Highly visible-light-active sulfur and carbon co-doped TiO2 (SC-TiO2) heterogeneous photocatalysts prepared by underwater discharge plasma.

To promptly and simply create highly crystalline S/C co-doped TiO2 (SC-TiO2) photocatalysts at room temperature and atmospheric pressure, we suggest a novel plasma-assisted sol-gel synthesis method. This method is a simultaneous synthetic process, in which an underwater plasma undergoes continuous reactions to generate high-energy atomic and molecular species that enable TiO2 to achieve crystallinity, a large surface area, and a heterogeneous structure within a few minutes. In particular, it was demonstrated that the heterogeneously structured TiO2 was formed by doping that sulfur and carbon replace O or Ti atoms in the TiO2 lattice depending on the composition of the synthesis solution during underwater plasma treatment. The resultant SC-TiO2 photocatalysts had narrowed bandgap energies and extended optical absorption scope into the visible range by inducing the intermediate states within bandgap due to generation of oxygen vacancies on the surface of TiO2 through synthesis, crystallization, and doping. Correspondingly, SC-TiO2 showed a significant degradation efficiency ([k] = 6.91 h-1) of tetracycline (TC, antibiotics) under solar light irradiation, up to approximately 4 times higher compared to commercial TiO2 ([k] = 1.68 h-1), resulting in great water purification. Therefore, we anticipate that this underwater discharge plasma system will prove to be an advantageous technique for producing heterostructural TiO2 photocatalysts with superior photocatalytic efficiency for environmental applications.

Light emitting diode (LED) irradiation of liposomes enhances drug encapsulation and delivery for improved cancer eradication.

Liposomes are widely used as drug delivery nanoplatforms because of their versatility and biocompatibility; however, their ability to load certain drugs may be suboptimal. In this study, we generated liposomes using a combination of DSPE and DSPE-PEG-2 k lipids and loaded them with doxorubicin (DOX) and paclitaxel (PTX), to investigate the effects of light emitting diode (LED) irradiation on liposome structure and drug loading efficiency. Scanning and transmission electron microscopy revealed that the surface of liposomes irradiated with blue or near-infrared LEDs (LsLipo) was rougher and more irregular than that of non-LED-irradiated liposomes (NsLipo). Nuclear magnetic resonance analysis showed that the hydrogen peak originating from the lipid head groups was lower in LsLipo than in NsLipo preparations, indicating that LED irradiation changed the chemical and physical properties of the liposome. Structural changes, such as reduced rigidity, induced by LED irradiation, increased the loading efficiency of DOX and PTX. In vitro and in vivo experiments showed that LsLipo were more effective at inhibiting the growth of cancer cells than NsLipo. Our findings suggest that LED irradiation enhances the drug delivery efficacy of liposomes and offer new possibilities for improving drug delivery systems.

Upconverting-photon quenching-mediated perforation influx as an intracellular delivery method using posAuNP@UCNPs nanocomposites for osteoarthritis treatment.

Photoporation techniques based on plasmonic nanoparticles such as gold nanoparticles have been extensively studied for the intracellular delivery of substances via cell membrane disruption. However, the clinical application of AuNP is challenging due to its absorption in the 500 nm region of the light spectrum. To overcome this challenge, upconversion nanoparticles were employed to stimulate AuNP at NIR wavelengths. posAuNP@UCNPs nanocomposites were produced by coating 30 nm UCNPs on 80 nm AuNPs using DOPA-PEI, which were then irradiated with 980 nm NIR light to facilitate their intracellular delivery. TEM and DLS confirmed that posAuNP and UCNP combine to form nanocomposites. Additionally, multiphysics simulation was used to analyze the distribution of the posAuNP electric field based on morphological differences that change as the UCNP ratio increases. Next, effective LED irradiation conditions were established by applying upconverting-photon quenching-mediated perforation influx to C28/I2 cells as suspensions or spheroids. posAuNP@UCNP nanocomposites were confirmed to be effective for the delivery of baricitinib as a treatment for osteoarthritis in a three-dimensional osteoarthritis model. Finally, chondrocyte differentiation was induced through intracellular delivery of baricitinib using posAuNP@UCNPs. The findings suggest that posAuNP@UCNPs have great potential as a tool for non-invasive drug delivery via UCPPin.

DEEPOMICS FFPE, a deep neural network model, identifies DNA sequencing artifacts from formalin fixed paraffin embedded tissue with high accuracy.

Formalin-fixed, paraffin-embedded (FFPE) tissue specimens are routinely used in pathological diagnosis, but their large number of artifactual mutations complicate the evaluation of companion diagnostics and analysis of next-generation sequencing data. Identification of variants with low allele frequencies is challenging because existing FFPE filtering tools label all low-frequency variants as artifacts. To address this problem, we aimed to develop DEEPOMICS FFPE, an AI model that can classify a true variant from an artifact. Paired whole exome sequencing data from fresh frozen and FFPE samples from 24 tumors were obtained from public sources and used as training and validation sets at a ratio of 7:3. A deep neural network model with three hidden layers was trained with input features using outputs of the MuTect2 caller. Contributing features were identified using the SHapley Additive exPlanations algorithm and optimized based on training results. The performance of the final model (DEEPOMICS FFPE) was compared with those of existing models (MuTect filter, FFPolish, and SOBDetector) by using well-defined test datasets. We found 41 discriminating properties for FFPE artifacts. Optimization of property quantification improved the model performance. DEEPOMICS FFPE removed 99.6% of artifacts while maintaining 87.1% of true variants, with an F1-score of 88.3 in the entire dataset not used for training, which is significantly higher than those of existing tools. Its performance was maintained even for low-allele-fraction variants with a specificity of 0.995, suggesting that it can be used to identify subclonal variants. Different from existing methods, DEEPOMICS FFPE identified most of the sequencing artifacts in the FFPE samples while retaining more of true variants, including those of low allele frequencies. The newly developed tool DEEPOMICS FFPE may be useful in designing capture panels for personalized circulating tumor DNA assay and identifying candidate neoepitopes for personalized vaccine design. DEEPOMICS FFPE is freely available on the web ( http://deepomics.co.kr/ffpe ) for research.

Fusogenic liposomes encapsulating mitochondria as a promising delivery system for osteoarthritis therapy.

Many attempts have been made to use mitochondria (MT) to treat human diseases; however, MT are large, making them difficult to deliver effectively. Therefore, a transfer strategy based on membrane fusion was established. Fusogenic mitochondrial capsules (FMCs) comprising a neutral lipid (PE), a cationic lipid (DOTAP), an aromatic lipid (Liss Rhod PE), and three types of liposome (FMC0, FMC1, and FMC2), were designed and synthesized. The amount of DOTAP, which affects membrane fusion efficiency, differed between FMC preparations. The characteristics of these FMCs were analyzed by DLS, TEM, and AFM, and the encapsulation and fusion efficiency between FMC-MT and FMC-chondrocytes were confirmed by FRET, mtDNA copy number, and CLSM, respectively. Compared with naked MT, delivery of FMCs to chondrocytes was faster and more efficient. Moreover, fusion was a more stable delivery method than endocytosis, as evidenced by reduced induction of mitophagy. In vitro and in vivo experiments revealed that FMCs reduced expression of inflammatory cytokines and MMP13, increased expression of extracellular matrix components, and promoted cartilage regeneration. These findings suggest that FMCs are a highly effective and promising strategy for delivery of MT to promote cartilage regeneration, and highlight their potential as a novel platform for MT transfer therapy.

Melatonin loaded PLGA nanoparticles effectively ameliorate the in vitro maturation of deteriorated oocytes and the cryoprotective abilities during vitrification process.

Almost all cells can be exposed to stress, but oocytes, which are female germ cells, are particularly vulnerable to damage. In this study, melatonin, a well-known antioxidant, was loaded into biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and delivered to damaged oocytes in order to improve their quality and restoration. Etoposide (ETP)-induced deteriorated oocytes show poor maturity, mitochondrial aggregation, and DNA damage. Treatment of NPs not only reduced DNA damage but also improved mitochondrial stability, as evidenced by increased ATP levels and mitochondrial homogeneity. When melatonin was added to the culture medium at the same concentration as that present in NPs, DNA and mitochondrial repair was insignificant due to the half-life of melatonin, whereas DNA repair in damaged oocytes upon multiple treatments with melatonin was similar to that observed with melatonin-loaded NPs. Next, we evaluated whether the oocytes treated with NPs could have cryoprotective abilities during vitrification/thawing. Vitrified-oocytes were stored at -196 °C for 0.25 h (T1) or 0.5 h (T2). After thawing, live oocytes were subjected to in vitro maturation. The NP-treated group showed maturity similar to the control group (77.8% in T1, 72.7% in T2) and the degree of DNA damage was reduced compared to the ETP-induced group (p < 0.05).

Probiotic Characteristics and Safety Assessment of Lacticaseibacillus casei KGC1201 Isolated from Panax ginseng.

Panax ginseng is one of the most important herbal medicinal plants consumed as health functional food and can be fermented to achieve better efficacy. Lacticaseibacillus, one of the representative genera among lactic acid bacteria (LAB), has also been used as a probiotic material for health functional foods due to its beneficial effects on the human body. To achieve a synergistic effect by using these excellent dietary supplement ingredients together, a novel LAB strain was isolated from the root of 6-year-old ginseng. Through similarity analysis of 16S rRNAs and whole-genome sequences, the strain was confirmed as belonging to the genus Lacticaseibacillus and was named L. casei KGC1201. KGC1201 not only met all safety standards as food, but also showed excellent probiotic properties such as acid resistance, bile salt resistance, and intestinal adhesion. In particular, KGC1201 exhibited superior acid resistance through morphological observation identifying that the cell surface damage of KGC1201 was less than that of the L. casei type strain KCTC3109. Gene expression studies were conducted to elucidate the molecular mechanisms of KGC1201's acid resistance, and the expression of the glycosyltransferase gene was found to be significantly elevated under acidic conditions. Exopolysaccharides (EPSs) biosynthesized by glycosyltransferase were also increased in KGC1201 compared to KCTC3109, which may contribute to better protection of KGC1201 cells from strong acidity. Therefore, KGC1201, with its increased acid resistance through molecular mechanisms and excellent probiotic properties, can be used in health functional foods to provide greater benefit to overall human health and well-being.

Strategies for accelerating osteogenesis through nanoparticle-based DNA/mitochondrial damage repair.

The efficiency of gene therapy is often dictated by the gene delivery system. Cationic polymers are essential elements of gene delivery systems. The relatively cheap cationic polymer, polyethyleneimine, has high gene delivery efficiency and is often used for gene delivery. However, the efficiency of gene therapy with polyethyleneimine-pDNA polyplex (PEI) is low. Human mesenchymal stem cells transfected with polyethyleneimine and a plasmid carrying the important osteogenic differentiation gene runt-related transcription factor 2 (RUNX2) accumulated DNA double-strand breaks and mitochondrial damage proportional to the amount of polyethyleneimine, reducing viability. Genomic/cellular stabilizer mediating RUNX2 delivery (GuaRD), a new reagent incorporating RS-1 NPs developed in this study, promoted DNA repair and prevented the accumulation of cell damage, allowing the delivery of pRUNX2 into hMSCs. while maintaining genome and mitochondrial stability. DNA damage was significantly lower and the expression of DNA repair-related genes significantly higher with GuaRD than with PEI. In addition, GuaRD improved mitochondrial stability, decreased the level of reactive oxygen species, and increased mitochondrial membrane potential. Osteogenic extracellular matrix (ECM) expression and calcification were higher with GuaRD than with PEI, suggesting improved osteogenic differentiation. These results indicate that lowering the cytotoxicity of PEI and improving cell stability are key to overcoming the limitations of conventional gene therapy, and that GuaRD can help resolve these limitations.

Efficient CRISPR-Cas9-based knockdown of RUNX2 to induce chondrogenic differentiation of stem cells.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system recognizes and deletes specific nucleotide sequences in cells for gene editing. This study aimed to edit and knockdown the RUNX2 gene, a key transcription factor that is directly involved in all stages of stem cell differentiation into osteoblasts. The RUNX2 gene was depleted using the CRISPR-Cas9 system to inhibit osteoblast differentiation of stem cells. shRNA vectors targeting RUNX2 were used as a control. The surface of nanoparticles (NPs) was coated with the cationic polymer linear polyethyleneimine. Thereafter, negatively charged CRISPR-Cas9 and shRNA vectors were complexed with positively charged NPs via ionic interactions. Several analytical methods were used to determine the size, surface charge, and morphology of NPs and to characterize the complexed genes. NPs complexed with CRISPR-Cas9 and shRNA vectors were delivered into human mesenchymal stem cells (hMSCs) via endocytosis. The mRNA and protein expression patterns of various genes in hMSCs were measured over time following internalization of NPs complexed with CRISPR-Cas9 and shRNA vectors in two- and three-dimensional culture systems. Knockdown of the RUNX2 gene decreased osteogenic differentiation and increased chondrogenic differentiation of hMSCs. As a result of investigating the efficiency of NPs complexed with CRISPR-Cas9 (CASP-NPs), Runx2 effectively knocked down in mesenchymal stem cells to enhance differentiation into chondrocytes, therefore CASP-NPs proved to be an effective gene carrier in hMSCs.

High removal efficiency of industrial toxic compounds through stable catalytic reactivity in water treatment system.

We identified optimal conditions for the disposal of high concentration of organic contaminants within a short time using a hybrid advanced oxidation process (AOP) combining various oxidizing agents. Plasma-treated water (PTW) containing many active species, that play dominant roles in the degradation of organic substances like hydroxyl radicals, atomic oxygen, ozone, and hydrogen peroxide, was used in this study as a strategy to improve degradation performance without the use of expensive chemical reagents like hydrogen peroxide. In particular, the optimal decomposition conditions using PTW, which were combined with 10 mg/h ozone, 2 g/L iron oxide, and 4 W UV light, demonstrated excellent removal abilities of a high concentration of reactive black 5 (RB5; 100 mg/L, >99%, [k] = 4.15 h-1) and tetracycline (TC; 10 mg/L, >96.5%, [k] = 3.35 h-1) for 25 min, approximately 1.5 times higher than that without PTW (RB5; 100 mg/L, 94%, [k] = 2.80 h-1). These results confirmed that the production of strong reactive hydroxyl radicals from the decomposition process, as well as various reactive species included in PTW efficiently attacked pollutant substances, resulting in a higher removal rate. This suggests that a water treatment system with this optimal condition based on complex AOP systems using PTW could be useful in critical environmental and biomedical applications.

A rare case of acute meningitis shortly after lumbar selective nerve root block: a case report.

A 57-year-old man underwent lumbar selective nerve root block (SNRB) for low back pain and lower radiating pain caused by left-sided L4 disc herniation. He presented to the emergency department with fever, headache and aggravated low back pain approximately 3 hours after the procedure. Infection was suspected; hence, blood tests, cerebrospinal fluid (CSF) tests, lumbar magnetic resonance imaging, and brain computed tomography were performed. Imaging findings were not suggestive of infection. The CSF was turbid and yellowish with pleiocytosis; however, the CSF culture was negative. Based on these findings, the patient was diagnosed with acute meningitis. Broad-spectrum antibiotics and steroid therapy were initiated considering the patient's age and general condition. From hospital day (HD) 2, fever and headache were reduced and disappeared completely by HD 5. At the last follow-up, 1 month after discharge, the patient had no symptoms. Acute meningitis is associated with a high mortality and neurologic deficits. Hence, timely tests, diagnosis, and treatment are critical for positive outcomes. Symptoms of meningitis following a nerve block generally occur within 24-48 hours after the procedure. This case is notable, as it involved a quicker and more sudden onset of symptoms; meningitis occurred only a few hours after lumbar selective nerve root block.

Organelle targeting using a fluorescent probe that selectively penetrates the zona pellucida.

The characteristics of oocytes, which are female germ cells, have not been studied using optical materials. The structural layers (zona pellucida, ZP) around oocytes make it difficult to deliver drugs aimed at treating infertility. Here, we investigated whether the fluorescent probes sulforhodamine, fluorescein 5(6)-isothiocyanate, tetramethylrhodamine isothiocyanate, cyanine 3 carboxylic acid, and cyanine 5 carboxylic acid penetrate oocytes. By targeting the ZP layer of the oocyte, the characteristics of the model drug, a fluorescent probe, were analyzed, and the position of the probe in the oocyte was confirmed for differences in the characteristics. Penetration of the ZP and delivery into the cytoplasm differed between the fluorescent probes. This was due to their different physiochemical properties, including hydrophobicity (contact angle and surface tension), surfactant activity, and electrical charge. Among the fluorescent probes delivered to cytoplasm, unlike TRITC, Cy3 and Cy5 perturbed oocyte development. These results suggest that in oocytes with high physical barriers (cell membrane, zona pellucida), the delivery efficiency can be estimated by considering the properties (molecular weight and structure, solubility and functional structure, etc.) of the drug. In addition, it suggests that an encapsulated or bound carrier of a drug with properties similar to that of a fluorescent probe can be efficiently delivered into oocytes.

Ultrasound-Guided Anterior Quadratus Lumborum Block Reduces Postoperative Opioid Consumption and Related Side Effects in Patients Undergoing Total Hip Replacement Arthroplasty: A Propensity Score-Matched Cohort Study.

Quadratus lumborum block (QLB) has been shown to be effective for pain relief after hip surgery. This study evaluated the efficacy of ultrasound-guided anterior QLB in pain control after total replacement hip arthroplasty (TRHA). A total of 115 patients receiving anterior QLB were propensity score-matched with 115 patients who did not receive the block. The primary outcome was opioid consumption at 24, 24-48, and 48 postoperative hours. Secondary outcomes included pain scores at the post-anesthesia care unit (PACU), 8, 16, 24, 32, 40, and 48 h length of hospital stay, time to first ambulation, and the incidence of opioid-related side effects. Postoperative opioid consumption 48 h after surgery was significantly lower in the QLB group. Resting, mean, worst, and the difference of resting pain scores compared with preoperative values were significantly lower in the QLB group during the 48 postoperative hours. The length of hospital stay was shorter in the QLB group. The incidence of postoperative nausea and vomiting was significantly lower in the QLB group during the 48 postoperative hours, except at the PACU. This study suggests that anterior QLB provides effective postoperative analgesia for patients undergoing THRA performed using the posterolateral approach.

Development of a three-layer consecutive gene delivery system for enhanced bone regeneration.

This study developed a three-layer consecutive gene delivery system (T-CGDS) for timely gene delivery into human mesenchymal stem cells (hMSCs). The timing of transcription factor expression is important to effectively induce bone differentiation. Therefore, a three-layered nanocomposite was fabricated using differently sized gold nanoparticles to promote bone regeneration and osteogenic differentiation. The core layer comprised 80 nm gold nanoparticles coupled with ATF4 pDNA. Following coating with heparin-conjugated Pluronic F-127 (HP-F127), 50 nm gold nanoparticles coupled with SP7 pDNA were added to fabricate a bi-layer system. After further coating with HP-F127, 20 nm gold nanoparticles combined with RUNX2 pDNA were added. Consequently, a T-CGDS measuring 350-450 nm was fabricated. Genes were released for more than 8 days, while the size of the T-CGDS decreased over time. When the T-CGDS was applied to hMSCs, the gene in the outer layer (RUNX2) was expressed first, followed by those in the middle (SP7) and core (ATF4) layers. The T-CGDS effectively induced bone differentiation and regeneration in vitro and in vivo. Timely delivery of the ATF4 gene to stem cells via the T-CGDS can greatly assist osteogenic differentiation involved in bone regeneration.

In situ pocket-type microcarrier (PMc) as a therapeutic composite: Regeneration of cartilage with stem cells, genes, and drugs.

We prepared pocket-type micro-carriers (PMc) with pores larger than 30 µm for use in cell delivery by adding 40 mg pluronic F-127 copolymers (F-127) to biodegradable PLGA dissolved in dichloromethane solution. The controlling the size of the pockets in this way facilitates the adhesion of cells by regulating the size of the pockets according to the cells having various sizes. The size of PMc pores could be controlled within a range of 2 to 30 µm by varying the F-127 content. The ratio of F-127 to DOPA-bPEI was most appropriate at 1: 1, and the pocket size at 10 mg/ml of F-127 was appropriate for adhering 20-30 µm stem cells. F-127 containing SOX9 pDNA, in combination with DOPA-polyethylene-coated gold nanoparticles and dexamethasone loaded in PMcs, promoted cartilage differentiation. Gold nanoparticles complex and dexamethasone (DEX) loaded in PMcs were identified by micro-CT imaging and fluorescence imaging, respectively. By captured in pore generated on/in microspheres, the stem cells were safe and stable for use in delivery, both in vitro and in an animal model. Thus, microsphere pores can safely capture stem cells, and at the same time provide a microenvironment in which the captured stem cells can differentiate into chondrocytes.

Clinical efficacy and plausibility of a smartphone-based integrated online real-time diabetes care system via glucose and diet data management: a pilot study.

BACKGROUND: Smartphones have become novel healthcare tools for patients with diabetes. However, it is uncertain whether the smartphone application support system helps in glycaemic control in patients with type 2 diabetes. AIMS: To evaluate the efficacy and plausibility of smartphone-based integrated online real-time diabetes care. METHODS: Forty patients with type 2 diabetes were randomly assigned to the smartphone-based care (SC) (n = 20) and conventional care (CC) (n = 20) groups for 12 weeks. The SC group was instructed to use smartphone application (Noom Coach) and a glucose meter, and was provided medical supervision based on blood glucose level and food intake information sent to the central database server. The efficacy was evaluated by glycated haemoglobin (A1C ≤ 6.5%). The Summary of Diabetes Self-Care Activities (SDSCA) questionnaire was collected at baseline and at week 12. RESULTS: Seventeen and 18 patients of the SC and CC groups completed the study respectively. In the SC group, more patients achieved target A1C compared with the CC group (47.1% vs 11.1%, P = 0.019). In both group, SDSCA scores excluding the exercise item showed overall improvement (general diet, 1.4 ± 2.0 → 2.6 ± 2.3 vs 0.4 ± 1.1 → 1.8 ± 2.2; specific diet, 4.2 ± 1.7 → 5.4 ± 1.2 vs 3.8 ± 1.6 → 5.1 ± 1.1; blood glucose test, 3.3 ± 2.8 → 4.9 ± 2.3 vs 1.0 ± 2.2 → 4.7 ± 2.3; foot care, 1.5 ± 1.6 → 3.6 ± 2.8 vs 1.4 ± 1.9 → 6.1 ± 1.4; all P < 0.05). There was no difference between both groups other than the aspect of foot care (P = 0.008). CONCLUSIONS: The smartphone-based integrated online real-time diabetes care system through glucose and diet data management showed clinical plausibility in glucose control in real clinical practice.

CD44 Receptor-Specific and Redox-Sensitive Nanophotosensitizers of Hyaluronic Acid-Chlorin e6 Tetramer Having Diselenide Linkages for Photodynamic Treatment of Cancer Cells.

For reactive oxygen species (ROS)-sensitive and CD44 receptor-mediated delivery of photosensitizers, chlorin e6 (ce6) tetramer was synthesized using tetra acid (TA) via selenocystamine linkages and then conjugated with hyaluronic acid (HA) (abbreviated as HAseseCe6TA). HAseseCe6TA nanophotosensitizers were fabricated by dialysis procedure. HAseseCe6TA nanophotosensitizers showed spherical morphology with small particle sizes less than 100 nm and monomodal pattern. When H2O2 was added, size distribution was changed to multimodal pattern and morphological observation showed disintegration of nanophotosensitizers, indicating that HAseseCe6TA nanophotosensitizers have ROS sensitivity. Furthermore, H2O2 addition resulted in acceleration of Ce6 release from HAseseCe6TA nanophotosensitizers. In vitro cell culture study, HAseseCe6TA nanophotosensitizers increase Ce6 uptake ratio, ROS production efficiency, and photodynamic therapy efficacy in both B16F10 cells and CT26 cells. Especially, CD44-receptor blocking of cancer cells by pretreatment of HA showed that fluorescence intensity in B16F10 cells was significantly decreased while fluorescence intensity in CT26 cells was not significantly changed, indicating that HAseseCe6TA nanophotosensitizers can be delivered by CD44 receptor-mediated pathway. In vivo animal tumor xenograft study, HAseseCe6TA nanophotosensitizers was selectively delivered to B16F10 tumor rather than CT26 tumor. These results indicated that HAseseCe6TA nanophotosensitizers have ROS sensitivity and have CD44 receptor-recognition properties.

ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs.

Tumor-associated lymphatic vessels (LV) serve as a route of cancer dissemination through the prometastatic crosstalk between lymphatic endothelial cells (LECs) lining the LVs and cancer cells. Compared to blood endothelial cell-derived angiocrine factors, however, LEC-secreted factors in the tumor microenvironment and their roles in tumor metastasis are poorly understood. Here, we report that ELK3 expressed in LECs contributes to the dissemination of cancer cells during tumor growth by providing oncogenic miRNAs to tumor cells through exosomes. We found that conditioned medium from ELK3-suppressed LECs (LCM) lost its ability to promote the migration and invasion of breast cancer cells such as MDA-MB-231, Hs578T and BT20 in vitro. Suppression of ELK3 in LECs diminished the ability of LECs to promote tumor growth and metastasis of MDA-MB-231 in vivo. Exosomes derived from LECs significantly increased the migration and invasion of MDA-MB-231 in vitro, but ELK3 suppression significantly diminished the pro-oncogenic activity of exosomes from LECs. Based on the miRNA expression profiles of LECs and functional analysis, we identified miR-503-3p, miR-4269 and miR-30e-3p as downstream targets of ELK3 in LECs, which cause the above phenotype of cancer cells. These findings strongly suggest that ELK3 expressed in LECs is a major regulator that controls the communication between the tumor microenvironment and tumors to support cancer metastasis.

Studies on mass production and highly solar light photocatalytic properties of gray hydrogenated-TiO2 sphere photocatalysts.

In this paper, it is first reported that gray hydrogenated TiO2 sphere photocatalysts (H-TiO2) with high reactivity to solar light are mass produced within a few minutes using an underwater discharge plasma modified sol-gel method at room temperature and atmospheric pressure. This plasma modified system is an easy one-step in-situ synthetic process and the crystallinity, hydrogenation, and spherical structure of H-TiO2 are achieved by the synergy effect between the continuous reaction of highly energetic atomic and molecular species generated from the underwater plasma and surface tension of water. The resultant H-TiO2 demonstrated high anatase/rutile bicrystallinity and extended optical absorption spectrum from the ultraviolet (UV) to visible range. Furthermore, various defects including oxygen vacancies and hydroxyl species on the TiO2 surface permitted the enhancement of the photocatalytic performance. It was demonstrated that H-TiO2 photocatalysts showed significant degradation efficiencies for reactive black 5 (RB 5), rhodamine B (Rho B), and phenol (Ph) under solar light irradiation, up to approximately 5 times higher than that of commercial anatase TiO2 (C-TiO2), which resulted in good water purification. Notably, it was also possible to cultivate HepG2 cells using such well-purified water (to degrees up to 76%), with minimal cytotoxicity. Considering all these results, we believe that this novel plasma technology is promising for important environmental applications.

Novel function of E26 transformation-specific domain-containing protein ELK3 in lymphatic endothelial cells.

Lymphatic endothelial cells (LEC) are major components of the tumor microenvironment and, due to the relative leakiness of lymphatic vessels compared with blood vessels, are essential for tumor dissemination and metastasis. In the present study, small interfering RNA-mediated suppression of E26 transformation-specific domain-containing protein Elk-3 (ELK3) inhibited the proliferation, migration and tube-forming ability of LEC. Suppression of ELK3 decreased vascular endothelial-cadherin expression levels and increased the phosphorylation of ß-catenin. Furthermore, vascular endothelial growth factor receptor-3 (VEGFR-3) mRNA and protein expression levels were suppressed by the transfection of LEC with siELK3. As VEGFR-3 serves a major role in lymphangiogenesis, ELK3 may be a novel therapeutic target to inhibit tumor dissemination through the lymphatic system.