Mechanistic Investigation into Single-Electron Oxidative Addition of Single-Atom Cu(I)-N4 Site: Revealing the Cu(I)-Cu(II)-Cu(I) Catalytic Cycle in Photochemical Hydrophosphinylation.

Understanding the valency and structural variations of metal centers during reactions is important for mechanistic studies of single-atom catalysis, which could be beneficial for optimizing reactions and designing new protocols. Herein, we precisely developed a single-atom Cu(I)-N4 site catalyst via a photoinduced ligand exchange (PILE) strategy. The low-valent and electron-rich copper species could catalyze hydrophosphinylation via a novel single-electron oxidative addition (OA) pathway under light irradiation, which could considerably decrease the energy barrier compared with the well-known hydrogen atom transfer (HAT) and single electron transfer (SET) processes. The Cu(I)-Cu(II)-Cu(I) catalytic cycle, via single-electron oxidative addition and photoreduction, has been proven by multiple in situ or operando techniques. This catalytic system demonstrates high efficiency and requires room temperature conditions and no additives, which improves the turnover frequency (TOF) to 1507 h-1. In particular, this unique mechanism has broken through the substrate limitation and shows a broad scope for different electronic effects of alkenes and alkynes.

Preclinical Pharmacology Characterization of Sovleplenib (HMPL-523), an Orally Available Syk Inhibitor.

Spleen tyrosine kinase (Syk) is an intracellular tyrosine kinase involved in the signal transduction in immune cells mainly. Its aberrant regulation is associated with diversified allergic disorders, autoimmune diseases and B cell malignancies. Therefore, inhibition of Syk is considered a reasonable approach to treat autoimmune/inflammatory diseases and B cell malignancies. Here we described the preclinical characterization of sovleplenib, a novel, highly potent and selective, oral Syk inhibitor, in several rodent autoimmune disease models. Sovleplenib potently inhibited Syk activity in a recombinant enzymatic assay and Syk-dependent cellular functions in various immune cell lines and human whole blood in vitro. Furthermore, sovleplenib, by oral administration, demonstrated strong in vivo efficacies in murine models of immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and chronic graft-versus-host disease (cGVHD), and a rat model of collagen induced arthritis (CIA) respectively, in a dose-dependent manner. Collectively, these results clearly supported sovleplenib as a therapeutic agent in the treatment of autoimmune diseases. Sovleplenib is being globally developed for ITP (Phase III, NCT05029635, Phase Ib/II, NCT03951623), wAIHA (Phase II/III, NCT05535933) and B-cell lymphoma (Phase I, NCT02857998, NCT03779113). SIGNIFICANCE STATEMENT: Syk is a key mediator of signaling pathways downstream of a wide array of receptors important for immune functions, including the B cell receptor, immunoglobulin receptors bearing Fc receptors. Inhibition of Syk could provide a novel therapeutic approach for autoimmune diseases and hematologic malignancies. The manuscript describes the preclinical pharmacology characterization of sovleplenib, a novel Syk inhibitor, in enzymatic and cellular assays in vitro and several murine autoimmune disease models in vivo.

Ultrastable PLGA-Coated 177Lu-Microspheres for Radioembolization Therapy of Hepatocellular Carcinoma.

Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.

Multifunctional Hydrogel Enhances Inflammatory Control, Antimicrobial Activity, and Oxygenation to Promote Healing in Infectious Wounds.

Chronic infected wounds often fail to heal through normal repair mechanisms, and the persistent response of reactive oxygen species (ROS) and inflammation is a major contributing factor to the difficulty in their healing. In this context, we developed an ROS-responsive injectable hydrogel. This hydrogel is composed of ε-polylysine grafted (EPL) with caffeic acid (CA) and hyaluronic acid (HA) grafted with phenylboronic acid (PBA). Before the gelation process, a mixture CaO2@Cur-PDA (CCP) consisting of calcium peroxide (CaO2) coated with polydopamine (PDA) and curcumin (Cur) is embedded into the hydrogel. Under the conditions of chronic refractory wound environments, the hydrogel gradually dissociates. HA mimics the function of the extracellular matrix, while the released caffeic acid-grafted ε-polylysine (CE) effectively eliminates bacteria in the wound vicinity. Additionally, released CA also clears ROS and influences macrophage polarization. Subsequently, CCP further decomposes, releasing Cur, which promotes angiogenesis. This multifunctional hydrogel accelerates the repair of diabetic skin wounds infected with Staphylococcus aureus in vivo and holds promise as a candidate dressing for the healing of chronic refractory wounds.

Identification of angiogenesis-related subtypes, the development of a prognosis model, and features of tumor microenvironment in colon cancer.

Angiogenesis is associated with tumor progression, prognosis, and treatment effect. However, the angiogenesis' underlying mechanisms in the tumor microenvironment (TME) still remain unclear. Understanding the dynamic interactions between angiogenesis and TME in colon adenocarcinoma (COAD) is necessary. We downloaded the transcriptome data and corresponding clinical data of colon cancer patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. We identified two distinct angiogenesis-related molecular subtypes (subtype A and subtype B) and assessed the clinical features, prognosis, and infiltrating immune cells of patients in the two subtypes. According to the prognostic differential genes, we defined two different gene clusters to further explore the correlation between angiogenesis and tumor heterogeneity. Then, we construct the prognostic risk scoring model angiogenesis-related gene (ARG-score) including seven genes (ARMCX2, latent transforming growth factor ß binding protein 1, ADAM8, FABP4, CCL11, CXCL11, ITLN1) using Lasso-multivariate cox method. We analyzed the correlation between ARG-score and prognosis, clinicopathological features, TME, molecular feature, cancer stem cells (CSCs), and microsatellite instability (MSI) status. To assess the application value of ARG-score in clinical treatment, immunophenotype score was used to predict patients' immunotherapy response in colon cancer. We found the mutations of ARGs in TCGA-COAD dataset from genetic levels and discussed their expression patterns based on TCGA and GEO datasets. We observed important differences in clinicopathological features, prognosis, immune feature, molecular feature between the two molecular subgroups. Then, we established an ARG-score for predicting OS and validated its predictive capability. A high ARG-score characterized by higher transcription level of ARGs, suggested lower MSI-high (MSI-H), lower immune score, and worse clinical stage and survival outcome. Additionally, the ARG-score was remarkably related to the CSCs index and immunotherapy sensitivity. We found two new molecular subtypes and two gene clusters based on ARGs and established an ARG-score. Multilayered analysis revealed that ARGs were remarkably correlated to the heterogeneity of colon cancer patients and explained the process of tumorigenesis and progression better. The ARG-score can help us better assess patients' survival outcomes and provide guidance for individualized treatment.

Programmable DNA Hydrogel Provides Suitable Microenvironment for Enhancing TSPCS Therapy in Healing of Tendinopathy.

Tendon stem/progenitor cells (TSPCs) therapy is a promising strategy for enhancing cell matrix and collagen synthesis, and regulating the metabolism of the tendon microenvironment during tendon injury repair. Nevertheless, the barren microenvironment and gliding shear of tendon cause insufficient nutrition supply, damage, and aggregation of injected TSPCs around tendon tissues, which severely hinders their clinical application in tendinopathy. In this study, a TSPCs delivery system is developed by encapsulating TSPCs within a DNA hydrogel (TSPCs-Gel) as the DNA hydrogel offers an excellent artificial extracellular matrix (ECM) microenvironment by providing nutrition for proliferation and protection against shear forces. This delivery method restricts TSPCs to the tendons, significantly extending their retention time. It is also found that TSPCs-Gel injections can promote the healing of rat tendinopathy in vivo, where cross-sectional area and load to failure of injured tendons in rats are significantly improved compared to the free TSPCs treatment group at 8 weeks. Furthermore, the potential healing mechanism of TSPCs-Gel is investigated by RNA-sequencing to identify a series of potential gene and signaling pathway targets for further clinical treatment strategies. These findings suggest the potential pathways of using DNA hydrogels as artificial ECMs to promote cell proliferation and protect TSPCs in TSPC therapy.

Predictors of and predictive nomogram for cut-out of proximal femur nail anti-rotation device in intertrochanteric fractures.

PURPOSE: This study determined independent predictors and developed a predictive nomogram for failed correction of intertrochanteric fractures due to cut-out of the proximal femur nail anti-rotation (PFNA) device. METHODS: Demographic and radiological data of 592 adult patients with intertrochanteric fractures (AO 31A) treated by PFNA were collected retrospectively. Independent predictors of cut-out were obtained through univariate and multivariate analyses, and a predictive nomogram was established. The discrimination, calibration, and clinical utility of the nomogram were based on receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis, respectively. RESULTS: Overall, 18 (3.04%) cases of cut-out occurred. Independent predictors according to the multivariate analysis were body mass index (BMI), poor-to-acceptable quality of reduction, PFNA blade position, and tip-apex distance (TAD). AUC of the nomogram was 0.849, and C-index was 0.849 (95% CI [0.844-0.854]). Bootstrapping yielded a corrected C-index of 0.849. The calibration and decision curves indicated good agreement and clinical benefit of the nomogram. CONCLUSION: A reliable predictive nomogram was developed for cut-out of the PFNA in intertrochanteric fractures, based on BMI, quality of reduction, blade position, and TAD.

A Renal-Clearable Activatable Molecular Probe for Fluoro-Photacoustic and Radioactive Imaging of Cancer Biomarkers.

In vivo simultaneous visualization of multiple biomarkers is critical to accurately diagnose disease and decipher fundamental processes at a certain pathological evolution, which however is rarely exploited. Herein, a multimodal activatable imaging probe (P-125 I) is reported with activatable fluoro-photoacoustic and radioactive signal for in vivo imaging of biomarkers (i.e., hepsin and prostate-specific membrane antigen (PSMA)) associated with prostate cancer diagnosis and prognosis. P-125 I contains a near-infrared (NIR) dye that is caged with a hepsin-cleavable peptide sequence and linked with a radiolabeled PSMA-targeted ligand (PSMAL). After systemic administration, P-125 I actively targets the tumor site via specific recognition between PSMA and PSMAL moiety and in-situ generates of activated fluoro-photoacoustic signal after reacting with hepsin to release the free dye (uncaged state). P-125 I achieves precisely early detection of prostate cancer and renal clearance to alleviate toxicity issues. In addition, the accumulated radioactive and activated photoacoustic signal of probe correlates well with the respective expression level of PSMA and hepsin, which provides valuable foreseeability for cancer progression and prognosis. Thus, this study presents a multimodal activatable probe for early detection and in-depth deciphering of prostate cancer.

Uncovering potential genes in colorectal cancer based on integrated and DNA methylation analysis in the gene expression omnibus database.

BACKGROUND: Colorectal cancer (CRC) is major cancer-related death. The aim of this study was to identify differentially expressed and differentially methylated genes, contributing to explore the molecular mechanism of CRC. METHODS: Firstly, the data of gene transcriptome and genome-wide DNA methylation expression were downloaded from the Gene Expression Omnibus database. Secondly, functional analysis of differentially expressed and differentially methylated genes was performed, followed by protein-protein interaction (PPI) analysis. Thirdly, the Cancer Genome Atlas (TCGA) dataset and in vitro experiment was used to validate the expression of selected differentially expressed and differentially methylated genes. Finally, diagnosis and prognosis analysis of selected differentially expressed and differentially methylated genes was performed. RESULTS: Up to 1958 differentially expressed (1025 up-regulated and 993 down-regulated) genes and 858 differentially methylated (800 hypermethylated and 58 hypomethylated) genes were identified. Interestingly, some genes, such as GFRA2 and MDFI, were differentially expressed-methylated genes. Purine metabolism (involved IMPDH1), cell adhesion molecules and PI3K-Akt signaling pathway were significantly enriched signaling pathways. GFRA2, FOXQ1, CDH3, CLDN1, SCGN, BEST4, CXCL12, CA7, SHMT2, TRIP13, MDFI and IMPDH1 had a diagnostic value for CRC. In addition, BEST4, SHMT2 and TRIP13 were significantly associated with patients' survival. CONCLUSIONS: The identified altered genes may be involved in tumorigenesis of CRC. In addition, BEST4, SHMT2 and TRIP13 may be considered as diagnosis and prognostic biomarkers for CRC patients.

Prognostic significance of frailty in older patients with hip fracture: a systematic review and meta-analysis.

PURPOSE: Hip fracture (HF) has become a major healthcare concern associated with higher mortality in older patients. Frailty is one of the most important problems in aging population but its prognostic value in HF remains susceptible. This systematic review and meta-analysis aimed to evaluate the association between frailty and adverse outcomes in older patients with HF. METHODS: We systematically searched electrical databases including PubMed and Embase to find eligible literature with end-search restriction of February 20, 2021. The main endpoints were all-cause mortality, peri-operative complications, abnormal discharge, and length of stay (LOS). Pooled effect size was calculated by random-effects or fixed-effect model according to study heterogeneity. Three subgroup analyses based on follow-up times, study design, and frailty criteria were conducted. RESULTS: We screened 22 studies out of 1599 identified studies in our analysis. Compared with normal patients, frail ones had a higher risk of mortality both before (OR = 3.48, 95% CI: 2.50-4.85, I2 = 87.2%, P < 0.001) and after (OR = 1.87, 95% CI: 1.44-2.44, I2 = 85.5%, P < 0.001) adjustment. The incidence of peri-operative complications, abnormal discharge, and prolonged LOS also significantly increased in frail subjects. There was no publication bias observed and the pooled results were stable based on sensitivity analysis. CONCLUSION: Overall, more attention needs to be paid to the prognostic effects caused by frailty in seniors with HF. Better understanding of the association between frailty and adverse outcomes in HF could help doctors perform co-management across orthopaedic and geriatric departments.

A minimally invasive periacetabular osteotomy improves the radiographic parameters and functional outcomes in the treatment of developmental dysplasia of the hip in adolescents and adults: surgical technique and early results.

PURPOSE: To introduce West China Hospital periacetabular osteotomy (WCH PAO) for acetabular dysplasia in adolescent and young adult patients and evaluate the early clinical results of WCH PAO. METHODS: A retrospective analysis of 34 patients with developmental dysplasia of the hip was performed from October 2019 to April 2021. Baseline data with surgical time and perioperative blood-loss volume were retrieved from medical record systems. The lateral center-to-edge angle (LCEA), acetabular inclination (AI), hip disability and osteoarthritis outcome score (HOOS), University of California Los Angeles (UCLA), and modified Harris hip score (mHHS) were compared preoperatively and postoperatively. RESULTS: All patients had significant postoperative radiology improvements, including LCEA and AI. The LCEA was improved from 12.9 to 33.2°, and the AI was decreased from 27.2 to 8.5°. In addition, hip functional outcomes, including HOOS, UCLA and mHHS, were improved. The UCLA was improved from 3.9 to 6.3, and the HOOS was decreased from 71.0 to 10.5. The Harris hip score improved from 50.8 before surgery to 87.4 after surgery. The mean operative time was 155 min (range 120 to 190 min), and the mean intra-operative blood loss was 580.2 ± 285.5 ml. Furthermore, no major complications, including nerve injury or bone nonunion, occurred in the cohort study. CONCLUSION: WCH PAO is a minimally invasive surgical method for acetabular dysplasia in adolescent and young adult patients who that simplifies the surgical procedure and decreases the incidence of complications related to osteotomy.

The Role of Intrathecal Morphine for Postoperative Analgesia in Primary Total Joint Arthroplasty under Spinal Anesthesia: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the efficacy and safety of intrathecal morphine (ITM) for postoperative analgesia in primary total joint arthroplasty (TJA) under spinal anesthesia and to explore the dose-response relationship for analgesic efficacy or risk of side effects. METHODS: We searched MEDLINE, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov for any studies meeting the inclusion criteria. All the data were summarized using the random effects model. Subgroup analyses were performed based on the surgical procedure and dose of ITM. Meta-regression was used to explore the dose-response relationship. RESULTS: Eighteen randomized controlled trials were included. Compared with the placebo or blank control, ITM reduced the postoperative 24-h morphine consumption by 10.07 mg and prolonged the duration of analgesia. However, ITM significantly increased the risk of pruritus by 2.79 fold, with a tendency to increase the risk of postoperative nausea and/or vomiting (P = 0.08). No difference was observed regarding the length of stay (LOS) and incidence of respiratory depression or urinary retention. Furthermore, meta-regression showed a linear dose-response relationship for the postoperative 24-h morphine consumption but no linear dose-response relationship for the risk of side effects. CONCLUSIONS: Adding morphine to intrathecal anesthetics provides a prolonged and robust analgesic effect without significantly increasing the risk of side effects other than pruritus. Although we found a linear dose-response relationship for the postoperative 24-h morphine consumption, the optimal dose of ITM remains to be further explored in high-quality RCTs with a large sample size.

Semiconducting polymer nano-radiopharmaceutical for combined radio-photothermal therapy of pancreatic tumor.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. RESULTS: We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope 177Lu (177Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. 177Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), 177Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, 177Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. CONCLUSION: Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects.

Impact of tourniquet on short-term outcomes in opening wedge high tibial osteotomy with modern tranexamic acid protocols: a retrospective cohort study.

BACKGROUND: The use of a tourniquet during high tibial osteotomy (HTO) is a routine procedure, but there is currently no research on the benefits and potential risks of tourniquet use during HTO. The aim of this study was to investigate the impact of tourniquet on perioperative blood loss, early functional recovery and complications in opening wedge HTO with modern tranexamic acid protocols. METHODS: This was a retrospective cohort study of patients who underwent unilateral opening wedge HTO between January 2019 and September 2020. All patients were divided into two groups according to whether a tourniquet was applied during HTO. Patients in both groups received the same surgical procedures, tranexamic acid protocols and other perioperative treatments. Preoperative baseline data, intraoperative data, early postoperative recovery and all complications during the 3-month follow-up were collected and compared between the two groups. RESULTS: A total of 62 patients were enrolled in this study, including 32 in the tourniquet group and 30 in the non-tourniquet group. There was no significant difference in preoperative baseline data between the two groups (P > 0.05 in all). Intraoperative blood loss in the tourniquet group was significantly lower than that in the non-tourniquet group (80.22 ml versus 94.00 ml, P < 0.001), but there was no difference in total blood loss (187.39 ml versus 193.31 ml, P = 0.714). And no patient in either group required blood transfusion. In terms of early postoperative recovery, tourniquet use significantly increased pain scores and reduced knee range of motion on the first and second postoperative days, but there was no significant difference between the two groups at postoperative third day and third month. Furthermore, there was no significant difference between the two groups in terms of lower limb force line correction, length of stay, Knee Society Score or the incidence of complications during the 3-month follow-up (P > 0.05 in all). CONCLUSIONS: In opening wedge HTO with modern tranexamic acid protocols, not using a tourniquet does not increase perioperative total blood loss or the risk of complications, but facilitates early postoperative recovery by reducing pain and increasing range of motion.

Predicting venous thromboembolism in hospitalized trauma patients: a combination of the Caprini score and data-driven machine learning model.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of hospitalized trauma patients and has an adverse impact on patient outcomes. However, there is still a lack of appropriate tools for effectively predicting VTE for trauma patients. We try to verify the accuracy of the Caprini score for predicting VTE in trauma patients, and further improve the prediction through machine learning algorithms. METHODS: We retrospectively reviewed emergency trauma patients who were admitted to a trauma center in a tertiary hospital from September 2019 to March 2020. The data in the patient's electronic health record (EHR) and the Caprini score were extracted, combined with multiple feature screening methods and the random forest (RF) algorithm to constructs the VTE prediction model, and compares the prediction performance of (1) using only Caprini score; (2) using EHR data to build a machine learning model; (3) using EHR data and Caprini score to build a machine learning model. True Positive Rate (TPR), False Positive Rate (FPR), Area Under Curve (AUC), accuracy, and precision were reported. RESULTS: The Caprini score shows a good VTE prediction effect on the trauma hospitalized population when the cut-off point is 11 (TPR = 0.667, FPR = 0.227, AUC = 0.773), The best prediction model is LASSO+RF model combined with Caprini Score and other five features extracted from EHR data (TPR = 0.757, FPR = 0.290, AUC = 0.799). CONCLUSION: The Caprini score has good VTE prediction performance in trauma patients, and the use of machine learning methods can further improve the prediction performance.

Nanoagents Based on Poly(ethylene glycol)-b-Poly(l-thyroxine) Block Copolypeptide for Enhanced Dual-Modality Imaging and Targeted Tumor Radiotherapy.

Future healthcare requires development of novel theranostic agents that are capable of not only enhancing diagnosis and monitoring therapeutic responses but also augmenting therapeutic outcomes. Here, a versatile and stable nanoagent is reported based on poly(ethylene glycol)-b-poly(l-thyroxine) (PEG-PThy) block copolypeptide for enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual-modality imaging and targeted tumor radiotherapy in vivo. PEG-PThy acquired by polymerization of l-thyroxine-N-carboxyanhydride (Thy-NCA) displays a controlled Mn , high iodine content of ≈49.2 wt%, and can spontaneously form 65 nm-sized nanoparticles (PThyN). In contrast to clinically used contrast agents like iohexol and iodixanol, PThyN reveals iso-osmolality, low viscosity, and long circulation time. While PThyN exhibits comparable in vitro CT attenuation efficacy to iohexol, it greatly enhances in vivo CT imaging of vascular systems and soft tissues. PThyN allows for surface decoration with the cRGD peptide achieving enhanced CT imaging of subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. Taking advantages of a facile iodine exchange reaction, 125 I-labeled PThyN enables SPECT/CT imaging of tumors and monitoring of PThyN biodistribution in vivo. Besides, 131 I-labeled and cRGD-functionalized PThyN displays remarkable growth inhibition of the B16F10 tumor in mice (tumor inhibition rate > 89%). These poly(l-thyroxine) nanoparticles provide a unique and versatile theranostic platform for varying diseases.

Radial breathing modes coupling in plasmonic molecules.

Metallic hexamer, very much the plasmonic analog of benzene molecule, provides an ideal platform to mimic modes coupling and hybridization in molecular systems. To demonstrate this, we present a detailed study on radial breathing mode (RBM) coupling in a plasmonic dual-hexamers. We excite RBMs of hexamers by symmetrically matching the polarization state of the illumination with the distribution of electric dipole moments of the dual-hexamer. It is found that the RBM coupling exhibits a nonexponential decay when the inter-hexamer separation is increased, owing to the dark mode nature of RBM. When the outer hexamer is subjected to the in-plane twisting, resonant wavelengths of two coupled RBMs as well as the coupling constant show cosine variations with the twist angle, indicating the symmetry of hexamer structure plays a critical role in the coupling of RBMs. Moreover, it is demonstrated that the coupling of RBMs is dominated by the in-plane interaction as the outer hexamer is under an out-of-plane tilting, causing convergence of resonant wavelengths of the two coupled RBMs with increasing tilt angle. Our results not only provide an insight into the plasmonic RBM coupling mechanism, but also pave the way to systematically control the spectral response of plasmonic molecules.

Supercapsular percutaneously-assisted total hip (SuperPath) versus posterolateral total hip arthroplasty in bilateral osteonecrosis of the femoral head: a pilot clinical trial.

BACKGROUND: The supercapsular percutaneously-assisted total hip arthroplasty (SuperPath) was proposed to be minimally invasive and tissue sparing with possible superior postoperative outcomes to traditional approaches of total hip arthroplasty (THA). Here, we compared the short-term outcomes of staged THA with the SuperPath or through posterolateral approach (PLA) for bilateral osteonecrosis of the femoral head (ONFH). METHODS: Patients with bilateral late-stage ONFH were prospectively recruited from our department from March 2017 to March 2018. Staged bilateral THAs with one side SuperPath and the other side PLA were performed consecutively in the same patients with right and left hips alternating within approaches. The average time interval between the staged THAs was 3 months. Perioperative status (operation time, incision length, intraoperative blood loss, soft tissue damage, and length of hospital stay) and postoperative function (range of motion, pain, and hip function) were recorded and compared between the SuperPath and PLA approaches within 12-month postoperatively. RESULTS: Four male patients (age, 51.00 ± 4.54; BMI, 21.49 ± 1.73) with bilateral alcohol-induced ONFH (Ficat III/IV) were followed up over 12 months postoperatively. Compared with the PLA, the SuperPath yielded shorter incision length (7.62 vs. 11.12 cm), longer operation time (103.25 vs. 66.50 min), more blood loss (1108.50 vs. 843.50 ml), deficient abduction angle of the acetabular cup (38.75° vs. 44.50°), and inferior early-term hip function (Harris hip score, 72.50 vs. 83.25) at 12-month postoperatively. Soft tissue damage, length of hospital stay, postoperative pain, postoperative range of motion, and 12-month patient satisfaction were comparable between both approaches. CONCLUSION: The SuperPath may be a minimally invasive technique but the present study shows less favorable short-term outcomes than PLA for total hip arthroplasty in osteonecrosis of the femoral head. More investigations are required to provide convincing favorable evidences of the SuperPath over other traditional THA approaches. TRIAL REGISTRATION INFORMATION: The trial was retrospectively registered in https://www.researchregistry.com (No. Researchregistry4993) on July 04, 2019. The first participant was enrolled on March 13, 2017.

Infection-free rates and Sequelae predict factors in bone transportation for infected tibia: a systematic review and meta-analysis.

BACKGROUND: Tibia infected nonunion and chronic osteomyelitis are challenging clinical presentations. Bone transportation with external or hybrid fixators (combined external and internal fixators) is versatile to solve these problems. However, the infection-free rates of these fixator systems are unknown. Additionally, the prognosis factors for results of bone transportation are obscure. Therefore, this systematic review and meta-analysis was conducted to answer these questions. METHODS: A systematic review was conducted following the PRISMA-IPD guidelines. Relevant publications from January 1995 to September 2018 were compiled from Medline, Embase, and Cochrane. The infection-free rates of external and hybrid fixators were achieved by synthesizing aggregate data and individual participant data (IPD). IPD was analyzed by two-stage method with logistical regression to identify prognosis factors of sequelae. RESULTS: Twenty-two studies with 518 patients were identified, including 11 studies with 167 patients' IPD, and 11 studies with 351 patients' aggregate data. The infection-free rate of hybrid fixator group was 86% (95%CI: 79-94%), lower than that of external fixator which was 97% (95%CI: 95-98%,). The number of previous surgeries was found predict factor of bone union sequelae (p = 0.04) and function sequelae(p < 0.01); The external fixation time was found predict factor of function sequelae (p = 0.015). CONCLUSIONS: Hybrid fixators may be associated with a greater risk of infection-recurrence in the treatment of tibia infected nonunion and chronic osteomyelitis. The number of previous surgeries and external fixation time can be used as predictors of outcomes. Proper fixators and meticulously designed surgery are important to avoid unexpected operations and shorten external fixation time.

Biomimetic porous silk fibroin/biphasic calcium phosphate scaffold for bone tissue regeneration.

The purpose of our study is to prepare a biomimetic porous silk fibroin (SF)/biphasic calcium phosphate (BCP) scaffold, and evaluate its performance in bone tissue regeneration. The differences in pore size, porosity, mechanical strength and biocompatibility of four different fibroin-containing scaffolds (0, 20, 40, and 60% SF) were studied in vitro. After inoculation with MC3T3-E1 cells, the ectopic bone formation ability of the SF/BCP bionic scaffold was evaluated in a rat model. The SEM and CT demonstrated that compared with pure BCP group (0% SF), the pore size and porosity of SF/BCP scaffolds were proportional to SF content, of which 40% of SF and 60% of SF groups were more suitable for cell growth. The compressive strength of SF/BCP scaffold was greater than that of the pure BCP scaffold, and showed a trend of first increasing and then decreasing with the increase of SF content, among which 40% of SF group had the maximum compressive strength (40.80 + 0.68) MPa. The SF/BCP scaffold had good biocompatibility, under the electron microscope, the cells can be smoothly attached to and propagated on the scaffold. After loading the osteoblasts, it showed excellent osteogenic capacity in the rat model. The SF/BCP scaffold can highly simulate the micro-environment of natural bone formation and can meet the requirements of tissue engineering. The SF/BCP biomimetic porous scaffold has excellent physical properties and biocompatibility. It can highly simulate the natural bone matrix composition and microenvironment, and can promote the adhesion and proliferation of osteoblasts. The SF/BCP scaffold has good ectopic osteogenesis after loading with osteoblasts, which can meet the requirements of scaffold materials in tissue engineering, and has broad application prospects in clinical application.