[Microtubule-associated tumor suppressor 1 inhibits hemin-induced apoptosis of vascular endothelial cells via hemeoxygenase 1].

This study aimed to investigate the effects of microtubule associated tumor suppressor 1 (MTUS1) on hemeoxygenase 1 (HMOX1) expression and hemin-induced apoptosis of vascular endothelial cells and its regulatory mechanism. RNA sequencing, RT-qPCR and Western blot were used to assess altered genes of hemin binding proteins, the expression of cAMP response element-binding protein (CREB) and nuclear respiratory factor 2 (NRF2), hemin-induced HMOX1 expression in MTUS1 knockdown human umbilical vein endothelial cells (HUVEC), and the effect of overexpression of CREB and NRF2 on HMOX1 expression in MTUS1 knockdown 293T cells. The effect of MTUS1 or HMOX1 knockdown on hemin-induced apoptosis in HUVEC, and the overexpression of NRF2 on hemin-induced apoptosis in MTUS1 knockdown 293T cells were assayed with CCK8 and Western blot. The results showed that MTUS1 was knocked down significantly in HUVEC by siRNA (P < 0.01), accompanied by decreased HMOX1 expression (P < 0.01). The increased HMOX1 expression induced by hemin was also inhibited by MTUS1 knockdown (P < 0.01). And the apoptosis of HUVEC induced by hemin was amplified by MTUS1 or HMOX1 knockdown (P < 0.01). Moreover the expression of CREB and NRF2 were both inhibited by MTUS1 knockdown in HUVEC (P < 0.01). The decreased HMOX1 regulated by MTUS1 knockdown could be rescued partly by overexpression of NRF2 (P < 0.01), however, not by overexpression of CREB. And the MTUS1 knockdown mediated decreased 293T cells viability induced by hemin could be partly rescued by NRF2 overexpression (P < 0.01). These results suggest that MTUS1 can inhibit hemin-induced apoptosis of HUVEC, and the mechanism maybe related to MTUS1/NRF2/HMOX1 pathway.

Application of Four-Dimensional Pelvic Floor Ultrasound in the Diagnosis of Postpartum Pelvic Floor Dysfunction and Evaluation of Curative Effect.

Objective: To explore the application of four-dimensional pelvic floor ultrasound in the diagnosis of postpartum pelvic floor dysfunction (PFD) and evaluation of curative effect. Methods: A total of 100 patients with postpartum PFD undergoing vaginal delivery in the hospital were enrolled as the research objects between January 2020 and January 2023. A total of 100 postpartum women with good pelvic floor muscle function during the same period were enrolled as a control group. Both groups underwent four-dimensional pelvic floor ultrasound detection. The bladder neck descent (BND), retrovesical angle (RVA), urethral tilt angle (UTA), urethral rotation angle (ROT), levator ani thickness under rest state (LATr), levator ani thickness under Valsalva state (LATs), levator ani hiatus area under rest state (LHAr) and levator ani hiatus area under Valsalva state (LHAs) in both groups were compared. The patients in the study group were given Kegel training for pelvic floor muscle rehabilitation exercise and bio-feedback electrical stimulation. According to the clinical curative effect, patients in the study group were divided into a recovery group (n=87) and a non-recovery group (n=13). The value of four-dimensional pelvic floor ultrasound in the diagnosis of PFD and evaluation of curative effect was analyzed. Results: In the observation group, BND, RVA, UTA, ROT, LHAr, and LHAs were higher, while LATr and LATs were lower compared to the control group. (P < .05). The results of ROC curves analysis showed that the AUC of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs in the diagnosis of PFD was 0.818, greater than that of the single index (0.728, 0.705, 0.680, 0.715, 0.677, 0.696, 0.719, 0.654; P < .05). BND, RVA, UTA, ROT, LHAr, and LHAs in the non-recovery group were higher than those in the recovery group, while LATr and LATs were lower than those in the recovery group (P < .05). The results of ROC curves analysis showed that the Area Under the Curve (AUC）of BND combined with RVA, UTA, ROT, LATr, LATs, LHAr, and LHAs for predicting the curative effect were 0.804, greater than that of a single index (0.725, 0.653, 0.651, 0.744, 0.733, 0.720, 0.661, 0.718; P < .05). Conclusion: Four-dimensional pelvic floor ultrasound can be applied to intuitively evaluate the structure and function of postpartum pelvic floor tissues, which can provide a reliable basis for the diagnosis of postpartum PFD and evaluation of curative effect.

Circ_0001665 Contributes to the Occurrence of Vestibular Schwannoma via Targeting miR-302a-3p/Adam9/EGFR Signaling Pathway.

Vestibular schwannoma (VS) is a benign, slow-growing neoplasm, which is an important cause of sensorineural hearing loss. Circular RNAs (circRNAs) have been widely reported to be dysregulated and participate in multiple biological processes of human diseases. However, roles of most circRNAs still remain explored. In the present study, the main aim was to uncover the impacts of circ_0001665, a cricRNA derived from ADAM metallopeptidase domain 9 (Adam9), on the biological behaviors of VS cells. Firstly, RT-qPCR was done to analyze circ_0001665 expression in VS cells and it was suggested that circ_001665 was distinctly up-regulated in rat VS cells. Supported by western blot analysis, circ_0001665 inhibition was validated to impede the proliferation while inducing the apoptosis of VS cells via functional assays. Additionally, results of mechanism assays demonstrated that circ_0001665 could function as a sponge of microRNA-302a-3p (miR-302a-3p) to enhance Adam9 expression and to activate EGFR signaling pathway in VS cells. Eventually, it was indicated in rescue assays that circ_0001665 expedited proliferation and restrained apoptosis of VS cells via modulation on miR-302a-3p/Adam9. Collectively, our study identified a novel perspective for exploration into molecular mechanisms in VS.

TRIM28 regulates SARS-CoV-2 cell entry by targeting ACE2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, it binds to angiotensin-converting enzyme 2 (ACE2) to enter into human cells. The expression level of ACE2 potentially determine the susceptibility and severity of COVID-19, it is thus of importance to understand the regulatory mechanism of ACE2 expression. Tripartite motif containing 28 (TRIM28) is known to be involved in multiple processes including antiviral restriction, endogenous retrovirus latency and immune response, it is recently reported to be co-expressed with SARS-CoV-2 receptor in type II pneumocytes; however, the roles of TRIM28 in ACE2 expression and SARS-CoV-2 cell entry remain unclear. This study showed that knockdown of TRIM28 induces ACE2 expression and increases pseudotyped SARS-CoV-2 cell entry of A549 cells and primary pulmonary alveolar epithelial cells (PAEpiCs). In a co-culture model of NK cells and lung epithelial cells, our results demonstrated that NK cells inhibit TRIM28 and promote ACE2 expression in lung epithelial cells, which was partially reversed by depletion of interleukin-2 and blocking of granzyme B in the co-culture medium. Furthermore, TRIM28 knockdown enhanced interferon-γ (IFN-γ)- induced ACE2 expression through a mechanism involving upregulating IFN-γ receptor 2 (IFNGR2) in both A549 and PAEpiCs. The upregulated ACE2 induced by TRIM28 knockdown and co-culture of NK cells was partially reversed by dexamethasone in A549 cells. Our study identified TRIM28 as a novel regulator of ACE2 expression and SARS-CoV-2 cell entry.

TRIM28 regulates sprouting angiogenesis through VEGFR-DLL4-Notch signaling circuit.

Sprouting angiogenesis is a highly coordinately process controlled by vascular endothelial growth factor receptor (VEGFR)-Notch signaling. Here we investigated whether Tripartite motif-containing 28 (TRIM28), which is an epigenetic modifier implicated in gene transcription and cell differentiation, is essential to mediate sprouting angiogenesis. We observed that knockdown of TRIM28 ortholog in zebrafish resulted in developmental vascular defect with disorganized and reduced vasculatures. Consistently, TRIM28 knockdown inhibited angiogenic sprouting of cultured endothelial cells (ECs), which exhibited increased mRNA levels of VEGFR1, Delta-like (DLL) 3, and Notch2 but reduced levels of VEGFR2, DLL1, DLL4, Notch1, Notch3, and Notch4.The regulative effects of TRIM28 on these angiogenic factors were partially mediated by hypoxia-inducible factor 1 α (HIF-1α) and recombination signal-binding protein for immunoglobulin kappa J region (RBPJκ). In vitro DNA-binding assay showed that TRIM28 knockdown increased the association of RBPJκ with DNA sequences containing HIF-1α-binding sites. Moreover, the phosphorylation of TRIM28 was controlled by VEGF and Notch1 through a mechanism involving RBPJκ-dual-specificity phosphatase (DUSP)-p38 MAPK, indicating a negative feedback mechanism. These findings established TRIM28 as a crucial regulator of VEGFR-Notch signaling circuit through HIF-1α and RBPJκ in EC sprouting angiogenesis.

The imaginal and detailed nymphal characters of Cincticostella fusca (Kang amp; Yang, 1995) (Ephemeroptera: Ephemerellidae).

Among the 17 known species of the genus Cincticostella, only five of them have been reported as both nymphs and imagoes, which does not include the Chinese species C. fusca Kang et Yang (1995). Here the nymphs are redescribed and reared imagoes are reported for the first time, based on material collected from southeastern China. Morphologically, the nymph is unique because of its large body size, expanded genae, pale median stripe on the anterior of the head, and dark tarsi. The male imago can be differentiated from congeners by its large body size, pigmented forewings, and the mesothoracic scutellum having a pair of membranous lamellae. More importantly, its penes are distinct, being fused for most of their length and having complex ventral projections. Adults emerge in early spring (March to April).

TRIM28 and TRIM27 are required for expressions of PDGFRß and contractile phenotypic genes by vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.

Design and Biosensing of a Ratiometric Electrochemiluminescence Resonance Energy Transfer Aptasensor between a g-C3N4 Nanosheet and Ru@MOF for Amyloid-ß Protein.

A dual-wavelength ratiometric electrochemiluminescence resonance energy transfer (ECL-RET) aptasensor based on the carbon nitride nanosheet (g-C3N4 NS) and metal-organic frameworks (Ru@MOFs) as energy donor-receptor pairs is first designed for the detection of the amyloid-ß (Aß) protein. The cathode ECL of g-C3N4 NS gradually decreased, whereas the anode ECL from Ru@MOF pyramidally enhanced along with the increasing concentration of Aß in a 0.1 M phosphate-buffered saline solution containing 0.1 M S2O82-. Additionally, it is worth noting that 2-amino terephthalic acid from MOF not only can load abundant amounts of luminophor Ru(bpy)32+ but also promote the conversion of more amounts of S2O82- that served as a coreactant accelerator into SO4•-, further enhancing the ECL signal of Ru@MOF. Besides, the ECL intensity from the g-C3N4 NS had a tremendous spectrum overlap with the UV-vis spectrum of Ru@MOF, demonstrating the high-efficiency ECL-RET from g-C3N4 NS to Ru@MOF. According to the ratio of ECL460nm/ECL620nm, the constructed aptasensor for the detection of Aß showed a wide linear range from 10-5 to 500 ng/mL and a low detection limit of 3.9 fg/mL (S/N = 3) with a correction coefficient of 0.9965. The obtained results certified that the dual-wavelength ratiometric ECL sensor could provide a reliable direction and have the potential for application in biosensing and clinical diagnosis fields.

NR6A1 regulates lipid metabolism through mammalian target of rapamycin complex 1 in HepG2 cells.

BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .

Correction to: Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response.

In the original publication of this article [1], the Gene Expression Omnibus (GEO) accession code GSE79772 is wrong. The correct accession code should be GSE86213.

Correction to: Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response.

In the original publication of this article [1], the Gene Expression Omnibus (GEO) accession code GSE79772 is wrong. The correct accession code should be GSE86213.

Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response.

BACKGROUND: Ionizing radiation (IR) therapy is the standard first-line treatment for newly diagnosed patients with glioblastoma (GBM), the most common and malignant primary brain tumor. However, the effects of IR are limited due to the aberrant radioresistance of GBM. METHODS: Transcriptome analysis was performed using RNA-seq in radioresistant patient-derived glioma stem-like cells (GSCs). Survival of glioma patient and mice bearing-brain tumors was analyzed by Kaplan-Meier survival analysis. Lipid droplet and γ-H2AX foci-positive cells were evaluated using immunofluorescence staining. RESULTS: Lipolytic inhibitor G0/G1 switch gene 2 (G0S2) is upregulated in radioresistant GSCs and elevated in clinical GBM. GBM patients with high G0S2 expression had significantly shorter overall survival compared with those with low expression of G0S2. Using genetic approaches targeting G0S2 in glioma cells and GSCs, we found that knockdown of G0S2 promoted lipid droplet turnover, inhibited GSC radioresistance, and extended survival of xenograft tumor mice with or without IR. In contrast, overexpression of G0S2 promoted glioma cell radiation resistance. Mechanistically, high expression of G0S2 reduced lipid droplet turnover and thereby attenuated E3 ligase RNF168-mediated 53BP1 ubiquitination through activated the mechanistic target of rapamycin (mTOR)-ribosomal S6 kinase (S6K) signaling and increased 53BP1 protein stability in response to IR, leading to enhanced DNA repair and glioma radioresistance. CONCLUSIONS: Our findings uncover a new function for lipolytic inhibitor G0S2 as an important regulator for GSC radioresistance, suggesting G0S2 as a potential therapeutic target for treating gliomas.

Electroluminescent aptasensor based on RuSiO2 nanoparticles for detection cytochrome c using ferrocene as quenching probe.

A stable sandwiched electrochemiluminescence (ECL) aptasensor was originally constructed established upon Ru(bpy)32+-doped silica nanoparticles (RuSiO2 NPs) with ferrocene carboxylic acid-aptamer (Fc-aptamer) to quantitatively detect cytochrome c (Cyt C). Herein, RuSiO2 NPs and Fc-aptamer were respectively prepared through the microemulsion method and amide reaction to fabricate the ECL aptasensor. Furthermore, Fc-aptamer was used as quenching probe for quenching the ECL emission of RuSiO2 NPs. In detail, RuSiO2 NPs were primarily immobilized onto the electrodes by the film-forming function of chitosan. Subsequently, the aptamer was incubated onto the decorated GCE via crosslinking with glutaraldehyde (GA). After Cyt C was connected to the GCE via immunoreaction, Fc-aptamer was immobilized onto the modified electrodes owing to the specific recognition between antigens and aptamer. Ultimately, ECL signals markedly descended owing to the poor electricity conductivity of proteins and superior quenching effect of Fc-aptamer. Under optimum conditions, the designed ECL aptasensor indicated an accurate analysis for Cyt C in a rang of 0.001-100 nM with a detection limit of 0.48 pM (S/N = 3).

Electrochemiluminescence resonance energy transfer biosensor between the glucose functionalized MnO2 and g-C3N4 nanocomposites for ultrasensitive detection of concanavalin A.

An electrochemiluminescence (ECL) analytical platform was initially proposed based on the electrochemiluminescence resonance energy transfer (ECL-RET) mechanism for ultrasensitive detection of Concanavalin A (Con A). In this protocol, the glucose functionalized carboxylic g-C3N4 nanosheets (g-C3N4-COOH@Glu) and MnO2 nanoparticles covered carboxylic multi-wall carbon nanotubes (BSA@MnO2-MWCNTs-COOH@Glu) were synthesized and acted as ECL-RET electron donor and acceptor, respectively. Herein, glucose was served as the recognition element for binding Con A and MWCNTs was utilized as the carrier materials for loading MnO2. When the quenching probe BSA@MnO2-MWCNTs-COOH@Glu was incubated onto the modified electrodes via the specific carbohydrate-Con A interaction, the ECL signals of g-C3N4-COOH@Glu which used S2O82- as its coreactant have drastically declined. Under optimum conditions, this biosensor performed a sensitive detection of the Con A ranging from 1 × 10-5 to 1 × 104 ng/mL with a detection limit of 2.2 fg/mL (S/N = 3). Moreover, favorable analytical outcomes for detecion Con A in actual serum samples were obtained, exhibiting huge applications in clinical diagnosis of this assay.

3D carbon nanosphere and gold nanoparticle-based voltammetric cytosensor for cell line A549 and for early diagnosis of non-small cell lung cancer cells.

An electrochemical cytosensor for the detection of the non-small-cell lung cancer cell line A549 (NSCLC) had been developed. A microwave-hydrothermal method was employed to prepare monodisperse colloidal carbon nanospheres (CNSs). Gold nanoparticles (AuNPs) were placed on the surface of the colloidal CNSs by self-assembly to obtain 3D-structured microspheres of the type CNS@AuNP. The results of an MTT assay show the microspheres to possess good biocompatibility. The CNS@AuNP nanocomposite was then placed, in a chitosan film, on a glassy carbon electrode (GCE). The voltammetric signals and detection sensitivity are significantly enhanced owing to the synergistic effect of CNSs and AuNPs. A cytosensor was then obtained by immobilization of antibody against the carcinoembryonic antigen (which is a biomarker for NSCLC) on the GCE via crosslinking with glutaraldehyde. Hexacyanoferrate is used as an electrochemical probe, and the typical working voltage is 0.2 V (vs. SCE). If exposed to A549 cells, the differential pulse voltammetric signal decreases in the 4.2 × 10-1 to 4.2 × 10-6 cells mL-1 concentration range, and the detection limit is 14 cells mL-1 (at S/N = 3). Graphical abstract Schematic presentation of design strategy and fabrication process of the electrochemical cytosensor for A549 cells. (CNS: carbon nanospheres; GA: glutaraldehyde; PEI: polyethyleneimine; AuNPs: gold nanoparticles; BSA: Bovine serum albumin).

HDAC6 inhibition protects cardiomyocytes against doxorubicin-induced acute damage by improving α-tubulin acetylation.

Doxorubicin (Dox) is an efficacious antineoplastic drug but is limited used for its cardiotoxicity. Histone Deacetylase 6 (HDAC6) has been indicated to participate in cardiomyopathies, however, its role in Dox-induced cardiac injury is largely unknown. In this study, we firstly aimed to determine the role of HDAC6 in Dox-induced cardiomyopathy. Immunoblotting revealed that Dox increased HDAC6 protein level and activity and decreased α-tubulin acetylation level in vitro and vivo. HDAC6 knockout (HDAC6-/-) mice showed obvious anti-Dox cardiotoxicity by conserved cardiac function monitored by echocardiography and the protection was reversed by Nocodazole, one drug lowering α-tubulin acetylation. Further mechanism investigation showed that improvement of mitochondria function and autophagy flux was partially inhibited by Nocodazole and Colchicine which lowers α-tubulin acetylation in neonatal rat cardiac myocytes. Aiming at transforming this research to clinical application, we then explored the effect of combined utilization of HDAC6 inhibitor and Dox on tumour and cardiac function. Results showed that Tubastatin A, one HDAC6 selective inhibitor, protected against Dox-induced acute cardiomyopathy without influencing the effect of Dox on inhibiting MDA-MB-231 subcutaneous tumour growth. These findings suggest a new treatment for cancer with Dox by combined utilization with HDAC6 selective inhibitors.

An ultrasensitive electrochemiluminescence immunosensor based on platinum nickel nanocubes-L-cysteine-luminol nanocomposite.

An ultrasensitive electrochemiluminescence (ECL) immunosensor was initially developed for quantitative detection of carbohydrate antigen 15-3 (CA15-3) using platinum nickel nanocubes-L-cysteine-luminol nanocomposite (PtNi NCs-L-Cys-luminol) as signal probe. Herein, the PtNi NCs-L-Cys-luminol nanocomposite was modified on the glassy carbon electrode (GCE) surface via the film-forming properties of chitosan. Then, the CA15-3 antibody was attached to the modified electrode surface by amidating reaction to construct the ECL immunosensor. Experimental results showed that with the capturing of CA15-3 antigen molecules on the immunosensor, the ECL signal intensity observably decreased, indicating the quenching detection principle of electrochemiluminescence. Under optimal experimental conditions, the constructed ECL immunosensor displayed remarkable performance for CA15-3 detection ranging from 0.0005 U/mL to 500 U/mL, with a relatively low detection limit of 0.000167 U/mL (S/N = 3). It might be ascribed to the fact that the PtNi NCs could dramatically promote the decomposition of H2O2 to produce various active free radical, thereby the ECL responses of luminol were prominently magnified and its sensitivity was effectively increased. The immunosensor exemplified its advantages of easy fabrication, fast analysis, high sensitivity, good reproducibility and selectivity. Moreover, the recovery tests exhibited that the sensor can be used to sensitively detect CA15-3 in serum samples, suggesting potential application prospect in bioanalysis.

Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knockdown of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs. Knockdown of MTUS1 disturbed the elongated mitochondrial network and induced the formation of perinuclear clusters of mitochondria. Importantly, mitochondrial motility and fusion were suppressed, whereas generation of reactive oxygen species was increased in MTUS1 knockdown ECs. Mechanistically, we showed that the N-terminal coiled-coil domain of MTUS1 interacted with the mitochondrial membrane proteins, mitofusin-1 and mitofusin-2, to maintain mitochondrial morphology in ECs. This study illustrated a novel role of MTUS1 in mitochondrial morphology and EC angiogenic responses.-Wang, Y., Huang, Y., Liu, Y., Li, J., Hao, Y., Yin, P., Liu, Z., Chen, J., Wang, Y., Wang, N., Zhang, P. Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells.

Electrochemiluminescence resonance energy transfer system between GNRs and Ru(bpy)32+: Application in magnetic aptasensor for ß-amyloid.

Electrochemiluminescent (ECL) assay has gradually drawn increasing interest in the biomedical analysis. This paper proposed a new methodology for ultrasensitive and facile detection of Alzheimer's disease marker ß-amyloid (Aß) by fabricating a sandwich-type ECL sensing platform. Herein, electrochemiluminescence resonance energy transfer (ECL-RET) was employed to determine Aß concentration, which can be attributed to the quenching effect from RET between Ru(bpy)32+ and gold nanorods (GNRs) acting as ECL-RET electron donor and acceptor, respectively. In this protocol, mesoporous carbon nanospheres were adopted to immobilize ECL reactant Ru(bpy)32+ and antibody via nafion to acquire the RET donor nanocomposites (MOCs/nafion/Ru(bpy)32+/antibody), which were tightly interconnected with epoxy group functionalized Fe3O4 nanoparticles. It is of vital importance that GNRs with exquisite rod shape were synthesized and exhibited a typical absorption peak at 650nm to quench ECL signal of Ru(bpy)32+ effectively. In addition, the ECL emission decreased linearly with the logarithm of Aß concentration in a wide linear range from 1.0 × 10-5 to 100ng/mL with a detection limit of 4.2 × 10-6ng/mL. Furthermore, distinctive and desirable properties were verified to declare the promise for being applicable to analyze the Aß content in real Alzheimer's cerebrospinal fluid samples with satisfactory results.

Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR-1 and -2 and VEGFR2 in endothelial cells.

Angiogenesis and inflammation are regarded as important factors in the pathogenesis of chronic inflammation, cancer, and wound healing. Recent studies have supported prior evidence that common signaling pathways are involved in angiogenesis and inflammatory responses; however, key factors controlling both processes remain unclear. Although tripartite motif-containing (TRIM)-28 is known to have an immunosuppressive role in immune cells, its expression level and role in endothelial cells (ECs) are still unclear. In this study, we investigated the role of TRIM28 in inflammatory responses and angiogenic activity of ECs for the first time. We showed that TRIM28 is the most abundant TRIM family member and is localized in nuclei of ECs. Small interfering RNA-mediated knockdown of TRIM28 strikingly suppressed expression of TNF receptor (TNFR)-1 and -2, decreased TNF-α-induced phosphorylation of IKKα/ß and IκBα and degradation of IκBα and nuclear translocation of p65, and suppressed basal level and TNF-α-induced expression of chemokines and adhesion molecules, including VCAM-1, IL-6, ICAM-1, E-selectin, and monocyte chemoattractant protein (MCP)-1. Unexpectedly, IL-8 was potentiated by TRIM28 knockdown in ECs in an NF-κB-inducing kinase-dependent manner. Meanwhile, knockdown of TRIM28 inhibited expression of VEGF receptor 2 and suppressed VEGF-induced proliferation and tube formation by ECs. Finally, knockdown of TRIM28 suppressed recruitment of ECs in vivo in a murine synthetic basement membrane model. In summary, we found that TRIM28 acts as a central factor in controlling endothelial inflammatory responses and angiogenic activities by retaining expression of TNFR-1 and -2 and VEGF receptor 2 in ECs.-Wang, Y., Li, J., Huang Y., Dai, X., Liu, Y., Liu, Z., Wang, Y., Wang, N., Zhang, P. Tripartite motif-containing 28 bridges endothelial inflammation and angiogenic activity by retaining expression of TNFR1 and -2 and VEGFR2 in endothelial cells.