Development of biodegradable Zn-Mn-Li and CaP coatings on Zn-Mn-Li alloys and cytocompatibility evaluation for bone graft.

Zn-based alloys are considered as new kind of potential biodegradable implanted biomaterials recently. The difficulty of metal implanted biomaterials and bone tissue integration seriously affects the applications of metal implanted scaffolds in bone tissue-related fields. Herein, we self-designed Zn0.8Mn and Zn0.8Mn0.1Li alloys and CaP coated Zn0.8Mn and Zn0.8Mn0.1Li alloys, then evaluated the degradation property and cytocompatibility. The results demonstrated that the Zn0.8Mn0.1Li alloys had profoundly modified the degradation property and cytocompatibility, but Zn0.8Mn0.1Li alloys had particularly adverse effects on the surface morphology of osteoblasts. The results furtherly showed that the CaP-coated Zn0.8Mn and Zn0.8Mn0.1Li alloys scaffold had better biocompatibility, which would further guarantee the biosafety of this new kind of biodegradable Zn-based alloys implants for future clinical applications.

Microporous structures on mineralized collagen mediate osteogenesis by modulating the osteo-immune response of macrophages.

It is a new hot pot in tissue engineering and regenerative medicine to study the effects of physicochemical properties of implanted biomaterials on regulating macrophage polarization to promote bone regeneration. In this study, we designed and fabricated mineralized collagen (MC) with different microporous structures via in vitro biomimetic mineralization method. The microporous structures, mechanical properties, shore hardness and water contact angle measurements were tested. Live/dead cell staining, CCK-8 assay, phalloidine staining, staining of focal adhesions were used to detect cell behavior. ELISA, qRT-PCR, ALP, and alizarin red staining (ARS) were performed to appraise osteogenic differentiation and investigated macrophage response and their subsequent effects on the osteogenic differentiation. The results showed that RAW264.7 and MC3T3-E1 cells were able to survive on the MC. MC with the microporous structure of approximately 84 µm and 70%-80% porosity could promote M2 macrophage polarization and increase the expression level of TGF-ß and VEGF. Moreover, the gene expression of the osteogenic markers ALP, COL-1, and OCN increased. Therefore, MC with different microporous structures mediated osteoimmunomodulation in bone regeneration. These data will provide a new idea of biomaterials inducing bone repair and direct the optimal design of novel immune biomaterials, development, and rational usage.

Structural basis for the tethered peptide activation of adhesion GPCRs.

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes1-6. Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence7-12. Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with Gs: GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an α-helical-bulge-ß-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W6.53 and the constitution of a hydrogen-bond network formed by Q7.49/Y7.49 and the P6.47/V6.47φφG6.50 motif (φ indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and Gs coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common Gs-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with Gs. Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their Gs coupling.

Corrigendum to: Enhancement of BMP-2 and VEGF Carried by Mineralized Collagen for Mandibular Bone Regeneration.

[This corrects the article DOI: 10.1093/rb/rbaa022.].

Quantitative assessment of left ventricular myocardial work in chronic kidney disease patients by a novel non-invasive pressure-strain loop analysis method.

This study aimed to quantitatively evaluate myocardial work (MW) in advanced stage 3-5 chronic kidney disease (CKD) by a novel non-invasive left ventricular (LV) Pressure-strain loop analysis (PSL). 144 patients with CKD were included (68 with stage 3 CKD group, 76 with stage 4/5 CKD group), and 48 healthy patients were recruited as the control group. All subjects had undergone transthoracic echocardiography. LV myocardial work and efficiency were estimated from LV PSL analysis. There was a significant progressive increase in global work waste (GWW) and reduction in global work efficiency (GWE) in CKD compared to normal controls. No difference in global work index (GWI) and global constructive work (GCW) was observed among the three groups. Subdivided analysis according to systolic blood pressure (SBP) and LV geometry discovered that increased GWW seems to be present frequently in CKD patients with elevated SBP or LV hypertrophy (LVH). Multivariate analysis showed increased peak strain dispersion (PSD), SBP, LV mass index (LVMI), and decreased estimated glomerular filtration rate (eGFR) were significantly associated with increased GWW. The decline of renal function followed by impaired paralleled myocardial energy exploitation. Moreover, increased PSD, SBP, LVMI, and decreased eGFR might be potential drivers of increased GWW.

Macrophage-Derived Exosomes Promote Bone Mesenchymal Stem Cells Towards Osteoblastic Fate Through microRNA-21a-5p.

The effective healing of a bone defect is dependent on the careful coordination of inflammatory and bone-forming cells. In the current work, pro-inflammatory M1 and anti-inflammatory M2 macrophages were co-cultured with primary murine bone mesenchymal stem cells (BMSCs), in vitro, to establish the cross-talk among polarized macrophages and BMSCs, and as well as their effects on osteogenesis. Meanwhile, macrophages influence the osteogenesis of BMSCs through paracrine forms such as exosomes. We focused on whether exosomes of macrophages promote osteogenic differentiation. The results indicated that M1 and M2 polarized macrophage exosomes all can promote osteogenesis of BMSCs. Especially, M1 macrophage-derived exosomes promote osteogenesis of BMSCs through microRNA-21a-5p at the early stage of inflammation. This research helps to develop an understanding of the intricate interactions among BMSCs and macrophages, which can help to improve the process of bone healing as well as additional regenerative processes by local sustained release of exosomes.

Etched multicore fiber sensor using copper oxide and gold nanoparticles decorated graphene oxide structure for cancer cells detection.

A compact, portable, label-free, and ultra-sensitive sensor is proposed to detect cancerous cells based on Multi-Core Fiber (MCF) comprising of seven cores arranged in a hexagonal shape spliced with Single-Mode Fiber (SMF). Here, cytosensing based on fiber optic Localized Surface Plasmon Resonance (LSPR) is used for the efficient detection of different types of cancer cells. The proposed sensor structure is etched in a controlled manner to increase the evanescent wave (EWs) and coupling of modes between the cores of MCF. The etched MCF based LSPR probe has high refractive index sensitivity (RIS). To further increase the sensitivity, the sensor structure is immobilized with different nanomaterials (NMs) such as optimized size of gold nanoparticles (AuNPs), graphene oxide (GO), and copper oxide nanoflowers (CuO-NFs). AuNPs increase the sensitivity using LSPR, whereas, GO and CuO-NFs helps to increase the biocompatibility of sensor. The developed probe is further coated with 2-deoxy-D-glucose (2-DG) over NMs that are specific for the detection of cancer cells. In this work, various cancerous cell lines i.e. HepG2, Hepa 1-6, MCF-7, A549, and normal cell lines i.e. NCF and LO2 are detected using the developed sensing probe. Various analysis of proposed sensor such as selectivity, reusability, anti-interference ability, and involvement of GLUT receptor in detection has also been performed. The proposed etched sensor is ultra-sensitive for detection of HepG2, Hepa1 6, A549, MCF-7, LO2, and NCF cell lines with a limit of detection (LoD) of 3, 2, 2, 2, 4, 10 cells/mL, respectively in the linear range of 1 × 102-1 × 106 cells/mL.

Enhancement of BMP-2 and VEGF carried by mineralized collagen for mandibular bone regeneration.

Repairing damage in the craniofacial skeleton is challenging. Craniofacial bones require intramembranous ossification to generate tissue-engineered bone grafts via angiogenesis and osteogenesis. Here, we designed a mineralized collagen delivery system for BMP-2 and vascular endothelial growth factor (VEGF) for implantation into animal models of mandibular defects. BMP-2/VEGF were mixed with mineralized collagen which was implanted into the rabbit mandibular. Animals were divided into (i) controls with no growth factors; (ii) BMP-2 alone; or (iii) BMP-2 and VEGF combined. CT and hisomputed tomography and histological staining were performed to assess bone repair. New bone formation was higher in BMP-2 and BMP-2-VEGF groups in which angiogenesis and osteogenesis were enhanced. This highlights the use of mineralized collagen with BMP-2/VEGF as an effective alternative for bone regeneration.

The observed difference of macrophage phenotype on different surface roughness of mineralized collagen.

Biomaterials regulate macrophages and promote regeneration function, which is a new hot pot in tissue engineering and regenerative medicine. The research based on macrophage materials biology has appeared happy future, but related research on regulating macrophages and promoting tissue regeneration is still in its infancy. The surface roughness of biomaterials is one of the important factors affecting macrophage behavior. Previous study also found that the surface roughness of many biomaterials regulating macrophage polarization, but not including mineralized collagen (MC). In this study, we designed and fabricated MC with different roughness and investigated the influence of MC with different roughness on macrophages. In the study, we found that on the rough surface of MC, macrophages exhibited M1 phenotype-amoeboid morphology and high-level secretory of inflammatory factor (tumor necrosis factor-α and interleukin-6), while smoother surface exhibited M2 phenotype. These data will be beneficial to understand the mechanism deeply and enrich biomaterials tissue regeneration theory, provide a new train of thought biomaterials inducing tissue regeneration and repair and guide the optimum design of new biomaterials, development and reasonable applications.

Development of Uric Acid Biosensor Using Gold Nanoparticles and Graphene Oxide Functionalized Micro-Ball Fiber Sensor Probe.

A highly sensitive and selective optical fiber-based enzymatic biosensor has been proposed in the present study for detection of uric acid (UA) in human serum. The working mechanism of sensor depends on surface plasma property and localized surface plasmon resonance technique. For this purpose, a micro-ball fiber sensor probe of [Formula: see text] diameter was fabricated using advanced fusion-splicer and coated with gold nanoparticles (AuNPs) and graphene oxide (GO) in order to enhance its sensitivity. UV-Visible spectrophotometer and high-resolution transmission electron microscope (HR-TEM) were used to characterize the AuNPs solution and GO aqueous dispersion. The absorbance spectrum of AuNPs and GO are recorded at 519 nm and 230 nm, respectively. The coating of AuNPs and GO over fiber surface were verified by using a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). Thereafter, sensor probe was functionalized with the specific enzyme i.e. uricase for the UA detection. The linearity response of uricase/GO/AuNPs-coated micro-ball optical fiber sensor is reported in the range of [Formula: see text]-1 mM UA concentrations. The reflectance of sensor linearly decreases with the increasing UA concentrations. Sensitivity of the sensor is 2.1 %/mM with a good slope of linearity with detection limit of [Formula: see text]. To test the accuracy of proposed sensor, UA concentration in serum samples have also tested by using proposed sensor and A5800 Automatic Biochemical Analyzer. The results of the developed sensor are consistent with the results of A5800 Automatic Biochemical Analyzer. Thus, proposed sensor can be successfully utilized for UA detection in human serum samples.

The efficacy of polidocanol sclerotherapy in mucocele of the minor salivary gland.

OBJECTIVES: Mucocele of the minor salivary gland is usually caused when the duct is injured, mucus leaks into the tissue space and the mucous gland are obstructed, which lead to cystic lesion formation and dilatation. Currently, there are multiple therapeutic methods available with various outcomes. This study aims to provide clinical evidence of polidocanol sclerotherapy for the treatment of mucocele of the minor salivary gland. METHODS: In this study, we injected polidocanol into 112 patients who were diagnosed with mucocele of the minor salivary gland and evaluated the treatment efficacy and safety systematically. RESULTS: Of the 122 cases, 102 cases were cured, eight cases showed remarkable remission, and two cases had partial remission. No recurrence was found during follow-up, and none of the cases showed an invalid effect, resulting in a total cure rate of 91.07%. No severe side effects were observed during treatment or the follow-up period. No significant difference in efficacy between different genders was found (P = 0.490). Polidocanol sclerotherapy for mucocele on the lower lip was more effective compared to mucocele on the inferior surface of the lingual apex (P = 0.035). CONCLUSION: Polidocanol sclerotherapy showed satisfying curative effects for mucocele of the minor salivary gland without causing side effects of anesthesia, trauma, or severe pain.

Comparison of rabbit rib defect regeneration with and without graft.

Rib segment, as one of the most widely used autologous boneresources for bone repair, is commonly isolated with an empty left in the defect. Although defective rib repair is thought to be unnecessary traditionally, it's of vital importance actually to promote rib regeneration for patients with better postoperative recovery and higher life quality. Comparative investigations on rabbit rib bone regeneration with and without graft were reported in this article. A segmental defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The mineralized collagen bone graft (MC) was implanted into the defect and evaluated for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8 and 12 weeks and histological examinations at 12 weeks after surgery, which showed a higher bone remodeling activity in the groups with MC implantation in comparison with blank control group, especially at the early stage of remodeling.

[Leaf physiological traits at pod-setting stage in peanut cultivars with different drought resistance].

With twelve peanut cultivars grown under artificial water control, the drought resistance related physiological and biochemical traits and the drought resistance mechanism of peanut leaves were studied. Two water treatments were designed, that were 50% and 70% of the soil relative water content of the 0-80 cm soil layer, respectively, at pod-setting stage. The results showed that the twelve peanut cultivars could be grouped into three different resistance levels based on their yield drought resistance coefficient. The A596, Shanhua 11 and Rugaoxiyangsheng were grouped as cultivars with high resistance, while Huayu 20, Nongda 818, Haihua 1, Shanhua 9 and 79266 with moderate resistance, and the ICG6848, Baisha 1016, Hua 17 and Penglaiyiwohou with weak resistance. The mechanism of high drought resistance in peanut cultivars of A596, Shanhua 11 and Rugaoxiyangsheng were due to more powerful antioxidant capacity, higher activity of photosystem II (PS II) and photosynthetic rate (Pn). By contrast, the moderate resistant cultivars Haihua 1 had stronger antioxidant protection capability, and the Shanhua 9 had much higher PS II activity. The Pn, stomatal limitation value (Ls), maximal photochemical efficiency of PS II (Fv/Fm), photochemical quenching coefficient (q(p)), content of malondialdehyde (MDA), relative electric conductivity and superoxide dismutase (SOD) activity of leaves were very significantly correlated with the drought resistance coefficient. Therefore, they were important indicative traits for the drought resistance at pod-setting stage of peanuts. These traits could be evaluated under normal irrigation condition except that the SOD activity should be identified under drought stress. Based on this study, we proposed that Shanhua 11 and 79266 could serve as standard cultivars of high drought resistance and weak drought resistance, respectively. Shanhua 11 could also serve as a standard cultivar for identification of leaf drought resistance traits in peanut.

[Response of photosynthetic characteristics of peanut seedlings leaves to low light].

To investigate the effects of shading and light recovery on the photosynthetic characteristics of peanut seedlings leaves, different shading treatments including no shading, 27% shading, 43% shading, and 77% shading were performed with black sunshade net at the seedling stage of two peanut cultivars Fenghua 1 and Fenghua 2, with related parameters determined. It was shown that with the increase of shading degree, the leaf chlorophyll content, actual PSII photochemical efficiency under irradiance (phi(PS II)), and maximum PS II photochemical efficiency (Fv/Fm) of test cultivars increased, while the Chl a/b ratio and photosynthetic rate (Pn) decreased. On the first day after light recovery, the Pn and stomatal conductance (Gs) decreased while the intercellular CO2 concentration (Ci) increased with increasing shading degree when measured under high light, but the Pn increased and the Gs and Ci decreased with increasing shading degree when measured under low light. The ratio of Pn measured under low light to that measured under high light increased significantly. With increasing shading degree, the light compensation point, light saturation point, CO2 compensation point, CO2 saturation point, and carboxylation efficiency decreased, while the apparent quantum yield increased. After the removal of shading, the Pn, phi(PS II), and Fv/Fm under natural light decreased immediately, but increased gradually 3-5 days after. 15 days after light recovery, the Pn, phi(PS II) and Fv/Fm in treatment 27% shading recovered to the level of no shading. As for the other treatments, the restored extent differed with shading degree and test variety. In the same treatments, the leaf chlorophyll content, Pn and phi(PS II) of Fenghua 1 were higher than those of Fenghua 2. The results demonstrated that shading at seedling stage improved the capabilities of test varieties in using low light, but reduced the capabilities in using high light.