Dissipative coupling-induced phonon lasing.

Phonon lasers, as the counterpart of photonic lasers, have been intensively studied in a large variety of systems; however, (all) most of them are based on the directly coherent pumping. Intuitively, dissipation is unfavorable for lasing. Here, we experimentally demonstrate a mechanism of generating phonon lasing from the dissipative coupling in a multimode optomechanical system. By precisely engineering the dissipations of two membranes and tuning the intensity modulation of the cavity light, the two-membrane-in-the-middle system exhibits non-Hermitian characteristics and the cavity-mediated interaction between two nanomechanical resonators becomes purely dissipative. The level attraction and damping repulsion are clearly exhibited as the signature of dissipative coupling. After the exceptional point, a non-Hermitian phase transition, where eigenvalues and the corresponding eigenmodes coalesce, two phonon modes are simultaneously excited into the self-sustained oscillation regime by increasing the interaction strength over a critical value (threshold). In distinct contrast to conventional phonon lasers, the measurement of the second-order phonon correlation reveals the oscillatory and biexponential phases in the nonlasing regime as well as the coherence phase in the lasing regime. Our study provides a method to study phonon lasers in a non-Hermitian open system and could be applied to a wide range of disciplines, including optics, acoustics, and quantum many-body physics.

Low Temperature Synthesis of 2D p-Type α-In2Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2/Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2Te3 nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2/Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1 s-1, and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Investigation of unidirectional coupling of dipole emitters in valley photonic heterostructure waveguides.

Photonic heterostructure has recently become a promising platform to study topological photonics with the introduction of mode width degree of freedom (DOF). However, there is still a lack of comprehensive analysis on the coupling of dipole emitters in photonic heterostructures, which constrains the development of on-chip quantum optics based on chiral dipole sources. We systematically analyze the unidirectional coupling mechanism between dipole emitters and valley photonic heterostructure waveguides (VPHWs). With the eigenmode calculations and full-wave simulations, the Stokes parameters are obtained to compare the coupling performance of two types of valley-interface VPHWs. Simulation results show that compared to the zigzag interface with inversion symmetry, the strategy of bearded interface with glide symmetry is easier to realize high-efficiency coupling. By adjusting the position and chirality of dipole emitters in VPHWs, the transmission of light reverses with guided modes coupled to different directions. Furthermore, a topological beam modulator is realized based on VPHWs, which maintains the robustness to large-area potential barriers and sharp corners. Our work supplies a powerful guide for chiral light-matter interaction, which is expected to be applied to increasingly compact and efficient on-chip optical platforms in the future.

Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study.

INTRODUCTION: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). METHODS: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse. RESULTS: Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment. CONCLUSION: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

Calculated plasma volume status in hemodialysis patients.

BACKGROUND: Plasma volume (PV) calculated from hematocrit and body weight has applications in cardiovascular disease. The current study investigated the validity of the calculated PV for predicting volume overload and its prognostic utility in patients undergoing hemodialysis (HD). PATIENTS AND METHODS: Fifty-four HD patients were prospectively enrolled, and their actual PV (aPV) and relative PV status (PVS) were calculated. Bioelectrical impedance analysis (BIA) with assessment of and total body water (TBW), intracellular water (ICW), extracellular water (ECW), and overhydration (OH) and routine blood examinations were performed before dialysis. A second cohort of 164 HD patients was retrospectively enrolled to evaluate the relationship between the calculated PVS and the outcome, with an endpoint of all-cause mortality. RESULTS: aPV was significantly associated with TBW, ICW, ECW, OH, and ECW/TBW (all p < 0.001), and most strongly with ECW (r = 0.83). aPV predicted the extent of volume overload with an AUC of 0.770 (p < 0.001), but PVS did not (AUC = 0.617, p = 0.091). Median follow-up time was 53 months, during the course of which 60 (36.58%) patients died. Values for PVS (12.94 ± 10.87% vs. 7.45 ± 5.90%, p = 0.024) and time-averaged PVS (12.83 ± 11.20 vs. 6.78 ± 6.22%, p < 0.001) were significantly increased in patients who died relative to those who survived. A value of time-averaged PVS >8.72% was significantly associated with an increased incidence of all-cause mortality (HR = 2.48, p = 0.0023). CONCLUSIONS: aPV was most strongly associated with ECW measured using BIA. HD patients with higher time-averaged PVS had a higher rate of all-cause mortality.

Heterocyclic Modulated Electronic States of Alkynyl-Containing Conjugated Microporous Polymers for Efficient Oxygen Reduction.

The oxygen reduction reaction (ORR) is a key process in green energy conversion technology. Heteroatom doping has been proven to be a prospective strategy to prepare metal-free carbon-based electrocatalysts, but such methods often suffer from uncontrollable catalyst frameworks and imprecise active sites. Herein, an organic heterocyclic strategy is adopted to modulate the charge redistribution of alkynyl-containing conjugated microporous polymers (CMPs) by introducing varied five-membered heterocyclic structures. Among these CMPs, the S, 2N-containing thiadiazole heterocyclic molecule (CMP-Tdz) with carbonized alginate materials (CCA ) displays a remarkable quasi-four-electron-transfer ORR pathway, exhibiting an excellent half-wave potential (E1/2 ) of 0.77 V, coupled with superior methanol tolerance and electrochemical stability, which are among the highest performance in the metal-free organic catalytic material systems. Density functional theory calculations prove that the high catalytic performance of these catalysts originates from the sp-hybridized C atom (site-2) which is activated by their adjacent heterocyclic structures. Importantly, the five-membered heterocyclic structures can also modulate the local charge distribution, and increase dipole moment, with significantly improved catalytic kinetics. This incorporation of chemically designed heterocyclic-containing alkynyl-CMPs provides a new approach to developing efficient metal-free carbon-based electrocatalysts for fuel cells.

Terahertz narrowband filter metasurfaces based on bound states in the continuum.

The electromagnetically induced transparency (EIT) effect realized by metasurfaces have potential for narrowband filtering due to their narrow bandwidth. In optics, bound states in the continuum (BIC) can produce strong localized resonances, which means that light can be trapped and stored for long periods of time to produce very high Q-factors. This has potential applications in designing highly efficient sensors and narrow bandpass filters. Here, we present two metal-flexible dielectric metasurfaces consisting of copper structures and polyimide substrates. Quasi BICs are obtained by breaking C2 symmetry of the metal structures. Resonance-captured quasi-BICs with ultra-high q-factor resonances satisfy the dark modes required to realize the EIT and couple to the bright modes in the structure to achieve narrowband filtering. The peak transmission rates are around 0.9 at 0.29 THz-0.32 THz and 0.23 THz-0.27 THz, respectively. Our results have practical implications for the realization of low-frequency terahertz communications.

Mechano/acousto-electric coupling between ReS2and surface acoustic wave.

Two-dimensional (2D) materials are promising candidates for developing next generation electronic/optoelectronic devices with programmable multi functions, due to their widely tunable properties by various physical stimuli. Mechanical strain is one of the most promising means to effectively modulate the physical properties of 2D materials. Nevertheless, few studies reported micro/nano scale controllable strain application platforms, limiting the development of novel mechano-electrical/optoelectrical devices based on 2D materials. This work proposes surface acoustic wave (SAW) device as a controllable strain modulation platform for 2D materials with sub-micro scale resolution. The platform uses the piezoelectric material (LiNbO3) as the substrate, which is deposited with interdigitated transducers (IDT) to generate SAW on the surface. The propagation of SAW causes surface deformation, which is then transferred to the 2D materials on the substrate. The period of the surface deformation/strain is related with that of SAW, which is determined by the period of IDT with nano meter scale. It is demonstrated that the photo luminescence spectrum of a 2D ReS2flake on this platform gradually shifts with the SAW excitation power, which reaches a shift of 3 nm as the SAW excitation power achieves 26 dBm, corresponding to a band gap increase of 5 meV. Meanwhile, the platform is also capable to provide acousto-electric coupling between SAW and 2D materials, which is demonstrated by the shift of the SAW resonant frequency due to the re-distribution of photo-generated carriers in ReS2upon light illumination.

New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders.

As a large and heterogeneous group of disorders, neurodegenerative diseases are characterized by the progressive loss of structure or function in neurons, finally leading to neuronal death. Neurodegenerative diseases cause serious threat to a patient's quality of life and the most common are Alzheimer's disease and Parkinson's disease. Currently, little is known of the detailed etiology of these disorders; as such, there are no effective treatments available. Furthermore, the lack of targeted, effective, and resolvable therapy for neurodegenerative diseases, represents an expanding research field for the discovery of new therapeutic strategies. Investigations of the potential pathogenesis of neurodegenerative diseases will become the basis of preventing the occurrence and development of neurodegenerative diseases and finding effective therapies. Existing theories and mechanisms, such as genetic and environmental factors, abnormal protein accumulation, and oxidative stress, are intricately associated with each other. However, there is no molecular theory that can entirely explain the pathological processes underlying neurodegenerative diseases. Due to the development of experimental technology and the support of multidisciplinary integration, it has been possible to perform more in-depth research on potential targets for neurodegenerative diseases and there have been many exciting discoveries in terms of original theories and underlying mechanisms. With this review, we intend to review the existing literature and provide new insights into the molecular mechanisms underlying neurodegenerative diseases.

A functionalized Sup35NM nanofibril-assisted oriented antibody capture in lateral flow immunoassay for sensitive detection of dengue type II NS1.

Rapid and sensitive dengue non-structural protein 1 (NS1) detection assay is essential for the treatment of disease and currently releases high medical cost burdens. To address the limitations of conventional LFIA strips, we have developed an improved Sup35NM-Z-based LFIA that immobilizes antibodies on cellulose membranes in an orientated manner to increase the sensitivity of LFIA strips. A dual-functional Sup35NM nanofibril was fabricated by fusion with the antibody binding domain; resultant nanofibril from the amyloid Sup35NM was sprayed on the T-line to orientate the capture antibody and produces fluorescence signals. Antibody binding analysis showed that self-assembly of the Sup35NM monomer does not affect the binding activity of the Z-domain with the antibody. The NS1 for DENV-2 infection was chosen as a model target antigen to assess the feasibility of the Sup35NM-Z-domain-based LFIA platform. Under optimal conditions, the Sup35NM-Z-domain-based LFIA detected NS1 within 15 min with a detection limit of 1.29 ng/ml, while the detection limit of traditional LFIA with the same concentration of anti-NS1-Ab1 on the T-line by conventional physical adsorption was 2.20 ng/ml, 1.7 times higher than that of Sup35NM-Z-domain-based LFIA. As compared to traditional LFIAs, the Sup35NM-Z-based LFIA had a wide detection range of 1.29-625 ng/mL. The LFIA's clinical performance in identifying NS1 was also assessed using 15 clinical samples. The LFIA accurately recognized positive and negative samples, equal to 86.7% accuracy. The developed Sup35NM-Z-domain-based LFIA in this study offers great potential for the identification of target markers because of its greatly improved sensitivity and wider detection range.

A flexible electrostatic nanogenerator and self-powered capacitive sensor based on electrospun polystyrene mats and graphene oxide films.

Electrostatic nanogenerators or capacitive sensors that leverage electrostatic induction for power generation or sensing, has attracted significant interests due to their simple structure, ease of fabrication, and high device stability. However, in order for such devices to work, an additional power source or a post-charging process is necessary to activate the electrostatic effect. In this work, an electrostatic nanogenerator is fabricated using electrospun polystyrene (PS) mats and dip-coated graphene oxide (GO) films as the self-charged components. The electret performances of the PS mats and GO films are characterized via the electrostatic force microscopy phase shift and surface potential measurements. With a multilayer device structure that consists of top electrodes/GO films/spacer/electrospun PS mats/bottom electrodes, the resultant device acts as an electrostatic generator that operates in the noncontact mode. The nanogenerator can output a peak voltage of ca. 6.41 V and a peak current of ca. 6.57 nA at a rate of 1 Hz of mechanical compression, and with no attenuation of electrical outputs even after 50 000 cycles over a 13 h period. Furthermore, this as-prepared device is also capable of serving as a self-powered capacitive sensor for detection of tiny mechanical impacts and measurement of human finger bending. This results of this work provides a new avenue to easily fabricate electrostatic nanogenerators with high durability and self-powered capacitive sensors for the detection of small impacts.

Long-range common-path spectral domain optical coherence tomography.

Fiber-based common-path spectral domain optical coherence tomography (SD-OCT) is compact and polarization insensitive, which is usually used in endoscopic biomedical imaging. In this study, we investigate a method to extend the working distance of a common-path SD-OCT system. Common-path OCT light, which consisting of sample and reference light signal, is directed into a free space optical interferometer. The OCT light is split spatially into two beam segments by a wavefront-splitting mirror, and the two parallel beams interfere noncollinearly in the interferometer. Distance between the end of the probing fiber, which serves as the reference plane of our OCT system, and the OCT sample is about 140 mm. The OCT performance is demonstrated by imaging biological samples. The proposed method can be used to develop polarization insensitive OCT probe for biomedical imaging applications.

Investigating the mechanism by which SMAD3 induces PAX6 transcription to promote the development of non-small cell lung cancer.

BACKGROUND: This study investigated the function of SMAD3 (SMAD family member 3) in regulating PAX6 (paired box 6) in non-small cell lung cancer. METHODS: First, qRT-PCR was employed to detect SMAD3 expression in cancer tissues along with normal tissues and four cell lines, including BEAS-2B, H125, HCC827 and A549 cells. SMAD3 was knocked down by small interference RNA (siRNA), and then its expression was determined via qRT-PCR and Western blot analysis. The correlation between SMAD3 and PAX6 was determined by double luciferase reporter experiments and chromatin immunoprecipitation (ChIP) assay. Cell viability was evaluated by CCK-8 and colony forming assays, while cell migration and invasion were detected by Transwell analysis. RESULTS: SMAD3 and PAX6 were upregulated in lung cancer tissues and cancer cells. Knocking down SMAD3 and PAX6 by transfection with siRNAs specifically suppressed the expression of SMAD3 and PAX6 mRNA and protein levels. SMAD3 could promote PAX6 transcriptional activity by binding to its promoter. Reduced expression of SMAD3 led to the downregulation of PAX6 mRNA and protein levels along with decreased cell migration, invasion, proliferation and viability in A549 and HCC827 cells. PAX6 overexpression altered the si-SMAD3-induced inhibition of cell migration, invasion, proliferation and viability in A549 and HCC827 cells. Additionally, PAX6 knockdown alone also repressed the cell migration, invasion, proliferation and viability of the cell lines. CONCLUSIONS: SMAD3 promotes the progression of non-small cell lung cancer by upregulating PAX6 expression.

Flexible gas sensor based on graphene/ethyl cellulose nanocomposite with ultra-low strain response for volatile organic compounds rapid detection.

Minimizing the strain-induced undesirable effects is one of the major efforts to be made for flexible electronics. This work demonstrates a highly sensitive flexible gas sensor with ultra-low strain response, which is potentially suitable for wearable electronics applications. The gas sensing material is a free-standing and flexible thin film made of graphene/ethyl cellulose (EC) nanocomposite, which is then integrated with flexible substrate of polyethylene terephthalate. The sensor exhibits relative resistance change within 0.3% at a minimum bending radius of 3.18 mm and 0.2% at the bending radius of 5 mm after 400 bending cycles. The limited strain response attributes to several applied strategies, including using EC with high Young's modulus as the matrix material, maintaining high graphene concentration and adopting suspended device structure. In contrast to the almost negligible strain sensitivity, the sensor presents large and rapid responses toward volatile organic compounds (VOCs) at room temperature. Specifically, the sensor resistance rapidly increases upon the exposure to VOCs with detection limits ranging from 37 to 167 ppm. A preliminary demo of wearable gas sensing capability is also implemented by wearing the sensor on human hand, which successfully detects several VOCs, instead of normal hand gestures.

Cryptococcal meningitis in adult patients with primary nephrotic syndrome
.

BACKGROUND: Cryptococcal meningitis (CM) is a rare condition in patients with primary nephrotic syndrome (PNS). Here, we describe the clinical characteristics, possible risk factors, and outcomes of eleven patients with PNS and CM. MATERIALS AND METHODS: A systematic review of medical records from 11 patients with PNS and CM admitted to the First Affiliated Hospital of Wenzhou Medical University from April 2005 to April 2015 was performed. A total of 30 cases were randomly selected as controls from PNS inpatients without infection during the same period. RESULTS: The mean age at presentation was 64.6 years (range: 47.8 - 72.2 years), and the female-to-male ratio was 5 : 6. The mean duration of PNS was 14.0 months (range: 1 - 25 months); the cumulative prednisone dose over the preceding year was 3.8 ± 1.98 g; the mean albumin level was 25.8 ± 10.1 g/L; the mean serum creatinine level was 116.4 ± 64.3 µmol/L. Three patients died, 1 patient survived with sequelae, and 7 patients survived without sequelae. Unfavorable outcomes were associated with low serum albumin levels (p = 0.004) and higher cumulative prednisone dose over the preceding year (p = 0.025). Compared with PNS patients without infections, those with CM were older (p < 0.001) and usually had higher serum creatinine levels (p < 0.001). CONCLUSION: Old age and high serum creatinine levels are important risk factors for the development of CM in patients with PNS.
.

Synthesis and magnetic properties of Fe3C-C core-shell nanoparticles.

Fe3C-C core-shell nanoparticles were fabricated on a large scale by metal-organic chemical vapor deposition at 700 °C with ferric acetylacetonate as the precursor. Analysis results of x-ray diffraction, transmission electron microscope and Raman spectroscope showed that the Fe3C cores with an average diameter of ∼35 nm were capsulated by the graphite-like C layers with the thickness of 2-5 nm. The comparative experiments revealed that considerable Fe3O4-Fe3C core-shell nanoparticles and C nanotubes were generated simultaneously at 600 and 800 °C, respectively. A formation mechanism was proposed for the as-synthesized core-shell nanostructures, based on the temperature-dependent catalytic activity of Fe3C nanoclusters and the coalescence process of Fe3C-C nanoclusters. The Fe3C-C core-shell nanoparticles exhibited a saturation magnetization of 23.6 emu g(-1) and a coercivity of 550 Oe at room temperature.

Ni3C-assisted growth of carbon nanofibres 300 °C by thermal CVD.

Ni-assisted thermal chemical vapor deposition (TCVD) is one of the most common techniques for the growth of carbon nanofibres/nanotubes (CNFs/CNTs). However, some fundamental issues related to the catalytic growth of CNFs/CNTs, such as the low-limit growth temperature, the limiting steps and the state of Ni, are still controversial. Here, we report the growth of CNFs at 300 °C; that is the lowest temperature for the growth of CNFs by TCVD using Ni as the catalyst so far. The results showed that the Ni existed in rhombohedral Ni3C, not in the normal form of face-centered cubic Ni, and the C atoms for building the CNFs were precipitated from the (001) planes of the faceted Ni3C nanoparticles. The CNFs are believed to be formed by the decomposition-formation cycle of metastable Ni3C that has a low-limit decomposition temperature of about 300 °C. Our results strongly suggest that TCVD is a valuable tool for the synthesis of CNFs/CNTs at temperatures below 400 °C, which is generally considered as the upper-limit temperature for fabricating complementary metal oxide semiconductor devices but is the low-limit temperature for growing CNFs/CNTs by TCVD at present.

Heat-shock protein beta 1 regulates androgen-mediated bovine myogenesis.

To elucidate the functional significance of heat-shock protein beta 1 (HSPB1) in androgen-mediated myogenesis of bovine cells, we conducted 'loss and gain of function of HSPB1' assays by siRNA inhibition and gene overexpression. siRNA inhibition of HSPB1 expression reduced the expression of desmin (a myogenic marker) and repressed the formation of myotubes in cells induced for myogenic differentiation. In contrast, overexpression of HSPB1 enhanced the expression of desmin and accelerated formation of myotubes. The loss and gain of HSPB1 function was closely associated with the expression level of androgen receptor (AR). Our findings suggest that HSPB1 mediates androgen signaling by binding directly to AR and then enhancing androgen-mediated myogenesis in myogenic cells.

Polyxylitol-based gene carrier improves the efficiency of gene transfer through enhanced endosomal osmolysis.

Endosomal escape is one of the important processes for efficient non-viral gene delivery. In this study, we synthesized a novel non-viral vector called polyxylitol-based gene carrier (XGC) through a Miachael addition reaction between xylitol diacrylate as a crosslinking agent and low molecular weight polyethylenimine (PEI 1.2kDa). The small amount of xylitol integrated into XGC (3.9% w/w) contributed 50% of the osmotic pressure of XGC, and enhaned the osmolysis of endosome cooperatively with the proton sponge effect, thus improving endosomal escape. Furthermore, XGC showed higher transfection efficiency in vivo in muscle tissue than pDNA alone or PEI 25kDa. In conclusion, our results show that XGC enhanced transfection efficiency compared with PEI 25kDa, the golden standard non-viral gene carrier, by enhancing endosomal escape without increasing the number of transfected cells. FROM THE CLINICAL EDITOR: Enhanced gene delivery methods would greatly facilitate the development of gene therapies. These authors demonstrate that a polyxylitol-based gene carrier enhanced the transfection efficiency compared with the gold standard non-viral gene carrier, as a result of enhancing endosomal escape without increasing the number of transfected cells, warranting further studies of this method.

Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-ß/SMAD2 and PI3K/Akt pathways.

In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-ß1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and LY294002, inhibitors of TGF-ß/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-ß/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-ß/SMAD2 and PI3K/AKT pathways.