Expression of CD40L by the ALVAC-Simian Immunodeficiency Virus Vector Abrogates T Cell Responses in Macaques.

Immunization with recombinant ALVAC/gp120 alum vaccine provided modest protection from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) acquisition in humans and macaques. Vaccine-mediated protection was associated with the elicitation of IgG against the envelope V2 loop and of envelope-specific CD4+ T cell responses. We hypothesized that the simultaneous expression of the costimulatory molecule CD40L (CD154) by the ALVAC-HIV vector could increase both protective humoral and cellular responses. We engineered an ALVAC-SIV coexpressing CD40L with SIVmac251 (ALVAC-SIV/CD40L) gag, pol, and env genes. We compared its immunogenicity in macaques with that of a canonical ALVAC-SIV, with both given as a vector-prime/gp120 in alum boost strategy. The ALVAC-SIV/CD40L was superior to the ALVAC-SIV regimen in inducing binding and tier 1 neutralizing antibodies against the gp120. The increase in humoral responses was associated with the expression of the membrane-bound form of the CD40L by CD4+ T cells in lymph nodes. Unexpectedly, the ALVAC-SIV/CD40L vector had a blunting effect on CD4+ Th1 helper responses and instead favored the induction of myeloid-derived suppressor cells, the immune-suppressive interleukin-10 (IL-10) cytokine, and the down-modulatory tryptophan catabolism. Ultimately, this strategy failed to protect macaques from SIV acquisition. Taken together, these results underlie the importance of balanced vaccine-induced activating versus suppressive immune responses in affording protection from HIV.IMPORTANCE CD40-CD40 ligand (CD40L) interaction is crucial for inducing effective cytotoxic and humoral responses against pathogens. Because of its immunomodulatory function, CD40L has been used to enhance immune responses to vaccines, including candidate vaccines for HIV. The only successful vaccine ever tested in humans utilized a strategy combining canarypox virus-based vector (ALVAC) together with an envelope protein (gp120) adjuvanted in alum. This strategy showed limited efficacy in preventing HIV-1/SIV acquisition in humans and macaques. In both species, protection was associated with vaccine-induced antibodies against the HIV envelope and CD4+ T cell responses, including type 1 antiviral responses. In this study, we tested whether augmenting CD40L expression by coexpressing it with the ALVAC vector could increase the protective immune responses. Although coexpression of CD40L did increase humoral responses, it blunted type 1 CD4+ T cell responses against the SIV envelope protein and failed to protect macaques from viral infection.

Comparison of elastic stable intramedullary nailing versus Kirschner wires in treatment of pediatric radial neck fractures.

Purpose: The aim of the study was to compare the different internal fixations between elastic stable intramedullary nailing and Kirschner wires in treatment of angulated radial neck fractures. Methods: We retrospectively reviewed the patients with radial neck fracture without associated injuries who underwent surgery approach in our department during April 2011-March 2020. There were 62 patients meeting all the criteria with complete clinical data, with median age of 7.5 (IQR 5.8-9.5) years, 34 males and 28 females. The preoperative fracture pattern was assessed according to the Judet classification system. Depending on the materials implanted and fixation strategy, the patients could be divided into a Kirschner wire group and an elastic stable intramedullary nailing group. Final functional outcomes of patients were assessed by the Mayo Elbow Performance Score and Tibone-Stoltz functional evaluation classification. Results: The Kirschner wire group included 37 patients, with 4.8 years median follow-up. The elastic stable intramedullary nailing group included 25 patients with 5.9 years median follow-up. There were no significant differences in gender, age, Judet classification, average operative time, Mayo Elbow Performance Score, Tibone-Stoltz classification, or length of hospital stay between groups. However, the time to union in the Kirschner wire group was significantly shorter than that in the elastic stable intramedullary nailing group (p < 0.05). Both groups achieved satisfactory functional and cosmetic results. Conclusion: In the management of pediatric radial neck fractures, both elastic stable intramedullary nailing and Kirschner wire internal fixation have shown equivalent therapeutic results, leading to satisfactory functional outcomes. The selection of the internal fixation approach can be influenced by the patient's fracture characteristics and the surgeon's preferences. Level of evidence: Level III; Retrospective Comparison; Treatment Study.

Bone cemented K-wire fixation versus elastic stable intramedullary nailing fixation of paediatric proximal humerus fractures: A prospective cohort study.

BACKGROUND: The objective of this study is to compare the treatments of pediatric displaced proximal humerus fractures with external-fixation technique using the combination of K-wires and bone-cement versus close reduction and internal fixation technique using elastic stable intramedullary nail. METHODS: From April 2016 to March 2020, 72 children with proximal humeral fractures were allocated to group A and 44 children with proximal humeral fractures were allocated to group B. Patients in group A were treated with bone-cemented K-wire fixation, and patients in group B were treated with elastic stable intramedullary nailing. The function of the upper limb was assessed using the Shortened Version of the Disabilities of the Arm, Shoulder and Hand questionnaire and Neer score. Patient satisfaction was assessed using the 10-cm visual analogue scale. RESULTS: Bone healing was achieved in group A and B after a mean time of 6.1 ± 1.2 and 6.4 ± 1.1 weeks, respectively. The mean surgical time of groups was 33 ± 9 and 54 ± 12 minutes, respectively. The mean Quick Disabilities of the Arm, Shoulder and Hand questionnaire score of groups were 0.5 ± 1.4 and 0.7 ± 1.5, respectively. Based on Neer score, we obtained 69 excellent and 3 good results in group A, and 41 excellent and 3 good results in group B. There were significant differences regarding duration of operation, cost of treatment, and postoperative angle at bone healing (P < .05). CONCLUSIONS: The external cemented K-wire fixation is a useful and reliable alternative technique for the treatment of severely displaced proximal humerus fractures in children. The technique is a minimally invasive procedure with minimal complications.

A benign form of congenital anterolateral bowing of the tibia associated with ipsilateral polydactyly of the hallux: case report and literature review.

Congenital anterolateral bowing of the tibia is generally considered a precursor of congenital pseudarthrosis of the tibia (CPT), which is usually associated with neurofibromatosis type 1 (NF1), a common autosomal dominant genetic disorder. In many cases, NF1 is initially suspected following the presentation of a child with anterolateral tibial bowing. The prognosis of CPT is poor, and amputation may be required. Congenital anterolateral bowing of the tibia combined with ipsilateral polydactyly of the hallux (CABTP) is a rare entity that resembles the anterolateral tibial bowing that occurs in association with CPT, and may be misdiagnosed as NF1. However, spontaneous correction of the tibial bowing with an almost normal fibula has been described in all previously reported cases. Here, we report three patients with CABTP and discuss the physical and imaging characteristics and follow-up results. We suggest that given the spontaneous resolution of bowing, the absence of neurocutaneous signs and the relatively favorable prognosis, CABTP is a distinct entity that merits its own place within the field of anterolateral bowing of the tibia and has no association with CPT or NF1. This should help avoid unnecessary investigations and interventions for NF1. This article shows for the first time tibial duplication in the area of bowing, with two medullary canals surrounded by well-defined cortex on CT.

Wood-Derived Bimetallic and Heteroatomic Hierarchically Porous Carbon Aerogel for Rechargeable Flow Zn-Air Batteries.

It is necessary to correctly research and synthesize efficient and inexpensive catalysts to achieve reversible oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), which is also a prerequisite for zinc-air batteries (ZABs). However, it is still a huge challenge to manufacture electrocatalysts with durable and high electrocatalytic performance from biomass. Here, a convenient method of delignification was used to transform natural balsa wood into a layered porous carbon material, FeCo alloy supported on a N, S-doped wood-based carbon aerogel (FeCo@NS-CA) as the cathode in rechargeable flow ZAB. The obtained FeCo@NS-CA with the porous lamellar architecture exhibits superior bifunctional electrocatalysis, including excellent electrochemical activities and superior stabilities. For ORR, relative to the reversible hydrogen electrode, the onset potential of FeCo@NS-CA is 0.97 V, and the half-wave potential is 0.85 V, which is consistent with the potential of commercial Pt/C. For OER, FeCo@NS-CA obtained an overpotential of 450 mV, which is very similar to the overpotential of the benchmark RuO2. The superior performance could be owing to the alloy carrier interaction between the FeCo alloy and the wood-based carbon aerogel co-doped with N and S. Moreover, the bifunctional air cathode in a flow ZAB assembled with the FeCo@NS-CA catalyst at a current density of 10 mA cm-2; the power density is 140 mW cm-2, and the specific capacitance is 760 mA h gZn-1, with a remarkable long-term stability of 400 h better than ZAB of benchmark Pt/C + RuO2. This research lays the foundation for transforming abundant biomass resources into high environmental protection materials for energy-related applications.

Implantable and Biodegradable Micro-Supercapacitor Based on a Superassembled Three-Dimensional Network Zn@PPy Hybrid Electrode.

Transient supercapacitors (TSCs), a new type of advanced supercapacitor (SC) that can completely dissolve with environmentally and biologically benign byproducts in vivo after performing their specified function, have broad application prospects in the fields of green electronics, implantable devices, personalized medicine, military security, and other fields. However, research on TSCs is still in its infancy, and there are still many challenges to be solved, such as the complex preparation process and low energy density. Herein, we report a facile superassembly manufacturing method for an implantable and fully biodegradable three-dimensional network Zn@PPy hybrid electrode by screen printing and electrochemical deposition. The produced superassembled interdigital pseudocapacitor exhibits superior electrochemical performances due to the high capacitances and excellent rate performances of the pattern Zn@PPy electrode and NaCl/agarose electrolyte. An optimized biodegradable SC exhibits a maximum energy density of 0.394 mW h cm-2 and can be fully degraded in vivo in 30 days without any adverse effects in the host organism. This work provides a new platform for transient electronic technology for diverse implantable electronic applications.

IFNγ and TNFα synergistically promote galectin 9 secretion by human osteosarcoma cells MG-63 to prevent T cell killing.

OBJECTIVES: Osteosarcoma is the most common bone tumor usually distributed in adolescence and the elderly. IFNγ and TNFα play double-sided roles in tumor immunity. The fundamental mechanism of IFNγ and TNFα in osteosarcoma remains elusive. We speculated that TNFα and IFNγ serve a role in regulating immune checkpoint molecule, Galectin 9, expression of MG-63 osteosarcoma cells. METHODS: The human osteosarcoma cell line, MG-63, was stimulated with recombinant human IFNγ and TNFα. Cytokine stimulated MG-63 cells were cocultured with human peripheral T cells. Real-time PCR, flow cytometry and ELISA were used to detect related molecule expression. RESULTS: IFNγ and TNFα up-regulate Galectin 9 expression of MG-63 cells synergistically. IFNγ and TNFα stimulated MG-63 cells induce CD4 and CD8 T cell apoptosis and inhibit cytokine production through the Tim-3/Galectin 9 pathway. A High level of serum Galectin 9 and highly expressed Tim-3 of peripheral T cells were detected in osteosarcoma patients. CONCLUSION: We found that Galectin-9 is induced by IFNγ and TNFα stimuli in osteosarcoma cells. Furthermore, Tim-3/Galectin-9 pathway contributes to the inducible immunomodulatory functions of osteosarcoma cells, which may provide a new clue to novel strategies for the osteosarcoma therapy.

External Fixator-assisted Ulnar Osteotomy: A Novel Technique to Treat Missed Monteggia Fracture in Children.

OBJECTIVE: The treatment of missed Monteggia fracture remains a challenge, despite the various surgical methods described. The purpose of this study was to explore a new surgical technique utilizing external fixator-assisted ulnar osteotomy and to assess the surgical results in a case series. METHODS: Thirteen patients with missed Monteggia fractures were treated at our institution using this new surgical technique from August 2012 to January 2016. Our series included 11 boys and 2 girls. The left elbow was involved in 6 patients and the right elbow was involved in 7 patients. According to the Bado classification, 10 fractures were classified as Bado type I with anterior radial head dislocation and 3 were classified as Bado type III with anterolateral dislocation. The average age at the time of surgery was 5 years 8 months (range, 2 years 2 months-10 years). The mean trauma-to-surgery interval was 12 months (range, 2-36 months). All patients underwent ulnar osteotomy with angulation and lengthening using a temporary external fixator, plate fixation of the osteotomy, and open reduction of the radial head dislocation without annular ligament reconstruction. RESULTS: The average follow-up was 27 months (range, 16-44 months). The average operation time was 175 min (range, 140-215 min). The average length of distraction was 0.7 cm (range, 0.5-1.2 cm) and the average angulation was 28° (range, 20°-30°) at the ulnar osteotomy site intraoperatively. The elbow performance score (Kim's) was excellent in 10 cases and good in 3 cases. No neurovascular complications, compartment syndrome or implant breakage occurred. No pain in the distal radioulnar joint or limited range of motion of the wrist occurred in any patient. The radial head remained reduced in all patients with no subluxation or redislocation. However, delayed ulnar union occurred in 3 cases, all of which were successfully treated with plaster cast immobilization within approximately 6 months postoperatively. One patient presented with cubitus valgus postoperatively with a carrying angle of 30°, which was 10° greater than the contralateral carrying angle. CONCLUSIONS: External fixator-assisted ulnar osteotomy offers substantial flexibility for achieving the optimal positioning of the transected ulna to reduce the radial head prior to the final ulnar osteotomy fixation with a plate, thereby facilitating an effective operative performance. Our procedure is a safe and effective method to treat missed pediatric Monteggia fractures.