Single-Cell RNA Sequencing Reveals the Tumor Heterogeneity and Immunosuppressive Microenvironment in Urothelial Carcinoma.

Urothelial carcinoma (UC) can arise from either the lower urinary tract or the upper tract; they represent different disease entities and require different clinical treatment strategies. A full understanding of the cellular characteristics in UC may guide the development of novel therapies. Here, we performed single-cell transcriptome analysis from four patients with UC of the bladder (UCB), five patients with UC of the ureter (UCU), and four patients with UC of the renal pelvis (UCRP) to develop a comprehensive cell atlas of UC.

Artificial Nanovesicles Derived from Cells: A Promising Alternative to Extracellular Vesicles.

As naturally secreted vesicles by cells, extracellular vesicles (EVs) play essential roles in modulating cell-cell communication and have significant potential in tissue regeneration, immune regulation, and drug delivery. However, the low yield and uncontrollable heterogeneity of EVs have been obstacles to their widespread translation into clinical practice. Recently, it has been discovered that artificial nanovesicles (NVs) produced by cell processing can inherit the components and functions of the parent cells and possess similar structures and functions to EVs, with significantly higher yields and more flexible functionalization, making them a powerful complement to natural EVs.

Characteristics of T-Cell Receptor Repertoire for Differential Response to Methotrexate Treatment for Rheumatoid Arthritis.

Background: Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated.

DNA Origami-Constructed Nanotapes for Sunitinib Adsorption and Inhibition of Renal Clear Carcinoma Cells.

Sunitinib (SUN) is a first-line drug for the treatment of renal clear carcinoma cells by targeting receptor tyrosine kinases (RTK) on the cell membrane. However, the effective delivery of SUN to the cell membrane remains a significant challenge. In this study, we fabricated precisely structured DNA nanotapes with strong surface SUN adhesion, enabling RTK inhibition of renal clear carcinoma cells.

Extracellular Vesicle Spherical Nucleic Acids.

Extracellular vesicles (EVs) are naturally occurring vesicles secreted by cells that can transport cargo between cells, making them promising bioactive nanomaterials. However, due to the complex and heterogeneous biological characteristics, a method for robust EV manipulation and efficient EV delivery is still lacking. Here, we developed a novel class of extracellular vesicle spherical nucleic acid (EV-SNA) nanostructures with scalability, programmability, and efficient cellular delivery.

Identification of novel protein biomarkers from the blood and urine for the early diagnosis of bladder cancer via proximity extension analysis.

Background: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC.

Methods: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique.

Directing the Encapsulation of Single Cells with DNA Framework Nucleator-Based Hydrogel Growth.

Encapsulating individual mammalian cells with biomimetic materials holds potential in ex vivo cell culture and engineering. However, current methodologies often present tradeoffs between homogeneity, stability, and cell compatibility. Here, inspired by bacteria that use proteins stably anchored on their outer membranes to nucleate biofilm growth, we develop a single-cell encapsulation strategy by using a DNA framework structure as a nucleator (DFN) to initiate the growth of DNA hydrogels under cell-friendly conditions.

Centrifugal Flows Drive Reverse Rotation of Feynman's Sprinkler.

The issue of reversibility in hydromechanical sprinklers that auto-rotate while ejecting fluid from S-shaped tubes raises fundamental questions that remain unresolved. Here, we report on precision experiments that reveal robust and persistent reverse rotation under suction and a model that accounts for the observed motions. We implement an ultralow friction bearing in an apparatus that allows for free rotation under ejection and suction for a range of flow rates and arbitrarily long times.

Covalently hybridized carbon dots@mesoporous silica nanobeads as a robust and versatile phosphorescent probe for time-resolved biosensing and bioimaging.

Phosphorescence analyses have attracted broad attention due to their remarkable merits of the elimination of auto-fluorescence and scattering light. However, it remains a great challenge to develop novel materials with uniform size and morphology, stability, long lifetime, and aqueous-phase room temperature phosphorescence (RTP) characteristics. Herein, monodisperse and uniform RTP nanobeads were fabricated by an covalent hybridization of carbon dots (CDs) and dendritic mesoporous silicon nanoparticles (DMSNs) silane hydrolysis.

DNA Nanomaterial-Empowered Surface Engineering of Extracellular Vesicles.

Extracellular vesicles (EVs) are cell-secreted biological nanoparticles that are critical mediators of intercellular communication. They contain diverse bioactive components, which are promising diagnostic biomarkers and therapeutic agents. Their nanosized membrane-bound structures and innate ability to transport functional cargo across major biological barriers make them promising candidates as drug delivery vehicles.

DNA-Programmed Stem Cell Niches via Orthogonal Extracellular Vesicle-Cell Communications.

Extracellular vesicles (EVs) are natural carriers for intercellular transfer of bioactive molecules, which are harnessed for wide biomedical applications. However, a facile yet general approach to engineering interspecies EV-cell communications is still lacking. Here, the use of DNA to encode the heterogeneous interfaces of EVs and cells in a manner free of covalent or genetic modifications is reported, which enables orthogonal EV-cell interkingdom interactions in complex environments.

Persistent corotation of the large-scale flow of thermal convection and an immersed free body.

Inspired by the superrotation of the Earth's solid core, we investigate the dynamics of a free-rotating body as it interacts with the large-scale circulation (LSC) of the Rayleigh-Bénard thermal convection in a cylindrical container. A surprising and persistent corotation of both the free body and the LSC emerges, breaking the axial symmetry of the system. The corotational speed increases monotonically with the intensity of thermal convection, measured by the Rayleigh number Ra, which is proportional to the temperature difference between the heated bottom and cooled top.

MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.

Purpose: Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms.

Patients And Methods: In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy.

3D diversiform dynamic process of microvilli in living cells.

Microvilli are membrane protrusions involved in many membrane-associated physiological processes. Previous studies have focused on the dynamics of individual microvilli, however, the morphological classification of microvilli and the dynamics of microvillar clusters as the basic functional domain remain largely unknown. Here we used atomic force microscopy (AFM) to achieve nanoscale resolution 3D microvilli images of living HeLa cells.

Programmable DNA Hydrogels as Artificial Extracellular Matrix.

The cell microenvironment plays a crucial role in regulating cell behavior and fate in physiological and pathological processes. As the fundamental component of the cell microenvironment, extracellular matrix (ECM) typically possesses complex ordered structures and provides essential physical and chemical cues to the cells. Hydrogels have attracted much attention in recapitulating the ECM.

Exosomes mediate an epithelial-mesenchymal transition cascade in retinal pigment epithelial cells: Implications for proliferative vitreoretinopathy.

Exosomes have recently emerged as a pivotal mediator of many physiological and pathological processes. However, the role of exosomes in proliferative vitreoretinopathy (PVR) has not been reported. In this study, we aimed to investigate the role of exosomes in PVR.

Label-Free and Three-Dimensional Visualization Reveals the Dynamics of Plasma Membrane-Derived Extracellular Vesicles.

Plasma membrane-derived extracellular vesicles (PEVs) are carriers of biological molecules that perform special cell-cell communications. Nevertheless, the characterization of complicated PEV biology is hampered by the failure of current methods, mainly due to lack of specific labels and insufficient resolution. Here, we employed atomic force microscopy and scanning ion conductance microscopy, both capable of three-dimensional nanoscale resolution, for the label-free visualization of the PEV morphology, release, and uptake at the single-vesicle level.

[Progress in extracellular vesicle imaging methods].

Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer-enclosed nanovesicles secreted by cells. These EVs are important mediators of intercellular communication by serving as vehicles for transfer of proteins, mRNA, miRNA and lipids between cells. Various visualization methods have been established to explore the characteristics of EVs and their role in physiological and pathological processes.

Spatial high resolution of actin filament organization by PeakForce atomic force microscopy.

Objectives: To investigate the heterogeneous feature of actin filaments (ACFs) associated with the cellular membrane in HeLa and HCT-116 cells at the nanoscale level.

Materials And Methods: Fluorescence microscopy coupled with atomic force microscopy (AFM) was used to identify and characterize ACFs of cells. The distribution of ACFs was detected by Fluor-488-phalloidin-labelled actin.

Atomic force microscopy-based single-molecule force spectroscopy detects DNA base mismatches.

Atomic force microscopy-based single-molecule-force spectroscopy is limited by low throughput. We introduce addressable DNA origami to study multiple target molecules. Six target DNAs that differed by only a single base-pair mismatch were clearly differentiated a rupture force of only 4 pN.

Starvation effect on the morphology of microvilli in HeLa cells.

Microvilli are membrane protrusions enabling the increase of the cell surface area by over hundreds fold, thereby enhancing nutrition absorption. However, the correlation between the morphology of the microvilli and absorption capability of cells remains elusive. Herein, by combining atomic force microscopy with fluorescence microscopy, we explored the effects of starvation on the morphology of microvilli in HeLa cells at the single cell level.

Mechanical Stress-Dependent Autophagy Component Release via Extracellular Nanovesicles in Tumor Cells.

Tumor cells metastasizing through the bloodstream or lymphatic systems must withstand acute shear stress (ASS). Autophagy is a cell survival mechanism that functions in response to stressful conditions, but also contributes to cell death or apoptosis. We predicted that a compensation pathway to autophagy exists in tumor cells subjected to mechanical stress.

Induced neural progenitor cells abundantly secrete extracellular vesicles and promote the proliferation of neural progenitors via extracellular signal-regulated kinase pathways.

Neural stem/progenitor cells (NPCs) are known to have potent therapeutic effects in neurological disorders through the secretion of extracellular vesicles (EVs). Despite the therapeutic potentials, the numbers of NPCs are limited in the brain, curbing the further use of EVs in the disease treatment. To overcome the limitation of NPC numbers, we used a three transcription factor (Brn2, Sox2, and Foxg1) somatic reprogramming approach to generate induced NPCs (iNPCs) from mouse fibroblasts and astrocytes.

[Progress in the applications of high-speed atomic force microscopy in cell biology].

Without losing its high resolution, high-speed atomic force microscope (HS-AFM) represents a perfect combinationof scanning speed and precision and allows real-time and observation of the dynamic processes in a biological system atboth the cellular and molecular levels. By combining the extremely high temporal resolution with the spatial resolution andcoupling with other advanced technologies, HS-AFM shows promising prospects for applications in life sciences such as cellbiology. In this review, we summarize the latest progress of HS-AFM in the field of cell biology, and discuss the impact ofenvironmental factors on conformation dynamics of DNA, the binding processes between DNA and protein, the domainchanges of membrane proteins, motility of myosin, and surface structure changes of living cells.