A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

Skin-integrated systems for power efficient, programmable thermal sensations across large body areas.

Thermal sensations contribute to our ability to perceive and explore the physical world. Reproducing these sensations in a spatiotemporally programmable manner through wireless computer control could enhance virtual experiences beyond those supported by video, audio and, increasingly, haptic inputs. Flexible, lightweight and thin devices that deliver patterns of thermal stimulation across large areas of the skin at any location of the body are of great interest in this context. Applications range from those in gaming and remote socioemotional communications, to medical therapies and physical rehabilitation. Here, we present a set of ideas that form the foundations of a skin-integrated technology for power-efficient generation of thermal sensations across the skin, with real-time, closed-loop control. The systems exploit passive cooling mechanisms, actively switchable thermal barrier interfaces, thin resistive heaters and flexible electronics configured in a pixelated layout with wireless interfaces to portable devices, the internet and cloud data infrastructure. Systematic experimental studies and simulation results explore the essential mechanisms and guide the selection of optimized choices in design. Demonstration examples with human subjects feature active thermoregulation, virtual social interactions, and sensory expansion.

Does TFAP2C govern conflicting cell fates in mouse preimplantation embryos?

Transcription factor AP2 gamma (TFAP2C) is a well-established regulator of the trophoblast lineage in mice and humans, but a handful of studies indicate that TFAP2C may play an important role in pluripotency. Here, we hypothesize and provide new evidence that TFAP2C functions as an activator of trophoblast and pluripotency genes during preimplantation embryo development.

Loss of function of ribosomal protein L13a blocks blastocyst formation and reveals a potential nuclear role in gene expression.

Ribosomal proteins play diverse roles in development and disease. Most ribosomal proteins have canonical roles in protein synthesis, while some exhibit extra-ribosomal functions. Previous studies in our laboratory revealed that ribosomal protein L13a (RPL13a) is involved in the translational silencing of a cohort of inflammatory proteins in myeloid cells. This prompted us to investigate the role of RPL13a in embryonic development. Here we report that RPL13a is required for early development in mice. Crosses between Rpl13a+/- mice resulted in no Rpl13a-/- offspring. Closer examination revealed that Rpl13a-/- embryos were arrested at the morula stage during preimplantation development. RNA sequencing analysis of Rpl13a-/- morulae revealed widespread alterations in gene expression, including but not limited to several genes encoding proteins involved in the inflammatory response, embryogenesis, oocyte maturation, stemness, and pluripotency. Ex vivo analysis revealed that RPL13a was localized to the cytoplasm and nucleus between the two-cell and morula stages. RNAi-mediated depletion of RPL13a phenocopied Rpl13a-/- embryos and knockdown embryos exhibited increased expression of IL-7 and IL-17 and decreased expression of the lineage specifier genes Sox2, Pou5f1, and Cdx2. Lastly, a protein-protein interaction assay revealed that RPL13a is associated with chromatin, suggesting an extra ribosomal function in transcription. In summary, our data demonstrate that RPL13a is essential for the completion of preimplantation embryo development. The mechanistic basis of the absence of RPL13a-mediated embryonic lethality will be addressed in the future through follow-up studies on ribosome biogenesis, global protein synthesis, and identification of RPL13a target genes using chromatin immunoprecipitation and RNA-immunoprecipitation-based sequencing.

Ginsenoside Rb1 alleviates lipopolysaccharide-induced inflammation in human dental pulp cells via the PI3K/Akt, NF-κB, and MAPK signalling pathways.

AIM: Among numerous constituents of Panax ginseng, a constituent named Ginsenoside Rb1 (G-Rb1) has been studied to diminish inflammation associated with diseases. This study investigated the anti-inflammatory properties of G-Rb1 on human dental pulp cells (hDPCs) exposed to lipopolysaccharide (LPS) and aimed to determine the underlying molecular mechanisms. METHODOLOGY: The KEGG pathway analysis was performed after RNA sequencing in G-Rb1- and LPS-treated hDPCs. Reverse-transcription polymerase chain reaction (RT-PCR) and western blot analysis were used for the assessment of cell adhesion molecules and inflammatory cytokines. Statistical analysis was performed with one-way ANOVA and the Student-Newman-Keuls test. RESULTS: G-Rb1 did not exhibit any cytotoxicity within the range of concentrations tested. However, it affected the levels of TNF-α, IL-6 and IL-8, as these showed reduced levels with exposure to LPS. Additionally, less mRNA and protein expressions of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were shown. With the presence of G-Rb1, decreased levels of PI3K/Akt, phosphorylated IκBα and p65 were also observed. Furthermore, phosphorylated ERK and JNK by LPS were diminished within 15, 30 and 60 min of G-Rb1 exposure; however, the expression of non-phosphorylated ERK and JNK remained unchanged. CONCLUSIONS: G-Rb1 suppressed the LPS-induced increase of cell adhesion molecules and inflammatory cytokines, while also inhibiting PI3K/Akt, phosphorylation of NF-κB transcription factors, ERK and JNK of MAPK signalling in hDPCs.

Single-cell transcriptomics suggest distinct upstream drivers of IL-17A/F in hidradenitis versus psoriasis.

BACKGROUND: On the basis of the mounting evidence that type 17 T (T17) cells and increased IL-17 play a key role in driving hidradenitis suppurativa (HS) lesion development, biologic agents used previously in psoriasis that block signaling of IL-17A and/or IL-17F isoforms have been repurposed to treat HS. OBJECTIVE: Our research aimed to characterize the transcriptome of HS T17 cells compared to the transcriptome of psoriasis T17 cells, along with their ligand-receptor interactions with neighborhood immune cell subsets. METHODS: Single-cell data of 12,300 cutaneous immune cells from 8 deroofing surgical HS skin samples including dermal tunnels were compared to single-cell data of psoriasis skin (19,525 cells from 11 samples) and control skin (11,920 cells from 10 samples). All single-cell data were generated by the same protocol. RESULTS: HS T17 cells expressed lower levels of IL23R and higher levels of IL1R1 and IL17F compared to psoriasis T17 cells (P < .05). HS Treg cells expressed higher levels of IL1R1 and IL17F compared to psoriasis Treg cells (P < .05). Semimature dendritic cells were the major immune cell subsets expressing IL1B in HS, and IL-1ß ligand-receptor interactions between semimature dendritic cells and T17 cells were increased in HS compared to psoriasis (P < .05). HS dermal tunnel keratinocytes expressed inflammatory cytokines (IL17C, IL1A, IL1B, and IL6) that differed from the HS epidermis keratinocytes (IL36G) (P < .05). IL6, which synergizes with IL1B to maintain cytokine expression in T17 cells, was mainly expressed by fibroblasts in HS, which also expressed IL11+ inflammatory fibroblast genes (IL11, IL24, IL6, and POSTN) involved in the paracrine IL-1/IL-6 loop. CONCLUSION: The IL-1ß-T17 cell cytokine axis is likely a dominant pathway in HS with HS T17 cells activated by IL-1ß signaling, unlike psoriasis T17 cells, which are activated by IL-23 signaling.

Natural peloids originating from subsea depths of 200 m in the hupo basin, South Korea: physicochemical properties for potential pelotherapy applications.

The present study firstly reports surface sediment from the subsea depth of 200 m as a potential natural peloid. The fine-silt sediment exhibited a consistent clay mineral composition dominated by illite, chlorite, kaolinite, and diatomite. The most abundant clay mineral was illite/mica, with other minerals loosely packed in a face-to-face orientation. The thermal conductivity, specific heat capacity, and cation-exchange capacity of the sediment were in the range 0.855-0.885 W/m K, 2.718-2.821 J/g °C, and 23.06-32.96 cmol/kg, respectively. The concentrations of most toxic elements in the sediment were considerably lower than the limits set by domestic cosmetic regulations and other international standards. The analyzed samples exhibited similar properties to those of previously reported peloids, thus making them suitable for use in the field of pelotherapy; furthermore, the consistency in data across a wide peloid-distribution area is expected to enable economically viable mining. Future investigations should aim to to evaluate the long-term effects on the skin, the bioavailability of potentially hazardous substances, and the therapeutic efficacy for various skin conditions.

Sonographic and computed tomographic features of intestinal mast cell tumors mimicking alimentary lymphoma in 2 dogs.

Two shih tzu dogs were referred to our clinic because of hematochezia and vomiting. Abdominal ultrasonography revealed a focal, asymmetric, exophytic small intestinal mass with loss of wall layering and muscular layer thickening of the adjacent intestine. Computed tomography (CT) in both dogs revealed a focal, asymmetric, homogenously contrast-enhanced exophytic jejunal and duodenal mass with an intact mucosal layer and generalized lymphadenopathy. Metastasis and ulceration were not detected on CT. The initial imaging diagnosis was lymphoma in both dogs; however, histopathological examination revealed the presence of intestinal mast cell tumors (iMCTs). Despite its similarity to alimentary lymphoma, iMCT should be considered a possible diagnosis, based on imaging characteristics, to ensure that proper treatments are selected. This is the first veterinary report describing detailed ultrasonographic and CT characteristics of iMCTs. Key clinical message: This is the first veterinary case report demonstrating sonographic and computed tomographic features of canine iMCT, which can be misdiagnosed as alimentary lymphoma. This report provides another differential diagnosis to consider when determining the appropriate patient treatment direction and histopathological examination.

Caractéristiques échographiques et tomodensitométriques de mastocytomes intestinaux imitant un lymphome alimentaire chez 2 chiens. Deux chiens shih tzu ont été référés à notre clinique en raison d'une hématochézie et de vomissements. L'échographie abdominale a révélé une masse focale, asymétrique et exophytique de l'intestin grêle avec perte de stratification pariétale et épaississement de la couche musculaire de l'intestin adjacent. La tomodensitométrie (TDM) chez les deux chiens a révélé une masse jéjunale et duodénale exophytique focale, asymétrique, homogène et contrastée avec une couche muqueuse intacte et une lymphadénopathie généralisée. Les métastases et les ulcérations n'ont pas été détectées par TDM. Le diagnostic initial d'imagerie était un lymphome chez les deux chiens; cependant, l'examen histopathologique a révélé la présence de mastocytomes intestinaux (iMCT). Malgré sa similitude avec le lymphome alimentaire, l'iMCT doit être considérée comme un diagnostic possible, basé sur les caractéristiques de l'imagerie, afin de garantir la sélection des traitements appropriés. Il s'agit du premier rapport vétérinaire décrivant les caractéristiques échographiques et tomodensitométriques détaillées des iMCT.Message clinique clé :Il s'agit du premier rapport de cas vétérinaire démontrant les caractéristiques échographiques et tomodensitométriques de l'iMCT canin, qui peuvent être diagnostiquées à tort comme un lymphome alimentaire. Ce rapport fournit un autre diagnostic différentiel à prendre en compte lors de la détermination de l'orientation thérapeutique et de l'examen histopathologique appropriés du patient.(Traduit par Dr Serge Messier).

Cross-Cultural Validation and the Psychometric Properties of the Korean Version of the Brief Religious Coping Scale.

This study examined the psychometric properties of the Korean version of the Brief Religious Coping Scale (RCOPE) among Korean Protestant Christians to determine its reliability and validity in South Korea considering the unique characteristics of Korean Protestant Christianity. Exploratory Factor Analysis (n = 251) and confirmatory factor analysis (n = 268) identified the original two-factor structure of the positive and negative religious coping subscales. Also, the scale exhibited robust reliability and construct validity. This study affirmed the scale is a valid and reliable instrument for measuring religious coping in Korean Christian adults.

Left ventricular remodeling in end-stage liver disease and post-transplant mortality assessed using end-diastolic pressure-volume relation analysis: Observational retrospective study.

BACKGROUND: Diastolic dysfunction is regarded as an important predictor of outcome after liver transplantation (LT). We investigated the influence of liver disease severity on left ventricular diastolic properties using end-diastolic pressure-volume relationship (EDPVR) analysis in patients with end-stage liver disease (ESLD). Association between alterations of the EDPVR and mortality after LT was evaluated. METHODS: In this observational retrospective cohort study, 3,211 patients who underwent LT for ESLD were included in analysis. Variables derived from single-beat EDPVR (diastolic stiffness-coefficient [ß] and end-diastolic volume at an end-diastolic pressure of 20 mmHg [EDVI20] indicating ventricular capacitance) were estimated using preoperative echocardiographic data. Alterations in EDPVR with increased stiffness (ß > 6.16) were categorized into 3 groups; leftward-shifted (EDVI20 <51 mL/m2), rightward-shifted (EDVI20 > 69.7 mL/m2), and intermediate (EDVI20 51-69.7 mL/m2). RESULTS: As the model for ESLD score increases, both EDVI20 and ß gradually increased, which indicated ventricular remodeling with larger capacitance and higher diastolic stiffness. Among patients with increased stiffness (ß > 6.16, n = 1,090), survival rates after LT were lower in leftward-shifted EDPVR than in rightward-shifted EDPVR (73.7% vs 82.9%; log-rank P = 0.002). In the adjusted Cox proportional hazard model, risk of cumulative all-cause mortality at 11 years was the highest in leftward-shifted EDPVR (hazard ratio [HR]: 1.93; 95% confidence interval [CI]: 1.27-2.92), followed by intermediate EDPVR (HR: 1.55; 95% CI: 1.12-2.26), compared with rightward-shifted EDPVR. The SHapley Additive exPlanation model revealed that the variables associated with leftward-shifted EDPVR were diabetes, female sex, old age, and hypertension. CONCLUSIONS: As ESLD advances, diastolic ventricular properties are characterized by increased EDVI20 and ß on rightward-shifted EDPVR, indicating larger capacitance and higher stiffness. However, leftward-shifted EDPVR with left ventricle remodeling failure is associated with poor post-LT survival.

Modified Chemoselective Reduction and Consecutive Regioselective Deuteration Reaction Catalyzed by B(C6F5)3.

An efficient chemoselective reduction of isatin derivatives using catalyst B(C6F5)3, benzyldimethylsilane, and H2O is described. Notably, a small amount of water is shown to be a highly effective reaction promoter that decreases the reaction time and temperature for the synthesis of indolin-3-ones. Moreover, using method, excellent deuterium incorporation is achieved via the catalytic α-deuteration of indolin-3-ones using B(C6F5)3 and D2O.

Wafer Type Ion Energy Monitoring Sensor for Plasma Diagnosis.

We propose a wafer-type ion energy monitoring sensor (IEMS) that can measure the spatially resolved distribution of ion energy over the 150 mm plasma chamber for the in situ monitoring of the semiconductor fabrication process. The IEMS can directly be applied to the semiconductor chip production equipment without further modification of the automated wafer handling system. Thus, it can be adopted as an in situ data acquisition platform for plasma characterization inside the process chamber. To achieve ion energy measurement on the wafer-type sensor, the injected ion flux energy from the plasma sheath was converted into the induced currents on each electrode over the wafer-type sensor, and the generated currents from the ion injection were compared along the position of electrodes. The IEMS operates without problems in the plasma environment and has the same trends as the result predicted through the equation.

Impaired Blastocyst Formation in Lnx2-Knockdown Mouse Embryos.

Ligand of Numb-protein X 2 (LNX2) is an E3 ubiquitin ligase that is known to regulate Notch signaling by participating in NUMB protein degradation. Notch signaling is important for differentiation and proliferation in mammals, and plays a significant role in blastocyst formation during early embryonic development. In this study, we investigated Lnx2 in mouse preimplantation embryos. Expression analysis showed that Lnx2 is expressed in oocytes and preimplantation embryos. Lnx2-knockdown embryos normally progress to the morula stage, but the majority of them do not develop into normal blastocysts. Transcript analysis revealed that the expression levels of genes critical for cell lineage specification, including octamer-binding transcription factor 4 (Oct4), are increased in Lnx2 knockdown embryos. Furthermore, the expression levels of Notch and Hippo signaling-related genes are also increased by Lnx2 knockdown. Collectively, our results show that Lnx2 is important for blastocyst formation in mice, suggest that this may act via lineage specification of inner cell mass, and further show that Lnx2 may be involved in transcriptionally regulating various genes implicated in early embryonic development.

Computed tomographic findings may be useful for differentiating small intestinal adenocarcinomas, lymphomas, and spindle cell sarcomas in dogs.

An improved understanding of the CT characteristics for histologically confirmed primary intestinal tumors would be helpful for guiding prognosis and treatment plans in affected dogs. This retrospective, multi-center, analytical study aimed to evaluate the CT characteristics for the differentiation of adenocarcinoma, lymphoma, and spindle cell sarcoma (SCS) in dogs. Thirty-seven dogs who underwent contrast CT and histopathological examinations were included (adenocarcinomas, n = 11; lymphomas, n = 12; SCS, n = 14). Quantitative and qualitative CT parameters, including tumor morphology, contrast enhancement pattern, Hounsfield unit (HU) value, and presence or absence of intraabdominal lymphadenopathy, were evaluated for each included small intestine tumor CT case. Adenocarcinomas tended to show endophytic growth, intestinal obstruction, and a heterogeneous enhancement pattern. Lymphomas tended to show exophytic growth, contrast enhancement of the intestinal tumor mucosal layer, a homogeneous enhancement pattern, and the presence of lymphadenopathies in the abdominal cavity. SCSs tended to show lobulated growth, a large cystic portion within the tumor, a heterogeneous enhancement pattern, a large size with fat stranding sign, and lower HU values in postcontrast images. Cut-off values of the minimum diameter/fifth lumbar vertebral mid-body height (≥5.80; area under the curve [AUC] = 0.97, P < 0.001) and minimum HU value/HU value of the aorta (≤0.26; AUC = 0.96, P < 0.001) were derived to discriminate SCS from the two other tumor types. In conclusion, contrast CT characteristics may be useful in differentiating small intestinal adenocarcinomas, lymphomas, and SCSs in dogs.

Deep learning-based diagnosis of stifle joint diseases in dogs.

In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.

Electroreductive Radical Borylation of Unactivated (Hetero)Aryl Chlorides Without Light by Using Cumulene-Based Redox Mediators.

Single-electron transfer (SET) plays a critical role in many chemical processes, from organic synthesis to environmental remediation. However, the selective reduction of inert substrates (Ep/2 <-2 V vs Fc/Fc+ ), such as ubiquitous electron-neutral and electron-rich (hetero)aryl chlorides, remains a major challenge. Current approaches largely rely on catalyst photoexcitation to reach the necessary deeply reducing potentials or suffer from limited substrate scopes. Herein, we demonstrate that cumulenes-organic molecules with multiple consecutive double bonds-can function as catalytic redox mediators for the electroreductive radical borylation of (hetero)aryl chlorides at relatively mild cathodic potentials (approximately -1.9 V vs. Ag/AgCl) without the need for photoirradiation. Electrochemical, spectroscopic, and computational studies support that step-wise electron transfer from reduced cumulenes to electron-neutral chloroarenes is followed by thermodynamically favorable mesolytic cleavage of the aryl radical anion to generate the desired aryl radical intermediate. Our findings will guide the development of other sustainable, purely electroreductive radical transformations of inert molecules using organic redox mediators.

Ultrafast Na Transport into Crystalline Sn via Dislocation-Pipe Diffusion.

The charging process of secondary batteries is always associated with a large volume expansion of the alloying anodes, which in many cases, develops high compressive residual stresses near the propagating interface. This phenomenon causes a significant reduction in the rate performance of the anodes and is detrimental to the development of fast-charging batteries. However, for the Na-Sn battery system, the residual stresses that develop near the interface are not stored, but are relieved by the generation of high-density dislocations in crystalline Sn. Direct-contact diffusion experiments show that these dislocations facilitate the preferential transport of Na and accelerate the Na diffusion into crystalline Sn at ultrafast rates via "dislocation-pipe diffusion". Advanced analyses are performed to observe the evolution of atomic-scale structures while measuring the distribution and magnitude of residual stresses near the interface. In addition, multi-scale simulations that combined classical molecular dynamics and first-principles calculations are performed to explain the structural origins of the ultrafast diffusion rates observed in the Na-Sn system. These findings not only address the knowledge gaps regarding the relationship between pipe diffusion and the diffusivity of carrier ions but also provide guidelines for the appropriate selection of anode materials for use in fast-charging batteries.

Cellulose Nanofiber Films and Their Vibration Energy Harvesting.

Cellulose, the most abundant sustainable material on Earth, has excellent mechanical and physical properties, high optical transparency, biocompatibility, and piezoelectricity. So, it has many possibilities for future materials, and many researchers are interested in its application. In this paper, cellulose nanofiber (CNF) and CNF/polyvinyl alcohol (PVA) films are made, and their vibration energy harvesting is studied. CNF was isolated by chemical and physical methods, and the CNF suspension was cast on a flat substrate to make a film. A cast CNF wet film stayed in a 5 Tesla superconductor magnet for 7 days, which resulted in CNF alignment perpendicular to the magnetic field. To further improve the mechanical properties of the CNF film, mechanical stretching was applied. The CNF suspension was mixed with PVA, giving the film toughness. The cast CNF/PVA wet film was mechanically stretched and dried, which improved the CNF alignment. The fabricated CNF and CNF/PVA films were characterized using scanning electron microscopy and X-ray diffraction to verify the alignment. By stretching, the aligned CNF/PVA film exhibits the largest mechanical properties along the aligned direction. The maximum Young's modulus and tensile strength of the 50% stretched CNF/PVA film are 14.9 GPa and 170.6 MPa, respectively. Finally, a vibration energy harvesting experiment was performed by invoking the piezoelectric behavior of the pure CNF, and 50% stretched CNF/PVA films. The harvester structure was innovated by adopting a cymbal structure, which was beneficial to producing large in-plane strain on the films. The designed cymbal structure was analyzed using ANSYS, and its natural frequency was experimentally verified. The CNF/PVA film performs better vibration energy harvesting than the pure CNF film. The CNF/PVA film is applicable for biocompatible and flexible vibration energy harvesting.

Single-cell transcriptomics applied to emigrating cells from psoriasis elucidate pathogenic versus regulatory immune cell subsets.

BACKGROUND: In previous human skin single-cell data, inflammatory cells constituted only a small fraction of the overall cell population, such that functional subsets were difficult to ascertain. OBJECTIVE: Our aims were to overcome the aforesaid limitation by applying single-cell transcriptomics to emigrating cells from skin and elucidate ex vivo gene expression profiles of pathogenic versus regulatory immune cell subsets in the skin of individuals with psoriasis. METHODS: We harvested emigrating cells from human psoriasis skin after incubation in culture medium without enzyme digestion or cell sorting and analyzed cells with single-cell RNA sequencing and flow cytometry simultaneously. RESULTS: Unsupervised clustering of harvested cells from psoriasis skin and control skin identified natural killer cells, T-cell subsets, dendritic cell subsets, melanocytes, and keratinocytes in different layers. Comparison between psoriasis cells and control cells within each cluster revealed that (1) cutaneous type 17 T cells display highly differing transcriptome profiles depending on IL-17A versus IL-17F expression and IFN-γ versus IL-10 expression; (2) semimature dendritic cells are regulatory dendritic cells with high IL-10 expression, but a subset of semimature dendritic cells expresses IL-23A and IL-36G in psoriasis; and (3) CCL27-CCR10 interaction is potentially impaired in psoriasis because of decreased CCL27 expression in basal keratinocytes. CONCLUSION: We propose that single-cell transcriptomics applied to emigrating cells from human skin provides an innovative study platform to compare gene expression profiles of heterogenous immune cells in various inflammatory skin diseases.

Generation of a Dystrophin Mutant in Dog by Nuclear Transfer Using CRISPR/Cas9-Mediated Somatic Cells: A Preliminary Study.

Dystrophinopathy is caused by mutations in the dystrophin gene, which lead to progressive muscle degeneration, necrosis, and finally, death. Recently, golden retrievers have been suggested as a useful animal model for studying human dystrophinopathy, but the model has limitations due to difficulty in maintaining the genetic background using conventional breeding. In this study, we successfully generated a dystrophin mutant dog using the CRISPR/Cas9 system and somatic cell nuclear transfer. The dystrophin mutant dog displayed phenotypes such as elevated serum creatine kinase, dystrophin deficiency, skeletal muscle defects, an abnormal electrocardiogram, and avoidance of ambulation. These results indicate that donor cells with CRISPR/Cas9 for a specific gene combined with the somatic cell nuclear transfer technique can efficiently produce a dystrophin mutant dog, which will help in the successful development of gene therapy drugs for dogs and humans.