Odontogenesis-Empowered Extracellular Vesicles Safeguard Donor-Recipient Stem Cell Interplay to Support Tooth Regeneration.

Harnessing the developmental events of mesenchymal condensation to direct postnatal dental stem cell aggregation represents a cutting-edge and promising approach to tooth regeneration. Tooth avulsion is among the most prevalent and serious dental injuries, and odontogenic aggregates assembled by stem cells from human exfoliated deciduous teeth (SHED) have proven effective in revitalizing avulsed teeth after replantation in the clinical trial. However, whether and how SHED aggregates (SA) communicate with recipient components and promote synergistic tissue regeneration to support replanted teeth remains elusive. Here, it is shown that SA-mediated avulsed tooth regeneration involves periodontal restoration and recovery of recipient Gli1+ stem cells, which are mobilized and necessarily contribute to the reestablishment of the tooth-periodontal ligament-bone interface. Mechanistically, the release of extracellular vesicles (EVs) is revealed indispensable for the implanted SA to mobilize recipient Gli1+ cells and regenerate avulsed teeth. Furthermore, SHED aggregates-released EVs (SA-EVs) are featured with odontogenic properties linked to tissue regeneration, which enhance migration, proliferation, and differentiation of Gli1+ cells. Importantly, local application of SA-EVs per se empowers recipient Gli1+ cells and safeguards regeneration of avulsed teeth. Collectively, the findings establish a paradigm in which odontogenesis-featured EVs govern donor-recipient stem cell interplay to achieve tooth regeneration, inspiring cell-free translational regenerative strategies.

Lactobacillus Reuteri Vesicles Regulate Mitochondrial Function of Macrophages to Promote Mucosal and Cutaneous Wound Healing.

The interplay between bacteria and their host influences the homeostasis of the human immune microenvironment, and this reciprocal interaction also affects the process of tissue damage repair. A variety of immunomodulatory commensal bacteria reside in the body, capable of delivering membrane vesicles (MVs) to host cells to regulate the local immune microenvironment. This research revealed, for the initial time, the significant enhancement of mucosal and cutaneous wound healing by MVs secreted by the human commensal Lactobacillus reuteri (RMVs) through modulation of the inflammatory environment in wound tissue. Local administration of RMVs reduces the proportion of pro-inflammatory macrophages in inflamed tissues and mitigates the level of local inflammation, thereby facilitating the healing of oral mucosa and cutaneous wounds. The elevated oxidative stress levels in activated pro-inflammatory macrophages can be modulated by RMVs, resulting in phenotypic transformation of macrophages. Furthermore, 3-hydroxypropionaldehyde present in RMVs can decrease the mitochondrial permeability of macrophages and stabilize the mitochondrial membrane potential, thereby promoting the conversion of macrophages to an anti-inflammatory phenotype. This study pioneers the significance of commensal bacterial MVs in tissue injury repair and presents a novel concept for the repair of tissue damage.

Effect of Solder Layer Void Damage on the Temperature of IGBT Modules.

Solder layer void is one of the main failure causes of power semiconductor devices, which will seriously affect the reliability of the devices. In this study, a 3D model of IGBT (Insulated Gate Bipolar Transistor) packaging was built by DesignModeler. Based on ANSYS Workbench, the influence of void size, location, solder layer type, and thickness on the temperature distribution of the IGBT module was simulated. The results show that the larger the void radius, the higher the temperature of the IGBT module. The closer the void is to the center of the solder layer, the higher the temperature of the module. The void on the top corner of the solder layer had the greatest impact on the junction temperature of the IGBT module, and the shape of the void is also one of the factors that affect the temperature of the module. The denser the void distribution, the higher the temperature of the module. The temperature of the IGBT module was reduced from 62.656 °C to 59.697 °C by using nanosilver solder paste, and the overall heat dissipation performance of the module was improved by 5%. The temperature of the module increased linearly with the increase in solder layer thickness, and the temperature increased by 0.8 °C for every 0.025 mm increase in solder layer thickness. The simulation results have a guiding significance for improving the thermal stability of IGBT modules.

Integrating Pillar[5]arene and BODIPY for a Supramolecular Nanoplatform To Achieve Synergistic Photodynamic Therapy and Chemotherapy.

BODIPY photosensitizers have been integrated with a hypoxia-activated prodrug to achieve synergistic photodynamic therapy (PDT) and chemotherapy. A novel BODIPY derivative BDP-CN was designed and synthesized. It had two cyano groups to make it complex well with a water-soluble pillar[5]arene. Their association constant was calculated to be (6.8±0.9)×106  M-1 . After self-assembly in water, regular spherical nanocarriers can be formed; these were used to encapsulate the hypoxia-activated prodrug tirapazamine (TPZ). BDP-CN displayed excellent photodynamic activity to complete PDT. In this process, O2 can be continuously consumed to activate TPZ to allow it to be converted to a benzotriazinyl (BTZ) radical with high cytotoxicity to complete chemotherapy. As a result, the formed nanoparticles showed excellent synergistic photodynamic therapy and chemotherapy efficacy. The synergistic therapy mechanism is discussed in detail.

Reliability Analysis of Flip-Chip Packaging GaN Chip with Nano-Silver Solder BUMP.

Gallium nitride (GaN) power devices have many benefits, including high power density, small footprint, high operating voltage, and excellent power gain capability. However, in contrast to silicon carbide (SiC), its performance and reliability can be negatively impacted by its low thermal conductivity, which can cause overheating. Hence, it is necessary to provide a reliable and workable thermal management model. In this paper, a model of a flip-chip packing (FCP) GaN chip was established, and it was assigned to the Ag sinter paste structure. The different solder bumps and under bump metallurgy (UBM) were considered. The results indicated that the FCP GaN chip with underfill was a promising method because it not only reduced the size of the package model but also reduced thermal stress. When the chip was in operation, the thermal stress was about 79 MPa, only 38.77% of the Ag sinter paste structure, lower than any of the GaN chip packaging methods currently in use. Moreover, the thermal condition of the module often has little to do with the material of the UBM. Additionally, nano-silver was found to be the most suitable bump material for FCP GaN chip. Temperature shock experiments were also conducted with different UBM materials when nano-silver was used as bump. It was found that Al as UBM is a more reliable option.

Construction, Characterization, and Regenerative Application of Self-Assembled Human Mesenchymal Stem Cell Aggregates.

Mesenchymal stem cells (MSCs), characterized by their self-renewal ability and multilineage differentiation potential, can be derived from various sources and are emerging as promising candidates for regenerative medicine, especially for regeneration of the tooth, bone, cartilage, and skin. The self-assembled approach of MSC aggregation, which notably constructs cell clusters mimicking the developing mesenchymal condensation, allows high-density stem cell delivery along with preserved cell-cell interactions and extracellular matrix (ECM) as the microenvironment niche. This method has been shown to enable efficient cell engraftment and survival, thus promoting the optimized application of exogenous MSCs in tissue engineering and safeguarding clinical organ regeneration. This paper provides a detailed protocol for the construction and characterization of self-assembled aggregates based on umbilical cord mesenchymal stem cells (UCMSCs), as well as an example of the cranial bone regenerative application. The implementation of this procedure will help guide the establishment of an efficient MSC transplantation strategy for tissue engineering and regenerative medicine.

Amyloid-mediated remineralization for tooth hypoplasia of cleidocranial dysplasia.

Introduction: Cleidocranial dysplasia (CCD) is an autosomal-dominant, heritable skeletal and dental disease, involving hypoplastic clavicles, defective ossification of the anterior fontanelle, dentin and enamel hypoplasia, and supernumerary teeth, which can seriously affect the oral and mental health of patients. Amyloid-like protein aggregation, which is established by lysozyme conjugated with polyethylene glycol (Lyso-PEG), forms a mineralized nanofilm layer on a healthy enamel surface. However, whether it can form a remineralization layer in dental tissues from CCD remains unclear. Methods: This study evaluated deciduous teeth from healthy individuals and a patient with CCD. Because pulp and dentin are functionally closely related, stem cells from human exfoliated deciduous teeth (SHED) from CCD patients and healthy individuals were collected to compare their biological properties. Results: The results found that deciduous teeth from patients with CCD exhibited dentin hypoplasia. In addition, the proliferative ability and osteogenic potential of SHED from patients with CCD were lower than those of control individuals. Finally, Lyso-PEG was applied to dentin from the CCD and control groups, showing a similar remineralization-induced effect on the dentin surfaces of the two groups. Conclusion: These results extend our understanding of the dentin and SHED of patients with CCD, exhibiting good caries-preventive capacity and good biocompatibility of Lyso-PEG, thus providing a novel dental therapy for CCD and patients with tooth hypoplasia.

Mesenchymal stem cells: Emerging concepts and recent advances in their roles in organismal homeostasis and therapy.

Stem cells play a crucial role in re-establishing homeostasis in the body, and the search for mechanisms by which they interact with the host to exert their therapeutic effects remains a key question currently being addressed. Considering their significant regenerative/therapeutic potential, research on mesenchymal stem cells (MSCs) has experienced an unprecedented advance in recent years, becoming the focus of extensive works worldwide to develop cell-based approaches for a variety of diseases. Initial evidence for the effectiveness of MSCs therapy comes from the restoration of dynamic microenvironmental homeostasis and endogenous stem cell function in recipient tissues by systemically delivered MSCs. The specific mechanisms by which the effects are exerted remain to be investigated in depth. Importantly, the profound cell-host interplay leaves persistent therapeutic benefits that remain detectable long after the disappearance of transplanted MSCs. In this review, we summarize recent advances on the role of MSCs in multiple disease models, provide insights into the mechanisms by which MSCs interact with endogenous stem cells to exert therapeutic effects, and refine the interconnections between MSCs and cells fused to damaged sites or differentiated into functional cells early in therapy.

TXNIP Participated in NLRP3-Mediated Inflammation in a Rat Model of Cervical Spondylotic Myelopathy.

Background: Cervical spondylotic myelopathy (CSM) is a spinal cord disease caused by cervical disc degeneration and related pathological changes. Cervical spondylotic myelopathy may result from inflammation responses and neuronal damage. Thioredoxin-interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling promotes inflammation. However, the effects of TXNIP/NLRP3 on the pathogenesis of CSM have not been reported. Methods: A rat model of chronic cervical cord compression was established to observe changes in the levels of of TNXIP/NeuN and NLRP3/NeuN expression in the damaged anterior horn of the spinal cord following progression of CSM. Rats were injected with TXNIP small interfering RNA (siRNA) and scrambled control to determine the effects of TXNIP inhibition on NLRP3-mediated inflammation in rats with CSM. Behaviors effects and the expression of NLRP3 and pro-caspase-1 in the damaged spinal cord were evaluated. Results: The expression levels of TXNIP and NLRP3 were significantly increased in the damaged anterior horn of the spinal cord following CSM. Injection of TXNIP siRNA significantly improved behavioral measures and decreased apoptosis in the damaged anterior horn of spinal cord. Furthermore, the levels of NLRP3 and pro-caspase-1 in the lesioned area were reduced by the TXNIP siRNA injection. Conclusion: Thioredoxin-interacting protein participated in NLRP3 mediated inflammation in a rat model of CSM, which indicated that TXNIP may be a potential therapeutic target in improving CSM.

Amyloid-Mediated Remineralization in Pit and Fissure for Caries Preventive Therapy.

The pits and fissures of teeth have high caries susceptibility, and sealing these areas is considered as an effective method to prevent caries. However, long-term caries prophylaxis cannot be maintained because of the negative effects derived from the technical sensitivity and disadvantages of sealing materials. Herein, a new strategy is proposed to occlude fossae by amyloid-mediated biomimetic remineralization. In contrast to conventional inward blocking from the outside of fossae, amyloid-mediated biomimetic mineralization delivers an amyloid-like protein nanofilm into the deepest zone of the fossae and induces the formation of remineralized enamel inside. Such assembly from lysozyme conjugated with poly (ethylene glycol) enriches the interface with strongly bonded ionsand directs in situ nucleation to achieve enamel epitaxial growth. Not only is the structure of the enamel-like crystalline hydroxyapatite layer but also its mechanical stability is similar to that of natural enamel. Furthermore, the layer shows good biocompatibility and antibacterial properties. On the basis of the findings, it is demonstrated that amyloid-like protein aggregation may provide an enamel remineralization strategy to modify the current clinically available methods of pit and fissure sealing and shows great promise in preventing caries.

Cacna2d2 inhibits axonal regeneration following surgical decompression in a rat model of cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM) is a clinically symptomatic condition due to spinal cord compression, leading to spinal cord dysfunction. Surgical decompression is the main treatment of CSM, but the mechanisms of axonal regeneration after surgical decompression are still fragmentary. METHODS: In a rat model of CSM, the cacna2d2 (α2δ2) expression levels in anterior horn of spinal cord were observed following compression and decompression by western blot and immunofluorescence. The expression levels of 5 hydroxytryptamine (5HT) and GAP43 were also analyzed by immunofluorescence. Furthermore, gabapentin intervention was performed for 4 weeks after decompression to analyze the changes of behaviors and anterior horn of spinal cords. RESULTS: Following decompression, the expression levels of α2δ2 in the anterior horn of spinal cord were decreased, but the expression levels of 5HT andGAP43 were increased. Compared with the vehicle treated rats, gabapentin treatment for 4 weeks ameliorated the behaviors of rats and improved the damaged anterior horn of spinal cord. Besides, inhibition of α2δ2 through gabapentin intervention enhanced the axonal regeneration in the anterior horn of damaged spinal cord. CONCLUSIONS: Inhibition of α2δ2 could enhance axonal recovery in anterior horn of damaged spinal cord induced by CSM after surgical decompression, providing a potential method for promoting axon regeneration following surgery.

Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration.

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.

Heat Dissipation Characteristics of IGBT Module Based on Flow-Solid Coupling.

With the increase of power level and integration in electric vehicle controllers, the heat flux of the key silicon-based IGBT (Insulated Gate Bipolar Transistor) device has reached its physical limit. At present, third-generation semiconductor devices including SiC MOSFETs (Metal-Oxide-Semiconductor Field-Effect Transistor) are gradually replacing the dominant IGBT module. The hybrid IGBT module consists of both and can improve the performance and reduce the cost of controllers. Limits due to the installation space, location, and other conditions in the car make it difficult to meet the requirements of controllers with an air-cooled heatsink due to their large size and limited heat dissipation capacity. A smaller and more powerful water-cooled heatsink case is required to ensure the heat dissipation of the IGBT in the controller. Based on previous experience in finite element numerical simulation, hydrodynamics calculation, and heat transfer calculation, ANSYS Workbench finite element software was used to analyze the thermal resistance of each structure inside the module and the heatsink structure. The fluid characteristics and heat transfer performance of three different flow channel structures were analyzed, and the design of the cooling flow fin was improved to provide a reference for the heat dissipation of the hybrid IGBT module.

Development of LED Package Heat Dissipation Research.

LEDs are widely used in medicine, navigation and landscape lighting. The development of high-power LED is a severe challenge to LED heat dissipation. In this review, packaging technology and packaging structure are reviewed in terms of the thermal performance of LED packaging, and related technologies that promote heat dissipation in LED packaging are introduced. The design of three components to enhance heat dissipation in LED packaging is described: substrate, lens and phosphor layer. By conducting a summary of the technology and structure of the package, the defects of LED package technology and structure are deeply investigated, and the package is prospected. This has reference value for the heat dissipation design of the LED package and helps to improve the design and manufacture of the LED package.

Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis.

Early orthodontic correction of skeletal malocclusion takes advantage of mechanical force to stimulate unclosed suture remodeling and to promote bone reconstruction; however, the underlying mechanisms remain largely unclear. Gli1+ cells in maxillofacial sutures have been shown to participate in maxillofacial bone development and damage repair. Nevertheless, it remains to be investigated whether these cells participate in mechanical force-induced bone remodeling during orthodontic treatment of skeletal malocclusion. In this study, rapid maxillary expansion (RME) mouse models and mechanical stretch loading cell models were established using two types of transgenic mice which are able to label Gli1+ cells, and we found that Gli1+ cells participated in mechanical force-induced osteogenesis both in vivo and in vitro. Besides, we found mechanical force-induced osteogenesis through inositol 1,4,5-trisphosphate receptor (IP3R), and we observed for the first time that inhibition of Gli1 suppressed an increase in mechanical force-induced IP3R overexpression, suggesting that Gli1+ cells participate in mechanical force-induced osteogenesis through IP3R. Taken together, this study is the first to demonstrate that Gli1+ cells in maxillofacial sutures are involved in mechanical force-induced bone formation through IP3R during orthodontic treatment of skeletal malocclusion. Furthermore, our results provide novel insights regarding the mechanism of orthodontic treatments of skeletal malocclusion.

Research on Heat Dissipation of Multi-Chip LED Filament Package.

By studying the substrate material, structure, chip distribution, and array form of the multi-chip light-emitting diode (LED) package, the heat-dissipation capacity of the LED package is improved. Finite element analysis and steady-state thermal analysis are used to simulate and analyze LED packages with different materials and structures. Using the theory of LED illuminance and uniformity, the illuminance of some structures is computed. The results show that the change of substrate material and structure can greatly impact heat dissipation, while changing array forms has little effect on heat dissipation. By improving the spatial distribution of the chip, the temperature superposition problem of the substrate is solved, and the illuminance and uniformity are improved while dissipating heat. The LED filaments of the combined, equidistant, chip-distribution mode have improved heat dissipation. The S-type equal difference has the highest illumination and high illumination uniformity.

Erratum to "Gli1+ Cells Residing in Bone Sutures Respond to Mechanical Force via IP3R to Mediate Osteogenesis".

[This corrects the article DOI: 10.1155/2021/8138374.].

Macrophage-Specific IκB Kinase α Contributes to Ventricular Remodelling and Dysfunction After Myocardial Infarction.

BACKGROUND: The IκB kinase (IKK) complex has been found to have critical functions in cancer and the immune system. In particular, IKKα, which is a member of the IKK complex, has been shown to influence the inflammatory response and malignant diseases. However, the role of IKKα in macrophages after myocardial infarction (MI) remains largely unknown. METHODS: Sham or MI operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ-/-) mice and IKKɑflox/flox littermates. We ligated the left anterior descending coronary artery of the MI group and observed the results at 3, 7, and 30 days after MI. RESULTS: We discovered more severe cardiac dysfunction with reduced angiogenesis, fibrosis, and collagen deposition in mIKKɑ-/- than in IKKɑflox/flox. In addition, we also observed that macrophages in mIKKɑ-/- were easier to polarize to the M1 phenotype and expressed more proinflammatory factors than IKKɑflox/flox. Mechanistically, IKKα deficiency in macrophages inhibited the alternative nuclear factor-κB/RelB pathway and enhanced the MEK1/2/ERK1/2 pathway. CONCLUSIONS: Overall, our data identified IKKɑ in the heart as a novel mediator that protected the heart from a severe inflammatory response and attenuated ventricular remodelling after MI by negatively regulating macrophage polarization to the M1 phenotype. Therefore, IKKα may serve as a potential therapeutic target for treatment after MI.

Rapid and High-Efficiency Laser-Alloying Formation of ZnMgO Nanocrystals.

Applications of ZnMgO nanocrystals (NCs), especially in photoelectric detectors, have significant limitations because of the unresolved phase separation in the synthesis process. Here, we propose a rapid and highly efficient ZnMgO NC alloying method based on pulsed laser ablation in liquid. The limit value of homogeneous magnesium (Mg) is pushed from 37% to 62%, and the optical band gap is increased to 3.7 eV with high doping efficiency (>100%). Further investigations on the lattice geometry of ZnMgO NCs indicate that all ZnMgO NCs are hexagonal wurtzite structures, and the (002) and (100) peaks shift to higher diffraction angles with the increase in Mg doping content. The calculated results of the lattice constants a and c slightly decrease based on Bragg's law and lattice geometry equations. Furthermore, the relationship between annealing temperature and the limit value of homogeneous Mg is examined, and the results reveal that the latter decreases with the former because of the phase separation of MgO. A probable mechanism of zinc magnesium alloy is introduced to expound on the details of the laser-alloying process.

[Comparison of clinical efficacies of single segment transforaminal lumbar interbody fusion with cage versus autogenous morselized bone for degenerative lumbar spinal stenosis: a prospective randomized controlled study].

OBJECTIVE: To compare the clinical efficacies of single segment transforaminal lumbar interbody fusion (TLIF) with cage versus autogenous morselized bone for degenerative lumbar spinal stenosis. METHODS: A total of 87 patients undergoing single segment TLIF were randomly divided into 2 groups. A cage was implanted into intervertebral space in group A patients while autogenous morselized bone in group B patients. Operative duration, blood loss, length of stay and cost of hospitalization of two groups were recorded. They were followed up at 1 week, 12, 24 months post-operation. Oswestry disability index (ODI), visual analogue scale (VAS) fusion rates, intervertebral space and foramen height restoration, lumbar lordosis and postoperative complications were compared between two groups. RESULTS: No significant inter-group difference existed in operative duration, blood loss or length of stay. However, the average hospitalization cost in group A were 18% higher than that of group B (P < 0.05). Both groups achieved excellent clinical outcomes within 2 years. ODI, VAS score improvement rates and postoperative complication rates were not statistically different. Lumbar fusion rate was 86.7% in group A versus 85.7% in group B after 2 years. And there was no significant difference (P > 0.05). The heights of intervertebral space and foramen in group A achieved a better recovery than those of group B. Both groups had similar improvements of lumbar lordosis. CONCLUSION: For degenerative lumbar spinal stenosis, usage of interbody cage is more effective in terms of recovery of intervertebral space and foraminal height compared with usage of bone graft. However it brings no better clinical efficacy while the usage of autogenous morselized bone is more cost-effective. Two grafting methods yield similar overall clinical outcomes.