Crystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms

N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalyticN-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 Å resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing a binding site for the allosteric activator, L-arginine, and an N-terminal proline-rich motif that is likely to function in signal transduction to CPS1. Crystalline hNAT forms a dimer similar to the NAT-NAT dimers that form in crystals of bifunctional N-acetylglutamate synthase/kinase (NAGS/K) from Maricaulis maris and also exists as a dimer in solution. The structure of the NAG binding site, in combination with mutagenesis studies, provide insights into the catalytic mechanism. We also show that native NAGS from human and mouse exists in tetrameric form, similar to those of bifunctional NAGS/K

Posterior ankle arthroscopic treatment of a talar chondroblastoma with allograft and a platelet-rich plasma-fibrin glue: A case report and literature review

Talar chondroblastoma, which is a benign tumor of immature cartilage cells, is an uncommon but easily missed diagnosis of foot pain. Arthroscopic treatment for this condition is a safe, powerful, and promising technique with definitive advantages of visualization and minimal invasion. Here, we report a case of a talar chondroblastoma treated by posterior ankle arthroscopic curettage, allograft bone graft, and platelet-rich plasma-fibrin glue (PRP-FG) application.Level of evidenceCase Report. Level IV

A Novel N-Acetylglutamate Synthase Architecture Revealed by the Crystal Structure of the Bifunctional Enzyme from Maricaulis maris

Novel bifunctional N-acetylglutamate synthase/kinases (NAGS/K) that catalyze the first two steps of arginine biosynthesis and are homologous to vertebrate N-acetylglutamate synthase (NAGS), an essential cofactor-producing enzyme in the urea cycle, were identified in Maricaulis maris and several other bacteria. Arginine is an allosteric inhibitor of NAGS but not NAGK activity. The crystal structure of M. maris NAGS/K (mmNAGS/K) at 2.7 Å resolution indicates that it is a tetramer, in contrast to the hexameric structure of Neisseria gonorrhoeae NAGS. The quaternary structure of crystalline NAGS/K from Xanthomonas campestris (xcNAGS/K) is similar, and cross-linking experiments indicate that both mmNAGS/K and xcNAGS are tetramers in solution. Each subunit has an amino acid kinase (AAK) domain, which is likely responsible for N-acetylglutamate kinase (NAGK) activity and has a putative arginine binding site, and an N-acetyltransferase (NAT) domain that contains the putative NAGS active site. These structures and sequence comparisons suggest that the linker residue 291 may determine whether arginine acts as an allosteric inhibitor or activator in homologous enzymes in microorganisms and vertebrates. In addition, the angle of rotation between AAK and NAT domains varies among crystal forms and subunits within the tetramer. A rotation of 26° is sufficient to close the predicted AcCoA binding site, thus reducing enzymatic activity. Since mmNAGS/K has the highest degree of sequence homology to vertebrate NAGS of NAGS and NAGK enzymes whose structures have been determined, the mmNAGS/K structure was used to develop a structural model of human NAGS that is fully consistent with the functional effects of the 14 missense mutations that were identified in NAGS-deficient patients

First metatarsal single-screw minimally invasive chevron-akin osteotomy: A cost effective and clinically reliable technique

PurposeThe common disease hallux valgus results in foot discomfort and dysfunction. Less soft tissue damage and faster wound healing have made minimally invasive surgery (MIS) more popular. However, little research has compared the fixation results of minimally invasive chevron-akin (MICA) osteotomy thus far. In this study, the clinical and radiographic results of MICA with first metatarsal single- or dual-screw fixation are being examined.MethodsA total of 107 feet of 103 patients with mild to moderate symptomatic hallux valgus treated MICA from January 2018 to June 2020 were retrospective evaluated, with at least 12-months follow-up. 51 patients underwent single-screw fixation procedures and 52 patients received dual-screw fixation procedures. Patients were assessed preoperatively and at the final follow-up with radiographic measurements [hallux valgus angle (HVA), intermetatarsal angle (IMA) and distal metatarsal articular angle (DMAA)] and clinical scores (american orthopaedic foot and ankle society (AOFAS) forefoot score, visual analog scale (VAS) and Manchester-Oxford Foot Questionnaire (MOxFQ) scores). The coughlin satisfaction scores were also obtained.ResultsBoth groups showed significantly improved HVA, IMA and DMAA at the final follow-up (P < 0.001). Regarding clinical outcomes, the AOFAS, VAS and MOxFQ in two categories also significantly improved postoperatively (P < 0.001). There was no obvious difference in the clinical and radiographic outcomes between the two groups (HVA, P = 0.833; IMA, P = 0.073; DMAA, P = 0.35; AOFAS, P = 0.48; VAS, P = 0.86; MOxFQ, P = 0.87). However, the single-screw fixation group showed significantly lower operation time and less number of intraoperative fluoroscopy (P < 0.001). No serious complications were observed in either group. The single-screw fixation technique saves at least $1,086 compared with the dual-screw group.ConclusionAt the final follow-up, both the single- and dual-screw fixation groups had comparable good to excellent clinical and radiographic outcomes, as well as a similar incidence of complications. Additionally, the single-screw fixation group reduces overall surgical costs, number of intraoperative fluoroscopy and operational time

Promoted Photocharge Separation in 2D Lateral Epitaxial Heterostructure for Visible‐Light‐Driven CO2 Photoreduction

Photocarrier recombination remains a big barrier for the improvement of solar energy conversion efficiency. For 2D materials, construction of heterostructures represents an efficient strategy to promote photoexcited carrier separation via an internal electric field at the heterointerface. However, due to the difficulty in seeking two components with suitable crystal lattice mismatch, most of the current 2D heterostructures are vertical heterostructures and the exploration of 2D lateral heterostructures is scarce and limited. Here, lateral epitaxial heterostructures of BiOCl @ Bi2O3 at the atomic level are fabricated via sonicating‐assisted etching of Cl in BiOCl. This unique lateral heterostructure expedites photoexcited charge separation and transportation through the internal electric field induced by chemical bonding at the lateral interface. As a result, the lateral BiOCl @ Bi2O3 heterostructure demonstrates superior CO2 photoreduction properties with a CO yield rate of about 30 µmol g−1 h−1 under visible light illumination. The strategy to fabricate lateral epitaxial heterostructures in this work is expected to provide inspiration for preparing other 2D lateral heterostructures used in optoelectronic devices, energy conversion, and storage fields

Application of mixed reality technology in talocalcaneal coalition resection

ObjectivesWith positive outcomes recorded, the mixed reality (MR) technology has lately become popular in orthopedic surgery. However, there are few studies that specifically address the utility of MR in talocalcaneal coalitions (TCC) resection. Our goal in this retrospective study is to assess certain data while examining the viability of using MR to treat TCC resection.MethodsSix consecutive patients with TCC diagnosed by computed tomography (CT) for which nonoperative therapy had failed and MR system assisted TCC resection were included in this study from March 2021 to December 2021. The feasibility and accuracy of TCC resection were assessed by post-operation radiography. The American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and visual analog scale (VAS) score were used to assess the recovery condition and pain level pre- and post-operation.ResultsThe surgeon can accurately resect the TCC according to the preoperatively determined range by superimposing the holographic model with the actual anatomy of the TCC using an MR system. Additionally, no additional x-ray was necessary while operating. Mean follow-up was 10.3 months, with a minimum of 6 months. There is a significant difference between the preoperative AOFAS score of 53.4 ± 3.8 and the 6-month follow-up AOFAS score of 97.3 ± 2.2 (p < 0.05). There is also a significant difference between the preoperative VAS score of 8.1 ± 0.7 and the 6-month follow-up VAS score of 1.7 ± 0.4 (p < 0.05). All individuals had clinical subtalar mobility without stiffness following surgery.ConclusionWhile the TCC resection operation is being performed, the application of MR technology is practicable, effective, and radiation-free, giving surgeons satisfactory support

Robot-assisted percutaneous screw fixation in the treatment of navicular fracture

BackgroundLong recovery time, large scar, postoperative swelling and pain are possible side effects of open reduction internal fixation (ORIF) for tarsal navicular fractures. Early exercise instruction is made possible by the use of an intraoperative robot-assisted percutaneous invasive closed reduction internal fixation. The goal of the trial was to determine whether percutaneous screw internal fixation with robot assistance might be used to treat navicular fractures.Methods27 patients with navicular fractures had surgical treatment between June 2019 and December 2021. Of those, 20 instances were treated with ORIF, while 7 cases had robot-assisted percutaneous screw internal fixation. At the final follow-up, the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score and the visual analogue scale (VAS) score were compared to determine outcomes and function.ResultsFollow-up was obtained in all 27 patients after surgery, with a mean follow-up time of 21.81 months, ranging from 15 to 29 months . In the 7 instances of robot-assisted group, percutaneous guide wire insertion and screw placement only needed one attempt and the depth and position of the implant were both satisfactory. In the ORIF group, there were two patients who sustained cutaneous nerve injuries. The AOFAS score and the VAS score of the group receiving robot-assisted navigation percutaneous screw fixation were 92.25 ± 2.22 and 0.75 ± 0.25 respectively at the last follow-up, while 82.25 ± 7.15 and 0.50 ± 0.29 were the respective values for the ORIF group.ConclusionIntraoperative robot-assisted percutaneous closed reduction internal fixation for tarsal navicular fractures can accomplish exact localization of fracture site, reduce soft tissue damage and operative time. According to current view, this method offers fewer complications, a faster recovery after surgery, and more patient satisfaction

Lateral approach for insertional Achilles tendinitis with Haglund deformity

ObjectiveThe study aims to investigate the functional outcome of the lateral approach for insertional Achilles tendinitis (IAT) with Haglund deformity.MethodsFrom January 2016 to September 2019, 14 cases of IAT with Haglund deformity that resisted conservative treatment received surgery in our department. A lateral approach was used to debride the bony and soft tissue and reattach the insertion of the Achilles tendon. The Visual Analog Scale (VAS), American Orthopedic Foot and Ankle Score (AOFAS), and Victorian Institute of Sport Tendon Study Group-Achilles Tendinopathy score (VISA-A) were used to evaluate clinical outcomes.ResultThe mean patient age was 39.57 years at the time of surgery. The mean follow-up was 14.74 months. The mean VAS score significantly decreased from 4.86 ± 0.86 preoperatively to 1.21 ± 1.58 postoperatively (P < 0.001). The mean AOFAS score significantly improved from 66.64 ± 6.23 preoperatively to 90.21 ± 11.50 postoperatively (P < 0.001). The mean preoperative and the last follow-up VISA-A were 66 (range 56.75–69.25) and 86 (range 75.75–97.00) points, respectively (P < 0.05).ConclusionThe lateral approach was effective and safe for IAT with Haglund deformity. Moreover, the mid-term functional outcome was promising.Level of Clinical EvidenceI

Target density effects on charge tansfer of laser-accelerated carbon ions in dense plasma

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft X-ray regime. We used the tri-cellulose acetate (C$_{9}$H$_{16}$O$_{8}$) foam of 2 mg/cm$^{-3}$ density, and $1$-mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. The plasma parameters were diagnosed to be T$_{e}$=17 eV and n$_{e}$=4 $\times$ 10$^{20}$ cm$^{-3}$. The average charge states passing through the plasma were observed to be higher than those predicted by the commonly-used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. In previsous measurement with partially ionized plasma from gas discharge and z-pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we were able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-Glass laser radiation. The finding is important for heavy ion beam driven high energy density physics and fast ignitions.Comment: 7 pages, 4 figures, 35 conference