This study reports a three‐dimensional (3D) bioprinting technique that is capable of producing a full‐thickness skin model containing pigmentation. Multiple layers of fibroblast (FB)‐containing ...collagen hydrogel precursor were printed and crosslinked through neutralization using sodium bicarbonate, constituting the dermal layer. Melanocytes (MCs) and keratinocytes (KCs) were sequentially printed on top of the dermal layer to induce skin pigmentation upon subsequent air‐liquid interface culture. Histological analysis was performed not only to confirm the formation of distinct skin layers, but also to identify the presence of pigmentation. The bioprinted skin structure showed the dermal and epidermal layers as well as the terminal differentiation of the KC that formed the stratum corneum. Moreover, the MC‐containing epidermal layer showed freckle‐like pigmentations at the dermal‐epidermal junction, without the use of external ultraviolet light or chemical stimuli. The presented method offers the capability of producing engineered ephelides in biomimetic skin, thus rendering 3D bioprinting techniques as productive on‐demand options for the creation of skin models available for therapeutic or research use.
Bimolecular and trap‐assisted recombination mechanisms are investigated in small molecule‐based phosphorescent organic light emitting diodes (PhOLEDs) using the current−voltage−luminance ...characteristics in the diffusion current region, along with transient electroluminescence and capacitance measurements. Two different PhOLEDs, one with a single host, 4,4′‐Bis(carbazol‐9‐yl)biphenyl, and the other with an exciplex‐forming co‐host, are studied. Trap‐assisted recombination with a large number of trapped charges is dominant in the PhOLED with the single host because of the large energy gap between the host and the dopant state. In contrast, bimolecular Langevin recombination is dominant in the PhOLED with the exciplex forming co‐host, where a phosphorescent dye is doped in the co‐host. As a result, the accumulated charge density is lower in the co‐host system than in the single host emission layer, leading to high efficiency that approaches the theoretical limit, with an extremely low efficiency roll‐off.
The origin
of the ultimate efficiency with extremely low efficiency roll‐off in a PhOLED with exciplex‐forming co‐host (quasi‐single host) is unveiled. Unlike the other PhOLEDs with single host which is dominantly governed by trap assisted recombination, Langevin assisted recombination is dominated in the PhOLED with quasi‐single host system, resulting in low accumulation of charges in the device.
Abstract We developed a methodology using 3D bio-printing technology to create a functional in vitro vascular channel with perfused open lumen using only cells and biological matrices. The fabricated ...vasculature has a tight, confluent endothelium lining, presenting barrier function for both plasma protein and high-molecular weight dextran molecule. The fluidic vascular channel is capable of supporting the viability of tissue up to 5 mm in distance at 5 million cells/mL density under the physiological flow condition. In static-cultured vascular channels, active angiogenic sprouting from the vessel surface was observed whereas physiological flow strongly suppressed this process. Gene expression analysis was reported in this study to show the potential of this vessel model in vascular biology research. The methods have great potential in vascularized tissue fabrication using 3D bio-printing technology as the vascular channel is simultaneously created while cells and matrix are printed around the channel in desired 3D patterns. It can also serve as a unique experimental tool for investigating fundamental mechanisms of vascular remodeling with extracellular matrix and maturation process under 3D flow condition.
Halide perovskites have emerged as promising candidates for various applications, such as photovoltaic, optoelectronic and thermoelectric applications. The knowledge of the thermal transport of ...halide perovskites is essential for enhancing the device performance for these applications and improving the understanding of heat transport in complicated material systems with atomic disorders. In this work, the current understanding of the experimentally and theoretically obtained thermal transport properties of halide perovskites is reviewed. This study comprehensively examines the reported thermal conductivity of methylammonium lead iodide, which is a prototype material, and provides theoretical frameworks for its lattice vibrational properties. The frameworks and discussions are extended to other halide perovskites and derivative structures. The implications for device applications, such as solar cells and thermoelectrics, are discussed.
Low-intensity focused ultrasound (FUS) has significant potential as a non-invasive brain stimulation modality and novel technique for functional brain mapping, particularly with its advantage of ...greater spatial selectivity and depth penetration compared to existing non-invasive brain stimulation techniques. As previous studies, primarily carried out in small animals, have demonstrated that sonication parameters affect the stimulation efficiency, further investigation in large animals is necessary to translate this technique into clinical practice. In the present study, we examined the effects of sonication parameters on the transient modification of excitability of cortical and thalamic areas in an ovine model. Guided by anatomical and functional neuroimaging data specific to each animal, 250 kHz FUS was transcranially applied to the primary sensorimotor area associated with the right hind limb and its thalamic projection in sheep (n = 10) across multiple sessions using various combinations of sonication parameters. The degree of effect from FUS was assessed through electrophysiological responses, through analysis of electromyogram and electroencephalographic somatosensory evoked potentials for evaluation of excitatory and suppressive effects, respectively. We found that the modulatory effects were transient and reversible, with specific sonication parameters outperforming others in modulating regional brain activity. Magnetic resonance imaging and histological analysis conducted at different time points after the final sonication session, as well as behavioral observations, showed that repeated exposure to FUS did not damage the underlying brain tissue. Our results suggest that FUS-mediated, non-invasive, region-specific bimodal neuromodulation can be safely achieved in an ovine model, indicating its potential for translation into human studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Focused ultrasound (FUS) has recently been investigated as a new mode of non-invasive brain stimulation, which offers exquisite spatial resolution and depth control. We report on the elicitation of ...explicit somatosensory sensations as well as accompanying evoked electroencephalographic (EEG) potentials induced by FUS stimulation of the human somatosensory cortex. As guided by individual-specific neuroimage data, FUS was transcranially delivered to the hand somatosensory cortex among healthy volunteers. The sonication elicited transient tactile sensations on the hand area contralateral to the sonicated hemisphere, with anatomical specificity of up to a finger, while EEG recordings revealed the elicitation of sonication-specific evoked potentials. Retrospective numerical simulation of the acoustic propagation through the skull showed that a threshold of acoustic intensity may exist for successful cortical stimulation. The neurological and neuroradiological assessment before and after the sonication, along with strict safety considerations through the individual-specific estimation of effective acoustic intensity in situ and thermal effects, showed promising initial safety profile; however, equal/more rigorous precautionary procedures are advised for future studies. The transient and localized stimulation of the brain using image-guided transcranial FUS may serve as a novel tool for the non-invasive assessment and modification of region-specific brain function.
The exciplex forming co‐host with phosphorescent dopant system has potential to realize highly efficient phosphorescent organic light emitting didoes (PhOLEDs). However, the exciplex forming co‐host ...for blue phosphorescent OLEDs has been rarely introduced because of higher triplet level of the blue dopant than green and red dopants. In this work, a novel exciplex forming co‐host with high triplet energy level is developed by mixing a phosphine oxide based electron transporting material, PO‐T2T, and a hole transporting material, N,N′‐dicarbazolyl‐3,5‐benzene (mCP). Photo‐physical analysis shows that the exciplexes are formed efficiently in the host and the energy transfer from the exciplex to blue phosphorescent dopant (iridium(III)bis(4,6‐difluorophenyl)‐pyridinato‐N,C2′picolinate; FIrpic) is also efficient, enabling the triplet harvest without energy loss. As a result, an unprecedented high performance blue PhOLED with the exciplex forming co‐host is demonstrated, showing a maximum external quantum efficiency (EQE) of 30.3%, a maximum power efficiency of 66 lm W−1, and low driving voltage of 2.75 at 100 cd m−2, 3.29 V at 1000 cd m−2, and 4.65 V at 10 000 cd m−2, respectively. The importance of the exciton confinement in the exciplex forming co‐host is further investigated which is directly related to the performance of PhOLEDs.
A novel exciplex forming host, composed of mCP and PO‐T2T, is realized. Using the host and efficient energy transfer to FIrpic, unprecedented high performance blue phosphorescent OLED is demonstrated, showing a maximum EQE of 30.3%, power efficiency of 66 lm W−1, and extremely low operating voltages of 2.75 at 100 cd m−2, and 4.65 V at 10 000 cd m−2.
The mammalian circadian clock involves a transcriptional feedback loop in which CLOCK and BMAL1 activate the Period and Cryptochrome genes, which then feed back and repress their own transcription. ...We have interrogated the transcriptional architecture of the drcadian transcriptional regulatory loop on a genome scale in mouse liver and find a stereotyped, time-dependent pattern of transcription factor binding, RNA polymerase II (RNAPII) recruitment RNA expression, and chromatin states. We find that the drcadian transcriptional cycle of the clock consists of three distinct phases: a poised state, a coordinated de novo transcriptional activation state, and a repressed state. Only 22% of messenger RNA (mRNA) cycling genes are driven by de novo transcription, suggesting that both transcriptional and posttranscriptional mechanisms underlie the mammalian circadian clock. We also find that drcadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling.
Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the ...observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.
Despite the well-known prognostic value of the tumor-immune microenvironment (TIME) in colorectal cancers, objective and readily applicable methods for quantifying tumor-infiltrating lymphocytes ...(TIL) and the tumor-stroma ratio (TSR) are not yet available.
We established an open-source software-based analytic pipeline for quantifying TILs and the TSR from whole-slide images obtained after CD3 and CD8 IHC staining. Using a random forest classifier, the method separately quantified intraepithelial TILs (iTIL) and stromal TILs (sTIL). We applied this method to discovery and validation cohorts of 578 and 283 stage III or high-risk stage II colorectal cancers patients, respectively, who were subjected to curative surgical resection and oxlaliplatin-based adjuvant chemotherapy.
Automatic quantification of iTILs and sTILs showed a moderate concordance with that obtained after visual inspection by a pathologist. The K-means-based consensus clustering of 197 TIME parameters that showed robustness against interobserver variations caused colorectal cancers to be grouped into five distinctive subgroups, reminiscent of those for consensus molecular subtypes (CMS1-4 and mixed/intermediate group). In accordance with the original CMS report, the CMS4-like subgroup (cluster 4) was significantly associated with a worse 5-year relapse-free survival and proved to be an independent prognostic factor. The clinicopathologic and prognostic features of the TIME subgroups have been validated in an independent validation cohort.
Machine-learning-based image analysis can be useful for extracting quantitative information about the TIME, using whole-slide histopathologic images. This information can classify colorectal cancers into clinicopathologically relevant subgroups without performing a molecular analysis of the tumors.
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