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To develop a novel 3D abdominal CEST MRI technique at 3 T using MR multitasking, which enables entire-liver coverage with free-breathing acquisition.k-Space data were continuously acquired with repetitive steady-state CEST (ss-CEST) modules. The stack-of-stars acquisition pattern was used for k-space sampling. MR multitasking was used to reconstruct motion-resolved 3D CEST images of 53 frequency offsets with entire-liver coverage and 2.0 × 2.0 × 6.0 mmBoth APT-CEST and glycoCEST signals showed high sensitivity between post-fasting and post-meal acquisitions. APT-CEST and glycoCEST MTRasym signals from post-mean scans were significantly increased (APT-CEST: -0.019 ± 0.017 in post-fasting scans, 0.014 ± 0.021 in post-meal scans, p 0.01; glycoCEST: 0.003 ± 0.009 in post-fasting scans, 0.027 ± 0.021 in post-meal scans, p 0.01).The proposed 3D abdominal steady-state CEST method using MR multitasking can generate CEST images of the entire liver during free breathing.

Chestnut-like aroma is one of the unique qualities of Chinese green tea and has become an important factor influencing consumer decisions. However, the chemical formation mechanism of chestnut-like aroma during green tea processing remains unclear. In this study, the dynamic changes of key components contributing to chestnut-like aroma and their precursors were analyzed in fresh leaves, fixation leaves, first baking tea leaves, and green tea.The thermal process had an important effect on volatile components in tea leaves, causing a significant decrease of alcohols and esters and a significant increase of ketones, acids, phenols, and sulfur compounds. Furthermore, 31 volatiles were identified as the key odorants responsible for chestnut-like aroma of green tea, including dimethyl sulfide, methyl isobutenyl ketone, 2-methylbutanal, 2,4-dimethylstyrene, d-limonene, methyl 2-methylvalerate, linalool, decanal, longifolene, phenylethyl alcohol, l-α-terpineol, jasmone, and so on. And the majority of these odorants were only formed in the drying stage. Additionally, isoleucine, theanine, methionine, and glucose were found to be involved in the formation of chestnut-like aroma of green tea.The drying process played a vital important role in the formation of chestnut-like aroma of green tea. © 2022 Society of Chemical Industry.

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of

This study aimed to clarify the attitudes, knowledge and vaccination willingness of patients with chronic diseases toward COVID-19 vaccines and the influencing factors.Vaccination against COVID-19 is an important way to protect patients with chronic diseases, but the vaccination acceptance varies across diseases and populations. A better understanding of this condition will lead to tailored intervention strategies and high vaccination rates.Cross-sectional study.Data were collected between March 2021 and May 2021 in China. A self-compiled questionnaire was used in the survey. Two independent-samples t-tests/one-way analysis of variance or U test/H test was used to measure the differences between groups. Multivariate regression analysis was used to identify the influencing factors. The study adhered to the EQUATOR checklist, STROBE.A total of 998 patients participated in the study. Score rates of attitudes, knowledge and vaccination willingness were 69.9%, 68.4% and 70.6% respectively. Age, vaccination status of family members, education levels, vaccine side effects and economic level were positive factors that could influence patients' vaccination acceptances, while time of illness, type of disease and political affiliations were negative predictors. The top reasons for willingness toward vaccination were supporting national strategies, belief on the vaccines and fearing of contracting COVID-19, while physical reasons, side effects and having a wait-and-see attitude were unwillingness factors.Patients' attitudes, knowledge and vaccination willingness were medium. Nurses should pay attention to patients who are from lower socioeconomic backgrounds, under 30 or over 70 years old, have no political affiliations, have damage to vital organs, have a long course of illness, family members have not received COVID-19 vaccines and had no side effects after receiving other vaccines.Clinical nurses are recommended to take measures from patients' duration of illness, damaged organs, demographic characteristics and families to improve patients' vaccination acceptances.

Sweet potato, commonly planted in Southeast Asia and South America with abundant rainfall, often suffers from waterlogging. The aerenchyma formation in roots is an effective way for plants to facilitate gas exchange. In the present study, tolerant and sensitive varieties, respectively, designated NC1 and C211, were evaluated under water oxygen content at 2.0 mg·L-1 (hypoxia treatment) and 8.0 mg·L-1 (control). The results showed that NC1 variety has a relatively higher root growth rate under low oxygen condition. In NC1 plants, aerenchyma was observed in the mid-section of the main adventitious root and spread to the proximal and distal ends, forming a complete channel in the cortex. However, in C211 plants, the aerenchyma occurred relatively later and could not turn into a whole channel. Ethylene synthesis-related (ACS1, ACS4, ACS5, etc.) and signal transduction-related (ETR1, ERS1, EIN2, etc.) genes were upregulated in the NC1 plants and led to changes in the reactive oxygen species-related genes (RBOHA, SOD, CAT, etc.) and enzyme activities. It was found that programmed cell death was induced by H2 O2 accumulation. A regulatory model of lysigenous aerenchyma formation in the root of sweet potato was constructed. Our study enriches the understanding of the mechanisms of the aerenchyma formation in plants.

Chronic hepatitis B virus (HBV) infection changes the composition of the extracellular matrix (ECM) and enables the onset and progression of hepatocellular carcinoma (HCC). The ensemble of ECM proteins and associated factors is a major component of the tumor microenvironment. Our aim was to unveil the matrisome genes from HBV‐related HCC. Transcriptomic and clinical profiles from 444 patients with HBV‐related HCC were retrieved from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) repositories. Matrisome genes associated with HBV‐related hepatocarcinogenesis, matrisome gene modules, HCC subgroups, and liver‐specific matrisome genes were systematically analyzed, followed by identification of their biological function and clinical relevance. Eighty matrisome genes, functionally enriched in immune response, ECM remodeling, or cancer‐related pathways, were identified as associated with HBV‐related HCC, which could robustly discriminate HBV‐related HCC tumor from nontumor samples. Subsequently, four significant matrisome gene modules were identified as showing functional homogeneity linked to cell cycle activity. Two subgroups of patients with HBV‐related HCC were classified based on the highly correlated matrisome genes. The high‐expression subgroup (15.0% in the TCGA cohort and 17.9% in the GEO cohort) exhibited favorable clinical prognosis, activated metabolic activity, exhausted cell cycle, strong immune infiltration, and lower tumor purity. Four liver‐specific matrisome genes (F9, HPX [hemopexin], IGFALS [insulin‐like growth‐factor‐binding protein, acid labile subunit], and PLG [plasminogen]) were identified as involved in HBV‐related HCC progression and prognosis. Conclusion: This study identified the expression and function of matrisome genes from HBV‐related hepatocarcinogenesis, providing major insight to understand HBV‐related HCC and develop potential therapeutic opportunities., Matrisome genes function as modules and sub‐classify HBV‐related HCC patients that exhibit distinct molecular patterns and clinical outcomes. Liver‐specific matrisome genes are involved in HBV‐related HCC, which could be ideal candidate therapeutic targets.

Background and purpose Abnormal vascular smooth muscle cell (VSMC) proliferation and migration lead to neointima formation, which eventually results in cardiovascular hyperplastic diseases. However, the molecular mechanisms underlying these cellular processes have not been fully understood. Cytokine induced apoptosis inhibitor 1 (CIAPIN1) has been identified as an anti-apoptotic molecule, but little is known about its target genes and related pathways in VSMC dysfunction, or about its clinical implication in neointima formation following vascular injury. Experimental approach We used loss/gain-of-function approaches by gene delivery to determine whether CIAPIN1 modulates VSMC proliferation, migration, and neointima formation, and to define the underlying mechanisms. Balloon-injury or ligation, and local delivery of lentivirus, were performed on rat or mouse carotid arteries. Rat aortic SMCs (RASMCs), known as the primary cell, were applied as the cell model to evaluate the effect of CIAPIN1 on proliferation and migration. Key results CIAPIN1 was overexpressed in the neointimal region of rat arteries. A deficiency of CIAPIN1 markedly inhibited injury-induced or ligation-induced intimal hyperplasia and suppressed PDGF-BB-induced VSMC proliferation, migration, and cell cycle progression, while CIAPIN1 overexpression promoted VSMC proliferation, migration, and neointima formation in vascular injury conditions. Mechanistically, CIAPIN1 (i) negatively regulated p53 transcription, which promoted cell cycle progression and migration via (ii) cyclin E1-CDK2/pRb/PCNA and the MMP-2 pathway. In addition, CIAPIN1 (iii) increased JAK2 expression, thus (iv) enhancing JAK2 and STAT3 phosphorylation by vascular injury, which (v) forced phenotypic switching from contractile to synthetic state in injured arteries. Conclusions and implications These findings provide new insights into the mechanism by which CIAPIN1 regulates vascular remodelling and suggest a novel therapeutic target for treating vascular proliferative diseases.

Purpose To develop a 3D multitasking multi-echo (MT-ME) technique for the comprehensive characterization of liver tissues with 5-min free-breathing acquisition; whole-liver coverage; a spatial resolution of 1.5 × 1.5 × 6 mm3 ; and simultaneous quantification of T1 , water-specific T1 (T1w ), proton density fat fraction (PDFF), and R 2 ∗ . Methods Six-echo bipolar spoiled gradient echo readouts following inversion recovery preparation was performed to generate T1 , water/fat, and R 2 ∗ contrast. MR multitasking was used to reconstruct the MT-ME images with 3 spatial dimensions: 1 T1 recovery dimension, 1 multi-echo dimension, and 1 respiratory dimension. A basis function-based approach was developed for T1w quantification, followed by the estimation of R 2 ∗ and T1 -corrected PDFF. The intrasession repeatability and agreement against references of MT-ME measurements were tested on a phantom and 15 clinically healthy subjects. In addition, 4 patients with confirmed liver diseases were recruited, and the agreement between MT-ME measurements and references was assessed. Results MT-ME produced high-quality, coregistered T1 , T1w , PDFF, and R 2 ∗ maps with good intrasession repeatability and substantial agreement with references on phantom and human studies. The intra-class coefficients of T1 , T1w , PDFF, and R 2 ∗ from the repeat MT-ME measurements on clinically healthy subjects were 0.989, 0.990, 0.999, and 0.988, respectively. The intra-class coefficients of T1 , PDFF, and R 2 ∗ between the MT-ME and reference measurements were 0.924, 0.987, and 0.975 in healthy subjects and 0.980, 0.999, and 0.998 in patients. The T1w was independent to PDFF (R = -0.029, P = .904). Conclusion The proposed MT-ME technique quantifies T1 , T1w , PDFF, and R 2 ∗ simultaneously and is clinically promising for the comprehensive characterization of liver tissue properties.

Purpose To develop a single-scan method for B 1 + -corrected T1 mapping and apply it for free-breathing (FB) cardiac MR multitasking without electrocardiogram (ECG) triggering. Methods One dual flip-angle (2FA) inversion recovery (IR)-FLASH scan provides two observations of T 1 ∗ (apparent T1 ) corresponding to two distinct combinations of the nominal FA α and B 1 + . Spatiotemporally coregistered T1 and B 1 + spin history maps are obtained by fitting the 2FA signal model. T1 estimate accuracy and repeatability for single flip-angle (1FA) and 2FA IR-FLASH sequence MR multitasking were evaluated at 3T. A T1 phantom was first imaged on the scanner table, then on two human subjects' thoraxes in both breath-hold (BH) and FB conditions. IR-turbo spin echo (IR-TSE) static phantom T1 measurements served as reference. In 10 healthy subjects, myocardial T1 was evaluated with ECG-free, FB multitasking sequences alongside ECG-triggered BH MOLLI. Results For phantom-on-table T1 estimates, 2FA agreed better with IR-TSE (intraclass correlation coefficient [ICC] = 0.996, mean error ± SD = -1.6% ± 1.9%) than did 1FA (ICC = 0.922; mean error ± SD = -4.3% ± 12%). For phantom-on-thorax, 2FA was more repeatable and robust to respiration than 1FA (coefficient of variation [CoV] = 1.2% 2FA, = 11.3% 1FA). In vivo, in intrasession T1 repeatability, 2FA (septal CoV = 2.4%, six-segment CoV = 4.4%) outperformed 1FA (septal CoV = 3.1%, six-segment CoV = 5.5%). In six-segment T1 homogeneity, 2FA (CoV = 7.9%) also outperformed 1FA (CoV = 11.1%). Conclusion The 2FA IR-FLASH improves T1 estimate accuracy and repeatability over 1FA IR-FLASH, and enables single-scan B 1 + -corrected T1 mapping without BHs or ECG when used with MR multitasking.

In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed.

Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR-448-3p has been reported to be involved in the development of DM, but whether miR-448-3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR-448-3p therein, Sprague-Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR-448-3p levels in vivo and in vitro were upregulated by adeno-associated virus serotype 2 (AAV2)-miR-448-3p injection and miR-448-3p mimic transfection, respectively. Our results showed that AAV2-miR-448-3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR-448-3p level was significantly decreased and the dipeptidyl peptidase-4 (DPP-4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR-448-3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial-mesenchymal transition (EndMT), while AAV2-miR-448-3p injection relieved those situations. In vitro experiments demonstrated that miR-448-3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor-β/Smad pathway. We further proved that miR-448-3p negatively regulated DPP-4 by binding to its 3'-untranslated region, and DPP-4 overexpression reversed the effect of miR-448-3p overexpression on EndMT. Overall, we conclude that miR-448-3p overexpression inhibits EndMT via targeting DPP-4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR-448-3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.

Renal ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI), which is closely related to high morbidity and mortality. However, the pathogenesis underlying renal IRI is complex and not fully defined. N6-methyladenosine (m6A) was recently found to be an abundant modification in mammalian messenger RNAs. It is implicated in various biological processes, while the role of m6A in IRI is not illustrated. Here we show that the m6A-methylated RNA level and its methyltransferase METTL14 are elevated in human AKI renal tissues and IRI HK-2 cells. Moreover, METTL14 knockdown protects the kidney against IRI in vitro and in vivo. Mechanistically, we identified that YAP1 is a direct target of METTL14 in AKI progression. Inhibition of YAP1-TEAD signaling by peptide 17 abrogates the protective effect of METTL14 against IRI in vitro and in vivo. Taken together, these results reveal that the N6-methyladenosine mRNA methylase METTL14 promotes the renal IRI via suppressing YAP1. The discovery of the METTL14-YAP1 pathway provides an important new perspective for understanding AKI and is conducive to revealing new therapeutic strategies and targets.

Spiropyran (SP) and its derivatives operate between their ring opening and closing forms as a versatile molecular platform for the fluorescence detection of cations and anions, using a colour change for signalling. A functionalized SP fluorescence probe, L, was prepared and characterized. Probe L can detect Ca2+ with a fluorescence 'turn-on' response in ethanol solution. It selectively binds Ca2+ to form a 1:1 ligand/metal complex, which produced a new emission band centred at 604 nm. The sensing result was clearly observed by the solution colour change from colourless to pink under visible light, and from blue to red under ultraviolet light. The detection limit was calculated to be 4.53 × 10-8 M for Ca2+ . The probe provides another possibility that SP-based derivatives could be used for the development and detection of metal ions in environmental and physiological systems.

Amide bond formation is one of the most important reactions in organic chemistry because of the widespread presence of amides in pharmaceuticals and biologically active compounds. Existing methods for amides synthesis are reaching their inherent limits. Described herein is a novel rhodium-catalyzed three-component reaction to synthesize amides from organic azides, carbon monoxide, and (hetero)arenes via nitrene-intermediates and direct C-H functionalization. Notably, the reaction proceeds in an intermolecular fashion with N2 as the only by-product, and either directing groups nor additives are required. The computational and mechanistic studies show that the amides are formed via a key Rh-nitrene intermediate.

Background China has not yet incorporated routine human T-lymphotropic virus (HTLV)-1/2 blood donor screening, even though HTLV has been reported in the southeastern coastal region. This study was conducted to investigate the prevalence of HTLV in five major regions across of China. Methods From January 2016 to December 2017, blood samples were collected in 20 blood centers located in different regions of China. These samples were screened for HTLV-1/2 antibodies using enzyme-linked immunosorbent assay (ELISA). If the test samples were reactive, the samples were confirmed with a western blot (WB) assay. If the results of WB were indeterminate, the donor was interviewed after a minimum lapse of 8 weeks. All follow-up samples from donors were tested for anti-HTLV-1/2 with ELISA and WB. Results There were 875,453 donor samples tested for anti-HTLV-1/2 by ELISA. In all, 365 samples tested negative, 22 samples tested positive by WB, and 14 samples with HTLV status undetermined due to being lost to follow-up. The prevalences were 11.09, 5.96, 3.16, 2.88 and 0.98 per 100,000 in Xiamen, Changsha, Beijing, Shenzhen, and Nanjing blood center, respectively. The prevalences were 0 per 100,000 for all 15 other blood centers. There was significant differences in the prevalence of HTLV in different regions of China (p = 0.0011). Conclusion In China, HTLV-1 confirmed positive donors are mainly from southeastern coastal areas. It may be necessary to conduct HTLV screening in these areas to reduce the risk of transfusion-transmitted HTLV.

Prostate cancer (PCa) is one of the major cancers affecting males with high mortality around the world. Recent studies have found that some long noncoding RNAs play a critical part in the cellular processes of PCa. In our study, aberrant expressed lymphoid enhancer-binding factor-1 antisense RNA 1 (LEF1-AS1), microRNA-330-5p (miR-330-5p), and lymphoid enhancer-binding factor-1 (LEF1) were screened out from a microarray database, the role of the novel noncoding RNA regulatory circuitry in the initiation and development of PCa was investigated. LEF1-AS1 and LEF1 were highly expressed while miR-330-5p was poorly expressed in PCa. Following that, the PCa PC-3 cell line was adopted for subsequently experiments, in which the expression of LEF1-AS1 and miR-330-5p was subsequently altered by means of exogenous transfection. After that, the effects of up- or downregulation of LEF1-AS1 and miR-330-5p on epithelial-mesenchymal transition (EMT) and the cell ability for proliferation, invasion, migration in vitro, and tumorigenesis and lymph node metastasis (LNM) in vivo were evaluated. RNA crosstalk revealed that LEF1-AS1 bound to miR-330-5p and LEF1 was the target gene of miR-330-5p. Silenced LEF1-AS1 or elevated miR-330-5p exhibited inhibited EMT processes, reduced ability of proliferation, invasion and migration, coupling with decreased tumorigenesis and LNM in nude mice. The key findings of this study collectively propose downregulation of LEF1-AS1 competing with miR-330-5p to inhibit EMT, invasion and migration of PCa by LEF1 repression.

Bergapten is a natural compound and has potent anticancer activities. In this study, we explored the cytotoxicity of bergapten on colorectal cancer (CRC) cell DLD-1 and LoVo and its underlying mechanisms. We observed that bergapten (30 and 50 μM) decreased the viability of the CRC cells and induced the G0/G1 and sub-G1 phase arrest. Furthermore, immunoblotting results indicated that bergapten increased p53, phospho-p53(Ser-46), p21, PUMA, Bax, PTEN, and the caspase-9 and caspase-3 cleavage, but decreased cyclin E, CDK2, and phosphor-AKT(Ser-473) in the CRC cells. Inhibition of p53 by pifithrin-α reversed the bergapten-induced p53-mediated apoptotic cascade and restored the survival signaling and cell viability. Collectively, our findings reveal that bergapten decrease the cell viability and induce cell cycle arrest in the CRC cells, which may be attributed to p53-mediated apoptotic cascade, upregulation of p21 and PTEN, and inhibition of AKT.

Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity-induced diabetes are explored and the underlying mechanisms are investigated.C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular CaThese findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity-induced diabetes.

The aim of this study was to investigate the relationship between androgen deprivation therapy and heart failure among prostate cancer patients. This cohort study used the data from the Taiwan Longitudinal Health Insurance Database 2005. In the full cohort study, we identified 1244 prostate cancer patients who had received androgen deprivation therapy as the study cohort and 1806 prostate cancer patients who did not receive androgen deprivation therapy as the comparison cohort. To eliminate potential bias, we performed a propensity score-matched cohort study. Each prostate cancer patient was tracked for 1 year from the index date to ascertain whether they were subsequently diagnosed with heart failure. In the full cohort study, incidence rates of heart failure per 100 person-years within the 1-year follow-up period were 4.00 (95%CI, 2.95-5.30) and 1.89 (95%CI, 1.30-2.66) for androgen deprivation therapy users and nonusers, respectively. In addition, the multivariable Cox regression indicated that the hazard ratio (HR) of heart failure among androgen deprivation therapy users was 1.72 (95%CI, 1.08-2.73) compared with those androgen deprivation therapy nonusers. In the propensity score-matched cohort study, the adjusted HR for heart failure among androgen deprivation therapy users was 1.92 (95%CI, 1.15-3.18) compared with propensity score-matched nonusers. In conclusion, this study found that androgen deprivation therapy users had a higher risk of heart failure than nonusers among prostate cancer patients in both the full cohort study and the propensity score-matched study.

In this study, the baseline separations of xylene isomers and phthalate acid esters on a homemade DUT-67(Zr) packed column were achieved, respectively. The high selectivity for xylene isomers and phthalate acid esters was obtained with the increase in temperature and decrease in the retention time. The hydrophobicity of xylene isomers and phthalate acid esters resulted in the different separation time on the DUT-67(Zr) packed column. The relative standard deviation values of retention time, peak area, peak height, and half peak width for five repeat separation of the xylene isomers were 0.26-0.35, 2.11-2.26, 1.51-2.03, and 0.29-0.77%, and the values of the phthalate acid esters on DUT-67(Zr) column were 0.1-0.4, 4.4-5.2, 3.9-6.3, and 0.6-2.1%, respectively. The thermodynamic properties indicated that the separation of xylene isomers was controlled by ΔH and ΔS, but the separation of phthalate acid esters was mainly controlled by ΔS.

BACKGROUND AND PURPOSE The proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) are important steps in cardiovascular diseases, including neointimal lesion formation, myocardial infarction, and atherosclerosis. Here, we evaluated the rubiarbonone C-mediated signaling pathways that regulate PDGF-induced VSMC proliferation and migration. EXPERIMENTAL APPROACH Cell proliferation and migration were measured in cells treated with rubiarbonone C followed by PDGF-BB treatment using the MTT assay, [3H]-thymidine incorporation, flow cytometry, and wound healing migration assay, matrix metalloproteinase (MMP) gelatin zymography, a fluorescence assay for F-actin. Western blotting of molecules including mitogen-activated protein (MAP) kinase, focal adhesion kinase (FAK), and signal transducer and activator of transcription 3 (STAT3) and an immunofluorescence assay using anti-proliferating cell nuclear antigen (PCNA) and -STAT3 antibodies were performed to evaluate rubiarbonone C signaling pathway(s). Medial thickness of carotid artery was evaluated using mouse carotid ligation model. KEY RESULTS Rubiarbonone C inhibited PDGF-induced VSMC proliferation and migration, and diminished ligation-induced medial thickness of carotid artery. The effects of rubiarbonone C on PDGF-stimulated VSMCs included decreased (i) levels of cyclin-dependent kinases (CDKs), cyclins, PCNA, and hyperphosphorylated retinoblastoma protein (pRb), and (ii) levels and activity of MMP2 and MMP9, (iii) activation of MAP kinase, (iv) F-actin reorganization via reduced FAK activation, and (v) activation of STAT3. CONCLUSIONS AND IMPLICATIONS These findings suggest that rubiarbonone C inhibits VSMC proliferation and migration by inhibiting the FAK, MAP kinase, and STAT3 signaling pathways. Therefore, rubiarbonone C can be a good candidate for the treatment of cardiovascular disease.

Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (CKD) and immune cells influence this process. The roles of monocytes/macrophages, T cells, and mast cells have been carefully examined, whilst only a few studies have focused on the effect of B cells. We investigated B-cell function in tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), using genetic B-cell-deficient μMT mice or CD20 antibody-mediated B-cell-depleted mice. Obstructed kidneys of μMT and anti-CD20-treated mice showed lower levels of monocyte/macrophage infiltration and collagen deposition compared to wild-type mice. Mechanistically, anti-CD20 attenuated UUO-induced alterations of renal tumour necrosis factor-α (TNF-α), vascular cell adhesion molecule 1 (VCAM-1) pro-inflammatory genes, and CC chemokine ligand-2 (CCL2) essential for monocyte recruitment; B cells were one of the main sources of CCL2 in post-UUO kidneys. Neutralization of CCL2 reduced monocyte/macrophage influx and fibrotic changes in obstructed kidneys. Therefore, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration, aggravating the fibrosis resulting from acutely induced kidney nephropathy. © 2016 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.