Search

Adult mammals have limited potential for cardiac regeneration after injury. In contrast, neonatal mouse heart, up to 7 days post birth, can completely regenerate after injury. Therefore, identifying the key factors promoting the proliferation of endogenous cardiomyocytes (CMs) is a critical step in the development of cardiac regeneration therapies. In our previous study, we predicted that mitogen-activated protein kinase (MAPK) interacting serine/threonine-protein kinase 2 (MNK2) has the potential of promoting regeneration by using phosphoproteomics and iGPS algorithm. Here, we aimed to clarify the role of MNK2 in cardiac regeneration and explore the underlying mechanism. In vitro , MNK2 overexpression promoted, and MNK2 knockdown suppressed cardiomyocyte proliferation. In vivo , inhibition of MNK2 in CMs impaired myocardial regeneration in neonatal mice. In adult myocardial infarcted mice, MNK2 overexpression in CMs in the infarct border zone activated cardiomyocyte proliferation and improved cardiac repair. In CMs, MNK2 binded to eIF4E and regulated its phosphorylation level. Knockdown of eukaryotic translation initiation factor (eIF4E) impaired the proliferation-promoting effect of MNK2 in CMs. MNK2-eIF4E axis stimulated CMs proliferation by activating cyclin D1. Our study demonstrated that MNK2 kinase played a critical role in cardiac regeneration. Over-expression of MNK2 promoted cardiomyocyte proliferation in vitro and in vivo, at least partly, by activating the eIF4E-cyclin D1 axis. This investigation identified a novel target for heart regenerative therapy. [Display omitted] • Neonatal mice can regenerate completely after heart injury, while adult mice lose this ability • MNK2 protein kinase is first found to promote cardiomyocyte proliferation and cardiac regeneration • MNK2 do not affect heart growth of healthy mouse • MNK2-eIF4E-cyclin D1 axis is first proved to promoted cardiomyocyte proliferation [ABSTRACT FROM AUTHOR]

[Display omitted] • Detailed ATR-SEIRAS study of the cation effects on CO 2 RR on practical Pd/C catalysts. • Spectral evidence of increased interfacial CO 2 concentration and electric field by larger cations. • Mechanistic understanding of cation effects on potential dependent CO 2 RR pathways. Electrochemical carbon dioxide (CO 2) reduction reaction (CO 2 RR) has long been known to be affected by the electrolyte cations, yet the interpretations of these effects remain controversial. In this work, taking advantage of the unique catalytic characteristics of Pd, we investigated the cation effects on the CO 2 RR. It was found that the productions of formate and carbon monoxide (CO) are accelerated, and the competitive hydrogen evolution reaction (HER) is suppressed on Pd surfaces by larger cations. Detailed ATR-SEIRAS measurements revealed the promotion of CO 2 RR comes from two aspects. First, the CO 2 molecules can be concentrated at the electrode–electrolyte interface by larger cations through electrostatic interaction. Second, a stronger interfacial electric field brought by the larger cations can accelerate the CO 2 RR and stabilize the negatively charged intermediates. The potential-dependent spectral transitions of adsorbed CO and interfacial water shed new light on the cation-dependent electric double layer structures. In light of these findings, the cation effects on the formate and CO pathways at different overpotentials were further revealed. [ABSTRACT FROM AUTHOR]

Sarcopenia is an important factor affecting the prognostic outcomes in adult cancer patients. Gastric cancer is considered an age-related disease and is one of the leading causes of global cancer mortality. We aimed to establish an effective age-related model at a molecular level to predict the prognosis of patients with gastric cancer. TCGA STAD (stomach adenocarcinoma) and NCBI GEO database were utilized in this study to explore the expression, clinical relevance and prognostic value of age-related mRNAs in stomach adenocarcinoma through an integrated bioinformatics analysis. WGCNA co-expression network, Univariate Cox regression analysis, LASSO regression and Multivariate Cox regression analysis were implemented to construct an age-related prognostic signature. As a result, sarcopenia is not only an unfavorable factor for OS (overall survival) in patients with tumor of gastric (HR: 1.707, 95%CI: 1.437–2.026), but also increases the risk of postoperative complications in patients with gastric cancer (OR: 2.904, 95%CI: 2.150–3.922). A panel of 5 mRNAs (DCBLD1, DLC1, IGFBP1, RNASE1 and SPC24) were identified to dichotomize patients with significantly different OS and independently predicted the OS in TCGA STAD (HR = 3.044, 95%CI = 2.078–4.460, P < 0.001). The study provided novel insights to understand STAD at a molecular level and indicated that the 5 mRNAs might act as independent promising prognosis biomarkers for STAD. Sarcopenia and the 5-mRNA risk module as a combined factor to predict prognosis may play an important role in clinical diagnosis. • The strong association between sarcopenia and short- and long-term clinical outcomes of STAD patients • Age play important roles in sarcopenia and gastric cancer. • WGCNA analysis was used to screen age-related mRNAs. • Sarcopenia and the 5-mRNA module as a combined factor to predict prognosis might play an important role in STAD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four undescribed coumarins derivatives, including ficusalt A (1) and ficusalt B (2), and a pair of racemic coumarins, (±) ficudimer A (3a / 3b), were isolated from the roots of Ficus hirta. • Compound 5 had distinct cytotoxic activity against HeLa cells, induced their apoptosis, and significantly inhibited their invasion and migration. • Compound 5 obviously increased the cleavage of PARP, the phosphorylation level of p38 and JNK, and the expression of pro-apoptotic protein of Bax, whereas inhibited the expression of p-ERK and p-AKT. Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a / 3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

The rational structure design and controllable surface modification of electrode materials plays a decisive role in constructing high performance energy storage and conversion devices. Herein, the P-doped cobalt carbonate hydroxide@NiMoO 4 (P-CoCH@NiMoO 4) nanowires@nanosheets double-shell hierarchical structure is successfully fabricated on nickel foam. The unique nanowire@nanosheet structure with gradient porous distribution and hydrophilic nature can facilitate both the charge and electron transfer based on the synergetic effects with conductive NiMoO 4 array. Importantly, the dopant of P element can enrich oxygen vacancies on the surface of CoCH nanowire, thus increase the effective active sites and enhance the electrocatalytic performance. Therefore, when act as the supercapacitor electrode, the bi-functional P-CoCH@NiMoO 4 /NF material achieves high areal capacitance (5.08 F cm−2 at 2 mA cm−2, 0.75 mAh cm−2) and good cyclic stability (82.7% capacitance retention after 2000 cycles). Meanwhile, when utilize as the hydrogen evolution electrode in alkaline solution, a low overpotential (115 mV at 10 mA cm−2) and Tafel slope (113.5 mV dec−1) can also be achieved. [ABSTRACT FROM AUTHOR]

As a class of endogenous non-coding RNAs with closed-loop structure, circular RNAs (circRNAs) are receiving more and more attention. CircRNAs have been reported to be widely expressed in various human cancers and are implicated in tumorigenesis and progression. The present study aimed to systematically evaluate the clinicopathological, diagnostic and prognostic values of circRNAs in lung cancer. We searched literature from PubMed, Web of science, Cochrane Library, EMBASE and Ovid online databases up to May 29, 2020. Statistical analyses were undertaken based on Stata 11.0, Meta-DiSc 1.4, and RevMan 5.3 software. Finally, a total of 63 eligible articles were included in our meta-analysis, including 18 studies for diagnosis, 22 studies for prognosis and 57 studies for clinicopathological features. In terms of diagnostic values, circRNAs could discriminate between lung cancer patients and the normal individuals with a relatively high pooled area under the curve (AUC) of 0.83 (95%CI, 0.80–0.86). For the prognostic values, we found that elevated expression of oncogenic circRNAs could predict poor survival outcomes based on multivariate analysis (HR = 2.430, 95%CI = 2.003–2.948, P < 0.001 for OS; HR = 2.228, 95%CI = 1.289–3.853, P = 0.004 for DFS) while tumor-suppressor circRNAs was correlated with better OS in univariate analysis (HR = 0.627, 95%CI = 0.519–0.757, P < 0.001). The pooled results suggested that elevated expression of carcinogenic circRNAs was associated with tumor size (OR = 1.676, 95%CI = 1.209–2.323, P = 0.002), smoking statue (OR = 1.260, 95%CI = 1.062–1.494, P = 0.008), TNM stage (OR = 2.345, 95%CI = 1.617–3.399, P < 0.001), differentiation grade (OR = 1.843, 95%CI = 1.228–2.765, P = 0.003), and lymphatic metastasis (OR = 2.097, 95%CI = 1.482–2.967, P < 0.001). Moreover, the expression of tumor-suppressor circRNAs was related to the improved clinicopathological features (lymphatic metastasis: OR = 0.536, 95%CI = 0.311–0.926, P = 0.025). Our meta-analysis demonstrated that circRNAs could be used as feasible and important biomarkers for diagnosis, prognosis and clinicopathological features in lung cancer. [ABSTRACT FROM AUTHOR]

Abstract Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 μM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway. Highlights • The mRNA-seq data showed a vital role of PFKFB3 in LPS-caused cardiac dysfunction. • LPS stimulated significant protein upregulation of PFKFB3 in cardiomyocytes. • PFKFB3 blocker alleviated LPS-induced cardiac dysfunction and myocardial injury. • PFKFB3 may promote cardiac dysfunction via mediating inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Ship ballasting operations may transfer harmful aquatic organisms across global ocean. This study aims to reveal the occurrences and abundances of antibiotic resistance genes (ARGs) and human bacterial pathogens (HBPs) in ballast tank sediments. Nine samples were collected and respectively analyzed by real-time quantitative PCR and high-throughput sequencing technologies. Ten ARGs ( aadA1 , blaCTX-M , blaTEM , ermB , mefA , strB , sul1 , sul2 , tetM , and tetQ ) and the Class-I integron gene ( intI1 ) were highly prevalent (10 5 –10 9 gene copies/g) in ballast tank sediments. The sul1 was the most abundant ARG with the concentration of 10 8 –10 9 copies/g and intI1 was much more abundant than the ARGs in ballast tank sediments. The strong positive correlations between intI1 and ARGs ( blaCTX-M , sul1 , sul2 and tetM ) indicated the potential spread of ARGs via horizontal gene transfer. In ballast tank sediments, 44 bacterial species were identified as HBPs and accounted for 0.13–21.46% of the total bacterial population although the three indicator pathogenic microbes ( Vibrio cholerae , Escherichia coli , and Enterococci ) proposed by the International Maritime Organization were not detected. Pseudomonas pseudoalcaligenes , Enterococcus hirae , Shigella sonnei and Bacillus anthracis were the dominant pathogens in ballast tank sediments. Zn and P in sediments had positive effects on the ARGs. Network analysis results indicated that sul1 and sul2 genes existed in several bacterial pathogens. Ballast tank sediments could be regarded as a carrier for the migration of ARGs. It is important to manage ballast tank sediments reasonably in order to prevent the dissemination of ARGs and bacterial pathogens. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly heterogeneous disease, with biologically and prognostically different subtypes. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. The molecular mechanism underlying AML needs to be further investigated. Here we identify IRF9 as a negative regulator of human AML. We show that IRF9 mRNA and protein levels are down-regulated in human AML samples compared with samples from healthy donors. IRF9 knockdown promotes proliferation, colony formation and survival of OCI/AML-2 and OCI/AML-3 cells, whereas IRF9 overexpression obtains oppose results. Mechanism analysis shows that IRF9 binds SIRT1 promoter and represses SIRT1 expression in OCI/AML-2 and OCI/AML-3 cells. In AML samples, the expression of SIRT1 is up-regulated and negatively correlated with IRF9 level. IRF9 also increases the acetylation of p53, a deacetylation substrate of SIRT1, and promotes the expression of p53 target genes. Knockdown of p53 blocks the effects of IRF9 on cell survival and growth in vitro . These findings provide evidence that IRF9 serves as an important regulator in human AML by repressing SIRT1-p53 pathway and that IRF9 may be a potential target for AML treatment. [ABSTRACT FROM AUTHOR]

Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA-1523 (5 μM) sensitized the ABCG2 overexpressing cancer cells and ABCG2 transfected cells to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2; also there was no change in the protein expression or the localization of the ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was reversible. Importantly, co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken together, our findings indicate that CCTA-1523 is a potent, selective and reversible modulator of ABCG2 that may offer therapeutic promise for multidrug- resistant malignancies. [ABSTRACT FROM AUTHOR]

A QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) method, for reliable semi-quantitative screening of 27 organic contaminants including phthalates (PAEs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) by gas chromatography-mass spectrometry (GC-MS) in edible oil, was developed. N-hexane saturated with acetonitrile and C 18 -Z-Sep+ was used for extraction and cleanup in liquid liquid extraction-dispersive solid phase extraction (LLE-dSPE) combined with freezing-lipid precipitation. Subsequently, NAGINATA2.0 software with a constructed calibration-locking database was used to detect the organic contaminants and validate the method. The calibration curves were observed to be linear in the range of 0.01–0.5 µg/mL for PAEs and PAHs, and 0.02–1 µg/mL for PCBs. The recoveries for most of the organic contaminants were in range of 70.9–110% with relative standard deviation less than 20%. The proposed method should provide an efficient tool for semi-quantitative screening of numerous organic contaminants in edible oil samples simultaneously. • A semi-quantitative screening of organic pollutants in edible oil was developed. • LLE-dSPE combined with freezing-lipid precipitation was used for the pretreatment. • The method possessed excellent accuracy, precision and repeatability. • The method contributes to the safety risk monitoring of edible oil. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four undescribed seco -polyprenylated acylphloroglucinols from H. elodeoides. • A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. • Compound 1 induced MCF-7 cell apoptosis. • Compound 1 arrested cell cycle at S phase via inducing oxidative DNA damage. Four undescribed seco -polyprenylated acylphloroglucinols (seco -PAPs), elodeoidesones A-D (1 – 4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6- seco -PAPs with fascinating 5/5 fused ring, while 2 – 4 possess a 1,2- seco -PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1 – 4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC 50 value of 7.34 μM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a serious disease of the hematopoietic system characterized by de-differentiation and uncontrolled proliferation of immature hematopoietic precursor cells in the bone marrow. However, the underlying mechanism of AML development remains largely unknown. Here in this study, we report the function of IRF3, a member of the interferon-regulatory factor (IRF) family, in human AML. We first show that IRF3 mRNA and protein levels are significantly up-regulated in human AML compared with healthy donors. IRF3 knockdown inhibits cellular proliferation and colony formation in OCI/AML-2 and OCI/AML-3 cells. In addition, IRF3 knockdown induces apoptosis of OCI/AML-2 and OCI/AML-3 cells, whereas IRF3 overexpression promotes cell survival. Further mechanism study shows that IRF3 is positively correlated with miR-155, which is considered as an oncogenic microRNA in AML. We show that IRF3 binds to the promoter of miR-155 and promotes the expression of miR-155 in OCI/AML-2 and OCI/AML-3 cells. In conclusion, our evidence show that IRF3 overexpression in AML promotes cell growth and survival, and miR-155 is involved, indicating that IRF3 may be a potential new biomarker and therapeutic target for AML. [ABSTRACT FROM AUTHOR]

Cardiac dysfunction is a vital complication of endotoxemia (ETM) with limited therapeutic options. Transient receptor potential canonical channel (TRPC)1 was involved in various heart diseases. While, the role of TRPC1 in ETM-induced cardiac dysfunction remains to be defined. In this study, we found that TRPC1 protein expression was significantly upregulated in hearts of lipopolysaccharide (LPS)-challenged mice. What's more, TRPC1 knockdown significantly alleviated LPS-induced cardiac dysfunction and injury. Further myocardial mRNA-sequencing analysis revealed that TRPC1 might participate in pathogenesis of ETM-induced cardiac dysfunction via mediating myocardial apoptosis and autophagy. Data showed that knockdown of TRPC1 significantly ameliorated LPS-induced myocardial apoptotic injury, cardiomyocytes autophagosome accumulation, and myocardial autophagic flux. Simultaneously, deletion of TRPC1 reversed LPS-induced molecular changes of apoptosis/autophagy signaling pathway in cardiomyocytes. Moreover, TRPC1 could promote LPS-triggered intracellular Ca2+ release, subsequent calpain activation and caveolin-1 degradation. Either blocking calpain by PD150606 or enhancing the amount of caveolin-1 scaffolding domain that interacts with TRPC1 by cell-permeable peptide cavtratin significantly alleviated the LPS-induced cardiac dysfunction and cardiomyocytes apoptosis/autophagy. Furthermore, cavtratin could inhibit LPS-induced calpain activation in cardiomyocytes. caveolin-1 could directly interact with calpain 2 both in vivo and in vitro. Importantly, cecal ligation and puncture-stimulated cardiac dysfunction and mortality were significantly alleviated in Trpc1 -/- and cavtratin-treated mice, which further validated the contribution of TRPC1-caveolin-1 signaling axis in sepsis-induced pathological process. Overall, this study indicated that TRPC1 could promote LPS-triggered intracellular Ca2+ release, mediate caveolin-1 reduction, and in turn activates calpain to regulate myocardial apoptosis and autophagy, contributing to ETM-induced cardiac dysfunction of mice. [Display omitted] • Deletion of TRPC1 alleviates LPS-induced cardiac dysfunction. • TRPC1 knockdown inhibits LPS-stimulated myocardial apoptosis and autophagy. • TRPC1 facilitates LPS-induced Ca2+ release and caveolin-1 degradation. • Direct protein interaction exists between caveolin-1 and calpain 2. • Targeting TRPC1-caveolin-1-calpain axis alleviates endotoxic cardiac dysfunction. [ABSTRACT FROM AUTHOR]

[Display omitted] • Chiral ionone alkaloid ION-31a inhibits breast cancer metastasis and angiogenesis. • Its direct target was identified as HSP90α. • ION-31a downregulates HSP90/HIF-1α/VEGF/VEGFR2 pathway. Breast cancer has become the number one killer of women. In our previous study, an active compound, ION-31a, with potential anti-metastasis activity against breast cancer was identified through the synthesis of ionone alkaloid derivatives. In the present study, we aimed to identify the therapeutic target of ION-31a. We used a fluorescence tag labeled probe, molecular docking simulation, and surface plasmon resonance (SPR) analysis to identify the target of ION-31a. The main target of ION-31a was identified as heat shock protein 90 (HSP90). Thus, ION-31a is a novel HSP90 inhibiter that could suppress the metastasis of breast cancer and angiogenesis significantly in vitro and in vivo. ION-31a acts via inhibiting the HSP90/hypoxia inducible factor 1 alpha (HIF-1α)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway and downregulating downstream signal pathways, including protein kinase B (AKT)/mammalian target of rapamycin (mTOR), AKT2/protein kinase C epsilon (PKCζ), extracellular regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and mitogen-activated protein kinase 14 (p38MAPK) pathways. ION-31a affects multiple effectors implicated in tumor metastasis and has the potential to be developed as an anti-metastatic agent to treat patients with breast cancer. [ABSTRACT FROM AUTHOR]

Cadmium is a highly toxic metal threatening human and animal health. N-acetyl-L-cysteine (NAC) was reported to play a positive role in disease treatment and immune regulation. The present study aimed to explore the effect of NAC administration on Cd-induced cytotoxicity and abnormal immune response on chicken peritoneal macrophages. Peritoneal macrophages isolated from Isa Brown male chickens were exposed to CdCl 2 (20 or 50 μ M) and/or NAC (500 μ M) for different time periods. Results showed that Cd caused dose-dependent damage on chicken peritoneal macrophages characterized by morphologic and ultrastructural alterations, increased cell apoptosis, reactive oxygen species accumulation and mitochondrial injury. Cd exposure inhibited phagocytic activity of chicken peritoneal macrophages, and promoted transcriptional status of pro-inflammatory cytokines (IL-1 β , IL-6 and TNF-α) in both unactivated macrophages and cells in response to lipopolysaccharide (LPS) stimuli. Pretreatment with 500 μ M NAC did not affect growth of normal chicken peritoneal macrophages, while remarkably inhibiting Cd-caused cell death, oxidative stress, and mitochondrial membrane depolarization. NAC pretreatment significantly prevented intracellular Cd2+ accumulation in the Cd-exposed macrophages. Inhibitory effects of NAC on Cd-induced ROS accumulation and mitochondrial injury on chicken macrophages were confirmed in HD-11 macrophage cell line. In addition, NAC pretreatment promoted the phagocytic activity of Cd-exposed chicken peritoneal macrophages, and significantly inhibited expression of pro-inflammatory factors (IL-1 β , IL-6 and TNF-α) in both Cd-exposed macrophages and Cd-treated cells in response to LPS stimuli. In conclusion, the present study firstly demonstrated the antagonistic effect of NAC against Cd-caused damage and abnormal immune response on chicken peritoneal macrophages. Protective effect of NAC on chicken macrophages was highly related to its suppression on Cd-induced ROS overproduction, pro-inflammatory reaction and intracellular Cd2+ accumulation. • Cadmium (Cd) exposure led to dose-dependent cytotoxicity and abnormal immune response in chicken peritoneal macrophages. • N-acetyl-L-cysteine (NAC) pretreatment antagonized Cd cytotoxicity in both chicken peritoneal macrophages and HD-11 cells. • NAC pretreatment protected the immune response in Cd-exposed chicken peritoneal macrophages. [ABSTRACT FROM AUTHOR]

Abstract Hypoxic pulmonary vasoconstriction (HPV) can be modulated by Rho/Rho kinase signaling, which can alter HPV vascular function via regulating myosin light chain phosphorylation, in a manner generally believed to be Ca2+-independent. We hypothesized that the RhoA/ROCK signaling pathway also can regulate HPV vascular function via a Ca2+-dependent mechanism, signaling through the functional transient receptor potential canonical (TRPC) channels. In this study, male BALB/c mice were exposed to normoxic or 10% oxygen (hypoxic) conditions for six weeks, after which systolic pressure and right ventricular hypertrophy were assessed. Transient intracellular calcium was monitored using a fluorescence imaging system. Muscle tension was measured with a contractile force recording system, and protein expression was assessed by immunoblotting. We found that the expressions of RhoA and ROCK were increased in mouse pulmonary arteries (PAs) under conditions of chronic hypoxia. Inhibition of the RhoA/ROCK signaling pathway prevented the development of hypoxic pulmonary hypertension (HPH), as evidenced by significantly reduced PA remodeling and pulmonary vasoconstriction. Immunoblotting results revealed that inhibition of the RhoA/ROCK signaling pathway significantly decreased the expression of HIF-1α. Knockdown of HIF-1α down-regulated the expression and function of the TRPC1 and TRPC6 channels in PASMCs under conditions of hypoxia. Contraction of the PAs and a Ca2+ influx into PASMCs through either receptor- or store-operated Ca2+ channels were also increased after hypoxia. However, RhoA/ROCK inhibitors markedly attenuated these changes. These results indicate that inhibition of the RhoA/ROCK signaling pathway ameliorates HPH via HIF-1α-dependent functional TRPCs. Graphical abstract Unlabelled Image Highlights • Inhibition of the RhoA/ROCK pathway prevents the development of HPH. • Inhibition of the RhoA/ROCK pathway decreases the expression of HIF-1α. • HIF-1α deficiency down-regulates the expressions and functions of TRPC channels. • RhoA/ROCK regulates vascular function via Ca2+-dependent mechanism in HPV by TRPCs. [ABSTRACT FROM AUTHOR]

To compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs). A total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared. With a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed. pCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence. [ABSTRACT FROM AUTHOR]

[Display omitted] The self-standing graphene membranes are considered as ideal electrode materials for supercapacitors. However, maintaining highly regularized and uniform graphene membranes with satisfied electrochemical performance is still a challenge. Herein, with the chelation of metal cation and the radial shear force introduced by high-speed spinning, the uniform interlayer channels and shrunken cracks between adjacent nanosheets can be achieved in the metal-intercalated graphene oxide (GO) membranes, thus realizing regularization both in normal and radial direction. With the promotion in electron transfer and electrolyte penetration, the iron cross-linked GO membrane with spin coating for 40 cycles exhibits a high specific capacitance (427 F g−1 at 1 A g−1) and rate capability (42.6% capacitance retention from 1 to 40 A g−1), as well as excellent cyclic capability (90.5% capacitance retention after 20,000 cycles). Particularly, a 21% increasement in capacitance can be achieved after high-speed spinning treatment. Moreover, the spin regularization strategy can be extended to GO membranes cross-linked by various multi-valence metal cations, the electrochemical performance of metal-cation cross-linked GO membrane electrodes after high-speed spinning treatment can also be improved obviously. Therefore, this paper provides a novel method to fabricate highly ordered GO membranes with promising electrochemical performance, which presents an immense potential application in membrane materials applied in energy storage, separation and catalysis. [ABSTRACT FROM AUTHOR]

Ballast water and sediments can serve as prominent vectors for the widespread dispersal of pathogens between geographically distant areas. However, information regarding the diversity and distribution of the bacterial pathogens in ballast water and sediments is highly limited. In this study, using high-throughput sequencing and quantitative PCR, we investigated the composition and abundance of potential pathogens, and their associations with indicator microorganisms. We accordingly detected 48 potential bacterial pathogens in the assessed ballast water and sediments, among which there were significant differences in the compositions and abundances of pathogenic bacterial communities characterizing ballast water and sediments. Rhodococcus erythropolis , Bacteroides vulgatus , and Vibrio campbellii were identified as predominant pathogens in ballast water, whereas Pseudomonas stutzeri , Mycobacterium paragordonae , and Bacillus anthracis predominated in ballast sediments. Bacteroidetes , Vibrio alginolyticus , Vibrio parahaemolyticus , and Escherichia coli were generally detected with median values of 8.54 × 103−1.22 × 107 gene copies (GC)/100 mL and 1.16 × 107−3.97 × 109 GC/100 g in ballast water and sediments, respectively. Notably, the concentrations of Shigella sp., Staphylococcus aureus , and V. alginolyticus were significantly higher in ballast sediments than in the water. In addition, our findings tend to confirm that the indicator species specified by the International Maritime Organization (IMO) might underestimate the pathogen risk in the ballast water and sediments, as these bacteria were unable to predict some potential pathogens assessed in this study. In summary, this study provides a comprehensive insight into the spectrum of the potential pathogens that transferred by ship ballast tanks and emphasizes the need for the implementation of IMO convention on ballast sediment management. • Pathogen level was assessed using high throughput sequencing and quantitative PCR. • Pathogens composition and abundance varied between ballast water and sediments. • Ballast sediments displayed higher abundance of potential pathogenic bacteria. • Enteric pathogens were prevalent both in ballast water and sediments. • Indicator microorganisms underestimate the potential pathogen risk in ballast tank. [ABSTRACT FROM AUTHOR]

The ligands occupy/stabilize the abundant oxygen vacancies on the δ-MnO 2 surface and inside the interlayer channels, which can effectively regulate the surface electronic structure, stabilize the interlayer channel structure and improve the electrochemical performance. [Display omitted] • Oxygen vacancies refilling and K+ intercalation is developed to modify the δ-MnO 2. • K+ intercalate into the lamellar δ-MnO 2 enables a wide operation potential of 1.3 V. • Ligands occupy/stabilize oxygen vacancies on surface or inside lamellar channels. • The surface modified δ-MnO 2 reveals high supercapacitor performance and stability. • 2.3 V aqueous asymmetric supercapacitor exhibits high energy and power densities. Oxygen vacancies occupation and coordination environment modulation of the transition-metal based electrodes are effective strategies to improve the structural stability and electrochemical performance. In this work, the 2-methylimidazole (2-MI) doped manganese dioxide (MnO 2) anchored on carbon cloth (CC) is fabricated via a simple method (MI-MnO 2-x /CC), where the oxygen defects on/inside the K+ doped δ-MnO 2 nanosheets are in-situ created by reductive ethanol/Mn2+ and occupied by 2-MI ligands. With the pre-embedded K+ ions and abundant ligand-refilled defects, the electronic coordination structure, structural stability and electron/ion diffusion efficiency can be effectively enhanced. Therefore, the MI-MnO 2-x /CC reveals a remarkable specific capacitance of 721.2 mF cm−2 with excellent cycle durability (capacitance retention of 93.4% after 10,000 cycles) under 1.3 V operation potential window. In addition, an asymmetric supercapacitor assembled by MI-MnO 2-x /CC and activated mechanical exfoliated graphene oxide yields a maximum energy density of 57.0 Wh kg−1 and a highest power density of 23.0 kW kg−1 under 2.3 V. This effective oxygen defect stabilization strategy by ligands refilling can be extended to various metal oxide-based electrodes for energy storage and conversion. [ABSTRACT FROM AUTHOR]

The mesoporous Cd-Zn-S solid solutions (E-Cd x Zn 1-x S) with abundant surface defects synthesized via ingenious inorganic self-template co-precipitation method at room temperature, exhibiting high-efficient activity and stability for photocatalytic hydrogen evolution. The practical application of photocatalytic water splitting for hydrogen evolution hinges on the development of high-efficient and low-cost photocatalysts. Defects engineering has emerged as a promising strategy to enhance photocatalytic activity effectively. Herein, a facile and versatile co-precipitation method is proposed to fabricate mesoporous Cd-Zn-S solid solutions (E-Cd x Zn 1-x S) with abundant surface defects by the inorganic salts formed in the reaction system as self-template. Compared with Cd-Zn-S solid solutions (W-Cd 0.65 Zn 0.35 S) prepared by the traditional co-precipitation method, the enhanced specific surface area and abundant surface defects endow E-Cd 0.65 Zn 0.35 S with more accessible active sites and effective separation of electron-hole pairs for the photocatalytic water splitting reaction. The E-Cd 0.65 Zn 0.35 S solid solution exhibits hydrogen evolution rate of 5.2 mmol h−1 g−1 without loading noble metal as cocatalyst under visible light, which is 1.13 times higher than that of W-Cd 0.65 Zn 0.35 S sample. The present work provides a simple, low-cost and prospective strategy for the synthesis of defective Cd-Zn-S solid solutions, and it also delivers guidance to design and develop the advanced visible-light photocatalyst in the future. [ABSTRACT FROM AUTHOR]

[Display omitted] • 9-methyl-9 H -purine and thieno[3,2- d ]pyrimidine derivatives were designed as mTOR inhibitors. • 15i was a potent and selective mTOR inhibitor. • 15i inhibited the proliferation of cancer cells by inducing cell cycle arrest at the G0/G1 phase. • 15i could induce autophagy by activating autophagic flux. The mammalian target of rapamycin (mTOR) has been proved to be an effective target for cancer therapy. Two kinds of mTOR inhibitors, the rapalogs and mTOR kinase inhibitors (TORKi), have been developed and clinically validated in several types of malignancies. Compared with rapalogs, TORKi can exert better antitumor activity by inhibiting both mTORC1 and mTORC2, but the clinical development of current TORKi candidates has been relative slow, more TORKi with novel scaffold need to be developed to expand the current pipelines. In this study, a series of 9-methyl-9 H -purine and thieno[3, 2- d ]pyrimidine derivatives were designed, synthesized and biological evaluation. Most of these compounds exhibited good mTOR kinase inhibitory activity and selectivity over PI3Kα. Subsequent antiproliferative assay allowed us to identify the lead compound 15i , which display nanomolar to low micromolar IC 50 s against six human cancer cell lines. 15i could induce cell cycle arrest of MCF-7, PC-3 and A549 cells at the G0/G1 phase and suppress the migration and invasion of these cancer cells by suppressing the phosphorylation of AKT and P70S6 kinase. It could also regulate autophagy-related proteins to induce autophagy. Therefore, 15i would be a starting point for the development of new TORKi as anticancer drug. [ABSTRACT FROM AUTHOR]

Abstract: Both T-helper 17 cells (Th17) and CD4+CD25+ regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis. However, the relationship between Th17 and Treg cells and their dynamic variations in psoriasis remain unclear. In this study, we found that both Th17 and FoxP3+ Treg cells were increased in psoriasis patients both in the peripheral circulation and skin tissue lesions and were positively correlated with disease severity. The ratio of Th17 to Treg cells in skin tissue lesions was inversely correlated with PASI scores, while it was positively correlated with PASI scores in the circulation. IL-17 secretion by CD4+ T cells was not regulated by Treg cells, even though Treg cells exhibited significant inhibition on CD4+ T cells proliferation and IFN-γ production. These findings provide new information regarding the association between Th17 and Treg cells, which will further our understanding of the pathogenesis of psoriasis. [Copyright &y& Elsevier]

Deguelin is a rotenoid of the flavonoid family, which can be extracted from Lonchocarpus, Derris, or Tephrosia. It possesses the inhibition of cancer cell proliferation by inducing apoptosis through regulating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, the NF-κB signaling pathway, the Wnt signaling pathway, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway and epidermal growth factor receptor (EGFR) signaling, activating the p38 mitogen-activated protein kinase (MAPK) pathway, repression of Bmi1, targeting cyclooxygenase-2 (COX-2), targeting galectin-1, promotion of glycogen synthase kinase-3β (GSK3β)/FBW7-mediated Mcl-1 destabilization and targeting mitochondria via down-regulating Hexokinases II-mediated glycolysis, PUMA-mediation, which are some crucial molecules which modulate closely cancer cell growth and metastasis. Deguelin inhibits tumor cell propagation and malignant transformation through targeting angiogenesis, targeting lymphangiogenesis, targeting focal adhesion kinase (FAK), inhibiting the CtsZ/FAK signaling pathway, targeting epithelial–mesenchymal transition (EMT), the NF-κB signaling pathway, regulating NIMA-related kinase 2 (NEK2). In addition, deguelin possesses other biological activities, such as targeting cell cycle arrest, modulation of autophagy, inhibition of hedgehog pathway, inducing differentiation of mutated NPM1 acute myeloid leukemia etc. Therefore, deguelin is a promising chemopreventive agent for cancer therapy. Anticancer activity of deguelin and its derivatives: recent advances in mechanisms of action (AMPK: Adenosine 5'-monophosphate (AMP)-activated protein kinase; COX-2: Cyclooxygenase; EGFR: Epidermal growth factor receptor; EMT: Epithelial–mesenchymal transition; FAK: Focal adhesion kinase; GSK3β: Glycogen synthase kinase-3; Hh: Hedgehog; MAPK: p38 mitogen-activated protein kinase; NF-κB: Nuclear factor κB; PI3K/Akt: Phosphoinositide 3-kinase/protein kinase B). [Display omitted] [ABSTRACT FROM AUTHOR]

• Three new polyprenylated phloroglucinols from Hypericum elodeoides. • The absolute configurations of 1 – 3 were elucidated by ECD calculation. • The plausible biogenetic pathways of 1 – 3 were proposed. • Compound 1 might modulate the RXRα transactivation by interacting with RXRα-LBD. Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E–F (2 – 3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1 – 3 were proposed. [ABSTRACT FROM AUTHOR]

Chicken erythrocytes participated in immunity, but the role of erythrocytes in the immunity of Marek's disease virus (MDV) has not been reported related to the immunity genes. The purpose of this study was to screen and verify the immune-related genes of chicken erythrocytes which could be proven as a biomarker in MDV. The datasets (GPL8764-Chicken Gene Expression Microarray) were downloaded from the GEO profile database for control and MDV infected chickens to obtain differentially expressed genes (DEGs) through bioinformatics methods. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to find enriched pathways, including Gene Ontology (GO). Based on enriched pathways, the top 19 immune-related genes were screened-out and process further to construct the protein-protein interaction (PPI) networks. The screened genes were validated on RT-PCR and qPCR. Results suggested that the mRNA transcription of Toll-like receptors 2, 3, 4, 6 (TLR2, TLR3, TLR4, TLR6), major histocompatibility complex-II (MHCII), interleukin-7 (IL-7), interferon-βeta (IFN-β), chicken myelomonocytic growth factor (cMGF) and myeloid differentiation primary response 88 (MyD88) were significantly up-regulated. The expression of toll-like receptor 5, 7 (TLR5, TLR7) interleukin-12 (IL-12 p40), interleukin-13 (IL-13), and interferon-αlpha (IFN-α) were significantly down-regulated in the erythrocytes of the infected group (P < 0.05). In contrast, the expression of toll-like receptor-1, 15, 21 (TLR1, TLR15, TLR21), major histocompatibility complex I (MHCI) and Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) were not significant. In conclusion, it has been verified on qRT-PCR results that 19 immune-related genes, which included TLRs, cytokines and MHC have immune functions in MDV infected chickens. Image 1 • Role of erythrocytes in the immunity of Marek's disease virus (MDV) has not been reported related to the immunity genes. • Integrated bioinformatics methods identified the important genes expressed in MDV. • Based on enriched pathways, the top 19 immune-related genes were screened-out. • The expression of 19 immune-related genes verified on qRT-PCR. • Immune genes, including TLRs, cytokines and MHC, have immune functions in MDV infected chickens. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of glycinin basic polypeptide (GBP) on the qualities of Scomberomorus niphonius surimi (SNS) during a 24-day storage period at 4 °C. The effects of GBP on the sensory, physicochemical and microbial properties of SNS were determined during the 24 days of storage. The physicochemical and microbial parameters consisted of pH, total volatile base nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARS) and total viable count (TVC). The results showed GBP markedly (P < 0.05) increased the hardness, springiness, gumminess and chewiness of SNS but had little effect on its cohesiveness and resilience. However, these textural parameters did not obviously change during the period of storage. Compared with the control and 0.2% GBP, the 0.4 and 0.6% GBP treatments effectively retained the whiteness of SNS after 12 days storage. The values of pH, TVB-N, TBARS and TVC of SNS treated with GBP were obviously lower than those of the control, especially at higher GBP doses. The overall acceptability scores of SNS treated with GBP were higher than those of the control. These results indicated GBP improved the textural properties and inhibited the undesirable physicochemical and microbial changes, thus enhancing the qualities and extending the shelf-life of SNS. • Glycinin basic polypeptide (GBP) could improve the textural properties of surimi. • GBP maintained the whiteness and pH of surimi during storage. • GBP decreased the TVB-N, TVC and TBARS values of surimi during storage. • GBP could retain the quality properties and extend the shelf life of surimi. [ABSTRACT FROM AUTHOR]