Nanoengineering Natural Leather for Dynamic Thermal Management and Electromagnetic Interference Shielding.

Unpredictable and extreme weather conditions, along with increasing electromagnetic pollution, have resulted in a significant threat to human health and productivity, causing irreversible damage to society's well-being and economy. However, existing personal temperature management and electromagnetic protection materials lack adaptability to dynamic environmental changes. To address this, a unique asymmetric bilayer leather/a-MWCNTs/CA fabric is developed by vacuum-infiltrating interconnected a-MWCNTs networks into natural leather's microfiber backbone and spraying porous acetic acid (CA) on the reverse side. Such fabric achieves simultaneous passive radiation cooling, heating, and anti-electromagnetic interference functions without external energy input. The fabric's cooling layer has high solar reflectance (92.0%) and high infrared emissivity (90.2%), providing an average subambient radiation cooling effect of 10 °C, while the heating layer has high solar absorption (98.0%), enabling excellent passive radiative heating and effective compensation for warming via Joule heating. Additionally, the fabric's 3D conductive a-MWCNTs network provides electromagnetic interference shielding effectiveness of 35.0 dB mainly through electromagnetic wave absorption. This multimode electromagnetic shielding fabric can switch between cooling and heating modes to adapt to dynamic cooling and heating scenarios, providing a new avenue for sustainable temperature management and electromagnetic protection applications.

Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM.

BACKGROUND: Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. RESULTS: The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. CONCLUSIONS: The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.

Identification and characterization of immune-related microRNAs in hybrid snakehead(Channa maculata♀ × Channa argus♂)after treated by Echinacea purpurea (Linn.) Moench.

Echinacea purpurea (Linn.) Moench (EP) is a globally popular herbal medicine, which showed effects on growth promotion, antioxidant and immunomodulatory activities in fish culture world widely. However, there are few studies about the effects on miRNAs by EP in fish. The hybrid snakehead fish (Channa maculate♀ × Channa argus ♂) was new important economic specie of freshwater aquaculture in China with high market value and demand while there were only a few reports about its miRNAs. To overview immune-related miRNAs of the hybrid snakehead fish and to further understand the immune regulating mechanism of EP, we herein constructed and analyzed three small RNA libraries of immune tissues including liver, spleen and head kidney of the fish with or without EP treatment via Illumina high-throughput sequencing technology. Results showed that EP can affect the immune activities of fish by the miRNA-regulated ways. Totally, 67 (47 up and 20 down) miRNAs in liver, 138 (55 up and 83 down) miRNAs in spleen, and 251 (15 up and 236 down) miRNAs in spleen were detected, as well as 30, 60, 139 kinds of immune-related miRNAs belonging to 22, 35 and 66 families of the three tissues respectively. The expressions of 8 immune-related miRNA family members were found in all the three tissues, including miR-10, miR-133, miR-22 and etc. Some miRNAs have been identified involved in the innate and adaptive immune responses, such as the miR-125, miR-138, and miR-181 family. Ten miRNA families with antioxidant target genes were also discovered, including miR-125, miR-1306, and miR-138, etc. Results from Gene Ontology (GO) and KEGG pathway analysis further confirmed there are a majority immune response targets of the miRNAs involved in the EP treatment process. Our study deepened understanding roles of miRNAs in fish immune system and provides new ideas for the study of immune mechanism of EP.

Endothelium-Targeted Deletion of microRNA-15a/16-1 Promotes Poststroke Angiogenesis and Improves Long-Term Neurological Recovery.

RATIONALE: Angiogenesis promotes neurological recovery after stroke and is associated with longer survival of stroke patients. Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. However, the function of the miR-15a/16-1 cluster in endothelium on postischemic cerebral angiogenesis is not known. OBJECTIVE: To investigate the functional significance and molecular mechanism of endothelial miR-15a/16-1 cluster on angiogenesis in the ischemic brain. METHODS AND RESULTS: Endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice and wild-type littermate controls were subjected to 1 hour middle cerebral artery occlusion followed by 28-day reperfusion. Deletion of miR-15a/16-1 cluster in endothelium attenuates post-stroke brain infarction and atrophy and improves the long-term sensorimotor and cognitive recovery against ischemic stroke. Endothelium-targeted deletion of the miR-15a/16-1 cluster also enhances post-stroke angiogenesis by promoting vascular remodeling and stimulating the generation of newly formed functional vessels, and increases the ipsilateral cerebral blood flow. Endothelial cell-selective deletion of the miR-15a/16-1 cluster up-regulated the protein expression of pro-angiogenic factors VEGFA (vascular endothelial growth factor), FGF2 (fibroblast growth factor 2), and their receptors VEGFR2 (vascular endothelial growth factor receptor 2) and FGFR1 (fibroblast growth factor receptor 1) after ischemic stroke. Consistently, lentiviral knockdown of the miR-15a/16-1 cluster in primary mouse or human brain microvascular endothelial cell cultures enhanced in vitro angiogenesis and up-regulated pro-angiogenic proteins expression after oxygen-glucose deprivation, whereas lentiviral overexpression of the miR-15a/16-1 cluster suppressed in vitro angiogenesis and down-regulated pro-angiogenic proteins expression. Mechanistically, miR-15a/16-1 translationally represses pro-angiogenic factors VEGFA, FGF2, and their receptors VEGFR2 and FGFR1, respectively, by directly binding to the complementary sequences within 3'-untranslated regions of those messenger RNAs. CONCLUSIONS: Endothelial miR-15a/16-1 cluster is a negative regulator for postischemic cerebral angiogenesis and long-term neurological recovery. Inhibition of miR-15a/16-1 function in cerebrovascular endothelium may be a legitimate therapeutic approach for stroke recovery.

Vitamin E performs antioxidant effect via PAP retrograde signaling pathway in Nile tilapia (Oreochromis niloticus).

PAP (3'-phosphoadenosine 5'-phosphate) is a ubiquitous phosphoric acid and a natural inhibitor of the XRN (5'-3'exoribonuclease) family. It was proved to enter the nucleus through the retrograde signaling pathway and inhibit XRN2 to prevent the degradation of miRNA precursors, thus promoting the anti-oxidation miRNA level in Arabidopsis thaliana. Vitamin E (tocopherol) was proved to promote the accumulation of PAP in the plant, which facilitates PAP into the nucleus to accomplish its antioxidant function. However, the relationship between VE and PAP in animals is unclear. To identify the relationship between VE and PAP and to uncover the function of PAP in fish, we investigated the performance of VE and PAP in Nile tilapia by comparing the antioxidant indicators (SOD, GSH-Px, and CAT), the Keap1-Nrf2 signaling pathway, and the miRNA expression profiles. Results showed that the antioxidant effect of VE and PAP showed similar character either in tilapia liver or in serum: the activities of GSH-Px and CAT of both groups were significantly increased (P < 0.05); the SOD activity of the VE group was significantly increased (P < 0.05), and although the result of the PAP group was not so significant (P > 0.05), PAP improved the SOD level, too. The two groups also showed similar character in the tilapia liver; both did not significantly increase the liver δ-VE content (P > 0.05). However, VE significantly increased the content of α-VE and γ-VE (P < 0.05), while the PAP group was insignificant (P > 0.05). Feed with VE and intraperitoneal injection of PAPs reagent both increased the PAP content in the liver of tilapia, and the effect of the VE group was more significant (P < 0.05) than that of the PAP group (P > 0.05). Both groups reduced the expression of Keap1 and Cullin3 genes and improved the level of HO-1 gene expression, with the improved miRNA level of Nrf2. As a logical result, they decreased the expression of XRN1 and XRN2. By profile sequencing, we further identified some antioxidant closely related miRNAs shared in the VE and PAP groups, including miR-30, miR-24, miR-19b, and miR-100. By comparing the regulating mechanism of VE and PAP of feed supply and intraperitoneal injection, we proved that VE and PAP were closely related in fish; VE promoted the gathering of PAP. The latter retrograded into the nucleus of the fish liver to inhibit the expression of XRN genes and to up-regulate antioxidant miRNA levels as it does in plants. Only the PAP can accomplish the antioxidant activities, while VE promotes the process. Our study laid the foundation for the application of PAP as a new antioxidant agent in fish farming and benefit a further understanding of the VE antioxidant function in fish.

Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency.

BACKGROUND AND AIMS: Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. METHODS: Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. RESULTS: The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria-Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. CONCLUSION: Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

MicroRNAs and Related Cytokine Factors Quickly Respond in the Immune Response of Channel Catfish to Lipopolysaccharides and ß-Glucan Stimulation.

MicroRNAs (miRNAs) are well-known as powerful regulators of gene expression, with their potential to serve for immunology widely researched in mammals and birds but rarely in fishes. To better understand fish immunology behavior, we herein investigated nine immune-related miRNAs that were reported in other animals, as well as five related cytokine factors and lysozyme (LZM) in the liver, anterior kidney, and spleen of Channel Catfish Ictalurus punctatus after being stimulated by lipopolysaccharides (LPS) and ß-glucan. We also predicated the potential targets of these miRNAs via bioinformatics and further investigated nine of them via quantitative real-time PCR. Results showed that expressions of the nine miRNAs were quickly changed in varying extent after stimulation by LPS, especially for miR-122, miR-142a, miR-155, and miR-223, which were significantly changed in spleen, and the same occurred for the LZM and three cytokine factors TNF-α, IFN-γ and TLR2. Compared with LPS, although most of the miRNAs and the cytokine genes were also affected by ß-glucan, the extent of the effect was weak. Bioinformatics analysis revealed many immune-related targets of the miRNAs, with some of them reported by previous studies. For the nine investigated target genes, seven targets (77.8%) were significantly upregulated after the stimulation of LPS. It therefore can be inferred that the immune-related miRNAs, LZM, and cytokine factors elicited quick immune responses of Channel Catfish to LPS stimulation as in other animals, but the regulation mechanism of miRNAs might be complex and diverse. This research will contribute to a better understanding will support further immunology research in fishes.

The miR-155 regulates cytokines expression by SOSC1 signal pathways of fish in vitro and in vivo.

MiR-155 is reported as immune regulated miRNA in mammalian corresponding to immunity, antibacterial and antiviral effects regulation. However, the roles and mechanisms of the miRNA have remained largely undefined. We herein comprehensively investigated the functions of miR-155 in vitro and in vivo by miR-155 mimics, agomir and antagomir in Cyprinus carpio and Ictalurus punctatus, with the target genes in the SOSC1 pathway certified in I. punctatus via luciferase reporter assays. Results showed that the miR-155 regulated the expressions of cytokines, including TNF-α, IFN-γ, IL-1ß, IL-6 and IL-10. Further research confirmed SOSC1 as one of the targets of the miRNA, and the JAK1/STAT3/SOSC1 signal pathway involved in the miR-155 effects on the expression of immune cytokines as well. Additionally, the changes of TLR2 in fish may also be related to miR-155 along with its target SOCS1, and the TLR2/MyD88 pathway may partly participate in the effects of the miR-155 on the cytokines. The research here confirmed that the miR-155 can regulate cytokines expression by SOSC1 signal pathways of fish in vitro and in vivo, which would provide resources for understanding and studying about immune regulation in fish.

Long Noncoding RNA Malat1 Regulates Cerebrovascular Pathologies in Ischemic Stroke.

The study was designed to determine the role of long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (Malat1), in ischemic stroke outcome. Primary mouse brain microvascular endothelial cells (BMECs) were cultured and treated with Malat1 GapmeR before 16 h oxygen and glucose depravation (OGD). Cell death was assayed by LDH and MTT methods. Malat1 knock-out and wild-type mice were subjected to 1 h of middle cerebral artery occlusion (MCAO) and 24-72 h of reperfusion. To explore the underlying mechanism, apoptotic and inflammatory factors were measured by qPCR, ELISA, and Western blotting. The physical interaction between Malat1 and apoptotic or inflammatory factors was measured by RNA immunoprecipitation. Increased Malat1 levels were found in cultured mouse BMECs after OGD as well as in isolated cerebral microvessels in mice after MCAO. Silencing of Malat1 by Malat1 GapmeR significantly increased OGD-induced cell death and Caspase 3 activity in BMECs. Silencing of Malat1 also significantly aggravated OGD-induced expression of the proapoptotic factor Bim and proinflammatory cytokines MCP-1, IL-6, and E-selectin. Moreover, Malat1 KO mice presented larger brain infarct size, worsened neurological scores, and reduced sensorimotor functions. Consistent with in vitro findings, significantly increased expression of proapoptotic and proinflammatory factors was also found in the cerebral cortex of Malat1 KO mice after ischemic stroke compared with WT controls. Finally, we demonstrated that Malat1 binds to Bim and E-selectin both in vitro and in vivo Our study suggests that Malat1 plays critical protective roles in ischemic stroke.SIGNIFICANCE STATEMENT Accumulative studies have demonstrated the important regulatory roles of microRNAs in vascular and neural damage after ischemic stroke. However, the functional significance and mechanisms of other classes of noncoding RNAs in cerebrovascular pathophysiology after stroke are less studied. Here we demonstrate a novel role of Malat1, a long noncoding RNA that has been originally identified as a prognostic marker for non-small cell lung cancer, in cerebrovascular pathogenesis of ischemic stroke. Our experiments have provided the first evidence that Malat1 plays anti-apoptotic and anti-inflammatory roles in brain microvasculature to reduce ischemic cerebral vascular and parenchymal damages. Our studies also suggest that lncRNAs can be therapeutically targeted to minimize poststroke brain damage.

Long Non-Coding RNA Malat1 Regulates Angiogenesis in Hindlimb Ischemia.

Angiogenesis is a complex process that depends on the delicate regulation of gene expression. Dysregulation of transcription during angiogenesis often leads to various human diseases. Emerging evidence has recently begun to show that long non-coding RNAs (lncRNAs) may mediate angiogenesis in both physiological and pathological conditions; concurrently, underlying molecular mechanisms are largely unexplored. Previously, our lab identified metastasis associates lung adenocarcinoma transcript 1 (Malat1) as an oxygen-glucose deprivation (OGD)-responsive endothelial lncRNA. Here we reported that genetic deficiency of Malat1 leads to reduced blood vessel formation and local blood flow perfusion in mouse hind limbs at one to four weeks after hindlimb ischemia. Malat1 and vascular endothelial growth factor receptor 2 (VEGFR2) levels were found to be increased in both cultured mouse primary skeletal muscle microvascular endothelial cells (SMMECs) after 16 h OGD followed by 24 h reperfusion and in mouse gastrocnemius muscle that underwent hindlimb ischemia followed by 28 days of reperfusion. Moreover, Malat1 silencing by locked nucleic acid (LNA)-GapmeRs significantly reduced tube formation, cell migration, and cell proliferation in SMMEC cultures. Mechanistically, RNA subcellular isolation and RNA-immunoprecipitation experiments demonstrate that Malat1 directly targets VEGFR2 to facilitate angiogenesis. The results suggest that Malat1 regulates cell-autonomous angiogenesis through direct regulation of VEGFR2.

MicroRNA-15a/16-1 Antagomir Ameliorates Ischemic Brain Injury in Experimental Stroke.

BACKGROUND AND PURPOSE: Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. METHODS: Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1-specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion. The neurological scores, brain infarct volume, brain water content, and neurobehavioral tests were then evaluated and analyzed. To explore underlying signaling pathways associated with alteration of miR-15a/16-1 activity, major proinflammatory cytokines were measured by quantitative polymerase chain reaction or ELISA and antiapoptotic proteins were examined by Western blotting. RESULTS: Genetic deletion of the miR-15a/16-1 cluster or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain water content, and improved neurological outcomes in stroke mice. Inhibition of miR-15a/16-1 significantly decreased the expression of the proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule 1, tumor necrosis factor alpha, and increased Bcl-2 and Bcl-w levels in the ischemic brain regions. CONCLUSIONS: Our data indicate that pharmacological inhibition of the miR-15a/16-1 cluster reduces ischemic brain injury via both upregulation of antiapoptotic proteins and suppression of proinflammatory molecules. These results suggest that the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.

[Decreases of progressive motility, total motility, and acrosin activity of sperm from oligoasthenoteratospermia males at different time points after sperm activation].

OBJECTIVE: To investigate the progressive motility, (PR), total motility (progressive + non-progressive motility, PR + NP), and acrosin activity of sperm from normal and infertile men at different time points after sperm activation. METHODS: Based on the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen and the results of modified Papanicolaou staining, we divided the semen samples into groups A (normal, n = 28), B (oligoasthenoteratospermia, n = 30), and C (asthenoteratospermia, n = 32). At 1, 24, and 48 hours after sperm activation, we detected sperm PR and PR + NP by CASA and chemical colorimetry, and determined sperm acrosin activity using the modified Kennedy method. RESULTS: Sperm PR and PR + NP were significantly decreased in all the three groups at 1-24 hours and even more significantly at 24-48 hours after sperm activation as compared with the baseline (P < 0.05). Sperm acrosin activity showed remarkable reduction in group A (P = 0. 013) , even more significant at 1-24 hours than at 24-48 hours after sperm activation, but not in groups B and C (P = 0.519 and 0.979). CONCLUSION: Sperm PR, PR + NP, and acrosin activity are all decreased with the extension of time after sperm activation, each in a specific manner. Examination of sperm acrosin activity should be applied as a routine tool in the assessment of male fertility.

Rare flavanone-diarylheptanoid hybrids from Typha angustifolia shows anti breast cancer activity via activating TGF-ß1/Smad signaling pathway.

Four new flavanone-diarylheptanoid hetero dimers, typhatifolins A-D (1-4), were separated from the pollen of a widely distributed medicinal plant Typha angustifolia. Structures of these rare hybrids were elucidated by detailed interpretation of spectroscopic data, and their absolute configurations were determined on the basis of Mosher's method and ECD analyses. All the four compounds showed moderate to significant cytotoxicities against a panel of tumor cell lines with IC50 values ranging from 0.67 to 12.48 µM. Further in vitro antitumor evaluation for typhatifolin B (TTB, 2) on two breast cancer cells (4T1 and MDA-MB231) revealed that it could remarkably induce cell apoptosis and G0/G1 cycle arrest, as well as block cell migration and invasion. Mechanistically, TTB could exert its antitumor effect via activating the TGF-ß1 (transforming growth factor beta 1) signaling pathway as evidenced by RNA-seq analysis and immunoblotting experiments, which was further corroborated by treating cancer cells with a TGF-ß signaling inhibitor. Lastly, the in vivo anti breast cancer activity was demonstrated by applying the mixture of typhatifolins A-D to a preclinical animal model.

Toll-like receptor 4/nuclear factor-κB signaling pathway is involved in ACTG-toxin H-mediated anti-inflammatory effect.

ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the molecular mechanism underlying the anti-inflammatory properties of AH. Treatment with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1ß, inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH inhibited LPS-induced nuclear factor-κB (NFκB) DNA-binding activity. Using transfection assay and measurement of an NFκB-sensitive promoter region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS-induced NFκB transcription activity in 293T cells. AH significantly blocked LPS-induced NFκB activation in TLR4-transfected cells. Taken together, our data indicated that anti-inflammatory properties of AH resulted from the inhibition of proinflammatory cytokines and enzyme production via the TLR4/NFκB signaling pathway.

Effects of vitamin E on expressions of eight microRNAs in the liver of Nile tilapia (Oreochromis niloticus).

Currently, microRNAs (miRNAs) are known to regulate cellular processes such as apoptosis, differentiation, cell cycle, and immune functions, and their expression can be altered by distinct stress conditions, such as oxidative stress. In immune systems of fish, vitamin E (VE) has a defined role as an antioxidant. In order to understand the molecular mechanism of vitamin E defending from oxidative stress, three groups of juvenile Nile tilapia (Oreochromis niloticus) (initial weight 3.25 ± 0.02 g) were fed to satiation with 3 semi-purified diets containing VE (DL-α-tocopherol acetate) of 0, 50, and 2500 mg/kg supplementation, respectively, with the expressions of eight miRNAs (miR-21, miR-223, miR-146a, miR-125b, miR-181a, miR-16, miR-155 and miR-122) in the liver of tilapia subsequently detected after 8-week growth experiment. Results showed that VE-deficient (0 mg/kg supplementation) decreased the activity of superoxide dismutase (SOD), and decreased the expressions of miR-223, miR-146a, miR-16 and miR-122, while excessive supplementation of VE (2500 mg/kg) decreased SOD activity and increased the expressions of all the eight miRNAs. The targets of the eight miRNAs were further predicated with bioinformatic approach and the possible regulating mechanisms of VE via miRNAs were analyzed. The present study confirmed that the differences in dietary VE affected expression of hepatic miRNAs which may partly demonstrate the molecular mechanism of VE, and the new idea of introducing miRNAs into research will provide the basic data for researches of molecular nutrition.

CCL21/CCR7 axis regulates demyelination and vascular cognitive impairment in a mouse model for chronic cerebral hypoperfusion.

OBJECTIVES: White matter lesions (WML) are usually accompanied by cognitive decline, which consist of axonal loss and demyelination. CC chemokine ligand 21 (CCL21) and its receptor C-C chemokine receptor 7 (CCR7) belong to the chemokine family, which are involved in many diseases. However, their function in the central nervous system (CNS) is still unexplored. This study aimed to explore the role of CCL21/CCR7 axis in the pathological process of chronic ischemia-induced WML. METHODS: Bilateral common carotid artery stenosis (BCAS) was employed in C57BL/6 mice as the in vivo WML model. Microarray analysis was performed to detect the overall molecular changes induced in the endothelial cells by BCAS. Q-PCR, Western blotting, and immunofluorescence staining were performed to evaluate expression levels of the related molecules. The mice were injected with LV-CCL21-GFP virus in the corpus callosum to overexpress CCL21. WML degree was determined via MRI, and cognitive ability was assessed by Y-maze and novel object recognition tests. Myelin sheath integrity was evaluated via immunofluorescence staining. RESULTS: CCL21 was significantly downregulated in endothelial cells after BCAS and CCL21 overexpression alleviated BCAS-induced cognitive deficits and demyelination. Furthermore, CCR7 was found to be mainly expressed in oligodendrocytes (OLs) after exposed to hypoxia and CCR7 silencing blocked the protective effects induced by CCL21 overexpression. Conclusions CCL21/CCR7 axis may play a key role in demyelination induced by BCAS. This might provide a novel therapeutic target for WML.

Receptivity assessment of an ultrasonographic homogeneous endometrium in the late follicular phase of infertile women with natural cycles.

OBJECTIVE: The purpose of this study was to assess the receptivity of the homogeneous endometrium in the late follicular phase in infertile women with natural cycles. STUDY DESIGN: Twenty-eight infertile women with ultrasonographically homogeneous (group 1) or trilaminar (group 2) endometria in the late follicular phase underwent endometrial biopsies. Some molecular markers and development of pinopodes were evaluated. RESULTS: In the late follicular phase, the mean level of vascular endothelial growth factor was significantly lower in group 1 than in group 2 (0.96 ± 0.37 marks vs 1.39 ± 0.46 marks; P = .010). In the mid luteal phase, a decreased leukemia inhibitory factor and integrin alpha v beta 3 levels were found in group 1 (1.58 ± 0.99 marks vs 2.59 ± 0.61 marks; 1.85 ± 0.72 marks vs 2.60 ± 0.73 marks; 1.92 ± 0.91 marks vs 2.83 ± 0.57 marks; P = .003; P = .011; P = .004). The rate of fully developed pinopodes in the mid luteal phase was significantly decreased in group 1 (P = .018). CONCLUSION: An ultrasonographically homogeneous endometrium in the late follicular phase was associated with poor receptivity in infertile women with natural cycles.

Protective effects of the ethanolic extract of Melia toosendan fruit against colon cancer.

Colorectal cancer is one of the leading causes of death in the world. Plant-derived products have proven to be valuable sources for discovery and development of unique anticancer drugs. In this study, the inhibitory effects of ethanolic extract of Melia toosendan fruit (EMTF), a traditional medicine in the Chinese Pharmacopeia were evaluated in vitro and in vivo against colon cancer. Human colon cancer cells SW480 and murine colorectal adenocarcinoma cells CT26 were used to investigate cell proliferation. The results showed that EMTF inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation. Through increasing mitochondrial membrane permeability and cytochrome c release from mitochondria, EMTF induced caspase-9 activity which further activated caspase-3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis. The in vivo results confirmed reduction of tumor volume and apoptotic effects and the side effects were not induced by EMTF. Therefore, EMTF may be an effective chemotherapeutic agent for colon cancer treatment.

New Schemes for Investment in of Small and Medium-Sized Enterprises of China: Role of Access to Finance, Innovation, and Sustainability.

Firm innovation relies heavily on financing, which is why it is a hot topic in the fields of finance and innovation management. Organizations can make strategic investments in production factors to develop competitive advantages because they have access to financial resources. This study investigated how financial literacy, innovativeness, and environmental sustainability influence the sustainability of small and medium-sized enterprises (SMEs). This was set as the primary objective in order to better understand the nature of the impact of financial literacy and innovation on the sustainability of SME firms. To test the hypotheses, structural equation modeling (SEM) was applied using data collected from 300 small businesses firms in China. The results revealed that financial literacy and innovativeness significantly influence small firms' sustainability. Additionally, social inclusion significantly affects small firms' sustainability, and sequentially has a significant effect on their performance. Research findings suggested that small businesses incorporate sustainability models into their operations and enhance financial knowledge in order to maintain sustainability.

The Impact of the Scale of Third-Party Logistics Guaranteeing Firms on Bank Credit Willingness in Supply Chain Finance: An ERP Study.

Supply chain financing guaranteed by third-party logistics (3PL) firms is an effective way to solve the financing difficulties of small and medium-sized enterprises (SMEs). Studies have explored factors that affect the willingness of supply chain financial credit providers under guarantee of 3PL firms (e.g., the scale of financing enterprises and credit). However, whether the scale of 3PL firms will affect the bank's credit decision has not been studied, as well as the neural processing of credit decisions. To clarify these issues, this study extracted behavioral and event-related potentials (ERPs) data when participants performed a selection task of judging whether to grant credit to guaranteed financing-seeking enterprises according to the large or small scale of the 3PL guaranteeing firms. The behavioral results showed that under the condition of a large-scale 3PL guaranteeing firm, the willingness to provide credit to SMEs was higher than that under the condition of a small-scale 3PL guaranteeing firm. This finding indicates there was credit scale discrimination against 3PL guaranteeing firms in supply chain finance. The ERP results showed that compared with the condition of a large-scale 3PL guaranteeing firm, a greater N2 amplitude was induced under the condition of a small-scale 3PL guaranteeing firm, which indicated that credit decision makers experienced greater perceived risk and more decision-making conflict. In contrast, a larger LPP amplitude was detected under the condition of a large-scale 3PL guaranteeing firm (as opposed to a small-scale firm), which indicated that large-scale 3PL guaranteeing firms received more positive comments and more positive emotions from credit decision makers than small-scale 3PL guaranteeing firms. Based on these results, this study reveals the cognition process of credit decision makers regarding the impact of the 3PL guaranteeing firm scale on the willingness to provide credit in supply chain finance and explains the theory of credit scale discrimination from the perspective of decision neuroscience.