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BACKGROUND: Neuroarthropathy of the knee or Charcot knee, leading to chronic joint destruction, is a rare disease that is difficult to diagnose. The treatment of this condition is difficult and controversial. CASE PRESENTATION: A 74-year-old Asian woman has had bilateral knee pain for 22 years and deformity for 10 years, which has been aggravating for 2 months. Physical examination showed bilateral knee varus deformity greater than 15°, and -20 to 90° range of motion. X-ray revealed bilateral varus deformity with massive free body hyperplasia. Combined with medical history as syringomyelia, the patient was diagnosed with bilateral Charcot knees and bilateral joint replacements were performed using Legacy Constrained Condylar Knee prostheses (LCCK; Zimmer, USA). The patient reported satisfactory treatment outcomes, pain relief, and improved range of motion in both knees, without postoperative complications or prosthesis loosening at 2 year after operation. CONCLUSIONS: Total knee arthroplasty (TKA) may be considered a viable option for treating the Charcot knee. The use of constrained condylar prostheses can produce satisfactory results. Attention should be given to survival risks, complications, and other potential determining factors associated with TKA when devising a treatment strategy for the Charcot knee.

OBJECTIVE: Musculoskeletal pain is the most prominent clinical manifestation of more than 150 musculoskeletal disease conditions, and its effective long-term management poses a great challenge to healthcare systems globally. For this, it is important to understand current research progress on musculoskeletal pain management. The purpose of the present study is to provide a comprehensive insight into the current state of research and global trends in musculoskeletal pain management. METHODS: Publications on musculoskeletal pain management from 1972 to 2021 were retrieved from the Science Citation Index-Expanded (SCIE) database. Included articles were any article type related to aspects of musculoskeletal pain management, including etiology, mechanisms, epidemiology, treatment, outcomes, side effects, and patient compliance. Publication data were analyzed using bibliometric methods. The software VOSviewer was employed to perform bibliographic coupling, co-authorship, co-citation, and co-occurrence analysis, and to visualize publication tendencies in musculoskeletal pain management. RESULTS: A total of 5475 articles were included in this study. The number of global publications on musculoskeletal pain management has escalated annually. Based on the number of publications and citations from the published literature, as well as the H-index, the United States led global contributions in this area. The institutions making the highest contributions were the League of European Research Universities (LERU), the University of Sydney, and Harvard University. The journal BMC Musculoskeletal Disorders published the highest number of articles in this area. The published studies fall under six groups: "Prevention and rehabilitation," "Etiology and diagnosis," "Clinical study," "Epidemiology," "Mental health," and "Education." High-quality primary studies and epidemiology are predicted to be the next prevailing topics in this field of research. CONCLUSIONS: Based on current global trends, the number of publications on musculoskeletal pain management will continue to increase. Future studies will likely place more emphasis on high-quality randomized controlled trials (RCTs) and epidemiological studies.

AIM: To provide a systematic analysis of the study design in knee osteoarthritis (OA) preclinical studies, focusing on the characteristics of animal models and cell doses, and to compare these to the characteristics of clinical trials using mesenchymal stem cells (MSCs) for the treatment of knee OA. METHOD: A systematic and comprehensive search was conducted using the PubMed, Web of Science, Ovid, and Embase electronic databases for research papers published in 2009-2020 on testing MSC treatment in OA animal models. The PubMed database and ClinicalTrials.gov website were used to search for published studies reporting clinical trials of MSC therapy for knee OA. RESULTS: In total, 9234 articles and two additional records were retrieved, of which 120 studies comprising preclinical and clinical studies were included for analysis. Among the preclinical studies, rats were the most commonly used species for modeling knee OA, and anterior cruciate ligament transection was the most commonly used method for inducing OA. There was a correlation between the cell dose and body weight of the animal. In clinical trials, there was large variation in the dose of MSCs used to treat knee OA, ranging from 1 × 106 to 200 × 106 cells with an average of 37.91 × 106 cells. CONCLUSION: Mesenchymal stem cells have shown great potential in improving pain relief and tissue protection in both preclinical and clinical studies of knee OA. Further high-quality preclinical and clinical studies are needed to explore the dose effectiveness relationship of MSC therapy and to translate the findings from preclinical studies to humans.

OBJECTIVE: Prosthetic joint infection (PJI) is the main reason of failure of total joint arthroplasty (TJA). This study aimed to investigate the global trends and network visualization in research of PJI. METHODS: Publications in PJI search during 1980-2022 were extracted from the Science Citation Index-Expanded of Web of Science Core Collection database (WoSCC). The source data was investigated and analyzed by bibliometric methodology. For network visualization, VOS viewer and R software was used to perform bibliographic coupling, co-citation, co-authorship and co-occurrence analysis and to predict the publication trends in PJI research. RESULTS: There were 7288 articles included. The number of publications and relative research interests increased gradually per year globally. The USA made the highest contributions in the world and with the highest H-index and the most citations. Journal of Arthroplasty published the highest number of articles in this area. The Mayo Clinic, Thomas Jefferson University (Rothman Institute), Hospital Special Surgery and the Rush University were the most contributive institutions by network visualization. Included studies were divided into four clusters: bacterial pathogenic mechanism and antibacterial drugs study, TJA complications, risk factors and epidemiology of PJI, diagnosis of PJI, and revision surgical management. More articles in PJI could be published over the next few years. CONCLUSION: The number of publications about PJI will be increasing dramatically based on the global trends and network visualization. The USA made the highest contributions in PJI. Diagnosis and revision management may be the next hot spots in this field.

N-heterocyclic carbenes (NHCs) have become attractive ligands for functionalizing gold nanoparticle surfaces with applications ranging from catalysis to biomedicine. Despite their great potential, NHC stabilized gold colloids (NHC@AuNPs) are still scarcely explored and further efforts should be conducted to improve their design and functionalization. Here, the 'bottom-up' synthesis of two water-soluble gold nanoparticles (AuNP-1 and AuNP-2) stabilized by hydrophilic mono- and bidentate NHC ligands is reported together with their characterization by various spectroscopic and analytical methods. The NPs showed key differences likely to be due to the selected NHC ligand systems. Transmission electron microscopy (TEM) images showed small quasi-spherical and faceted NHC@AuNPs of similar particle size (ca. 2.3-2.6 nm) and narrow particle size distribution, but the colloids featured different ratios of Au(I)/Au(0) by X-ray photoelectron spectroscopy (XPS). Furthermore, the NHC@AuNPs were supported on titania and fully characterized. The new NPs were studied for their catalytic activity towards the reduction of nitrophenol substrates, the reduction of resazurin and for their photothermal efficiency. Initial results on their application in photothermal therapy (PTT) were obtained in human cancer cells in vitro. The aforementioned reactions represent important model reactions towards wastewater remediation, bioorthogonal transformations and cancer treatment.

High yield and large scale synthesis are highly demanded for the studies of gold nanoclusters. We developed a "cluster from cluster" approach to assemble gold nanoclusters with preformed atomically precise Au 13 precursors. This facile approach has proved to be very effective in the synthesis of the well-known magic cluster [Au 25 (SR) 18 ] - , which could prepare the target cluster in high yield (overall yield up to ~100%) at large scale (gram-scale based on gold). This method can be applied in the synthesis of 10 Au 25 clusters with different R groups. This work presents an important approach that may be extended to high yield and large scale synthesis of other metal nanoclusters.

Anions have been used to regulate the structures and luminescence of heterometallic clusters. Introducing ClO

Aim Mesenchymal stem cell (MSC)-based therapy is being explored in treating osteoarthritis (OA). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are least reported. In this study, we investigated the effects of single intra-articular injections of hUC-MSCs on a rat OA model. Method hUC-MSCs were isolated from the Wharton's jelly of the human umbilical cord and identified. Eighteen Sprague-Dawley rats were used for the OA model. All rats were divided into 3 groups: hyaluronic acid (HA)+MSCs (n = 6), HA (n = 6), and control group (n = 6). One by 106 hUC-MSCs in 100 μL HA, 100 μL HA or 100 μL saline were injected into the knee joint 4 weeks post-surgery as a single dose. Cartilage degeneration was evaluated at 6 and 12 weeks after treatment with macroscopic examination, micro-computed tomography analysis, behavioral analysis, and histology. Results At 6 weeks, the HA + MSCs group had a significantly better International Cartilage Repair Society score in the femoral condyle compared to the HA and control groups. Histological analysis also showed more proteoglycan and less cartilage loss, with lower modified Mankin score in the HA + MSCs group. However, at 12 weeks there were no significant differences between groups from macroscopic examination and histological analysis. Subchondral bone sclerosis of the medial femoral condyle and behavioral tests showed no significant differences between groups at 6 and 12 weeks. Conclusion These findings indicate that single injection of hUC-MSCs can have temporary effects on decelerating the progression of cartilage degeneration in OA rats, but may not inhibit OA progression in the long-term.

By directly reducing alkynyl-silver precursors, we successfully obtained a large alkynyl-protected silver nanocluster, (C7 H17 ClN)3 [Ag112 Cl6 (C≡CAr)51 ], which is hitherto the largest structurally characterized silver nanocluster in the alkynyl family. The cluster exhibits four concentric core-shell structures (Ag13 @Ag42 @Ag48 @Ag9 ), and four types of alkynyl-silver binding modes are observed. Chloride was found to be critical for the stabilization and formation of the silver nanocluster. The release of chloride ions in situ from CH2 Cl2 solvent has been confirmed by mass spectrometry. This study suggests that the combination of alkynyl and halide ligands will pave a new way for the synthesis of large silver nanoclusters.

Pseudomonas aeruginosa biofilm formation is a primary cause of chronic infections. This has been a highly active area of research over the past two decades due to causing high mortality risks in immunocompromised patients. This study evaluates global trends in the dynamic and rapidly evolving field of P. aeruginosa biofilm research through bibliometric and visualized analyses. Publications from 1994 to 2018 on P. aeruginosa biofilm research were retrieved from Web of Science, Scopus, and PubMed, and their bibliometric data were systematically studied. The VOSviewer software was used to conduct global analyses of bibliographic coupling, coauthorship, cocitation, and co‐occurrence. A total of 9,527 publications were included in this study. The overall number of publications and research interest in the field displayed a strongly rising trend. The USA made the greatest contributions to the field, with the highest h‐index and number of citations compared with other countries, while Denmark had the highest average citation per publication. The Journal of Bacteriology had the highest number of publications in the field, while the University of Copenhagen was the institution with the highest contribution influence. Co‐occurrence network maps revealed that the most prominent topics in P. aeruginosa biofilm research were mechanistic studies, in vitro/in vivo studies, and biofilm formation studies. Pseudomonas aeruginosa biofilms constitute a dynamic research area in microbiology with increasing global research interest. Future studies will likely focus on investigating the mechanisms of biofilm formation to solve infection‐associated clinical problems., Pseudomonas aeruginosa biofilm formation is a primary cause of chronic infections and has been a highly active area of research over the past two decades. This study evaluates global trends in the dynamic and rapidly evolving field of P. aeruginosa biofilm research through bibliometric and visualized analyses.

An alkynyl-protected gold nanocluster, Au22 (t BuC≡C)18 (1), has been synthesized and its structure has been determined by single-crystal X-ray diffraction. The molecular structure consists of a Au13 cuboctahedron kernel and three [Au3 (t BuC≡C)4 ] trimeric staples. The cluster 1 has strong luminescence in the solid state with a 15 % quantum yield, and it displays interesting thermochromic luminescence as revealed by temperature-dependent emission spectra. The enhanced room-temperature emission is characterized as thermally activated delayed fluorescence.

We report the structures, stability and catalysis properties of two Ag

Two homoleptic alkynyl-protected gold clusters with compositions of Na[Au25 (C≡CAr)18 ] and (Ph4 P)[Au25 (C≡CAr)18 ] (Na⋅1 and Ph4 P⋅1, Ar=3,5-bis(trifluoromethyl)phenyl) were synthesized via a direct reduction method. 1 is a magic cluster analogous to [Au25 (SR)18 ]- in terms of electron counts and metal-to-ligand ratio. Single-crystal structure analysis reveals that 1 has an identical Au13 kernel to [Au25 (SR)18 ]- , but adopts a distinctly different arrangement of the six peripheral dimer staple motifs. The steric hindrance of alkynyl ligands is responsible for the D3 arrangement of Au25 . The introduction of alkynyl also significantly changes the optical absorption features of the nanocluster as supported by DFT calculations. This magic cluster confirms that there is a similar but quite different parallel alkynyl-protected metal cluster universe in comparison to the thiolated one.

Total structure determination of a ligand-protected gold nanocluster, Au144 , has been successfully carried out. The composition of title nanocluster is Au144 (C≡CAr)60 (1; Ar=2-FC6 H4 -). The cluster 1 exhibits a quasi-spherical Russian doll-like architecture, comprising a Au54 two-shelled Mackay icosahedron (Au12 @Au42 ), which is further enclosed by a Au60 anti-Mackay icosahedral shell. The Au114 kernel is enwrapped by thirty linear ArC≡C-Au-C≡CAr staple motifs. The absorption spectrum of 1 shows two bands at 560 and 620 nm. This spectrum is distinctly different from that of thiolated Au144 , which was predicted to have an almost identical metal kernel and very similar ligands arrangement in 1. These facts indicate the molecule-like behavior of 1 and significant involvement of ligands in the electronic structure of 1. The cluster 1 is hitherto the largest coinage metal nanocluster with atomically precise molecular structure in the alkynyl family. The work not only addresses the concern of structural information of Au144 , which had been long-pursued, but also provides an interesting example showing ligand effects on the optical properties of ligand protected metal nanoclusters.

Achieving adequate healing in large or load-bearing bone defects is highly challenging even with surgical intervention. The clinical standard of repairing bone defects using autografts or allografts has many drawbacks. A bioactive ceramic scaffold, strontium-hardystonite-gahnite or "Sr-HT-Gahnite" (a multi-component, calcium silicate-based ceramic) is developed, which when 3D-printed combines high strength with outstanding bone regeneration ability. In this study, the performance of purely synthetic, 3D-printed Sr-HT-Gahnite scaffolds is assessed in repairing large and load-bearing bone defects. The scaffolds are implanted into critical-sized segmental defects in sheep tibia for 3 and 12 months, with bone autografts used for comparison. The scaffolds induce substantial bone formation and defect bridging after 12 months, as indicated by X-ray, micro-computed tomography, and histological and biomechanical analyses. Detailed analysis of the bone-scaffold interface using focused ion beam scanning electron microscopy and multiphoton microscopy shows scaffold degradation and maturation of the newly formed bone. In silico modeling of strain energy distribution in the scaffolds reveal the importance of surgical fixation and mechanical loading on long-term bone regeneration. The clinical application of 3D-printed Sr-HT-Gahnite scaffolds as a synthetic bone substitute can potentially improve the repair of challenging bone defects and overcome the limitations of bone graft transplantation.

DYRK1A is characterized by the early development and regulation of neuronal proliferation, and its over expression gives rise to neurological abnormalities. As the promising DYRK1A inhibitors, the binding mechanism between DYRK1A and pyrido[2,3-d]pyrimidines derivatives at molecular level are still veiled. In this article, it was achieved to get the structural insights into pyrido[2,3-d]pyrimidines derivatives as DYRK1A inhibitors by means of comprehensive computational approaches involving molecular docking, molecular dynamics simulation, free energy calculation, and energy decomposition analysis. The calculated energy values were highly consistent with the experimental activities. Based on the individual energy terms analysis, the van der Waals interaction was the major leading force in the DYRK1A-ligand interaction. Lys188 was the important residue that formed the hydrogen bond, which improved the inhibitory activity. Furthermore, four novel inhibitors with higher predicted activity were designed based on the obtained findings and confirmed by molecular simulations. Our study is expected to provide significant drug design strategy for the development of more promising DYRK1A inhibitors. (C) 2016 Wiley Periodicals, Inc.

Extensive bone loss due to trauma or disease leads to impaired healing. Current bone grafts and substitutes have major drawbacks that limit their effectiveness for treating large bone defects. A number of bone substitutes in development are undergoing preclinical testing, but few studies specifically investigate the in vivo material-tissue interactions that provide an important indicator to long-term implant safety and efficacy. This study is the first of its kind to specifically investigate in vivo material-tissue interactions at the bone-implant interface. Baghdadite scaffolds implanted in critical-sized segmental defects in sheep tibia for 26 weeks are analyzed by focused ion beam scanning electron microscopy, multiphoton microscopy, and histology. The scaffolds are seen to induce extensive bone formation that directly abut the implant surfaces with no evidence of chronic inflammation or fibrous capsule formation. Bone remodeling is influenced by slow in vivo degradation around and within the implant, causing portions of the implant to be incorporated into the newly formed bone. These findings have important implications for predicting the long-term effects of baghdadite ceramics in promoting defect healing, and support the translation of baghdadite scaffolds as a new generation of bone graft substitutes with improved properties for the repair of large bone defects.