Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Performance enhancement of quantum Brayton engine via Bose-Einstein condensation.

Bose-Einstein condensation is a quintessential characteristic of Bose systems. We investigate the finite-time performance of an endoreversible quantum Brayton heat engine operating with an ideal Bose gas with a finite number of particles confined in a d-dimensional harmonic trap. The working medium of these engines may work in the condensation, noncondensation, and near-critical point regimes, respectively. We demonstrate that the existence of the phase transition during the cycle leads to enhanced engine performance by increasing power output and efficiencies corresponding to maximum power and maximum efficient power. We also show that the quantum engine working across the Bose-Einstein condensation in N-particle Bose gas outperforms an ensemble of independent single-particle heat engines. The difference in the machine performance can be explained in terms of the behavior of specific heat at constant pressure near the critical point regime.

Enhancing Faraday and Kerr rotations based on the toroidal dipole mode in an all-dielectric magneto-optical metasurface.

The magneto-optical Faraday and Kerr effects are widely used in modern optical devices. In this Letter, we propose an all-dielectric metasurface composed of perforated magneto-optical thin films, which can support the highly confined toroidal dipole resonance and provide full overlap between the localized electromagnetic field and the thin film, and consequently enhance the magneto-optical effects to an unprecedented degree. The numerical results based on the finite element method show that the Faraday and Kerr rotations can reach -13.59° and 8.19° in the vicinity of toroidal dipole resonance, which are 21.2 and 32.8 times stronger than those in the equivalent thickness of thin films. In addition, we design an environment refractive index sensor based on the resonantly enhanced Faraday and Kerr rotations, with sensitivities of 62.96 nm/RIU and 73.16 nm/RIU, and the corresponding maximum figures of merit 132.22°/RIU and 429.45°/RIU, respectively. This work provides a new, to the best of our knowledge, strategy for enhancing the magneto-optical effects at nanoscale, and paves the way for the research and development of magneto-optical metadevices such as sensors, memories, and circuits.

Concentrated ultrasound-processed fat (CUPF): More than a mechanically emulsified graft.

INTRODUCTION: Autologous fat grafting is still an evolving technique. Researchers have attempted to increase the survival rate of grafts by concentrating adipose-derived stem cells (ASCs). In this study, we investigate a novel method that combines ultrasonic processing and centrifugation to generate small fat particles termed concentrated ultrasound-processed fat (CUPF) for grafting. METHODS: The standard approach for obtaining CUPF is described. The properties of processed fat, including CUPF, microfat, centrifuged fat, and nanofat, were investigated using histological observation. Comparative analyses were conducted on the cell number, viability, and immunophenotypic profile of stromal vascular fraction cells (SVFs). Cultured ASCs were evaluated for cell proliferation and adipogenic, osteogenic, and chondrogenic potential. The processed fats were transplanted and evaluated using in vivo and histological studies. RESULTS: Compared with microfat, centrifuged fat, and nanofat, CUPF had a condensed tissue content and higher concentration of viable cells in a small tissue structure and could smoothly pass through a 27-gauge cannula. In the CUPF group, SVFs were isolated in great numbers, with high viability and a high proportion of CD29- and CD105-positive cells. ASCs from the CUPF group exhibited high proliferation and multilineage differentiation potential. The grafts from the CUPF group were well preserved, and histological quantification revealed an increase in the abundance of Ki67- and CD31-positive cells in the tissue. CONCLUSIONS: Our study established a new fat processing strategy that combines ultrasonic processing and centrifugation to harvest small particle grafts named CUPF. CUPF concentrated a large number of ASCs and has great potential for regenerative therapy.

Performance of Quantum Heat Engines Enhanced by Adiabatic Deformation of Trapping Potential.

We present a quantum Otto engine model alternatively driven by a hot and a cold heat reservoir and consisting of two isochoric and two adiabatic strokes, where the adiabatic expansion or compression is realized by adiabatically changing the shape of the potential. Here, we show that such an adiabatic deformation may alter operation mode and enhance machine performance by increasing output work and efficiency, even with the advantage of decreasing work fluctuations. If the heat engine in the sudden limit operates under maximal power by optimizing the control parameter, the efficiency shows certain universal behavior, η*=ηC/2+ηC2/8+O(ηC3), where ηC=1-ßhr/ßcr is the Carnot efficiency, with ßhr(ßcr) being the inverse temperature of the hot (cold) reservoir. However, such efficiency under maximal power can be produced by our machine model in the regimes where the machine without adiabatic deformation can only operate as a heater or a refrigerator.

Diagnosis and Management of Pseudoblepharoptosis in Eastern Asians: A Commonly Observed But Easily Overlooked Type of Blepharoptosis.

BACKGROUND: Pseudoblepharoptosis, which is characterized by ptotic eyelid appearance with normal levator function, is a common abnormality observed in Eastern Asians. Misdiagnosis of pseudoblepharoptosis may lead to inappropriate treatments and unwanted complications. Using the data obtained from a modified levator function examination, this study sought to improve the diagnosis and explore the appropriate treatment of pseudoblepharoptosis based on the typical eyelid anatomy of Eastern Asians. METHODS: This retrospective study included patients with drooping and bulky eyelids who had been preoperatively diagnosed between January 2018 and December 2018 using a modified approach. Debulking of the retro-orbicularis oculus fat and orbital septum fat and release of the ligament-like structure were performed to correct pseudoblepharoptosis without manipulating the levator muscle. The functional and aesthetic outcomes were evaluated postoperatively. RESULTS: The proposed modified approach was significantly more accurate than the traditional technique. Of the patients, 78 (84.8%) and 9 (9.8%) showed good and moderate cosmetic outcomes, respectively. The margin reflex distance 1 value significantly improved from 1.74±0.87 mm preoperatively to 4.56±0.71 mm postoperatively ( P <0.05). Moreover, 179 (97.3%) of the 184 eyelids examined achieved adequate correction. CONCLUSIONS: The modified levator function examination approach used in this study may help improve the diagnosis of pseudoblepharoptosis. Surgical intervention focused on correcting the bulky and drooping upper eyelids and orbital septum may lead to satisfactory outcomes in Eastern Asians with pseudoblepharoptosis without manipulating the levator muscle.

Autologous Concentrated Growth Factor Increases Skin Thickness and Area during Tissue Expansion: A Randomized Clinical Trial.

BACKGROUND: Mechanical stretching of the skin (ie, tissue expansion) could generate additional skin, but it is limited by the intrinsic growth capacity. The authors conducted a study of autologous concentrated growth factor (CGF) to promote skin regeneration by increasing skin thickness and area during tissue expansion. METHODS: A single-center randomized controlled trial was conducted from 2016 to 2019. Participants undergoing skin expansion received either CGF or saline by means of intradermal injection on the expanded skin (0.02 mL/cm 2 ), for a total of three treatments at 4-week intervals. The primary endpoint was the expanded skin thickness at 12 weeks, which was measured by ultrasound. The secondary endpoints included skin thickness at 4 and 8 weeks and surface area, expansion index, and skin texture score of the expanded skin at 12 weeks. Safety assessments, for infection symptoms and nodule formation, were assessed at 24 weeks. RESULTS: In total, 26 patients were enrolled and assigned to the CGF or control group. Compared with the control group, the CGF group had significantly increased skin thickness at 8 (control, 1.1 ± 0.1 mm; CGF, 1.4 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047) and 12 weeks (control, 1.0 ± 0.1 mm; CGF, 1.3 ± 0.1 mm; -0.6 to 0.0 mm; P = 0.047). Compared with the baseline thickness (control, 1.6 ± 0.1 mm; CGF, 1.5 ± 0.1 mm; -0.3 to 0.5 mm; P = 0.987), skin thickness was sustained in the CGF group at 8 weeks after treatment (-0.1 to 0.3 mm; P = 0.711) but decreased in the control group (0.3 to 0.7 mm; P < 0.001). At 12 weeks, the CGF group showed greater increases in surface area (control, 77.7 ± 18.5 cm 2 ; CGF, 135.0 ± 15.7 cm 2 ; 7.2 cm 2 to 107.4 cm 2 ; P = 0.027) and expansion index (control, 0.9 ± 0.1; CGF, 1.4 ± 0.2; 0.0 to 0.8; P = 0.030) than the control group. In addition, CGF-treated skin showed an improvement in texture [CGF: grade 3, n = 2 (15.8%), grade 2, n = 4 (30.7%); control: grade 3, n = 0 (0.0%), grade 2, n = 3 (23.0%)]. No severe adverse events occurred. CONCLUSION: CGF treatment increases skin thickness and area during tissue expansion, and represents a safe and effective strategy for managing skin expansion. CLINICAL RELEVANCE STATEMENT: The findings of this study indicate that it is practically feasible to improve skin regeneration by applying autologous platelet concentrate therapy for skin expansion management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Angiogenesis modulation-mediated inhibitory effects of tacrolimus on hypertrophic scar formation.

Hypertrophic scar (HS) is a fibroproliferative disorder that causes cosmetic as well as functional problems; however, to our knowledge, there is no satisfactory treatment for HS to date. Previous studies have indicated that angiogenesis plays a crucial role in HS formation; therefore, anti-angiogenetic therapies are considered effective in improving HS. Although tacrolimus (TAC) has been proven effective in preventing HS formation in vivo and in vitro, its underlying mechanism remains controversial and ambiguous. Because of its anti-angiogenic effects in other diseases, we aimed to determine whether TAC reduces HS by suppressing angiogenesis. Using a rabbit ear HS model that we developed, HS was treated once a week with normal saline, dimethyl sulfoxide, or TAC for 3 weeks. Histological evaluation indicated that TAC significantly reduced collagen deposition and microvessel density in scar tissues. Moreover, immunofluorescence staining for CD31 and vascular endothelial growth factor (VEGF)-A revealed that TAC significantly inhibited HS angiogenesis. In vitro analysis showed that TAC inhibited endothelial cell migration and tubulogenesis as well as the viability and proliferation of human umbilical vascular endothelial cells (HUVECs) and HS fibroblasts (HSFBs). Furthermore, TAC significantly downregulated the expression of the human angiogenetic factors VEGF-A, FGF-2, PDGF-ß, and TGF-ß1 in HUVECs and HSFBs. Additionally, TAC-mediated inhibition of angiogenesis decreased the gene expression of crucial fibrotic markers, including α- smooth muscle actin and collagens 1 and 3, in HSFBs. This is the first study to demonstrate the inhibitory effects of TAC on HS formation mediated by a mechanism involving the suppression of scar angiogenesis.

Mechanical Stretching Can Modify the Papillary Dermis Pattern and Papillary Fibroblast Characteristics during Skin Regeneration.

Clinical application of mechanical stretching is a reconstructive method for skin repair. Although studies have reported dermal fibroblast heterogeneity, whether stretching affects individual fibroblast subpopulations equally remains unclear. In this study, we show the changes in dermal structure and papillary fibroblast (Fp) in regenerated human skin. Exhausted skin regeneration caused dermal‒epidermal junction flattening, papillary dermis thinning, and an increase in type III collagen-to-type I collagen ratio, with upregulated hallmarks of aging. Well-regenerated skin displayed a notable increase in the Fp population. Consistent changes were observed in the rat expansion model. Moreover, we found that TGFß1 expression was especially increased in skin showing good regeneration. Activation of the TGFß1/SMAD2/3 pathway improved exhausted skin regeneration and resulted in increased collagen content and Fp proliferation, whereas pharmacological inhibition of TGFß1 action impacted well-regenerated skin. Short-term mechanical stretching that promoted skin regeneration enhanced Fp proliferation, extracellular matrix synthesis, and increased TGFß1 expression, leading to good regeneration. Conversely, long-term stretching induced premature Fp senescence, leading to poor regeneration. This work shows the mechanism of mechanical stretching in well-skin regeneration that enhances Fp proliferation and extracellular matrix synthesis through the TGFß1/SMAD2/3 pathway and highlights a crucial role of Fps in stretching-induced skin regeneration.

Power statistics of Otto heat engines with the Mpemba effect.

The Mpemba effect is a counterintuitive relaxation phenomenon whereby a system with a higher initial temperature may cool down to the thermal state faster than an identical system that was initially prepared at a lower temperature. Here, we investigate heat and work in a Markovian state transition system with cyclic switching hot-cold temperatures, which operates as an Otto heat engine working in long but finite time, either with or without the Mpemba effect. Under the condition of the periodic steady state having been reached, the time durations of the heating and cooling relaxation processes are determined by exploring a distance-from-equilibrium equivalent to the Kullback-Leibler divergence. We then numerically evaluate and compare the averages and variances of both the work and the power output of two scenarios with and without the Mpemba effect. The results show that the Markovian Mpemba effect can enhance the machine performance by significantly increasing the power output for a given efficiency without sacrificing the stability.

Sub-brow skin excision Combined with retro-orbicularis fat resection: A Technique for upper eyelid bulkiness and laxity correction.

BACKGROUND: Many people are characterized by a swollen appearance and loose skin of upper eyelids, especially Asians. Retro-orbicularis oculus fat (ROOF) lying in the lateral canthus area is a critical factor of the bulkiness formation. Although several approaches have been reported, most of them intend to remove orbicularis muscle and preaponeurotic fat through a double-eyelid incision, leaving ROOF untreated. Consequently, an unnatural eyelid fold is formed and the lateral supraorbital region remains bloated . METHODS: Sixty-seven patients underwent sub-brow skin excision combined with ROOF resection. The key point was to excise the loose skin and thick ROOF through an incision along with the lower 1/3 of the eyebrow. Surgical outcomes were evaluated 6 months postoperatively by the heights of the designed line from the palpebral margin to the pupil center (HPPC), medial cornea (HPMC), and lateral canthus (HPLC). The pinch test, photographs, and complications were also recorded. RESULTS: The preoperative average HPPC, HPMC, and HPLC were 9.68 ± 1.73, 7.68 ± 1.24, and 6.82 ± 1.12 mm, while the postoperative average measurements were 7.25 ± 0.51, 5.99 ± 0.54, and 5.54 ± 0.61 mm, respectively. The result of the pinch test was improved and postoperative scarring was inconspicuous. Two patients had transient numbness in the eyebrow region that subsided within seven days. Two patients had slight asymmetry of eyebrow position but did not need a second operation. CONCLUSIONS: Sub-brow skin excision combined with ROOF resection is an effective technique for improving upper eyelid bulkiness and skin excess with low revision rates.

Fluctuations in irreversible quantum Otto engines.

We derive the general probability distribution function of stochastic work for quantum Otto engines in which both the isochoric and driving processes are irreversible due to finite time duration. The time-dependent work fluctuations, average work, and thermodynamic efficiency are explicitly obtained for a complete cycle operating with an analytically solvable two-level system. The effects of the irreversibility originating from finite-time cycle operation on the thermodynamic efficiency, work fluctuations, and relative power fluctuations are discussed.

Quantum Otto engine working with interacting spin systems: Finite power performance in stochastic thermodynamics.

A quantum Otto engine using two-interacting spins as its working medium is analyzed within framework of stochastic thermodynamics. The time-dependent power fluctuations and average power are explicitly derived for a complete cycle of engine operation. We find that the efficiency and power fluctuations are affected significantly by interparticle interactions, but both of them become interaction-independent under maximal power via optimizing the external control parameter. The behavior of the efficiency at maximum power is further explained by analyzing the optimal protocol of the engine.

Three-terminal refrigerator based on resonant-tunneling quantum wells.

A three-terminal refrigerator based on resonant-tunneling quantum wells is proposed. With the help of the Landauer formula, the expressions for the cooling rate and the coefficient of performance (COP) are derived. The working regions of the refrigerator are determined and the three-dimensional projection graphs of the cooling rate and the COP varying with the positions of the two energy levels are plotted. Moreover, the influence of the bias voltage, the asymmetric factor, and the temperature difference on the optimal performance parameters is analyzed in detail. Finally, the performance characteristics of the refrigerator in the case of negative temperature difference are discussed.

Finite-time performance of a quantum heat engine with a squeezed thermal bath.

We consider the finite-time performance of a quantum Otto engine working between a hot squeezed and a cold thermal bath at inverse temperatures ß_{h} and ß_{c}(>ß_{h}) with (k_{B}≡1)ß=1/T. We derive the analytical expressions for work, efficiency, power, and power fluctuations, in which the squeezing parameter is involved. By optimizing the power output with respect to two frequencies, we derive the efficiency at maximum power as η_{mp}=(η_{C}^{gen})^{2}/[η_{C}^{gen}-(1-η_{C}^{gen})ln(1-η_{C}^{gen})], where the generalized Carnot efficiency η_{C}^{gen} in the high-temperature or small squeezing limit simplifies to an analytic function of squeezing parameter γ: η_{C}^{gen}=1-ß_{h}/[ß_{c}cosh(2γ)]. Within the context of irreversible thermodynamics, we demonstrate that the expression of efficiency at maximum power satisfies a general form derived from nonlinear steady state heat engines. We show that, the power fluctuations are considerably increased, although the engine efficiency is enhanced by squeezing.

Finite-power performance of quantum heat engines in linear response.

We investigate the finite-power performance of quantum heat engines working in the linear response regime where the temperature gradient is small. The engine cycles with working substances of ideal harmonic systems consist of two heat transfer and two adiabatic processes, such as the Carnot cycle, Otto cycle, and Brayton cycle. By analyzing the optimal protocol under maximum power we derive the explicitly analytic expression for the irreversible entropy production, which becomes the low dissipation form in the long duration limit. Assuming the engine to be endoreversible, we derive the universal expression for the efficiency at maximum power, which agrees well with that obtained from the phenomenological heat transfer laws holding in the classical thermodynamics. Through appropriate identification of the thermodynamic fluxes and forces that a linear relation connects, we find that the quantum engines under consideration are tightly coupled, and the universality of efficiency at maximum power is confirmed at the linear order in the temperature gradient.

Efficiency Bounds for Minimally Nonlinear Irreversible Heat Engines with Broken Time-Reversal Symmetry.

We study the minimally nonlinear irreversible heat engines in which the time-reversal symmetry for the systems may be broken. The expressions for the power and the efficiency are derived, in which the effects of the nonlinear terms due to dissipations are included. We show that, as within the linear responses, the minimally nonlinear irreversible heat engines can enable attainment of Carnot efficiency at positive power. We also find that the Curzon-Ahlborn limit imposed on the efficiency at maximum power can be overcome if the time-reversal symmetry is broken.

A Novel Model for Cutaneous Wound Healing and Scarring in the Rat.

BACKGROUND: Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. METHODS: Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. RESULTS: Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. CONCLUSIONS: The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.

Dynamic robustness of endoreversible Carnot refrigerator working in the maximum performance per cycle time.

In this work, we study the dynamic robustness of an endoreversible Carnot cycle working at the maximum per-unit-time performance regime, based on the linearization technique for dynamical systems and the local stability analysis. Our analysis is focused on the endoreversible Carnot refrigerator model, which works in the maximum per-unit-time coefficient of performance. At the steady-state of the maximum performance, the expressions of the relaxation times describing the stability of the system are derived. It is found that the relaxation times in the cycle condition are the function of thermal conductances σh and σc, the temperatures of the heat reservoirs Th and Tc, and the heat capacity C. The influence of the temperature ratio τ = Tc/Th and the thermal conductance ratio σr = σh/σc on the relaxation times is discussed in detail. The results obtained here are useful and provide a potential guidance for the design of an endoreversible Carnot refrigerator working in the maximum performance per cycle time optimization condition.

Identification of hub genes related to silicone-induced immune response in rats.

Silicone implants are used widely in the field of plastic surgery and are used in a large population. However, their safety profile, especially the silicone-induced immune response, has been a major concern for plastic surgeons for decades. It has been hypothesized that there is a cause and effect relation between silicone and immunity, but this is controversial. The objective of the present study was to determine the hub genes and key pathways related to silicone implant-induced immune responses in a rat model. In addition to cluster and enrichment analyses, we used weighted gene co-expression network analysis (WGCNA) to examine the gene expression profiles in a systematic context. A total five genes (Fes, Aif1, Gata3, Tlr6, Tlr2) were identified as hub genes that are most likely related to the silicone-induced immune response, four of which (Aif1, Gata3, Tlr6, Tlr2) have been associated with autoimmunity as target genes or disease markers. The Toll-like receptor signaling pathway (p < 0.01, fold enrichment: 7.01) and systemic lupus erythematosus signaling pathway (p < 0.05, fold enrichment: 5.01), which are considered strongly associated with autoimmunity, were significantly enriched in the silicone-implanted skin samples. The results indicate that silicone implants might trigger the localized immune response, as various immune reaction genes were detected after silicone implantation. The identified five hub genes will hopefully serve as novel therapeutic targets for silicone-related complications and the associated autoimmune diseases.