Interleukin-6 classic and trans-signaling utilize glucose metabolism reprogramming to achieve anti- or pro-inflammatory effects.

Interleukin (IL)-6 has anti- and pro-inflammatory functions, controlled by IL-6 classic and trans-signaling, respectively. Differences in the downstream signaling mechanism between IL-6 classic and trans-signaling have not been identified. Here, we report that IL-6 activates glycolysis to regulate the inflammatory response. IL-6 regulates glucose metabolism by forming a complex containing signal-transducing activators of transcription 3 (STAT3), hexokinase 2 (HK2), and voltage-dependent anion channel 1 (VDAC1). The IL-6 classic signaling directs glucose flux to oxidative phosphorylation (OxPhos), while IL-6 trans-signaling directs glucose flux to anaerobic glycolysis. Classic IL-6 signaling promotes STAT3 translocation into mitochondria to interact with pyruvate dehydrogenase kinase-1 (PDK1), leading to pyruvate dehydrogenase α (PDHA) dissociation from PDK1. As a result, PDHA is dephosphorylated, and STAT3 is phosphorylated at Ser727. By contrast, IL-6 trans-signaling promotes the interaction of sirtuin 2 (SIRT2) and lactate dehydrogenase A (LDHA), leading to the dissociation of STAT3 from SIRT2. As a result, LDHA is deacetylated, and STAT3 is acetylated and phosphorylated at Tyr705. IL-6 classic signaling promotes the differentiation of regulatory T cells via the PDK1/STAT3/PDHA axis, whereas IL-6 trans-signaling promotes the differentiation of Th17 cells via the SIRT2/STAT3/LDHA axis. Conclusion: IL-6 classic signaling generates anti-inflammatory functions by shifting energy metabolism to OxPhos, while IL-6 trans-signaling generates pro-inflammatory functions by shifting energy metabolism to anaerobic glycolysis.

An implantable composite scaffold for amplified chemodynamic therapy and tissue regeneration.

Tissue regeneration and tumor cell killing after surgical resection are the two keys to achieving effective tumor therapy. In this study, an implantable system with combined functions of tumor therapy and tissue repair was constructed. Tannic acid (TA)/Fe3+ nanoparticles with Fenton catalytic activity were loaded with GSH inhibitor BSO drug (BTF), and acted as the therapeutic factor to realize amplified chemodynamic tumor treatment. Bioactive glass (BG) fibers loaded with vascular endothelial growth factor (VEGF) were used as the drug carrier matrix with tissue repair function (BGV). Then the BGV@BTF composite fibers were obtained by anchoring BTF nanoparticles on the surface of BGV fibers. Under tumorous acidic conditions, BTF nanoparticles can be released from the composite fibers, and taken up by tumor cells. Facilitated by BSO with the GSH suppression effect and TA with Fe3+ reducing properties, BTF nanoparticles can realize high oxidative stress in tumor cells and subsequent cell death. In addition, BG fibers and VEGF can both promote tissue regeneration and accelerate postoperative wound healing. The simultaneous suppression of tumor growth and promotion of tissue repair in this work is inspiring in the field of postoperative tumor treatment and recovery.

A Volumetric Absorptive Microsampling UPLC-MS/MS Method for Simultaneous Quantification of Tacrolimus, Mycophenolic Acid and Creatinine in Whole Blood of Renal Transplant Recipients.

(1) Background: Continuous monitoring of tacrolimus (TAC), mycophenolic acid (MPA), and creatinine (Cre) after renal transplantation is vitally important. In this study, we developed a new method based on volumetric absorptive microsampling (VAMS) combined with Ultra Performance Liquid Chromatography−Tandem Mass Spectrometry (UPLC-MS/MS) to simultaneously quantify three analytes including TAC, MPA, and Cre in whole blood. (2) Methods: The VAMS-based UPLC-MS/MS assay used a shared extraction and a single injection to simultaneously quantify the included TAC, MPA, and Cre. Development and validation were carried out following the Food and Drug Administration and European Medicines Agency guidelines for the validation of bioanalytical methods. Moreover, clinical validation for the three analytes was performed in both dried blood spot (DBS) and VAMS. Furthermore, a willingness survey was conducted using the system usability scale (SUS) for renal transplant recipients. (3) Results: The assay was successfully validated for all analytes. No interference, carryover, or matrix effects were observed, and extraction recoveries and process efficiencies were >90.00%. Analysis was unaffected by hematocrit (0.20~0.60, L/L) and anticoagulants (EDTA-2K). Dried VAMS samples were stable for 7 days at ambient temperature and stable for at least 1 month at −20 °C. During clinical validation, the measured TAC, corrected MPA, and Cre concentrations of VAMS samples met the analytical standards (95.00%, 88.57%, and 92.50%). When more stringent clinical acceptance criteria were set, the results obtained by VAMS (90.00%, 71.43%, and 85.00%) better than DBS (77.50%, 62.86%, and 70.00%). Compared with DBS, the survey found that renal transplant recipients are more inclined to use VAMS. (4) Conclusions: A robust extraction and UPLC-MS/MS analysis method in VAMS tips was developed and fully validated for the simultaneous quantification of TAC, MPA, and Cre concentrations. This method provides analytical support for the one-sample remote monitoring of both immunosuppressive drug concentrations and renal function in allo-renal recipients. Based on the good consistency between this method and the routine detection of venous blood samples and higher patient satisfaction than DBS, we believe that VAMS sampling can be a better alternative to venous whole-blood sampling.

A Modularized IoT Monitoring System with Edge-Computing for Aquaponics.

Aquaponics is a green and efficient agricultural production model that combines aquaculture and vegetable cultivation. It is worth looking into optimizing the proportion of fish and plants to improve the quality and yield. However, there is little non-destructive monitoring of plant growth in aquaponics monitoring systems currently. In this paper, based on the Internet of Things technologies, a monitoring system is designed with miniaturization, modularization, and low-cost features for cultivation-breeding ratio research. The system can realize remote monitoring and intelligent control of parameters needed to keep fish and plants under optimal conditions. First, a 32-bit chip is used as the Microcontroller Unit to develop the intelligent sensing unit, which can realize 16 different data acquisitions as stand-alone extensible modules. Second, to achieve plant data acquisition and upload, the Raspberry Pi embedded with image processing algorithms is introduced to realize edge-computing. Finally, all the collected data is stored in the Ali-cloud through Wi-Fi and a WeChat Mini Program is designed to display data and control devices. The results show that there is no packet loss within 90 m for wireless transmission, and the error rate of environment parameters is limited to 5%. It was proven that the system is intelligent, flexible, low-cost, and stable which is suitable for small-scale aquaponics well.

A Single Approach to Arthroscopic Reduction and Debridement for Developmental Dislocation of the Hip in 12 Infants.

BACKGROUND Developmental dislocation of the hip (DDH) results in osteoarthritis in infants and children. This study aimed to investigate the effects of a single approach to arthroscopic reduction and debridement on clinical outcome in 12 infants with DDH. MATERIAL AND METHODS Twelve infants with irreducible DDH underwent single approach arthroscopic reduction and debridement followed by the use of a frog-leg position plaster cast with fixed flexion and abduction of the hips combined with external fixation for 6-8 weeks. Magnetic resonance imaging (MRI) or plain X-ray images were analyzed. Intra-articular obstructive factors for reduction were evaluated. The safety angle, medialization rate of the femoral head, and the acetabular angle were measured before and after arthroscopic reduction. RESULTS Imaging showed that the signs of DDH were significantly improved following arthroscopic reduction. Obstructive factors included hypertrophy of the round ligament, fibrous tissue and fat in the acetabular base, arthrocapsular constriction, and varus deformity of the hip. The safety angle was significantly increased following arthroscopic reduction (53.5°) compared with the safety angle before treatment (18.5°) (p<0.05). Medialization of the femoral head was significantly increased (127%) compared with that before treatment (72%) (p<0.05). Arthroscopic reduction significantly reduced the acetabular angle (25°) compared with that before treatment (37.5°) (p<0.05). CONCLUSIONS Single approach arthroscopic reduction and debridement was an effective method for treating DDH that significantly improved the medialization rate of the femoral head, acetabular angle, and the outcome of external fixation when a plaster cast was used with fixed flexion and abduction of the hips.

Biomechanical analysis of pinning configurations for a supracondylar humerus fracture with coronal medial obliquity.

Despite hundreds of studies of pinning configurations for transverse supracondylar humerus fractures, very few studies have investigated the optimal pin configurations in the treatment of supracondylar humerus fractures with coronal medial obliquity. The aim of this study was to develop a model of supracondylar humerus fractures with coronal medial obliquity and compare the stability of three various pin configurations to provide an acceptable pin placement. Oblique cuts were made in synthetic humeri at the level of the coronoid and olecranon fossae to simulate a humeral supracondylar fracture with coronal medial obliquity. Each fracture was reduced and fixed using two 0.062 inch K-wires in three different configurations, and sequentially tested in extension, varus, valgus, and internal and external rotations using an MTS 858 Minibionix materials testing load frame. We performed analysis of variance to compare construction stiffness of different pin configurations and the standard level of significant (P-value ≤ 0.05) was used indicate statistical significance. In resistance to extension and valgus loading, there was no statistical difference between all the three pin configurations (P=0.22 and 0.130, respectively). During the varus loading condition, the greatest stiffness values were obtained with the two crossed pin configuration, followed by the two medial pins, and the two lateral pin configuration showed the lowest values. For resistance in internal and external rotation testing, although there was no statistical difference between the two medial pins and the two crossed pins configurations (P=0.06 and 0.75, respectively), they were significantly greater than that of the two lateral pin configuration (P=0.003 and 0.004; P=0.001 and 0.02, respectively). In a synthetic humerus model of supracondylar humerus fractures with coronal medial obliquity, the two crossed pin configuration provided statistically greatest or comparable stability in the varus, and internal and external rotation loading conditions.