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Background: Our study aims to investigate the mechanisms through which Fc receptor‐like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration. Materials and Methods: The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein–protein interaction (PPI) network analyses were performed for FCRLA and its co‐expressed genes. FCRLA was knocked down in RCC cell lines to evaluate its impact on biological behavior. Then the potential downstream regulators of FCRLA were determined by western blotting, and rescue experiments were performed for verification. The relevance between FCRLA and various immune cells was analyzed through GSEA, TIMER, and GEPIA tools. TIDE and ESTIMATE algorithms were used to predict the effect of FCRLA in immunotherapy. Results: Fc receptor‐like A was associated with clinical and T stages and could predict the M stage (AUC = 0.692) and 1–3‐ and 5‐year survival rates (AUC = 0.823, 0.834, and 0.862) of RCC patients. Higher expression of FCLRA predicted an unfavorable overall survival (OS) in TCGA‐RCC and GSE167573 datasets (p = 0.03, p = 0.04). FCRLA promoted the malignant biological behavior of RCC cells through the pERK1/2/‐MMP2 pathway and was associated with tumor immune microenvironment in RCC. Conclusion: Fc receptor‐like A is positively correlated with poor outcomes in RCC patients and plays an oncogenic role in RCC through the pERK1/2‐MMP2 pathway. Patients with RCC might benefit from immunotherapy targeting FCRLA. [ABSTRACT FROM AUTHOR]

For effectively strengthening the comprehensive properties of intumescent flame‐retardant epoxy resins (EPs), a microencapsulating γ‐Fe2O3 by polypyrrole (PPy) named PPy‐Fe2O3 was synthesized and used as a synergist to simultaneously enhance the flame retardancy, smoke toxicity suppression and mechanical strength of EP composites containing diaminodiphenylmethane modified ammonium polyphosphate (DDP). The results demonstrate that the mixture of PPy‐Fe2O3 and DDP exhibits a surprising synergistic effect on strengthening the comprehensive properties of EP composites. Specifically, EP composite containing 0.2 wt% PPy‐Fe2O3 and 9.8 wt% DDP achieves the UL94 V‐0 rating with a limiting oxygen index (LOI) value of 35.5%, while 10 wt% DDP only imparts a UL94 V‐1 rating and a LOI value of 34.0% to EP. Furthermore, 0.2 wt% PPy‐Fe2O3 shows a 11.0% reduction in peak smoke production rate and a 12.3% reduction in peak heat release rate of the EP/DDP system. The enhanced fire security of EP/DDP/PPy‐Fe2O3 is attributed to the formation of more phosphorus‐rich structures retained in the char, thus reducing the release of harmful gases including NH3, CO, and CO2, and generating more incombustible gases including H2O to weaken burning intensity. Meanwhile, the satisfactory compatibility of PPy‐Fe2O3 with epoxy matrix imparts a superior mechanical strength to EP composites. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) exhibits highly metastatic potential even in the early stages of tumor progression. Gallic acid (GA), a common phenolic compound in plants, is known to possess potent antioxidant and anticancer activities, thereby inducing cell death or cell cycle arrest. However, whether GA reduces the invasiveness of CRC cells without inducing cell death remains unclear. Herein, we aimed to investigate the antimetastatic activity of low‐dose GA on CRC cells and determine its underlying mechanism. Cell viability and tumorigenicity were analyzed by MTS, cell adhesion, and colony formation assay. Invasiveness was demonstrated using migration and invasion assays. Changes in protein phosphorylation and expression were assessed by Western blot. The involvement of microRNAs was validated by microarray analysis and anti‐miR antagonist. Our findings showed that lower dose of GA (≤100 μM) did not affect cell viability but reduced the capabilities of colony formation, cell adhesion, and invasiveness in CRC cells. Cellularly, GA downregulated the cellular level of integrin αV/β3, talin‐1, and tensin and diminished the phosphorylated FAK, paxillin, Src, and AKT in DLD‐1 cells. Microarray results revealed that GA increased miR‐1247‐3p expression, and pretreatment of anti‐miR antagonist against miR‐1247‐3p restored the GA‐reduced integrin αV/β3 and the GA‐inhibited paxillin activation in DLD‐1 cells. Consistently, the in vivo xenograft model showed that GA administration inhibited tumor growth and liver metastasis derived from DLD‐1 cells. Collectively, our findings indicated that GA inhibited the metastatic capabilities of CRC cells, which may result from the suppression of integrin/FAK axis mediated by miR1247‐3p. [ABSTRACT FROM AUTHOR]

Patients with advanced liver cancer may benefit from 5‐fluorouracil (5‐FU) therapy. However, most of them eventually faced drug resistance, resulting in a poor prognosis. The present study aims to explore the potential mechanism of let‐7g/ABCC10 axis in the regulation of 5‐FU resistance in liver cancer cells. Huh‐7 cells were used to construct 5‐FU resistant Huh‐7/4X cells. CCK8, flow cytometry, and TUNEL staining were used to detect the characterization of Huh‐7 cells and Huh‐7/4X cells. Double luciferase report, PCR, and western blot analyses were used to detect the regulatory effects between let‐7g and ABCC10. The levels of biomarkers related to cell cycle progression and apoptosis were detected by western blot assays. The role of let‐7g in 5‐FU sensitivity of liver cancer cells was evaluated in nude mice. Compared with LX‐2 cells, the expression of let‐7g was decreased in Hep3B, HepG2, Huh‐7, and SK‐Hep1 cells, with the lowest expression in Huh‐7 cells. The sensitivity of Huh‐7 cell to 5‐FU was positively correlated with let‐7g expression. Transfection of let‐7g mimics inhibited the viability of Huh‐7/4X cells by prolonging the G1 phase, with the downregulation of ABCC10, PCNA, Cyclin D1, and CDK4. Meanwhile, let‐7g promoted apoptosis to increase 5‐FU sensitivity of Huh‐7/4X by downregulating ABCC10, Bcl‐XL as well as upregulating Bax, C‐caspase 3, and C‐PARP. Dual‐luciferase assay further confirmed that let‐7g inhibited ABCC10 expression by binding to the ABCC10 3'‐UTR region. Furthermore, let‐7g increased the sensitivity of Huh‐7/4X to 5‐FU in vitro and in vivo, which can be reversed by ABCC10 overexpression. In conclusion, let‐7g sensitized liver cancer cells to 5‐FU by downregulating ABCC10 expression. [ABSTRACT FROM AUTHOR]

Condensed films of functional luminophores dominated by the magnitude and dimensionality of the intermolecular interactions play important roles in sensing performance. However, controlling the molecular assembly and regulating photophysical properties remain challenging. In this study, a new luminophore, ortho‐PBI‐Au, was synthesized by anchoring a cyclometalated alkynyl‐gold(III) unit at the ortho‐position of perylene bisimide. An unprecedented T‐type packing model driven by weak Au‐π interaction and Au−H bonds was observed, laying foundation for striking properties of the luminophore. Controlled assembly of ortho‐PBI‐Au at the air‐water interface, realized using the classical Langmuir–Schaeffer technique, afforded the obtained luminescent films with different packing structures. With an optimized film, sensitive, selective, and rapid detection of a hazardous new psychoactive substance, phenylethylamine (PEA), was achieved. The detection limit, response time, and recovery time were <4 ppb, <1 s, and <5 s, respectively, surpassing the performance of the PEA sensors known thus far. The relationship between the characters of films and the sensing performance was systematically examined by grey relational analysis (GRA). The present study suggests that designing novel molecular aggregation with definite adlayer structure is a crucial strategy to enhance the sensing performance, which could be favorable for the film‐based fluorescent sensors. [ABSTRACT FROM AUTHOR]

To enhance the flame retardancy and aging resistance of grouting fireproof glass, different molecular weights of polyethylene glycol (PEG) were mixed with acrylamide (AM) to construct interpenetrating network hydrogels, then the obtained hydrogels were mixed with flame retardants to prepare a series of transparent flame‐retarded hydrogels applied in the fireproof glass. The effects of PAM/PEG hydrogel with varying PEG molecular weight on the optical transparency, heat insulation and aging resistance of fireproof glass were investigated. Optical transparency analysis shows that the light transmittance of grouting fireproof glass decreases with the increase of PEG molecular weight in the PAM/PEG interpenetrating network. Fire tests show that PAM/PEG hydrogel significantly enhances the heat insulation and aging resistance of the grouting fireproof glass compared to the single PAM network hydrogel. The flame‐retarded and anti‐aging effects of PAM/PEG hydrogel in the fireproof glass varies with the PEG molecular weight, and the order is PAM/PEG2000 > PAM/PEG1500 > PAM/PEG1000 > PAM/PEG800. Accelerated aging test shows that PAM/PEG interpenetrating network hydrogel is less affected by aging conditions and exerts durable heat insulation and transmittance. Especially, the backside temperature of 3600 s and transmittance of PAM/PEG2000 system after 264 h aging test only changed 38.3°C and 1.3%, respectively, compared to the unaged PAM/PEG2000 system. [ABSTRACT FROM AUTHOR]

The regulatory network between signaling pathways and transcription factors (TFs) is crucial for the maintenance of pluripotent stem cells. However, little is known about how the key TF OCT4 coordinates signaling pathways to regulate self‐renewal and lineage differentiation of porcine pluripotent stem cells (pPSCs). Here, we explored the function of OCT4 in pPSCs by transcriptome and chromatin accessibility analysis. The TFs motif enrichment analysis revealed that, following OCT4 knockdown, the regions of increased chromatin accessibility were enriched with EOMES, GATA6, and FOXA1, indicating that pPSCs differentiated toward the mesoendoderm (ME) lineage. Besides, pPSCs rapidly differentiated into ME when the WNT/β‐catenin inhibitor XAV939 was removed. However, the ME differentiation of pPSCs caused by OCT4 knockdown did not rely on the activation of WNT/β‐catenin signaling because the target gene of WNT/β‐catenin signaling, AXIN2 was not upregulated after OCT4 knockdown, despite significant upregulation of WLS and some WNT ligands. Importantly, OCT4 is directly bound to the promoter and enhancers of EOMES and repressed its transcription. Overexpression of EOMES was sufficient to induce ME differentiation in the presence of XAV939. These results demonstrate that OCT4 can regulate WNT/β‐catenin signaling and prevent ME differentiation of pPSCs by repressing EOMES transcription. [ABSTRACT FROM AUTHOR]

Enhancing the fire safety of epoxy resin (EP) concomitant with less mechanical performance degradation is still a challenge for traditional flame retardants. Hence, polypyrrole (PPy) was used as a film material to fabricate microencapsulated urea ammonium polyphosphate (UAPP) for simultaneously improving the fire safety, thermal stability and compatibility of epoxy composites. The obtained polypyrrole‐coated urea ammonium polyphosphate (PPy‐UAPP) at a load of 10 wt% endows the EP with a UL94 V‐0 rating and a limiting oxygen index (LOI) value of 32.3%, while 10 wt% ammonium polyphosphate (APP) only endows EP with a LOI of 28.5%. Furthermore, the peak heat release rate (PHRR) and peak smoke production rate (PSPR) of EP containing 10 wt% PPy‐UAPP are decreased by 12.3% and 21.4% compared to EP containing 10 wt% APP. The decreased fire hazard of EP/PPy‐UAPP is attributed to the reduction of hazardous gases including CO2 and CO and the generation of more incombustible gases including H2O and NH3 to reduce the combustion intensity. Meanwhile, the good compatibility between EP matrix and PPy‐UAPP endows the resulting EP composites with a superior balance between fire safety and mechanical properties. [ABSTRACT FROM AUTHOR]

Objectives: BCL2‐associated athanogene 6 (BAG6) plays critical roles in spermatogenesis by maintaining testicular cell survival. Our previous data showed porcine BAG6 exon24‐skipped transcript is highly expressed in immature testes compared with mature testes. The objective of this study is to reveal the functional significance of BAG6 exon24 in mammalian spermatogenesis. Materials and Methods: CRISPR/Cas9 system was used to generate Bag6 exon24 knockout mice. Testes and cauda epididymal sperm were collected from mice. TMT proteomics analysis was used to discover the protein differences induced by Bag6 exon24 deletion. Testosterone enanthate was injected into mice to generate a high‐testosterone mice model. H&E staining, qRT‐PCR, western blotting, vector/siRNA transfection, immunofluorescence, immunoprecipitation, transmission electron microscopy, TUNEL and ELISA were performed to investigate the phenotypes and molecular basis. Results: Bag6 exon24 knockout mice show sub‐fertility along with partially impaired blood‐testis barrier, increased apoptotic testicular cell rate and abnormal sperm morphology. Endoplasmic reticulum stress occurs in Bag6 exon24‐deficient testes and sterol regulatory element‐binding transcription factor 2 is activated; as a result, cytochrome P450 family 51 subfamily A member 1 expression is up‐regulated, which causes a high serum testosterone level. Additionally, serine/arginine‐rich splicing factor 1 down‐regulates BAG6 exon24‐skipped transcripts in porcine Sertoli cells by binding to 35–51 nt on BAG6 exon24 via its N‐terminal RNA‐recognition domain. Conclusions: Our findings reveal the critical roles of BAG6 exon24 in testosterone biosynthesis and male fertility, which provides new insights into the regulation of spermatogenesis and pathogenesis of subfertility in mammals. [ABSTRACT FROM AUTHOR]

The Philippine Sea is a typical region of aeolian dust reposition and is located within the Western Pacific Warm Pool. Here, we use the paleomagnetic stratigraphy and the grain‐size distributions of Quaternary abyssal deposits in the Central Philippine Sea to investigate the factors controlling regional sedimentary and paleoenvironmental changes. Our principal results are as follows: (a) A reliable geochronologic framework for Quaternary sediments in the Central Philippine Sea is established. (b) An eastward expansion of the regional depocenter in the Middle Pleistocene is observed. (c) The mean grain size of the abyssal sediments is 7–8 µm, and there are only minor differences between the sites. Comparison of the geochronological framework with various paleoenvironmental events during the Mid‐Pleistocene Transition shows that sedimentary processes can be correlated to a major transition in global climate which affected regions from the Asian interior to the tropical Pacific, and that changes in aeolian sedimentation are likely the predominant factor responsible. A derived grain‐size proxy of the sedimentary dynamics and its comparison with various paleoenvironmental proxies show that the relative contributions are roughly estimated as 23%, 9%, and 68% for aeolian inputs, oceanic circulation, and the tropical Pacific zonal SST gradient, respectively, in the studied region. The relative importance of tropical processes in abyssal sedimentary dynamics highlights the possibility of the long‐term influence of (sub)mesoscale eddies in the upper ocean, via regional upwelling and unique submarine topography, on the deepest part (>5,000 m) of the Central Philippine Sea, from meteorological to geological timescales. Plain Language Summary: The Philippine Sea is of paleoclimatic and paleoceanographic significance. Likely because of water depth largely over 5,000 m, the sedimentary processes are relatively poorly understood. In this study, integrating magnetic stratigraphy in the Central Philippine Sea reveals an eastward expansion of regional depocenter since ∼0.8 Ma, and this expansion may be responded to a major transition in climate changes from the Asian interior to the tropical Pacific. By analyzing sediment grain sizes and comparing them with various paleoenvironmental proxies, the influences of aeolian inputs, oceanic circulation, and tropical climate processes are evaluated during the Quaternary. The relative importance of the tropical Pacific zonal SST gradient suggests that the long‐term influence of (sub)mesoscale eddies in the upper ocean may be the major factor dominating abyssal sedimentation on different timescales, via a topography‐induced deep‐reaching effect. Key Points: A geochronologic framework in Central Philippine Sea is established, inferring an eastward expansion of depocenter in Middle PleistoceneA sedimentary transition at ∼1.3–1.2 Ma can be correlated to changes in aeolian sedimentation as the predominant factorSedimentary dynamics are predominantly controlled by ENSO, demonstrating long‐term influence of (sub)mesoscale eddies in upper ocean [ABSTRACT FROM AUTHOR]

We present a mechanism for how ornithine decarboxylase (ODC) regulates the crosstalk between autophagy and apoptosis. In cancer cells, low‐intensity ultraviolet B (UVBL) induces autophagy while high‐intensity UVB (UVBH) induces apoptosis. Overexpression of ODC decreases UVBL‐induced autophagy by inhibiting Atg5‐Atg12 conjugation and suppressing the expression of autophagy markers LC3, Atg7, Atg12, and BECN1 proteins. In contrast, when ODC‐overexpressing cells are exposed to UVBH radiation, the levels of LC3‐II, Atg5‐Atg12 conjugate, BECN1, Atg7, and Atg12 increase, while the apoptosis marker cleaved‐PARP proteins decrease, indicating that ODC overexpression induced UVBH‐induced autophagy but inhibited UVBH‐induced cellular apoptosis. Additionally, when exposed to UVBH radiation, silencing BECN1, Atg5, and Atg12 genes results in a decrease in the level of LC3‐II proteins but an increase in the level of cleaved‐PARP proteins, and apoptotic bodies were significantly increased while autophagosomes were significantly decreased. These findings imply that ODC inhibits apoptosis in cells via the autophagy pathway. The role of Atg12 in ODC‐overexpressing cells exposed to UVBH radiation is investigated using site‐directed mutagenesis. Our results indicate that the Atg12‐D111S mutant has increased cell survival. The Atg12‐ΔG186 mutant impairs autophagy and enhances apoptosis. We demonstrate that when ODC‐overexpressing cells are silenced for the Atg12 protein, autophagy and apoptosis are strongly affected, and ODC‐induced autophagy protects against UVBH‐induced apoptosis via the Atg12 protein. [ABSTRACT FROM AUTHOR]

When the structures of 1342 molecules are optimized by 30 methods and 7 basis sets, there appear 289 (21.54%) problematic molecules and 112 (8.35%) failed ones. When 278 problematic molecules are compared, the best methods are BHandH and LC‐wPBE, while B97D, BP86, HFS, VSXC, and HCTH are very unreliable. When 179 problematic molecules are computed with larger basis sets, the smallest mean absolute deviation (MAD) of bond angle (2.3°) is shown by QCISD(T)/cc‐pVTZ, while the smallest MAD of bond length (0.021 Å), the best SUM1 (4.9 unit), and the best SUM2 (2.4 unit) are shown by DSDPBEP86(Full), DSDPBEP86, PBE1PBE‐D3, MP2, and MP2(Full) in combination with aug‐cc‐pVQZ, cc‐pVQZ, Def2QZVP, Def2TZVPP, and/or 6–311++G(3df,3pd). Very large basis sets, for example, larger than cc‐pVTZ usually have to be used to obtain very good structures and the performances of many density‐functional theory methods are encouraging. The best results may be the limit of modern computational chemistry. [ABSTRACT FROM AUTHOR]

This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4‐overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C‐terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4‐mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology. [ABSTRACT FROM AUTHOR]

The Philippine Sea is a well‐preserved, extinct, marginal basin, and due to generally deeper than the carbonate compensation depth, the geochronology and its geological significance of the abyssal sediments are less studied in previous researches. In this work, we studied the magnetostratigraphy of four gravity cores from the centre of the West Philippian Basin and establish a reliable chronology for sedimentary sequences in the Pleistocene. The main results include: (a) several magnetozones are recognized in the studied four cores, which can be correlated to the geomagnetic polarity timescale from chrons C1n to C2An (0–3.0 Ma); (b) since ~1.2 Ma, the depositional rates across the West Pacific are relatively consistent, about 160–250 cm/Myr; (c) a transition in depositional rates around ~1.2 Ma was identified in the studied area, from a spatial variety in the Early Pleistocene to a persistent pattern since the Middle Pleistocene. Based on these findings, we report that this sedimentary shift in the Philippian Sea can be correlated to global climate changes during the Mid‐Pleistocene transition, representing a major change in the studied area. Therefore, we suggest that the sedimentary processes in the studied area can be linked to a common shift in palaeoclimatology across the inner Asian continent, the Philippian Sea, and the tropical Pacific during the late Early Pleistocene. [ABSTRACT FROM AUTHOR]

Objective: The present study examined the moderation role of pre‐parenthood self‐esteem and sense of mastery in psychological well‐being across the transition to parenthood. Background: Past research has identified negative changes in new parents' psychological well‐being. Less studied are the protective factors that can alleviate this transition impact. Informed by theories of psychological well‐being, the protective role of pre‐parenthood positive sense of self in parenthood transitions was examined. Method: Longitudinal data for 2,588 individuals collected from adolescence through their transition to parenthood were analyzed. Pre‐parenthood sense‐of‐self trajectory groups were formed using data collected during adolescence. Piecewise multilevel models were constructed to explore the effect of pre‐parenthood sense of self on new parents' psychological well‐being measured by depressive symptoms, self‐esteem, and sense of mastery. Results: Compared to nonparent peers, the transitions to parenthood lowered new parents' psychological well‐being. This aforementioned change differed by pre‐parenthood sense‐of‐self trajectory groups. Contrary to expectations, new parents with high self‐esteem or sense of mastery during adolescence experienced greater negative immediate impacts at childbirth, compared to their low sense of self counterparts. Furthermore, new parents with both high pre‐parenthood self‐esteem and sense of mastery demonstrated gradual declines in sense of self after childbirth. Conclusion: Positive pre‐parenthood sense of self during adolescence may not protect individuals against the immediate and longitudinal impact of the transition to parenthood. Implications for research and practice were discussed. [ABSTRACT FROM AUTHOR]

The faithful execution of molecular programme underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for efficient mammalian reproduction. However, the organization and principle of molecular circuits and modules for oocyte meiosis remain obscure. Here, we employed the recently developed single‐cell RNA‐seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non‐coding RNAs (lncRNAs) during oocyte in vitro meiotic maturation. During the transition from GV to MII, total number of detected RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1,807 (602 up‐ and 1,205 down‐regulated) mRNAs and 313 (177 up‐ and 136 down‐regulated) lncRNAs were significantly differentially expressed (DE), i.e., more mRNAs down‐regulated, but more lncRNAs up‐regulated. During maturation of pig oocytes, mitochondrial mRNAs were actively transcribed, eight of which (ND6, ND5, CYTB, ND1, ND2, COX1, COX2 and COX3) were significantly up‐regulated. Both DE mRNAs and targets of DE lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co‐expression network analysis (WGCNA) revealed 20 hub mRNAs in three modules to be important for oocyte meiosis and maturation. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in in vitro meiotic maturation of pig oocytes. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) regulate a variety of physiological and pathological processes. However, the biological function of lncRNAs in mammalian germ cells remains largely unexplored. Here we identified one novel lncRNA (lncRNA2193) from single‐cell RNA sequencing performed on porcine oocytes and investigated its function in oocyte meiosis. During in vitro maturation (IVM), from germinal vesicle (GV, 0 hr), GV breakdown (GVBD, 24 hr), to metaphase II stage (MII, 44 hr), the transcriptional abundance of lncRNA2193 remained stable and high. LncRNA2193 interference by small interfering RNA microinjection into porcine GV oocytes could significantly inhibit rates of GVBD and the first polar body extrusion, but enhance the rates of oocytes with a nuclear abnormality. Moreover, lncRNA2193 knockdown disturbed cytoskeletal organization (F‐actin and spindle), and decreased DNA 5‐methylcytosine (5mC) and histone trimethylation (H3K4me3, H3K9me3, H3K27me3, and H3K36me3) levels. The lncRNA2193 downregulation induced a decrease of 5mC level could be partially due to the reduction of DNA methyltransferase 3A and 3B, and the elevation of 5mC‐hydroxylase ten‐11 translocation 2 (TET2). After parthenogenetic activation of MII oocytes, parthenotes exhibited higher fragmentation but lower cleavage rates in the lncRNA2193 downregulated group. However, lncRNA2193 interference performed on mature MII oocytes and parthenotes at 1‐cell stage did not affect the cleavage and blasctocyst rates of pathenotes. Taken together, lncRNA2193 plays an important role in porcine oocyte maturation, providing more insights for relevant investigations on mammalian germ cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the leading cause of cancer death, and its 5‐year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin‐specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/β‐catenin pathway. We found that USP44 overexpression increased the Axin1 protein while decreasing β‐catenin, c‐myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/β‐catenin pathway. Moreover, we found that two Wnt/β‐catenin activators, LiCl and SKL2001, both attenuated oeUSP44‐mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/β‐catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the Axin1 mRNA level. Further study uncovered that USP44 interacted with Axin1 and reduced the ubiquitination of Axin1. Furthermore, Axin1 knock‐down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/β‐catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/β‐catenin pathway via Axin1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy. [ABSTRACT FROM AUTHOR]

The Mariana Trench is the deepest part of Earth's surface, with a maximum depth of close to 11,000 m in the Challenger Deep. Great progress has been made in studying the trench in the past years; however, several basic issues regarding the sedimentology and geochronology of the abyssal surficial sediments in the trench remain unclear. In this study, two gravity cores of Plio‐Pleistocene sediments were retrieved from the southern slope of the Mariana Trench. They were used for an integrated investigation of magnetostratigraphy, authigenic 10Be/9Be dating, and element manganese content. The principal results are as follows. (1) Ten magnetozones are recognized for Core A25, which can be correlated to the geomagnetic polarity time scale from Chrons C1n to C3r. (2) The paleomagnetic and 10Be/9Be‐based ages agree well for both of the two cores, yielding a continuous depositional hiatus since the middle Pleistocene (0.63–0.74 Ma). (3) The sediment accumulation rates prior to ~1.3 Ma are 35–83 cm/Myr and then increased substantially to 167–200 cm/Myr. Based on these results, a sedimentary transition at ~1.3–1.2 Ma is confirmed, which can be potentially correlated to climatic, oceanic, and tectonic changes in the Mid‐Pleistocene transition. In addition, an elemental Mn proxy is derived to reflect changes in bottom‐water ventilation, which is consistent with Lower Circumpolar Deep Water and North Atlantic Deep Water on glacial‐interglacial time scales. We conclude that the sedimentary record of the Mariana Trench provides a unique window for investigating the integrated effects of long‐term climatic, oceanic, and tectonic processes. Key Points: Surface ages of 0.63–0.74 Ma likely reflect a continuous depositional hiatus since the middle Pleistocene in the trenchA sedimentary transition in the trench at ~1.3–1.2 Ma can potentially be correlated to the Mid‐Pleistocene climatic transitionThe sedimentary record provides a unique window for the integrated effects of long‐term climatic, oceanic, and tectonic processes [ABSTRACT FROM AUTHOR]

As a member of parabens (PBs), Isobutylparaben (IBP) has a broad‐spectrum antimicrobial activity and widely used in personal care products and cosmetics. Recent studies have indicated that usage of IBP poses a potential threat to reproductive health. In this study, we aimed to reveal the effects of acute exposure to IBP on the meiotic maturation of porcine cumulus oocyte complexes. Initial study showed that 200 μM of IBP significantly reduced the rate of the first polar body extrusion with no significant effect on cumulus cell expansion; however, 400 μM of IBP could significantly affect both. Further research revealed that abnormal spindles, misalignment chromosomes, and aberrant distributed actin filaments were detected in IBP‐treated oocytes, which indicates that the cytoskeleton architecture of oocyte could be the target of IBP. At the same time, ROS level and apoptosis rate of oocyte were significantly increased by IBP exposure. Moreover, the levels of H3K9me3 and H3K27me3 were significantly induced in oocytes by IBP. Collectively, these results demonstrate that acute exposure to IBP could disrupt porcine oocyte maturation through affecting cytoskeleton, oxidative stress, viability and epigenetic modification. Environ. Mol. Mutagen. 2020. © 2020 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Malathion (MAL) is a common organophosphorus pesticide and affects both animal and human reproduction. However, the mechanisms regarding how MAL affects the mammalian oocyte quality and how to prevent it have not been fully investigated. In this study, we used porcine oocyte as a model and proved that MAL impaired porcine oocyte quality in a dose‐dependent manner during maturation. MAL decreased the first polar body extrusion, disrupted spindle assembly and chromosome alignment, impaired cortical granules (CGs) distribution, and increased reactive oxygen species (ROS) level in oocytes. RNA‐seq analysis showed that MAL exposure altered the expression of 2,917 genes in the porcine maturated oocytes and most genes were related to ROS, the lipid droplet process, and the energy supplement. Nevertheless, these defects could be remarkably ameliorated by adding melatonin (MLT) into the oocyte maturation medium. MLT increased oocyte maturation rate and decreased the abnormities of spindle assembly, CGs distribution and ROS accumulation in MAL‐exposed porcine oocytes. More important, MLT upregulated the expression of genes related to lipid droplet metabolism (PPARγ and PLIN2), decreased lipid droplet size and lipid peroxidation in MAL‐exposed porcine oocytes. Finally, we found that MLT increased the blastocysts formation and the cell numbers of blastocysts in MAL‐exposed porcine oocytes after parthenogenetic activation, which was mediated by reduction of ROS levels and maintaining lipid droplet metabolism. Taken together, our results revealed that MLT had a protective action against MAL‐induced deterioration of porcine oocyte quality. [ABSTRACT FROM AUTHOR]

Chemical transformations based on cascade reactions have the potential to simplify the preparation of diverse and architecturally complex molecules dramatically. Herein, we disclose an unprecedented and efficient method for the cross‐coupling of radical precursors, dienes, and electrophilic coupling partners via a photoredox‐ and nickel‐enabled cascade cross‐coupling process. The cascade reaction furnishes a diverse array of saturated carbo‐ and heterocyclic scaffolds, thus providing access to a quick gain in C−C bond saturation. [ABSTRACT FROM AUTHOR]

This paper proposes a new control design to compensate for the residual control error from charge feedback control. A part of the applied voltage is consumed by the hysteresis effect because of the nature of the piezoelectric material; moreover, this effect is difficult to overcome because it is rate dependent. This work utilizes a piezoelectric electromechanical model to propose a precompensation algorithm for a piezoelectric actuator. A nonlinear compensator can be used to treat both the hysteresis nonlinearity and the rate dependency of the system, and the adjustable parameters are specified through adaptive identification with only basic system information. The proposed design can position a piezoelectric stage with a magnifying mechanism within a few nanometers of a target, and the leftover hysteresis phenomenon is negligible. [ABSTRACT FROM AUTHOR]

Tris(1,3‐dichloro‐2‐propyl) phosphate (TDCPP) is a kind of additive flame retardants (FRs) and was found to affect early embryonic development in zebrafish; however, there are few studies to investigate whether TDCPP will disturb the development of early mouse embryos. In our studies, we used mouse embryos as models to study the toxicology of TDCPP on the early embryos. The results showed that TDCPP disturbed the development of early mouse embryos in a dose‐dependent manner. 10 μM TDCPP decreased the blastocyst formation and 100 μM TDCPP was a lethal concentration for the mouse embryos. We proved that TDCPP was detrimental to embryonic development potential by increasing the reactive oxygen species level and inducing early apoptosis. Furthermore, TDCPP changed the DNA methylation patterns of imprinted genes in treated blastocysts. The methylation of H19 and Snrpn promoter regions was increased from 37.67% to 46.00% and 31.56% to 44.38% in treated groups, respectively. In contrast, Peg3 promoter region methylation was declined from 86.55% to 73.27% in treated embryos. Taken together, our results demonstrated that TDCPP could adversely impair the early embryonic development in mouse. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Protein regulator of cytokinesis 1 (PRC1) has been reported in correlation with various malignancies. Functionality of PRC1 in nasopharyngeal carcinoma (NPC) was investigated, in perspective of long noncoding RNA (lncRNA) regulatory circuitry. Aberrant expressed messenger RNA and lncRNA were screened out from the Gene Expression Omnibus microarray database. NPC cell line CNE‐2 was adopted for in vitro study and transfected with mimic or short hairpin RNA of miR‐194‐3p and PTPRG‐AS1. The radioactive sensitivity, cell viability, migration, invasion, and apoptosis were detected. PTPRG‐AS1 and PRC1 were upregulated in NPC, whereas miR‐194‐3p was downregulated. PTPRG‐AS1 was found to specifically bind to miR‐194‐3p as a competing endogenous RNA and miR‐194‐3p targets and negatively regulates PRC1. Overexpressed miR‐194‐3p or silenced PTPRG‐AS1 resulted in enhanced sensitivity to radiotherapy and cell apoptosis along with suppressed cell migration, invasion and proliferation in NPC. Furthermore, impaired tumor formation was also caused by miR‐194‐3p overexpression or PTPRG‐AS1 suppression through xenograft tumor in nude mice. In our study, PTPRG‐AS1/miR‐194‐3p/PRC1 regulatory circuitry was revealed in NPC, the mechanism of which can be of clinical significance for treatment of NPC. [ABSTRACT FROM AUTHOR]

Poly(di(pyridin‐2‐yl)methyl acrylate) (PDPyMA), which was obtained by the free radical polymerization of designed coordinative monomer of di(pyridin‐2‐yl)methyl acrylate, is able to coordinate with various metal ions to form heterogeneous catalysts for diverse catalytic reactions. The Pd and Cu complexes supported by PDPyMA were developed for the heterogeneous Suzuki‐Miyaura reaction and Friedel‐Crafts alkylation, respectively. The PDPyMA‐based catalysts showed no significant decline of reactivity after five times recycling. However, the hydrolysis of the PDPyMA backbone under alkaline conditions limited the catalytic efficiency of this heterogeneous catalyst so that the coordinative monomer was redesigned as 1,1‐di(pyridine‐2‐yl)‐2‐(4‐vinylphenyl)ethan‐1‐ol and then 2,2′‐(1‐methoxy‐2‐(4‐vinylphenyl)ethane‐1,1‐diyl)dipyridine (MVPhDPy). With copolymerization of N‐isopropyl acrylamide (NIPAM), the efficiency of polymer‐based heterogeneous catalysts could be further raised, demonstrated by the increased turn over number in the Suzuki‐Miyaura reaction, which approached 5,260 by using the catalyst formed from poly(MVPhDPy‐co‐NIPAM) and Pd(OAc)2. poly(MVPhDPy‐co‐NIPAM) copolymer, therefore, could be a versatile platform to support different metal ions for various heterogeneous catalytic reactions. [ABSTRACT FROM AUTHOR]

The nonmotile, spherical, picoplanktonic (2‐μm‐sized) pelagophyte Aureococcus anophagefferens has caused numerous harmful blooms ("brown tides") across global marine ecosystems. Blooms have developed along the east coast of the USA since 1985, a limited number of times in South Africa around 1997, and frequently in China since 2009. As a consequence, the harmful blooms have caused massive losses in aquaculture and coastal ecosystems, particularly mortalities in cultured shellfish. Therefore, whether A. anophagefferens was recently introduced to China via natural/artificial transport of resting stage cells or has been an indigenous species has become a question of profound ecological significance and broad interest, which motivated our extensive investigation on the geographic and historical presence of this species in the seas of China. We applied a combined approach of extensive PCR‐based detection and sequencing, germination experiments and monoclonal antibody staining of germlings to samples of surface sediment and sediment core (dated via combined isotopic measurements) collected from all four seas of China, and searched the supplementary data set of a recent Science publication. We discovered that A. anophagefferens does have a resting stage in the sediment, but it also has a wide geographic distribution both in China (covering a range of ~30° in latitude, ~15.7° in longitude and 2.5–3,456 m in water depth; temperate to tropical and coastal to open oceans) and in almost all oceans of the world and a historical presence of >1,500 years in the Bohai Sea, China. The work revealed that A. anophagefferens is not a recently introduced, but an indigenous species in China and has in fact a globally cosmopolitan distribution. [ABSTRACT FROM AUTHOR]

It is assumed that the potential intensity of tropical cyclones (TC) will increase with rising global temperature. The western North Pacific is one of the three principal TC centers, but TC records from the region are scarce and sometimes controversial. Here we present grain‐size distributions and element contents of sediment cores from the East China Sea, in the western North Pacific. We interpret changes in the mean grain size of the coarse fraction as a proxy for TC intensity, and we infer a linkage of TC intensity to temperature changes over the last two millennia. Supported by model simulations, our results show that TC intensity increased (decreased) during relatively warm (cool) periods, confirming the control of temperature on TC intensity on a multicentennial scale. Our results suggest that long‐term TC intensity in the western North Pacific may increase with continued global warming. Plain Language Summary: It is assumed that the potential intensity of tropical cyclones (TC) will increase with rising global temperature. However, the long‐term observational trend of TC intensity, and thus its relationship with temperature changes, is debated. Here we present a 2,000‐year TC reconstruction using physical and geochemical proxies from sediments of the East China Sea in the western North Pacific. Our results suggest that TC intensity increased (decreased) during relatively warm (cool) periods on a multicentennial scale. Our finding provides improved insinto the relationship between TC intensity and changes in global temperature. Key Points: The coarse fraction of Chinese coastal sediments is used as a proxy for TC intensityA 2,000‐year record of TC intensity in the western North Pacific is reconstructedTC intensity increased during relatively warm periods on a multicentennial scale [ABSTRACT FROM AUTHOR]

Maintaining the frequency within an allowable range is the necessity to ensure the stable operation of the grid. When a large-scale frequency disturbance occurs in the grid, the synchronous generators (SGs) will temporarily release the kinetic energy to make the generation and demand balanced. This is well known as the inertial response of the SG. However, the traditional variable-speed wind turbines (VSWTs) only generate a negligible inertial response when a frequency disturbance happens. The traditional VSWT is designed to maximise the wind energy injected into the grid. Thus, when a frequency disturbance is detected in the grid, the traditional VSWT cannot change the active power output to support the grid. To solve this problem, the concepts of the inertial control and inertial support capability for VSWT were proposed. The inertial control measures the frequency of the grid and adjusts the active power output of VSWT. Thus, during the frequency disturbance, the VSWT has the inertial support capability. The purpose of this study is to provide a comprehensive review of the inertial control for the wind power plant (WPP) consisting of VSWTs. With the inertial control, the integration of the WPPs can enhance the frequency stability of the grid. [ABSTRACT FROM AUTHOR]

Objectives: To date, many efforts have been made to establish porcine embryonic stem (pES) cells without success. Extraembryonic endoderm (XEN) cells can self‐renew and differentiate into the visceral endoderm and parietal endoderm. XEN cells are derived from the primitive endoderm of the inner cell mass of blastocysts and may be an intermediate state in cell reprogramming. Materials and methods: Porcine XEN cells (pXENCs) were generated from porcine pluripotent stem cells (pPSCs) and were characterized by RNA sequencing and immunofluorescence analyses. The developmental potential of pXENCs was investigated in chimeric mouse embryos. Results: Porcine XEN cells derived from porcine pPSCs were successfully expanded in N2B27 medium supplemented with bFGF for least 30 passages. RNA sequencing and immunofluorescence analyses showed that pXENCs expressed the murine and canine XEN markers Gata6, Gata4, Sox17 and Pdgfra but not the pluripotent markers Oct4, Sox2 and TE marker Cdx2. Moreover, these cells contributed to the XEN when injected into four‐cell stage mouse embryos. Supplementation with Chir99021 and SB431542 promoted the pluripotency of the pXENCs. Conclusions: We successfully derived pXENCs and showed that supplementation with Chir99021 and SB431542 confer them with pluripotency. Our results provide a new resource for investigating the reprogramming mechanism of porcine‐induced pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Fluorene‐9‐bisphenol (BHPF), a substitute of bisphenol A (BPA) used in the production of the so‐called "BPA‐free" plastics, has now been shown to be released from commercial plastic bottles into drinking water and has strong anti‐estrogenic activity in mice, which suggests that BHPF is also an environmental toxin. However, whether BHPF exposure has effects on mouse oocyte development is unknown. In this study, the influence of acute exposure to BHPF (50–150 μM, 12 hr) on mouse oocyte maturation and its possible mechanisms were investigated. Of note, 50‐μM BHPF had no effects on the maturation of mouse oocytes, whereas 100‐ and 150‐μM BHPF significantly blocked germinal vesicle breakdown and led to the failure of first polar body extrusion. Particularly, 100‐μM BHPF exposure severely decreased the cellular adenosine triphosphate in a time‐dependent manner, which finally brought out the loss of spindles. In addition, the actin cytoskeleton was also impaired. The defective mitochondrial dynamics and decreased mitochondrial DNA implied the damage of mitochondria in BHPF‐treated oocytes. Increased PINK1, Beclin1, and LC3B protein level and decreased TOMM20 and TOMM17A protein level illustrated that mitophagy was induced, which also confirmed that BHPF exposure impaired the cellular mitochondria. Moreover, BHPF induced reactive oxygen species accumulation and early apoptosis. Oocyte quality was also impaired by BHPF exposure through altering histone modifications evidenced by increased H3K9me3 and H3K27me3 levels. Collectively, our results indicated that BHPF exposure disrupted mouse oocyte maturation and reduced oocyte quality through affecting cytoskeleton architecture, mitochondrial function, oxidative stress, apoptosis, and histone modifications. Environ. Mol. Mutagen. 60:243–253, 2019. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

To control the carbon dioxide phase more effectively during supercritical carbon dioxide fracturing, a fully coupled mathematical model is proposed for the investigation of the wellbore temperature and pressure. Our model assumes that the heat transfer is steady in the wellbore but unsteady in the formation. The physical parameters of carbon dioxide vary with temperature and pressure, and the influence of casing, tubing, and cement sheath thermal resistance on heat transfer are all considered. The heat generated by fluid friction losses is also taken into consideration. Based on this model, the influence of the injection temperature, injection rate, tubing roughness, and geothermal gradient on the wellbore pressure and temperature are discussed. The results indicate that the wellbore carbon dioxide temperature increases as the injection temperature, injection rate, tubing roughness, and geothermal gradient increase, and the wellbore carbon dioxide pressure decreases as the injection temperature, injection rate, and tubing roughness increase. To ensure that the carbon dioxide is in the supercritical state when it enters the formation, engineers need to increase the injection temperature. The heat generated by fluid friction losses has a significant impact on the wellbore temperature and pressure; this effect should therefore not be ignored. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Multi‐subunit cullin‐RING ligases (CRLs) are the largest family of ubiquitin E3 ligases in humans. CRL activity is tightly regulated to prevent unintended substrate degradation or autocatalytic degradation of CRL subunits. Using a proteomics strategy, we discovered that CRL4AMBRA1 (CRL substrate receptor denoted in superscript) targets Elongin C (ELOC), the essential adapter protein of CRL5 complexes, for polyubiquitination and degradation. We showed that the ubiquitin ligase function of CRL4AMBRA1 is required to disrupt the assembly and attenuate the ligase activity of human CRL5SOCS3 and HIV‐1 CRL5VIF complexes as AMBRA1 depletion leads to hyperactivation of both CRL5 complexes. Moreover, CRL4AMBRA1 modulates interleukin‐6/STAT3 signaling and HIV‐1 infectivity that are regulated by CRL5SOCS3 and CRL5VIF, respectively. Thus, by discovering a substrate of CRL4AMBRA1, ELOC, the shared adapter of CRL5 ubiquitin ligases, we uncovered a novel CRL cross‐regulation pathway. [ABSTRACT FROM AUTHOR]

Sodium fluoride (NaF) is used as a medicine to prevent tooth decay; however, excessive NaF could cause a pathological damage to the health. Recent studies showed that NaF impaired mouse oocyte maturation, included of abnormal spindle configuration, actin cap formation, cortical granule‐free domain formation, and the following development after fertilization. However, few studies used large animals as models to study the toxicology of NaF on oocytes maturation. We proposed a hypothesis that NaF would affect the nuclear and cytoplasmic maturation of porcine oocytes and DNA methylation pattern of imprinted genes in oocytes. Our results showed that NaF affected cumulus expansion, polar body emission, spindle morphology, cortical granule distribution, early apoptosis, and the following development after parthenogenetic activation during porcine oocyte maturation. Moreover, NaF increased the DNA methylation of NNAT and decreased its expression, which disturbed the glucose transport in oocytes. These results suggest that NaF impairs the porcine oocytes maturation epigenetically, which provides a new toxicological mechanism of NaF on the oocyte maturation. Environ. Mol. Mutagen. 59:223–233, 2018. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The Qianhe River flows between the Liupanshan Orogen and the Ordos Block, with the river valley controlled by the southern margin fault of the Ordos Block. Five asymmetrical terraces exist on the banks of the Qianhe River, which correspond to the five terraces of the Wei River. Each terrace is composed of alluvial deposits at the bottom beneath loess deposits, which are characterized by alternating loess (L) and paleosol (S) layers, with the basal layers of the loess deposits being S0, S1, S53, S8, and L15 from T1 to T5. The heights of the five terraces T5, T4, T3, T2, and T1 are 220 to 260 m, 130 to 160 m, 60 to 80 m, 20 to 30 m, and 8 to 10 m, respectively, above the present valley, and their ages are 1.2, 0.8, 0.5, 0.13, and 0.01 Ma, respectively. These ages are generally consistent with the several uplift periods of the Qinghai–Tibet Plateau in the medium and late stages. Therefore, neotectonic movement is the controlling factor of river terrace formation in the periphery of the Ordos Block. According to the south‐west movement of the river channel in the lower reaches of the Qianhe River, it can be estimated that the Ordos Block rotated about 20° counterclockwise in the Pleistocene. [ABSTRACT FROM AUTHOR]

This cover by Miaotian Long describes a facile strategy to construct microencapsulated urea ammonium polyphosphate (PPy-UAPP) with a polypyrrole shell. This work may open a new route for developing a super flame retardant and corresponding high-performance flame-retarded resins. The good compatibility between epoxy matrix and PPy-UAPP endows the resulting EP composites with a satisfactory balance between fire safety and mechanical properties. [Extracted from the article]

Neurotensin ( NTS) has long been recognized as a neurotransmitter or neuromodulator in the central nervous system and as an endocrine agent in the periphery via actions mediated through neurotensin receptors ( NTSRs). Many studies support a role for NTS in the endocrine, autocrine and paracrine growth stimulation of cancer, with oncogenic actions described for NTS in different types of cancers and cancer cell lines at each step of cancer progression, ranging from tumour growth and survival to metastatic spread. The mechanisms underlying the effects of the NTS/ NTSR system in cell proliferation, migration and invasion, as well as the anti-apoptotic effects of this system, have been elucidated in different types of cancers, and include mitogen-activated protein kinases, phosphatidylinositol 3-kinase and Rho GTPases. The present mini review summarizes recent findings relating to the oncogenic function of the NTS/ NTSR system. [ABSTRACT FROM AUTHOR]

Aim: Vascular access in haemodialysis is critical for effective therapy. We aim to evaluate the outcomes of arteriovenous fistula (AVF) creation in incident haemodialysis patients, impact of preoperative vein mapping and predictors of successful AVF maturation in our centre. Methods: Data of End-stage Renal Disease (ESRD) patients initiated on haemodialysis from January 2010 to December 2012 in our centre were retrospectively obtained from electronic medical records and clinical notes. Demographic characteristics, medical comorbidities, perioperative details were collected, and patients were followed up until 1 January 2014. Results: A total of 708 patients (median age 64, IQR 55-72)were includedwith mean duration of follow up of 2.3 ± 1.2 years, with access of AVF and arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight patients were lost to follow-up. Successful AVF maturation was achieved in 542 patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis revealed male gender, upper arm AVF and good postoperative thrill and pulse as predictors of successful AVF maturation. Preoperative vein mapping was performed in 42.5% (295/694) of patients, with mean vein diameter of 2.44± 0.82mm. Maturation rates with and without vein mapping were 72.2%and 82.4%, respectively, (P = 0.001). In patients with vein diameters of <2mm and =2mm, there was no statistically significant difference in maturation rates (71.3% vs. 72.6%; P=0.887) and median maturation time (66 vs. 78days; P=0.73). Conclusion: Arteriovenous fistula can be successfully created in most incident haemodialysis patients. Routine vein mapping is not necessary if veins are suitable on physical examination alone, and vein sizes of<2mmon ultrasound is not associated with lower AVF maturation rate. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to determine the diagnostic and prognostic values of serum KL-6 levels in Chinese patients with interstitial lung disease (ILDs). Methods A total of 1084 subjects including 373 cases of ILDs, 584 cases of non-ILD pulmonary diseases, and 127 healthy individuals were recruited from three clinical centers in China between January 2011 and December 2013. A total of 106 patients undergoing treatments for ILDs in Shanghai Pulmonary Hospital between January 2011 and December 2013 were enrolled. Baseline and posttreatment serum KL-6 levels were determined. Results Serum KL-6 levels in patients with ILDs were significantly higher than those in patients with non-ILD pulmonary diseases or in healthy individuals (1492.09 ± 2230.08 U/mL vs 258.67 ± 268.73 U/mL or 178.73 ± 71.17 U/mL, all P < 0.05). At the cut-off value of 500 U/mL, the sensitivity and specificity of serum KL-6 as a diagnostic marker for ILDs was 77.75% and 94.51%, respectively. The Kappa value was 0.743 ( P < 0.001). The area below the receiver operating characteristic curve was 0.922 with a 95% Confidence interval of 0.904-0.941 ( P < 0.001). The posttreatment serum KL-6 levels significantly reduced in patients with improved ILDs, whereas markedly increased in patients with exacerbated ILDs (All P < 0.05). Conclusions Serum KL-6 levels might be a promising diagnostic biomarker for ILDs in Chinese patients. The prognostic value of serum KL-6 levels for ILDs remains to be verified by large-scaled studies. [ABSTRACT FROM AUTHOR]

The N-heterocyclic carbene-catalyzed [3+3] annulation of indoline-2-thiones and bromoenals has been developed, giving the corresponding indolo[2,3- b]dihydrothiopyranones in high yields. [ABSTRACT FROM AUTHOR]

In the presence of a quinone, Brønsted acid-catalyzed intramolecular C−N bond formation of o-vinylanilines by electrophilic cyclization was developed, giving the corresponding N-arylindoles in good to high yields. The reaction worked well for o-vinylanilines with terminal and internal C=C double bonds. [ABSTRACT FROM AUTHOR]

When there are external disturbances acting on the system, the conventional Luenberger observer design for state estimation usually results in a biased state estimate. This paper presents a robust state and disturbance observer design that gives both accurate state and disturbance estimates in the face of large disturbances. The proposed robust observer is structurally different from the conventional one in the sense that a disturbance estimation term is included in the observer equation. With this disturbance estimation term, the robust observer design problem is skillfully transformed into a disturbance rejection control problem. We then can utilize the standard H ∞ control design tools to optimize the robust observer between the disturbance rejection ability and noise immune ability. An important advantage of the proposed robust observer is that it applies to both minimum-phase systems and non-minimum phase systems. [ABSTRACT FROM AUTHOR]

Peritoneal dissemination of tumor has high mortality and is associated with the loss of epithelial features, acquisition of motile mesenchymal morphology characteristics, and invasive properties by tumor cells. Melatonin is an endogenously produced molecule in all plant species that is known to exert antitumor activity, but to date, its underlying mechanisms and antiperitoneal metastasis efficacy is not well defined. This study determined the antiperitoneal dissemination potential of melatonin in vivo and assessed its association with the inhibition of epithelial-to-mesenchymal transition ( EMT) signaling mechanism by endoplasmic reticulum ( ER) stress, which may be a major molecular mechanism of melatonin against cancer. The results demonstrate that melatonin inhibited peritoneal metastasis in vivo and activated ER stress in Cignal ERSE Reporter Assay, organelle structure in transmission electron microscopy images, calpain activity, and protein biomarkers like p-elf2 α. Moreover, the overexpression of transcription factor C/ EBP β in gastric cancer interacted with NF κB and further regulates COX-2 expression. These were dissociated and downregulated by melatonin, as proven by immunofluorescence imaging, immunoprecipitation, EMSA, and Ch IP assay. Melatonin or gene silencing of C/ EBP β decreased the EMT protein markers (E-cadherin, Snail, and Slug) and Wnt/beta-catenin activity by Topflash activity, and increased ER stress markers. In an animal study, the results of melatonin therapy were consistent with those of in vitro findings and attenuated systemic proangiogenesis factor production. In conclusion, C/ EBP β and NF κB inhibition by melatonin may impede both gastric tumor growth and peritoneal dissemination by inducing ER stress and inhibiting EMT. [ABSTRACT FROM AUTHOR]