High‐frequency actuators are reported based on non‐flammable lithium‐ion conducting phosphate liquid crystal–polymer composite electrolytes, which exhibit a bending response at frequencies up to ...80 Hz under an AC voltage of 2 V, owing to its high ionic conductivity reaching 10−4 S cm−1 at room temperature. An equimolar complex of a phosphate‐containing mesogenic molecule and lithium bis(trifluoromethylsulfonyl)imide through the ion‐dipole interactions induced a room‐temperature smectic A liquid‐crystalline (LC) phase forming 2D ion‐transport pathways comprising the 2D array of the phosphate moieties. A blend of 80 wt% LC electrolyte and 20 wt% polymers (poly(vinyl chloride) and poly(vinylidene fluoride‐co‐hexafluoropropylene)) formed a flexible, mechanically robust LC–polymer composite film. Scanning electron microscopy and white light interference microscopy revealed a microphase‐segregated structure consisting of a continuous LC phase and a porous polymer matrix. In addition, the continuity of porous structure across the film is confirmed by permeation experiments of solvents thorough the membrane with a homemade filter in a dead‐end filtration mode. The LC–polymer composite film sandwiched between two poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonic acid) electrodes is found to simultaneously exhibit high bending strain (0.63%) and high output force (0.35 mN), owing to the high ion migration into the composite electrolyte and electrode.
In this study, a new type of phosphate‐based ionic liquid crystal–polymer composite actuator is developed exhibiting a high ionic conductivity reaching 10−4 S cm−1 at room temperature and an ultrafast bending response up to 80 Hz under AC. Moreover, high bending strain (0.63%) is achieved owing to the high ion migration in the composite electrolyte and electrode.
Elucidating the mechanism underlying the poor proliferative capacity of adult pancreatic β-cells is critical to regenerative therapeutic approaches for diabetes. Here, we show that the microRNA ...(miR)-7/7ab family member miR-7a is enriched in mouse adult pancreatic islets compared with miR-7b. Remarkably, miR-7a targets five components of the mTOR signaling pathway. Further, inhibition of miR-7a activates mTOR signaling and promotes adult β-cell replication in mouse primary islets, which can be reversed by the treatment with a well-known mTOR inhibitor, rapamycin. These data suggest that miR-7 acts as a brake on adult β-cell proliferation. Most importantly, this miR-7-mTOR proliferation axis is conserved in primary human β-cells, implicating miR-7 as a therapeutic target for diabetes.
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes ...respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). A Spike-enabled pseudo-entry virus infects pancreatic endocrine cells, liver organoids, cardiomyocytes, and dopaminergic neurons. Recent clinical studies show a strong association with COVID-19 and diabetes. We find that human pancreatic beta cells and liver organoids are highly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and adult hepatocyte and cholangiocyte organoids. SARS-CoV-2 infection caused striking expression of chemokines, as also seen in primary human COVID-19 pulmonary autopsy samples. hPSC-derived cells/organoids provide valuable models for understanding the cellular responses of human tissues to SARS-CoV-2 infection and for disease modeling of COVID-19.
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•A hPSC-derived cell and organoid platform is used to study SARS-CoV-2 tissue tropism•Human pancreatic alpha and beta cells are permissive to SARS-CoV-2 infection•Human hepatocyte and cholangiocyte organoids are permissive to SARS-CoV-2 infection•hPSC-derived cells/organoids show similar chemokine responses as COVID-19 tissues
Yang et al. show that hPSC-derived cells and organoids provide valuable models to study SARS-CoV-2 tropism and to model COVID-19. They find that hPSC-derived pancreatic endocrine cells and human adult hepatocyte and cholangiocyte organoids are permissive to SARS-CoV-2 infection.
Human pancreatic islets consist of multiple endocrine cell types. To facilitate the detection of rare cellular states and uncover population heterogeneity, we performed single-cell RNA sequencing ...(RNA-seq) on islets from multiple deceased organ donors, including children, healthy adults, and individuals with type 1 or type 2 diabetes. We developed a robust computational biology framework for cell type annotation. Using this framework, we show that α- and β-cells from children exhibit less well-defined gene signatures than those in adults. Remarkably, α- and β-cells from donors with type 2 diabetes have expression profiles with features seen in children, indicating a partial dedifferentiation process. We also examined a naturally proliferating α-cell from a healthy adult, for which pathway analysis indicated activation of the cell cycle and repression of checkpoint control pathways. Importantly, this replicating α-cell exhibited activated Sonic hedgehog signaling, a pathway not previously known to contribute to human α-cell proliferation. Our study highlights the power of single-cell RNA-seq and provides a stepping stone for future explorations of cellular heterogeneity in pancreatic endocrine cells.
The rate of population aging has reached a high level in China that age-friendly design should be concerned when designing gardens in urban place. Although the generation-skipping guardianship ...phenomenon always exists in present situation of elderly people in China that grandchildren are taken with the elderly and are involved in their daily activities in most family, the needs of children are neglected in urban garden design. The paper generalized guidelines of age-friendly garden design according to LEED, Chinese garden design standard, and the guideline of global age-friendly cities in Europe. Childrenfriendliness have also been included based on the above-mentioned new guidelines. 29 reports have been collected in the case study of WANSHOU Park which can be characterized as an age-friendly garden involving basic information and scoring records on its environment and facilities. Through the increasement of children-friendly features and installments in the park, the design will have great potential to deal with aging problems.
This study presents a novel micellar cubic ionic liquid‐crystalline polymer electrolyte, featuring an alignment‐free spherical structure with unimpeded 3D ionic pathways, aimed at enhancing the ...performance of an ionic electroactive polymer actuator. The development involved creating a mechanically tough and high ion‐conductive cubic polymer film through the self‐assembly of a wedge‐shaped vinyl imidazolium salt and an imidazolium ionic liquid, followed by in situ photopolymerization. The 300 µm‐thick‐trilayer films, consisting of the cubic polymer electrolyte sandwiched between poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) electrodes, exhibit remarkable capabilities. These include bearing substantial loads of 4 g with a high blocking force under a DC voltage of 2 V, achieving a high bending strain of 0.63% under a low input voltage (±2 V, 0.1 Hz), and boasting a maximum response frequency of 70 Hz. These properties position the material for potential applications in soft robots and tactile sensing devices.
The trilayer membrane actuator, comprising a photocured micellar cubic liquid‐crystalline polymer electrolyte between PEDOT:PSS electrodes, demonstrates remarkable performance with a force generation of 4 gf, a bending strain of 0.63%, and a high‐frequency response up to 70 Hz under 2 V. Its success is attributed to the intricate development of 3D connected ion pathways within the mechanically resilient film.
The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed ...assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. We employed this panel to analyze 12 pancreata obtained from donors with clinically diagnosed T1D and 6 pancreata from non-diabetic controls. In the pancreata from donors with T1D, we simultaneously visualized significant alterations in islet architecture, endocrine cell composition, and immune cell presentation. Indeed, we demonstrate the utility of IMC to investigate complex events on the cellular level that will provide new insights on the pathophysiology of T1D.
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•Imaging mass cytometry enables multiplexed histological analyses at 1-μm resolution•Islets are altered in architecture and composition during T1D progression•Islet cells show changes in protein expression during T1D progression•Immune cells are highly proliferative in T1D pancreata
Wang et al. use imaging mass cytometry (IMC) to profile the pancreata of type 1 diabetes donors at varying stages of disease progression. They see significant alterations in islet architecture, endocrine cell composition, and immune cell presentation, highlighting the utility of IMC to dissect cellular events underlying disease pathology.
Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in ...autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
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•SARS-CoV-2 viral antigen is detected in beta cells of autopsies of COVID-19 subjects•SARS-CoV-2 infection causes beta cell transdifferentiation•SARS-CoV-2-induced beta cell transdifferentiation is mediated by eIF2 pathway•Trans-ISRIB reverses SARS-CoV-2 infection-induced beta cell transdifferentiation
Here, Tang et al. reported the detection of SARS-CoV-2 viral antigen in autopsy samples from COVID-19 subjects. In addition, SARS-CoV-2 infection induces eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that can be reversed by trans-ISRIB.
Transplantation of stem cell-derived β (SC-β) cells represents a promising therapy for type 1 diabetes (T1D). However, the delivery, maintenance, and retrieval of these cells remain a challenge. ...Here, we report the design of a safe and functional device composed of a highly porous, durable nanofibrous skin and an immunoprotective hydrogel core. The device consists of electrospun medical-grade thermoplastic silicone-polycarbonate-urethane and is soft but tough (~15 megapascal at a rupture strain of >2). Tuning the nanofiber size to less than ~500 nanometers prevented cell penetration while maintaining maximum mass transfer and decreased cellular overgrowth on blank (cell-free) devices to as low as a single-cell layer (~3 micrometers thick) when implanted in the peritoneal cavity of mice. We confirmed device safety, indicated as continuous containment of proliferative cells within the device for 5 months. Encapsulating syngeneic, allogeneic, or xenogeneic rodent islets within the device corrected chemically induced diabetes in mice and cells remained functional for up to 200 days. The function of human SC-β cells was supported by the device, and it reversed diabetes within 1 week of implantation in immunodeficient and immunocompetent mice, for up to 120 and 60 days, respectively. We demonstrated the scalability and retrievability of the device in dogs and observed viable human SC-β cells despite xenogeneic immune responses. The nanofibrous device design may therefore provide a translatable solution to the balance between safety and functionality in developing stem cell-based therapies for T1D.
The deep network model relies on sufficient training samples to achieve superior processing performance, which limits its application in hyperspectral image (HSI) classification. In order to perform ...HSI classification with noisy labels, a robust weakly supervised feature learning (WSFL) architecture combined with multi-model attention is proposed. Specifically, the input noisy labeled data are first subjected to multiple groups of residual spectral attention models and multi-granularity residual spatial attention models, enabling WSFL to refine and optimize the extracted spectral and spatial features, with a focus on extracting clean samples information and reducing the model’s dependence on labels. Finally, the fused and optimized spectral-spatial features are mapped to the multilayer perceptron (MLP) classifier to increase the constraint of the model on the noisy samples. The experimental results on public datasets, including Pavia Center, WHU-Hi LongKou, and HangZhou, show that WSFL is better at classifying noise labels than excellent models such as spectral-spatial residual network (SSRN) and dual channel residual network (DCRN). On Hangzhou dataset, the classification accuracy of WSFL is superior to DCRN by 6.02% and SSRN by 7.85%, respectively.
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