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Cells often migrate on curved surfaces inside the body, such as curved tissues, blood vessels, or highly curved protrusions of other cells. Recent in vitro experiments provide clear evidence that motile cells are affected by the curvature of the substrate on which they migrate, preferring certain curvatures to others, termed "curvotaxis." The origin and underlying mechanism that gives rise to this curvature sensitivity are not well understood. Here, we employ a "minimal cell" model which is composed of a vesicle that contains curved membrane protein complexes, that exert protrusive forces on the membrane (representing the pressure due to actin polymerization). This minimal-cell model gives rise to spontaneous emergence of a motile phenotype, driven by a lamellipodia-like leading edge. By systematically screening the behavior of this model on different types of curved substrates (sinusoidal, cylinder, and tube), we show that minimal ingredients and energy terms capture the experimental data. The model recovers the observed migration on the sinusoidal substrate, where cells move along the grooves (minima), while avoiding motion along the ridges. In addition, the model predicts the tendency of cells to migrate circumferentially on convex substrates and axially on concave ones. Both of these predictions are verified experimentally, on several cell types. Altogether, our results identify the minimization of membrane-substrate adhesion energy and binding energy between the membrane protein complexes as key players of curvotaxis in cell migration.
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Actinas , Proteínas de Membrana , Movimento Celular , Fenômenos Físicos , Fenótipo , Actinas/metabolismoRESUMO
The momentum space Josephson effect describes the supercurrent flow between weakly coupled Bose-Einstein condensates (BECs) at two discrete momentum states. Here, we experimentally observe this exotic phenomenon using a BEC with Raman-induced spin-orbit coupling, where the tunneling between two local band minima is implemented by the momentum kick of an additional optical lattice. A sudden quench of the Raman detuning induces coherent spin-momentum oscillations of the BEC, which is analogous to the ac Josephson effect. We observe both plasma and regular Josephson oscillations in different parameter regimes. The experimental results agree well with the theoretical model and numerical simulation and showcase the important role of nonlinear interactions. We also show that the measurement of the Josephson plasma frequency gives the Bogoliubov zero quasimomentum gap, which determines the mass of the corresponding pseudo-Goldstone mode, a long-sought phenomenon in particle physics. The observation of momentum space Josephson physics offers an exciting platform for quantum simulation and sensing utilizing momentum states as a synthetic degree.
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In recent years, computer vision has witnessed remarkable advancements in image classification, specifically in the domains of fully convolutional neural networks (FCNs) and self-attention mechanisms. Nevertheless, both approaches exhibit certain limitations. FCNs tend to prioritize local information, potentially overlooking crucial global contexts, whereas self-attention mechanisms are computationally intensive despite their adaptability. In order to surmount these challenges, this paper proposes cross-and-diagonal networks (CDNet), innovative network architecture that adeptly captures global information in images while preserving local details in a more computationally efficient manner. CDNet achieves this by establishing long-range relationships between pixels within an image, enabling the indirect acquisition of contextual information. This inventive indirect self-attention mechanism significantly enhances the network's capacity. In CDNet, a new attention mechanism named "cross and diagonal attention" is proposed. This mechanism adopts an indirect approach by integrating two distinct components, cross attention and diagonal attention. By computing attention in different directions, specifically vertical and diagonal, CDNet effectively establishes remote dependencies among pixels, resulting in improved performance in image classification tasks. Experimental results highlight several advantages of CDNet. Firstly, it introduces an indirect self-attention mechanism that can be effortlessly integrated as a module into any convolutional neural network (CNN). Additionally, the computational cost of the self-attention mechanism has been effectively reduced, resulting in improved overall computational efficiency. Lastly, CDNet attains state-of-the-art performance on three benchmark datasets for similar types of image classification networks. In essence, CDNet addresses the constraints of conventional approaches and provides an efficient and effective solution for capturing global context in image classification tasks.
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Klebsiella pneumoniae (K. pneumoniae) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) K. pneumoniae in this study. The antibiofilm activity of FLD against K. pneumoniae was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within K. pneumoniae biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (AcrB, kexD, ketM, kdeA, and kpnE), outer membrane (OM) porin proteins (OmpK35, OmpK36), the quorum-sensing (QS) system (luxS), lipopolysaccharide (LPS) production (wzm), and EPS production (pgaA). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of G. mellonella infected with MDR K. pneumoniae. These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating K. pneumoniae infections.
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Cloridrato de Fingolimode , Klebsiella pneumoniae , Cloridrato de Fingolimode/farmacologia , Biofilmes , Percepção de Quorum , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
Platelet activation is closely related to thrombosis. Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterifying aspirin with eugenol using the pro-drug principle. Pharmacological and pharmacodynamic experiments showed that AEE has excellent anti-inflammatory, antioxidant, and inhibitory platelet activation effects, preventing thrombosis. However, the regulatory network and action target of AEE in inhibiting platelet activation remain unknown. This study aimed to investigate the effects of AEE on platelets of thrombosed rats to reveal its regulatory mechanism via a multi-omics approach. The platelet proteomic results showed that 348 DEPs were identified in the AEE group compared with the model group, of which 87 were up- and 261 down-regulated. The pathways in this result were different from previous results, including mTOR signaling and ADP signaling at P2Y purinoceptor 12. The metabolomics of heart and abdominal aortic tissue results showed that the differential metabolites were mainly involved in steroid biosynthesis, the citric acid cycle, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, and glutathione metabolism. Molecular docking results showed that AEE had a better binding force to both the COX-1 and P2Y12 protein. AEE could effectively inhibit platelet activation by inhibiting COX-1 protein and P2Y12 protein activity, thereby inhibiting platelet aggregation. Therefore, AEE can have a positive effect on inhibiting platelet activation.
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Aspirina , Plaquetas , Eugenol , Metabolômica , Simulação de Acoplamento Molecular , Proteômica , Trombose , Animais , Eugenol/farmacologia , Eugenol/análogos & derivados , Eugenol/uso terapêutico , Ratos , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Trombose/prevenção & controle , Trombose/metabolismo , Trombose/tratamento farmacológico , Aspirina/farmacologia , Aspirina/análogos & derivados , Proteômica/métodos , Metabolômica/métodos , Masculino , Modelos Animais de Doenças , Ativação Plaquetária/efeitos dos fármacos , Ratos Sprague-Dawley , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacosRESUMO
Bulk-edge correspondence, with quantized bulk topology leading to protected edge states, is a hallmark of topological states of matter and has been experimentally observed in electronic, atomic, photonic, and many other systems. While bulk-edge correspondence has been extensively studied in Hermitian systems, a non-Hermitian bulk could drastically modify the Hermitian topological band theory due to the interplay between non-Hermiticity and topology, and its effect on bulk-edge correspondence is still an ongoing pursuit. Importantly, including non-Hermicity can significantly expand the horizon of topological states of matter and lead to a plethora of unique properties and device applications, an example of which is a topological laser. However, the bulk topology, and thereby the bulk-edge correspondence, in existing topological edge-mode lasers is not well defined. Here, we propose and experimentally probe topological edge-mode lasing with a well-defined non-Hermitian bulk topology in a one-dimensional (1D) array of coupled ring resonators. By modeling the Hamiltonian with an additional degree of freedom (referred to as synthetic dimension), our 1D structure is equivalent to a 2D non-Hermitian Chern insulator with precise mapping. Our Letter may open a new pathway for probing non-Hermitian topological effects and exploring non-Hermitian topological device applications.
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Context: Approximately 1.5- to 2-million new patients suffer from stroke annually in China. 60% of patients suffering from stroke will sustain different degrees of upper limb dysfunction at six months after onset. Recovery of upper limb function after stroke is of great significance in improving patients' quality of life. Objective: The study intended to explore the rehabilitative the effects of transcranial direct current stimulation combined with neuromuscular joint therapy on the rehabilitation of patients with upper-limb motor disorders after strokes to provide new ideas for rehabilitative treatment. Design: The study was a paired control test. Setting: The study took place in the Department of Rehabilitation Medicine at Heping Hospital of Changzhi Medical College in Changzhi, Shanxi, China. Participants: Participants were 80 stroke patients with upper-limb motor disorders who were treated at the hospital between January 2020 and December 2020. Intervention: According to the natural grouping method, the research team divided participants into an intervention group (n = 42) and a control group (n = 38). The control group received transcranial direct-current stimulation, and the intervention group received transcranial direct-current stimulation combined with neuromuscular joint therapy. Outcome Measures: The measurements included the scores on the Fugl-Meyer Assessment (FMA) scale, the Action Research Arm Test (ARAT), activities of daily living (ADL), and National Institutes of Health Stroke Scale (NIHSS) as well as the serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and superoxide dismutase (SOD). The team also measured the maximum isometric torque of flexion and extension of the elbow joint. The research team compared the differences in the scores between the groups for all variables. Results: Postintervention, the FMA, ARAT, and ADL scores, the torques of elbow flexion and extension maximum isometric contraction, the amplitude, and the serum BDNF, NGF, and SOD levels were significantly higher in the intervention group than those in the control group, while the NIHSS score and the incubation period of evoked potential were significantly lower than those in the control group. Conclusions: Transcranial direct current stimulation combined with the neuromuscular joint method demonstrated good rehabilitative effects on upper-limb movement disorders for stroke patients and significantly improved their upper-limb function and promoted recovery of nerve functions.
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Transtornos Motores , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Estimulação Transcraniana por Corrente Contínua/métodos , Atividades Cotidianas , Fator Neurotrófico Derivado do Encéfalo , Reabilitação do Acidente Vascular Cerebral/métodos , Qualidade de Vida , Transtornos Motores/etiologia , Fator de Crescimento Neural , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Extremidade Superior , Resultado do TratamentoRESUMO
Intestinal inflammation is a complex and recurrent inflammatory disease. Pharmacological and pharmacodynamic experiments showed that aspirin eugenol ester (AEE) has good anti-inflammatory, antipyretic, and analgesic effects. However, the role of AEE in regulating intestinal inflammation has not been explored. This study aimed to investigate whether AEE could have a protective effect on LPS-induced intestinal inflammation and thus help to alleviate the damage to the intestinal barrier. This was assessed with an inflammation model in Caco-2 cells and in rats induced with LPS. The expression of inflammatory mediators, intestinal epithelial barrier-related proteins, and redox-related signals was analyzed using an enzyme-linked immunosorbent assay (ELISA), Western blotting, immunofluorescence staining, and RT-qPCR. Intestinal damage was assessed by histopathological examination. Changes in rat gut microbiota and their functions were detected by the gut microbial metagenome. AEE significantly reduced LPS-induced pro-inflammatory cytokine levels (p < 0.05) and oxidative stress levels in Caco-2 cells and rats. Compared with the LPS group, AEE could increase the relative expression of Occludin, Claudin-1, and zonula occludens-1 (ZO-1) and decrease the relative expression of kappa-B (NF-κB) and matrix metalloproteinase-9. AEE could significantly improve weight loss, diarrhea, reduced intestinal muscle thickness, and intestinal villi damage in rats. Metagenome results showed that AEE could regulate the homeostasis of the gut flora and alter the relative abundance of Firmicutes and Bacteroidetes. Flora enrichment analysis indicated that the regulation of gut flora with AEE may be related to the regulation of glucose metabolism and energy metabolism. AEE could have positive effects on intestinal inflammation-related diseases.
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Enteropatias , Lipopolissacarídeos , Humanos , Ratos , Animais , Lipopolissacarídeos/farmacologia , Células CACO-2 , Aspirina/farmacologia , Aspirina/metabolismo , Mucosa Intestinal/metabolismo , Inflamação/metabolismo , Eugenol/farmacologia , Eugenol/metabolismo , Enteropatias/metabolismoRESUMO
Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of H2O2-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of H2O2-induced oxidative damage in Caco-2 cells. In the Caco-2 cell transport model, it was observed that the uptake and transport of resveratrol (10, 20, 40, and 80 µM) were time dependent and concentration dependent. Different temperatures (37 °C vs. 4 °C) could significantly affect the uptake and transportation of resveratrol. The apical to basolateral transport of resveratrol was markedly reduced by STF-31, a GLUT1 inhibitor, and siRNA intervention. Furthermore, resveratrol pretreatment (80 µM) improves the viability of Caco-2 cells induced by H2O2. In a cellular metabolite analysis combined with ultra-high performance liquid chromatography-tandem mass spectrometry, 21 metabolites were identified as differentials. These differential metabolites belong to the urea cycle, arginine and proline metabolism, glycine and serine metabolism, ammonia recycling, aspartate metabolism, glutathione metabolism, and other metabolic pathways. The transport, uptake, and metabolism of resveratrol suggest that oral resveratrol could prevent intestinal diseases caused by oxidative stress.
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Antioxidantes , Peróxido de Hidrogênio , Humanos , Resveratrol/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Células CACO-2 , Transportador de Glucose Tipo 1/metabolismo , Peróxido de Hidrogênio/metabolismo , Transporte BiológicoRESUMO
All-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL) has been the most famous differentiation induction therapy during which the expression of PU.1, a key transcription factor (TF) for myeloid lineage determination in normal hematopoiesis is restored. In our previous studies, we found a stress-inducible H3K27 demethylase, JMJD3, to directly upregulate PU.1 expression to promote myeloid commitment during normal myelopoiesis. In addition, JMJD3 acts as an oncorepressor and plays a critical regulatory role in the initiation and progression of malignant hematopoiesis. In this study, we further resolved the relationship between JMJD3 and PU.1 in APL therein JMJD3 exerts oncorepressor activity via promoting PU.1 expression.
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Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Transativadores/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Tretinoína/farmacologia , Tretinoína/uso terapêutico , Fatores de Transcrição/genética , Diferenciação CelularRESUMO
The higher-order topological insulator (HOTI) is a new type of topological system which has special bulk-edge correspondence compared with conventional topological insulators. In this work, we propose a scheme to realize Floquet HOTI with ultracold atoms in optical lattices. With the combination of periodically spin-dependent driving of the superlattices and a long-range coupling term, a Floquet second-order topological insulator with four zero-energy corner states emerges, whose Wannier bands are gapless and exhibit interesting bulk topology. Furthermore, the nearest-neighbor anisotropic coupling term also induced other intriguing topological phenomena, e.g. non-topologically protected corner states and topological semimetal for two different types of lattice structures respectively. Our scheme may give insight into the construction of different types of higher-order topological insulators in synthetic systems. It also provides an experimentally feasible platform to research the relations between different types of topological states and may have a wide range of applications in future.
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The emergence of parity-time (PT) symmetry has greatly enriched our study of symmetry-enabled non-Hermitian physics, but the realization of quantum PT symmetry faces an intrinsic issue of unavoidable symmetry-breaking Langevin noises. Here we construct a quantum pseudo-anti-PT (pseudo-APT) symmetry in a two-mode bosonic system without involving Langevin noises. We show that the spontaneous pseudo-APT symmetry breaking leads to an exceptional point, across which there is a transition between different types of quantum squeezing dynamics; i.e., the squeezing factor increases exponentially (oscillates periodically) with time in the pseudo-APT-symmetric (broken) region. Such dramatic changes of squeezing factors and quantum dynamics near the exceptional point are utilized for ultraprecision quantum sensing. These exotic quantum phenomena and sensing applications can be experimentally observed in two physical systems: spontaneous wave mixing nonlinear optics and atomic Bose-Einstein condensates. Our Letter offers a physical platform for investigating exciting APT symmetry physics in the quantum realm, paving the way for exploring fundamental quantum non-Hermitian effects and their quantum technological applications.
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Triply degenerate points (TDPs), which correspond to new types of topological semimetals, can support novel quasiparticles possessing effective integer spins while preserving Fermi statistics. Here by mapping the momentum space to the parameter space of a three-level system in a trapped ion, we experimentally explore the transitions between different types of TDPs driven by spin-tensor-momentum couplings. We observe the phase transitions between TDPs with different topological charges by measuring the Berry flux on a loop surrounding the gap-closing lines, and the jump of the Berry flux gives the jump of the topological charge (up to a 2π factor) across the transitions. For the Berry flux measurement, we employ a new method by examining the geometric rotations of both spin vectors and tensors, which lead to a generalized solid angle equal to the Berry flux. The controllability of a multilevel ion offers a versatile platform to study high-spin physics, and our Letter paves the way to explore novel topological phenomena therein.
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Organoids have been widely used in fundamental, biomimetic, and therapeutic studies. These multicellular systems form via cell-autonomous self-organization where a cohort of stem cells undergoes in vivo-like proliferation, differentiation, and morphogenesis. They also recapitulate a series of physiological cell organization, complexity and functions that are untouchable by conventional bio-model systems using immortal cell lines. However, the development of organoids is often not easily controlled and their shape and size are yet fully physiological. Recent research has demonstrated that multiple bioengineering tools could be harnessed to control important internal and external cues that dictate stem cell behavior and stem-cell based organoid development. In this review, we introduce the current development of organoid systems and their potentials, as well as their limitations that impede their further utility in research and clinical fields. In comparison to conventional autonomous organoid system, we then review bioengineering approaches that offer improved control over organoid growth and development. We focus on the genetic editing tools that allow the program of build-in responses and phenotypes for organoid systems with enhanced physiological relevance. We also highlight the advances in bioengineering methods to modify cellular external milieus to generate desirable cell composition, 3D micro-architectures, and complex microfluidic systems. We conclude that the emerging biomimetic methods that employ multidisciplinary approaches could prevail in the future development of organoid systems.
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Bioengenharia , Organoides , Diferenciação Celular , Humanos , Células-TroncoRESUMO
BACKGROUND: Inflammation plays a key role in the initiation and progression of atrial fibrillation (AF). Lymphocyte-to-monocyte ratio (LMR) has been proved to be a reliable predictor of many inflammation-associated diseases, but little data are available on the relationship between LMR and AF. We aimed to evaluate the predictive value of LMR in predicting all-cause mortality among AF patients. METHODS: Data of patients diagnosed with AF were retrieved from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. X-tile analysis was used to calculate the optimal cutoff value for LMR. The Cox regression model was used to assess the association of LMR and 28-day, 90-day, and 1-year mortality. Additionally, a propensity score matching (PSM) method was performed to minimize the impact of potential confounders. RESULTS: A total of 3567 patients hospitalized with AF were enrolled in this study. The X-tile software indicated that the optimal cutoff value of LMR was 2.67. A total of 1127 pairs were generated, and all the covariates were well balanced after PSM. The Cox proportional-hazards model showed that patients with the low LMR (≤2.67) had a higher 1-year all-cause mortality than those with the high LMR (>2.67) in the study cohort before PSM (HR = 1.640, 95% CI: 1.437-1.872, p < 0.001) and after PSM (HR = 1.279, 95% CI: 1.094-1.495, p = 0.002). The multivariable Cox regression analysis for 28-day and 90-day mortality yielded similar results. CONCLUSIONS: The lower LMR (≤2.67) was associated with a higher risk of 28-day, 90-day, and 1-year all-cause mortality, which might serve as an independent predictor in AF patients.
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Fibrilação Atrial/imunologia , Linfócitos , Monócitos , Pontuação de Propensão , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Feminino , Humanos , Contagem de Leucócitos , Masculino , Prognóstico , Modelos de Riscos ProporcionaisRESUMO
AIM: It is known that miR-504 can target p53 to promote cancer progression. Our bioinformatics analysis revealed that miR-504 could bind miR-143 host gene (miR143HG), suggesting that miR143HG might also have crosstalk with p53 in cancer progression. This study aimed to analyze the function of miR143HG in glioblastoma (GBM). METHODS: This study selected 64 GBM patients. GBM and non-tumor tissues were obtained from the patients. RT-qPCR was used to analyze gene expression. Survival curve analysis was performed to analyze the prognostic values of miR143HG for GBM. The crosstalk between miR143HG and miR-504 was analyzed by overexpressing them in GBM cells, followed by RT-qPCRs to detect their expression. CCK-8 assay was used to detect the cell proliferation ability. RESULTS: We found that miR143HG was downregulated in GBM and predicted poor survival. The mRNA expression levels of miR143HG and p53 were positively correlated in GBM tissues. Bioinformatics analysis suggested that miR143HG could form base paring with miR-504, which has been reported to target p53. Overexpression experiments revealed that miR143HG overexpression upregulated the expression of p53, while miR-504 overexpression inhibited the effect of miR143HG overexpression on the expression of p53. Moreover, overexpression of miR143HG and p53 decreased GBM cell proliferation, while overexpression of miR-504 increased GBM cell proliferation. In addition, overexpression of miR-504 attenuated the effect of miR143HG overexpression on GBM cell proliferation. CONCLUSION: Therefore, miR143HG may decrease the proliferation of GBM cells by sponging miR-504 to upregulate p53.
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Glioblastoma , MicroRNAs , RNA Longo não Codificante , Humanos , Glioblastoma/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Movimento Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , RNA Mensageiro , Regulação Neoplásica da Expressão Gênica/genéticaRESUMO
Insulin secretion by pancreatic islet ß-cells is regulated by glucose levels and is accompanied by proton generation. The voltage-gated proton channel Hv1 is present in pancreatic ß-cells and extremely selective for protons. However, whether Hv1 is involved in insulin secretion is unclear. Here we demonstrate that Hv1 promotes insulin secretion of pancreatic ß-cells and glucose homeostasis. Hv1-deficient mice displayed hyperglycemia and glucose intolerance because of reduced insulin secretion but retained normal peripheral insulin sensitivity. Moreover, Hv1 loss contributed much more to severe glucose intolerance as the mice got older. Islets of Hv1-deficient and heterozygous mice were markedly deficient in glucose- and K+-induced insulin secretion. In perifusion assays, Hv1 deletion dramatically reduced the first and second phase of glucose-stimulated insulin secretion. Islet insulin and proinsulin content was reduced, and histological analysis of pancreas slices revealed an accompanying modest reduction of ß-cell mass in Hv1 knockout mice. EM observations also indicated a reduction in insulin granule size, but not granule number or granule docking, in Hv1-deficient mice. Mechanistically, Hv1 loss limited the capacity for glucose-induced membrane depolarization, accompanied by a reduced ability of glucose to raise Ca2+ levels in islets, as evidenced by decreased durations of individual calcium oscillations. Moreover, Hv1 expression was significantly reduced in pancreatic ß-cells from streptozotocin-induced diabetic mice, indicating that Hv1 deficiency is associated with ß-cell dysfunction and diabetes. We conclude that Hv1 regulates insulin secretion and glucose homeostasis through a mechanism that depends on intracellular Ca2+ levels and membrane depolarization.
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Intolerância à Glucose/complicações , Intolerância à Glucose/metabolismo , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Secreção de Insulina , Canais Iônicos/metabolismo , Envelhecimento/patologia , Animais , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Tamanho Celular , Grânulos Citoplasmáticos/metabolismo , Grânulos Citoplasmáticos/ultraestrutura , Citosol/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Regulação para Baixo/efeitos dos fármacos , Deleção de Genes , Glucose/farmacologia , Concentração de Íons de Hidrogênio , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Células Secretoras de Insulina/ultraestrutura , Canais Iônicos/deficiência , Canais Iônicos/genética , Potenciais da Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Narrowband mid-infrared emitters, quantified by the Q-factor, have garnered a lot of attention due to their emerging applications from chemical and biosensing to efficient thermal utilization. Previous studies reported high Q-factor emitters within several selected wavelengths, still lacking a large database of emitter structures with very high Q-factors. In this Letter, we utilized the Monte Carlo Tree Search (MCTS) algorithm under the framework of material informatics to optimize the Tamm emitters at the infrared range (from 3 to 10 µm) for achieving a high Q-factor and high emissivity simultaneously, providing a large database of high and sharp emission peaks in the infrared. Through the MCTS algorithm, the structure with a Q-factor of 508 and an emissivity peak of 0.92 at 4.225 µm is obtained, far surpassing the previous results, and the underlying mechanism is discussed by electric field simulations. The high Q-factor emitters in the database show good monochromatism and high emissivity, accelerating the selection of proper perfect emitters for desired wavelengths. This Letter also paves a feasible avenue for the emitter and absorber design with ultrahigh monochromatism.
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Moiré superlattices in twisted bilayer graphene and transition-metal dichalcogenides have emerged as a powerful tool for engineering novel band structures and quantum phases of two-dimensional quantum materials. Here we investigate Moiré physics emerging from twisting two independent hexagonal optical lattices of atomic (pseudo-)spin states (instead of bilayers) that exhibit remarkably different physics from twisted bilayer graphene. We employ a momentum-space tight-binding calculation that includes all range real-space tunnelings and show that all twist angles θâ²6° can become magic and support gapped flat bands. Because of the greatly enhanced density of states near the flat bands, the system can be driven to superfluidity by weak attractive interaction. Strikingly, the superfluid phase corresponds to a Larkin-Ovchinnikov state with finite momentum pairing that results from the interplay between flat bands and interspin interactions in the unique single-layer spin-twisted lattice. Our work may pave the way for exploring novel quantum phases and twistronics in cold atomic systems.
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The scope of analog simulation in atomic, molecular, and optical systems has expanded greatly over the past decades. Recently, the idea of synthetic dimensions-in which transport occurs in a space spanned by internal or motional states coupled by field-driven transitions-has played a key role in this expansion. While approaches based on synthetic dimensions have led to rapid advances in single-particle Hamiltonian engineering, strong interaction effects have been conspicuously absent from most synthetic dimensions platforms. Here, in a lattice of coupled atomic momentum states, we show that atomic interactions result in large and qualitative changes to dynamics in the synthetic dimension. We explore how the interplay of nonlinear interactions and coherent tunneling enriches the dynamics of a one-band tight-binding model giving rise to macroscopic self-trapping and phase-driven Josephson dynamics with a nonsinusoidal current-phase relationship, which can be viewed as stemming from a nonlinear band structure arising from interactions.