Porcine Epidemic Diarrhea Virus Infection Disrupts the Nasal Endothelial Barrier To Favor Viral Dissemination.

Crossing the endothelium from the entry site and spreading in the bloodstream are crucial but obscure steps in the pathogenesis of many emerging viruses. Previous studies confirmed that porcine epidemic diarrhea virus (PEDV) caused intestinal infection by intranasal inoculation. However, the role of the nasal endothelial barrier in PEDV translocation remains unclear. Here, we demonstrated that PEDV infection causes nasal endothelial dysfunction to favor viral dissemination. Intranasal inoculation with PEDV compromised the integrity of endothelial cells (ECs) in nasal microvessels. The matrix metalloproteinase 7 (MMP-7) released from the PEDV-infected nasal epithelial cells (NECs) contributed to the destruction of endothelial integrity by degrading the tight junctions, rather than direct PEDV infection. Moreover, the proinflammatory cytokines released from PEDV-infected NECs activated ECs to upregulate ICAM-1 expression, which favored peripheral blood mononuclear cells (PBMCs) migration. PEDV could further exploit migrated cells to favor viral dissemination. Together, our results reveal the mechanism by which PEDV manipulates the endothelial dysfunction to favor viral dissemination and provide novel insights into how coronavirus interacts with the endothelium. IMPORTANCE The endothelial barrier is the last but vital defense against systemic viral transmission. Porcine epidemic diarrhea virus (PEDV) can cause severe atrophic enteritis and acute viremia. However, the mechanisms by which the virus crosses the endothelial barrier and causes viremia are poorly understood. In this study, we revealed the mechanisms of endothelial dysfunction in PEDV infection. The viral infection activates NECs and causes the upregulation of MMP-7 and proinflammatory cytokines. Using NECs, ECs, and PBMCs as in vitro models, we determined that the released MMP-7 contributed to the destruction of endothelial barrier, and the released proinflammatory cytokines activated ECs to facilitate PBMCs migration. Moreover, the virus further exploited the migrated cells to promote viral dissemination. Thus, our results provide new insights into the mechanisms underlying endothelial dysfunction induced by coronavirus infection.

Persulfidation maintains cytosolic G6PDs activity through changing tetrameric structure and competing cysteine sulfur oxidation under salt stress in Arabidopsis and tomato.

Glucose-6-phosphate dehydrogenases (G6PDs) are essential regulators of cellular redox. Hydrogen sulfide (H2 S) is a small gasotransmitter that improves plant adaptation to stress; however, its role in regulating G6PD oligomerization to resist oxidative stress remains unknown in plants. Persulfidation of cytosolic G6PDs was analyzed by mass spectrometry (MS). The structural change model of AtG6PD6 homooligomer was built by chemical cross-linking coupled with mass spectrometry (CXMS). We isolated AtG6PD6C159A and SlG6PDCC155A transgenic lines to confirm the in vivo function of persulfidated sites with the g6pd5,6 background. Persulfidation occurs at Arabidopsis G6PD6 Cystine (Cys)159 and tomato G6PDC Cys155, leading to alterations of spatial distance between lysine (K)491-K475 from 42.0 Å to 10.3 Å within the G6PD tetramer. The structural alteration occurs in the structural NADP+ binding domain, which governs the stability of G6PD homooligomer. Persulfidation enhances G6PD oligomerization, thereby increasing substrate affinity. Under high salt stress, cytosolic G6PDs activity was inhibited due to oxidative modifications. Persulfidation protects these specific sites and prevents oxidative damage. In summary, H2 S-mediated persulfidation promotes cytosolic G6PD activity by altering homotetrameric structure. The cytosolic G6PD adaptive regulation with two kinds of protein modifications at the atomic and molecular levels is critical for the cellular stress response.

Synthetic MRI in differentiating benign from metastatic retropharyngeal lymph node: combination with diffusion-weighted imaging.

OBJECTIVES: This study aimed to evaluate the synthetic MRI (syMRI), its combination with diffusion-weighted imaging (DWI), and morphological features for discriminating benign from metastatic retropharyngeal lymph nodes (RLNs). METHODS: Fifty-eight patients with a total of 63 RLNs (21 benign and 42 metastatic) were enrolled. The mean and standard deviation of syMRI-derived relaxometry parameters (T1, T2, PD; T1SD, T2SD, PDSD) were obtained from two different regions of interest (namely, partial-lesion and full-lesion ROI). The parameters derived from benign and metastatic RLNs were compared using Student's t or chi-square tests. Logistic regression analysis was used to construct a multi-parameter model of syMRI, syMRI + DWI, and syMRI + DWI + morphological features. Areas under the curve (AUC) were compared using the DeLong test to determine the best diagnostic approach. RESULTS: Benign RLNs had significantly higher T1, T2, PD, and T1SD values compared with metastatic RLNs in both partial-lesion and full-lesion ROI (all p < 0.05). The T1SD obtained from full-lesion ROI showed the best diagnostic performance among all syMRI-derived single parameters. The AUC of combined syMRI multiple parameters (T1, T2, PD, T1SD) were higher than those of any single parameter from syMRI. The combination of synthetic MRI and DWI can improve the AUC regardless of ROI delineation. Furthermore, the combination of synthetic MRI, DWI-derived quantitative parameters, and morphological features can significantly improve the overall diagnostic performance. CONCLUSIONS: The value of syMRI has been validated in differential diagnosis of benign and metastatic RLNs, and syMRI + DWI + morphological features can further improve the diagnostic efficiency for discriminating these two entities. KEY POINTS: • Synthetic MRI was useful in differential diagnosis of benign and metastatic RLNs. • The combination of syMRI, DWI, and morphological features can significantly improve the diagnostic efficiency.

Characteristics of the nasal mucosa of commercial pigs during normal development.

The nasal mucosa is constantly exposed to inhaled pathogens and is the first defence against respiratory infections. Here, we investigated the structural and compositional characteristics of the nasal mucosa of commercial pigs at various growth stages. The epithelial thickness, number of capillaries, and secretion function of the nasal mucosa dramatically increased with age; however, underlying lymphoid follicles in the respiratory region were rarely observed across the growth stages. The nasal mucosa was explored at the epithelial, immunological, and biological (commensal microbiota) barriers. In the epithelial barrier, the proliferative capacity of the nasal epithelia and the expression of tight junction proteins were high after birth; however, they decreased significantly during the suckling stage and increased again during the weaning stage. In the immunological barrier, most pattern recognition receptors were expressed at very low levels in neonatal piglets, and the innate immune cell distribution was lower. During the suckling stage, increased expression of Toll-like receptor (TLR) 2 and TLR4 was observed; however, TLR3 expression decreased. TLR expression and innate immune cell quantity significantly increased from the weaning to the finishing stage. In the biological barrier, Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes comprised the dominant phyla in neonatal piglets. A dramatic decrease in nasal microbial diversity was observed during the suckling stage, accompanied by an increase in potentially pathogenic bacteria. Proteobacteria, Bacteroidetes, and Firmicutes were identified as the core phyla of the nasal microbiota; among these, the three dominant genera, Actinobacter, Moraxella, and Bergerella, may be opportunistic pathogens in the respiratory tract. These characteristics comprise an essential reference for respiratory infection prevention at large-scale pig farms.

Feeding with 4,4'-diaponeurosporene-producing Bacillus subtilis enhances the lactogenic immunity of sow.

Specific antibodies produced sow by oral porcine epidemic diarrhea virus (PEDV) vaccines would transfer to newborn piglets via colostrum, and it is an effective strategy to prevent porcine epidemic diarrhea (PED). However, there is a lag in the development of corresponding vaccines due to the rapid mutation of PEDV, which could increase the difficulty of PED prevention and control in pig farms. Hence, congenital lactogenic immunity was assessed by feeding 4,4'-diaponeurosporene-producing Bacillus subtilis (B.S-Dia) to sow on the 80th day of gestation in order to protect newborn piglets from PEDV infection. Firstly, we found that the quantities of T lymphocytes and monocytes in the blood and colostrum after oral administration of B.S-Dia were significantly increased as observed by flow cytometry, whereas the proliferative activity of T lymphocytes in colostrum was also markedly increased. Furthermore, enzyme-linked immunosorbent assay (ELISA) results revealed that levels of TGF (Transforming growth factor) -ß, Interleukin (IL) -6, lysozyme and lactoferrin were significantly increased. Finally, it was found in the piglets' challenge protection test that offspring pigs of the sows feeding B.S-Dia during pregnancy did not develop diarrhea symptoms and intestinal pathological changes at 48 h after infection with PEDV, and PEDV load in the jejunum and ileum was significantly reduced, but offspring pigs of the sows taking orally PBS during pregnancy developed pronounced diarrhea symptoms and extensive PEDV colonization was noted both in the jejunum and ileum. In summary, sow by oral administration of B.S-Dia substantially increased congenital lactogenic immunity, thereby preventing newborn piglets from being infected with PEDV.

Hydrogen sulfide improves salt tolerance through persulfidation of PMA1 in Arabidopsis.

KEY MESSAGE: A new interaction was found between PMA1 and GRF4. H2S promotes the interaction through persulfidated Cys446 of PMA1. H2S activates PMA1 to maintain K+/Na+ homeostasis through persulfidation under salt stress. Plasma membrane H+-ATPase (PMA) is a transmembrane transporter responsible for pumping protons, and its contribution to salt resistance is indispensable in plants. Hydrogen sulfide (H2S), a small signaling gas molecule, plays the important roles in facilitating adaptation of plants to salt stress. However, how H2S regulates PMA activity remains largely unclear. Here, we show a possible original mechanism for H2S to regulate PMA activity. PMA1, a predominant member in the PMA family of Arabidopsis, has a non-conservative persulfidated cysteine (Cys) residue (Cys446), which is exposed on the surface of PMA1 and located in cation transporter/ATPase domain. A new interaction of PMA1 and GENERAL REGULATORY FACTOR 4 (GRF4, belongs to the 14-3-3 protein family) was found by chemical crosslinking coupled with mass spectrometry (CXMS) in vivo. H2S-mediated persulfidation promoted the binding of PMA1 to GRF4. Further studies showed that H2S enhanced instantaneous H+ efflux and maintained K+/Na+ homeostasis under salt stress. In light of these findings, we suggest that H2S promotes the binding of PMA1 to GRF4 through persulfidation, and then activating PMA, thus improving the salt tolerance of Arabidopsis.

Spatiotemporal Release of Reactive Oxygen Species and NO for Overcoming Biofilm Heterogeneity.

The heterogeneity in biofilms is a major challenge in biofilm therapies due to different susceptibility of bacteria and extracellular polymeric substances (EPS) to antibacterial agents. Here, we describe a therapeutic strategy that overcame biofilm heterogeneity, where antibacterial agent (NO) and EPS dispersant (reactive oxygen species (ROS)-inducing Fe3+ ) were separately loaded in the yolk and shell compartment of a yolk-shell nanoplatform. Compared with traditional combinational chemotherapies which suffer from inconsistent pharmacokinetics profiles, this strategy drew on the pharmacokinetic complementarity of ROS and NO, where ROS with a short diffusion distance and a high redox potential corrupted the EPS, facilitating NO, which has a long diffusion distance and a broad antimicrobial spectrum, to penetrate the biofilm and eliminate the resident bacteria. Additionally, the construction of a three-dimensional spherical biofilm model is novel and clinically relevant.

MiR-145 alleviates Hcy-induced VSMC proliferation, migration, and phenotypic switch through repression of the PI3K/Akt/mTOR pathway.

The proliferation, migration, and cellular morphology of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis (AS). Homocysteine (Hcy) is a sulfur-containing amino acid, which is an intermediate product of methionine metabolism. Hcy can induce proliferation, migration, and phenotypic switch of VSMCs, but details of these mechanisms are still unclear. The phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) signaling pathway is involved in a host of cellular functions. In this study, we sought to determine if this multifunctional pathway played a role in Hcy-induced proliferation, migration, and phenotypic transformation of VSMCs, which has not been previously reported. miR-145 has been previously reported to suppress the effects of Hcy in VSMCs. In our study, using qRT-PCR, we found that Hcy itself reduced the expression of miR-145 in VSMCs, while overexpression of miR-145 reduced the proliferation, migration, and phenotypic transformation of VSMCs caused by Hcy. Using Western blot analysis, we found that VSMCs exposed to Hcy exhibited significant increases in the levels of PI3K, Akt, and mTOR proteins. Additionally, overexpression of miR-145 dramatically decreased PI3K, Akt, and mTOR expression. Using qRT-PCR we found that miR-145 expression increased after blocking PI3K using an inhibitor. Inhibition of the PI3K signaling pathway also prevented Hcy-induced VSMC proliferation, migration, and phenotypic switch. Taken together, our results suggest that miR-145 could inhibit VSMC proliferation, migration, and phenotype switching by preventing activation of the PI3K/Akt/mTOR signaling pathway.

One-Pot Synthesis of High-Quality Bimagnetic Core/Shell Nanocrystals with Diverse Exchange Coupling.

Exchange coupled bimagnetic core/shell nanoparticles are promising for emerging multiferroic and spintronic technologies compared with traditional, single-phase materials, as they deliver numerous appealing effects, such as large exchange bias, tailored coercivities, and tunable blocking temperatures. However, it remains a challenge to manipulate their magnetic properties via exchange coupling due to the lack of a straightforward method that enables the general preparation of desired composites. Here we report a robust and general one-pot approach for the synthesis of different kinds of bimagnetic core/shell nanostructures (BMCS NSs). The formation of highly crystalline and monodisperse BMCS NSs adopted a self-adaptive sequential growth, circumventing the employment of complex temperature control and elaborate seeded growth techniques. As a result of large lattice misfit, the presence of interfacial imperfections as an extra source of anisotropy induced diverse exchange coupling interactions in ferro-ferrimagnetic and ferro-antiferromagnetic systems, which had great effects on the improvement of the magnetic properties of BMCS NSs. We envision that this new strategy will open up exciting opportunities toward large-scalable production of such high-quality BMCS NSs, thereby greatly potentiating the prospective applications of nanomagnetic materials.

SOX9 dependent FOXA1 expression promotes tumorigenesis in lung carcinoma.

The malignant proliferation is one of the major characteristic for tumor cells, however the mechanism of lung cancer cells uncontrollable proliferation is still confusing. This study investigated the mechanism of up-regulated FOXA1 in lung cancer and its tumorigenic function in lung cancer. FOXA1 showed an increasing expression pattern with the pathological progression in lung cancer, and SOX9 expression pattern is positively correlated with FOXA1. Furthermore, combined up-regulated FOXA1 and SOX9 usually resulted in a poor survival prognosis of patients with lung cancer. In addition, SOX9 was identified as a transcription factor of FOXA1 in lung cancer and involved in affecting the expression of FOXA1 targeted genes-Bcl2, CDKN1B, RPRM and NKX2. What's more, SOX9 can rescue the declining tumorigenic ability of lung cancer cells caused by FOXA1 silenced. This study indicates that SOX9 dependent FOXA1 expression promotes tumorigenic ability of lung cancer cells.

Nanoparticle-Regulated Semiartificial Magnetotactic Bacteria with Tunable Magnetic Moment and Magnetic Sensitivity.

Micro-/nanomotors are widely used in micro-/nanoprocessing, cargo transportation, and other microscale tasks because of their ability to move independently. Many biological hybrid motors based on bacteria have been developed. Magnetotactic bacteria (MTB) have been employed as motors in biological systems because of their good biocompatibility and magnetotactic motion in magnetic fields. However, the magnetotaxis of MTB is difficult to control due to the lack of effective methods. Herein, a strategy that enables control over the motion of MTB is presented. By depositing synthetic Fe3 O4 magnetic nanoparticles on the surface of MTB, semiartificial magnetotactic bacteria (SAMTB) are produced. The overall magnetic properties of SAMTB, including saturation magnetization, residual magnetization, and blocking temperature, are regulated in a multivariate and multilevel fashion, thus regulating the magnetic sensitivity of SAMTB. This strategy provides a feasible method to manoeuvre MTB for applications in complex fluid environments, such as magnetic drug release systems and real-time tracking systems. Furthermore, this concept and methodology provide a paradigm for controlling the mobility of micro-/nanomotors based on natural small organisms.

Direct Measurement of Through-Bond Effects in Molecular Multivalent Interactions.

Multivalent interactions occur throughout biology, and have a number of characteristics that monovalent interactions do not. However, it remains challenging to directly measure the binding force of molecular multivalent interactions and identify the mechanism of interactions. In this study, the specific interaction between bivalent aptamer and thrombin has been measured directly and quantitatively by force-induced remnant magnetization spectroscopy to investigate the binding force and through-bond effects of the multivalent interactions. The measured differential binding forces enable through-bond effects in thrombin-aptamer complexes to be identified, where aptamer binding at exosite II produces visible effects on their binding at exosite I and vice versa. This method might be suitable for practical applications in the design of high-performance ligands.

One-step Preparation of Monodisperse Multifunctional Macroporous Particles through a Spontaneous Physical Process.

Macroporous particles that combine the property features of spherical structures and porous materials are expected to find use over micro- and macroscopic length scales from miniaturized systems such as cell imaging, drug and gene delivery to industrial applications. However, the capacity for de novo design of such materials is still limited. Here, a spontaneous process to fabricate monodisperse multifunctional macroporous particles (MMMPs) by high internal phase emulsion templating is reported. An interesting physical phenomenon involving self-emulsification and synergistic effects between nanoparticles and amphiphilic diblock copolymers is observed in this process. These MMMPs, featured with tailor-made pore structures, pH responsiveness, and magnetic response, could be used as stimuli-responsive carriers for multiple functional molecules with a high loading and releasing efficiency. This new understanding regarding the underlying phenomena that control self-emulsification behavior and synergistic action in emulsion systems provides a unique outlook and a novel approach to the design of potentially multifunctional porous materials for controllable release and delivery processes.

Generation, Characterization, and Application of Hierarchically Structured Self-Assembly Induced by the Combined Effect of Self-Emulsification and Phase Separation.

Hierarchically structured magnetic single-hole hollow spheres (MSHS) have been successfully obtained via a facile self-assembly strategy. This methodology allows the double emulsions generated via the combined effect of self-emulsification and phase separation to provide confinement for directing the self-assembly of magnetic nanoparticles (MNPs). The resulting MSHS fully capitalize on both the multifunctional properties of MNPs and container features of single-hole hollow spheres. Moreover, the magnetic properties showed obvious improvement and can be tuned by modulating the assembled structure. Thus, MSHS can be used as a smart platform with multiple functionalities including image contrast enhancement, selective encapsulation for biomacromolecules, on-demand release, and magnetically guided transport. This strategy is very promising in the design of hierarchically structured assemblies for desired applications in biomedicine and other fields.

Quantitative Characterization of Mechanical Property of Annealed Monolayer Colloidal Crystal.

Quantitative characterization of the mechanical properties of a polystyrene (PS) monolayer colloidal crystal (MCC) annealed with solvent vapor has been performed for the first time by means of atomic force microscopy nanoindentation. The results showed that both the compressive and bending elastic modulus of PS MCC increased with the prolongation of annealing time from initial to 13 min. When the annealing time reached 15 min or even more, the PS MCC almost deformed to a planar film, and the elastic modulus of the PS MCC presented a drastic increase. These results provide a basis for tailoring the mechanical properties of a polymer colloidal monolayer via solvent vapor annealing. Such self-supported and high-mechanical-strength colloidal monolayers can be transferred to other surfaces for potential and promising applications in the bottom-up fabrication of highly ordered nanostructured materials such as nano dot arrays, photonic crystals, and many others.

Silence of bFGF enhances chemosensitivity of glioma cells to temozolomide through the MAPK signal pathway.

Basic fibroblast growth factor (bFGF) is a multifunctional growth factor in glioma cells and has been proved to be associated with the grade malignancy of glioma and prognosis of patients. Although there is evidence showing that bFGF plays an important role in proliferation, differentiation, angiogenesis, and survival of glioma cells, the effect of bFGF on chemosensitivity of glioma has not been verified. In this study, we analyzed the relationship between bFGF and chemotherapy resistance, with the objective of offering new strategy for chemotherapy of glioma patients. Here, siRNA was used to silence the expression of bFGF in glioma cell lines including U87 and U251 followed by chemotherapy of temozolomide (TMZ). Then, the characters of glioma including proliferation, apoptosis, migration, and cell cycle were studied in U87 and U251 cell lines. Our results demonstrated that silencing bFGF enhanced the effect of TMZ by inhibiting proliferation and migration, blocking cell cycle in G0/G1, and promoting apoptosis. In addition, the phosphorylation level of MAPK was measured to explore the mechanism of chemosensitization. The results showed that bFGF could promote the activation of the MAPK signal pathway. Our data indicated that bFGF might be a potential target for chemotherapy through the MAPK signal pathway.

Blocking the bFGF/STAT3 interaction through specific signaling pathways induces apoptosis in glioblastoma cells.

We have reported that basic fibroblast growth factor (bFGF) demonstrates an intimate connection with signal transducer and activator of transcription 3 (STAT3) in malignant brain tumor cells. However, its mechanisms are still unclear. In this study, we used inhibitors to block specific signaling pathways, including JAK, PI3K/Akt, and Src pathways, to explore how bFGF mediates crosstalk with STAT3 in two glioblastoma(GBM) cell lines: U251 (mutant p53) and U87 (wild-type p53). Furthermore, we explored how the bFGF/STAT3 pathway affects GBM cell apoptosis. Our results suggest that bFGF can induce the activation of STAT3 mainly through the JAK and PI3K/Akt pathways, and that siRNA-mediated knockdown of STAT3 markedly reduces the bFGF levels in U251 cells. Our results also suggest that STAT3 knockdown increases the expression of pro-apoptotic genes and decreases the expression of anti-apoptotic genes, subsequently collapsing the mitochondrial membrane potentials in vitro and impairs tumor growth in vivo.

Expression of interleukin-17A in lung tissues of irradiated mice and the influence of dexamethasone.

PURPOSE: To investigate the expressions of IL-17A in different phases of radiation-induced lung injury and the effect of dexamethasone. METHODS: The thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone-treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day) every day for the first month after irradiation. IL-17A in lung tissues was detected by immunohistochemistry. IL-17A, TGF-ß1, and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. Lung inflammation and collagen deposition were observed by H&E and Masson methods. The degree of alveolitis and fibrosis was judged according to scoring. RESULTS: IL-17A expression was appreciable at 1 week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation. IL-17A was reduced after dexamethasone application at all the observation periods. Dexamethasone also inhibited expressions of TGF-ß, IL-6, and TNF-α in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the severity of lung injury by reducing the infiltration of inflammatory cells and collagen deposition. Terms of survival and the time of death in mice of treatment group were postponed and survival rate was improved. CONCLUSIONS: IL-17A plays an important role in the process of radiation-induced lung injury. And dexamethasone may provide a protective role in lung injury induced by radiation.

Multiplexed sensitivity-encoding versus single-shot echo-planar imaging: a comparative study for diffusion-weighted imaging of the thyroid lesions.

PURPOSE: To compare multiplexed sensitivity-encoding diffusion-weighted magnetic resonance imaging (MUSE-DWI) and conventional DWI (cDWI) techniques in thyroid MRI. MATERIALS AND METHODS: Nineteen patients who underwent thyroid MRI using both MUSE-DWI and cDWI at a 3.0 T MRI system were enrolled. Qualitative parameters (image quality, thyroid contour, and lesion conspicuity) and quantitative parameters (signal-to-noise ratio (SNR), lesion-to-thyroid contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC)) were compared between the two sequences. In addition, ADC values derived from MUSE-DWI and cDWI were separately compared between benign and malignant lesions. RESULTS: MUSE-DWI outperformed cDWI in terms of image quality, thyroid contour, and lesion conspicuity. Significantly, higher signal-to-noise ratio (SNR) in both the thyroid and its lesion were found in MUSE-DWI than those in cDWI (both P < 0.05). The lesion-to-thyroid contrast-to-noise ratio (CNR) values were also significantly higher in MUSE-DWI than those in cDWI (P < 0.05). The apparent diffusion coefficient (ADC) of the thyroid in MUSE-DWI was significantly lower than that in cDWI (P < 0.05). The ADC of the lesion in MUSE-DWI was also significantly lower than that in cDWI (P < 0.05). In addition, ADC values derived from MUSE-DWI and cDWI were significantly higher in benign lesions than malignant lesions (P < 0.05). CONCLUSION: Compared with cDWI, MUSE-DWI can improve the image quality, thyroid contour sharpness, lesion conspicuity, SNR in both the thyroid and its lesions, and enhancing the CNR between lesions and thyroid.

Proliferation, migration and phenotypic transformation of VSMC induced via Hcy related to up-expression of WWP2 and p-STAT3.

To provide a theoretical basis for the prevention and treatment of atherosclerosis (AS), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on regulating the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMC) via sirtuin-1 (SIRT1)/signal transducer and activator of transcription 3 (STAT3) through Nedd4-like E3 ubiquitin-protein ligase WWP2 (WWP2). Here, Based on the establishment of ApoE-/- mouse models of high Hcy As and the model of Hcy stimulation of VSMC in vitro to observe the interaction between WWP2 and STAT3 and its effect on the proliferation, migration, and phenotypic transformation of Hcy-induced VSMC, which has not been previously reported. This study revealed that WWP2 could promote the proliferation, migration, and phenotype switch of Hcy-induced VSMC by up-regulating the phosphorylation of SIRT1/STAT3 signaling. Furthermore, Hcy might up-regulate WWP2 expression by inhibiting histone H3K27me3 expression through up-regulated UTX. These data suggest that WWP2 is a novel and important regulator of Hcy-induced VSMC proliferation, migration, and phenotypic transformation.