Biomaterials and tissue engineering in traumatic brain injury: novel perspectives on promoting neural regeneration.

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Ultrasmall single-layered NbSe2 nanotubes flattened within a chemical-driven self-pressurized carbon nanotube.

Pressure can alter interatomic distances and its electrostatic interactions, exerting a profound modifying effect on electron orbitals and bonding patterns. Conventional pressure engineering relies on compressions from external sources, which raises significant challenge in precisely applying pressure on individual molecules and also consume substantial mechanical energy. Here we report ultrasmall single-layered NbSe2 flat tubes (< 2.31 nm) created by self-pressurization during the deselenization of NbSe3 within carbon nanotubes (CNTs). As the internal force (4-17 GPa) is three orders of magnitude larger than the shear strength between CNTs, the flat tube is locked to prevent slippage. Electrical transport measurements indicate that the large pressure within CNTs induces enhanced intermolecular electron correlations. The strictly one-dimensional NbSe2 flat tubes harboring the Luttinger liquid (LL) state, showing a higher tunneling exponent [Formula: see text] than pure CNTs ([Formula: see text]). This work suggests a novel chemical approach to self-pressurization for generating new material configurations and modulating electron interactions.

Synthesis of 12-Connected Three-Dimensional Covalent Organic Framework with lnj Topology.

The structural exploration of three-dimensional covalent organic frameworks (3D COFs) is of great significance to the development of COF materials. Different from structurally diverse MOFs, which have a variety of connectivity (3-24), now the valency of 3D COFs is limited to only 4, 6, and 8. Therefore, the exploration of organic building blocks with higher connectivity is a necessary path to broaden the scope of 3D COF structures. Herein, for the first time, we have designed and synthesized a 12-connected triptycene-based precursor (triptycene-12-CHO) with 12 symmetrical distributions of aldehyde groups, which is also the highest valency reported until now. Based on this unique 12-connected structure, we have successfully prepared a novel 3D COF with lnj topology (termed 3D-lnj-COF). The as-synthesized 3D COF exhibits honeycomb main pores and permanent porosity with a Brunauer-Emmett-Teller surface area of 1159.6 m2 g-1. This work not only provides a strategy for synthesizing precursors with a high connectivity but also provides inspiration for enriching the variety of 3D COFs.

Fluidization and Application of Carbon Nano Agglomerations.

Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small-size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas-solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self-similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle-fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era.

Application of CRISPR/Cas9-based genome editing in ecotoxicology.

Chemicals are widely used and released into the environment, and their degradation, accumulation, migration, and transformation processes in the environment can pose a threat to the ecosystem. The advancement in analytical methods with high-throughput screening of biomolecules has revolutionized the way toxicologists used to explore the effects of chemicals on organisms. CRISPR/Cas is a newly developed tool, widely used in the exploration of basic science and biologically engineered products given its high efficiency and low cost. For example, it can edit target genes efficiently, and save loss of the crop yield caused by environmental pollution as well as gain a better understanding of the toxicity mechanisms from various chemicals. This review briefly introduces the development history of CRISPR/Cas and summarizes the current application of CRISPR/Cas in ecotoxicology, including its application on improving crop yield and drug resistance towards agricultural pollution, antibiotic pollution and other threats. The benefits by applying the CRISPR/Cas9 system in conventional toxicity mechanism studies are fully demonstrated here together with its foreseeable expansions in other area of ecotoxicology. Finally, the prospects and disadvantages of CRISPR/Cas system in the field of ecotoxicology are also discussed.

Effect of implantable cardiac monitors on preventing stroke: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND AND AIM: Implantable cardiac monitors (ICM) can facilitate the detection of asymptomatic atrial fibrillation episodes. We performed a systematic review and meta-analysis to investigate whether ICM can prevent stroke in patients with prior stroke and risk factors for stroke. METHODS: This study included randomized controlled trials comparing ICM with conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. We searched Medline, Embase, and CENTRAL from inception until January 5, 2022, without language restriction. Quantitative pooling of the data was undertaken using a random-effects model. The primary outcome was ischemic stroke at the longest follow-up. RESULTS: Four trials comprising 7237 patients were included. ICM was significantly associated with decreased risk of ischemic stroke (RR 0.76; 95% CI, 0.59-0.97; moderate-quality evidence) in patients with prior stroke and risk factors for stroke. ICM was associated with higher detection of atrial fibrillation (RR 4.21, 95% CI 2.26-7.85) and use of oral anticoagulants (RR 2.29, 95% CI 2.07-2.55). CONCLUSIONS: ICM results in a significantly lower risk of ischemic stroke than conventional (non-ICM) external cardiac monitoring in patients with prior stroke and risk factors for stroke. Due to the clinical heterogeneity of study population and limited related studies, more trials were needed to furtherly explore the topic in patients with prior stroke or high risk of stroke.

Molecular Evolutionary Growth of Ultralong Semiconducting Double-Walled Carbon Nanotubes.

The self-assembling preparation accompanied with template auto-catalysis loop and the ability to gather energy, induces the appearance of chirality and entropy reduction in biotic systems. However, an abiotic system with biotic characteristics is of great significance but still missing. Here, it is demonstrated that the molecular evolution is characteristic of ultralong carbon nanotube preparation, revealing the advantage of chiral assembly through template auto-catalysis growth, stepwise-enriched chirality distribution with decreasing entropy, and environmental effects on the evolutionary growth. Specifically, the defective and metallic nanotubes perform inferiority to semiconducting counterparts, among of which the ones with double walls and specific chirality (n, m) are more predominant due to molecular coevolution. An explicit evolutionary trend for tailoring certain layer chirality is presented toward perfect near-(2n, n)-containing semiconducting double-walled nanotubes. These findings extend our conceptual understanding for the template auto-catalysis assembly of abiotic carbon nanotubes, and provide an inspiration for preparing chiral materials with kinetic stability by evolutionary growth.

Distinct binding mode of BAFF antagonist antibodies belimumab and tabalumab, analyzed by computer simulation.

B cell-activating factor (BAFF) can bind with specific receptors to activate signalling pathways associated with the B cell activation. Belimumab and tabalumab are anti-BAFF (B cell depleting) monoclonal antibodies, with therapeutic efficacy demonstrated for the treatment of autoimmune disorders, while belimumab was approved by FDA in 2011 as a targeted therapy for systemic lupus erythematosus (SLE) and exhibited better clinical outcome than tabalumab. In this investigation, the combination modes of BAFF-belimumab and BAFF-tabalumab complexes were simulated in silico to better understand the reason for the comparative inhibitory difference between belimumab and tabalumab. The structures of belimumab and tabalumab were constructed through homology modelling. The combination mode of BAFF-belimumab complex was analyzed by molecular dynamics simulation, while that of BAFF-tabalumab complex was analyzed by protein-protein docking following the molecular dynamics simulation. Both belimumab and tabalumab were bound with BAFF at the same hydrophobic center to which the natural receptors of BAFF bind as well. Belimumab heavy chain components I51, F54, K58, D100, D101, L102, L103, and P105 and R27, Y30, K49, and S65 of belimumab light chain contribute to the BAFF-belimumab interaction mainly via hydrogen bonds, salt bridges, and hydrophobic interactions. More importantly, belimumab could bind to L83 of BAFF and produce steric hindrance with the adjacent BAFF trimers, while tabalumab could not. Therefore, our results indicated that belimumab has a better clinical outcome compared with tabalumab mainly because belimumab could bind to L83 of BAFF and interfere the formation of a BAFF 60-mer, besides mediating inhibition of the interaction of BAFF with its receptors.

New therapeutic strategies based on biasing IL-2 mutants for cancers and autoimmune diseases.

Interleukin-2 (IL-2) is an immunomodulatory multifunctional cytokine. High-dose IL-2 was first approved by the U.S. Food and Drug Administration (FDA) in the 1990s for the treatment of metastatic renal cell carcinoma and metastatic melanoma. However, the short half-life of IL-2 and its toxicity caused by high-dose IL-2 limit the clinical use of IL-2. Recently, the development of cell-type-selective engineered IL-2 products become a hot research filed, mainly because IL-2 stimulates both regulatory T cells (Treg) and effector T cells (Teff) in vivo. The selective effect of IL-2 on Treg and Teff can be improved by designing biased IL-2 mutants, which showed reduced toxicity while being more effective in stimulating anti-tumor effector immunity or ameliorating autoimmune diseases. In this review we summarize the biological properties of IL-2 mutants reported so far. The design process and principle of IL-2 mutants, IL-2 mutant antibody complexes and IL-2 fusion proteins were discussed, which provided research basis for the design and application of IL-2 mutants in the future.

Elements of chronic disease management service system: an empirical study from large hospitals in China.

At present, more patients suffer from multiple chronic diseases. However, the hospital's existing chronic disease management is carried out according to the department. This means that a patient needs to go to more than one department for a chronic disease treatment. Therefore, this study proposes 6 dimensions (organizational management, medical service support, medical service, community alliance, self-management support, management information system) and 36 questions, to help evaluate the current chronic disease management system in China's large third-class hospitals. In this study, 143 survey samples from doctors and nurses were collected. A principal component analysis was used to extract three key elements of chronic disease management service delivery system (service management organization, management information system, medical core service). Then, multiple regression was used to establish the relationship model between the overall performance of the system and the main elements. Three key service nodes of the system (medical specialist support, patient tracking management and personalized intervention) were determined according to the weight of the regression model. The regression coefficients of the above three main elements show a similar impact on the overall performance of the system, but the key service nodes under each major element have relative differences, including medical specialist support, patient tracking management and personalized intervention. Finally, to establish a chronic disease management system with multiple departmental continuous care for chronic diseases, it is necessary to improve the chronic disease management system from three aspects of medical specialty support, patient tracking management and personalized intervention. This paper proposes corresponding improvement strategies.

Three-dimensional quantification of circulation using finite-element methods in four-dimensional flow MR data of the thoracic aorta.

PURPOSE: Three-dimensional (3D) quantification of circulation using a Finite Elements methodology. METHODS: We validate our 3D method using an in-silico arch model, for different mesh resolutions, image resolution and noise levels, and we compared this with a currently used 2D method. Finally, we evaluated the application of our methodology in 4D Flow MRI data of ascending aorta of six healthy volunteers, and six bicuspid aortic valve (BAV) patients, three with right and three with left handed flow, at peak systole. The in-vivo data was compared using a Mann-Whitney U-test between volunteers and patients (right and left handed flow). RESULTS: The robustness of our method throughout different image resolutions and noise levels showed subestimation of circulation less than 45 cm2 /s in comparison with the 55cm2 /s generated by the current 2D method. The circulation (mean ± SD) of the healthy volunteer group was 13.83 ± 28.78 cm2 /s, in BAV patients with right-handed flow 724.37 ± 317.53 cm2 /s, and BAV patients with left-handed flow -480.99 ± 387.29 cm2 /s. There were significant differences between healthy volunteers and BAV patients groups (P-value < .01), and also between BAV patients with a right-handed or left-handed helical flow and healthy volunteers (P-value < .01). CONCLUSION: We propose a novel 3D formulation to estimate the circulation in the thoracic aorta, which can be used to assess the differences between normal and diseased hemodynamic from 4D-Flow MRI data. This method also can correctly differentiate between the visually seen right- and left-handed helical flow, which suggests that this approach may have high clinical sensitivity, but requires confirmation in longitudinal studies with a large cohort.

Effect of lncRNA TUG1 on osteogenic/odontogenic differentiation of human dental pulp stem cells / 口腔疾病防治

Objective@#To explore the effects of long noncoding-RNA (lncRNA) taurine upregulated gene 1 (TUG1) on the proliferation and osteogenic/odontoblast differentiation of human dental pulp stem cells (hDPSCs). @*Methods @# hDPSCs were isolated and cultured. The surface antigens CD44, CD45, CD73, CD90, CD133 and STRO-1 were detected by flow cytometry. Alkaline phosphatase (ALP) staining and alizarin red staining were used to identify the ability of cells to differentiate. RNA was collected on Days 0, 7 and 14 of the osteogenic induction of hDPSCs, and qRT-PCR was used to detect the relative expression of TUG1. The hDPSCs were stably transfected with a lentiviral vector containing the TUG1-silenced pSLenti-U6-shRNA(TUG1)-CMV-EGFP-F2A-Puro-WPRE to silence TUG1. The ability of hDPSCs to proliferate was assessed with the CCK-8 method. ALP and alizarin red staining and quantitative detection were used to detect the ALP activity and formation of mineralized nodules of hDPSCs. The expression levels of dentin sialophosphoprotein (DSPP), dentin matrix protein-1 (DMP-1), Runt-associated transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) genes and proteins were measured by qRT-PCR and Western blot.@*Results @#The hDPSCs were successfully isolated and cultured, and TUG1 expression was significantly increased during osteogenic differentiation (P<0.05). The hDPSCs proliferation was suppressed after silencing TUG1(P<0.05). After osteogenic induction, ALP and alizarin red staining showed that ALP activity and mineralized nodules were suppressed by silencing TUG1. The expression levels of the odontogenic differentiation gene DSPP and DMP-1 and the osteogenic differentiation gene Runx2, OCN and OPN were also significantly decreased (P<0.05).@*Conclusion @# Knocking down TUG1 can inhibit the proliferation and osteogenic/odontogenic differentiation of hDPSCs.

Study on the Mechanism of Selective Interaction of BR3 and BCMA with BAFF and APRIL.

BACKGROUND: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) can activate signaling pathways by binding to specific receptors. BR3 (BAFF receptor) shows a unique selectivity for BAFF ligand, while B-cell maturation antigen (BCMA) exhibits a stronger interaction between APRIL-BCMA rather than BAFF-BCMA interaction. OBJECTIVE: The combined domains were fused with IgG1 Fc to better understand which domain affects the selective interaction of the receptor with BAFF and APRIL. METHODS: Since BR3 and BCMA both contain cysteine-rich repeat domains (CRD) with DxL motif, the binding domains of BR3 and BCMA were segmented into two parts in this study. BR3-1 (CFDLLVRHGVAC) and BCMA-1 (YFDSLLHACIPC) contained the conservative DxL motif, while BR3-2 (GLLRTPRPKPA) and BCMA-2 (QLRCSSNTPPLT) were adjacent to the CRDs yet still joined with BR3-1 and BCMA-1. Affinity between all possible combinations was then tested. RESULTS: The affinity of BR3-1-BCMA-2-Fc and BR3-1-BR3-2-Fc for BAFF was higher than BCMA-1-BR3-2-Fc and BCMA-1-BCMA-2-Fc. Moreover, BR3-1-BCMA-2-Fc and BCMA-1-BCMA- 2-Fc had affinity for APRIL, while BR3-1-BR3-2-Fc and BCMA-1-BR3-2-Fc hardly interacted with APRIL. CONCLUSION: BR3-1 region played a key role for interaction with BAFF, while BCMA-1 region exhibited weaker binding with BAFF. BCMA-2 region having an α-helix might contribute towards selectivity of APRIL-BCMA binding and BR3-2 rigid region had deleterious effects on the APRIL-BR3 interaction. These results provide comprehensive insights of the mechanism of selective interactions, and may promote specific antagonist design in the future.

Signet ring cell carcinoma arising from sacrococcygeal teratoma: a case report and review of the literature.

We report here a rare case of adult sacrococcygeal teratoma (SCT) that was pathologically diagnosed as signet ring cell carcinoma (SRCC). A 26-year-old man complained of lower abdominal distension and discomfort and difficulty in urinating, and he was admitted to our hospital. Pelvic magnetic resonance imaging showed multiple oval, solid-cystic masses around the anterior sacrococcygeal region that measured approximately 96 × 114 × 89 mm. Magnetic resonance imaging also showed irregular cysts around the posterior sacrococcygeal region that measured approximately 34 × 72 × 60 mm. The preliminary diagnosis was cystic SCT. The patient then underwent surgery, during which we incised the cysts. A large amount of viscous, jelly-like liquid was present in the anterior sacrococcygeal mass. Furthermore, a large amount of light yellow, porridge-like secretion was present in the posterior sacrococcygeal mass. A pathological examination and immunohistochemistry confirmed teratoma, specifically SRCC.

SMYD3-associated pathway is involved in the anti-tumor effects of sulforaphane on gastric carcinoma cells.

Sulforaphane (SFN), a natural compound derived from cruciferous vegetables, has been proved to possess potent anti-cancer activity. SMYD3 is a histone methyltransferase which is closely related to the proliferation and migration of cancer cells. This study showed that SFN could dose-dependently induce cell cycle arrest, stimulate apoptosis, and inhibit proliferation and migration of gastric carcinoma cells. Accompanied with these anti-cancer effects, SMYD3 and its downstream genes, myosin regulatory light chain 9, and cysteine-rich angiogenic inducer 61, was downregulated by SFN. Furthermore, overexpression of SMYD3 via transfection could abolish the effects of SFN, suggesting that SMYD3 might be an important mediator of SFN. To the best of our knowledge, this is the first report describing the role of SMYD3 in the anti-cancer of SFN. These findings might throw light on the development of novel anti-cancer drugs and functional food using SFN-rich cruciferous vegetables.

Poly(N-isopropylacrylamide) microgel-based etalons for the label-free quantitation of estradiol-17ß in aqueous solutions and milk samples.

A novel estradiol-17ß (E2) biosensor was constructed from poly(N-isopropylacrylamide) (pNIPAm) microgel-based etalons by modification of their outermost Au layer with an E2 binding 75-mer DNA aptamer. When E2 is not present in the solution, the aptamer forms a loose/linear structure that allows ions to pass through and into the microgel layer. The ions can change the solvation state of the microgels, which changes the optical properties of the etalon. When E2 is present in the solution, the aptamer binds the E2 and undergoes a conformational change to a form that can block the diffusion of salt ions into the microgel layer. This blocking decreases the response of the device to salt exposure, which can be related to the concentration of E2 in solution. Using this approach, E2 sensor showed a dynamic range of 0.9-200 pg/mL with a calculated detection limit of 0.9 pg/mL (3.2 pM) E2, and the lowest measured concentration of E2 is 5.0 pg/mL. This sensor also showed low cross reactivity with progesterone, a similar steroid hormone. Moreover, this sensor could be regenerated five times without losing its sensitivity. Finally, we demonstrated that the sensor could also be used to quantify E2 in commercial skim and 2% milk, as well as farm milk directly without any pre-treatment. The successful quantitation of E2 in unprocessed milk demonstrates its potential use as a "cow-side" testing device for the dairy industry. Graphical abstract ᅟ.

Application of forward osmosis membrane technology for oil sands process-affected water desalination.

The extraction process used to obtain bitumen from the oil sands produces large volumes of oil sands process-affected water (OSPW). As a newly emerging desalination technology, forward osmosis (FO) has shown great promise in saving electrical power requirements, increasing water recovery, and minimizing brine discharge. With the support of this funding, a FO system was constructed using a cellulose triacetate FO membrane to test the feasibility of OSPW desalination and contaminant removal. The FO systems were optimized using different types and concentrations of draw solution. The FO system using 4 M NH4HCO3 as a draw solution achieved 85% water recovery from OSPW, and 80 to 100% contaminant rejection for most metals and ions. A water backwash cleaning method was applied to clean the fouled membrane, and the cleaned membrane achieved 77% water recovery, a performance comparable to that of new FO membranes. This suggests that the membrane fouling was reversible. The FO system developed in this project provides a novel and energy efficient strategy to remediate the tailings waters generated by oil sands bitumen extraction and processing.

Coupling bioelectricity generation and oil sands tailings treatment using microbial fuel cells.

In this study, four dual-chambered microbial fuel cells (MFC1-4) were constructed and filled with different ratios of mature fine tailings and oil sands process-affected water to test the feasibility of MFCs to simultaneously generate electricity and treat oil sands tailings. After 800 h of operation, the maximum voltage was observed in MFC4 at 0.726 V with 1.2kΩ external resistance loaded. The maximum power density reached 392 ± 15 mW/m(2) during the 1,700 h of MFC4 operation. With continuous electricity generation, MFC4 removed 27.8% of the total COD, 81.8% of the soluble COD and 32.9% of the total acid extractable organics. Moreover, effective removal of eight heavy metals, includes 97.8% of (78)Se, 96.8% of Ba, 94.7% of (88)Sr, 81.3% for (66)Zn, 77.1% of (95)Mo, 66.9% of (63)Cu, 44.9% of (53)Cr and 32.5% of Pb, was achieved.

Trapping of BMP receptors in distinct membrane domains inhibits their function in pulmonary arterial hypertension.

Bone morphogenetic proteins (BMPs) are pleiotrophic growth factors that influence diverse processes such as skeletal development, hematopoiesis, and neurogenesis. They play crucial roles in diseases such as pulmonary arterial hypertension (PAH). In PAH, mutants of the BMP type II receptors (BMPR2) were detected, and their functions were impaired during BMP signaling. It is thought that expression levels of these receptors determine the fate of BMP signaling, with low levels of expression leading to decreased Smad activation in PAH. However, our studies demonstrate, for the first time, that the localization of receptors on the plasma membrane, in this case BMPR2, was misdirected. Three BMPR2 mutants, D485G, N519K, and R899X, which are known to be involved in PAH, were chosen as our model system. Our results show that all three BMPR2 mutants decreased BMP-dependent Smad phosphorylation and Smad signaling. Although the three mutants reached the cell membrane and their expression was lower than that of BMPR2, they formed smaller clusters and associated differently with membrane domains, such as caveolae and clathrin-coated pits. The disruption of these domains restored the Smad signaling of D485G and N519K to the level of wild-type BMPR2, showing that these mutants were trapped in the domains, rather than just expressed at a lower level on the surface. Therefore, new treatment options for PAH should also target receptor localization, rather than just expression level.

Single-molecule imaging reveals transforming growth factor-beta-induced type II receptor dimerization.

Transforming growth factor-beta (TGF-beta) elicits its signals through two transmembrane serine/threonine kinase receptors, type II (TbetaRII) and type I receptors. It is generally believed that the initial receptor dimerization is an essential event for receptor activation. However, previous studies suggested that TGF-beta signals by binding to the preexisting TbetaRII homodimer. Here, using single molecule microscopy to image green fluorescent protein (GFP)-labeled TbetaRII on the living cell surface, we demonstrated that the receptor could exist as monomers at the low expression level in resting cells and dimerize upon TGF-beta stimulation. This work reveals a model in which the activation of serine-threonine kinase receptors is also accomplished via dimerization of monomers, suggesting that receptor dimerization is a general mechanism for ligand-induced receptor activation.