Aerobic Oxidative Desulfurization by Supported Polyoxometalate Ionic Liquid Hybrid Materials via Facile Ball Milling.

With the increasingly strict limitations on emission standards of vehicles, deep desulfurization in fuel is indispensable for social development worldwide. In this study, a series of hybrid materials based on SiO2-supported polyoxometalate ionic liquid were successfully prepared via a facile ball milling method and employed as catalysts in the aerobic oxidative desulfurization process. The composition and structure of prepared samples were studied by various techniques, including FT-IR, UV-vis DRS, wide-angle XRD, BET, XPS, and SEM images. The experimental results indicated that the synthesized polyoxometalate ionic liquids were successfully loaded on SiO2 with a highly uniform dispersion. The prepared catalyst (C16PMoV/10SiO2) exhibited good desulfurization activity on different sulfur compounds. Moreover, the oxidation product and active species in the ODS process were respectively investigated via GC-MS and ESR analysis, indicating that the catalyst can activate oxygen to superoxide radicals during the reaction to convert DBT to its corresponding sulfone in the fuel.

First-line camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study.

Patients with advanced gastric cancer typically face a grim prognosis. This phase 1a (dose escalation) and phase 1b (dose expansion) study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapy for advanced gastric or gastroesophageal junction adenocarcinoma. The primary endpoints included maximum tolerated dose (MTD) in phase 1a and objective response rate (ORR) across phase 1a and 1b. Phase 1a tested three dose regimens of camrelizumab, apatinib, oxaliplatin, and S-1. Dose regimen 1: camrelizumab 200 mg on day 1, apatinib 250 mg every other day, oxaliplatin 100 mg/m² on day 1, and S-1 40 mg twice a day on days 1-14. Dose regimen 2: same as dose regimen 1, but oxaliplatin 130 mg/m². Dose regimen 3: same as dose regimen 2, but apatinib 250 mg daily. Thirty-four patients were included (9 in phase 1a, 25 in phase 1b). No dose-limiting toxicities occurred so no MTD was identified. Dose 3 was set for the recommended phase 2 doses and administered in phase 1b. The confirmed ORR was 76.5% (95% CI 58.8-89.3). The median progression-free survival was 8.4 months (95% CI 5.9-not evaluable [NE]), and the median overall survival (OS) was not mature (11.6-NE). Ten patients underwent surgery after treatment and the multidisciplinary team evaluation. Among 24 patients without surgery, the median OS was 19.6 months (7.8-NE). Eighteen patients (52.9%) developed grade ≥ 3 treatment-emergent adverse events. Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer (ChiCTR2000034109).

Effects of hydroxyapatite-coated porous titanium scaffolds functionalized by exosomes on the regeneration and repair of irregular bone.

As a traditional bone implant material, titanium (Ti) and its alloys have the disadvantages of lack of biological activity and susceptibility to stress shielding effect. Adipose stem cells (ADSCs) and exosomes were combined with the scaffold material in the current work to effectively create a hydroxyapatite (HA) coated porous titanium alloy scaffold that can load ADSCs and release exosomes over time. The composite made up for the drawbacks of traditional titanium alloy materials with higher mechanical characteristics and a quicker rate of osseointegration. Exosomes (Exos) are capable of promoting the development of ADSCs in porous titanium alloy scaffolds with HA coating, based on experimental findings from in vitro and in vivo research. Additionally, compared to pure Ti implants, the HA scaffolds loaded with adipose stem cell exosomes demonstrated improved bone regeneration capability and bone integration ability. It offers a theoretical foundation for the combined use of stem cell treatment and bone tissue engineering, as well as a design concept for the creation and use of novel clinical bone defect repair materials.

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.

Multi-Layer Graph Attention Network for Sleep Stage Classification Based on EEG.

Graph neural networks have been successfully applied to sleep stage classification, but there are still challenges: (1) How to effectively utilize epoch information of EEG-adjacent channels owing to their different interaction effects. (2) How to extract the most representative features according to confused transitional information in confused stages. (3) How to improve classification accuracy of sleep stages compared with existing models. To address these shortcomings, we propose a multi-layer graph attention network (MGANet). Node-level attention prompts the graph attention convolution and GRU to focus on and differentiate the interaction between channels in the time-frequency domain and the spatial domain, respectively. The multi-head spatial-temporal mechanism balances the channel weights and dynamically adjusts channel features, and a multi-layer graph attention network accurately expresses the spatial sleep information. Moreover, stage-level attention is applied to easily confused sleep stages, which effectively improves the limitations of a graph convolutional network in large-scale graph sleep stages. The experimental results demonstrated classification accuracy; MF1 and Kappa reached 0.825, 0.814, and 0.775 and 0.873, 0.801, and 0.827 for the ISRUC and SHHS datasets, respectively, which showed that MGANet outperformed the state-of-the-art baselines.

Fluorescence-based monitoring of the pressure-induced aggregation microenvironment evolution for an AIEgen under multiple excitation channels.

The development of organic solid-state luminescent materials, especially those sensitive to aggregation microenvironment, is critical for their applications in devices such as pressure-sensitive elements, sensors, and photoelectric devices. However, it still faces certain challenges and a deep understanding of the corresponding internal mechanisms is required. Here, we put forward an unconventional strategy to explore the pressure-induced evolution of the aggregation microenvironment, involving changes in molecular conformation, stacking mode, and intermolecular interaction, by monitoring the emission under multiple excitation channels based on a luminogen with aggregation-induced emission characteristics of di(p-methoxylphenyl)dibenzofulvene. Under three excitation wavelengths, the distinct emission behaviors have been interestingly observed to reveal the pressure-induced structural evolution, well consistent with the results from ultraviolet-visible absorption, high-pressure angle-dispersive X-ray diffraction, and infrared studies, which have rarely been reported before. This finding provides important insights into the design of organic solid luminescent materials and greatly promotes the development of stimulus-responsive luminescent materials.

Advances in the superhydrophilicity-modified titanium surfaces with antibacterial and pro-osteogenesis properties: A review.

In recent years, the rate of implant failure has been increasing. Microbial infection was the primary cause, and the main stages included bacterial adhesion, biofilm formation, and severe inhibition of implant osseointegration. Various biomaterials and their preparation methods have emerged to produce specific implants with antimicrobial or bactericidal properties to reduce implant infection caused by bacterial adhesion and effectively promote bone and implant integration. In this study, we reviewed the research progress of bone integration promotion and antibacterial action of superhydrophilic surfaces based on titanium alloys. First, the adverse reactions caused by bacterial adhesion to the implant surface, including infection and bone integration deficiency, are briefly introduced. Several commonly used antibacterial methods of titanium alloys are introduced. Secondly, we discuss the antibacterial properties of superhydrophilic surfaces based on ultraviolet photo-functionalization and plasma treatment, in contrast to the antibacterial principle of superhydrophobic surface morphology. Thirdly, the osteogenic effects of superhydrophilic surfaces are described, according to the processes of osseointegration: osteogenic immunity, angiogenesis, and osteogenic related cells. Finally, we discuss the challenges and prospects for the development of this superhydrophilic surface in clinical applications, as well as the prominent strategies and directions for future research.

Application of impedance spectroscopy in exploring electrical properties of dielectric materials under high pressure.

Impedance spectroscopy (IS) is an indispensable method of exploring electrical properties of materials. In this review, we provide an overview on the specific applications of IS measurement in the investigations of various electrical properties of materials under high pressure, including electric conduction in bulk and grain boundary, dielectric properties, ionic conduction, and electrostrictive effect. Related studies are summarized to demonstrate the method of analyzing different electrical transport processes with various designed equivalent circuits of IS and reveal some interesting phenomena of electrical properties of materials under high pressure.

Study on Exosomes Promoting the Osteogenic Differentiation of ADSCs in Graphene Porous Titanium Alloy Scaffolds.

Titanium and titanium alloys (Ti6Al4V and Ti) have been widely used in bone tissue engineering to repair maxillofacial bone defects caused by traumas and tumors. However, such materials are also bio-inert, which does not match the elastic modulus of bone. Therefore, different surface modifications have been proposed for clinical application. Based on the use of traditional titanium alloy in the field of bone repair defects, we prepared a compound Gr-Ti scaffold with ADSC-derived Exos. The results showed that Gr-Ti scaffolds have low toxicity and good biocompatibility, which can promote the adhesion and osteogenic differentiation of ADSCs. Exos played a role in promoting osteogenic differentiation of ADSCs: the mRNA levels of RUNX2, ALP, and Osterix in the Gr-Ti/Exos group were significantly higher than those in the Gr-Ti group, which process related to the Wnt signaling pathway. Gr-Ti scaffolds with ADSCs and ADSC-derived Exos successfully repaired rabbit mandibular defects. The bone mineral density and the bending strength of the Gr-Ti/Exos group was significantly higher than that of the Gr-Ti group. This study provides a theoretical basis for the research and development of new clinical bone repair materials.

Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is a distinct molecular subtype of GC with a favorable prognosis. However, the exact effects and potential mechanisms of EBV infection on immune checkpoint blockade (ICB) efficacy in GC remain to be clarified. Additionally, EBV-encoded RNA (EBER) in situ hybridization (ISH), the traditional method to detect EBV, could cause false-positive/false-negative results and not allow for characterizing other molecular biomarkers recommended by standard treatment guidelines for GC. Herein, we sought to investigate the efficacy and potential biomarkers of ICB in EBVaGC identified by next-generation sequencing (NGS). DESIGN: An NGS-based algorithm for detecting EBV was established and validated using two independent GC cohorts (124 in the training cohort and 76 in the validation cohort). The value of EBV infection for predicting ICB efficacy was evaluated among 95 patients with advanced or metastatic GC receiving ICB. The molecular predictive biomarkers for ICB efficacy were identified to improve the prediction accuracy of ICB efficacy in 22 patients with EBVaGC. RESULTS: Compared with orthogonal assay (EBER-ISH) results, the NGS-based algorithm achieved high performance with a sensitivity of 95.7% (22/23) and a specificity of 100% (53/53). EBV status was identified as an independent predictive factor for overall survival and progression-free survival in patients with DNA mismatch repair proficient (pMMR) GC following ICB. Moreover, the patients with EBV+/pMMR and EBV-/MMR deficient (dMMR) had comparable and favorable survival following ICB. Twenty-two patients with EBV+/pMMR achieved an objective response rate of 54.5% (12/22) on immunotherapy. Patients with EBVaGC with a high cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) level were less responsive to anti-programmed death-1/ligand 1 (PD-1/L1) monotherapy, and the combination of anti-CTLA-4 plus anti-PD-1/L1 checkpoint blockade benefited patients with EBVaGC more than anti-PD-1/L1 monotherapy with a trend close to significance (p=0.074). There were nearly significant differences in tumor mutational burden (TMB) level and SMARCA4 mutation frequency between the ICB response and non-response group. CONCLUSIONS: We developed an efficient NGS-based EBV detection strategy, and this strategy-identified EBV infection was as effective as dMMR in predicting ICB efficacy in GC. Additionally, we identified CTLA-4, TMB, and SMARCA4 mutation as potential predictive biomarkers of ICB efficacy in EBVaGC, which might better inform ICB treatment for EBVaGC.

Hybrid zeolite-based ion-exchange and sulfur oxidizing denitrification for advanced slaughterhouse wastewater treatment.

The discharge of slaughterhouse wastewater (SWW) is increasing and its wastewater has to be treated thoroughly to avoid the eutrophication. The hybrid zeolite-based ion-exchange and sulfur autotrophic denitrification (IX-AD) process was developed to advanced treat SWW after traditional secondary biological process. Compared with traditional sulfur oxidizing denitrification (SOD), this study found that IX-AD column showed: (1) stronger ability to resist NO3- pollution load, (2) lower SO42- productivity, and (3) higher microbial diversity and richness. Liaoning zeolites addition guaranteed not only the standard discharge of NH4+-N, but also the denitrification performance and effluent TN. Especially, when the ahead secondary biological treatment process run at the ultra-high load, NO3--N removal efficiency for IX-AD column was still ~100%, whereas only 64.2% for control SOD column. The corresponding average effluent TN concentrations for IX-AD and SOD columns were 5.89 and 65.55 mg/L, respectively. Therefore, IX-AD is a promising technology for advanced SWW treatment and should be widely researched and popularized.

Prevalence and spectrum of germline cancer susceptibility gene variants and somatic second hits in colorectal cancer.

Colorectal cancer (CRC) is one of the most heritable cancers, and genetic factors play an important role in the increased CRC risk. However, the well-established CRC-risk genes were limited for explaining the increased risk of CRC individuals. Germline mutations in DNA damage repair (DDR) genes have also been reported to be implicated in CRC heritability. Here, we aimed to determine the prevalence and significance of germline DDR and well-established CRC-risk gene variants in CRCs with paired somatic analyses. Next-generation sequencing (NGS) was performed on tumor tissues and paired white blood cells collected from 2160 Chinese patients with CRC using well-designed 381- or 733-cancer gene panel. Germline/somatic variations were identified and assessed for pathogenicity and likely pathogenicity. Of 2160 CRCs, 136 pathogenic germline mutations in 133 patients (133/2160, 6.1%) were identified in 21 genes, including 19 out of 32 examined DDR genes. Compared with non-carriers, individuals with germline variants were prone to a higher level of microsatellite instability (MSI) and tumor mutational burden (TMB), and an earlier age of onset. Somatic sequencing identified second hits in 24/133 (18%) patients with germline variants. Among the mismatch repair (MMR) genes with germline mutations, the second hit significantly increased MSI and TMB, particularly apparent in MSH6. All MMR germline variation carriers further with a second hit were all MSI-H and had an extraordinarily high level of TMB. Collectively, approximately 6.1% of CRC patients carried pathogenic germline variants, and additional somatic second hit increases the genomic instability in CRC, whereas the more clinical significance warrants further study.

Performance and mechanism of a novel woodchip embedded biofilm electrochemical reactor (WBER) for nitrate-contaminated wastewater treatment.

In this study, a woodchip biofilm electrode reactor (WBER) with woodchips embedded anode and cathode was developed, and its denitrification mechanism was analyzed by investigating the denitrification performance, organic matter change, redox environment and microbial community. The results show that the WBER with a carbon rod as anode (C-WBER) had a higher denitrification efficiency (2.58 mg NO- 3-N/(L·h)) and lower energy consumption (0.012 kWh/g NO- 3-N) at 350 mA/m2. By reducing the hydroxyl radical and dissolved oxygen concentrations, anode embedding technology effectively decreased the inhibition on microorganisms. Lignin decomposition, nitrification and aerobic denitrification were carried out in anode. Additionally, hydrogen autotrophic denitrification and heterotrophic denitrification were occurred in cathode. The WBER effectively removed nitrate and reduced the cost, providing a theoretical basis and direction for further develop BERs.

Individualized surgery combined with radiotherapy and triamcinolone acetonide injection for the treatment of auricular keloids.

BACKGROUND: Although multiple methods have been proposed to treat auricular keloids, low curative effects and high recurrence rates are currently major clinical problems. Thereinto, surgery combined with radiotherapy and triamcinolone acetonide injection is considered to be the proper choice for comprehensive treatment of auricular keloids. This study aimed at evaluating the therapeutic effect of individualized surgery combined with radiotherapy for the treatment of auricular keloids. METHODS: From February 2014 to February 2017, 67 patients with 113 auricular keloids in total were enrolled in this study. According to specific conditions of lesions, the local tissue and patients' individual wishes, different surgical methods were selected to analyze the scar excision and repairment of the defect. Within 24 h after the keloid was excised, 5 MeV electron beam irradiation by the linear accelerator was used by radiotherapy with a total dose of 20 Gy at interval of 1 day for 10 consecutive times. Triamcinolone acetonide was injected immediately after surgery, and per month afterward in the following three months. RESULTS: 113 keloids in total were received treatment. The follow-up period was 24 months. Fourteen keloids (12.39%) showed subjective recurrence with a success rate of 87.61%. Wilcoxon matched-pairs rank-sum test was used to compare the differences of the 24-month postoperative VSS scores and the preoperative VSS scores. The VSS scores were as follows: 82 keloids (72.57%) scored less than 5 points (good result), 21 keloids (18.58%) scored 6 to 10 points (fair result), and only 10 keloids (8.85%) scored more than 10 points (bad result). The effective rate was 91.15%. CONCLUSIONS: Individualized surgery combined with early postoperative radiotherapy and triamcinolone acetonide injection is an ideal treatment method to ensure good auricular appearance, low incidences of complications and recurrence based on effective treatment of auricular keloids.

Evaluation of advanced phosphorus removal from slaughterhouse wastewater using industrial waste-based adsorbents.

Slaughterhouse wastewater (SWW) contains high concentrations of phosphorus (P) and is considered as a principal industrial contaminant that causes eutrophication. This study developed two kinds of economical P removal adsorbents using flue gas desulfurization gypsum (FGDG) as the main raw material and bentonite, clay, steel slag and fly ash as the additives. The maximum adsorption capacity of the adsorbent composed of 60% FGDG, 20% steel slag, and 20% fly ash (DSGA2) was found to be 15.85 mg P/g, which was 19 times that of the adsorbent synthesized using 60% FGDG, 30% bentonite, and 10% clay (DSGA1) (0.82 mg P/g). Surface adsorption, internal diffusion, and ionic dissolution co-existed in the P removal process. The adsorption capacity of DSGA2 (2.50 mg P/g) was also evaluated in column experiments. The removal efficiency was determined to be higher than 92% in the first 5 days, while the corresponding effluent concentration was lower than the Chinese upcoming SWW discharge limit of 2 mg P/L. Compared with DSGA1, DSGA2 (synthesized from various industrial wastes) showed obvious advantages in improving adsorption capacity of P. The results showed that DSGA2 is a promising adsorbent for the advanced removal of P from SWW in practical applications.

The miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of human adipose-derived stem cells via the AKT and p38 signalling pathways.

BACKGROUND: Human adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs. METHODS: The expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays. RESULTS: miR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3'-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways. CONCLUSIONS: Our results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.

Identification of Keratinocyte Differentiation-Involved Genes for Metastatic Melanoma by Gene Expression Profiles.

BACKGROUND: Melanoma is the deadliest type of skin cancer. Until now, its pathological mechanisms, particularly the mechanism of metastasis, remain largely unknown. Our study on the identification of genes in association with metastasis for melanoma provides a novel understanding of melanoma. METHODS: From the Gene Expression Omnibus (GEO) database, the gene expression microarray datasets GSE46517, GSE7553, and GSE8401 were downloaded. We made use of R aiming at analyzing the differentially expressed genes (DEGs) between metastatic and nonmetastatic melanoma. R was also used in differentially expressed miRNA (DEM) data mining from GSE18509, GSE19387, GSE24996, GSE34460, GSE35579, GSE36236, and GSE54492 datasets referring to Li's study. Based on the DEG and DEM data, we performed functional enrichment analysis through the application of the DAVID database. Furthermore, we constructed the protein-protein interaction (PPI) network and established functional modules by making use of the STRING database. Through making use of Cytoscape, the PPI results were visualized. We predicted the targets of the DEMs through applying TargetScan, miRanda, and PITA databases and identified the overlapping genes between DEGs and predicted targets, followed by the construction of DEM-DEG pair network. The expressions of these keratinocyte differentiation-involved genes in Module 1 were identified based on the data from TCGA. RESULTS: 239 DEGs were screened out in all 3 datasets, which were inclusive of 21 positively regulated genes and 218 negatively regulated genes. Based on these 239 DEGs, we finished constructing the PPI network which was formed from 225 nodes and 846 edges. We finished establishing 3 functional modules. And we analyzed 92 overlapping genes and 26 miRNA, including 11 upregulated genes targeted by 11 negatively regulated DEMs and 81 downregulated genes targeted by 15 positively regulated DEMs. As proof of the differential expression of metastasis-associated genes, eleven keratinocyte differentiation-involved genes, including LOR, EVPL, SPRR1A, FLG, SPRR1B, SPRR2B, TGM1, DSP, CSTA, CDSN, and IVL in Module 1, were obviously downregulated in metastatic melanoma tissue in comparison with primary melanoma tissue based on the data from TCGA. CONCLUSION: 239 melanoma metastasis-associated genes and 26 differentially expressed miRNA were identified in our study. The keratinocyte differentiation-involved genes may take part in melanoma metastasis, providing a latent molecular mechanism for this disease.

Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells.

Exosomes exhibit great therapeutic potential in bone tissue engineering. The study aimed to investigate whether the exosomes derived from human adipose-derived stem cells (hADSCs-Exos) during different time-span of osteogenic differentiation could promote osteogenesis. The appropriate concentrations of hADSCs-Exos to enhance the proliferation, migration and osteogenesis of hADSCs-Exos were also examined. PKH67 labelled hADSCs-Exos was used to detect the internalization ability of hADSCs. The osteogenic differentiation abilities of hADSCs after treatment with hADSCs-Exos was evaluated by Alizarin red staining (ARS). The proliferation and migration of hADSCs was examined by cell counting kit-8 and wound healing assay, respectively. The expression of exosomal surface markers and osteoblast-related protein of hADSCs was assessed by Western blot. PKH67-labelled exosomes were internalized by hADSCs after 4 h incubation. ARS showed that the amount of mineralized nodules in Exo1-14d group was significantly higher than that in Exo15-28d group. hADSCs-Exos could promote the proliferation and migration capacity of hADSCs. Western blot analysis showed that after hADSCs-Exos treatment, ALP and RUNX2 were significantly enhanced. Specially, the Exo1-14d group of 15 µg/mL significantly upregulated the expression of RUNX2 than the other exosomes treated groups. Our findings suggest that exosomes secreted by hADSCs during osteogenic induction for 1-14 days could be efficiently internalized by hADSCs and could induce osteogenic differentiation of hADSCs. Moreover, administration of Exo1-14d at 15 µg/mL promoted the proliferation and migration of hADSCs. In conclusion, our research confirmed that comprised of hADSCs-Exos and hADSCs may provide a new therapeutic paradigm for bone tissue engineering.

Pressure-induced ionic to mixed ionic and electronic conduction transition in solid electrolyte LaF3.

The ionic transport properties of solid electrolyte LaF3 were systematically studied under high pressures up to 30.6 GPa with alternate-current impedance spectra measurements and first-principles calculations. From the impedance spectra measurements, LaF3 was found to transform from pure ionic conduction to mixed ionic and electronic conduction at 15.0 GPa, which results from the pressure-induced structural phase transition from a tysonite-type structure to an anti-Cu3Ti-type structure. F- ion migration can be suppressed by pressure, causing a decrease of the ionic conductivity of LaF3. By first-principles calculations, the pressure-dependent diffusion behaviors of the F- ions can be understood. The increased overlap of electron clouds at the interstitial site between rigid La3+ and liquid F- lattices leads to the appearance of electronic conduction in anti-Cu3Ti-type structured LaF3.

Exosomal miR-130a-3p regulates osteogenic differentiation of Human Adipose-Derived stem cells through mediating SIRT7/Wnt/ß-catenin axis.

OBJECTIVES: It is of profound significance for clinical bone regeneration to clarify the specific molecular mechanism from which we found that osteogenic differentiation of adipose-derived stem cells (ADSCs) will be probably promoted by exosomes. MATERIALS AND METHODS: By means of lentiviral transfection, miR-130a-3p overexpression and knockdown ADSCs were constructed. Alizarin Red S was used to detect the calcium deposits, and qPCR was used to detect osteogenesis-related genes, to verify the effect of miR-130a-3p on the osteogenic differentiation of ADSCs. CCK-8 was used to detect the effect of miR-130a-3p on the proliferation of ADSCs. The target binding between miR-130a-3p and SIRT7 was verified by dual-luciferase reporter gene assay. Furthermore, the role of Wnt signalling pathway in the regulation of ADSCs osteogenesis and differentiation by miR-130a-3p was further verified by detecting osteogenic-related genes and proteins and alkaline phosphatase activity. RESULTS: (a) Overexpression of miR-130a-3p can enhance the osteogenic differentiation of ADSCs while reducing protein and mRNA levels of SIRT7, a target of miR-130a-3p. (b) Our study further found that overexpression of miR-130a-3p leads to down-regulation of SIRT7 expression with up-regulation of Wnt signalling pathway-associated protein. (c) Overexpression of miR-130a-3p inhibited proliferation of ADSCs, while knockdown promoted it. CONCLUSIONS: The obtained findings indicate that exosomal miR-130a-3p can promote osteogenic differentiation of ADSCs partly by mediating SIRT7/Wnt/ß-catenin axis, which will hence promote the application of exosomal microRNA in the field of bone regeneration.