Competitive oxidation behavior of Ni-based superalloy GH4738 at extreme temperature

A high thrust-to-weight ratio poses challenges to the high-temperature performance of Ni-based superalloys. The oxidation behavior of GH4738 at extreme temperatures has been investigated by isothermal and non-isothermal experiments. As a result of the competitive diffusion of alloying elements, the oxide scale included an outermost porous oxide layer (OOL), an inner relatively dense oxide layer (IOL), and an internal oxide zone (IOZ), depending on the temperature and time. A high temperature led to the formation of large voids at the IOL/IOZ interface. At 1200℃, the continuity of the Cr-rich oxide layer in the IOL was destroyed, and thus, spallation occurred. Extension of oxidation time contributed to the size of Al-rich oxide particles with the increase in the IOZ. Based on this finding,the oxidation kinetics of GH4738 was discussed, and the corresponding oxidation behavior at 900-1100℃ was predicted.

3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porous scaffolds can significantly promote the regeneration of bone defects.

Lysine-specific demethylase 1 inhibitor rescues the osteogenic ability of mesenchymal stem cells under osteoporotic conditions by modulating H3K4 methylation

Bone tissue engineering may be hindered by underlying osteoporosis because of a decreased osteogenic ability of autologous seed cells and an unfavorably changed microenvironment in these patients. Epigenetic regulation plays an important role in the developmental origins of osteoporosis; however, few studies have investigated the potential of epigenetic therapy to improve or rescue the osteogenic ability of bone marrow mesenchymal stem cells(BMMSCs) under osteoporotic conditions. Here, we investigated pargyline, an inhibitor of lysine-specific demethylase 1(LSD1), which mainly catalyzes the demethylation of the di- and mono-methylation of H3K4. We demonstrated that 1.5 mmol·Lpargyline was the optimal concentration for the osteogenic differentiation of human BMMSCs. Pargyline rescued the osteogenic differentiation ability of mouse BMMSCs under osteoporotic conditions by enhancing the dimethylation level of H3K4 at the promoter regions of osteogenesis-related genes. Moreover, pargyline partially rescued or prevented the osteoporotic conditions in aged or ovariectomized mouse models, respectively. By introducing the concept of epigenetic therapy into the field of osteoporosis, this study demonstrated that LSD1 inhibitors could improve the clinical practice of MSC-based bone tissue engineering and proposes their novel use to treat osteoporosis.

Synthesis of CA_(6)/AlON composite with enhanced slag resistance

Different amounts of AlON have been introduced in calcium hexaaluminate(CA_(6)) using two approaches, that is, one-step and twostep methods, to improve the slag resistance of CA_(6). A one-step method can directly sinter the mixtures combining Al_(2)O_(3), CaCO_(3), and Al in flowing nitrogen, in which AlON clusters are always formed because of the poor wettability of Al by Al_(2)O_(3), leading to the high porosity of CA_(6)/AlON composite. In a two-step method, CA_(6)and AlON are prepared separately and then mixed and sintered in flowing nitrogen. Compared with the sample prepared by the one-step method, CA_(6)and AlON in composite by the two-step method are more uniformly distributed,and the optimized amount of AlON added is 10wt%. The slag corrosion and penetration test shows that the CA_(6)/AlON composite using the two-step method exhibits superior slag corrosion protection. The promoted effect of AlON on slag penetration and corrosion resistance is also discussed.

Magnesium alloys in tumor treatment:Current research status, challenges and future prospects

Cancer is a major threat to human life worldwide. Traditional cancer treatments, such as chemotherapy and surgery, have major limitations and can cause irreversible damage to normal tissues while killing the cancer cells. Magnesium(Mg) alloys are widely reported novel potential biomedical materials with acceptable mechanical properties and good osteogenic and angiogenic properties. In this review, we summarize the Mg alloys for antitumor applications, including pure Mg and Mg alloys(Mg-Ag, Mg-Gd, Mg-Li-Zn, Mg-Ca-Sr-Zn, et al.) fabricated by casting and extruding, selective laser melting methods. Mg alloys can exhibit antitumor effect on bone tumor, breast cancer, and liver tumor,etal. What's more, after tumor tissue is eliminated, Mg alloys prevent tumor recurrence, fill tissue defects and promote tissue regeneration.The antitumor effects of Mg alloys are mainly due to their degradation products. Overall, Mg alloys show great potential in tumor treatments due to the dual function of antitumor and tissue regeneration.

Metformin can mitigate skeletal dysplasia caused by Pck2 deficiency

As an important enzyme for gluconeogenesis, mitochondrial phosphoenolpyruvate carboxykinase(PCK2) has further complex functions beyond regulation of glucose metabolism. Here, we report that conditional knockout of Pck2 in osteoblasts results in a pathological phenotype manifested as craniofacial malformation, long bone loss, and marrow adipocyte accumulation. Ablation of Pck2 alters the metabolic pathways of developing bone, particularly fatty acid metabolism. However, metformin treatment can mitigate skeletal dysplasia of embryonic and postnatal heterozygous knockout mice, at least partly via the AMPK signaling pathway.Collectively, these data illustrate that PCK2 is pivotal for bone development and metabolic homeostasis, and suggest that regulation of metformin-mediated signaling could provide a novel and practical strategy for treating metabolic skeletal dysfunction.

Surface modification strategies to reinforce the soft tissue seal at transmucosal region of dental implants

Soft tissue seal around the transmucosal region of dental implants is crucial for shielding oral bacterial invasion and guaranteeing the long-term functioning of implants.Compared with the robust periodontal tissue barrier around a natural tooth,the peri-implant mucosa presents a lower bonding efficiency to the transmucosal region of dental implants,due to physiological structural differences.As such,the weaker soft tissue seal around the transmucosal region can be easily broken by oral pathogens,which may stimulate serious inflammatory responses and lead to the development of peri-implant mucositis.Without timely treatment,the curable peri-implant mucositis would evolve into irreversible peri-implantitis,finally causing the failure of implantation.Herein,this review has summarized current surface modification strategies for the transmucosal region of dental implants with improved soft tissue bonding capacities(e.g.,improving surface wettability,fabricating micro/nano topographies,altering the surface chemical composition and constructing bioactive coatings).Furthermore,the surfaces with advanced soft tissue bonding abilities can be incorporated with antibacterial properties to prevent infections,and/or with immunomodulatory designs to facilitate the establishment of soft tissue seal.Finally,we proposed future research orientations for developing multifunctional surfaces,thus establishing a firm soft tissue seal at the transmucosal region and achieving the long-term predictability of dental implants.

Research status of biodegradable metals designed for oral and maxillofacial applications:A review

The oral and maxillofacial regions have complex anatomical structures and different tissue types,which have vital health and aesthetic functions.Biodegradable metals(BMs)is a promising bioactive materials to treat oral and maxillofacial diseases.This review summarizes the research status and future research directions of BMs for oral and maxillofacial applications.Mg-based BMs and Zn-based BMs for bone fracture fixation systems,and guided bone regeneration(GBR)membranes,are discussed in detail.Zn-based BMs with a moderate degradation rate and superior mechanical properties for GBR membranes show great potential for clinical translation.Fe-based BMs have a relatively low degradation rate and insoluble degradation products,which greatly limit their application and clinical translation.Furthermore,we proposed potential future research directions for BMs in the oral and maxillofacial regions,including 3D printed BM bone scaffolds,surface modification for BMs GBR membranes,and BMs containing hydrogels for cartilage regeneration,soft tissue regeneration,and nerve regeneration.Taken together,the progress made in the development of BMs in oral and maxillofacial regions has laid a foundation for further clinical translation.

In vitro and in vivo investigation on biodegradable Mg-Li-Ca alloys for bone implant application

Magnesium alloys show promise for application in orthopedic implants, owing to their biodegradability and biocompatibility. In the present study, ternary Mg-(3.5,6.5 wt%) Li-(0.2, 0.5, 1.0 wt%) Ca alloys were developed. Their mechanical strength, corrosion behavior and cytocompatibility were studied. These alloys showed improved mechanical strength than pure Mg and exhibited suitable corrosion resistance. Furthermore, Mg-3.5Li-0.5Ca alloys with the best in vitro performance were implanted intramedullary into the femurs of mice for 2 and 8 weeks. In vivo results revealed a significant increase in cortical bone thickness around the Mg-3.5Li-0.5Ca alloy rods, without causing any adverse effects.Western blotting and immunofluorescence staining of β-catenin illustrated that Mg-3.5Li-0.5Ca alloy extracts induced osteogenic differentiation of human bone marrow-derived mesenchymal stem cells(hBMMSCs) through the canonical Wnt/β-catenin pathway. Our studies demonstrate that Mg-3.5Li-0.5Ca alloys hold much promise as candidates for the facilitation of bone implant application.

Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects.However,typical resorbable membranes composed of collagen(Col)have insufficient mechanical properties and high degradation rate,while non-resorbable membranes need secondary surgery.Herein,we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium(Col/PCLMA/Mg)composite membrane that provided spatiotemporal support effect after photocrosslinking.Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed;Col membranes and PCL membranes were used as controls.After photocrosslinking,an interpenetrating polymer network was observed by scanning electron microscopy(SEM)in Col/PCL and Col/PCL/Mg membranes.The elastic modulus,swelling behavior,cytotoxicity,cell attachment,and cell proliferation of the membranes were evaluated.Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM.The membranes were implanted into calvarial bone defects of rats for 8 weeks.The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus(p<0.05),and a lower swelling rate(p<0.05),than Col membranes,and there were no differences in cell biocompatibility among groups(p>0.05).The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes,both in vivo and in vitro(p<0.05).The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8(p<0.05).The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential,which meets clinical needs.

Characterization of mesenchymal stem cells in human fetal bone marrow by single-cell transcriptomic and functional analysis

Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma,cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics ofMSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of humanfetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis. Unexpectedly, while the common cell surfacemarkers such as CD146, CD271, and PDGFRa used for isolating MSCs were not detected, LIFR+PDGFRB+ were identified to bespecific markers of MSCs as the early progenitors. In vivo transplantation demonstrated that LIFR+PDGFRB+CD45-CD31-CD235a-MSCs could form bone tissues and reconstitute the hematopoietic microenvironment (HME) effectively in vivo. Interestingly, wealso identified a subpopulation of bone unipotent progenitor expressing TM4SF1+CD44+CD73+CD45-CD31-CD235a-, which hadosteogenic potentials, but could not reconstitute HME. MSCs expressed a set of different transcription factors at the different stagesof human fetal bone marrow, indicating that the stemness properties of MSCs might change during development. Moreover,transcriptional characteristics of cultured MSCs were significantly changed compared with freshly isolated primary MSCs. Ourcellular profiling provides a general landscape of heterogeneity, development, hierarchy, microenvironment of the human fetal BMderivedstem cells at single-cell resolution.

The PCK2-glycolysis axis assists three-dimensional-stiffness maintaining stem cell osteogenesis

Understanding mechanisms underlying the heterogeneity of multipotent stem cells offers invaluable insights into biogenesis and tissue development. Extracellular matrix (ECM) stiffness has been acknowledged as a crucial factor regulating stem cell fate. However, how cells sense stiffness cues and adapt their metabolism activity is still unknown. Here we report the novel role of mitochondrial phosphoenolpyruvate carboxykinase (PCK2) in enhancing osteogenesis in 3D ECM via glycolysis. We experimentally mimicked the physical characteristics of 3D trabeculae network of normal and osteoporotic bone with different microstructure and stiffness, observing that PCK2 promotes osteogenesis in 3D ECM with tunable stiffness in vitro and in vivo. Mechanistically, PCK2 enhances the rate-limiting metabolic enzyme pallet isoform phosphofructokinase (PFKP) in 3D ECM, and further activates AKT/extracellular signal-regulated kinase 1/2 (ERK1/2) cascades, which directly regulates osteogenic differentiation of MSCs. Collectively, our findings implicate an intricate crosstalk between cell mechanics and metabolism, and provide new perspectives for strategies of osteoporosis.

Effect of Sn doping concentration on the oxidation of Al-containing MAX phase(Ti_(3)AlC_(2))combining simulation with experiment

Sn doping is usually adopted to prepare Ti_(3)AlC_(2)in mass production because it can reduce the synthesis temperature while increasing the phase purity.However,excessive Sn doping usually deteriorates the oxidation resistance of Ti_(3)AlC_(2).Therefore,an appropriate Sn doping concentration is a vital issue.In this work,the effect of Sn doping concentration on the oxidation behavior of Ti_(3)AlC_(2)was systematically investigated by combining theoretical calculations and experimental methods.Density function theory calculations suggest that the oxygen adsorption mechanisms for the(001)surface of Ti_(3)AlC_(2)with and without Sn doping are similar,and Ti-O bonds are always preferentially formed.The molecular dynamics simulation further indicates that Al atoms have a faster diffusion rate during the oxidation process.Therefore,a continuous Al_(2)O_(3)layer can form rapidly at high temperature.Nevertheless,when the Sn doping concentration exceeds 10 mol%,the continuity of the Al_(2)O_(3)layer is destroyed,thereby impairing the oxidation resistance of Ti_(3)AlC_(2).Furthermore,oxidation experiments verify the above results.The oxidation mechanisms of Ti3AlC2 with different Sn doping concentrations are also proposed.

Population genomic analysis reveals distinct demographics and recent adaptation in the black flying fox(Pteropus alecto)

As the only mammalian group capable of powered flight,bats have many unique biological traits.Previous comparative genomic studies in bats have focused on long-term evolution.However,the microevolutionary processes driving recent evolution are largely under-explored.Using resequencing data from 50 black flying foxes(Pteropus alecto),one of the model species for bats,we find that black flying fox has much higher genetic diversity and lower levels of linkage disequilibrium than most of the mammalian species.Demographic inference reveals strong population fluctuations(>100 fold)coinciding with multiple historical events including the last glacial change and Toba super eruption,suggesting that the black flying fox is a very resilient species with strong recovery abilities.While long-term adaptation in the black flying fox is enriched in metabolic genes,recent adaptation in the black flying fox has a unique landscape where recently selected genes are not strongly enriched in any functional category.The demographic history and mode of adaptation suggest that black flying fox might be a well-adapted species with strong evolutionary resilience.Taken together,this study unravels a vibrant landscape of recent evolution for the black flying fox and sheds light on several unique evolutionary processes for bats comparing to other mammalian groups.

Exosomes derived from human adipose-derived stem cells ameliorate osteoporosis through miR-335-3p/Aplnr axis

Treatment of osteoporosis is still a challenge in clinic,which leads to an increasing social burden as the aging of population.Exosomes originated from human adipose-derived stem cells(hASCs)hold promise to promote osteogenic differentiation,thus may ameliorate osteoporosis.The main purpose of this study was to investigate the novel usage of hASC-derived exosomes in the treatment of osteoporosis and their underlying mechanism.Two types of exosomes,i.e.,exosomes derived from hASCs cultured in proliferation medium(P-Exos)and osteogenic induction medium(O-Exos),were obtained.As compared with P-Exos,O-Exos could promote the osteogenic differentiation of mouse bone marrow-derived stem cells(mBMSCs)from osteoporotic mice in vitro and ameliorated osteoporosis in vivo.Then,microRNA(miRNA)-335-3p was identified to be the key differentially expressed microRNA between the two exosomes by small RNA sequencing,gene overexpression and knock-down,qRT-PCR,and dual-luciferase reporter assay,and Aplnr was confirmed to be the potential target gene of miRNA-335-3p.In addition,miR335-3p inhibitor-optimized O-Exos were established by transfection of miR-335-3p inhibitor,which significantly enhanced the osteogenic differentiation of mBMSCs in vitro,and bone density and number of trabecular bones in vivo compared with unoptimized O-Exos.Our results indicated that the ASC-exosome-based therapy brings new possibilities for osteoporosis treatment.Besides,engineered exosomes based on transfection of miRNA are a promising strategy to optimize the therapeutic effect of exosomes on osteoporosis.

Consequential fate of bisphenol-attached PVC microplastics in water and simulated intestinal fluids

The ever-increasing prevalence of microplastics and different bisphenols made the presence of bisphenol-attached microplastics a critical concern.In this study,experiments were performed to examine desorption behaviors and cytotoxicity performance of contaminated microplastics in aquatic surroundings and intestinal environment after ingestion by organisms(cold-/warm-blooded).The kinetic study shows that the rate of desorption for bisphenols can be enhanced threefold under simulated warm intestinal conditions.The Freundlich isotherms indicate multiple-layer desorption of the bisphenols on the heterogeneous surfaces of polyvinyl chloride(PVC)microplastics.Hysteresis was detected in the adsorption/desorption of bisphenols in a water environment,but no adsorption/desorption hysteresis was observed in the simulated intestinal conditions of warm-blooded organisms.Due to enhanced bioaccessibility,the desorption results imply that the environmental risk of contaminated PVC microplastics may be significantly increased after ingestion at a high bisphenols dosage.Although with different IC_(50),the five bisphenols released under the intestinal conditions of warm-blooded organisms can cause higher proliferation reduction in fish and human cell lines than the bisphenols released in water.This study helps elucidate the consequential fate and potential cytotoxicity of contaminated microplastics and the possible implications of the microplastics as a critical vector for bisphenols to increase the potential health risks.

Sustained release of magnesium and zinc ions synergistically accelerates wound healing

Skin wounds are a major medical challenge that threaten human health.Functional hydrogel dressings demonstrate great potential to promote wound healing.In this study,magnesium(Mg)and zinc(Zn)are introduced into methacrylate gelatin(GelMA)hydrogel via low-temperature magnetic stirring and photocuring,and their effects on skin wounds and the underlying mechanisms are investigated.Degradation testing confirmed that the GelMA/Mg/Zn hydrogel released magnesium ions(Mg^(2+))and zinc ions(Zn^(2+))in a sustained manner.The Mg^(2+) and Zn^(2+)not only enhanced the migration of human skin fibroblasts(HSFs)and human immortalized keratinocytes(HaCats),but also promoted the transformation of HSFs into myofibroblasts and accelerated the production and remodeling of extracellular matrix.Moreover,the GelMA/Mg/Zn hydrogel enhanced the healing of full-thickness skin defects in rats via accelerated collagen deposition,angiogenesis and skin wound re-epithelialization.We also identified the mechanisms through which GelMA/Mg/Zn hydrogel promoted wound healing:the Mg^(2+) promoted Zn^(2+)entry into HSFs and increased the concentration of Zn^(2+)in HSFs,which effectively induced HSFs to differentiate into myofibroblasts by activating the STAT3 signaling pathway.The synergistic effect of Mg^(2+) and Zn^(2+)promoted wound healing.In conclusion,our study provides a promising strategy for skin wounds regeneration.