Using a single emitter of Cu−Ga−S/ZnS quantum dots, all‐solution‐processed white electroluminescent lighting device that not only exhibits the record quantities of 1007 cd m−2 in luminance and 1.9% ...in external quantum efficiency but also possesses satisfactorily high color rendering indices of 83−88 is demonstrated.
Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting HPV antigens to dendritic cells, elicits a significant ...E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of nine patients exhibit an enhanced polyfunctional HPV-specific CD8 T-cell response as shown by an increase in cytolytic activity, proliferative capacity and secretion of effector molecules. Notably, seven out of nine patients display complete regression of their lesions and viral clearance within 36 weeks of follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at all administered doses. These findings indicate that the magnitude of systemic polyfunctional CD8 T-cell response is the main contributing factor for histological, cytological and virological responses, providing valuable insights into the design of therapeutic vaccines for effectively treating persistent infections and cancers in humans.
Exosomes are a type of extracellular vesicles containing mRNA, miRNA, and proteins of origin cells, which can control the characteristics of other cells or surroundings. Despite increasing evidence ...on oncogenic properties of tumor-derived exosomes, fibrosarcoma-derived exosomes remain largely unrevealed. While the proper extraction and characterization of exosomes is critical in exosomes research, there are various limitations in techniques to measure the size and homogeneity of exosomes. Here, we analyzed exosomes from a fibrosarcoma cell line WEHI-164 compared with a breast cancer cell line MDA-MD-231 as a control. Results from dot blot and western blot analysis demonstrated that GM1 ganglioside, and TSG101, HSC70 and GAPDH proteins were contained in exosomes from the WEHI-164 fibrosarcoma cell line. The existence of tetraspanins such as CD81, CD63 and CD9 was confirmed in the exosomes by ExoView analysis. The results obtained from TEM showed their sphere-like shapes of around 50 to 70 nm in radius. Through DLS, we found out that the mean radius of the exosomes derived from WEHI-164 and MDA-MB-231 cell lines was 94.4 nm and 107.8 nm, respectively, with high homogeneity. When comparing the radius measured by TEM with the radius measured by DLS, it was revealed that the difference between the two methods was about 40 nm. This study has significance in characterizing the molecular properties of exosomes from a fibrosarcoma, which has not been researched much before, and in providing clear evidence that DLS can be used as an efficient, convenient and noninvasive technique to simply check the homogeneity and size of exosomes.
Non-segmental vitiligo (NSV) is the most common type of vitiligo, which is characterized by chronic and progressive loss of melanocytes. Genetic factors have been shown to play a key role in NSV in ...association and family studies. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells that play an important role in inducing apoptotic changes of target cells. Several recent studies have provided evidence that polymorphism in the GZMB gene might be associated with autoimmune disease. A total of 249 NSV patients and 455 healthy controls were recruited to determine whether single nucleotide polymorphisms (SNPs) rs2236337 (3' untranslated region, UTR), rs2236338 (Tyr247His), rs11539752 (Pro94Ala), rs10909625 (Lys80Lys), rs8192917 (Arg55Gln), and rs7144366 (5' near gene) in GZMB gene contribute to the risk of developing NSV. Genotyping was performed using a single 192.24 Dynamic Array IFC. Data were analyzed using EP1 SNP Genotyping Analysis software to obtain genotype calls. Among the six SNPs tested, five SNPs (rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917) showed significant association with NSV susceptibility. Among them, rs2236338, rs11539752, rs10909625, and rs8192917 remained a statistically significant association following multiple correction test. The five SNPs were located within a block of linkage disequilibrium. Haplotypes T-A-G-T-T and C-G-C-C-C consisting of rs2236337, rs2236338, rs11539752, rs10909625, and rs8192917 demonstrated significant association with NSV. Our results suggest that GZMB polymorphisms are associated with the development of NSV.
Small plaque psoriasis is the typical form of chronic plaque psoriasis affecting adults in South Korea. The effectiveness of calcipotriol/betamethasone dipropionate (Cal/BD) aerosol foam for large ...and small psoriasis plaques has not previously been examined. We performed a post hoc analysis of a recent, 4‐week observational study of Cal/BD aerosol foam use in routine clinical practice in South Korea. Investigator Global Assessment response (IGA 0/1 at week 4), Patient Global Assessment response (PaGA 0/1 at week 4), change in Psoriasis Area and Severity Index (PASI), changes in psoriasis symptom scores, change in the Dermatology Life Quality Index (DLQI), and the proportion of patients achieving DLQI ≤5 were analyzed for patients with small (≤5 cm; n = 131) or large (>5 cm; n = 35) baseline plaque size. IGA response rates were similar for patients with small and large plaques (59.5% and 51.4% respectively). Similarly, there was no significant difference between the small and large groups in mean change in PASI (−2.20 vs −3.34), the proportions of patients with DLQI ≤5 (62.3% vs 54.3%) or PaGA 0/1 (29.2% vs 40.0%). Mean improvements in DLQI (−4.04 vs −6.20) and in psoriasis symptoms including itching (−1.50 vs −2.83), sleep loss (−0.67 vs −1.89), dryness (−1.57 vs −2.97), scaling (−1.21 vs −3.57), and redness (−1.17 vs −3.11) were greater in patients with large plaques than those with small plaques. Itching and DLQI differences were not statistically significant after adjustment for baseline characteristics. Stratification by body surface area affected eliminated statistically significant differences between the groups for most outcomes. In conclusion, this analysis suggests that Cal/BD aerosol foam is an effective, well‐accepted treatment for adult patients with the small plaques typical of chronic plaque psoriasis in South Korea, as well as for those with large plaques.
An innovative foam formulation for the fixed‐dose combination of calcipotriol and betamethasone dipropionate (Cal/BD) has recently become available for the treatment of psoriasis vulgaris. ...Observational studies of patients treated with Cal/BD foam in routine practice have been conducted in several Western countries, but there are limited data on outcomes in Asian patients. We performed a prospective, open‐label, noncomparative, noninterventional study to investigate treatment outcomes and satisfaction in adult patients receiving Cal/BD foam for psoriasis vulgaris in dermatological centers and outpatient clinics in Korea. Data were collected at the time of enrollment (Visit 1) and at a routine clinic visit ~4 weeks later (Visit 2). In total, 218 patients were enrolled, of whom 175 were included in the safety analysis set (58.9% male; mean age ± standard deviation 46.7 ± 15.1 years; use of Cal/BD foam at least once daily 74.3%). Of the safety analysis set, 166 patients had at least mild psoriasis (Investigator Global Assessment IGA ≥ 2) and were analyzed for treatment outcomes and satisfaction. Of the 166 patients, 71.7% had mild psoriasis (IGA 2) at baseline. The majority (57.8%) achieved an IGA of 0/1 (clear/almost clear) at Visit 2. The Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) showed significant improvements from Visit 1 to Visit 2 (PASI −2.4 ± 3.0, DLQI −4.5 ± 5.2, both P < 0.0001). Most of the patients were satisfied with the Cal/BD foam treatment; 77.0%, 60.0%, and 73.9% were satisfied in terms of effectiveness, ease of use, and global satisfaction, respectively. In the safety analysis set, adverse events were reported in 13 patients (7.4%). In conclusion, this first Korean real‐world study of Cal/BD foam shows improvement of lesions and health‐related quality of life after 4 weeks of treatment, with high global satisfaction and good overall tolerability and safety.
Radial glial cells (RGCs) as primary neural stem cells in the developing mammalian cortex give rise to diverse types of neurons and glial cells according to sophisticated developmental programs with ...remarkable spatiotemporal precision. Recent studies suggest that regulation of the temporal competence of RGCs is a key mechanism for the highly conserved and predictable development of the cerebral cortex. Various types of epigenetic regulations, such as DNA methylation, histone modifications, and 3D chromatin architecture, play a key role in shaping the gene expression pattern of RGCs. In addition, epitranscriptomic modifications regulate temporal pre-patterning of RGCs by affecting the turnover rate and function of cell-type-specific transcripts. In this review, we summarize epigenetic and epitranscriptomic regulatory mechanisms that control the temporal competence of RGCs during mammalian corticogenesis. Furthermore, we discuss various developmental elements that also dynamically regulate the temporal competence of RGCs, including biochemical reaction speed, local environmental changes, and subcellular organelle remodeling. Finally, we discuss the underlying mechanisms that regulate the interspecies developmental tempo contributing to human-specific features of brain development.
To evaluate pregnancy outcomes after laparoscopic myomectomy (LSM), focusing on the risk of uterine rupture.
Retrospective cohort study (Canadian Task Force classification III).
University hospital.
...Of 676 women who visited the obstetrics department for a pregnancy after undergoing LSM performed at the same center between 1994 and 2012, we included the 523 women who had follow-up through the end of pregnancy.
All patients underwent LSM, and their medical charts were retrospectively reviewed.
Multiple myomas were removed in 35.2% of cases, intramural-type lesions occurred in 46.5% of cases, and the mean myoma diameter was 4.9 cm. Pregnancy outcomes after LSM included 400 (76.5%) full-term deliveries and 100 (19.1%) vaginal deliveries, with other adverse outcomes being no different than the general population. The mean interval between LSM and pregnancy was 14 months, and only 3 (0.6%) cases of uterine rupture occurred during pregnancy. In analysis, by reviewing the published cases of uterine rupture, we found that the mean diameter, myoma number and type, and the rate of uterine suture were similar between the ruptured cases and all of our cases of LSM.
LSM can be safely used in women of reproductive age who want to become pregnant. Uterine rupture occurs in rare cases, regardless of myoma features, but further large-scale studies are required to ascertain the detailed effects of various surgical techniques.
Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established.
To investigate the risks of ...skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions.
This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed.
The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients).
Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment.
Among the 60 321 patients with vitiligo in this study (33 617 women; mean SD age, 50.2 14.9 years), the risks of Bowen disease (<50 sessions of phototherapy: hazard ratio HR, 0.289 95% CI, 0.060-1.392; 50-99 sessions: HR, 0.603 95% CI, 0.125-2.904; 100-199 sessions: HR, 1.273 95% CI, 0.329-4.924; ≥200 sessions: HR, 1.021 95% CI, 0.212-4.919), nonmelanoma skin cancer (<50 sessions: HR, 0.914 95% CI, 0.533-1.567; 50-99 sessions: HR, 0.765 95% CI, 0.372-1.576; 100-199 sessions: HR, 0.960 95% CI, 0.453-2.034; ≥200 sessions: HR, 0.905 95% CI, 0.395-2.073), and melanoma (<50 sessions: HR, 0.660 95% CI, 0.286-1.526; 50-99 sessions: HR, 0.907 95% CI, 0.348-2.362; 100-199 sessions: HR, 0.648 95% CI, 0.186-2.255; ≥200 sessions: HR, 0.539 95% CI, 0.122-2.374) did not increase after phototherapy. The risk of actinic keratosis increased significantly for those who had undergone 200 or more NBUVB phototherapy sessions (HR, 2.269 95% CI, 1.530-3.365). A total of 717 patients with vitiligo underwent at least 500 sessions of NBUVB phototherapy; their risks of nonmelanoma skin cancer and melanoma were no greater than those of the patients who did not undergo NBUVB phototherapy (nonmelanoma skin cancer: HR, 0.563 95% CI, 0.076-4.142; melanoma: HR, not applicable).
Our results suggest that long-term NBUVB phototherapy is not associated with an increased risk of skin cancer in patients with vitiligo and that NBUVB phototherapy may be considered a safe treatment.
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