Dynamic response of axle box bearing for high-speed train considering wheelset flexibility and polygonal wear.

In this study, a flexible wheelset was added to a rigid-flexible coupled vehicle dynamics model, in which the axle box bearings are accurately modeled. The measured wheel's polygon wear profile and Wuhan-Guangzhou track spectrum are used in the model to define the wheel tread and track irregularity, respectively. We conducted a field test on the Wuhan-Guangzhou railway line to validate the model. Then, we investigate how the dynamic properties of the axle box bearing are impacted by the wheelset flexibility and polygonal wear of wheel. We found that the polygonal wheel with a rigid wheelset causes high-frequency vibration in wheelset and axle box, and increases the axle box bearing's internal contact force. Additionally, the flexible wheelset with a normal wheel tread can alleviate the wheel/rail impact and reduce the axle box's vertical vibration as well as the axle box bearing's internal contact force. When the vehicle is running at v = 300 km/h, the excitation frequency caused by the wheel's 20th-order polygon is 576.5 Hz, and the flexible wheelset's 20th-order modal frequency is 577 Hz. The two frequencies are similar, when considering the polygonal wheel and flexible wheelset simultaneously, the wheelset will resonate. And the resonate of wheelset will increase the local deformation of the axle end and deteriorate the bearing operating environment, causing a significant increase in the bearing contact force. Finally, the axle box bearing's dynamic characteristics are summarized when vehicle velocity varies from 50 to 350 km/h and wheel polygon wear amplitude ranges from 0.01 to 0.05 mm.

Adipose-Derived Stem Cell Extracellular Vesicles Improve Wound Closure and Angiogenesis in Diabetic Mice.

BACKGROUND: Currently, there is a lack in therapy that promotes the reepithelialization of diabetic wounds as an alternative to skin grafting. Here, the authors hypothesized that extracellular vesicles from adipose-derived stem cells (ADSC-EVs) could accelerate wound closure through rescuing the function of keratinocytes in diabetic mice. METHODS: The effect of ADSC-EVs on the biological function of human keratinocyte cells was assayed in vitro. In vivo, 81 male severe combined immune deficiency mice aged 8 weeks were divided randomly into the extracellular vesicle-treated diabetes group (n = 27), the phosphate-buffered saline-treated diabetes group (n = 27), and the phosphate-buffered saline-treated normal group (n = 27). A round, 8-mm-diameter, full-skin defect was performed on the back skin of each mouse. The wound closure kinetics, average healing time, reepithelialization rate, and neovascularization were evaluated by histological staining. RESULTS: In vitro, ADSC-EVs improved proliferation, migration, and proangiogenic potential, and inhibited the apoptosis of human keratinocyte cells by suppressing Fasl expression with the optimal dose of 40 µg/mL. In vivo, postoperative dripping of ADSC-EVs at the dose of 40 µg/mL accelerated diabetic wound healing, with a 15.8% increase in closure rate and a 3.3-day decrease in average healing time. ADSC-EVs improved reepithelialization (18.2%) with enhanced epithelial proliferation and filaggrin expression, and suppressed epithelial apoptosis and Fasl expression. A 2.7-fold increase in the number of CD31-positive cells was also observed. CONCLUSION: ADSC-EVs improve diabetic wound closure and angiogenesis by enhancing keratinocyte-mediated reepithelialization and vascularization. CLINICAL RELEVANCE STATEMENT: ADSC-EVs could be developed as a regenerative medicine for diabetic wound care.

Ultralight, Elastic, Hybrid Aerogel for Flexible/Wearable Piezoresistive Sensor and Solid-Solid/Gas-Solid Coupled Triboelectric Nanogenerator.

Aerogels have been attracting wide attentions in flexible/wearable electronics because of their light weight, excellent flexibility, and electrical conductivity. However, multifunctional aerogel-based flexible/wearable electronics for human physiological/motion monitoring, and energy harvest/supply for mobile electronics, have been seldom reported yet. In this study, a kind of hybrid aerogel (GO/CNT HA) based on graphene oxide (GO) and carboxylated multiwalled carbon nanotubes (CMWCNTs) is prepared which can not only used as piezoresistive sensors for human motion and physiological signal detections, but also as high performance triboelectric nanogenerator (TENG) coupled with both solid-solid and gas-solid contact electrifications (CE). The repeatedly loading-unloading tests with 20 000 cycles exhibit its high and ultrastable piezoresistive sensor performances. Moreover, when the obtained aerogel is used as the electrode of a TENG, high electric output performance is produced due to the synergistic effect of solid-solid, and gas-solid interface CEs (3D electrification: solid-solid interface CE between the two solid electrification layers; gas-solid interface CE between the inner surface of GO/CNT HA and the air filled in the aerogel pores). This kind of aerogel promises good applications for human physiological/motion monitoring and energy harvest/supply in flexible/wearable electronics such as piezoresistive sensors and flexible TENG.

Flexible GaN-based microscale light-emitting diodes with a batch transfer by wet etching.

Flexible inorganic GaN-based microscale light-emitting diodes (µLEDs) show potential applications in wearable electronics, biomedical engineering, and human-machine interfaces. However, developing cost-effective products remains a challenge for flexible GaN-based µLEDs. Here, a facile and stable method is proposed to fabricate flexible GaN-based µLEDs from silicon substrates in an array-scale manner by wet etching. Circular and square µLED arrays with a size and pitch of 500 µm were fabricated and then transferred to a flexible acrylic/copper substrate. The as-fabricated flexible µLEDs can maintain their structure intact while exhibiting a significant increase in external quantum efficiency. This Letter promotes the application of simple and low-cost flexible µLED devices, especially for virtual displays, wearables, and curvilinear displays.

A new technique for Asian nasal tip shaping: "twin tower" folding ear cartilage transplantation.

Rhinoplasty focuses on the establishment of the structural support of nasal cartilage and the shaping of the nasal tip. The purpose of this study was to explore the application of "double tower" folding ear cartilage transplantation for nasal tip shaping in rhinoplasty.

Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α-Mediated Neovascularization of Random Skin Flap in Rats.

BACKGROUND: Random flaps are widely used for wound repair. However, flap necrosis is a serious complication leading to the failure of operation. Our previous study demonstrated a great proangiogenic potential of hypoxia-treated adipose-derived stem cells-extracellular vesicles (HT-ASC-EVs). Thus, we aim to evaluate the effect of HT-ASC-EVs in the survival and angiogenesis of random skin flap in rats. METHODS: Adipose-derived stem cells-extracellular vesicles were respectively isolated from adipose-derived stem cell culture medium of 3 donors via ultracentrifugation. The expression of hypoxia-inducible factor 1α (HIF-1α) and proangiogenic potential of HT-ASC-EVs and ASC-EVs were compared by co-culturing with human umbilical vein endothelial cells. Forty male Sprague-Dawley rats were randomly divided into 3 group (n = 10/group). A 9 × 3-cm random skin flap was separated from the underlying fascia with both sacral arteries sectioned on each rat. The survival and angiogenesis of flaps treated by ASC-EVs or HT-ASC-EVs were also compared. Laser Doppler flowmetry and immunohistochemistry were used to evaluate skin perfusion and angiogenesis of skin flaps on postoperative day 7. RESULTS: Hypoxia-treated adipose-derived stem cells-extracellular vesicles further improve the proliferation, migration, tube formation with upregulated HIF-1α, and VEGF expression of human umbilical vein endothelial cells in vitro, compared with ASC-EVs. In vivo, postoperatively injecting HT-ASC-EVs suppressed necrosis rate (29.1 ± 2.8% vs 59.2 ± 2.1%) and promoted the angiogenesis of skin flap including improved skin perfusion (803.2 ± 24.3 vs 556.3 ± 26.7 perfusion unit), increased number of CD31-positive cells, and upregulated expression of HIF-1α in vascular endothelium on postoperative day 7, compared with ASC-EVs. CONCLUSIONS: Intradermal injecting HT-ASC-EVs improve the survival of random skin flap by promoting HIF-1α-mediated angiogenesis in rat model.

Enhanced Photoluminescence of Flexible InGaN/GaN Multiple Quantum Wells on Fabric by Piezo-Phototronic Effect.

Fabric-based wearable electronics are showing advantages in emerging applications in wearable devices, Internet of everything, and artificial intelligence. Compared to the one with organic materials, devices based on inorganic semiconductors (e.g., GaN) commonly show advantages of superior characteristics and high stability. Upon the transfer of GaN-based heterogeneous films from their rigid substrates onto flexible/fabric substrates, changes in strain would influence the device performance. Here, we demonstrate the transfer of InGaN/GaN multiple quantum well (MQW) films onto flexible/fabric substrates with an effective lift-off technique. The physical properties of the InGaN/GaN MQWs film are characterized by atomic force microscopy and high-resolution X-ray diffraction, indicating that the transferred film does not suffer from huge damage. Excellent flexible properties are observed in the film transferred on fabric, and the photoluminescence (PL) intensity is enhanced by the piezo-phototronic effect, which shows an increase of about 10% by applying an external strain with increasing the film curvature to 6.25 mm-1. Moreover, energy band diagrams of the GaN/InGaN/GaN heterojunction at different strains are illustrated to clarify the internal modulation mechanism by the piezo-phototronic effect. This work would facilitate the guidance of constructing high-performance devices on fabrics and also push forward the rapid development of flexible and wearable electronics.

Extracellular Vesicles Derived from Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing by Suppressing the Expression of Matrix Metalloproteinase-9.

BACKGROUND: The healing of diabetic wounds is poor due to a collagen deposition disorder. Matrix metalloproteinase-9 (MMP-9) is closely related to collagen deposition in the process of tissue repair. Many studies have demonstrated that extracellular vesicles derived from adipose-derived stem cells (ADSC-EVs) promote diabetic wound healing by enhancing collagen deposition. OBJECTIVE: In this study, we explored whether ADSC-EVs could downregulate the expression of MMP-9 in diabetic wounds and promote wound healing by improving collagen deposition. The potential effects of ADSC-EVs on MMP-9 and diabetic wound healing were tested both in vitro and in vivo. METHODS: We first evaluated the effect of ADSC-EVs on the proliferation and MMP-9 secretion of HaCaT cells treated with advanced glycation end product-bovine serum albumin (AGE-BSA) using CCK-8, western blot and MMP-9 enzyme-linked immunosorbent assay(ELISA). Next, the effects of ADSC-EVs on healing, re-epithelialisation, collagen deposition, and MMP-9 concentration in diabetic wound fluids were evaluated in an immunodeficient mouse model via MMP-9 ELISA and haematoxylin and eosin, Masson's trichrome, and immunofluorescence staining for MMP-9. RESULTS: In vitro, ADSC-EVs promoted the proliferation and MMP-9 secretion of HaCaT cells. In vivo, ADSC-EVs accelerated diabetic wound healing by improving re-epithelialisation and collagen deposition and by inhibiting the expression of MMP-9. CONCLUSION: ADSC-EVs possess the potential of healing of diabetic wounds in a mouse model by inhibiting downregulating MMP-9 and improving collagen deposition. Thus, ADSC-EVs are a promising candidate for the treatment of diabetic wounds.

The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma.

OTU domain-containing protein 3 (OTUD3), a deubiquitinating enzyme, has been shown to participate in progression of multiple malignancies. The accurate function of OTUD3 in hepatocellular carcinoma (HCC) progression remains elusive. We found that OTUD3 was significantly overexpressed in HCC, and higher OTUD3 expression was correlated with larger tumor size, more distant metastasis, and worse TNM stage. A series of gain- and loss-of-function assays were also performed to examine the oncogenic function of OTUD3 in promoting HCC cell growth and metastasis in vitro. Using a xenograft mouse model, we showed that OTUD3 accelerated HCC progression in vivo. Furthermore, alpha-actinin 4 (ACTN4) was identified as a downstream target of OTUD3 through mass spectrometry analysis, and the ACTN4 protein level was significantly related to OTUD3 expression. Additionally, OTUD3 directly bound with ACTN4 and deubiquitinated ACTN4 to stabilize it. Finally, ACTN4 was found to be essential for OTUD3-mediated HCC proliferation and metastasis in vitro and in vivo. Collectively, our findings identify the oncogenic role of OTUD3 in HCC and suggest that OTUD3 can be considered as a pivotal prognostic biomarker and a potential therapeutic target.

Preparing Adipogenic Hydrogel with Neo-Mechanical Isolated Adipose-Derived Extracellular Vesicles for Adipose Tissue Engineering.

BACKGROUND: Subcutaneous transplantation of decellularized adipose tissue was capable of recellularization during soft tissue repair. However, further improvements are required to promote angiogenesis and adipogenesis. Here, the authors proposed a neo-mechanical protocol to isolate adipose tissue-derived extracellular vesicles (ATEVs) through lipoaspirate as a mediator for both angiogenesis and adipogenesis, and prepared ATEV-rich decellularized adipose tissue hydrogel for adipose tissue engineering. METHODS: Adipose liquid extract and lipid-devoid adipose tissue were extracted through homogenization and repeated freeze and thaw cycles. ATEVs were isolated from adipose liquid extract by ultracentrifugation. Decellularized adipose tissue hydrogel was prepared by optimized decellularization of lipid-devoid adipose tissue. The optimum dose of ATEVs for angiogenesis and adipogenesis was estimated by co-culturing with vascular endothelial cells and 3T3-L1 cells, then mixed with the hydrogel. ATEV-enriched hydrogel was injected subcutaneously into the back of severe combined immunodeficiency mice, and then subjected to supplementary injection of ATEVs on postoperative day 14. ATEV-free decellularized adipose tissue hydrogel was injected as control. The newly formed tissue samples were harvested at postoperative weeks 2, 4, and 8 and subjected to volume measurement, hematoxylin and eosin staining, and immunofluorescence (CD31 and perilipin) staining. RESULTS: The optimum dose of ATEVs for promoting angiogenesis and adipogenesis was 50 µg/ml. The newly formed tissue mediated by ATEV-enriched hydrogel had increased volume well as improved angiogenesis and adipogenesis at postoperative week 4 and 8. CONCLUSION: ATEV-enriched adipogenic hydrogel promotes enhanced angiogenesis and adipogenesis and could serve as a promising biomaterial for adipose tissue engineering.

[Effects of adipose-derived stem cell released exosomes on wound healing in diabetic mice].

OBJECTIVE: To investigate the effects of adipose-derived stem cell released exosomes (ADSC-Exos) on wound healing in diabetic mice. METHODS: The ADSCs were isolated from the adipose tissue donated by the patients and cultured by enzymatic digestion. The supernatant of the 3rd generation ADSCs was used to extract Exos (ADSC-Exos). The morphology of ADSC-Exos was observed by transmission electron microscopy. The membrane-labeled proteins (Alix and CD63) were detected by Western blot, and the particle size distribution was detected by nanoparticle tracking analyzer. The fibroblasts were isolated from the skin tissue donated by the patients and cultured by enzymatic digestion. The 5th generation fibroblasts were cultured with PKH26-labeled ADSC-Exos, and observed by confocal fluorescence microscopy. The effects of ADSC-Exos on proliferation and migration of fibroblasts were observed with cell counting kit 8 (CCK-8) and scratch method. Twenty-four 8-week-old Balb/c male mice were used to prepare a diabetic model. A full-thickness skin defect of 8 mm in diameter was prepared on the back. And 0.2 mL of ADSC-Exos and PBS were injected into the dermis of the experimental group ( n=12) and the control group ( n=12), respectively. On the 1st, 4th, 7th, 11th, 16th, and 21st days, the wound healing was observed and the wound healing rate was calculated. On the 7th, 14th, and 21st days, the histology (HE and Masson) and CD31 immunohistochemical staining were performed to observe the wound structure, collagen fibers, and neovascularization. RESULTS: ADSC-Exos were the membranous vesicles with clear edges and uniform size; the particle size was 40-200 nm with an average of 102.1 nm; the membrane-labeled proteins (Alix and CD63) were positive. The composite culture observation showed that ADSC-Exos could enter the fibroblasts and promote the proliferation and migration of fibroblasts. Animal experiments showed that the wound healing of the experimental group was significantly faster than that of the control group, and the wound healing rate was significantly different at each time point ( P<0.05). Compared with the control group, the wound healing of the experimental group was better. There were more microvessels in the early healing stage, and more deposited collagen fibers in the late healing stage. There were significant differences in the length of wound on the 7th, 14th, and 21st days, the number of microvessels on the 7th and 14th days, and the rate of deposited collagen fibers on the 14th and 21st days between the two groups ( P<0.05). CONCLUSION: ADSC-Exos can promote the wound healing in diabetic mice by promoting angiogenesis and proliferation and migration of fibroblasts and collagen synthesis.

[Effect of adipose-derived stem cell derived exosomes on angiogenesis after skin flap transplantation in rats].

OBJECTIVE: To investigate the effect of adipose-derived stem cell derived exosomes (ADSC-Exos) on angiogenesis after skin flap transplantation in rats. METHODS: ADSCs were isolated and cultured by enzymatic digestion from voluntary donated adipose tissue of patients undergoing liposuction. The 3rd generation cells were observed under microscopy and identified by flow cytometry and oil red O staining at 14 days after induction of adipogenesis. After cells were identified as ADSCs, ADSC-Exos was extracted by density gradient centrifugation. And the morphology was observed by transmission electron microscopy, the surface marker proteins (CD63, TSG101) were detected by Western blot, and particle size distribution was measured by nanoparticle size tracking analyzer. Twenty male Sprague Dawley rats, weighing 250-300 g, were randomly divided into ADSC-Exos group and PBS group with 10 rats in each group. ADSC-Exos (ADSC-Exos group) and PBS (PBS group) were injected into the proximal, middle, and distal regions of the dorsal free flaps with an area of 9 cm×3 cm along the long axis in the two groups. The survival rate of the flap was measured on the 7th day, and then the flap tissue was harvested. The tissue morphology was observed by HE staining, and mean blood vessel density (MVD) was measured by CD31 immunohistochemical staining. RESULTS: ADSCs were identified by microscopy, flow cytometry, and adipogenic induction culture. ADSC-Exos was a round or elliptical membrane vesicle with clear edge and uniform size. It has high expression of CD63 and TSG101, and its size distribution was 30-200 nm, which was in accordance with the size range of Exos. The distal necrosis of the flaps in the ADSC-Exos group was milder than that in the PBS group. On the 7th day, the survival rate of the flaps in the ADSC-Exos group was 64.2%±11.5%, which was significantly higher than that in the PBS group (31.0%±6.6%; t=7.945, P=0.000); the skin appendages in the middle region of the flap in the ADSC-Exos group were more complete, the edema in the proximal region was lighter and the vasodilation was more extensive. MVD of the ADSC-Exos group was (103.3±27.0) /field, which was significantly higher than that of the PBS group [(45.3±16.2)/field; t=3.190, P=0.011]. CONCLUSION: ADSC-Exos can improve the blood supply of skin flaps by promoting the formation of neovascularization after skin flap transplantation, thereby improve the survival rate of skin flaps in rats.

[Progress of mesenchymal stem cells derived exosomes in wound repair].

OBJECTIVE: To summarize the research progress of mesenchymal stem cells derived exosomes (MSCs-EXOs) in wound repair in recent years. METHODS: The literature about the role of MSCs-EXOs in wound repair at home and abroad was extensively consulted. The mechanism of MSCs-EXOs in wound repair and its clinical application prospects were summarized and analyzed. RESULTS: MSCs-EXOs can inhibit early inflammatory reaction, promote angiogenesis, proliferation, and migration of epithelial cells, regulate collagen synthesis, and inhibit scar proliferation in the later stage of wound healing. Compared with MSCs, MSCs-EXOs have many advantages, such as high stability, easy storage, non-tumorigenicity, no proliferation, easy quantitative use, and so on. It has broad clinical application prospects. CONCLUSION: MSCs-EXOs can promote wound repair and hopefully develop into a clinical product to promote the repair of acute or chronic wounds.