The ideal range of laser hair removal for microtia patients undergoing two-stage ear reconstruction.

Although the technologies for auricular reconstruction in microtia have improved, issues such as low hairlines or excessive hair growth can still pose aesthetic problems for the reconstructed ear. Laser depilation has been reported as a solution for hair problems. However, few studies have discussed the appropriate region for hair removal. A retrospective analysis was performed on 276 patients with unilateral microtia who underwent the Nagata two-stage ear reconstruction. The gender ratio of male to female was 2.5 (198 males/78 females). Intense pulsed light depilation was used to remove hair. To determine the proper hair removal area, we measured the extent of hair removal. Before the first stage, the average vertical distance between the upper point (after localization) and hairline was 3.42 ± 4.75 mm (-10-20 mm). After the first stage, the average vertical distance between the upper point of the reconstructed ear and the hairline was 1.27 ± 2.41 mm (-10-15 mm). By using chi-square test to assess differences in hair removal success rates among various regions, we aimed to identify the suitable depilation region. Before the first stage, a depilation vertical distance ≥ 10 mm led to a 92.1% success rate. After the first stage surgery, among the patients needing additional hair removal, a vertical depilation distance ≥ 4 mm resulted in an 81.3% success rate. Based on our observation, we suggested that a depilation region of ≥ 10 mm (before the first surgery) or ≥ 4 mm (after the first surgery) would be the ideal range for laser hair removal.

Surface astigmatism correction using segmented freeform surfaces for a progressive addition lens.

The undesired distribution of irregular surface astigmatism (SA) on the freeform surface has been the major concern of progressive addition lens (PAL) design. Herein, we proposed a segmented freeform surface (SFS) construction method, which relies on the lines of curvature to rule the surface segmentation and then eliminates the difference between principal curvatures to correct the SA. Based on ray tracing and numerical simulation results, the SFS-PAL design has superior performance in image quality within a dynamic field of view over the conventional freeform PAL. To verify the feasibility and the real performance of the new design, we used the diamond turning method with a fast tool servo to realize the rapid prototyping, and then used injection molding for the mass production of the high-quality SFS-PALs.

The Course of Superficial Temporal Artery in Patients with Microtia and its Relationship with the Remnant.

OBJECTIVE: Temporoparietal fascia is important for auricular reconstruction or repair after auricular reconstruction. Thus, the course of the superficial temporal artery (STA) is of vital importance to prevent destruction of the artery. The purpose of this study was to evaluate the course of the superficial temporal artery in patients with congenital microtia and its relationship with remnants. METHODS: This was a prospective study. Patients with microtia who underwent auricular reconstruction in our hospital from January 2021 to July 2021 underwent ultrasound examination of the STA. Under the guidance of ultrasound, the superficial temporal artery and its branches were located and marked on the body surface before the operation, ranging from the zygomatic arch plane to the temporal parietal artery. In addition, the hemodynamics of the STAs were recorded. RESULTS: A total of 108 patients with microtia were collected, including 106 patients with unilateral microtia and 2 patients with bilateral microtia. There were 82 cases of lobule type, 21 cases of small concha type, and 7 cases of large concha type. The superficial temporal artery in 103 ears was divided into two branches: the parietal branch and the frontal branch, but there was only one branch in 7 ears. The parietal branch was absent in 5 cases, and the frontal branch was absent in 2 cases. In most of the ears, the bifurcation was located above the zygomatic arch plane. Only in 2 ears was the bifurcation located below the zygomatic arch, and the most common bifurcation position was the eyebrow arch level (43.7%). Regarding the shortest distances between the STA and the remnant, they were less than 0.5 cm in 47 ears, more than 1 cm in 30 ears, and 0.5 cm to 1 cm in 33 ears. CONCLUSION: The course of STA varied greatly and there were occasional single branches. The distances between the STA and remnant were often near 0.5 cm by ultrasonography. Therefore, when removing the remnant and separating the pocket, care should be taken to avoid arterial injury. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. 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 .

Loading of Zn/ZnO particles in the precursor feedstock affects the characteristics of liquid plasma sprayed nano-ZnO coatings for photocatalytic applications.

It is known that ZnO is an n-type semiconductor with photocatalytic performances under ultraviolet light irradiation. Constructing a superior structure for a modified electron band has been one of the major research goals for photocatalytic ZnO. Here we report a new technical route for making nano-ZnO coatings with a porous topographic morphology. The coatings were fabricated by plasma spraying the mixture of suspension and solution liquid precursors. Pre-loading of ZnO and Zn powders in the precursor was carried out for the purpose of tailoring the structure of the coatings. The coatings in micron thicknesses showed a porous skeleton and a fluffy top layer consisting of ultrafine ZnO grains. Photocatalytic testing by measuring the degradation of methylene blue revealed significantly enhanced activities of the coatings deposited using the ZnO/Zn loaded precursor. The hybrid-structured ZnO coatings exhibited a narrowed band gap and modified oxygen defects as compared to those deposited from the single liquid feedstock. The results shed light on a one-step easy thermal spray fabrication of polytropic nanostructured functional coatings by employing solid powder-loaded liquid as the starting feedstock.

1064 nm Nd:YAG laser treatment of melanocytic nevi of the external auditory canal: a retrospective study of 15 cases.

The aim of this study was to evaluate the efficacy and safety of 1064 nm neodymium-doped yttrium-aluminum-garnet laser treatment of melanocytic nevus of the external auditory canal. Retrospective chart review of 15 patients operated by 1064 nm Nd:YAG laser in single center. Data from charts and video documentation were collected and analyzed. Between November 2017 and November 2018, 15 patients underwent 1064 nm Nd:YAG laser treatment for melanocytic nevus of the external auditory canal were analyzed in the study. The size of melanocytic nevus ranged from 4 to 8 mm in diameter. A gross total removed was achieved in all cases. Two patients received two sessions of Nd:YAG laser treatments, and the remaining thirteen patients received only one session. After laser treatment, wounds healing well and the average epithelialization time was 2.3 weeks. The mean follow-up was 12 months. There were no recurrence and adverse side effects in all cases. This research supports the use of 1064 nm Nd:YAG laser as a safe and efficacious treatment for melanocytic nevus of the external auditory canal.

Nanochannel-Based Transport in an Interfacial Memristor Can Emulate the Analog Weight Modulation of Synapses.

By exploiting novel transport phenomena such as ion selectivity at the nanoscale, it has been shown that nanochannel systems can exhibit electrically controllable conductance, suggesting their potential use in neuromorphic devices. However, several critical features of biological synapses, particularly their conductance modulation, which is both memorable and gradual, have rarely been reported in these types of systems due to the fast flow property of typical inorganic electrolytes. In this work, we demonstrate that electrically manipulating the nanochannel conductance can result in nonvolatile conductance tuning capable of mimicking the analog behavior of synapses by introducing a room-temperature ionic liquid (IL) and a KCl solution into the two ends of a nanochannel system. The gradual conductance-tuning mechanism is identified through fluorescence measurements as the voltage-induced movement of the interface between the immiscible IL and KCl solution, while the successful memorization of the conductance tuning is ascribed to the large viscosity of the IL. We applied a nanochannel-based synapse to a handwritten digit-recognition task, reaching an accuracy of 94%. These promising results provide important guidance for the future design of nanochannel-based neuromorphic devices and the manipulation of nanochannel transport for computing.

High-density immobilization of a ginsenoside-transforming ß-glucosidase for enhanced food-grade production of minor ginsenosides.

Use of recombinant glycosidases is a promising approach for the production of minor ginsenosides, e.g., Compound K (CK) and F1, which have potential applications in the food industry. However, application of these recombinant enzymes for food-grade preparation of minor ginsenosides are limited by the lack of suitable expression hosts and low productivity. In this study, Corynebacterium glutamicum ATCC13032, a GRAS strain that has been used extensively for the industrial-grade production of additives for foodstuffs, was employed to express a novel ß-glucosidase (MT619) from Microbacterium testaceum ATCC 15829 with high ginsenoside-transforming activity. A cellulose-binding module was additionally fused to the N-terminus of MT619 for immobilization on cellulose, which is an abundant and safe material. Via one-step immobilization, the fusion protein in cell lysates was efficiently immobilized on regenerated amorphous cellulose at a high density (maximum 984 mg/g cellulose), increasing the enzyme concentration by 286-fold. The concentrated and immobilized enzyme showed strong conversion activities against protopanaxadiol- and protopanaxatriol-type ginsenosides for the production of CK and F1. Using gram-scale ginseng extracts as substrates, the immobilized enzyme produced 7.59 g/L CK and 9.42 g/L F1 in 24 h. To the best of our knowledge, these are the highest reported product concentrations of CK and F1, and this is the first time that a recombinant enzyme has been immobilized on cellulose for the preparation of minor ginsenosides. This safe, convenient, and efficient production method could also be effectively exploited in the preparation of food-processing recombinant enzymes in the pharmaceutical, functional food, and cosmetics industries.

Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates.

The Mus81-Eme1 complex is a structure-selective endonuclease with a critical role in the resolution of recombination intermediates during DNA repair after interstrand cross-links, replication fork collapse, or double-strand breaks. To explain the molecular basis of 3' flap substrate recognition and cleavage mechanism by Mus81-Eme1, we determined crystal structures of human Mus81-Eme1 bound to various flap DNA substrates. Mus81-Eme1 undergoes gross substrate-induced conformational changes that reveal two key features: (i) a hydrophobic wedge of Mus81 that separates pre- and post-nick duplex DNA and (ii) a "5' end binding pocket" that hosts the 5' nicked end of post-nick DNA. These features are crucial for comprehensive protein-DNA interaction, sharp bending of the 3' flap DNA substrate, and incision strand placement at the active site. While Mus81-Eme1 unexpectedly shares several common features with members of the 5' flap nuclease family, the combined structural, biochemical, and biophysical analyses explain why Mus81-Eme1 preferentially cleaves 3' flap DNA substrates with 5' nicked ends.

Cutting Edge: Skin CCR10+ CD8+ T Cells Support Resident Regulatory T Cells through the B7.2/Receptor Axis To Regulate Local Immune Homeostasis and Response.

Resident T cells in barrier tissues are important in protecting against foreign agents but can also contribute to inflammatory diseases if dysregulated. How T cell homeostasis is maintained in barrier tissues is still poorly understood. We report that resident CD8(+) T cells directly support maintenance of regulatory T cells (Tregs) in the skin to promote immune homeostasis. Impaired establishment of resident CD8(+) T cells caused by knockout of the skin-homing chemokine receptor CCR10 resulted in an altered balance of resident Tregs and CD4(+) effector T cells in the skin and overreactive inflammatory responses to cutaneous stimulations. Furthermore, B7.2 expressed on skin CD8(+) T cells supports the survival of Tregs, likely through interaction with its receptor CTLA-4, which is highly expressed on skin Tregs. Our findings provide novel insights into T cell homeostatic regulation in the skin and may improve our understanding of the pathobiology of tissue inflammatory diseases.

Leucine zipper-mediated targeting of multi-enzyme cascade reactions to inclusion bodies in Escherichia coli for enhanced production of 1-butanol.

Metabolons in nature have evolved to facilitate more efficient catalysis of multistep reactions through the co-localization of functionally related enzymes to cellular organelles or membrane structures. To mimic the natural metabolon architecture, we present a novel artificial metabolon that was created by targeting multi-enzyme cascade reactions onto inclusion body (IB) in Escherichia coli. The utility of this system was examined by co-localizing four heterologous enzymes of the 1-butanol pathway onto an IB that was formed in E. coli through overexpression of the cellulose binding domain (CBD) of Cellulomonas fimi exoglucanase. To target the 1-butanol pathway enzymes to the CBD IB, we utilized a peptide-peptide interaction between leucine zipper (LZ) peptides. We genetically fused the LZ peptide to the N-termini of four heterologous genes involved in the synthetic 1-butanol pathway, whereas an antiparallel LZ peptide was fused to the CBD gene. The in vivo activity of the CBD IB-based metabolon was examined through the determination of 1-butanol synthesis using E. coli transformed with two plasmids containing the LZ-fused CBD and LZ-fused 1-butanol pathway genes, respectively. In vivo synthesis of 1-butanol using the engineered E. coli yielded 1.98g/L of 1-butanol from glucose, representing a 1.5-fold increase over that obtained from E. coli expressing the LZ-fused 1-butanol pathway genes alone. In an attempt to examine the in vitro 1-butanol productivity, we reconstituted CBD IB-based metabolon using CBD IB and individual enzymes of 1-butanol pathway. The 1-butanol productivity of in vitro reconstituted CBD IB-based metabolon using acetoacetyl-CoA as the starting material was 2.29mg/L/h, 7.9-fold higher than that obtained from metabolon-free enzymes of 1-butanol pathway. Therefore, this novel CBD-based artificial metabolon may prove useful in metabolic engineering both in vivo and in vitro for the efficient production of desired products.

Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation.

In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC subcomplex comprising ArgRS, glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)/p43. In this complex, the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilized the N-terminal helix of ArgRS and abrogated its catalytic activity. Mutation of the N-terminal helix of ArgRS liberated GlnRS, which is known to control cell death. This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. These findings demonstrate the importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex.

Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit.

Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth-associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP-immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in excitatory synapses in the VCN may represent a detrimental process that causes central hyperactivity, leading to tinnitus.

Fermentative production and direct extraction of (-)-α-bisabolol in metabolically engineered Escherichia coli.

BACKGROUND: (-)-α-Bisabolol, also known as levomenol, is an unsaturated sesquiterpene alcohol that has mainly been used in pharmaceutical and cosmetic products due to its anti-inflammatory and skin-soothing properties. (-)-α-Bisabolol is currently manufactured mainly by steam-distillation of the essential oils extracted from the Brazilian candeia tree that is under threat because its natural habitat is constantly shrinking. Therefore, microbial production of (-)-α-bisabolol plays a key role in the development of its sustainable production from renewable feedstock. RESULTS: Here, we created an Escherichia coli strain producing (-)-α-bisabolol at high titer and developed an in situ extraction method of (-)-α-bisabolol, using natural vegetable oils. We expressed a recently identified (-)-α-bisabolol synthase isolated from German chamomile (Matricaria recutita) (titer: 3 mg/L), converted the acetyl-CoA to mevalonate, using the biosynthetic mevalonate pathway (12.8 mg/L), and overexpressed farnesyl diphosphate synthase to efficiently supply the (-)-α-bisabolol precursor farnesyl diphosphate. Combinatorial expression of the exogenous mevalonate pathway and farnesyl diphosphate synthase enabled a dramatic increase in (-)-α-bisabolol production in the shake flask culture (80 mg/L) and 5 L bioreactor culture (342 mg/L) of engineered E. coli harboring (-)-α-bisabolol synthase. Fed-batch fermentation using a 50 L fermenter was conducted after optimizing culture conditions, resulting in efficient (-)-α-bisabolol production with a titer of 9.1 g/L. Moreover, a green, downstream extraction process using vegetable oils was developed for in situ extraction of (-)-α-bisabolol during fermentation and showed high yield recovery (>98%). CONCLUSIONS: The engineered E. coli strains and economically viable extraction process developed in this study will serve as promising platforms for further development of microbial production of (-)-α-bisabolol at large scale.

A New Three-Dimensional Template for the Fabrication and Localization of an Autogenous Cartilage Framework during Microtia Reconstruction.

AIMS: To assist with the accurate fabrication and localization of a costal cartilage framework for auricular reconstruction, three-dimensional (3D) digital and solid templates including the auricle and guide plate were made for microtia patients. METHODS: The computed tomography data of 60 patients with microtia were included. The 3D digital template of the auricle and guide plate on the healthy side was shaped using MIMICS software with graphic image processing and 3D reconstruction technology. The 3D digital template on the affected side was produced by mirror technique and made into a solid template for clinical application. RESULTS: All 60 patients had a good result of the location and the appearance of the constructed auricle. The time of operation was decreased by an average of half an hour. An individualized 3D solid model of the reconstructed auricular template on the affected side was successfully produced and used in auricular reconstruction. CONCLUSIONS: The new 3D template of the auricle and guide plate may be a major contribution to the engraving, assembling and localization of the microtia auricle in auricular reconstruction.

CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin.

BACKGROUND: CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. OBJECTIVE: We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation. METHODS: Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. RESULTS: CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin. CONCLUSION: CCR10 is a critical regulator of skin immune homeostasis.

The location of the mastoid portion of the facial nerve in patients with congenital aural atresia.

In order to investigate the location of the mastoid portion of the facial nerve in patients with congenital aural atresia and to assess its effect on the round window middle ear implant (MEI) transducer implantation approach, 70 patients with unilateral congenital aural atresia were examined by computer tomography (CT). The patients were divided into two groups based on their ages: 44 patients in Group A (2-12 years) and 26 patients in Group B (13-29 years). CT scans were reviewed for each patient. Based on the CT findings, the mastoid portion of the facial nerve's spatial configuration with respect to the oval and round windows was qualitatively recorded. Additionally, the exact location of the facial nerve was measured quantitatively. The results suggested that of the 70 deformed ears, 57 had facial nerves located at the round window, six at the oval window, and seven at the normal site. Of the 70 normal opposite ears, 63 had facial nerves located at the normal site, and the other seven had facial nerves located at the round window. Based on the quantitative measurements, the mastoid portion of the facial nerve was more anteriorly positioned in the deformed ears: 3.44-6.09 mm more anteriorly located in Group A and 4.35-7.41 mm more anteriorly located in Group B. In conclusion, in patients with congenital aural atresia, the dislocation of the facial nerve could have significant effects on the surgical approach to round window MEI transducer implantation.

Congenital aural atresia and stenosis: surgery strategies and long-term results.

OBJECTIVE: To compare the patients who underwent surgery for congenital aural atresia (CAA) with congenital aural stenosis (CAS) for the stability of hearing results and complications during long-term follow-up. DESIGN: Retrospective review. STUDY SAMPLE: Seventy-five CAA patients and fifty CAS patients who underwent congenital meatoplasty with canalplasty and tympanoplasty between 2007 and 2012. RESULTS: Paired comparison analyses detected no significant difference in preoperative ABG but significant changes in postoperative ABG, ΔABG, the number of ABG < 30 dB and ABG < 10 dB between CAA and CAS. Complications such as postoperative stenosis, bony regrowth, external aural canal (EAC) infection, EAC eczema, total deaf, and lateralization of the tympanic membrane (TM) were observed in 61.3% of patients with CAA and 20% of patients with CAS. Chi square test detected significant differences in complications between patients with CAA and CAS (χ(2) = 20.73, p < 0.01). CONCLUSION: Meatoplasty with canalplasty and tympanoplasty in individuals with CAS can yield reliable and lasting positive hearing results with a low incidence of severe complications. The existence and preoperative condition of patients' TM and EAC skin helped improve hearing results and decrease the incidence of complications. However, the final hearing results and complications required stricter indications for CAA patients.

LGR5 Modulates Differentiated Phenotypes of Chondrocytes Through PI3K/AKT Signaling Pathway.

BACKGROUND: Tissue engineering is increasingly viewed as a promising avenue for functional cartilage reconstruction. However, chondrocyte dedifferentiation during in vitro culture remains an obstacle for clinical translation of tissue engineered cartilage. Re-differentiated induction have been employed to induce dedifferentiated chondrocytes back to their original phenotype. Regrettably, these strategies have been proven to be only moderately effective. METHODS: To explore underlying mechanism, RNA transcriptome sequencing was conducted on primary chondrocytes (P0), dedifferentiated chondrocytes (P5), and redifferentiated chondrocytes (redifferentiation-induction of P5, P5.R). Based on multiple bioinformatics analysis, LGR5 was identified as a target gene. Subsequently, stable cell lines with LGR5 knocking-down and overexpression were established using P0 chondrocytes. The phenotypic changes in P1 and P5 chondrocytes with either LGR5 knockdown or overexpression were assessed to ascertain the potential influence of LGR5 dysregulation on chondrocyte phenotypes. Regulatory mechanism was then investigated using bioinformatic analysis, protein-protein docking, immunofluorescence co-localization and immunoprecipitation. RESULTS: The current study found that dysregulation of LGR5 can significantly impact the dedifferentiated phenotypes of chondrocytes (P5). Upregulation of LGR5 appears to activate the PI3K/AKT signal via increasing the phosphorylation levels of AKT (p-AKT1). Moreover, the increase of p-AKT1 may stabilize ß-catenin and enhance the intensity of Wnt/ß-catenin signal, and help to restore the dedifferentated phenotype of chondrocytes. CONCLUSION: LGR5 can modulate the phenotypes of chondrocytes in P5 passage through PI3K/AKT signaling pathway.