis.Next,we evaluate the race to the bottom of the system and the evolution process between bootkits and security mechanisms.At last,we present the possible future direction for bootkits in the context of continuous improvement of OS and firmware security mechanisms.
基金funded by the National Natural Science Foundation of China under Grant 62073305 and the Natural Science Foundation of Hubei Province under Grant 2022CFA041.
文摘Soft grippers have great potential applications in daily life,since they can compliantly grasp soft and delicate objects.However,the highly elastic fingers of most soft grippers are prone to separate from each other while grasping objects due to their low stiffness,thus reducing the grasping stability and load-bearing capacity.To tackle this problem,inspired from the venus flytrap plant,this work proposes a mutual-hook mechanism to restrain the separation and improve the grasping performance of soft fingers.The novel soft gripper design consists of three modules,a soft finger-cot,two Soft Hook Actuators(SHAs)and two sliding mechanisms.Here,the soft finger-cot covers on the soft finger,increasing the contact area with the target object,two SHAs are fixed to the left and right sides of the finger-cot,and the sliding mechanisms are designed to make SHAs stretch flexibly.Experiments demonstrate that the proposed design can restrain the separation of soft fingers substantially,and the soft fingers with the finger-cots can grasp objects three times heavier than the soft fingers without the proposed design.The proposed design can provide invaluable insights for soft fingers to restrain the separation while grasping,thus improving the grasping stability and the load-bearing capacity.
文摘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.
