Efficient production of R-2-(4-hydroxyphenoxy) propionic acid by Beauveria bassiana using biofilm-based two-stage fermentation.

In this work, a novel biofilm-based fermentation of Beauveria bassiana was employed to convert R-2- phenoxypropionic acid (R-PPA) to R-2-(4-hydroxyphenoxy) propionic acid (R-HPPA). The biofilm culture model of Beauveria bassiana produced a significantly higher R-HPPA titer than the traditional submerged fermentation method. Mannitol dosage, tryptone dosage, and initial pH were the factors that played a significant role in biofilm formation and R-HPPA synthesis. Under the optimal conditions, the maximum R-HPPA titer and productivity approached 22.2 g/L and 3.2 g/(L·d), respectively. A two-stage bioreactor combining agitation and static incubation was developed to further increase R-HPPA production. The process was optimized to achieve 100 % conversion of R-PPA, with a maximum R-HPPA titer of 50 g/L and productivity of 3.8 g/(L·d). This newly developed biofilm-based two-stage fermentation process provides a promising strategy for the industrial production of R-HPPA and related hydroxylated aromatic compounds.

Microplastic Distribution Characteristics and Sources on Beaches That Serve as the Largest Nesting Ground for Green Turtles in China.

The threat of microplastics to marine animals and habitats is increasing, which may affect sea turtle nesting grounds. The Qilianyu Islands are the largest remaining green turtle (Chelonia mydas) nesting grounds in China. Despite being far from the mainland, microplastic pollution cannot be ignored. In this study, the level of microplastic pollution in surface sediments from three different zones, namely, the bottom, intertidal, and supratidal zone, was investigated on North Island, Qilianyu Islands. The results showed that the abundance of microplastics in the supratidal zone was significantly higher than that in the bottom zone and intertidal zone (r = 3.65, p = 0.011), with the highest average abundance of microplastics located on the southwest coast of North Island. In the bottom zone, only plastic blocks (88%) and fibers (12%) were found. The main types of microplastics in the intertidal and supratidal zones were plastic blocks (48%) and foam (42%), with polyethylene (PE) (40%) and polystyrene (PS) (34%) being the predominant components. These types and components of microplastics differed from those in the surrounding seawater, but corresponding types and components were found in the plastic debris on the beach. Meanwhile, it was also observed that there were multiple instances of fragmented plastic on the beach. Thus, we suggest that the microplastics on the beach in North Island were mainly derived from the fragmentation of microplastic debris, indicating secondary microplastics. It is recommended to further strengthen the regular cleaning of plastic debris on the beach, especially the removal of small plastic debris, in order to reduce the pollution from secondary microplastics generated by the fragmentation of beach plastic debris and to better protect China's most important sea turtle nesting site in the South China Sea.

Enabling Stable and Low-Strain Lithium Plating/Stripping with 2D Layered Transition Metal Carbides by Forming Li-Zipped MXenes and a Li Halide-Rich Solid Electrolyte Interphase.

Two-dimensional (2D) layered materials demonstrate prominent advantage in regulating lithium plating/stripping behavior by confining lithium diffusion/plating within interlayer gaps. However, achieving effective interlayer confined lithium diffusion/plating without compromising the stability of bulk-structural and the solid electrolyte interphase (SEI) remains a considerable challenge. This paper presents an electrochemical scissor and lithium zipper-driven protocol for realizing interlayer confined lithium plating with pretty-low strain and volume change. In this protocol, lithium serves as a "zipper" to reunite the adjacent MXene back to MAX-like phase to markedly enhance the structural stability, and a lithium halide-rich SEI is formed by electrochemically removing the terminals of halogenated MXenes to maintain the stability and rapid lithium ions diffusion of SEI. When the Ti3 C2 I2 serves as the host for lithium plating, the average coulomb efficiency exceeds 97.0 % after 320 lithium plating/stripping cycles in conventional ester electrolyte. Furthermore, a full cell comprising of LiNi0.8 Mn0.1 Co0.1 O2 and Ti3 C2 I2 @Li exhibits a capacity retention rate of 73.4 % after 200 cycles even under high cathode mass-loading (20 mg cm-2 ) and a low negative/positive capacity ratio of 1.4. Our findings advance the understanding of interlayer confined lithium plating in 2D layered materials and provide a new direction in regulating lithium and other metal plating/stripping behaviors.

On-top plasty combined with modified Bilhaut-Cloquet procedure for reconstructing complicated radial polydactyly.

PURPOSE: To present a surgical technique of combining the on-top plasty with modified Bilhaut-Cloquet procedure for reconstructing a rare type of complicated radial polydactyly and evaluate the outcomes. METHODS: Fourteen complicated radial polydactyly in 13 patients were corrected by combining the on-top plasty with modified Bilhaut-Cloquet procedure. Osteotomies were performed as required, and the acral part of the ulnar thumb was transposed onto the proximal part of the radial thumb. The distal parts of the two thumbs were isolated as neurovascular pedicled composite tissue flaps, including part of the distal phalanx and nail bed, and were attached together in an extra-articular way. The tendons were rebalanced, and the nail bed was reconstructed. Objective and subjective outcomes were assessed. RESULTS: The average follow-up time was 32.4 months (6-60 months). All reconstructed thumbs were rated as good in appearance and function. The mean Vancouver Scar Scale score was 1.3 (range 1-2) and the mean Wang-Gao score of the reconstructed thumbnail was 9.4 (range 8-11). The Tada score for the function of the reconstructed thumb was 5.5 (range 5-6). The main active range of motion (ROM) of the interphalangeal joint (IPJ) was 2.1-38.9°. All parents were satisfied with the outcomes. CONCLUSIONS: Because of the diverse manifestations of thumb polydactyly, individualized surgical treatment is recommended, and careful preoperative planning should be made with the principle of combining the best parts of the two thumbs. By combining an on-top plasty with modified Bilhaut-Cloquet procedure, a satisfactory result can be achieved for treating complicated radial polydactyly.

Correlation analysis of serum levels of H19 and CRP levels and ulcerative colitis.

Background: To elucidate clinical applications of detecting serum levels of H19 and CRP in predicting the severity of ulcerative colitis (UC). Methods: Two hundred UC patients were recruited, and classified to mild/moderate group and severe group according to the Truelove-Witts grading system. Serum levels of H19 and CRP in UC patients were detected by turbidimetric inhibition immuno assay and qRT-PCR. Differences in serum levels of H19 and CRP between mild/moderate group and severe group were analyzed. By plotting ROC curves, the diagnostic potentials of H19 and CRP in UC were evaluated. Kappa conformance test was conducted to validate the conformance of detecting serum levels of H19 and CRP to clinical diagnosis of UC. Results: Serum levels of H19 and CRP were higher in UC patients of severe group than those of mild/moderate group. Their levels were both positively correlated to the severity of UC. High sensitivity (83.3%) and specificity (80.0%), as well as the maximum Youden index (0.633) were obtained at the cut-off value for H19 level of 2.755, and AUC was 0.8835. Meanwhile, Kappa coefficient (k) was 0.760 at the cut-off value for H19 level of 2.755, showing a high conformance to clinical diagnosis of UC. In addition, acceptable sensitivity (68.49%) and high specificity (85.83%), as well as the maximum Youden index (0.543) were obtained at the cut-off value for CRP level of 6.390 mg/L, and AUC was 0.8018. k was 0.435, showing an acceptable conformance to clinical diagnosis of UC based on serum level of CRP. Conclusions: Serum levels of H19 and CRP increase with the deterioration of UC. Detecting their serum levels has a consistent result to clinical diagnosis of UC, with a superior performance of H19 than that of CRP.

Molecular Dynamics Simulations on the Adsorbed Monolayers of N-Dodecyl Betaine at the Air-Water Interface.

Betaine is a kind of zwitterionic surfactant with both positive and negative charge groups on the polar head, showing good surface activity and aggregation behaviors. The interfacial adsorption, structures and properties of n-dodecyl betaine (NDB) at different surface coverages at the air-water interface are studied through molecular dynamics (MD) simulations. Interactions between the polar heads and water molecules, the distribution of water molecules around polar heads, the tilt angle of the NDB molecule, polar head and tail chain with respect to the surface normal, the conformations and lengths of the tail chain, and the interfacial thickness of the NDB monolayer are analyzed. The change of surface coverage hardly affects the locations and spatial distributions of the water molecules around the polar heads. As more NDB molecules are adsorbed at the air-water interface, the number of hydrogen bonds between polar heads and water molecules slightly decreases, while the lifetimes of hydrogen bonds become larger. With the increase in surface coverage, less gauche defects along the alkyl chain and longer NDB chain are obtained. The thickness of the NDB monolayer also increases. At large surface coverages, tilted angles of the polar head, tail chain and whole NDB molecule show little change with the increase in surface area. Surface coverages can change the tendency of polar heads and the tail chain for the surface normal.

A single-tube-braided stent for various airway structures.

Background: Airway stent has been widely used in airway procedures. However, the metallic and silicone tubular stents are not customized designed for individual patients and cannot adapt to complicated obstruction structures. Other customized stents could not adapt to complex airway structures with easy and standardized manufacturing methods. Object: This study aimed to design a series of novel stents with different shapes which can adapt to various airway structures, such as the "Y" shape structure at the tracheal carina, and to propose a standardized fabrication method to manufacture these customized stents in the same way. Methods: We proposed a design strategy for the stents with different shapes and introduced a braiding method to prototype six types of single-tube-braided stents. Theoretical model was established to investigate the radial stiffness of the stents and deformation upon compression. We also characterized their mechanical properties by conducting compression tests and water tank tests. Finally, a series of benchtop experiments and ex vivo experiments were conducted to evaluate the functions of the stents. Results: The theoretical model predicted similar results to the experimental results, and the proposed stents could bear a compression force of 5.79N. The results of water tank tests showed the stent was still functioning even if suffering from continuous water pressure at body temperature for a period of 30 days. The phantoms and ex-vivo experiments demonstrated that the proposed stents adapt well to different airway structures. Conclusion: Our study offers a new perspective on the design of customized, adaptive, and easy-to-fabricate stents for airway stents which could meet the requirements of various airway illnesses.

Molecular Dynamics Study on the Aggregation Behavior of Triton X Micelles with Different PEO Chain Lengths in Aqueous Solution.

The aggregation structure of Triton X (TX) amphiphilic molecules in aqueous solution plays an important role in determining the various properties and applications of surfactant solutions. In this paper, the properties of micelles formed by TX-5, TX-114, and TX-100 molecules with different poly(ethylene oxide) (PEO) chain lengths in TX series of nonionic surfactants were studied via molecular dynamics (MD) simulation. The structural characteristics of three micelles were analyzed at the molecular level, including the shape and size of micelles, the solvent accessible surface area, the radial distribution function, the micelle configuration, and the hydration numbers. With the increase of PEO chain length, the micelle size and solvent accessible surface area also increase. The distribution probability of the polar head oxygen atoms on the surface of the TX-100 micelle is higher than that in the TX-5 or TX-114 micelle. In particular, the tail quaternary carbon atoms in the hydrophobic region are mainly located at the micelle exterior. For TX-5, TX-114, and TX-100 micelles, the interactions between micelles and water molecules are also quite different. These structures and comparisons at the molecular level contribute to the further understanding of the aggregation and applications of TX series surfactants.

Surgical excision and skin grafting combined with intralesional injection of triamcinolone for the treatment of keloids after syndactyly release.

The purpose of this study was to investigate the efficacy of surgery combined with triamcinolone acetonide injection in managing the difficult problem of keloid formation after syndactyly release. Twenty-two patients with keloid formation after syndactyly release were retrospectively reviewed. They were divided into a simple surgery group and a surgery plus injection group. Complications, web quality, scar score and satisfaction were assessed and compared. In the surgery plus injection group, three patients (3/13) experienced recurrence and ten webs were good, whereas in the simple surgery group, seven patients (7/9) experienced recurrence and five webs were poor. The mean Vancouver Scar Scale score was significantly lower (4.3 versus 7.8) and the mean Faces Questionnaire satisfaction score was higher (4.2 versus 2.6) in the surgery plus injection group. Combining surgical excision with early and repeated intralesional injection can achieve better results with low recurrence rate and side effects.Level of evidence: IV.

A warm hug from a robot: A dual-mode e-skin with programming compliance.

Recent achievements in the field of electronic skin (e-skin) have provided promising technology for service robots. However, the development of a bionic perception system that exhibits superior performance in terms of safety and interaction quality remains a challenge. Here, we demonstrate a biomimetic soft e-skin that is composed of an array of capacitors and air pouches. It is a single platform that shows dual-mode sensing capabilities of tactile sensing and proximity perception. We optimized the shape and area of the electrode via simulation of the approach of a robot to an object. Moreover, the compliance and temperature of the e-skin can be actively adjusted by tuning the pressure and heat of the air inside the pouches. The e-skin provided dual-mode sensing feedback and soft touch for humanoid service robots, for example, when a robot hugged a man, which illustrated the potential of this e-skin for applications in human-robot interactions.

Kartogenin Induced Adipose-Derived Stem Cell Exosomes Enhance the Chondrogenic Differentiation Ability of Adipose-Derived Stem Cells.

Objective: The objective of this study is to explore the effect of kartogenin (KGN-)-pretreated adipose-derived stem cell-derived exosomes (ADSC-EXOs) on the chondrogenic differentiation ability of ADSCs. Methods: Adipose-derived stem cells (ADSCs) were treated with different doses of KGN, and exosomes (EXOs) were extracted. EXOs were then identified using an electron microscope (EM), nanoparticle tracking analyzer, nanoparticle tracking analysis software, and exosomal protein markers. EXOs were labeled with the fluorescent dye PKH67 and their uptake by cells was evaluated. A cell counting kit-8 (CCK-8) assay, flow cytometry, clonogenic assay, and a cell scratch assay were used to detect the abilities of proliferation, apoptosis, clone formation, and migration of ADSCs, respectively. Subsequently, Alcian blue staining and toluidine blue staining were used to detect the chondrogenic differentiation ability of ADSCs in each group. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) techniques were used to detect the expression of chondrogenic differentiation-related genes. Results: In this study, ADSCs and KGN-induced ADSC-EXOs were successfully extracted and isolated. EXOs and ADSCs coculturing results showed that KGN-induced ADSC-EXOs can significantly promote proliferation, clone formation, migration, and chondrogenic differentiation of ADSCs and inhibit apoptosis. In addition, KGN-induced ADSC-EXOs can increase the expression of chondrogenic-related genes in ADSCs (Aggrecan, Collagen III, Collagen II, and SOX9), and can significantly decrease the expression of chondrolysis-related genes (MMP-3, ADAMTS4, and ADAMTS5). Conclusion: KGN-induced ADSC-EXOs can enhance the chondrogenic differentiation ability of ADSCs by promoting cell proliferation and migration while inhibiting cell apoptosis. KGN treatment can also increase the expression of chondrogenic differentiation-related genes and decrease the expression of chondrolysis-related genes. These results provide a new approach to cartilage repair and regeneration.

Aesthetic correction of short nail deformity in congenital brachydactyly Type D by distraction lengthening.

Brachydactyly Type D is a congenital condition of the thumb in which there is a short and broad thumbnail. Although the thumb function is often unaffected, some patients seek surgery for cosmetic improvement. This study aimed to describe our method of distraction lengthening to correct nail deformity in brachydactyly Type D. A total of 163 thumbs in 95 patients underwent this surgery between 2018 and 2021.The mean thumbnail length improved from 9 mm to 15 mm, with a mean percentage increase of 62%. The ratio of nail length to width changed from 0.6 to 1.1, which was equal to normal. The mean increased fingernail length/width ratio was 0.5, with a percentage change of 78%. No obvious surgical scar was observed. The thumb function was not significantly affected. We conclude that aesthetic correction of short nail deformity in brachydactyly Type D can be achieved by distraction lengthening with high satisfaction and without functional impairment.Level of evidence: IV.

lncRNA-H19 in Fibroblasts Promotes Wound Healing in Diabetes.

Cutaneous wound healing in diabetes is impaired and would develop into nonhealing ulcerations. However, the molecular mechanism underlying the wound-healing process remains largely obscure. Here, we found that cutaneous PDGFRα+ fibroblast-expressing lncRNA-H19 (lncH19) accelerates the wound-healing process via promoting dermal fibroblast proliferation and macrophage infiltration in injured skin. PDGFRα+ cell-derived lncH19, which is lower in contents in the wound-healing cutaneous tissue of patients and mice with type 2 diabetes, is required for wound healing through promoting proliferative capacity of dermis fibroblasts as well as macrophage recruitments. Mechanistically, lncH19 relieves the cell cycle arrest of fibroblasts and increases macrophage infiltration in injured tissues via inhibiting p53 activity and GDF15 releasement. Furthermore, exosomes derived from adipocyte progenitor cells efficiently restore the impaired diabetic wound healing via delivering lncH19 to injured tissue. Therefore, our study reveals a new role for lncRNA in regulating cutaneous tissue repair and provides a novel promising insight for developing clinical treatment of diabetes.

Trajectory optimisation with musculoskeletal integration features for fracture reduction orthopaedic robot.

BACKGROUND: Human body is an integrated system of bones and muscles. To date, there are insufficient studies on the effect of muscles on the trajectory planning of orthopaedic robot. To this end, based on a Stewart-Gough platform (6-UPU) fracture reduction orthopaedic robot, a musculoskeletal trajectory optimisation method was constructed for the interference of soft tissue during the reduction process. METHODS: Firstly, pose description of the fracture reduction orthopaedic robot was introduced, and its working space was analysed. Secondly, an improved Hill muscle theory was used to construct the musculoskeletal system, and finite element analysis (FEA) was carried out. Thirdly, particle swarm optimisation (PSO) with variable weights was imported, and fracture reduction trajectory planning was obtained by quintic polynomial in the workspace. Then mathematical model for trajectory optimisation was presented, and targets of musculoskeletal optimisation were extracted, which include muscle energy consumption, robot-assisted repositioning time and trajectory length. In this sense, musculoskeletal integration trajectory optimisation method was put forward. Finally, comparative optimisation simulation with skeleton only and bone and muscle together were tested, and safety experiment with musculoskeletal integration was conducted. RESULTS: A cone shape workspace was got, whose range can be defined as 635.14 mm on the X axis, 720 mm on the Y axis, and 240 mm on the Z axis, respectively. Besides, different FEA displacements revealed the effect of bone and muscle on the movement of the robot. Moreover, the optimal results with and without muscle had showed different movement time: the former consumed about 27 s, but the latter spent about 25 s. Additionally, the speed and acceleration of the drive rods can be obtained from zero to zero during the reset. CONCLUSIONS: The results show that the optimised trajectory obtained with this method is safe and reliable. Furthermore, the presence of muscle has great influence on the trajectory of robot, which could prolong the reduction time so as to prevent the occurrence of uneven soft and hard traction rate problem. This paper could be helpful for the future trajectory planning study of fracture reduction orthopaedic robot.

Synergistic effects of myogenic cells and fibroblasts on the promotion of engineered tendon regeneration with muscle derived cells.

AIMS: Tendon development requires the coordinated interaction of muscles and tendons. Muscle-derived cells (MDCs), a mixed cell population containing both myogenic and fibroblastic cell subsets, have been found to be ideal seed cells for tendon regeneration. However, the necessity of these cell types for tendon regeneration has not yet been tested. In this study, we aim to explore the possible synergistic effects of myogenic cells and fibroblasts in engineered tendon regeneration. METHODS: MDCs were separated into rapidly adhering cell (RAC; fibroblasts) and slowly adhering cell (SAC; myogenic cells) populations. Myogenic- and tenogenic-related molecules were analyzed by immunofluorescent staining, RT-PCR and real-time PCR. The proliferative abilities of MDCs, RACs and SACs were also evaluated. Cell-scaffold constructs were implanted into nude mice, and subsequently evaluated for their histologic, ultrastructure, gene expression, and biomechanical characteristics. RESULTS: MDCs have better proliferative activity than RAC and SAC population. RACs could express higher levels of tenogenic-related molecules tenomodulin (TNMD) and scleraxis (SCX) than SACs. Whereas SACs only expressed myogenic-related molecules MyoD. In contrast to the tendons engineered using RACs and SACs, the tendons engineered using MDCs exhibited a relatively more mature and well-organized tissue structure and ultrastructure as well as better mechanical properties. CONCLUSIONS: Fibroblasts in muscle may be the primary cell population involved in tendon regeneration and that myogenic cells are an important component of the niche and control the fibroblast activity during tendon regeneration. The synergistic effects between fibroblasts and myogenic cells significantly contribute to efficient and effective regeneration of engineered tendons.

Continuous tension reduction technique in facial scar management: A comparison of W-plasty and straight-line closure on aesthetic effects in Asian patients.

W-plasty is a very popular scar excisional revision technique. The core of the technique is to break up the scar margins into small triangular components, so as to cause light scattering and make the scar less noticeable. However, due to skin tension, facial incision scars tend to spread. Applying W-plasty alone cannot achieve the ideal repair effect of facial scars. In this study, we proposed a scar revision technique combined W-plasty with continuous tension-reduction (CTR) technique to improve the appearance of facial scars. Sixty patients with facial scar were comprised in this retrospective study. Scars were assessed independently using the scar scale before and at 12-month follow-up. Clinical results showed a significant difference in scar appearance between different groups at 12-month follow-up. Vancouver scar scale (VSS), visual analogue scale (VAS) scores, and patient satisfaction were significant better in W-plasty and CTR than other groups at 12-month follow-up. No severe complications were reported. The application of the tension offloading device provides an environment where the tension is continuously reduced, which could greatly decrease tension on the surgical incision. Combined with W-plasty, this technique could significantly improve the scar's aesthetic appearance.

Microvascular Ear Replantation: A Multicenter Study of 22 Patients with Complete Ear Amputation.

Background: We aimed to report our experience in treating ear amputations with microvascular replantation, with the largest sample to date. Methods: Twenty-two patients with complete ear amputation underwent microvascular ear replantation at three medical centers between May 2003 and May 2020. Arterial anastomoses, venous anastomoses, or vein graft were performed depending on different situations. Re-exploration was performed in four patients due to venous congestion (n = 3) or arterial compromise (n = 1). Results: Eleven patients had vascular complications (venous congestion: 10, arterial compromise: 1) and four of them required re-exploration. Three ears were completely salvaged (75%) and one case failed. Eighteen (81.8%) replanted ears survived completely, with 15 repaired ears demonstrating a good contour and 3 ears showing atrophy. Three replanted ears sustained partial loss, and one sustained total loss. Three extraordinary cases with the longest ischemic time, smallest tissue size, and youngest age reported thus far all survived and had cosmetically satisfactory appearances. Statistical analysis indicated no significant correlation between replanted ear survival and potentially influential factors, including ischemic time, number of arterial and venous anastomoses, presence of vein graft, and re-exploration. Conclusions: Microvascular replantation for ear amputations achieved excellent results. It may be considered the primary choice for surgeons with microsurgical skill.

Hypoxic ADSCs-derived EVs promote the proliferation and chondrogenic differentiation of cartilage stem/progenitor cells.

Cartilage tissue engineering is a promising option for repairing cartilage defects, although harvesting a large number of seeding cells remains a major challenge. Cartilage stem/progenitor cells (CSPCs) seem to be a promising cell source. Hypoxic extracellular vesicles (EVs) may play a major role in cell-cell and tissue-tissue communication. In the current study, we aimed to evaluate the effect of hypoxic adipose-derived stem cells (ADSCs)-derived EVs on CSPCs proliferation and differentiation. The characteristics of ADSCs-derived EVs were identified, and proliferation, migration, and cartilage-related gene expression of CSPCs were measured with or without the presence of hypoxic ADSCs-derived EVs. SEM, histological staining, biochemical and biomechanical analysis was performed to evaluate the effect of hypoxic ADSCs-derived EVs on CSPCs in alginate hydrogel culture. The results indicated that the majority of ADSC-derived EVs exhibited a round-shaped or cup-shaped morphology with a diameter of 40-1000 nm and expressed CD9, CD63, and CD81. CSPCs migration and proliferation were enhanced by hypoxic ADSCs-derived EVs, which also increased the expression of cartilage-related genes. The hypoxic ADSCs-derived EVs induce CSPCs to produce significantly more cartilage matrix and proteoglycan. In conclusion, hypoxic ADSCs-derived EVs improved the proliferation and chondrogenic differentiation of CSPCs for cartilage tissue engineering.

Functional and aesthetic reconstruction of digital flexion contractures with full-thickness plantar skin grafts in children.

Hand burns are frequently seen in children, often resulting in digital flexion contractures. Traditional split-thickness or full-thickness skin grafts leave notably different skin texture and hyperpigmentation. The purpose of this study was to describe our operation for treating digital flexion contractures with full-thickness plantar skin grafts, and to evaluate the appearance and function outcomes. Hematoxylin and eosin staining, Masson trichrome staining and Melan A (marker of melanocyte) staining were used to evaluate palmar skin, plantar skin, groin skin and burn scars. Full-thickness plantar skin grafts were performed between 2008 and 2015 in 24 hand burn patients with digital flexion contracture. The average age at the time of surgery was 39.3 months and the average follow-up period was 5.5 years. The functional and cosmetic results were assessed. Plantar skin shared similar attributes with palmar skin histologically. Both plantar skin and palmar skin did not express melan A. All of the skin grafts survived well without hematoma, infection and necrosis. The grafts resembled the adjacent normal skin in regards to appearance and texture. The average TAM (total active movement) degree for the fingers was improved from 152.3° to 238.5°. The average VSS (Vancouver Scar Scale) score decreased dramatically from 10.4 to 1.1. Twenty one of twenty four patients (21/24, 87.5%) were very satisfied with function and appearance, and three in twenty four (3/24, 12.5%) were somewhat satisfied. This study indicates that full-thickness plantar skin grafts can achieve a satisfactory appearance and good function for hand burn child patients with digital flexion contractures.

Activating PIK3CA mutation promotes adipogenesis of adipose-derived stem cells in macrodactyly via up-regulation of E2F1.

Macrodactyly is a congenital malformation characterized by enlargement of bone and soft tissues in limbs, typically with excessive accumulation of adipose tissues. Although gain-of-function mutation of PIK3CA has been identified in macrodactyly, the mechanism of PIK3CA mutation in adipose accumulation is poorly understood. In this study, we found that adipocytes from macrodactyly were more hypertrophic than those observed in polydactyly. PIK3CA (H1047R) activating mutation and enhanced activity of PI3K/AKT pathway were detected in macrodactylous adipose-derived stem cells (Mac-ADSCs). Compared to polydactyly-derived ADSCs (Pol-ADSCs), Mac-ADSCs had higher potential in adipogenic differentiation. Knockdown of PIK3CA or inhibition by BYL-719, a potent inhibitor of PIK3CA, impaired adipogenesis of Mac-ADSCs in vitro. In vivo study, either transient treatment of ADSCs or intragastrical gavage with BYL-719 inhibited the adipose formation in patient-derived xenograft (PDX). Furthermore, RNA-seq revealed that E2F1 was up-regulated in Mac-ADSCs and its knockdown blocked the PIK3CA-promoted adipogenesis. Our findings demonstrated that PIK3CA activating mutation promoted adipogenesis of ADSCs in macrodactyly, and that this effect was exerted by the up-regulation of E2F1. This study revealed a possible mechanism for adipose accumulation in macrodactyly and suggested BYL-719 as a potential therapeutic agent for macrodactyly treatment.