Expert consensus on pediatric orthodontic therapies of malocclusions in children

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

蒸镀氧化铝、氧化硅型高阻隔性包装薄膜

阻隔膜材料因优异的阻隔性能在食品、药品、日化、电子等产品包装等领域具有广泛的应用,本文简要介绍了多种高阻隔材料,详细论述了蒸镀氧化铝、氧化硅型高阻隔性膜进程、技术工艺、阻隔性能及原理和应用。

Genetic modification of miR-34a enhances efficacy of transplanted human dental pulp stem cells after ischemic stroke

Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.

Business Model,Current Situation and Development Countermeas-ures of Maize in Shiyan City,Hubei Province

In order to understand the status of business model and scale business of maize in Shiyan City,Hubei Province,the situation of maize production in 314 households of 6 counties and cities of Shiyan City was investigated in terms of rural basic situation,business models,economic benefits and scale business. Targeting at the actual problems in business models and scale business,corresponding countermeasures of actively promoting the construction of industrialized business mechanism,improving the construction of agricultural infrastructure,strengthening land transfer management and promoting scientific and technological progress and innovation were put forward to provide reference for the future scale development of maize in Shiyan City.

Present Situation,Problems and Countermeasures of Land Transfer in the Process of Agricultural Industrialization in the Qinling-Daba Mountains(Shiyan)

In order to study the current situation of land transfer in the process of agricultural industrialization in the Qinling-Daba Mountains(Shiyan),27 villages of 14 townships(towns) of six counties(cities) were visited and investigated through questionnaires,and the current situation and characteristics of land transfer among large professional households( large grain producers),family farms,agricultural enterprises and cooperatives in the process of agricultural industrialization were analyzed and summarized. The main issues affecting land transfer were summarized,such as big difference of inflow and outflow will,single way of land transfer,high cost of planting,weak agricultural infrastructure,a lack of production and operation technology,insufficient funds and short land transfer period,and imperfect social security system.Meanwhile,some countermeasures were proposed,such as improving land transfer system,precise subsidy policy and social security mechanism of Shiyan City,guiding long-term and normalized land transfer,strengthening training of professional skills and improving the quality of human resources,actively promoting the " three-township project",and attracting the investment in land transfer projects.

Hierarchical method of task assignment for multiple cooperating UAV teams

The problem of task assignment for multiple cooperating unmanned aerial vehicle(UAV) teams is considered. Multiple UAVs forming several small teams are needed to perform attack tasks on a set of predetermined ground targets. A hierarchical task assignment method is presented to address the problem. It breaks the original problem down to three levels of sub-problems: target clustering, cluster allocation and target assignment. The first two sub-problems are centrally solved by using clustering algorithms and integer linear programming, respectively, and the third sub-problem is solved in a distributed and parallel manner, using a mixed integer linear programming model and an improved ant colony algorithm. The proposed hierarchical method can reduce the computational complexity of the task assignment problem considerably, especially when the number of tasks or the number of UAVs is large. Experimental results show that this method is feasible and more efficient than non-hierarchical methods.

Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries

Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.

Comprehensive strategy of conduit guidance combined with VEGF producing Schwann cells accelerates peripheral nerve repair

Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.

Mesoporous silica rods with cone shaped pores modulate inflammation and deliver BMP-2 for bone regeneration

Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of mesoporous silica rods with large cone-shaped pores(MSR-CP)to load and deliver large protein drugs.It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage.Furthermore,bone morphogenetic proteins 2(BMP-2)loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.In vivo tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance.This study provides a potential strategy for the design of drug delivery systems for bone regeneration.

A shear-thinning,ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis

Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.

MSC based gene delivery methods and strategies improve the therapeutic efficacy of neurological diseases

Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.

Beclin-1/LC3-II dependent macroautophagy was uninfluenced in ischemia-challenged vascular endothelial cells

Autophagy has been extensively studied and occurs in many biological settings.However,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has been previously thought.Furthermore,the effect of the level of autophagy on cell or skin flap survival still requires elucidation.We created a lethal ischemia model in human umbilical vascular endothelial cells(HUVECs),performed quantitative proteomics and bioinformatics analyses,and verified the autophagic status and effect both in vitro and in vivo.The significantly upregulated proteins encoded by autophagy-related genes(ATGs)included ATG2A,ATG3,ATG4B,ATG5,ATG7,ATG9A,ATG12,ATG16,and ATG101.The significantly enhanced lysosomal proteins were cathepsin B,cathepsin D,lysosome-associated membrane protein 1(LAMP1),and LAMP2.However,the differentially expressed proteins excluded Beclin-1,microtubule-associated protein light chain 3(LC3)-I,and LC3-II.Western blot analyses verified that the protein expression levels of Beclin-1,LC3-I,and LC3-II were neither upregulated nor downregulated in ischemia-challenged HUVECs.The autophagic status was not enhanced by rapamycin in ischemic HUVECs but appeared to be inhibited by chloroquine.Our in vivo study on rats showed that a downregulation in autophagic status jeopardized skin flap survival.In conclusion,Ischemia neither enhanced nor inhibited Beclin-1/LC3-II-dependent canonical macroautophagy both in vitro and in vivo,in contradiction to previous studies.An appropriate autophagic homeostasis can minimize cell or skin flap damage.

Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

In vivo performance of a rare earth free Mg-Zn-Ca alloy manufactured using twin roll casting for potential applications in the cranial and maxillofacial fixation devices

A magnesium alloy containing essential,non-toxic,biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process(TRC).Microstructure,mechanical properties,in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth(RE)element containing WE43 alloy.TRC Mg-0.5 wt% Zn-0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150μm.Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%.The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51±0.07 mm/y similar to that of the WE43 alloy(0.47±0.09 mm/y)in the rat model after 1 week of implantation.By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant.The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation.The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.

Myocardial protection by heparin-based coacervate of FGF10

Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.

Inorganic/organic combination:Inorganic particles/polymer composites for tissue engineering applications

Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones,and thus are highly desired.The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature.In this review,we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine.We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts.As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites,the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites.The inorganic particles that are covered in this review are categorised into two broad types(1)solid(e.g.,calcium phosphate,hydroxyapatite,etc.)and(2)porous particles(e.g.,mesoporous silica,porous silicon etc.),which are elaborated in detail with recent examples.The review also covers other new types of inorganic material(e.g.,2D inorganic materials,clays,etc.)based polymer composites for tissue engineering applications.Lastly,we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.

Corrigendum to‘Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries’[Bioactive Mater.6(3)(2021)638-654]

The authors regret that the author(A.H.)was removed as an agreement could not be reached between the two affiliations of the author.The authors would like to apologise for any inconvenience caused.