Fibroblast growth factor receptor 1 inhibition suppresses pancreatic cancer chemoresistance and chemotherapy-driven aggressiveness.

AIMS: Pancreatic ductal adenocarcinoma (PDAC) is often intrinsically-resistant to standard-of-care chemotherapies such as gemcitabine. Acquired gemcitabine resistance (GemR) can arise from treatment of initially-sensitive tumors, and chemotherapy can increase tumor aggressiveness. We investigated the molecular mechanisms of chemoresistance and chemotherapy-driven tumor aggressiveness, which are understood incompletely. METHODS: Differential proteomic analysis was employed to investigate chemotherapy-driven chemoresistance drivers and responses of PDAC cells and patient-derived tumor xenografts (PDX) having different chemosensitivities. We also investigated the prognostic value of FGFR1 expression in the efficacy of selective pan-FGFR inhibitor (FGFRi)-gemcitabine combinations. RESULTS: Quantitative proteomic analysis of a highly-GemR cell line revealed fibroblast growth factor receptor 1 (FGFR1) as the highest-expressed receptor tyrosine kinase. FGFR1 knockdown or FGFRi co-treatment enhanced gemcitabine efficacy and decreased GemR marker expression, implicating FGFR1 in augmentation of GemR. FGFRi treatment reduced PDX tumor progression and prolonged survival significantly, even in highly-resistant tumors in which neither single-agent showed efficacy. Gemcitabine exacerbated aggressiveness of highly-GemR tumors, based upon proliferation and metastatic markers. Combining FGFRi with gemcitabine or gemcitabine+nab-paclitaxel reversed tumor aggressiveness and progression, and prolonged survival significantly. In multiple PDAC PDXs, FGFR1 expression correlated with intrinsic tumor gemcitabine sensitivity. CONCLUSION: FGFR1 drives chemoresistance and tumor aggressiveness, which FGFRi can reverse.

Lithium Superionic Conductive Nanofiber-Reinforcing High-Performance Polymer Electrolytes for Solid-State Batteries.

Although composite solid-state electrolytes (CSEs) are considered promising ionic conductors for high-energy lithium metal batteries, their unsatisfactory ionic conductivity, low mechanical strength, poor thermal stability, and narrow voltage window limit their practical applications. We have prepared a new lithium superionic conductor (Li-HA-F) with an ultralong nanofiber structure and ultrahigh room-temperature ionic conductivity (12.6 mS cm-1). When it is directly coupled with a typical poly(ethylene oxide)-based solid electrolyte, the Li-HA-F nanofibers endow the resulting CSE with high ionic conductivity (4.0 × 10-4 S cm-1 at 30 °C), large Li+ transference number (0.66), and wide voltage window (5.2 V). Detailed experiments and theoretical calculations reveal that Li-HA-F supplies continuous dual-conductive pathways and results in stable LiF-rich interfaces, leading to its excellent performance. Moreover, the Li-HA-F nanofiber-reinforced CSE exhibits good heat/flame resistance and flexibility, with a high breaking strength (9.66 MPa). As a result, the Li/Li half cells fabricated with the Li-HA-F CSE exhibit good stability over 2000 h with a high critical current density of 1.4 mA cm-2. Furthermore, the LiFePO4/Li-HA-F CSE/Li and LiNi0.8Co0.1Mn0.1O2/Li-HA-F CSE/Li solid-state batteries deliver high reversible capacities over a wide temperature range with a good cycling performance.

Construction of LncRNA-Related ceRNA Networks in Longissimus Dorsi Muscle of Jinfen White Pigs at Different Developmental Stages.

The development of skeletal muscle in pigs might determine the quality of pork. In recent years, long non-coding RNAs (lncRNAs) have been found to play an important role in skeletal muscle growth and development. In this study, we investigated the whole transcriptome of the longissimus dorsi muscle (LDM) of Jinfen White pigs at three developmental stages (1, 90, and 180 days) and performed a comprehensive analysis of lncRNAs, mRNAs, and micro-RNAs (miRNAs), aiming to find the key regulators and interaction networks in Jinfen White pigs. A total of 2638 differentially expressed mRNAs (DE mRNAs) and 982 differentially expressed lncRNAs (DE lncRNAs) were identified. Compared with JFW_1d, there were 497 up-regulated and 698 down-regulated DE mRNAs and 212 up-regulated and 286 down-regulated DE lncRNAs in JFW_90d, respectively. In JFW_180d, there were 613 up-regulated and 895 down-regulated DE mRNAs and 184 up-regulated and 131 down-regulated DE lncRNAs compared with JFW_1d. There were 615 up-regulated and 477 down-regulated DE mRNAs and 254 up-regulated and 355 down-regulated DE lncRNAs in JFW_180d compared with JFW_90d. Compared with mRNA, lncRNA has fewer exons, fewer ORFs, and a shorter length. We performed GO and KEGG pathway functional enrichment analysis for DE mRNAs and the potential target genes of DE lncRNAs. As a result, several pathways are involved in muscle growth and development, such as the PI3K-Akt, MAPK, hedgehog, and hippo signaling pathways. These are among the pathways through which mRNA and lncRNAs function. As part of this study, bioinformatic screening was used to identify miRNAs and DE lncRNAs that could act as ceRNAs. Finally, we constructed an lncRNA-miRNA-mRNA regulation network containing 26 mRNAs, 7 miRNAs, and 17 lncRNAs; qRT-PCR was used to verify the key genes in these networks. Among these, XLOC_022984/miR-127/ENAH and XLOC_016847/miR-486/NRF1 may function as key ceRNA networks. In this study, we obtained transcriptomic profiles from the LDM of Jinfen White pigs at three developmental stages and screened out lncRNA-miRNA-mRNA regulatory networks that may provide crucial information for the further exploration of the molecular mechanisms during skeletal muscle development.

Transforming Undesired Corrosion Products into a Nanoflake-Array Functional Layer: A Gelatin-Assistant Modification Strategy for High Performance Zn Battery Anodes.

As corrosion products of Zn anodes in ZnSO4 electrolytes, Zn4 SO4 (OH)6 ·xH2 O with loose structure cannot suppress persistent side reactions but can increase the electrode polarization and induce dendrite growth, hindering the practical applications of Zn metal batteries. In this work, a functional layer is built on the Zn anode by a gelatin-assistant corrosion and low-temperature pyrolysis method. With the assistant of gelatin, undesired corrosion products are converted into a uniform nanoflake array comprising ZnO coated by gelatin-derived carbon on Zn foil (denoted Zn@ZnO@GC). It is revealed that the gelatin-derived carbons not only enhance the electron conductivity, facilitate Zn2+ desolvation, and boost transport/deposition kinetics, but also inhibit the occurrence of hydrogen evolution and corrosion reactions on the zincophilic Zn@ZnO@GC anode. Moreover, the 3D nanoflake array effectively homogenizes the current density and Zn2+ concentration, thus inhibiting the formation of dendrites. The symmetric cells using the Zn@ZnO@GC anodes exhibit superior cycling performance (over 7000 h at 1 mA cm-2 /1 mAh cm-2 ) and without short-circuiting even up to 25 mAh cm-2 . The Zn@ZnO@GC||NaV3 O8 full cell works stably for 5000 cycles even with a limited N/P ratio of ≈5.5, showing good application prospects.

Dietary Supplementation of Astragalus membranaceus Extract Affects Growth Performance, Antioxidant Capacity, Immune Response, and Energy Metabolism of Largemouth Bass (Micropterus salmoides).

The present study investigated the effects of Astragalus membranaceus extract (AME) on growth performance, immune response, and energy metabolism of juvenile largemouth bass (Micropterus salmoides). Seven diets containing 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, and 0.6% AME (Con, AME0.1, AME0.2, AME0.3, AME0.4, AME0.5, and AME0.6 groups) were formulated and fed to M. salmoides for 8 weeks. Final body weight (FBW), feed intake (FI), weight gain (WG), and specific growth rate (SGR) were all significantly higher in AME0.4 group than in Con group (P < 0.05). Feed conversion rate (FCR) was significantly improved in AME0.5 group compared with Con group (P < 0.05). Whole-body crude protein contents were significantly increased in AME0.2 group (P < 0.05). Whole-body crude lipid contents were significantly lower in AME0.2 and AME0.3 groups, while muscle lipid was upregulated by dietary AME (P < 0.05). Hepatic malondialdehyde (MDA) contents were significantly lowered in AME0.3 and AME0.4 groups, and catalase (CAT) activities were significantly increased in AME0.1 and AME0.2 groups (P < 0.05). Plasma aspartate aminotransferase (AST) level was significantly lowered in AME0.5, and AME0.6 groups, and alanine aminotransferase (ALT) level was lowered in AME0.5 groups (P < 0.05). Plasma triglyceride was declined in AME0.6 group, and glucose was decreased by 0.3%-0.5% AME (P < 0.05). Significantly higher hepatocyte diameter, lamina propria width, and submucosal layer thickness were recorded in AME0.6 groups, while the longest villi height was obtained in AME0.2 and AME0.3 groups (P < 0.05). The mRNA expression levels of insulin-like growth factor 1 (igf1) revealed the growth-promoting effect of AME. The anti-inflammatory and antiapoptotic effects of AME were demonstrated by transcription levels of interleukin 8 (il-8), tumor necrosis factor-alpha (tnf-a), caspase, B-cell lymphoma-xl (Bcl-xl), bcl-2 associated x (Bax), and bcl-2-associated death protein (Bad). The transcription levels of lipid metabolism and gluconeogenesis related genes, including acetyl-CoA carboxylase alpha (acc1), fatty acid synthase (fasn), fatty acid binding protein 1 (fabp1), phosphoenolpyruvate carboxykinase 2 (pepck2), and glucose-6-phosphatase catalytic subunit 1a (g6pc), were reduced by AME treatment, while the levels of glycolysis-related genes, including glucokinase (gck) and pyruvate kinase (pk), were the highest in AME0.2 and AME0.3 groups (P < 0.05). According to polynomial regression analysis of SGR, WG, FCR, whole-body crude lipid, MDA, and ALT, the optimal AME supplementation level was estimated to be 0.320%-0.429% of the diet. These results provided insights into the roles of AME in regulating immunity and metabolism, which highly indicated its potential as immunostimulants and metabolic regulators in diverse aquatic animals.

Species-Deconvolved Proteomics for In Situ Investigation of Tumor-Stroma Interactions after Treatment of Pancreatic Cancer Patient-Derived Xenografts with Combined Gemcitabine and Paclitaxel.

Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models recapitulate tumor-stroma interactions, but the conventional antibody-based immunoassay is inadequate to discriminate tumor and stromal proteins. Here, we describe a species-deconvolved proteomics approach embedded in IonStar that can unambiguously quantify the tumor (human-derived) and stromal (mouse-derived) proteins in PDX samples, enabling unbiased investigation of tumor and stromal proteomes with excellent quantitative reproducibility. With this strategy, we studied tumor-stroma interactions in PDAC PDXs that responded differently to Gemcitabine combined with nab-Paclitaxel (GEM+PTX) treatment. By analyzing 48 PDX animals 24 h/192 h after treatment with/without GEM+PTX, we quantified 7262 species-specific proteins under stringent cutoff criteria, with high reproducibility. For the PDX sensitive to GEM+PTX, the drug-dysregulated proteins in tumor cells were involved in suppressed oxidative phosphorylation and the TCA cycle, and in the stroma, inhibition of glycolytic activity was predominant, suggesting a relieved reverse Warburg effect by the treatment. In GEM+PTX-resistant PDXs, protein changes suggested extracellular matrix deposition and activation of tumor cell proliferation. Key findings were validated by immunohistochemistry (IHC). Overall, this approach provides a species-deconvolved proteomic platform that could advance cancer therapeutic studies by enabling unbiased exploration of tumor-stroma interactions in the large number of PDX samples required for such investigations.

Genome-wide analysis of circular RNA-mediated ceRNA regulation in porcine skeletal muscle development.

BACKGROUND: As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in various biological processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the role of circRNAs in muscle development in cultivated pigs. RESULTS: In this study, we used RNA-seq to construct circRNA expression profiles in skeletal muscle of Jinfen White pigs at the age of 1, 90, and 180 days. Among the 16,990 identified circRNAs, 584 circRNAs were differentially expressed. Moreover, the enrichment analysis of DE circRNA host genes showed that they were mainly involved in muscle contraction, muscle organ development and muscle system processes, as well as AMPK and cAMP-related signal pathways. We also constructed a circRNA-miRNA-mRNA co-expression network to find key circRNAs which many involved in the regulation of porcine skeletal muscle development through the competitive endogenous RNA (ceRNA) mechanism. It is noteworthy that circ_0018595/miR-1343/PGM1 axis may play a regulatory role in the development of porcine skeletal muscle. CONCLUSIONS: This study identified the circRNAs and present the circRNA expression profile in the development of pigs, revealed that DE circRNA host genes participate in different cell fates and enriched the porcine ceRNA network. Thus, this work will become a valuable resource for further in-depth study of the regulatory mechanism of circRNA in the development of porcine skeletal muscle.

Diet supplementation of organic zinc positively affects growth, antioxidant capacity, immune response and lipid metabolism in juvenile largemouth bass, Micropterus salmoides.

Zn is an important trace element involved in various biochemical processes in aquatic species. An 8-week rearing trial was thus conducted to investigate the effects of Zn on juvenile largemouth bass (Micropterus salmoides) by feeding seven diets, respectively, supplemented with no Zn (Con), 60 and 120 mg/kg inorganic Zn (Sul60 and Sul120), and 30, 60, 90 and 120 mg/kg organic Zn (Bio30, Bio60, Bio90 and Bio120). Sul120 and Bio120 groups showed significantly higher weight gain and specific growth rate than Con group, with Bio60 group obtaining the lowest viscerosomatic index and hepatosomatic index. 60 or 90 mg/kg organic Zn significantly facilitated whole body Zn retention. Up-regulation of hepatic superoxide dismutase, glutathione peroxidase and catalase activities and decline of malondialdehyde contents indicated augmented antioxidant capacities by organic Zn. Zn treatment also lowered plasma aminotransferase levels while promoting acid phosphatase activity and hepatic transcription levels of alp1, acp1 and lyz-c than deprivation of Zn. The alterations in whole body and liver crude lipid and plasma TAG contents illustrated the regulatory effect of Zn on lipid metabolism, which could be possibly attributed to the changes in hepatic expressions of acc1, pparγ, atgl and cpt1. These findings demonstrated the capabilities of Zn in potentiating growth and morphological performance, antioxidant capacity, immunity as well as regulating lipid metabolism in M. salmoides. Organic Zn could perform comparable effects at same or lower supplementation levels than inorganic Zn, suggesting its higher efficiency. 60 mg/kg supplementation of organic Zn could effectively cover the requirements of M. salmoides.

Cannulation via the external jugular vein--An alternative to conventional peripherally inserted central catheterisation for paediatric patients.

PURPOSE: This study aimed to describe a peripherally inserted central catheterisation (PICC) for paediatric patients with inaccessible access and a high risk of general anaesthesia (GA). METHODS: This was a retrospective observational study involving all paediatric inpatients who performed the PICC via an EJV approach without GA between September 2014 and September 2021 in a provincial key clinical speciality. RESULTS: A total of 290 EJV line placement attempts were performed, and 29 were excluded due to missing placement results, resulting in a sample size of 261. The anatomical localisation, punctures, and catheterisation success rates for this practice were 100%, 100%, and 90.04%, respectively. The placement success rate in children younger than one year was 93.75% (45/48). The median line duration of use was 19 days, with a median length of catheter insertion of 13 cm. The most common complications were catheter malposition (n = 20) and dislodgement (n = 7). CONCLUSION: The PICC via an EJV approach without GA is a feasible and safe practice with acceptable success and complication rates, and low costs. It might be an attractive alternative for obtaining central vascular access for paediatric patients.

Facile Self-Assembly of Exfoliated Graphene/PANI Film for High-Energy Zn-Ion Micro-Supercapacitors.

The Zn-ion micro-supercapacitor (ZMSC) is a promising candidate for developing miniaturized and integrated energy storage devices. To achieve high-performance functional groups with simple processing to composite with rod-like active PANI fibers, we prepared exfoliated graphene (EG) with an appropriate amount of O-containing functional groups. The appropriate O content simultaneously facilitated self-assembly of the EG and PANI fibers and maintained the electric conductivity of the composite, producing a free-standing EG/PANI film without additional conductive additives or current collectors. As an interdigital electrode for the ZMSC, the EG/PANI film showed ultrahigh capacitance of 1.8 F cm-2 at 2.6 mA cm-2 (361.3 F g-1 at 0.5 A g-1) and landmark energy density of 755.8 µWh cm-2 at 2.3 mW cm-2 (148.2 Wh kg-1 at 451.7 W kg-1). The facile preparation of the high-performance EG/PANI electrode provides a potential path for practical applications with ZMSCs.

A Chemically Bonded Ultraconformal Layer between the Elastic Solid Electrolyte and Lithium Anode for High-performance Lithium Metal Batteries.

Although high ionic conductivities have been achieved in most solid-state electrolytes used in lithium metal batteries (LMBs), rapid and stable lithium-ion transport between solid-state electrolytes and lithium anodes remains a great challenge due to the high interfacial impedances and infinite volume changes of metallic lithium. In this work, a chemical vapor-phase fluorination approach is developed to establish a lithiophilic surface on rubber-derived electrolytes, which results in the formation of a resilient, ultrathin, and mechanically integral LiF-rich layer after electrochemical cycling. The resulting ultraconformal layer chemically connects the electrolyte and lithium anode and maintains dynamic contact during operation, thus facilitating rapid and stable lithium-ion transport across interfaces, as well as promoting uniform lithium deposition and inhibiting side reactions between electrolyte components and metallic lithium. LMBs containing the novel electrolyte have an ultralong cycling life of 2500 h and deliver a high critical current density of 1.1 mA cm-2 in lithium symmetric cells as well as showing good stability over 300 cycles in a full cell.

The Diversity of Viral Community in Invasive Fruit Flies (Bactrocera and Zeugodacus) Revealed by Meta-transcriptomics.

RNA viruses are extremely diverse and rapidly evolving in various organisms. Our knowledge on viral evolution with interacted hosts in the manner of ecology is still limited. In the agricultural ecosystem, invasive insect species are posing a great threat to sustainable crop production. Among them, fruit flies (Diptera: Tephritidae Bactrocera and Zeugodacus) are destructive to fruits and vegetables, which are also closely related and often share similar ecological niches. Thus, they are ideal models for investigating RNA virome dynamics in host species. Using meta-transcriptomics, we found 39 viral sequences in samples from 12 fly species. These viral species represented the diversity of the viromes including Dicistroviridae, negev-like virus clades, Thika virus clades, Solemoviridae, Narnaviridae, Nodaviridae, Iflaviridae, Orthomyxoviridae, Bunyavirales, Partitiviridae, and Reoviridae. In particular, dicistrovirus, negev-like virus, orthomyxovirus, and orbivirus were common in over four of the fly species, which suggests a positive interaction between fly viromes that exist under the same ecological conditions. For most of the viruses, the virus-derived small RNAs displayed significantly high peaks in 21 nt and were symmetrically distributed throughout the viral genome. These results suggest that infection by these viruses can activate the host's RNAi immunity. Our study provides RNA virome diversity and evidence on their infection activity in ecologically associated invasive fruit fly species, which could help our understanding of interactions between complex species and viruses.

Effects of Dietary Carbohydrate Levels on Growth Performance, Body Composition, Antioxidant Capacity, Immunity, and Liver Morphology in Oncorhynchus mykiss under Cage Culture with Flowing Freshwater.

The purpose of this study is to investigate the effects of dietary carbohydrate levels on growth performance, body composition, antioxidant capacity, immunity, and liver morphology in Oncorhynchus mykiss under cage culture with flowing freshwater. Fish (initial body weight 25.70 ± 0.24 g) were fed five isonitrogenous (420 g/kg protein) and isolipidic (150 g/kg lipid) diets containing 50.6, 102.1, 151.3, 200.9 and 251.8 g/kg carbohydrate levels, respectively. The results indicated that fish fed diets containing 50.6-200.9 g/kg carbohydrate showed significantly higher growth performance, feed utilization, and feed intake than those fed 251.8 g/kg dietary carbohydrate levels. Based on the analysis of the quadratic regression equation for weight gain rate, the appropriate dietary carbohydrate requirement of O. mykiss was estimated to be 126.2 g/kg. 251.8 g/kg carbohydrate level activated Nrf2-ARE signaling pathway, suppressed superoxide dismutase activity and total antioxidant capacity, and increased MDA content in the liver. Besides, fish fed a diet containing 251.8 g/kg carbohydrate showed a certain degree of hepatic sinus congestion and dilatation in the liver. Dietary 251.8 g/kg carbohydrate upregulated the mRNA transcription level of proinflammatory cytokines and downregulated the mRNA transcription level of lysozyme and complement 3. Whole-body compositions were not affected by dietary carbohydrate levels. In conclusion, 251.8 g/kg carbohydrate level suppressed the growth performance, antioxidant capacity and innate immunity, resulting in liver injury and inflammatory response of O. mykiss. A diet containing more than 200.9 g/kg carbohydrate is not efficiently utilized by O. mykiss under cage culture with flowing freshwater.

[Study on Impedance of Implantable Cardiac Pacemaker in Unipolar/Bipolar Pacing Mode by in Vitro Experiment].

The unipolar/bipolar pacing mode of pacemaker is related to its circuit impedance, which affects the battery life. In this study, the in vitro experiment scheme of pacemaker circuit impedance test was constructed. The human blood environment was simulated by NaCl solution, and the experimental environment temperature was controlled by water bath. The results of in vitro experiments showed that under the experimental conditions similar to clinical human parameters, the difference between the circuit impedance of bipolar mode and unipolar mode is 120~200 Ω. The results of the in vitro experiment confirmed that the circuit impedance of bipolar circuit was larger than that of unipolar mode, which was found in clinical practice. The results of this study have reference value to the optimization of pacing mode and the reduction of pacemaker power consumption.

Gelatin-Derived 1D Carbon Nanofiber Architecture with Simultaneous Decoration of Single Fe-Nx Sites and Fe/Fe3 C Nanoparticles for Efficient Oxygen Reduction.

Exploring high-performance non-precious-metal electrocatalysts for the oxygen reduction reaction (ORR) is critical. Herein, a scalable and cost-effective strategy is reported for the construction of one-dimensional carbon nanofiber architectures with simultaneous decoration of single Fe-Nx sites and highly dispersed Fe/Fe3 C nanoparticles for efficient ORR, through the FeIII -complex-assisted electrospinning of gelatin nanofibers with subsequent pre-oxidation and carbonization. Results show that the presence of a FeIII complex enables the 1D gelatin nanofibers to be well retained during the pre-oxidation process. Owing to the distinct 1D nanofiber structure and the synergistic effect of Fe/Fe3 C and Fe-Nx sites, the resulting electrocatalyst is highly active for ORR with a half-wave potential of 0.885 V (outperforming commercial Pt/C) and a superior electrochemical stability in alkaline electrolytes. Similarly, it also shows a high power density (144.7 mW cm-2 ) and a superior stability in Zn-air batteries. This work opens a path for the design and synthesis of 1D carbon electrocatalyst for efficient ORR catalysis.

A Systematic Review and Meta-Analysis of the Effects of Perioperative Immunonutrition in Gastrointestinal Cancer Patients.

In this systematic review and meta-analysis, 25 clinical trials were systematically reviewed, and meta-analysis was performed with the results of 16 trials. It was found that the risk of surgical site infection was significantly lower in patients who received perioperative immunonutrition than those given standard nutrition. Furthermore, hospital stay was significantly shorter in patients receiving immunonutrition or early enteral nutrition after surgical resection of gastric cancer. Perioperative immunonutrition also significantly reduced white blood cell counts and the level of C-reactive protein in the patients. However, neither CD4+ T cells nor inflammatory cytokines were significantly affected even though immunonutrition was in favor. These findings suggested that patients with gastrointestinal cancer may benefit from perioperative immunonutrition support by reducing surgery-associated complications and shortening hospital stay. The effects and the underlying mechanism of immunonutrition on immunological modulation and inflammatory regulation, however, remain to be further defined.

Review of NEDDylation inhibition activity detection methods.

NEDDylation is a post-translational modification of a protein, which transfers Ubiquitin like protein NEDD8 (Neuronal Precursor Cell-expressed Developmentally Down-regulated Protein 8) to the lysine residue of the product through a three-stage enzymatic reaction, and widely regulates many biological processes, such as cell cycle signal transduction and immune recognition. In the past ten years, we have witnessed tremendous progress in the study of protein ubiquitination modification, from modification mechanisms to drug development. Which suggests that inhibition of NEDDylation is an effective way to inhibit tumor. A variety of biological detection methods have been developed during the development of the inhibitor. In this review, we briefly introduced the modification process and substrates of NEDDylation, and discussed detection methods of NEDDylation activity in detail. This review will provide an up-to-date and comprehensive review of the methods for detecting NEDDylation activity that will contribute to NEDDylation inhibitor development.

Discovery of N-aryl sulphonamide-quinazoline derivatives as anti-gastric cancer agents in vitro and in vivo via activating the Hippo signalling pathway.

Hippo signalling pathway plays a crucial role in tumorigenesis and cancer progression. In this work, we identified an N-aryl sulphonamide-quinazoline derivative, compound 9i as an anti-gastric cancer agent, which exhibited potent antiproliferative ability with IC50 values of 0.36 µM (MGC-803 cells), 0.70 µM (HCT-116 cells), 1.04 µM (PC-3 cells), and 0.81 µM (MCF-7 cells), respectively and inhibited YAP activity by the activation of p-LATS. Compound 9i was effective in suppressing MGC-803 xenograft tumour growth in nude mice without obvious toxicity and significantly down-regulated the expression of YAP in vivo. Compound 9i arrested cells in the G2/M phase, induced intrinsic apoptosis, and inhibited cell colony formation in MGC-803 and SGC-7901 cells. Therefore, compound 9i is to be reported as an anti-gastric cancer agent via activating the Hippo signalling pathway and might help foster a new strategy for the cancer treatment by activating the Hippo signalling pathway regulatory function to inhibit the activity of YAP.

Intermetallic FePt@PtBi Core-Shell Nanoparticles for Oxygen Reduction Electrocatalysis.

The development of active and stable platinum (Pt)-based oxygen reduction reaction (ORR) electrocatalysts with good resistance to poisoning is a prerequisite for widespread practical application of fuel cells. An effective strategy for enhancing the electrocatalytic performance is to tune or control the physicochemical state of the Pt surface. Herein, we show a general surface-engineering approach to prepare a range of nanostructured Pt alloys by coating with alloy PtBi shells. FePt@PtBi core-shell nanoparticles showed the best ORR performance with a mass activity of 0.96 A mgPt -1 and a specific activity of 2.06 mA cm-2 , respectively 7 times and 11 times those of the corresponding values for benchmark Pt/C. Moreover, FePt@PtBi shows much better tolerance to methanol and carbon monoxide than conventional Pt-based electrocatalysts. The observed comprehensive enhancement in ORR performance of FePt@PtBi can be attributed to the increased compressive strain of the Pt surface due to in-plane shearing resulting from the presence of the large Bi atoms in the surface-structured PtBi overlayers, as well as charge displacement via Pt-Bi bonding which mitigates crossover issues.

Phase Segregated Pt-SnO2 /C Nanohybrids for Highly Efficient Oxygen Reduction Electrocatalysis.

Strengthening the interfacial interaction in heterogeneous catalysts can lead to a dramatic improvement in their performance and allow the use of smaller amounts of active noble metal, thus decreasing the cost without compromising their activity. In this work, a facile phase-segregation method is demonstrated for synthesizing platinum-tin oxide hybrids supported on carbon black (PtSnO2 /C) in situ by air annealing PtSn alloy nanoparticles on carbon black. Compared with a control sample formed by preloading SnO2 on carbon support followed by deposition of Pt nanoparticles, the phase-segregation-derived PtSnO2 /C exhibits a more strongly coupled PtSnO2 interface with lattice overlap of Pt (111) and SnO2 (200), along with enhanced electron transfer from SnO2 to Pt. Furthermore, the PtSnO2 active sites show a strong ability to degrade reactive oxygen species. As a result, the PtSnO2 /C nanohybrids exhibit both excellent activity and stability as a catalyst for the oxygen reduction reaction, with an overall performance which is superior to both the control sample and commercial Pt/C catalyst. This phase-segregation method can be expected to be applicable in the preparation of other strongly coupled nanohybrids and offers a new route to high-performance heterogeneous catalysts for low-cost energy conversion devices.