Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).

Three-dimensional electronic microfliers inspired by wind-dispersed seeds.

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance.

Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood-brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood-brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.

Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.

Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.

ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature.

The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells. We show that ACVR1/ALK2 is a key modulator for the proliferation of endothelium in the retinal vessels. Loss of endothelial ALK2 leads to a significant reduction in endothelial proliferation and results in fewer branches/endothelial cells in the retinal vessels. Interestingly, venous endothelium appears to be more susceptible to ALK2 deletion. Mechanistically, ACVR1/ALK2 inhibits the expression of CDKN1A/p21, a critical negative regulator of cell cycle progression, in a SMAD1/5-dependent manner, thereby enabling the venous endothelium to undergo active proliferation by suppressing CDKN1A/p21. Taken together, our findings show that BMP signaling mediated by ACVR1/ALK2 provides a critical yet previously underappreciated input to modulate the proliferation of venous endothelium, thereby fine-tuning the context of angiogenesis in health and disease.

Scalable manufacturing of high-index atomic layer-polymer hybrid metasurfaces for metaphotonics in the visible.

Metalenses are attractive alternatives to conventional bulky refractive lenses owing to their superior light-modulating performance and sub-micrometre-scale thicknesses; however, limitations in existing fabrication techniques, including high cost, low throughput and small patterning area, have hindered their mass production. Here we demonstrate low-cost and high-throughput mass production of large-aperture visible metalenses using deep-ultraviolet argon fluoride immersion lithography and wafer-scale nanoimprint lithography. Once a 12″ master stamp is imprinted, hundreds of centimetre-scale metalenses can be fabricated using a thinly coated high-index film to enhance light confinement, resulting in a substantial increase in conversion efficiency. As a proof of concept, an ultrathin virtual reality device created with the printed metalens demonstrates its potential towards the scalable manufacturing of metaphotonic devices.

Colon cancer cells acquire immune regulatory molecules from tumor-infiltrating lymphocytes by trogocytosis.

Cancer cells can develop an immunosuppressive tumor microenvironment to control tumor-infiltrating lymphocytes. The underlying mechanisms still remain unclear. Here, we report that mouse and human colon cancer cells acquire lymphocyte membrane proteins including cellular markers such as CD4 and CD45. We observed cell populations harboring both a tumor-specific marker and CD4 in the tumor microenvironment. Sorted cells from these populations were capable of forming organoids, identifying them as cancer cells. Live imaging analysis revealed that lymphocyte membrane proteins were transferred to cancer cells via trogocytosis. As a result of the transfer in vivo, cancer cells also acquired immune regulatory surface proteins such as CTLA4 and Tim3, which suppress activation of immune cells [T. L. Walunas et al, Immunity 1, 405-413 (1994) and L. Monney et al., Nature 415, 536-541 (2002)]. RNA sequencing analysis of ex vivo-cocultured splenocytes with trogocytic cancer cells showed reductions in Th1 activation and natural killer cell signaling pathways compared with the nontrogocytic control. Cancer cell trogocytosis was confirmed in the patient-derived xenograft models of colorectal cancer and head and neck cancer. These findings suggest that cancer cells utilize membrane proteins expressed in lymphocytes, which in turn contribute to the development of the immunosuppressive tumor microenvironment.

Effects of a Rice-Farming Simulation Video Game on Nature Relatedness, Nutritional Status, and Psychological State in Urban-Dwelling Adults During the COVID-19 Pandemic: Randomized Waitlist Controlled Trial.

BACKGROUND: During the COVID-19 pandemic, urban inhabitants faced significant challenges in maintaining connections with nature, adhering to nutritional guidelines, and managing mental well-being. OBJECTIVE: Recognizing the urgent need for innovative approaches, this study was designed to explore the potential benefits of a specific digital intervention, the rice-farming simulation game Sakuna: Of Rice and Ruin, for nature relatedness, nutritional behaviors, and psychological well-being. METHODS: A total of 66 adults without any prior major psychiatric disorders residing in an urban area were recruited for the study. They were randomly assigned to 2 groups through block randomization: the immediate intervention group (IIG; 34/66, 52%) and the waitlist group (32/66, 48%). Participants in the IIG were instructed to play the game for at least 4 days per week for 3 weeks, with each session lasting from 30 minutes to 3 hours. Assessments were performed at baseline, week 1, and week 3. The Nature Relatedness Scale (NR) and Nutrition Quotient Scale were used to evaluate nature relatedness and nutritional state, respectively. Furthermore, psychological state was assessed using the World Health Organization Quality of Life-Brief Version (WHOQOL-BREF), Brief Fear of Negative Evaluation Scale, Social Avoidance and Distress Scale, Toronto Alexithymia Scale, State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale Revised, and Korean Resilience Quotient. RESULTS: This study's results revealed significant time interactions between the IIG and waitlist group for both the total NR score (P=.001) and the score of the self subdomain of NR (P<.001), indicating an impact of the game on nature relatedness. No group×time interactions were found for the total Nutrition Quotient Scale and subdomain scores, although both groups showed increases from baseline. For psychological state, a significant group×time interaction was observed in the total WHOQOL-BREF score (P=.049), suggesting an impact of the game on quality of life. The psychological (P=.01), social (P=.003), and environmental (P=.04) subdomains of the WHOQOL-BREF showed only a significant time effect. Other psychological scales did not display any significant changes (all P>.05). CONCLUSIONS: Our findings suggest that the rice-farming game intervention might have positive effects on nature relatedness, nature-friendly dietary behaviors, quality of life, anxiety, depression, interpersonal relationships, and resilience among urban adults during the COVID-19 pandemic. The impact of pronature games in confined urban environments provides valuable evidence of how digital technologies can be used to enhance urban residents' affinity for nature and psychological well-being. This understanding can be extended in the future to other digital platforms, such as metaverses. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0007657; http://tinyurl.com/yck7zxp7.

Prediction of impending mood episode recurrence using real-time digital phenotypes in major depression and bipolar disorders in South Korea: a prospective nationwide cohort study.

BACKGROUND: Mood disorders require consistent management of symptoms to prevent recurrences of mood episodes. Circadian rhythm (CR) disruption is a key symptom of mood disorders to be proactively managed to prevent mood episode recurrences. This study aims to predict impending mood episodes recurrences using digital phenotypes related to CR obtained from wearable devices and smartphones. METHODS: The study is a multicenter, nationwide, prospective, observational study with major depressive disorder, bipolar disorder I, and bipolar II disorder. A total of 495 patients were recruited from eight hospitals in South Korea. Patients were followed up for an average of 279.7 days (a total sample of 75 506 days) with wearable devices and smartphones and with clinical interviews conducted every 3 months. Algorithms predicting impending mood episodes were developed with machine learning. Algorithm-predicted mood episodes were then compared to those identified through face-to-face clinical interviews incorporating ecological momentary assessments of daily mood and energy. RESULTS: Two hundred seventy mood episodes recurred in 135 subjects during the follow-up period. The prediction accuracies for impending major depressive episodes, manic episodes, and hypomanic episodes for the next 3 days were 90.1, 92.6, and 93.0%, with the area under the curve values of 0.937, 0.957, and 0.963, respectively. CONCLUSIONS: We predicted the onset of mood episode recurrences exclusively using digital phenotypes. Specifically, phenotypes indicating CR misalignment contributed the most to the prediction of episodes recurrences. Our findings suggest that monitoring of CR using digital devices can be useful in preventing and treating mood disorders.

Composition of Organically Modified Silica for the Superhydrophobic Surface with Low Sliding Angle.

Extremely water-repellent surfaces with low sliding angle (SA) have been obtained with a facile single-step sol-gel strategy via co-condensation of tetraethoxysilane (TEOS) and hexadecyltrimethoxysilane (HDTMS) in basic media with an efficient self-cleaning property. We investigated the effect of the molar ratio of HDTMS and TEOS on the properties of the modified silica-coated poly(ethylene terephthalate) (PET) film. A high water contact angle (WCA) of 165° and a low SA of 1.35° were obtained at a molar ratio of 0.125. The dual roughness pattern for the low SA was developed by a one-step coating of the modified silica with a molar ratio of 0.125. The evolution of the surface to the dual roughness pattern by nonequilibrium dynamics depended on the size and shape factor of modified silica. The primitive size and the shape factor of the organosilica with a molar ratio of 0.125 were 70 nm and 0.65, respectively. We also presented a new method to determine the superficial surface friction (ζ) of the superhydrophobic surface. The ζ was a physical parameter that characterized the slip and rolling behavior of water droplets on the superhydrophobic surface along with the equilibrium property WCA and the static frictional property SA.

Ensemble Approach to Combining Episode Prediction Models Using Sequential Circadian Rhythm Sensor Data from Mental Health Patients.

Managing mood disorders poses challenges in counseling and drug treatment, owing to limitations. Counseling is the most effective during hospital visits, and the side effects of drugs can be burdensome. Patient empowerment is crucial for understanding and managing these triggers. The daily monitoring of mental health and the utilization of episode prediction tools can enable self-management and provide doctors with insights into worsening lifestyle patterns. In this study, we test and validate whether the prediction of future depressive episodes in individuals with depression can be achieved by using lifelog sequence data collected from digital device sensors. Diverse models such as random forest, hidden Markov model, and recurrent neural network were used to analyze the time-series data and make predictions about the occurrence of depressive episodes in the near future. The models were then combined into a hybrid model. The prediction accuracy of the hybrid model was 0.78; especially in the prediction of rare episode events, the F1-score performance was approximately 1.88 times higher than that of the dummy model. We explored factors such as data sequence size, train-to-test data ratio, and class-labeling time slots that can affect the model performance to determine the combinations of parameters that optimize the model performance. Our findings are especially valuable because they are experimental results derived from large-scale participant data analyzed over a long period of time.

Role of Venous Endothelial Cells in Developmental and Pathologic Angiogenesis.

BACKGROUND: Angiogenesis is a dynamic process that involves expansion of a preexisting vascular network that can occur in a number of physiological and pathological settings. Despite its importance, the origin of the new angiogenic vasculature is poorly defined. In particular, the primary subtype of endothelial cells (capillary, venous, arterial) driving this process remains undefined. METHODS: Endothelial cells were fate-mapped with the use of genetic markers specific to arterial and capillary cells. In addition, we identified a novel venous endothelial marker gene (Gm5127) and used it to generate inducible venous endothelium-specific Cre and Dre driver mouse lines. Contributions of these various types of endothelial cells to angiogenesis were examined during normal postnatal development and in disease-specific setting. RESULTS: Using a comprehensive set of endothelial subtype-specific inducible reporter mice, including tip, arterial, and venous endothelial reporter lines, we showed that venous endothelial cells are the primary endothelial subtype responsible for the expansion of an angiogenic vascular network. During physiological angiogenesis, venous endothelial cells proliferate, migrating against the blood flow and differentiating into tip, capillary, and arterial endothelial cells of the new vasculature. Using intravital 2-photon imaging, we observed venous endothelial cells migrating against the blood flow to form new blood vessels. Venous endothelial cell migration also plays a key role in pathological angiogenesis. This was observed both in formation of arteriovenous malformations in mice with inducible endothelium-specific Smad4 deletion mice and in pathological vessel growth seen in oxygen-induced retinopathy. CONCLUSIONS: Our studies establish that venous endothelial cells are the primary endothelial subtype responsible for normal expansion of vascular networks, formation of arteriovenous malformations, and pathological angiogenesis. These observations highlight the central role of the venous endothelium in normal development and disease pathogenesis.

Differential expression and sorting of exosomal microRNAs upon activation of the human monocyte-like cell line U937.

Extracellular vesicles such as exosomes in eukaryotes have drawn scrutiny due to their various roles in intercellular communication. Small RNAs, including microRNAs (miRNAs), are more abundant among the cargo of exosomes than other RNA types. MiRNAs loaded in secreted exosomes (or extracellular microRNAs) can be transported to recipient cells and may play a regulatory role although the miRNA loading (or sorting) mechanism in exosomes has not been clearly elucidated. Therefore, this study analyzed exosomal miRNA sequencing data from human myeloid U937 cells treated with phorbol 12-myristate 13-acetate (PMA) and compared it with data from PMA-untreated U937 cells. MiR-24 was highly expressed in the cytoplasm and exosomes of PMA-treated U937 cells. Also, miRNA pull-down and mass spectrophotometry analysis of PMA-treated U937 cells revealed that miR-24 was specifically associated with α-tubulin and hnRNP-E1 proteins. Furthermore, exosomal miR-24 was dramatically reduced when those proteins were inactivated with siRNAs, whereas cellular miR-24 showed no significant effect. We conclude that miR-24 is transported into exosomes from activated macrophages with the support of α-tubulin and hnRNP-E1.

Transcriptomic analysis identifies novel targets for individual bone morphogenetic protein type 1 receptors in endothelial cells.

Bone Morphogenetic Protein (BMP) signaling regulates diverse biological processes. Upon ligand binding, BMP receptors (BMPRs) phosphorylate SMAD1/5 and other noncanonical downstream effectors to induce transcription of downstream targets. However, the precise role of individual BMP receptors in this process remains largely unknown due to the complexity of downstream signaling and the innate promiscuity of ligand-receptor interaction. To delineate unique downstream effectors of individual BMPR1s, we analyzed the transcriptome of human umbilical endothelial cells (HUVECs) expressing three distinct constitutively active BMPR1s of which expression was detected in endothelial cells (ECs). From our analyses, we identified a number of novel downstream targets of BMPR1s in ECs. More importantly, we found that each BMPR1 possesses a distinctive set of downstream effectors, suggesting that each BMPR1 is likely to retain unique function in ECs. Taken together, our analyses suggest that each BMPR1 regulates downstream targets non-redundantly in ECs to create context-dependent outcomes of the BMP signaling.

Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.

AIM: Symptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD. METHOD: Drawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross-disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework. RESULTS: Evidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood-related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high-risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings. CONCLUSIONS: Future research in circadian rhythms and its role in BD is warranted. Well-powered studies that carefully define associations between BD-related and chronobiologically-related constructs, and integrate across levels of analysis will be most illuminating.

High-Resolution 3D Printing of Mechanically Tough Hydrogels Prepared by Thermo-Responsive Poloxamer Ink Platform.

High-resolution 3D-printable hydrogels with high mechanical strength and biocompatibility are in great demand because of their potential applications in numerous fields. In this study, a material system comprising Pluronic F-127 dimethacrylate (FDMA) is developed to function as a direct ink writing (DIW) hydrogel for 3D printing. FDMA is a triblock copolymer that transforms into micelles at elevated temperatures. The transformation increases the viscosity of FDMA and preserves its structure during DIW 3D printing, whereupon the printed structure is solidified through photopolymerization. Because of this viscosity shift, various functionalities can be incorporated through the addition of other materials in the solution state. Acrylic acid is incorporated into the pregel solution to enhance the mechanical strength, because the carboxylate group of poly(acrylic acid) ionically crosslinks with Fe3+ , increasing the toughness of the DIW hydrogel 37 times to 2.46 MJ m-3 . Tough conductive hydrogels are also 3D printed by homogenizing poly(3,4-ethylenedioxythiophene) polystyrene sulfonate into the pregel solution. Furthermore, the FDMA platform developed herein uses DIW, which facilitates multicartridges 3D printing, and because all the materials included are biocompatible, the platform may be used to fabricate complex structures for biological applications.

Filling gaps between exposure modeling and the analysis of urinary biomarkers using personal air monitoring: An intervention study of permethrin used in home insecticide spray.

Permethrin is one of the most widely used active ingredients in spray-type home insecticides. However, indoor permethrin exposure resulting from the use of home insecticides is not well-characterized, as measured permethrin concentrations in indoor environmental and biological media with a known application rate are scarce. We conducted an intervention study with four participants for seven days. We conducted personal air monitoring and collected 24-h urine samples in which we quantified time-weighted average (TWA) permethrin concentrations in indoor air (Cair ) and urinary concentrations of two permethrin metabolites, 3-phenoxybenzoic acid (3-PBA) and cis/trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis/trans-DCCA). We also estimated (1) TWA Cair using a simple indoor air model and (2) urinary excreted (UE) mass using a simple excretion model with both estimated and measured TWA Cair . Measurements of TWA Cair from personal air monitoring were lower than those estimated from the indoor model by a factor of 2.9 to 49.4. The ratio of estimated to measured UE mass ranged 3.5-18.2 when using estimated TWA Cair and 1.1-2.9 when using measured TWA Cair . Smaller ratios in estimating internal permethrin exposure from personal air monitoring suggest that personal air monitoring could reduce uncertainties in permethrin exposure assessment resulting from the use of spray-type insecticides.

Alaria alata (Digenea: Diplostomidae) from Korean Raccoon Dog, Nyctereutes procyonoides koreensis, in Korea.

We report a species of diplostomid fluke recovered from 3 carcasses of wild Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. A total of 107 diplostomid flukes were recovered from the small intestines of Korean raccoon dogs, which were obtained from the Gangwon Wildlife Medical Rescue Center. Worms fixed with 10% neutral formalin were subjected to microscopic observation and those fixed in 70% ethanol were used for molecular genomic analysis. The worm was divided into 2 separate parts, forebody and hindbody, with a total length of 3,020-4,090 (3,855) µm and a width of 1,210-1,770 (1,562) µm. The boat-shaped forebody has a pair of characteristic tentacular appendage, 2 suckers, holdfast organ, and vitelline follicles. The oval to cylindrical hindbody has reproductive organs. The ovary was round or elliptical and located in the anterior of the testes. Two large testes were slightly segmented and tandemly arranged, occupying almost half of hindbody. The short uterus contained a relatively small number of unembryonated eggs sized 130-140×85-96 µm. The partial sequence of 18S rRNA of this fluke was consistent with Alaria alata. Based on the morphological and molecular characteristics, the diplostomid flukes recovered from the small intestine of Korean raccoon dogs were identified as A. alata (Digenea: Diplostomidae).

Periodic Micropillar-Patterned FTO/BiVO4 with Superior Light Absorption and Separation Efficiency for Efficient PEC Performance.

In this study, a high-performance photoanode based on 3D periodic, micropillar-structured fluorine-doped tin oxide (FTO-MP) deposited with BiVO4 is fabricated using the patterned FTO by direct printing and spray pyrolysis, followed by the deposition of BiVO4 by sputtering and V ion heat-treatment on the patterned FTO. The FTO-MP enables light scattering owing to its 3D periodic structure and increases the light absorption efficiency. In addition, the high electron mobility of FTO and enlarged surface area of FTO-MP enhance the separation efficiency. Due to the combination of these enhancing strategies, the photocurrent density of micropillar-patterned BiVO4 at 1.23 VRHE reached 2.97 mA cm-2 , which is 67.8% higher than that of flat BiVO4 . The results suggest that the efficiency can increase significantly using the patterned FTO fabricated by an inexpensive and simple process (i.e., direct printing and spray pyrolysis), thereby indicating a new strategy for the enhancement of efficiency in various energy fields.

Magnetic Control and Real-Time Monitoring of Stem Cell Differentiation by the Ligand Nanoassembly.

Native extracellular matrix (ECM) exhibits dynamic change in the ligand position. Herein, the ECM-emulating control and real-time monitoring of stem cell differentiation are demonstrated by ligand nanoassembly. The density of gold nanoassembly presenting cell-adhesive Arg-Gly-Asp (RGD) ligand on Fe3 O4 (magnetite) nanoparticle in nanostructures flexibly grafted to material is changed while keeping macroscale ligand density invariant. The ligand nanoassembly on the Fe3 O4 can be magnetically attracted to mediate rising and falling ligand movements via linker stretching and compression, respectively. High ligand nanoassembly density stimulates integrin ligation to activate the mechanosensing-assisted stem cell differentiation, which is monitored via in situ real-time electrochemical sensing. Magnetic control of rising and falling ligand movements hinders and promotes the adhesion-mediated mechanotransduction and differentiation of stem cells, respectively. These rising and falling ligand states yield the difference in the farthest distance (≈34.6 nm) of the RGD from material surface, thereby dynamically mimicking static long and short flexible linkers, which hinder and promote cell adhesion, respectively. Design of cytocompatible ligand nanoassemblies can be made with combinations of dimensions, shapes, and biomimetic ligands for remotely regulating stem cells for offering novel methodologies to advance regenerative therapies.