Due to the highest theoretical specific capacity of 4200 mA h g−1 for Li4.4Si, silicon(Si)-based materials could fulfill the increasing demands of high-energy lithium-ion batteries (LIBs). However, ...the intrinsic huge volume expansion during the lithiation/delithiation process results in rapid capacity decay and short cycle life and restricts the satisfactory electrical performance of Si-based anodes. Binder plays an important role of maintaining the contact integrity between active material, conductive additive and the current collector, thereby reducing the pulverization of the Si particles during charge/discharge. Here, the review systematically summarizes the synthesis methods, design principles and working mechanisms, including chemical composition, superstructure, and various interactions between different functional moieties of synthetic binders and natural biomass binders, to reveal the structure-composition-performance relationship, offer practical solutions to challenging problems associated with defects of Si-based electrode materials in LIBs and aim at exploiting new family of binders that could be used in industrial level as well as providing design principles for other electrode binders in rechargeable batteries.
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•Working mechanisms and design principles of Si-based anodes binders are presented.•Synergistic strategy of combining binders with anode structure design is discussed.•Synthesis methods, applied anodes, ICE and cycling performance are listed.
Most human cancers develop from stem and progenitor cell populations through the sequential accumulation of various genetic and epigenetic alterations. Cancer stem cells have been identified from ...medulloblastoma (MB), but a comprehensive understanding of MB stemness, including the interactions between the tumor immune microenvironment and MB stemness, is lacking. Here, we employed a trained stemness index model based on an existent one‐class logistic regression (OCLR) machine‐learning method to score MB samples; we then obtained two stemness indices, a gene expression‐based stemness index (mRNAsi) and a DNA methylation‐based stemness index (mDNAsi), to perform an integrated analysis of MB stemness in a cohort of primary cancer samples (n = 763). We observed an inverse trend between mRNAsi and mDNAsi for MB subgroup and metastatic status. By applying the univariable Cox regression analysis, we found that mRNAsi significantly correlated with overall survival (OS) for all MB patients, whereas mDNAsi had no significant association with OS for all MB patients. In addition, by combining the Lasso‐penalized Cox regression machine‐learning approach with univariate and multivariate Cox regression analyses, we identified a stemness‐related gene expression signature that accurately predicted survival in patients with Sonic hedgehog (SHH) MB. Furthermore, positive correlations between mRNAsi and prognostic copy number aberrations in SHH MB, including MYCN amplifications and GLI2 amplifications, were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.
Here, we employed a trained stemness index model to perform an integrated analysis of medulloblastoma (MB) stemness. By combining the Lasso‐penalized Cox regression with univariate and multivariate Cox regression analyses, we identified a stemness‐related gene expression signature. Furthermore, positive correlations between gene expression‐based stemness index and prognostic copy number aberrations were detected. Analyses of the immune microenvironment revealed unanticipated correlations of MB stemness with infiltrating immune cells. Lastly, using the Connectivity Map, we identified potential drugs targeting the MB stemness signature.
Gallium oxide (Ga2O3) films had been fabricated on Al2O3(0001) substrate by employing pulsed laser deposition (PLD) and annealed at different temperatures under forming gas (FG) atmosphere (95% N2 + ...5% H2). The influence of annealing temperature on the structural, optical, chemical composition, and surface morphological properties of the Ga2O3 thin films was investigated comprehensively. The annealing processes with hydrogen gas play a crucial role in the characteristics of Ga2O3 thin films. A crystallization mechanism of Ga2O3 films controlled by annealing temperature has been proposed firstly and analyzed systematically, which contains three kinds of competitive mechanism, namely the thermal enhanced crystallization, the enhanced H2 dissociative adsorption on Ga2O3 surfaces, and the high‐temperature decomposition of Ga2O3. Both Ga+ and Ga3+ oxidation valence states were presented in all samples, which indicated lattice oxygen deficiency in Ga2O3 films. The variation of the non‐lattice oxygen proportion of Ga2O3 films related to the crystallization mechanism firstly increased and then decreased with the increase of annealing temperature. The detailed crystallization mechanism of PLD‐Ga2O3 films annealed in FG offers a guideline and references for the further fabrication of high‐quality Ga2O3 films and their applications in high‐performance devices.
Heat shock factor 1 (HSF1) is highly expressed in various malignancies and is a potential modulator of tumor progression. Emerging evidence suggests that HSF1 activation in stromal cells is closely ...related to poor patient prognosis. However, the role of HSF1 in oral squamous cell carcinoma (OSCC) remains elusive. We aimed to investigate the function of HSF1 in cancer‐associated fibroblasts (CAFs) of the tumor microenvironment (TME) and in tumor development. In the present study, we found that HSF1 was highly expressed in both CAFs and tumor cells, and was significantly correlated with poor prognosis and overall survival. Moreover, HSF1 overexpression in CAFs resulted in a fibroblast‐like phenotype of Cal27 cells, induced epithelial‐mesenchymal transition (EMT), and promoted proliferation, migration and invasion in Cal27 cells. HSF1 knockdown attenuated features of CAFs and reduced EMT, proliferation, migration and invasion in Cal27 cells. Furthermore, HSF1 in CAFs promoted tumor growth in nude mice. Taken together, these data suggest that HSF1 expression in CAFs drive OSCC progression, and could serve as an independent prognostic marker of patients with OSCC. Thus, HSF1 is a potent mediator of OSCC malignancy.
Infiltration of α‐SMA‐positive CAFs could promote OSCC progression. Furthermore, the expression of HSF1 in both CAFs and tumor cells was positively associated with poor prognosis and OS. Moreover, HSF1 expression in CAFs induced tumor cells to undergo partial EMT and enhanced the migration and invasion of cancer cells, and knockdown of HSF1 in CAFs reduced tumor growth.
Aptamers are oligonucleic acid or peptide molecules that bind to specific target molecules. As a novel and powerful class of ligands, aptamers are thought to have excellent potential for applications ...in the fields of biosensing, diagnostics and therapeutics. In this study, a new method for predicting aptamer-target interacting pairs was proposed by integrating features derived from both aptamers and their targets. Features of nucleotide composition and traditional amino acid composition as well as pseudo amino acid were utilized to represent aptamers and targets, respectively. The predictor was constructed based on Random Forest and the optimal features were selected by using the maximum relevance minimum redundancy (mRMR) method and the incremental feature selection (IFS) method. As a result, 81.34% accuracy and 0.4612 MCC were obtained for the training dataset, and 77.41% accuracy and 0.3717 MCC were achieved for the testing dataset. An optimal feature set of 220 features were selected, which were considered as the ones that contributed significantly to the interacting aptamer-target pair predictions. Analysis of the optimal feature set indicated several important factors in determining aptamer-target interactions. It is anticipated that our prediction method may become a useful tool for identifying aptamer-target pairs and the features selected and analyzed in this study may provide useful insights into the mechanism of interactions between aptamers and targets.
What is the physiological function of Yes-associated protein-1 (Yap1), a susceptibility gene for polycystic ovary syndrome (PCOS), in ovarian granulosa cells (GCs)?
Physiologically, steroid sex ...hormones stimulate follicle growth by activating YAP1; however, the preovulatory inhibition of YAP1 activity in GCs is a prerequisite of LH actions.
PCOS is a common gynecologic and endocrine disease with multiple short and long-term consequences. Many PCOS patients suffer anovulation caused by hyperandrogenism, but its etiology remains unclear.
To study the effect of acute hyperandrogenism on ovulation, we injected pregnant mare serum gonadotrophin (PMSG)-primed (44 h) pubertal mice with dihydrotestosterone (DHT), the major biologically active form of androgen, in a superovulation assay. We investigated if YAP1 is regulated by testosterone and if it is potentially involved in follicle development and ovulation. Cultured primary GCs were subjected to Yap1 depletion by RNA interference and Yap1 overexpression by adenoviral infections.
Female mice at postnatal day (PD)-21~23 were analyzed to avoid the complexity of ovarian functions associated with estrous cycles and endogenous surges of gonadotropins. Immature mice were injected intraperitoneally with five IU PMSG to stimulate preovulatory follicle development followed 44 h later with five IU hCG to stimulate ovulation. For DHT treatments, female mice at PD23 were injected intraperitoneally with five IU PMSG followed 44 h later with five IU hCG alone (as control) or five IU hCG plus 100 μg DHT, which was dissolved in 0.1 ml DMSO. Methods of gene expression detection used include immunohistochemistry, immunofluorescence, Western blotting and quantitative PCR. More than three biological and technical replicates were included in each experiments.
we provide novel evidence in a mouse model that YAP1 is required for proliferation of ovarian GCs, but is down-regulated by LH through the extracellular-regulated kinase-1/2 (ERK1/2) cascade. Acute hyperandrogenism blocks LH actions and causes oligo-ovulation by activating YAP1.
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Results shown were obtained only in mouse, and need to be further confirmed in human samples.
These findings not only elucidated the role of YAP1 in maintaining normal ovarian functions, but also link the YAP1 deregulation to the pathogenesis of PCOS.
This study is funded by the National Key Research and Development Program of China (2016YFC1000600 and 2017YFSF1001500) and National Natural Science Foundation of China (31528016, 31371449 and 31671558). The authors have no competing interests.
The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value‐added epoxides. However, due to the competitive reaction of ...water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br−/HOBr‐mediated method is developed to achieve a near‐quantitative selectivity and ≈100% FE of styrene oxide on α‐Fe2O3, in which low concentration of Br− as mediator and locally generated acidic micro‐environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH‐dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.
A method of PEC Br−/HBrO mediated alkene epoxidation with a near‐quantitative selectivity and 100% FE is achieved by modulating Br− concentration and the local acidity around the interface of α‐Fe2O3 photoanode, in which bromohydrin product is identified as the intermediate and transformed to epoxide with the removal of HBr when meeting OH−.
Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic β‐cells. ER stress or ROS causes c‐Jun ...N‐terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi‐stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual‐luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in β‐cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p‐JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome‐dependent manner. We found that NR4A1 increased the expression of cbl‐b (an E3 ligase); knocking down cbl‐b expression increased MKK4 and p‐JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl‐b promoter by physical association. We further confirmed that cbl‐b expression in β‐cells was reduced in NR4A1‐knockout mice compared with WT mice. NR4A1 down‐regulates JNK activation by ER stress or ROS in β‐cells via enhancing cbl‐b expression.
Pancreatic cancer is one of the most deadly neoplasm with a 5-year survival rate of less than 6% owing to its remarkable tolerance to nutrient starvation, and new drugs and treatment strategies are ...urgently needed. During a project aiming at discovery of anticancer agents, we performed a structure modification on polycyclic polyprenylated acylphloroglucinols (PPAPs) skeleton, and discovered that PPAP rearranged to a tetrahydroquinolin-2(1H)-one feature. Here, series of tetrahydroquinolin-2(1H)-one derivatives were designed, synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (PANC-1), and the structure-activity relationship was also discussed. Among them, derivative 11k showed the most potent inhibitory activity with an IC50 value of 4.9 μM under nutrient-deprived condition. In contrast, all these derivatives exhibited low cytotoxicity against PANC-1 cells under normal nutrient condition, suggesting that the derivatives appeared to allow alternative tumor cell death mechanisms, and led to less toxicity. Further evaluations demonstrated that 11k decreased colony formation and induced the apoptosis of PANC-1 under nutrient-deprived condition in a concentration dependent manner. In in vivo study, 11k significantly suppressed the tumor development and weight in nude mice. Preliminary mechanism research revealed that 11k clearly downregulated LC3-II expression and increased the level of p62, two key autophagy markers and critical signals for pancreatic tumor growth and progression. Our current findings demonstrated that 11k might be a promising candidate for the new chemotherapeutic molecule of pancreatic cancer, and deserve further study.
Series of tetrahydroquinolin-2(1H)-one derivatives were synthesized via modifications of 4-OH and side chain. Their anti-pancreatic cancer activity was evaluated in vitro and in vivo. Display omitted
•Series of tetrahydroquinolin-2(1H)-one derivatives were synthesized.•Compound 11k inhibited PANC-1 cells with an IC50 = 4.9 μM.•Compound 11k suppressed the pancreatic tumor development and weight in vivo.•Compound 11k downregulated LC3-II expression and increased the level of p62.
Post-translational modifications (PTMs) are crucial steps in protein synthesis and are important factors contributing to protein diversity. PTMs play important roles in the regulation of gene ...expression, protein stability and metabolism. Lysine residues in protein sequences have been found to be targeted for both types of PTMs: sumoylations and acetylations; however, each PTM has a different cellular role. As experimental approaches are often laborious and time consuming, it is challenging to distinguish the two types of PTMs on lysine residues using computational methods. In this study, we developed a method to discriminate between sumoylated lysine residues and acetylated residues. The method incorporated several features: PSSM conservation scores, amino acid factors, secondary structures, solvent accessibilities and disorder scores. By using the mRMR (Maximum Relevance Minimum Redundancy) method and the IFS (Incremental Feature Selection) method, an optimal feature set was selected from all of the incorporated features, with which the classifier achieved 92.14% accuracy with an MCC value of 0.7322. Analysis of the optimal feature set revealed some differences between acetylation and sumoylation. The results from our study also supported the previous finding that there exist different consensus motifs for the two types of PTMs. The results could suggest possible dominant factors governing the acetylation and sumoylation of lysine residues, shedding some light on the modification dynamics and molecular mechanisms of the two types of PTMs, and provide guidelines for experimental validations.
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