Search

As a key area in word reading, the left ventral occipitotemporal cortex is proposed for abstract orthographic processing, and its middle part has even been labeled as the visual word form area. Because the definition of the VWFA largely varies and the reading task differs across studies, the function of the left ventral occipitotemporal cortex in word reading is continuingly debated on whether this region is specific for orthographic processing or be involved in an interactive framework. By using representational similarity analysis (RSA), this study examined information representation in the VWFA at the individual level and the modulatory effect of reading task. Twenty-four subjects were scanned while performing the explicit (i.e., the naming task) and implicit (i.e., the perceptual task) reading tasks. Activation analysis showed that the naming task elicited greater activation in regions related to phonological processing (e.g., the bilateral prefrontal cortex and temporoparietal cortex), while the perceptual task recruited greater activation in visual cortex and default mode network (e.g., the bilateral middle frontal gyrus, angular gyrus, and the right middle temporal gyrus). More importantly, RSA also showed that task modulated information representation in the bilateral anterior occipitotemporal cortex and VWFA. Specifically, ROI-based RSA revealed enhanced orthographic and phonological representations in the bilateral anterior fusiform cortex and VWFA in the naming task relative to the perceptual task. These results suggest that lexical representation in the VWFA is influenced by the demand of phonological processing, which supports the interactive account of the VWFA.

Background Tumor-associated macrophages (TAMs) are key regulators of the complex interplay between cancer and the immune microenvironment. Tumor cell-derived spondin 2 (SPON2) is an extracellular matrix glycoprotein that has complicated roles in recruitment of macrophages and neutrophils during inflammation. Overexpression of SPON2 has been shown to promote tumor cell migration in colorectal cancer (CRC). However, the mechanism by which SPON2 regulates the accumulation of TAMs in the tumor microenvironment (TME) of CRC is unknown. Methods Immunohistochemistry was used to examine SPON2 expression in clinical CRC tissues. In vitro migration assays, transendothelial migration assays (iTEM), and cell adhesion assays were used to investigate the effects of SPON2 on monocyte/macrophage migration. Subcutaneous tumor formation and orthotopic implantation assays were performed in C57 BL/6 mice to confirm the effects of SPON2 on TAM infiltration in tumors. Results SPON2 expression is positively correlated with M2-TAM infiltration in clinical CRC tumors and poor prognosis of CRC patients. In addition, SPON2 promotes cytoskeletal remodeling and transendothelial migration of monocytes by activating integrin β1/PYK2 axis. SPON2 may indirectly induce M2-polarization through upregulating cytokines including IL10, CCL2 and CSF1 expression in tumor cells. Blocking M2 polarization and Macrophage depletion inhibited the SPON2-induced tumors growth and invasion. Furthermore, blocking the SPON2/integrin β1/PYK2 axis impairs the transendothelial migration of monocytes and cancer-promoting functions of TAMs in vivo. Conclusions Our findings demonstrate that SPON2-driven M2-TAM infiltration plays an important role during CRC tumor growth and metastasis. SPON2 may be a valuable biomarker guiding the use of macrophage-targeting strategies and a potential therapeutic target in advanced CRC.

Contracaecum species are economically important fish-borne larval nematodes with zoonotic significance. In June 2019, more than one hundred piscivorous birds were died in its habitats close to the Wild Duck Lake, located in Yanqing, northwest of Beijing, China. Post-mortem examination of Black Night Herons (Nycticorax) revealed the presence of numerous anisakid nematodes in the proventriculus. Recovered nematodes were identified as Contracaecum sp. based on morphological description. Phylogenetic analysis of the mitochondrial (mt) genome and the ITS gene showed that sequences of Contracaecum sp. Beijing isolates were grouped into a new individual cluster. Furthermore, the parasite was successfully isolated from fresh dead birds, feces of piscivorous birds, and fish and prevalence ranged from 8.0% to 81.8%. Consequently, our study demonstrated the Contracaecum sp. infections in different sources from China, which might constitute a threat to wildlife, aquaculture, and public health. This article is protected by copyright. All rights reserved.

Indoleamine 2,3 dioxygenase 1 (IDO1) is an attractive target for cancer immunotherapy. However, IDO1 inhibitors have shown disappointing therapeutic efficacy in clinical trials, mainly because of the activation of the aryl hydrocarbon receptor (AhR). Here, we show a post-transcriptional regulatory mechanism of IDO1 regulated by a proteasome-associated deubiquitinating enzyme, USP14, in colorectal cancer (CRC). Overexpression of USP14 promotes tryptophan metabolism and T-cell dysfunction by stabilizing the IDO1 protein. Knockdown of USP14 or pharmacological targeting of USP14 decreases IDO1 expression, reverses suppression of cytotoxic T cells, and increases responsiveness to anti-PD-1 in a MC38 syngeneic mouse model. Importantly, suppression of USP14 has no effects on AhR activation induced by the IDO1 inhibitor. These findings highlight a relevant role of USP14 in post-translational regulation of IDO1 and in the suppression of antitumor immunity, suggesting that inhibition of USP14 may represent a promising strategy for CRC immunotherapy.

Background cAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear. Methods Real-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC. Results We found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling. Conclusion Our study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.

Commensal rats (Rattus spp.), which are globally distributed, harbour many pathogens responsible for significant human diseases. Despite this, we have a poor understanding of the epidemiology and genetic diversity of some recently neglected zoonotic pathogens, such as Leptospira spp., Bartonella spp. and hepatitis E virus (HEV), which constitute a major public health threat. Thus, we surveyed the occurrences, co-infection and genetic diversity of these pathogens in 129 urban rats from China. For Rattus tanezumi, the prevalences of Leptospira spp., Bartonella spp. and HEV infection were 6.67%, 0% and 46.67%, respectively. The prevalences of Leptospira spp., Bartonella spp. and HEV infection were 57.89%, 9.65% and 57.89% for Rattus norvegicus respectively. Leptospira spp. and HEV infections were more likely to occur in mature R. norvegicus. Phylogenetic analyses showed that pathogenic Leptospira interrogans and Leptospira borgpetersenii might exist. We also found that Bartonella spp. showed high similarity to Bartonella elizabethae, Bartonella rochalimae and Bartonella tribocorum, which are implicated in human disease. Dual and triple infections were both detected. Moreover, dual infections with Leptospira spp. and HEV represented the most frequent co-infection, and there was a significantly positive association between them. High genetic diversity was observed in genes segments from Leptospira, Bartonella and HEV. Our results first discover the occurrence of multiple co-infections and genetic diversity of Leptospira, Bartonella and HEV in commensal rats from China. Altogether, the present study provides an insight into evaluating the risk of rat-borne zoonoses in urban China.

Additional file 1: Table S1. The relationship between CREB5 expression and clinicopathological parameters. Table S2. Primer sequences used for real-time PCR (5′ to 3′). Table S3. Sequence of primers for ChIP assay. Table S4. Sequence of primers for Luciferase reporter assay.

Background Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. Methods Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2′s expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. Results The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. Conclusion The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients. Electronic supplementary material The online version of this article (10.1186/s12935-019-0848-4) contains supplementary material, which is available to authorized users.

Influenza A virus (IAV) is an important pathogen that poses a severe threat to the health of humans. Nucleoprotein (NP) of IAV plays crucial roles in the viral life cycle by interacting with various cellular factors. Histone Acetyl Transferase TIP60 is a key target of several viral proteins during infection, including HIV-1 Tat, HPV E6, HTLV-1 p30II and HCMV UL27 proteins. However, Whether the interaction between the IAV NP and TIP60, and the role of TIP60 in IAV life cycle are largely unknown. Here, we showed that IAV infection up-regulated TIP60 protein and RNA expression. Overexpression of TIP60 inhibited viral protein and RNA expression and reduced the progeny viral titer. Further study revealed that TIP60 inhibited viral replication through activation of TBK1-IRF3 signaling pathway. Furthermore, we demonstrated that the NP protein of IAV interacted with TIP60. Together, these results indicate that TIP60 play a repressor in IAV infection, and it may be a possible target for antiviral drugs.

Forkhead box F1 (FOXF1) has been recently implicated in the progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms by which FOXF1 regulates the progression of colorectal cancer (CRC) are largely unknown. As shown in our previous study, FOXF1 is upregulated in 182 CRC tissues, and elevated FOXF1 expression is significantly associated with microvessel density and advanced TNM (T = primary tumour; N = regional lymph nodes; M = distant metastasis) stages. In this study, 43 CRC tissues collected from patients who underwent treatment with first-line standard chemotherapeutic regimens in combination with bevacizumab were used to explore the correlation between FOXF1 expression and resistance to bevacizumab. In addition, FOXF1 regulated angiogenesis by inducing the transcription of vascular endothelial growth factor A1 (VEGFA) in vitro and in vivo. Furthermore, upregulation of FOXF1 enhanced bevacizumab resistance in CRC, and inhibition of VEGFA attenuated angiogenesis and bevacizumab resistance in FOXF1-overexpressing CRC cells. These results suggest that FOXF1 plays critical roles in CRC angiogenesis and bevacizumab resistance by inducing VEGFA transcription and that FOXF1 represents a potentially new therapeutic strategy and biomarker for anti-angiogenic therapy against CRC.

Forkhead Box F1 (FOXF1) has been recently implicated in cancer progression and metastasis of lung cancer and breast cancer. However, the biological functions and underlying mechanisms of FOXF1 in the regulation of the progression of colorectal cancer (CRC) are largely unknown. We showed that FOXF1 was up-regulated in 93 paraffin-embedded archived human CRC tissue, and both high expression and nuclear location of FOXF1 were significantly associated with the aggressive characteristics and poorer survival of CRC patients. The GSEA analysis showed that the higher level of FOXF1 was positively associated with an enrichment of EMT gene signatures, and exogenous overexpression of FOXF1 induced EMT by transcriptionally activating SNAI1. Exogenous overexpression FOXF1 functionally promoted invasion and metastasis features of CRC cells, and inhibition of SNAI1 attenuates the invasive phenotype and metastatic potential of FOXF1-overexpressing CRC cells. Furthermore, the results of the tissue chip showed that the expression of FOXF1 was positively correlated with SNAI1 in CRC tissues chip. These results suggested that FOXF1 plays a critical role in CRC metastasis by inducing EMT via transcriptional activation of SNAI1, highlighting a potential new therapeutic strategy for CRC.

Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure-activity relationship of the miR-1 inhibitor.

Different from other α-diketones, photocycloadditions of trione (I) with oxazoles (II) proceed exclusively via a [2 + 2] pathway with exclusive involvement of the C(4) carbonyl group.

Direct C-H functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)(2)(dtbbpy)PF(6)] as photocatalyst in combination with Na(2)HPO(4), enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C=C double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C=C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.

A small molecule activator of microRNAs has been identified from photoreaction products of naphthalene-1,4-dione with acetylenes and the universal activation on miRNAs was realized through significant promotion on the processing of precursor microRNAs by the compound.

Irradiation of isoquinoline-1,3,4-trione with the oxazoles (II) results in regio- and stereoselective formation of spiroisoquinolineoxetanes.

Photocycloaddition of isoquinoline-1,3,4-trione and 5-methoxyoxazoles affords spiroisoquinolineoxetanes with high regio- and diastereoselectivity. The spiroisoquinolineoxetanes can be conveniently converted into novel spiroisoquinolineoxazoline derivatives through acid catalyzed sequential reactions.

A facile, efficient and general method for preparing deuteroporphyrin derivatives by using concentrated H 2 SO 4 and alcohol under ultrasound irradiation has been developed. A series of new deuteroporphyrin derivatives bearing different propionic ester groups have been synthesized in good yields starting from readily accessible deuterohemin. The characterization of these compounds confirms the synthetic methodology. Compared with conventional methods, the main advantages of the present procedure are shorter reaction time and higher yields.

In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5)S, the fused N-heterocyclic ring is distorted towards a half-boat conformation. The methyl formate moiety is disordered over two sets of sites with refined occupancies of 0.882 (5) and 0.118 (5). In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O hydrogen bonds into one-dimensional chains along [010].

In the isoquinoline ring system of the title mol-ecule, C(16)H(16)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxaaza-spiro ring is essentially planar [maximum deviation = 0.022 (1) Å] and forms a dihedral angle of 24.56 (4)° with the benzene ring.

In the isoquinoline ring system of the title mol-ecule, C(22)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-aza-spiro ring is essentially planar [maximum deviation = 0.026 (1) Å] and forms dihedral angles of 22.53 (5) and 64.46 (5)° with the benzene and phenyl rings, respectively. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O hydrogen bond, which generates an S(7) ring motif. In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds into layers parallel to (102).

In the isoquinoline ring system of the title compound, C(19)H(22)N(2)O(5), the N-heterocyclic ring is in a half-chair conformation. The dioxa-2-aza-spiro ring is essentially planar [maximum deviation of 0.025 (1) Å] and forms a dihedral angle of 23.51 (5)° with the benzene ring. In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds into chains along [010].

In the isoquinoline ring system of the title mol-ecule, C(18)H(20)N(2)O(5), the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-aza-spiro ring is essentially planar, with a maximum deviation of 0.029 (1) Å, and makes a dihedral angle of 30.63 (5)° with the benzene ring. The mol-ecular structure is stabilized by a weak intra-molecular C-H⋯O hydrogen bond, which generates a S(6) ring motif. In the crystal, mol-ecules are linked via weak inter-molecular C-H⋯O hydrogen bonds into a three-dimensional supra-molecular network. Additional stabilization is provided by π-π stacking inter-actions between symmetry-related benzene rings with a centroid-centroid distance of 3.6507 (5) Å.

Spirocyclic oxetanes were found to undergo versatile transformations under different acid-mediated conditions. Treatment of spirocyclopropyl oxetanes with excess amounts of hydrochloric or hydrobromic acid at room temperature resulted in the formation of spirocyclopropyl fused butenolides with good yields. The transformation of spirocyclopropyl oxetanes mediated by hydroiodic acid led to spirocyclopropyl fused γ-butyrolactones instead of butenolides. Transformation of spirocyclopropyl oxetanes catalyzed by Lewis acid was also explored and found to give distinct products such as spirobutyl indolinones. The reaction mechanisms involved in the acid-mediated transformations were proposed.

Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including β-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.