Interleukin-41: a novel serum marker for the diagnosis of alpha-fetoprotein-negative hepatocellular carcinoma.

Background: For the lack of effective serum markers for hepatocellular carcinoma(HCC) diagnosis, it is difficult to detect liver cancer and identify its recurrence early. Methods: Databases were used to analyze the genes potentially associated with alpha-fetoprotein(AFP). ELISA assay was used to detect the serum IL-41 in HCC, liver metastases, hepatitis, and healthy people. Immunohistochemical staining was used to analyze the relative quantification of IL-41 in HCC and paracancer tissues. Various survival curves were plotted according to clinical pathological data and helped us draw the ROC curve of IL-41 diagnosis of HCC. Results: The serum expression of IL-41 was highest in AFP negative HCC patients and significantly higher than that in AFP positive HCC and metastatic cancer patients. There was a significant negative correlation between elevated serum IL-41 and AFP(<1500ng/ml). The clinicopathological features suggested that the serum IL-41 level was significantly correlated with capsule invasion, low differentiation and AFP. High serum expression of IL-41 suggests poorer survival and earlier recurrence after resection, and IL-41 upregulated in patients with early recurrence and death. The expression of IL-41 was higher in HCC tissues of patients with multiple tumors or microvascular invasion. The ROC curve showed that serum IL-41 had a sensitivity of 90.17 for HCC and a sensitivity of 96.63 for AFP-negative HCC, while the specificity was higher than 61%. Conclusion: IL-41 in serum and tissue suggests poor prognosis and postoperative recurrence in HCC patients and could be a new serum diagnostic marker for AFP negative patients.

BCLAF1-induced HIF-1α accumulation under normoxia enhances PD-L1 treatment resistances via BCLAF1-CUL3 complex.

Bcl-2-associated transcription factor-1 (BCLAF1), an apoptosis-regulating protein of paramount significance, orchestrates the progression of various malignancies. This study reveals increased BCLAF1 expression in hepatocellular carcinoma (HCC) patients, in whom elevated BCLAF1 levels are linked to escalated tumor grades and diminished survival rates. Moreover, novel BCLAF1 expression is particularly increased in HCC patients who were not sensitive to the combined treatment of atezolizumab and bevacizumab, but not in patients who had tumors that responded to the combined regimen. Notably, overexpression of BCLAF1 increases HCC cell proliferation in vitro and in vivo, while the conditioned medium derived from cells overexpressing BCLAF1 strikingly enhances the tube-formation capacity of human umbilical vein endothelial cells. Furthermore, compelling evidence demonstrates that BCLAF1 attenuates the expression of prolyl hydroxylase domain protein 2 (PHD2) and governs the stability of hypoxia-inducible factor-1α (HIF-1α) under normoxic conditions without exerting any influence on transcription, as determined by Western blot and RT‒qPCR analyses. Subsequently, employing coimmunoprecipitation and immunofluorescence, we validated the reciprocal interaction between BCLAF1 and Cullin 3 (CUL3), through which BCLAF1 actively upregulates the ubiquitination and degradation of PHD2. The Western blot and RT‒qPCR results suggests that programmed death ligand-1 (PD-L1) is one of the downstream responders to HIF-1α in HCC. Thus, we reveal the pivotal role of BCLAF1 in promoting PD-L1 transcription and, through binding to CUL3, in promoting the accumulation of HIF-1α under normoxic conditions, thereby facilitating the ubiquitination and degradation of PHD2.

Rno_circRNA_006061 participates in apoptosis induced by formaldehyde via activating p38/ATF3 pathway.

Formaldehyde, a common indoor air pollutant, is significantly toxic to the respiratory system, whereas its mechanism is unclear. CircRNAs exert critical functions via sponging microRNAs (miRNAs). To evaluate the effect of long-term formaldehyde exposure on rno_circRNA_006061 expression profiles, the downstream targets and signaling pathways associated with rno_circRNA_006061 were predicted and validated using bioinformatics methods and dual-luciferase reporter assay. Previously, our circRNA microarray showed that rno_circRNA_006061 was up-regulated in the formaldehyde-exposed lung tissue. Subsequently, bioinformatics analysis predicted that rno_circRNA_006061 bound to rno-miR-128-3p and co-regulated the p38/ATF3 signaling pathway. Meanwhile, the expressions of rno_circRNA_006061, rno-miR-128-3p and p38 were correlated with the lung histomorphopathological injury assessment. Furthermore, TUNEL and Bax/Bcl-2 ratio results revealed that up-regulated rno_circRNA_00606 induced by formaldehyde stimulated apoptosis in the lung. After the knockdown of rno_circRNA_006061, the expression of rno-miR-128-3p increased and the expression of p38 decreased slightly, which partially restored formaldehyde-induced apoptosis in alveolar epithelial cells. In conclusion, our study hinted that the rno_circRNA_006061 might enhance p38/ATF3 pathway expression via sponging the rno-miR-128-3p, thus significantly promoting apoptosis in lung tissues, which may provide potential new targets for preventing and treating lung injury by formaldehyde inhalation.

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer.

Background: As a highly prevalent malignancy among women worldwide, breast cancer, remains a critical public health issue necessitating the development of novel therapeutics and biomarkers. Kruppel Like Factor 2 (KLF2), a member of the Kruppel family of transcription factors, has been implicated in various types of cancer due to its diminished expression; however, the potential implications of KLF2 expression in relation to breast cancer progression, prognosis, and therapy remain unclear. Methods: The present study employed the Tumor Immune Estimation Resource (TIMER) and The Human Protein Atlas databases to investigate the expression pattern of KLF2 in pan-cancer. The relationship between KLF2 expression and clinical features or immune infiltration of The Cancer Genome Atlas (TCGA) breast cancer samples was evaluated using Breast Cancer Integrative Platform (BCIP) and TIMER. The expression levels of KLF2 in breast cancer were validated via immunohistochemical staining analysis. Gene Set Enrichment Analysis (GSEA) to study the KLF2-related gene ontology. STRING database was employed to construct a protein-protein interaction (PPI) network of KLF2 in relation to vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1α (HIF1α). The expression of KLF2 following diverse breast cancer therapies was analyzed in the Gene Expression Omnibus (GEO) databases. The expression of KLF2 following treatment with simvastatin was validated via immunofluorescence and western blotting. Results: Our study reveals that KLF2 displays significantly reduced expression in cancerous tissues compared to non-cancerous controls. Patients with low KLF2 expression levels exhibited poor prognosis across multiple cancer types. KLF2 expression levels were found to be reduced in advanced cancer stages and grades, while positively correlated with the expression of estrogen receptor (ER), progesterone receptor (PR), and tumor size in breast cancer. KLF2 expression is associated with diverse immune infiltration cells, and may impact the breast tumor immune microenvironment by regulating dendritic cell activation. Additionally, we observed a negative correlation between KLF2 expression levels and angiogenesis, as well as the expression of VEGFA and HIF1α. Notably, the anticancer drug simvastatin could induce KLF2 expression in both breast cancer. Conclusion: Based on our observations, KLF2 has potential as a diagnostic, prognostic, and therapeutic biomarker for breast cancer.

Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types.

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti-angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic-related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient-derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET-1), an important regulator of angiogenesis and the hypoxia-related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET-1-induced hypoxia-inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.

Hypoxia-induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth fatal malignant tumour type worldwide. However, the exact molecular mechanism involved in HCC progression remains unclear. METHODS: Three pairs of HCC and matched portal vein tumour thrombus (PVTT) tissue samples were analysed by isobaric tags for relative and absolute quantification (iTRAQ) assay to investigate the differentially expressed proteins. Real-time quantitative PCR, immunostaining, and immunoblotting were performed to detect cofilin 1 (CFL1) in HCC and non-tumour tissues. CCK8 and EdU, and Transwell assays, respectively, determined cell proliferation, migration, and invasion of HCC cells. Further, subcutaneous and tail vein injection were performed in nude mice for investigating HCC growth and lung metastasis in vivo. Regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on CFL1 was confirmed by chromatin immunoprecipitation (ChIP) assay. Finally, interaction between CFL1 and phospholipase D1 (PLD1) was studied using immunoprecipitation (IP) assay. RESULTS: The iTRAQ analysis identified expression of CFL1 to be significantly upregulated in PVTT than in HCC tissues. Increased expression of CFL1 was closely associated with unfavourable clinical features, and was an independent risk predictor of overall survival in HCC patients. The knockdown of CFL1 inhibited cell growth viability, invasiveness, and epithelial-mesenchymal transformation (EMT) in HCC cells. Furthermore, CFL1 silencing significantly suppressed the growth and lung metastasis of HCC cells in nude mice. Next, HIF-1α directly regulated CFL1 transcription by binding to the hypoxia-responsive element (HRE) in the promoter. Moreover, we disclosed the interaction between CFL1 and PLD1 in HCC cells using IP assay. Mechanistically, CFL1 maintained PLD1 expression by repressing ubiquitin-mediated protein degradation, thereby activating AKT signalling in HCC cells. Notably, the CFL1/PLD1 axis was found mediating the hypoxia-induced activation of the AKT pathway and EMT. CONCLUSION: The analysis suggests that hypoxia-induced CFL1 increases the proliferation, migration, invasion, and EMT in HCC by activating the PLD1/AKT pathway.

Improving Single Shot Object Detection With Feature Scale Unmixing.

Due to the advantages of real-time detection and improved performance, single-shot detectors have gained great attention recently. To solve the complex scale variations, single-shot detectors make scale-aware predictions based on multiple pyramid layers. Typically, small objects are detected on shallow layers while large objects are detected on deep layers. However, the features in the pyramid are not scale-aware enough, which limits the detection performance. Two common problems in single-shot detectors caused by object scale variations can be observed: (1) false negative problem, i.e., small objects are easily missed due to the weak features; (2) part-false positive problem, i.e., the salient part of a large object is sometimes detected as an object. With this observation, a new Neighbor Erasing and Transferring (NET) mechanism is proposed for feature scale-unmixing to explore scale-aware features in this paper. In NET, a Neighbor Erasing Module (NEM) is designed to erase the salient features of large objects and emphasize the features of small objects in shallow layers. A Neighbor Transferring Module (NTM) is introduced to transfer the erased features and highlight large objects in deep layers. With this mechanism, a single-shot network called NETNet is constructed for scale-aware object detection. In addition, we propose to aggregate nearest neighboring pyramid features to enhance our NET. Experiments on MS COCO dataset and UAVDT dataset demonstrate the effectiveness of our method. NETNet obtains 38.5% AP at a speed of 27 FPS and 32.0% AP at a speed of 55 FPS on MS COCO dataset. As a result, NETNet achieves a better trade-off for real-time and accurate object detection.

TJU-DHD: A Diverse High-Resolution Dataset for Object Detection.

Vehicles, pedestrians, and riders are the most important and interesting objects for the perception modules of self-driving vehicles and video surveillance. However, the state-of-the-art performance of detecting such important objects (esp. small objects) is far from satisfying the demand of practical systems. Large-scale, rich-diversity, and high-resolution datasets play an important role in developing better object detection methods to satisfy the demand. Existing public large-scale datasets such as MS COCO collected from websites do not focus on the specific scenarios. Moreover, the popular datasets (e.g., KITTI and Citypersons) collected from the specific scenarios are limited in the number of images and instances, the resolution, and the diversity. To attempt to solve the problem, we build a diverse high-resolution dataset (called TJU-DHD). The dataset contains 115354 high-resolution images (52% images have a resolution of 1624×1200 pixels and 48% images have a resolution of at least 2, 560×1.440 pixels) and 709 330 labeled objects in total with a large variance in scale and appearance. Meanwhile, the dataset has a rich diversity in season variance, illumination variance, and weather variance. In addition, a new diverse pedestrian dataset is further built. With the four different detectors (i.e., the one-stage RetinaNet, anchor-free FCOS, two-stage FPN, and Cascade R-CNN), experiments about object detection and pedestrian detection are conducted. We hope that the newly built dataset can help promote the research on object detection and pedestrian detection in these two scenes. The dataset is available at https://github.com/tjubiit/TJU-DHD.

High-matrix-stiffness induces promotion of hepatocellular carcinoma proliferation and suppression of apoptosis via miR-3682-3p-PHLDA1-FAS pathway.

Hepatocellular carcinoma (HCC) with malignant behaviors related to death causes distant metastasis and is the fourth primary cancer in the whole world, which has taken millions lives in Asian countries such as China. The novel miR-3682-3p involving high-expression-related poor prognosis in HCC tissues and cell lines indicate oncogenesis functions in vitro and in vivo. According to TCGA database, our group find several none-coding RNAs showing abnormal expression including miR-3682-3p, thus we originally confirmed the inhibition of proliferation and acceleration of apoptosis are enhanced in miR-3682-3p knock-down cell lines. Then, in nude mice transplantation assays, we found the suppressor behaviors, smaller nodules and lower speed of tumor expansion in model of injection of cell cultured and transfected shRNA-miR-3682-3p. A combination of databases (Starbase, Targetscan and MiRgator) illustrates miR-3682-3p targets PHLDA1, which shows negative correlation demonstrated by dual-luciferase reporter system. To make functional verification of PHLDA1, we upregulate the gene and rescue tests are established to confirm that miR-3682-3p suppresses PHLDA1 to promotion of cell growth. Rescue experiments finish making confirmation of relation of miR-3682-3p and PHLDA1 subsequently. Cirrhotic tissues illustrate strong correlation to higher miR-3682-3p and clinical features make the hint that high-extracellular-matrix-stiffness environment promotes such miRNA. Functional tests on different stiffness provide the proof of underlying mechanism. In conclusion, the overexpression of miR-3682-3p mediates PHLDA1 inhibition could impede apoptosis and elevate proliferation of HCC through high-extracellular-matrix-stiffness environment potentially.

A Porous Mooncake-Shaped Li4 Ti5 O12 Anode Material Modified by SmF3 and Its Electrochemical Performance in Lithium Ion Batteries.

Reasonably designing and synthesizing advanced electrode materials is significant to enhance the electrochemical performance of lithium ion batteries (LIBs). Herein, a metal-organic framework (MOF, Mil-125) was used as a precursor and template to successfully synthesize the porous mooncake-shaped Li4 Ti5 O12 (LTO) anode material assembled from nanoparticles. Even more critical, SmF3 was used to modify the prepared porous mooncake-shaped LTO material. The SmF3 -modified LTO maintained a porous mooncake-shaped structure with a large specific surface area, and the SmF3 nanoparticles were observed to be attach on the surface of the LTO material. It has been proven that the SmF3 modification can further facilitate the transition from Ti4+ to Ti3+ , reduce the polarization of electrode, decrease charge transfer impedance (Rct ) and solid electrolyte interface impedance (Rsei ), and increase the lithium ion diffusion coefficient (DLi ), thereby enhancing the electrochemical performance of LTO. Therefore, the porous mooncake-shaped LTO modified using 2 wt % SmF3 displays a large specific discharge capacity of 143.8 mAh g-1 with an increment of 79.16 % compared to pure LTO at a high rate of 10 C (1 C=170 mAh g-1 ), and shows a high retention rate of 96.4 % after 500 cycles at 5 C-rate.

Hypoxia-induced miR-3677-3p promotes the proliferation, migration and invasion of hepatocellular carcinoma cells by suppressing SIRT5.

Hepatocellular carcinoma (HCC), with life-threatening malignant behaviours, often develops distant metastases and is the fourth most common primary cancer in the world, having taken millions of lives in Asian countries such as China. The novel miR-3677-3p is involved in a high-expression-related poor prognosis in HCC tissues and cell lines, indicating oncogenesis functions in vitro and in vivo. Initially, we confirmed the inhibition of proliferation, migration and invasion in miR-3677-3p knock-down MHCC-97H and SMMC-7721 cell lines, which are well known for their high degree of invasiveness. Then, we reversed the functional experiments in the low-miR-3677-3p-expression Hep3B cell line via overexpressing miR-3677-3p. In nude mice xenograft and lung metastasis assays, we found suppressor behaviours, smaller nodules and low density of organ spread, after injection of cells transfected with shRNA-miR-3677-3p. A combination of databases (Starbase, TargetScan and MiRgator) illustrated miR-3677-3p targets, and it was shown to suppress the expression of SIRT5 in a dual-luciferase reporter system. To clarify the conclusions of previous ambiguous research, we up-regulated SIRT5 in Hep3B cells, and rescue tests were established for confirmation that miR-3677-3p suppresses SIRT5 to enhance the migration and invasion of HCC. Interestingly, we discovered hypoxia-induced miR-3677-3p up-regulation benefited HCC malignancy and invasiveness. In conclusion, the overexpression of miR-3677-3p mediated SIRT5 inhibition, which could increase proliferation, migration and invasion of HCC in hypoxic microenvironments.

Anti-toll-like receptor 2 antibody ameliorates hepatic injury, inflammation, fibrosis and steatosis in obesity-related metabolic disorder rats via regulating MAPK and NF-κB pathways.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, which includes a spectrum of histological liver changes. Non-alcoholic steatohepatitis (NASH) is considered to be the progressive subtype of NAFLD, which is characterized by lobular inflammation and cellular ballooning on the basis of steatosis. There is a critical need to develop novel and effective therapeutic approaches for NAFLD/NASH. The activation of toll-like receptor 2 (TLR2) signaling pathway plays a key role in high-fat-related inflammation, triggering the occurrence and development of NASH. Herein, the anti-TLR2 monoclonal antibody (TLR2 mAb) was prepared and investigated for its ability to ameliorate the inflammatory response in vivo and in vitro. The anti-inflammatory role of TLR2 mAb in vitro was examined in NR8383 macrophage cells and THP-1 derived macrophage cells. For confirmation in vivo, three groups of SD rats were treated for 20 weeks: rats in the control were fed with a standard diet; rates in the IgG and TLR2 mAb groups were fed with a high-fat diet and with IgG or TLR2 mAb, respectively. Liver tissue and serum were collected for further analysis. Results showed that after 4-week treatment with TLR2 mAb, metabolic parameters in rats were improved markedly (body weight, fasting blood glucose level, liver steatosis, inflammatory response and fibrosis). Moreover, western blotting demonstrated that the TLR2 mAb blocked MAPKs and NF-κB activation, and inhibited the expression of inflammatory factors in rat liver tissue. These effects suggested that TLR2 mAb could improve HFD-induced hepatic injury, inflammation, fibrosis and steatosis by suppressing inflammatory response and regulating the hepatic MAPKs and NF-κB signaling pathways. This suggests that TLR2 may be a novel therapeutic target for metabolic diseases especially NASH.

Long Noncoding RNA lnc-HC Regulates PPARγ-Mediated Hepatic Lipid Metabolism through miR-130b-3p.

Nonalcoholic fatty liver disease (NAFLD) is due to the excessive lipid accumulation within hepatocytes. Metabolic nuclear receptors (MNRs) play great roles in lipid homeostasis. We have identified a novel long noncoding RNA (lncRNA), lnc-HC, which regulates hepatocytic cholesterol metabolism through reducing Cyp7a1 and Abca1 expression. Here, we further elucidate its roles in hepatic fatty acid and triglyceride (TG) metabolism through a novel lncRNA regulatory mechanism. The most prominent target of lnc-HC identified by in vitro study is PPARγ. Further studies revealed that lnc-HC negatively regulates PPARγ at both the mRNA and protein levels and suppresses hepatocytic lipid droplet formation. Importantly, the function of lnc-HC in regulating PPARγ expression depends on modulating miR-130b-3p expression from the transcriptional to the post-transcriptional level, not through lncRNA's critical modulating patterns. In vivo, the reduction of lnc-HC expression significantly decreases miR-130b-3p expression, induces PPARγ expression, and increases TG concentration in rat livers with hyperlipidemia. These findings further help in understanding the regulatory pattern of lnc-HC in hepatic lipid metabolism and might present a possible therapeutic target for improving lipid homeostasis.

Long non-coding RNA SNHG16 promotes proliferation and inhibits apoptosis of diffuse large B-cell lymphoma cells by targeting miR-497-5p/PIM1 axis.

The aberrant expression and dysfunction of long non-coding RNAs (lncRNAs) have been identified as critical factors governing the initiation and progression of different human cancers, including diffuse large B-cell lymphoma (DLBCL). LncRNA small nucleolar RNA host gene 16 (SNHG16) has been recognized as a tumour-promoting factor in various types of cancer. However, the biological role of SNHG16 and its underlying mechanism are still unknown in DLBCL. Here we disclosed that SNHG16 was overexpressed in DLBCL tissues and the derived cell lines. SNHG16 knockdown significantly suppressed cell proliferation and cell cycle progression, and it induced apoptosis of DLBCL cells in vitro. Furthermore, silencing of SNHG16 markedly repressed in vivo growth of OCI-LY7 cells. Mechanistically, SNHG16 directly interacted with miR-497-5p by acting as a competing endogenous RNA (ceRNA) and inversely regulated the abundance of miR-497-5p in DLBCL cells. Moreover, the proto-oncogene proviral integration site for Moloney murine leukaemia virus 1 (PIM1) was identified as a novel direct target of miR-497-5p. SNHG16 overexpression rescued miR-497-5p-induced down-regulation of PIM1 in DLBCL cells. Importantly, restoration of PIM1 expression reversed SNHG16 knockdown-induced inhibition of proliferation, G0/G1 phase arrest and apoptosis of OCI-LY7 cells. Our study suggests that the SNHG16/miR-497-5p/PIM1 axis may provide promising therapeutic targets for DLBCL progression.

MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/ß-catenin signaling through targeting BCL9.

Local and systemic metastasis of hepatocellular carcinoma (HCC) causes the poor prognosis and increasing evidence confirms that aberrant miRNAs were involved in cancer progression. However, the expression and mechanisms of a specific miR-3194-3p in HCC remains unknown. In this research, we demonstrated that miR-3194-3p, significantly down-regulated in HCC tissues and cell lines, was associated with metastasis and recurrence of HCC. Notably, gain- and loss-of-function assays demonstrated that miR-3194-3p inhibited the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro and in vivo. BCL9, up-regulated in HCC tissues, was a direct downstream target of miR-3194-3p and mediated the functional influence of miR-3194-3p. Most importantly, miR-3194-3p exerted its function by regulating ß-catenin pathway. Moreover, miR-3194-3p and BCL9 expression were markedly correlated with adverse clinical features and poor prognosis of HCC patients. We showed that hypoxia was responsible for the down-expression of miR-3194-3p in HCC. Also, the promoting effects of hypoxia on metastasis and EMT of HCC cells were reversed by miR-3194-3p. Altogether, our study suggested that miR-3194-3p inhibits HCC EMT via decreasing Wnt/ß-catenin signaling through targeting BCL9 and might be a therapeutic target for HCC.

Catalysts of self-assembled Pt@CeO2-δ-rich core-shell nanoparticles on 3D ordered macroporous Ce1-xZrxO2 for soot oxidation: nanostructure-dependent catalytic activity.

The catalytic performance in heterogeneous catalytic reactions consisting of solid reactants is strongly dependent on the nanostructure of the catalysts. Metal-oxides core-shell (MOCS) nanostructures have potential to enhance the catalytic activity for soot oxidation reactions as a result of optimizing the density of active sites located at the metal-oxide interface. Here, we report a facile strategy for fabricating nanocatalysts with self-assembled Pt@CeO2-δ-rich core-shell nanoparticles (NPs) supported on three-dimensionally ordered macroporous (3DOM) Ce1-xZrxO2via the in situ colloidal crystal template (CCT) method. The nanostructure-dependent activity of the catalysts for soot oxidation were investigated by means of SEM, TEM, H2-TPR, XPS, O2-isothermal chemisorption, soot-TPO and so on. A CeO2-δ-rich shell on a Pt core is preferentially separated from Ce1-xZrxO2 precursors and could self-assemble to form MOCS nanostructures. 3DOM structures can enhance the contact efficiency between catalysts and solid reactants (soot). Pt@CeO2-δ-rich core-shell nanostructures can optimize the density of oxygen vacancies (Ov) as active sites located at the interface of Pt-Ce1-xZrxO2. Remarkably, 3DOM Pt@CeO2-δ-rich/Ce1-xZrxO2 catalysts show super catalytic performance and strongly nanostructure-dependent activity for soot oxidation in the absence of NO and NO2. For example, the T50 of the 3DOM Pt@CeO2-δ-rich/Ce0.8Zr0.2O2 catalyst is lowered down to 408 °C, and the reaction rate of the 3DOM Pt@CeO2-δ-rich/Ce0.2Zr0.8O2 catalyst (0.12 µmol g-1 s-1) at 300 °C is 4 times that of the 3DOM Pt/Ce0.2Zr0.8O2 catalyst (0.03 µmol g-1 s-1). The structures of 3DOM Ce1-xZrxO2-supported Pt@CeO2-δ-rich core-shell NPs are decent systems for deep oxidation of solid reactants or macromolecules, and this facile technique for synthesizing catalysts has potential to be applied to other element compositions.

Stable atrogin-1 (Fbxo32) and MuRF1 (Trim63) gene expression is involved in the protective mechanism in soleus muscle of hibernating Daurian ground squirrels (Spermophilus dauricus).

Understanding the mechanisms that protect against or limit muscle atrophy in hibernators during prolonged inactivity has important implications for its treatment. We examined whether external factors influence the pathways regulating protein synthesis and degradation, leading to muscle atrophy prevention in Daurian ground squirrels (Spermophilus dauricus). We investigated the effects of 14-day hindlimb-unloading (HU) in different seasons and two-month hibernation on the soleus (SOL) muscle wet mass, muscle-to-body mass ratio, fiber cross sectional area (CSA), fiber distribution and muscle ultrastructure. We also measured changes in the protein expression and activation states of Akt, mTOR and FoxO1 and the mRNA expression of atrogin-1 and MuRF1. Compared with the control groups, autumn and winter HU significantly lowered SOL muscle wet mass and muscle-to-body mass ratio, decreased type I and II fiber CSA and induced ultrastructural anomalies. However, these measured indices were unchanged between Pre-hibernation and Hibernation groups. Furthermore, phosphorylation levels of Akt and mTOR significantly decreased, while the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 increased after HU. During hibernation, the phosphorylation levels of Akt and mTOR significantly decreased, but the phosphorylation level of FoxO1 and mRNA expression of atrogin-1 and MuRF1 remained unchanged. Overall, our findings suggest that disuse and seasonality may not be sufficient to initiate the innate protective mechanism that prevents SOL atrophy during prolonged periods of hibernation inactivity. The stable expression of atrogin-1 and MuRF1 may facilitate to prevent SOL atrophy via controlling ubiquitination of muscle proteins during hibernation.