Advances in the application of wearable sensors for gait analysis after total knee arthroplasty: a systematic review.

BACKGROUND: Wearable sensors have become a complementary means for evaluation of body function and gait in lower limb osteoarthritis. This study aimed to review the applications of wearable sensors for gait analysis after total knee arthroplasty (TKA). METHODS: Five databases, including Web of Science Core Collection, Embase, Cochrane, Medline, and PubMed, were searched for articles published between January 2010 and March 2023, using predetermined search terms that focused on wearable sensors, TKA, and gait analysis as broad areas of interest. RESULTS: A total of 25 articles were identified, involving 823 TKA patients. Methodologies varied widely across the articles, with inconsistencies found in reported patient characteristics, sensor data and experimental protocols. Patient-reported outcome measures (PROMs) and gait variables showed various recovery times from 1 week postoperatively to 5 years postoperatively. Gait analysis using wearable sensors and PROMs showed differences in controlled environments, daily life, and when comparing different surgeries. CONCLUSION: Wearable sensors offered the potential to remotely monitor the gait function post-TKA in both controlled environments and patients' daily life, and covered more aspects than PROMs. More cohort longitudinal studies are warranted to further confirm the benefits of this remote technology in clinical practice.

Crystal structure of Mycobacterium tuberculosis MenB, a key enzyme in vitamin K2 biosynthesis.

Bacterial enzymes of the menaquinone (Vitamin K2) pathway are potential drug targets because they lack human homologs. MenB, 1,4-dihydroxy-2-naphthoyl-CoA synthase, the fourth enzyme in the biosynthetic pathway leading from chorismate to menaquinone, catalyzes the conversion of O-succinylbenzoyl-CoA (OSB-CoA) to 1,4-dihydroxy-2-naphthoyl-CoA (DHNA-CoA). Based on our interest in developing novel tuberculosis chemotherapeutics, we have solved the structures of MenB from Mycobacterium tuberculosis and its complex with acetoacetyl-coenzyme A at 1.8 and 2.3 A resolution, respectively. Like other members of the crotonase superfamily, MenB folds as an (alpha3)2 hexamer, but its fold is distinct in that the C terminus crosses the trimer-trimer interface, forming a flexible part of the active site within the opposing trimer. The highly conserved active site of MenB contains a deep pocket lined by Asp-192, Tyr-287, and hydrophobic residues. Mutagenesis shows that Asp-192 and Tyr-287 are essential for enzymatic catalysis. We postulate a catalytic mechanism in which MenB enables proton transfer within the substrate to yield an oxyanion as the initial step in catalysis. Knowledge of the active site geometry and characterization of the catalytic mechanism of MenB will aid in identifying new inhibitors for this potential drug target.

Stereoselectivity of enoyl-CoA hydratase results from preferential activation of one of two bound substrate conformers.

Enoyl-CoA hydratase catalyzes the hydration of trans-2-crotonyl-CoA to 3(S)- and 3(R)-hydroxybutyryl-CoA with a stereoselectivity (3(S)/3(R)) of 400,000 to 1. Importantly, Raman spectroscopy reveals that both the s-cis and s-trans conformers of the substrate analog hexadienoyl-CoA are bound to the enzyme, but that only the s-cis conformer is polarized. This selective polarization is an example of ground state strain, indicating the existence of catalytically relevant ground state destabilization arising from the selective complementarity of the enzyme toward the transition state rather than the ground state. Consequently, the stereoselectivity of the enzyme-catalyzed reaction results from the selective activation of one of two bound substrate conformers rather than from selective binding of a single conformer. These findings have important implications for inhibitor design and the role of ground state interactions in enzyme catalysis.

Effect of mutagenesis on the stereochemistry of enoyl-CoA hydratase.

Enoyl-CoA hydratase catalyzes the hydration of trans-2-crotonyl-CoA to 3(S)-HB-CoA, 3(S)-hydroxybutyryl-CoA with a stereospecificity (k(S)/k(R)) of 400000 to 1 [Wu, W. J., Feng, Y., He, X., Hofstein, H. S., Raleigh, D. P., and Tonge, P. J. (2000) J. Am. Chem. Soc. 122, 3987-3994]. Replacement of E164, one of the catalytic glutamates in the active site, with either aspartate or glutamine reduces the rate of formation of the 3(S) product enantiomer (k(S)) without affecting the rate of formation of the 3(R) product (k(R)). Consequently, k(S)/k(R) is 1000 and 0.33 for E164D and E164Q, respectively. In contrast, mutagenesis of E144, the second catalytic glutamate, reduces the rate of formation of both product enantiomers. Thus, only E144 is required for the formation of 3(R)-HB-CoA, 3(R)-hydroxybutyryl-CoA. Modeling studies together with analysis of alpha-proton exchange rates and experiments with crotonyl-oxyCoA, a substrate analogue in which the alpha-proton acidity has been reduced 10000-fold, support a mechanism of 3(R)-hydroxybutyryl-CoA formation that involves the E144-catalyzed stepwise addition of water to crotonyl-CoA which is bound in an s-trans conformation in the active site. Finally, we also demonstrate that hydrogen bonds in the oxyanion hole, provided by the backbone amide groups of G141 and A98, are important for the formation of both product enantiomers.