Earliest Prepared core technology in Eurasia from Nihewan (China): Implications for early human abilities and dispersals in East Asia.

Organized flaking techniques to obtain predetermined stone tools have been traced back to the early Acheulean (also known as mode 2) in Africa and are seen as indicative of the emergence of advanced technical abilities and in-depth planning skills among early humans. Here, we report one of the earliest known examples of prepared core technology in the archaeological record, at the Cenjiawan (CJW) site in the Nihewan basin of China, dated 1.1 Mya. The operational schemes reconstructed from the CJW refit sets, together with shaping patterns observed in the retouched tools, suggest that Nihewan basin toolmakers had the technical abilities of mode 2 hominins, and developed different survival strategies to adapt to local raw materials and environments. This finding predates the previously earliest known prepared core technology from Eurasia by 0.3 My, and the earliest known mode 2 sites in East Asia by a similar amount of time, thus suggesting that hominins with advanced technologies may have migrated into high latitude East Asia as early as 1.1 Mya.

Fundamental understanding of nitrogen in biomass electrocatalysts for oxygen reduction and zinc-air batteries.

Exploring high-efficiency catalysts for oxygen reduction reactions (ORRs) is essential for the development of large-scale applications of fuel cell and metal-air batteries technology. The as-prepared Fe-NC-800 via polymerization-pyrolysis strategy exhibited superior ORR activity with onset potential of 1.030 V vs. reversible hydrogen electrode (RHE) and half-wave potential of 0.908 V vs. RHE, which is higher than that of the Pt/C catalyst and most of other Fe-based catalysts. The different d-band center values can be attributed to the influence of different N-doped carbon, leading to the adjustment in the ORR activity. In addition, Fe-NC-800-based Zn-air battery showed better electrochemical performance with a high discharge specific capacity of 806 mA h g-1 and a high-power density of 220 mW cm-2 than that of the Pt/C-based battery. Therefore, the biomass Fe-NC-800 catalyst may become a promising substitute for Pt/C catalysts in energy storage and conversion devices.

Does autologous fat grafting serve the need for reconstructive surgery in oral cancer patients? A prospective evaluation in cosmetic surgery patients.

BACKGROUND: The prevalence of cancer is growing daily. Oral cancer, which is primarily triggered by tobacco use, can have detrimental effects on facial appearance. Despite significant advances in the molecular underpinnings of cancer, surgery, chemotherapy and radiotherapy have become standard cancer treatment methods. These treatments remove the tumor but can significantly alter patient's appearance, which can impact their physical and mental wellbeing. The soft tissue augmentation technique of autologous fat grafting (AFG), commonly referred to as lipofilling, is frequently used in cosmetic and reconstructive surgery to promote facial rejuvenation and body form remodeling. The advantages of AFG include its biocompatibility, low immunogenicity and allergenicity, as well as its capability to heal wounds. OBJECTIVES: To explore the advantages of and patient satisfaction with the AFG technique as a potential facial restoration procedure in oral cancer patients. MATERIAL AND METHODS: We examined the effects of facial AFG in cosmetic surgery patients and investigated the prevalence of postoperative problems. Patient satisfaction and potential complications after autologous fat filling in different areas of the facial space were investigated using clinical evaluations, patient-reported outcomes and photographic assessments. RESULTS: All of the patients were satisfied with the results in terms of improved facial shape, skin glossiness, skin elasticity, ptosis, and facial expressions. More than 80% of the patients and surgeons reported overall satisfaction. CONCLUSIONS: Based on these findings, we hypothesize that the AFG approach may be beneficial as a reconstructive therapy for patients with oral cancer following treatment. This technique will improve the patient's physical appearance, confidence and mental wellbeing.

Pd/Et3N·HI-Catalyzed Intramolecular C-H Alkylation to Access [a]-Annulated Indoles via Highly Regioselective Ring-Opening of Epoxides.

A Pd/Et3N·HI-catalyzed intramolecular C-H alkylation of indoles with epoxides was achieved to furnish N-fused indole frameworks (5-, 6-, and 7-membered rings) bearing an alcohol group. The conversion proceeded smoothly in the presence of a catalytic amount of Et3N·HI together with a palladium catalyst and exhibited great functional group tolerance. The employment of Et3N·HI not only avoids the prior preparation of alkyl halide substrates but also is the key to the high chemoselective ring-opening of epoxides. Preliminary mechanism explorations strongly support a radical pathway, and the catalytic cycle was established tentatively according to the mechanism investigation experiments.

Innovative ochre processing and tool use in China 40,000 years ago.

Homo sapiens was present in northern Asia by around 40,000 years ago, having replaced archaic populations across Eurasia after episodes of earlier population expansions and interbreeding1-4. Cultural adaptations of the last Neanderthals, the Denisovans and the incoming populations of H. sapiens into Asia remain unknown1,5-7. Here we describe Xiamabei, a well-preserved, approximately 40,000-year-old archaeological site in northern China, which includes the earliest known ochre-processing feature in east Asia, a distinctive miniaturized lithic assemblage with bladelet-like tools bearing traces of hafting, and a bone tool. The cultural assembly of traits at Xiamabei is unique for Eastern Asia and does not correspond with those found at other archaeological site assemblages inhabited by archaic populations or those generally associated with the expansion of H. sapiens, such as the Initial Upper Palaeolithic8-10. The record of northern Asia supports a process of technological innovations and cultural diversification emerging in a period of hominin hybridization and admixture2,3,6,11.

Technological innovations at the onset of the Mid-Pleistocene Climate Transition in high-latitude East Asia.

The interplay between Pleistocene climatic variability and hominin adaptations to diverse terrestrial ecosystems is a key topic in human evolutionary studies. Early and Middle Pleistocene environmental change and its relation to hominin behavioural responses has been a subject of great interest in Africa and Europe, though little information is available for other key regions of the Old World, particularly from Eastern Asia. Here we examine key Early Pleistocene sites of the Nihewan Basin, in high-latitude northern China, dating between ∼1.4 and 1.0 million years ago (Ma). We compare stone-tool assemblages from three Early Pleistocene sites in the Nihewan Basin, including detailed assessment of stone-tool refitting sequences at the ∼1.1-Ma-old site of Cenjiawan. Increased toolmaking skills and technological innovations are evident in the Nihewan Basin at the onset of the Mid-Pleistocene Climate Transition (MPT). Examination of the lithic technology of the Nihewan sites, together with an assessment of other key Palaeolithic sites of China, indicates that toolkits show increasing diversity at the outset of the MPT and in its aftermath. The overall evidence indicates the adaptive flexibility of early hominins to ecosystem changes since the MPT, though regional abandonments are also apparent in high latitudes, likely owing to cold and oscillating environmental conditions. The view presented here sharply contrasts with traditional arguments that stone-tool technologies of China are homogeneous and continuous over the course of the Early Pleistocene.

Biomass-derived N,S co-doped 3D multichannel carbon supported Au@Pd@Pt catalysts for oxygen reduction.

A beancurd-derived mesoporous carbon (NSC) was prepared by an environmentally friendly procedure, and then it was investigated as Au@Pd@Pt core-shell catalysts support (Au@Pd@Pt-NSC) for oxygen reduction reaction (ORR). The Au@Pd@Pt-NSC (E1/2 = 0.91 V) has a marginally negative ORR half-wave potential compared with other materials, in particular Pt/C (E1/2 = 0.87 V) and Au@Pd@Pt-C (E1/2 = 0.81 V). The specific and mass activities of the Au@Pd@Pt-NSC were 5 and 13 times higher than the commercial a Pt/C catalyst. After 20000 cycles of rapid durability test, the Au@Pd@Pt-NSC sample showed a loss of just 4.9% compared with the initial ECSA area, which can be attributed to the favorable interaction between Au@Pd@Pt and NSC. These results can be considered of environmental relevance and high potential applicability.

Luminescence chronology for the Paleolithic site of Xinmiaozhuang Locality 1 (XMZ1) in the Nihewan Basin, northern China, and its paleoenvironmental and archaeological implications.

In contrast to the prevailing view that the Chinese Paleolithic has been dominated by the Mode 1 technology-with a slow and conservative development from the Early to the Late Pleistocene-recent discoveries indicate that the lithic technology might have developed into an 'advanced' phase in some parts of China, at least since the early Late Pleistocene. The Xinmiaozhuang Locality 1 (XMZ1), located on the southern edge of the Nihewan Basin in northern China, is one of the examples belonging to such an 'advanced' phase. Although the stone artifacts at this site still belong to the long-existing 'small-tool' industry (core-and-flake) in this basin, some 'advanced' traits, including discoidal cores, elongated flakes, and 'Mousterian-like' triangular points and scrapers, are present. We provide a dating of the XMZ1 using the multiple elevated temperatures (MET) post infrared (pIR) infrared stimulated luminescence (IRSL) procedure (MET-pIRIR) on both multigrained single aliquots and 'individual' grains of potassium-rich feldspars (K-feldspars). The consistency between the single-aliquot and single-grain K-feldspar equivalent dose results mutually confirmed the reliability of the obtained ages. Our chronology indicates that the cultural layer falls within the period of ca. 63-75 ka, corresponding to the early stage of the Marine Isotope Stage (MIS) 4. Based on the correlation of the cultural age to the environmental proxies of loess and stalagmites from China, we suggest that the site might have witnessed dramatic fluctuations of paleoclimate during the site formation. Additionally, based on the discoidal cores distribution, a potential corridor along the Xuefeng-Wu-Tainhang-Great Khingan Mountains for ancient humans migrating between South and North China is suggested. However, more archaeological and chronological studies are required to figure out the origin and the dispersal patterns of the discoidal core associated with lithic assemblage and the tool-makers in East Asia.

Highly active iron-nitrogen-boron-carbon bifunctional electrocatalytic platform for hydrogen peroxide sensing and oxygen reduction.

An iron-nitrogen-boron-carbon (Fe-N-B-C) bifunctional electrocatalyst was prepared by means of a facile one-step hydrothermal reduction of graphene oxide using dimethylamine borane as doping agent. In addition, hemins were efficiently anchored during doping/reducing process on this modified graphene. The as-prepared Fe-N-B-C electro-catalyst showed enhanced response as regards its potential for reduction of H2O2 and O2. In view of its catalytic activity, this Fe-N-B-C material was tested for the determination of H2O2 with a chronoamperometry method, obtaining a detection limit as low as 0.055 µM, which is better than that of some Hemin-N-C materials. Regarding O2 reduction reaction, a study performed using a rotating disk electrode indicated that this material exhibits a positive onset potential (0.90V vs. RHE), high selectivity (4e- process), high limiting-current density (4.75 mA cm-2) and strong resistance against the crossover-effect from methanol in alkaline medium, making it to be the promising candidate as alternative for commercial Pt/C catalysts. These results could have commercial and environmental relevance and would deserve further complementary investigation.

[Retracted] Epigenetic silencing of miR­130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling.

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that some tumours featured in Fig. 6A of the above paper were strikingly similar to those featured in Fig. 8A of an article appearing in the same journal [Fan F­Y, Deng R, Yi H, Sun H­P, Zeng Y, He G­C and Su Y: The inhibitory effect of MEG3/miR­214/AIFM2 axis on the growth of T­cell lymphoblastic lymphoma. Int J Oncol 51: 316­326, 2017]. Furthermore, flow cytometric images featured in Fig. 2G of the above paper were strikingly similar to data featured in the following article [Zhang H­j, Wei Q­f, Wang S­j, Zhang H­j, Zhang X­y, Geng Q, Cui Y­h and Wang X­h: LncRNA HOTAIR alleviates rheumatoid arthritis by targeting miR­138 and inactivating NF­κB pathway. Int Immunopharmacol 50: 283­290, 2017]. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from International Journal of Oncology. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 50: 1821­1831, 2017; DOI: 10.3892/ijo.2017.3943].

Mass production of nitrogen and oxygen codoped carbon nanotubes by a delicately-designed Pechini method for supercapacitors and electrocatalysis.

Heteroatom-doped carbon nanotubes (CNTs) have great potential in various fields owing to their extraordinary electronic, structural, and mechanical properties. However, large-scale production of heteroatom-doped CNTs in a simple, economical, and highly efficient manner still remains challenging. Here, we report a modified Pechini method (MPM) for high-yield synthesis of N- and O-codoped CNTs (N,O-CNTs), by rapid pyrolysis of a NiCo-polymer precursor forming via a simple sol-gel process. The carbon source (i.e., citric acid) is inexpensive, and the NiCo-polymer material is the single precursor for the preparation of N,O-CNTs via a thermolysis process without the introduction of additional catalysts or carrier gas. Appropriate NiCo-organic coordination and controlled pyrolysis (i.e. heating rate, pyrolysis temperature, and holding time) are demonstrated to play vital roles in this MPM, which are critical for quick generation of small NiCo nanocatalysts with high catalytic activity and simultaneous formation of sufficient space inside the material. The growth mechanism is well studied. Benefitting from the hierarchically porous structure and the synergistic effect of N,O-codoping in the CNTs, the as-synthesized N,O-CNTs manifest excellent electrochemical performance in both supercapacitors and electrocatalysis. Density functional theory simulations show that N and O dopants could increase the densities of states of CNTs near the Fermi level and charge densities of adjacent C atoms, thus leading to improved electrochemical activity. We anticipate that this work will open up a new avenue for a high-yield and economical synthesis of heteroatom-doped CNTs for energy-related applications and beyond.

1000-Fold Preconcentration of Per- and Polyfluorinated Alkyl Substances within 10 Minutes via Electrochemical Aerosol Formation.

We present a simple and efficient method for preconcentrating per- and polyfluorinated alkyl substances (PFAS) in water. Our method was inspired by the sea-spray aerosol enrichment in nature. Gas bubbles in the ocean serve to scavenge surface active material, carrying it to the air-ocean interface, where the bubbles burst and form a sea-spray aerosol. These aerosol particles are enriched in surface-active organic compounds such as free fatty acids and anionic surfactants. In our method, we in situ generate H2 microbubbles by electrochemical water reduction using a porous Ni foam electrode. These H2 bubbles pick up PFAS as they rise through the water column that contains low concentration PFAS. When these bubbles reach the water surface, they burst and produce aerosol droplets that are enriched in PFAS. Using this method, we demonstrated ∼1000-fold preconcentration for ten common PFAS in the concentration range from 1 pM to 1 nM (or ∼0.5 ng/L to 500 ng/L) in 10 min. We also developed a diffusion-limited adsorption model that is in quantitative agreement with the experimental data. In addition, we demonstrated using this method to preconcentrate PFAS in tap water, indicating its potential use for quantitative analysis of PFAS in real-world water samples.

A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing.

The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system was fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. The new HP-PEGs were synthesized via in situ reversible addition fragmentation chain transfer (RAFT) polymerization using an FDA approved anti-alcoholic drug-Disulfiram (DS) as the RAFT agent precursor. HP-PEGs can form injectable hydrogels with HA-SH rapidly via thiol-ene click reaction under physiological conditions. The hydrogels exhibited stable mechanical properties, non-swelling and anti-fouling properties. Hydrogels encapsulating adipose-derived stem cells (ADSCs) have demonstrated promising regenerative capabilities such as the maintenance of ADSCs' stemness and secretion abilities. The ADSCs embedded hydrogels were tested on the treatment of diabetic wound in a diabetic murine animal model, showing enhanced wound healing. STATEMENT OF SIGNIFICANCE: Diabetic wounds, which are a severe type of diabetes, have become one of the most serious clinical problems. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholic drug-Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment.

Injectable hyperbranched poly(ß-amino ester) hydrogels with on-demand degradation profiles to match wound healing processes.

Adjusting biomaterial degradation profiles to match tissue regeneration is a challenging issue. Herein, biodegradable hyperbranched poly(ß-amino ester)s (HP-PBAEs) were designed and synthesized via "A2 + B4" Michael addition polymerization, and displayed fast gelation with thiolated hyaluronic acid (HA-SH) via a "click" thiol-ene reaction. HP-PBAE/HA-SH hydrogels showed tunable degradation profiles both in vitro and in vivo using diamines with different alkyl chain lengths and poly(ethylene glycol) diacrylates with varied PEG spacers. The hydrogels with optimized degradation profiles encapsulating ADSCs were used as injectable hydrogels to treat two different types of humanized excisional wounds - acute wounds with faster healing rates and diabetic wounds with slower healing and neo-tissue formation. The fast-degrading hydrogel showed accelerated wound closure in acute wounds, while the slow-degrading hydrogel showed better wound healing for diabetic wounds. The results demonstrate that the new HP-PBAE-based hydrogel in combination with ADSCs can be used as a well-controlled biodegradable skin substitute, which demonstrates a promising approach in the treatment of various types of skin wounds.

SLC35E3 identified as a target of novel­m1061­5p via microRNA profiling of patients with cardiovascular disease.

MicroRNAs (miRNA) are considered to be potential therapeutic targets for the treatment of various cardiovascular diseases (CVDs). To understand the underlying mechanism of miRNAs and target genes associated with CVD, deep sequencing of blood samples from three patients with CVD and three controls was performed using the Illumina HiSeq 2000 system. The results of the present study revealed that 65 abnormal hsa­miRNAs targeted 2,784 putative genes in patients with CVD; 59 upregulated miRNAs targeted 2,401 genes and six downregulated miRNAs targeted 383 genes. In addition, a total of 49 Gene Ontology (GO) biological processes and were enriched, and the target genes of downregulated miRNAs were enriched in 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Most of these pathways are responsible for lipid and glycan metabolism. In particular, three downregulated miRNAs, hsa­miR­1268b, hsa­miR­1273d, hsa­miR­3187­5p, were involved in a­linolenic acid metabolism. The target genes of upregulated miRNAs were enriched in 15 KEGG pathways, mainly in the 'neurodegenerative diseases and cancers' class. In the present study five novel upregulated miRNAs, including m0499­5p, m0970­5p, m1042­5p, m1061­5p and m1953­5p, and a downregulated miRNA, novel­m1627­5p, were identified in patients with CVD. Novel­m1627­5p was demonstrated to target 146 human genes. Additionally, Novel­m1061­5p targeted four genes, including fumarylacetoacetate hydrolase domain containing 2A, potassium voltage­gated channel, Shaw­related subfamily, member 4, coiled­coil domain containing 85C and solute carrier family 35 member E3 (SLC35E3). The GO term, 'carbohydrate derivative transport involving in biological process', was associated with SLC35E3. Novel­m1061­5p in patients with CVD may repress the expression levels of SLC35E3, a member of the nucleoside sugar transporter subfamily E, which is known to cause defective glycol­conjugation in the Golgi complex and/or the endoplasmic reticulum. Further investigation is required to understand the underlying mechanisms of the novel miRNAs. Novel­m1061­5p may serve as a marker for prognosis or a potential target for the treatment of CVD.

Effect of laser therapy on plasma expression of VEGF and bFGF in infants with cutaneous hemangioma.

The present study aimed to investigate the effect of laser therapy on the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the plasma of infants diagnosed with cutaneous hemangioma, in order to identify biomarkers for assessing the clinical efficacy of laser therapy. In total, 109 infants with superficial abdominal hemangioma received laser treatment, of which 74 were diagnosed in the proliferation phase, 20 in the regression phase and 15 in the involution phase. In addition, 10 infants without cutaneous hemangioma were recruited as normal controls. The concentrations of VEGF and bFGF in peripheral plasma samples were measured using ELISAs. Dynamic changes in the VEGF and bFGF concentrations of 23 infants diagnosed in the proliferation phase were compared before and after laser therapy. The plasma concentration of VEGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P<0.01), whereas it did not differ significantly among the regression phase, involution phase and normal control groups (all P>0.05). The plasma concentration of bFGF in the proliferation phase group was significantly higher compared with that in the regression phase, involution phase and normal control groups (all P<0.01), while the bFGF level did not differ significantly among the regression phase, involution phase and normal control groups (all P>0.05). Following laser therapy, the plasma concentrations of VEGF and bFGF in infants with cutaneous hemangioma were significantly decreased (both P<0.01). These results suggested that VEGF and bFGF may serve as reliable indexes to evaluate the clinical efficacy of laser therapy for treating infantile cutaneous hemangioma.

Epigenetic silencing of miR-130a ameliorates hemangioma by targeting tissue factor pathway inhibitor 2 through FAK/PI3K/Rac1/mdm2 signaling.

Hemangiomas are the most common vascular tumors that occur frequently in prematures and females. microRNA (miR)-130a is associated with the growth and invasion in many tumors, and its role in hemangiomas has not been addressed so far. The present study revealed that miR­130a was overexpressed in infantile hemangioma tissues compared with matched tumor-adjacent tissues. The inhibitor of miR-130a restrained cell growth and induced cell apoptosis in vitro. miR­130a inhibitor also induced a cell cycle arrest at G2/M phase. Further studies revealed that tissue factor pathway inhibitor 2 (TFPI2) was a novel miR-130a target, due to miR-130a bound directly to its 3'-untranslated region and miR-130a inhibitor enhanced the expression of TFPI2. Contrary to the effects of miR-130a inhibitor, TFPI2 siRNA strongly promoted cell growth and colony formation, whereas TFPI2 overexpression contributed to the suppressing effect of miR-130a inhibitor in cell viability. Furthermore, miR-130a inhibitor reduced the activation of focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/Rac1/anti-mouse double minute (mdm2) pathway proteins, inhibited the expression and nuclear translocation of mdm2. Moreover, FAK overexpression prevented miR-130a inhibitor-induced cell cycle arrest and decrease of cell viability. In vivo experiments, miR-130a inhibition effectively suppressed the tumor growth, restrained angiogenesis by decreasing the expression of angiogenesis markers and the percentage of CD31+ and CD34+. Taken together, our research indicated that miR-130a functions as an oncogene by targeting TFPI2, miR-130a inhibition reduced the growth and angiogenesis of hemangioma by inactivating the FAK/PI3K/Rac1/mdm2 pathway. Thus, miR-130a may serve as a potential therapeutic strategy for the treatment of hemangioma.

Long noncoding RNA expression profile of infantile hemangioma identified by microarray analysis.

Infantile hemangioma (IH) is one of the most common vascular tumors of childhood. Long noncoding RNAs (lncRNAs) play a critical role in angiogenesis, but their involvement in hemangioma remains unknown. This study aimed to assess the expression profiles of lncRNAs in IH and adjacent normal tissue samples, exploring the biological functions of lncRNAs as well as their involvement in IH pathogenesis. The lncRNA expression profiles were determined by lncRNA microarrays. A total of 1259 and 857 lncRNAs were upregulated and downregulated in IH, respectively, at a fold change cutoff of 2.0 (p < 0.05); in addition, 1469 and 1184 messenger RNAs (mRNAs) were upregulated and downregulated, respectively (fold change cutoff of 2.0; p < 0.05). A total of 292 differentially expressed mRNAs were targeted by the lncRNAs with altered expression in hemangioma, including 228 and 64 upregulated and downregulated, respectively (cutoff of 2.0, p < 0.05). Gene ontology (GO) analyses revealed several angiogenesis-related pathways. An lncRNA-mRNA co-expression network for differentially expressed lncRNAs revealed significant associations of the lncRNAs MEG3, MEG8, FENDRR, and Linc00152 with their related mRNAs. The validation results of nine differentially expressed lncRNAs (MALAT1, MEG3, MEG8, p29066, p33867, FENDRR, Linc00152, p44557_v4, p8683) as well as two mRNAs (FOXF1, EGFL7) indicated that the microarray data correlated well with the QPCR results. Interestingly, MALAT1 knockdown induced apoptosis and S-phase cell cycle arrest in human umbilical vein endothelial cells (HUVECs). Overall, this study revealed the lncRNA expression profile of IH and that lncRNAs likely regulate several genes with important roles in angiogenesis.

One Possible Mechanism of Pulsed Dye Laser Treatment on Infantile Hemangioma: Induction of Endothelial Apoptosis and Serum vascular endothelial growth factor (VEGF) Level Changes.

INTRODUCTION: Pulsed dye laser (PDL) is an important treatment for superficial infantile hemangioma, but few studies report on its cellular mechanism. The aim of this study was to evaluate alterations of serum vascular endothelial growth factor (VEGF) level in infantile hemangioma (IH) patients after laser treatment and effects of PDL irradiation on human umbilical vein endothelial cells (HUVECs) in vitro, as well as to explore the biomolecular mechanisms and ultrastructure changes of the PDL effect. METHODS: 74 children with infant hemangioma including 45 patients in proliferating phase, 18 patients in involuting phase, 11 patients in involuted phase and 10 healthy children were engaged in this study. The plasma VEGF levels of children were measured with the enzymelinked immunosorbent assay (ELISA). 24 hours after, HUVECs cultured in vitro were irradiated with PDL, cell apoptosis, mRNA levels of VEGF, and changes of ultrastructure were evaluated using flow cytometry, real-time reverse transcriptase polymerase chain reaction (RT-PCR), and transmission electron microscopy, respectively. RESULTS: The serum VEGF concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting / involved hemangiomas and healthy patients. After receiving 3 laser treatments, the plasma VEGF levels of IH patients in proliferating hemangiomas decreased significantly. PDL irradiation could down-regulate VEGF mRNA expression of HUVECs, and increase cell apoptosis rate. CONCLUSION: The present study demonstrates that PDL irradiation imparts apoptosis induction effects on HUVECs in vitro. Furthermore, our results suggest that vascular endothelial growth factor may be of particular importance in pathophysiology and PDL treatment of hemangiomas, also serum VEGF levels may be used as an aid in the follow up of IH. This provides valuable evidence of the PDL effect on infantile hemangioma.