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In this work, designed growth of two type of N-doped graphene nanosheets has been investigated using NH 4 H 2 PO 4 and (NH 4 )2HPO 4 as buffering agents, respectively, in a mild hydrothermal process. X-ray photoelectron spectroscopy (XPS) characterization indicates that the graphene nanosheets grown using NH 4 H 2 PO 4 (NGC) have lower nitrogen but higher oxygen content than those using (NH4)2HPO4 (NGL). Electrochemical measurements in three-electrode systems show that both type of the graphene products exhibit superior electrochemical performance (383 and 356 F g-1 at 1 A g-1). While the specific capacitance of NGC is steadily higher than that of NGL under all investigated current densities, the capacitance attenuation of NGL is 4.80% from 500 to 10000 cycles showing more durable in cyclicity than that of NGC (8.81%). The two-electrode supercapacitor devices for NGC and NGL exhibit high energy density of 12.21 Wh kg −1 and 9.28 Wh kg −1 at 0.25 A g −1 . The difference in electrochemical behaviors between NGC and NGL electrodes can be attributed to the different contribution of nitrogen and oxygenic groups. The buffer agents assisted synthesis procedure coupled with the reasonable capacitance performance suggests an alternative way in the designed functionalization of graphene for developing high performance supercapacitors. [ABSTRACT FROM AUTHOR]

[Display omitted] • The slurryability of the mixed slurry was facilitated most with the lignite/DCLR mass ratio of 5:5. • The maximum solid concentration of the mixed slurry increased from 41.70 wt% to 53.91 wt%. • The combustion process of the mixed slurry was more concentrated and violent. • The DCLR promoted organic pollutant emissions in the wavenumber range of 1500–500 cm−1. • Except for Pb and Zn, more than 85% of Cr, Cu, and Ni were intercepted in solid residues. Direct coal liquefaction residue (DCLR) as an auxiliary feed material with lignite to prepare coal water slurry (CWS), which is then used as combustion fuels, enables recycle resources of DCLR and diminishes its impact on the surrounding environment. This paper aims to study the slurryability, combustion characteristics, and typical pollutant emissions of the lignite water slurry (LWS), DCLR water slurry (DCLRWS), and lignite-DCLR water slurry (L-DWS). Results showed that the DCLR and lignite were complementary in physicochemical properties for preparing the L-DWSs. The maximum solid concentration (ω max) of the DCLR was 73.19 wt% with poor static stability, whereas that of the LWS was 41.70 wt% with high pseudoplasticity. By contrast, the ω max of the L-DWS-5 prepared from the lignite and DCLR at mass ratio of 5:5 was 53.91 wt% with lower pseudoplasticity and static stability. Meanwhile, combustion experiments confirmed that the introduced DCLR was effective in improving the ignition, burnout, and comprehensive combustion performance of the L-DWS. The Q net, p of the slurrying samples increased from 6.70 MJ/Kg for the LWS to 14.41 MJ/Kg for the L-DWS-5. And the addition of the DCLR exhibited slight influences on the emissions of NOx and SO 2 , but significantly increased HCN and other organic compounds such as C n H m , CO, and NH 3 emissions. Furthermore, except for Pb and Zn, more than 85% Cr, Cu, and Ni were intercepted in solid residues. [ABSTRACT FROM AUTHOR]

• Induction of tetraploids of 'duli' and 'Xinli No.7′ with colchicine is feasible. • Tetraploids have desirable traits, such as dwarfism and enlarged leaves. • Both seeds and shoot tips could be used for pear tetraploid induction. • Mixed culture method is an effective way for pear tetraploid induction. Polyploid plants usually exhibit broader leaves, thicker stems, bigger flowers and fruits, dwarfing stature, as well as improved biotic and abiotic resistance. Therefore, increasing the polyploidy is one of the most important strategies used in plant breeding. Here, we reported the successful induction of tetraploids of two pear varieties, 'duli' pear (Pyrus betulaefolia), a wildtype pear used for rootstocks in grafting, and 'Xinli No.7′ pear (Pyrus bretschneideri), a popular cultivated pear variety in China. This was achieved by treating their seeds, shoot tips of tissue cultured or field grown seedlings with colchicine and pendimethalin using three different methods: impregnation, mixed culture and smearing. The best tetraploids induction condition for 'duli' pear seeds was impregnating them with 0.4% colchicine for 24 h where the mutation rate of 2.0% was achieved with no chimera found. For shoot tips of tissue cultured seedlings the best condition was impregnating them with 0.2% colchicine where 6.67% of 'duli' (48 h) and 13.0% of 'Xinli No.7′ (24 h) were mutated. In addition, we found that in the mixed culture method the best induction condition for 'duli' was mixing with 1.0% colchicine while for 'Xinli No.7′ it was 0.5% colchicine. In the smear method, for the shoot tips of field grown seedlings of 'duli', the best induction condition was treating them with 0.4% colchicine for 24 h. Subsequently, the DNA content of these putative polyploid seedlings was estimated by the flow cytometry, confirming their ploidy nature. Also, we compared the morphological differences between the tetraploid seedlings and the diploid seedlings. Obviously, the tetraploid seedlings appeared to be dwarfed with shorter internode length and reduced internode number of their stems. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains the leading malignant neoplasm among women globally, posing significant challenges in terms of treatment and prognostic evaluation. The metabolic pathway of polyamines is crucial in breast cancer progression, with a strong association to the increased capabilities of tumor cells for proliferation, invasion, and metastasis., Methods: We used a multi-omics approach combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to study polyamine metabolism. Data from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression identified 286 differentially expressed genes linked to polyamine pathways in breast cancer. These genes were analyzed using univariate COX and machine learning algorithms to develop a prognostic scoring algorithm. Single-cell RNA sequencing validated the model by examining gene expression heterogeneity at the cellular level., Results: Our single-cell analyses revealed distinct subpopulations with different expressions of genes related to polyamine metabolism, highlighting the heterogeneity of the tumor microenvironment. The SuperPC model (a constructed risk score) demonstrated high accuracy when predicting patient outcomes. The immune profiling and functional enrichment analyses revealed that the genes identified play a crucial role in cell cycle control and immune modulation. Single-cell validation confirmed that polyamine metabolism genes were present in specific cell clusters. This highlights their potential as therapeutic targets., Conclusions: This study integrates single cell omics with machine-learning to develop a robust scoring model for breast cancer based on polyamine metabolic pathways. Our findings offer new insights into tumor heterogeneity, and a novel framework to personalize prognosis. Single-cell technologies are being used in this context to enhance our understanding of the complex molecular terrain of breast cancer and support more effective clinical management., (© 2024. The Author(s).)

Circadian dysfunction is prevalent in neurodevelopmental disorders, particularly in autism spectrum disorder (ASD). A plethora of empirical studies demonstrate a strong correlation between ASD and circadian disruption, suggesting that modulation of circadian rhythms and the clocks could yield satisfactory advancements. Research indicates that circadian dysfunction associated with abnormal neurodevelopmental phenotypes in ASD individuals, potentially contribute to synapse plasticity disruption. Therefore, targeting circadian rhythms may emerge as a key therapeutic approach. In this study, we did a brief review of the mammalian circadian clock, and the correlation between the circadian mechanism and the pathology of ASD at multiple levels. In addition, we highlight that circadian is the target or modulator to participate in the therapeutic approaches in the management of ASD, such as phototherapy, melatonin, modulating circadian components, natural compounds, and chronotherapies. A deep understanding of the circadian clock's regulatory role in the neurodevelopmental phenotypes in ASD may inspire novel strategies for improving ASD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Chen, Li, Tang, Li and Feng.)

Solution-processed perovskite solar cells (PSCs) are at the forefront of next-generation photovoltaics, exhibiting outstanding photoelectric performance and cost-effective manufacturing. However, the prevalent use of polar aprotic solvents such as N , N -dimethylformamide and dimethyl sulfoxide in the preparation of perovskite precursor solution hinders complete solvent removal during film formation. Their high boiling points and strong coordinating abilities lead to solvated intermediates and heterogeneous perovskite crystal nucleation, particularly in the absence of the antisolvent-assisted crystallization. To address this, we developed a methylamine (MA)-based gel dispersion system that significantly improves the uniformity of perovskite films. By employing ethyl acetate (EA) antisolvent extraction, the gel precursor is extracted from a solution of MAI and PbI 2 in MA ethanol, which is then diluted in pure acetonitrile (ACN) solvent to form a clear perovskite precursor solution. Benefiting from the highly volatile nature of the ACN-based gel perovskite precursor solution and its rich concentration of high-valent PbI n 2-n coordination compounds, this approach enables the fabrication of high-quality MAPbI 3 perovskite films, yielding PCEs of 21.34% for PSC and 19.77% for a 5 × 5 cm 2 mini-module. This MA-based gel perovskite precursor strategy offers a promising avenue for potential applications in the scalable manufacture of PSCs.

Lignin, a renewable and abundant natural polymer, has emerged as a promising candidate for anticancer therapy due to its unique properties and biocompatibility. This review provides a comprehensive overview of recent advancements in the utilization of lignin-based nanomaterials for enhancing anticancer drug delivery and therapeutic outcomes. A detailed examination of the literature reveals several synthesis methods, including nanoprecipitation, microemulsion, and solvent exchange, which produce lignin nanoparticles with improved drug solubility and bioavailability. The anticancer mechanisms of lignin nanoparticles, such as the generation of reactive oxygen species (ROS), induction of apoptosis, and enhanced cellular uptake, are also explored. Lignin nanoparticles loaded with drugs like curcumin, doxorubicin, camptothecin, and resveratrol have demonstrated the ability to improve drug efficacy, selectively target cancer cells, overcome multidrug resistance, and minimize toxicity in both in vitro and in vivo studies. These nanoparticles have shown significant potential in suppressing tumor growth, inducing cell death through apoptotic pathways, and enhancing the synergistic effects of combination therapies, such as chemo-phototherapy. Future research directions include optimizing lignin nanoparticle formulations for clinical applications, refining targeted delivery mechanisms to cancer cells, and conducting thorough biocompatibility and toxicity assessments. Overall, this review highlights the significant progress made in utilizing lignin-based nanomaterials for cancer therapy and outlines promising areas for further exploration in this rapidly evolving field., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The unscientific application of nitrogen (N) fertilizer not only increases the economic input of pear growers but also leads to environmental pollution. Improving plant N use efficiency (NUE) is the most effective economical method to solve the above problems. The absorption and utilization of N by plants is a complicated process. Glutamine synthetase (GS) and glutamate synthase (GOGAT) are crucial for synthesizing glutamate from ammonium in plants. However, their gene family in pears has not been documented. This study identified 29 genes belonging to the GS and GOGAT family in the genomes of Pyrus betulaefolia ( P.be , 10 genes), Pyrus pyrifolia ( P.py , 9 genes), and Pyrus bretschneideri ( P.br , 10 genes). These genes were classified into two GS subgroups (GS1 and GS2) and two GOGAT subgroups (Fd-GOGAT and NADH-GOGAT). The similar exon-intron structures and conserved motifs within each cluster suggest the evolutionary conservation of these genes. Meanwhile, segmental duplication has driven the expansion and evolution of the GS and GOGAT gene families in pear. The tissue-specific expression dynamics of PbeGS and PbeGOGAT genes suggest significant roles in pear growth and development. Cis-acting elements of the GS and GOGAT gene promoters are crucial for plant development, hormonal responses, and stress reactions. Furthermore, qRT-PCR analysis indicated that PbeGSs and PbeGOGATs showed differential expression under exogenous hormones (GA 3 , IAA, SA, ABA) and abiotic stress (NO 3 - and salt stress). In which, the expression of PbeGS2.2 was up-regulated under hormone treatment and down-regulated under salt stress. Furthermore, physiological experiments demonstrated that GA 3 and IAA promoted GS, Fd-GOGAT, and NADH-GOGAT enzyme activities, as well as the N content. Correlation analysis revealed a significant positive relationship between PbeGS1.1 , PbeGS2.2 , PbeNADH - GOGATs , and the N content. Therefore, PbeGS1.1 , PbeGS2.2 , and PbeNADH - GOGATs could be key candidate genes for improving NUE under plant hormone and abiotic stress response. To the best of our knowledge, our study provides valuable biological information about the GS and GOGAT family in the pear for the first time and establishes a foundation for molecular breeding aimed at developing high NUE pear rootstocks.

The discharge of wastewater into rivers can lead to resistome coalescence, thereby enhancing the spread risk of antibiotic resistance genes (ARGs) through mixing of exogenous wastewater resistome communities with indigenous riverine communities. At present, the understanding on the role of resistome community coalescence in the dissemination of ARGs is still very limited, and little is known about the process and its ecological implications. To bridge the gap, this study has conducted field-based surveys and microcosm experiments to deeply dissect the coalescence of resistome community in wastewater within river environment, utilizing genome-centric metagenomic analysis approach. The field investigation suggests resistome coalescence enhances the abundance and diversity of ARGs in the receiving river. Furthermore, the microcosm experiments reveal the effect of mixing ratio on resistome coalescence in the water-sediment system and decipher the temporal attenuation dynamics of the coalesced resistome in the environment. The results show the higher proportion of wastewater has a greater impact on ARGs in the water, whereas the effect of mixing ratio is lesser in the sediments. Temporally, the source-specific ARGs originating from wastewater exhibit decreasing trends over the experimental duration, and relatively, the attenuation in the water is more pronounced than that in the sediments. Interestingly, natural light not only facilitates the attenuation of ARGs in the water but may also induce their deposition at the water-sediment interface. Variance partitioning analyses suggest the microbiome, mobilome, and abiotic factors collectively shape the coalescence of the resistome communities in the environment. The study provides empirical evidence on resistome coalescence in river systems, which is instrumental in gaining a better understanding of the spread mechanism of ARGs in the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Agrobacterium tumefaciens can harm various fruit trees, leading to significant economic losses in agricultural production. It is urgent to develop new pesticides to effectively treat this bacterial disease. In this study, four new sesquiterpene derivatives, trichoderenes A-D ( 1 - 4 ), along with six known compounds ( 5 - 10 ), were obtained from the marine-derived fungus Trichoderma effusum . The structures of 1 - 4 were elucidated by extensive spectroscopic analyses, and the calculated ECD, ORD, and NMR methods. Structurally, the hydrogen bond formed between the 1-OH group and the methoxy group enabled 1 to adopt a structure resembling that of resorcylic acid lactones, thereby producing the ECD cotton effect. Compound 3 represents the first example of C12 nor-sesquiterpene skeleton. Compounds 1 - 10 were tested for their antimicrobial activity against A. tumefactions . Among them, compounds 1 - 3 and 8 - 10 exhibited inhibitory activity against A. tumefactions with MIC values of 3.1, 12.5, 12.5, 6.2, 25.0, and 12.5 μg/mL, respectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Qi, Xu, Li, Liu, He and Zhang.)

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-beta peptides within cerebral blood vessels, leading to neurovascular complications. Ischemic strokes result from acute disruptions in cerebral blood flow, triggering metabolic disturbances and neurodegeneration. Both conditions often co-occur and are associated with respiratory dysfunctions. The retrotrapezoid nucleus (RTN), which is crucial for CO 2 sensing and breathing regulation in the brainstem, may play a key role in breathing disorders seen in these conditions. This study aims to investigate the role of Transforming Growth Factor Beta (TGF-β) signaling in the RTN on respiratory and cognitive functions in CAA, both with and without concurrent ischemic stroke., Methods: Adult male Tg-SwDI (CAA model) mice and C57BL/6 wild-type controls underwent stereotaxic injections of lentivirus targeting TGF-β2R2 in the RTN. Stroke was induced by middle cerebral artery occlusion using a monofilament. Respiratory functions were assessed using whole-body plethysmography, while cognitive functions were evaluated through the Barnes Maze and Novel Object Recognition Test (NORT). Immunohistochemical analysis was conducted to measure TGF-βR2 and GFAP expressions in the RTN., Results: CAA mice exhibited significant respiratory dysfunctions, including reduced respiratory rates and increased apnea frequency, as well as impaired cognitive performance. TGF-βR2 knockdown in the RTN improved respiratory functions and cognitive outcomes in CAA mice. In CAA mice with concurrent stroke, TGF-βR2 knockdown similarly enhanced respiratory and cognitive functions. Immunohistochemistry confirmed reduced TGF-βR2 and GFAP expressions in the RTN following knockdown., Conclusions: Our findings demonstrate that increased TGF-β signaling and gliosis in the RTN contribute to respiratory and cognitive dysfunctions in CAA and CAA with stroke. Targeting TGF-βR2 signaling in the RTN offers a promising therapeutic strategy to mitigate these impairments. This study is the first to report a causal link between brainstem gliosis and both respiratory and cognitive dysfunctions in CAA and stroke models., Competing Interests: Disclosures The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article.

Background: Accurate classification of breast nodules into benign and malignant types is critical for the successful treatment of breast cancer. Traditional methods rely on subjective interpretation, which can potentially lead to diagnostic errors. Artificial intelligence (AI)-based methods using the quantitative morphological analysis of ultrasound images have been explored for the automated and reliable classification of breast cancer. This study aimed to investigate the effectiveness of AI-based approaches for improving diagnostic accuracy and patient outcomes., Methods: In this study, a quantitative analysis approach was adopted, with a focus on five critical features for evaluation: degree of boundary regularity, clarity of boundaries, echo intensity, and uniformity of echoes. Furthermore, the classification results were assessed using five machine learning methods: logistic regression (LR), support vector machine (SVM), decision tree (DT), naive Bayes, and K-nearest neighbor (KNN). Based on these assessments, a multifeature combined prediction model was established., Results: We evaluated the performance of our classification model by quantifying various features of the ultrasound images and using the area under the receiver operating characteristic (ROC) curve (AUC). The moment of inertia achieved an AUC value of 0.793, while the variance and mean of breast nodule areas achieved AUC values of 0.725 and 0.772, respectively. The convexity and concavity achieved AUC values of 0.988 and 0.987, respectively. Additionally, we conducted a joint analysis of multiple features after normalization, achieving a recall value of 0.98, which surpasses most medical evaluation indexes on the market. To ensure experimental rigor, we conducted cross-validation experiments, which yielded no significant differences among the classifiers under 5-, 8-, and 10-fold cross-validation (P>0.05)., Conclusions: The quantitative analysis can accurately differentiate between benign and malignant breast nodules., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1652/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Postoperative hypoparathyroidism caused by parathyroid injury is a problem faced by thyroid surgeons. The current technologies for parathyroid imaging all have some defects., Methods: Patients with differentiated thyroid carcinoma (DTC) who underwent unilateral thyroidectomy plus ipsilateral central lymph node dissection were recruited. We dissected the main trunk of the superior thyroid artery entering the thyroid gland and placed the venous indwelling tube into the artery. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated., Results: A total of 132 patients enrolled in this single-arm clinical trial, 105 of them completed retrograde catheterization via the superior artery. The sensitivity was 69.23 and 83.33% respectively. The specificity was 72.91 and 64.89%. The accuracy was 72.91 and 64.89%. The PPV was 85.71 and 81.08%. The NPV was 22.58 and 45.45%. There were no patients with allergic reactions to the methylene blue, or methylene blue toxicity., Conclusions: Retrograde injection of methylene blue via the superior thyroid artery is an effective and safe method to visualize parathyroid glands. This method can accurately locate the target organ by ultraselecting the blood vessel and injecting the contrast agent while avoiding background contamination and reducing the amount of contrast agent., Trial Registration: Clinical trial registration numbers and date of registration: ChiCTR2300077263、02/11/2023., (© 2024. The Author(s).)

Background: This study employs bibliometric methods to comprehensively understand the fundamental structure of research about Autism Spectrum Disorder (ASD) Signaling Pathways by examining key indicators such as nations, institutions, journals, authors, and keywords., Methodology: We utilized the WoScc database to retrieve literature relevant to ASD Signaling Pathways published between 2013 and 2023. Through visual analysis and tools like CiteSpace and VosViewer, we explored nations, institutions, journals, authors, and keywords, thereby constructing relevant networks., Results: 26 The study encompasses 1,396 articles, revealing a consistent increase in publications. The United States, China, and Germany are leading nations in this literature. Regarding research institutions, the University of California system and Eric Klann have garnered significant attention due to their substantial contributions to the field of ASD Signaling Pathways. Most relevant research is published in the journal "Molecular Autism." Research interests are concentrated across various themes, including "elevating neuronal β-catenin levels," "Tunisian children," " Fmr1 knockout (KO) mice," " de novo mutations," "autistic children," "local translation," "propionic acid-induced mouse models," "neurosystems," "glucose metabolism," and "neuronal migration." Future research may emphasize exploring aspects such as gut microbiota, genes, stress, maternal immune activation, memory, and neurodevelopmental disorders of ASD., Conclusion: This study, through bibliometric analysis of key indicators such as nations, institutions, journals, authors, and keywords, provides a comprehensive overview of the current state of research on ASD Signaling Pathways. These investigations predominantly focus on molecular mechanisms, animal model studies, population-based research, and the structure and function of neurosystems. Future research directions are also clearly proposed. First, in-depth research on the genes and neurodevelopmental disorders associated with ASD will continue to reveal the genetic basis and provide support for precise treatments. At the same time, attention to the gut microbiota will help explore its association with ASD, which may provide clues for new treatments. In addition, the relationship between stress and ASD will become the focus of research to understand better the emotional and behavioral characteristics of ASD patients in stressful situations. Maternal immune activation will also be further studied to explore how environmental factors influence the risk and development of ASD. Finally, a deeper understanding of the cognitive functions of patients with ASD, especially memory and learning, will help develop individualized treatment strategies to improve patients' quality of life. These directions will work together and are expected to provide a more comprehensive understanding of Signaling Pathways research in ASD and provide new ideas and opportunities for future intervention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lyu, Li, Chen, Li, Zhang, Hu, Zhang and Feng.)

Forkhead box protein 3 (FOXP3), traditionally recognized as a specific transcription factor for regulatory T cells (Tregs), has also been identified in various tumor epithelial cells (named as cancer-FOXP3, c-FOXP3). However, the natural state and functional role of FOXP3 positive tumor epithelial cells remain unknown. Monoclonal cells expressing varying levels of c-FOXP3 were isolated from established PANC-1 cells using limited dilution. Whole transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) were conducted on these subsets, followed by in vitro and in vivo functional investigations. In addition, we identified c-FOXP3 + E-cadherin - epithelial cells in human pancreatic cancer tissues after radical resection by immunofluorescence co-staining. We also investigated the connection between c-FOXP3 + E-cadherin - epithelial cells and their clinicopathological features. Our study uncovered a distinct subset of c-FOXP3 + tumor epithelial cells characterized by reduced E-cadherin expression. C-FOXP3 + E-cadherin - cells displayed significant proliferation potential and pro-angiogenic effect through the expression of chemokines, including C-X-C motif ligand 1 (CXCL1), C-X-C motif ligand 5 (CXCL5), and C-X-C motif ligand 8 (CXCL8). Notably, higher counts of c-FOXP3 + E-Cadherin - cells correlated with poorer prognosis, lower tumor differentiation, lymph node metastasis, and vascular invasion in pancreatic ductal adenocarcinoma (PDAC). In conclusion, this work revealed the stable expression of FOXP3 in tumor epithelial cells, marking a distinct subset. C-FOXP3 + E-cadherin - epithelial cells exhibit active proliferation and promote angiogenesis in a vascular endothelial growth factor A (VEGFA) independent manner. These findings provide novel insights into PDAC prognosis and therapeutic avenues. NEW & NOTEWORTHY In this study, we revealed a novel c-FOXP3 + tumor epithelial cell subset marked by diminished E-cadherin and stable FOXP3 expression. These subpopulations not only show robust proliferation and drive angiogenesis via CXCL1, CXCL5, and CXCL8, bypassing VEGFA pathways, but their heightened presence also correlates with adverse PDAC outcomes. By challenging traditional epithelial cell definitions and extending lymphocyte markers to these cells, our findings present innovative targets for PDAC treatment and enrich our understanding of cell biology.

With the global warming and rapid urbanization in China, the urban built environment has undergone rapid changes, and the land surface temperatures (LSTs) of urban communities have obvious spatial heterogeneity. To explore the key driving factors of community LSTs, the multi-source data and spatial statistical methods being jointly used to analyze the spatial characteristics and main influencing factors of LST at the community level in the Beilin District of Xi'an City, China. The results are as follows: (1) Compared with communities dominated by construction land, communities with large area of green space and water bodies have lower LST. (2) According to the Akaike's information criterion (AICc) and maximum of adjusted R 2 , and other parameters, the No.1236 model was selected as the optimal model to analyze the influencing factors of community LST by exploratory data analysis, including building density (BD), building height standard deviation (BHS), percentage of public administration and public services land (PASL), percentage of green space and square land (PGSL), population density (POPD), normalized difference impervious surface index (NDISI), and perimeter-area fractal dimension (PAFRAC). (3) For each increase of one unit in NDISI and BHS when other factors remain unchanged, the LST will increase by 0.569 °C and decrease by 0.478 °C, respectively. (4) From the spatial stability and distribution of Local-R 2 , the warming factors of community LST are mainly NDISI, PAFRAC, BD, and PASL, while the cooling factors are BHS and PGSL. The spatial heterogeneity of community LST is not only related to the change of underlying surface properties but is also affected by intra-urban architectural morphology. Therefore, reasonable planning of urban built environment is of great significance for mitigating heat islands., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway., (© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

With the popularity of video surveillance technology, people are paying more and more attention to how to detect abnormal states or events in videos in time. Therefore, real-time, automatic and accurate detection of abnormal events has become the main goal of video-based surveillance systems. To achieve this goal, many researchers have conducted in-depth research on online video anomaly detection. This paper presents the background of the research in this field and briefly explains the research methods of offline video anomaly detection. Then, we sort out and classify the research methods of online video anomaly detection and expound on the basic ideas and characteristics of each method. In addition, we summarize the datasets commonly used in online video anomaly detection and compare and analyze the performance of the current mainstream algorithms according to the evaluation criteria of each dataset. Finally, we summarize the future trends in the field of online video anomaly detection.

Dusky-like (Dyl) is a transmembrane protein containing a zona pellucida domain. Its physiological roles during metamorphosis have been well explored in Drosophila melanogaster and have also been documented in Tribolium castaneum . However, Dyl has undergone a functional shift between Diptera and Coleoptera insects. Further investigation of Dyl in other insects will be helpful to further clarify its function in insect growth and development. Henosepilachna vigintioctopunctata is an important Coleoptera that causes enormous economic losses in agriculture in China. In this study, we found that the expression of Hvdyl was detectable in embryos, larvae, prepupae, pupae, and adults. We knocked down Hvdyl in third- and fourth-instar larvae and pupae with RNA interference (RNAi). RNAi of Hvdyl mainly caused two phenotypic defects. Firstly, the growth of epidermal cellular protuberances was suppressed. Injection of ds dyl (double-stranded dusky-like RNA) at the third-instar larval stage truncated the scoli throughout the thorax and abdomen and shortened the setae on the head capsules and mouthparts of the fourth-instar larvae. Introduction of ds dyl at the third- and fourth-instar stages led to misshapen pupal setae. The setae were shortened or became black nodules. Treatment with ds dyl at the larval and pupal stages resulted in deformed adults with completely suppressed wing hairs. Moreover, the knockdown of Hvdyl at the third-instar stage caused deformed larval mouthparts at the fourth-instar period. As a result, foliage consumption was inhibited, and larval growth was slowed. The results indicate that Dyl is associated with the growth of cellular protuberances throughout development and with the formation of the cuticle in H. vigintioctopunctata .

Hybridization is widely recognized as promoting both species and phenotypic diversity. However, its role in mammalian evolution is rarely examined. We report historical hybridization among a group of snub-nosed monkeys ( Rhinopithecus ) that resulted in the origin of a hybrid species. The geographically isolated gray snub-nosed monkey Rhinopithecus brelichi shows a stable mixed genomic ancestry derived from the golden snub-nosed monkey ( Rhinopithecus roxellana ) and the ancestor of black-white ( Rhinopithecus bieti ) and black snub-nosed monkeys ( Rhinopithecus strykeri ). We further identified key genes derived from the parental lineages, respectively, that may have contributed to the mosaic coat coloration of R. brelichi , which likely promoted premating reproductive isolation of the hybrid from parental lineages. Our study highlights the underappreciated role of hybridization in generating species and phenotypic diversity in mammals.

Peptide labeling by isobaric tags is a powerful approach for the relative quantitative analysis of proteomes in multiple groups. There has been a revolution in the innovation of new isobaric reagents; however, great effort is being made to expand simultaneous labeling groups to identify more labeled peptides and reduce reporter ion signal suppression. We redesigned the original chemical structure of the deuterium isobaric amine-reactive tag developed in our laboratory. We optimized the synthetic pathway to create a new set of 16-plex isobaric tags (IBT-16plex). The novel reagent enabled almost complete labeling of peptides within 90 min, with all labeling reporter ions exhibiting comparable MS/MS signals. Compared to a typical 16plex reagent, TMTpro-16plex, the peptides and proteins identified by IBT-16plex in trypsinized HeLa cells were significantly increased by 14.8 and 8.6%, respectively. Moreover, differences in peptide abundance within 10-fold among multiple groups were barely suppressed in IBT-16plex, whereas the dynamic range in TMTpro-16plex-labeled groups was smaller. After quantitative examination of MCF7 cell proteins, IBT-16plex was confirmed as feasible and useful for evaluating protein responses of glucose-starved MCF7 cells to a glucose-rich medium.

The technique of pig cloning holds great promise for the livestock industry, life science, and biomedicine. However, the prenatal death rate of cloned pig embryos is extremely high, resulting in a very low cloning efficiency. This limits the development and application of pig cloning. In this study, we utilized embryo biopsy combined with microproteomics to identify potential factors causing the developmental arrest in cloned pig embryos. We verified the roles of two potential regulators, PDCD6 and PLK1 , in cloned pig embryo development. We found that siRNA-mediated knockdown of PDCD6 reduced mRNA and protein expression levels of the pro-apoptotic gene, CASP3 , in cloned pig embryos. PDCD6 knockdown also increased the cleavage rate and blastocyst rate of cloned porcine embryos. Overexpression of PLK1 via mRNA microinjection also improved the cleavage rate of cloned pig embryos. This study provided a new strategy to identify key factors responsible for the developmental defects in cloned pig embryos. It also helped establish new methods to improve pig cloning efficiency, specifically by correcting the expression pattern of PDCD6 and PLK1 in cloned pig embryos.

Accumulating evidence suggests that astrocytes, the abundant cell type in the central nervous system (CNS), play a critical role in maintaining the immune response after cerebral infarction, regulating the blood-brain barrier (BBB), providing nutrients to the neurons, and reuptake of glutamate. The circadian clock is an endogenous timing system that controls and optimizes biological processes. The central circadian clock and the peripheral clock are consistent, controlled by various circadian components, and participate in the pathophysiological process of astrocytes. Existing evidence shows that circadian rhythm controls the regulation of inflammatory responses by astrocytes in ischemic stroke (IS), regulates the repair of the BBB, and plays an essential role in a series of pathological processes such as neurotoxicity and neuroprotection. In this review, we highlight the importance of astrocytes in IS and discuss the potential role of the circadian clock in influencing astrocyte pathophysiology. A comprehensive understanding of the ability of the circadian clock to regulate astrocytes after stroke will improve our ability to predict the targets and biological functions of the circadian clock and gain insight into the basis of its intervention mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhao, Zhang, Zeng, Yan, Chen, Li, Zhou and Liu.)

The circadian rhythm is an endogenous clock system that coordinates and optimizes various physiological and pathophysiological processes, which accord with the master and the peripheral clock. Increasing evidence indicates that endogenous circadian rhythm disruption is involved in the lesion volume and recovery of ischemic stroke. As a critical recovery mechanism in post-stroke, angiogenesis reestablishes the regional blood supply and enhances cognitive and behavioral abilities, which is mainly composed of the following processes: endothelial cell proliferation, migration, and pericyte recruitment. The available evidence revealed that the circadian governs many aspects of angiogenesis. This study reviews the mechanism by which circadian rhythms regulate the process of angiogenesis and its contribution to functional recovery in post-stroke at the aspects of the molecular level. A comprehensive understanding of the circadian clock regulating angiogenesis in post-stroke is expected to develop new strategies for the treatment of cerebral infarction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Liu, Zhao, Yan, Zeng and Zhou.)

Twelve Rho-related proteins (ROPs), namely PbROPs, were identified from the genome of the recently sequenced ' Duli ' pear ( Pyrus betulifolia Bunge), a wild-type pear variety routinely used for rootstocks in grafting in China. The length and molecular weight of these proteins are between 175 and 215 amino acids and 19.46 and 23.45 kDa, respectively. The 12 PbROPs are distributed on 8 of the 17 chromosomes, where chromosome 15 has the highest number of 3 PbROPs . Analysis of the deduced protein sequences showed that they are relatively conserved and all have the G domain, insertion sequence, and HVR motif. The expression profiles were monitored by quantitative RT-PCR, which showed that these 12 PbROP genes were ubiquitously expressed, indicating their involvement in growth and development throughout the life cycle of ' Duli ' pear. However, they were altered upon treatments with abscisic acid (ABA, mimicking abiotic stress), polyethylene glycol (PEG, mimicking drought), and sodium chloride (NaCl, mimicking salt) to tissue-cultured seedlings. Further, transgenic Arabidopsis expressing PbROP1 , PbROP2 , and PbROP9 exhibited enhanced sensitivity to ABA, demonstrating that these 3 PbROPs may play important roles in the abiotic stress of ' Duli ' pear. The combined results showed that the ' Duli ' genome encodes 12 typical ROPs and they appeared to play important roles in growth, development, and abiotic stress. These preliminary data may guide future research into the molecular mechanisms of these 12 PbROPs and their utility in molecular breeding for abiotic stress-resistant ' Duli ' pear rootstocks.

Polyolefins with branches produced by ethylene alone via chain walking are highly desired in industry. Selective branch formation from uncontrolled chain walking is a long-standing challenge to generate exclusively branched polyolefins, however. Here we report such desirable microstructures in ethylene polymerization by using sterically constrained α-diimine nickel(II)/palladium(II) catalysts at 30 °C-90 °C that fall into industrial conditions. Branched polyethylenes with exclusive branch pattern of methyl branches (99%) and notably selective branch distribution of 1,4-Me 2 unit (86%) can be generated. The ultrahigh degree of branching (>200 Me/1000 C) enables the well-defined product to mimic ethylene-propylene copolymers. More interestingly, branch distribution is predictable and computable by using a simple statistical model of p(1-p) n (p: the probability of branch formation). Mechanistic insights into the branch formation including branch pattern and branch distribution by an in-depth density functional theory (DFT) calculation are elucidated., (© 2022. The Author(s).)

Vascular hyporesponsiveness in the shock decompensation period is an important factor leading to death. Myosin light chain 20 (MLC 20 ) is the main effector protein that regulates vascular reactivity. However, whether the change in semicarbazide-sensitive amine oxidase (SSAO) expression during hypoxia can change the MLC 20 phosphorylation level, and its underlying mechanism were not clear. The amine oxidase copper containing 3 (AOC3) overexpressing adenovirus vector was constructed and transfected into rat intestinal microvascular endothelial cells (RIMECs) to overexpress SSAO, and the RIMECs were co-cultured with rat intestinal microvascular smooth muscle cells (RIMSCs). The changes in SSAO/inducible nitric oxide synthase (iNOS)/Rho associate coiled-coil containing protein kinase 1 (ROCK1) expression levels and MLC 20 phosphorylation level were detected. Here we found that the increased SSAO by AOC3 overexpression can decrease the iNOS expression level and its activity after hypoxia. In addition, RIMSCs co-cultured with RIMECs overexpressed with AOC3 gene had significantly higher ROCK1 protein level and MLC 20 phosphorylation level than RIMSCs co-cultured with normal RIMECs. Our study demonstrated that SSAO overexpression can significantly inhibit iNOS activity, promote RhoA/ROCK pathway activation, and increase the phosphorylation level of MLC 20 , which might be the potential mechanism in relieving the vascular hyporesponsiveness during shock decompensation., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2021 Yuxing Zhang et al., published by De Gruyter.)

The Eucalyptus spp. is fast-growing and is usually harvested at a young age, which enables efficient and sufficient timber supply. However, its negative impact on soil fertility incurs wide debates. Therefore it is necessary to study on the growing traits of eucalytpus to provide scientific guidance on its plantation management and associated policy-making. In this study, we collected the sample plot data from 9 National Forest Inventories (NFIs) during 1973-2018, China Forest-Land Database Map in 2003 and 2016, as well as climate and elevation data and analyzed how the spatial distribution of eucalyptus plantations in China changes with time. We quantitatively characterized and evaluated the productivity, carbon accumulation capacity, and abandonment rate of eucalyptus plantations. Statistical models on how eucalyptus productivity and abandonment rate change with time are established to evaluate the soil fertility and feasibility for growing eucalyptus plantations and predict the temporal productivity variation. The results show that regions with annual mean temperature of 19-21 °C, annual precipitation of 1400-1600 mm, and elevation of 0-300 m above sea level is most suitable for the growth of eucalyptus. The annual mean productivity of eucalyptus plantations ranges from 4.14-8.57 m 3  hm -2  a -1 . Higher productivity (9.32-10.88 m 3  hm -2  a -1 ) could be reached in newly cultivated lands. Based on data from the 9th inventory (2014-2018), the mean carbon fixation of eucalyptus is 5.29 t hm -2  a -1 , which is 2.95 and 2.18 times greater than Pinus massoniana Lamb. and Cunninghamia lanceolata Lamb. Its plantations area accounts for 6.85% of total plantations in China, but it contributes to more than 17.96% of total annual cut from plantations. In Guangdong and Guangxi provinces, areas of eucalyptus plantations are 30.32% and 34.91% of the total plantation area in each province respectively, but eucalyptus plantations contribute to 66.29% and 49.97% of harvested timber stock volume Eucalyptus pla consumes soil fertility significantly. The cumulative abandonment rate (based on area) is about 25%, 50%, and 75% after 5, 10, and 20 years of growing eucalyptus, respectively. The soil fertility decreases significantly after 50 years of growing eucalyptus continuously. In such case, it is difficult to restore the soil fertility. It is suggested that with improved management measures such as proper crop rotation rotating crops properly, it is possible for the abandoned plantations to be reused for growing eucalyptus. Currently the rates of replanting eucalyptus are still below 20% and 30% after 20 and 50 years of without growing eucalyptus, respectively. Although the proportion of eucalyptus area replanted to its abandoned area is now less than 20% in 20 years and less than 30% in 50 years, there is potential to keep increasing the replanting rate. We argue that developing eucalyptus plantations could contribute to global timber supply, help to protect natural forests, increase global carbon storage and fixation, and help to slow down global warming. In conclusion, we should not stop growing eucalyptus despite its high consumption of soil fertility., (© 2021. The Author(s).)

Branched polyolefin microstructures resulting from so-called "chain walking" are a fascinating feature of late transition metal catalysts; however, to date it has not been demonstrated how desirable branched polyolefin microstructures can be generated thereby. We demonstrate how highly branched polyethylenes with methyl branches (220 Me/1000 C) exclusively and very high molecular weights (ca. 10 6  g mol -1 ), reaching the branch density and microstructure of commercial ethylene-propylene elastomers, can be generated from ethylene alone. At the same time, polar groups on the main chain can be generated by in-chain incorporation of methyl acrylate. Key to this strategy is a novel rigid environment in an α-diimine Pd II catalyst with a steric constraint that allows for excessive chain walking and branching, but restricts branch formation to methyl branches, hinders chain transfer to afford a living polymerization, and inverts the regioselectivity of acrylate insertion to a 1,2-mode., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The N 6 -Methyladenosine (m 6 A) modification plays an important role in many biological processes, especially tumor development. However, little is still known about how it affects colorectal cancer (CRC) carcinogenesis. Here, we first systematically investigate the association of variants related to m 6 A modification with the CRC risk in 1,062 CRC cases and 2,184 controls by using our exome-wide association data and followed by two replication sets including 7,341 CRC cases and 7,902 controls. The variant rs8100241 located in ANKLE1 was significantly associated with CRC risk (odds ratio = 0.88, 95% confidence interval = 0.84-0.92, p = 4.85 × 10 -8 ) in 8,403 cases and 10,086 controls. This variant was previously identified to be associated with the susceptibility of breast cancer with BRCA1 mutation triple negative breast cancer. Further functional analysis indicated that overexpression of the rs8100241[A] allele significantly increased the ANKLE1 m 6 A level and facilitated the ANKLE1 protein expression compared to that of rs8100241[G] allele. We further found the ANKLE1 m 6 A modification was catalyzed by the "writer" complex (METTL3, METTL14, or WTAP) and recognized by the "reader" YTHDF1. Mechanistically, we found that the ANKLE1 functions as a potential tumor suppressor that inhibits cell proliferation and facilitates the genomic stability. An elevated frequency of micronucleated cells, increased cell proliferation, and colony formation ability were observed when ANKLE1 knockdown. Our study illustrated that the germline missense variant can increase CRC risk by influencing ANKLE1 m 6 A level, highlighting a clinical potential of variants-associated m 6 A modification as a risk marker for CRC prevention., (© 2019 UICC.)

Pt-based one-dimensional hollow nanostructures are promising catalysts in fuel cells with excellent activity. Herein, one-dimensional hollow FePt nanochains were shown to be efficient nanocatalysts in the hydrolysis of NaBH 4 . The characterization of composition, structure and morphology identifies an ultrathin shell (∼3 nm) with uniformly distributed Fe 30 Pt 70 constituents. The H 2 generation rate of hollow Fe 30 Pt 70 nanochains achieves 16.9 l/(min · g) at room temperature, while the activation energy is as low as 17.6 kJ mol -1 based on the fitting over the whole reaction time span. After the catalysis of NaBH 4 hydrolysis, the morphology and composition of hollow FePt nanochains remain unchanged. Furthermore, the structural stability of hollow FePt nanochains under Ga + ion irradiation is clarified. Theoretical simulation indicates that the stopping range of such a Fe 30 Pt 70 shell is 7.7 keV, which offers a prediction that structure evolves diversely under Ga + ions below and above such energy. The Ga + ion irradiation experiments show a consistent trend with the simulation, where Ga + ions with kinetic energy of 30 keV make the hollow architecture subside and sputter away, while Ga + ions with kinetic energy of 5 keV only etch the top and lead to an eggshell structure.

Purpose: We investigated the effectiveness of the Charlson comorbidity index (CCI) for predicting postoperative 30-day complications and long-term survival outcomes of elderly patients who underwent laparoscopic surgery for colon cancer with radical intent., Methods: We reviewed 178 patients aged ≥70 years who underwent laparoscopic surgery for colon cancer with radical intent between January 2008 and December 2015. Patients were divided into high CCI (CCI ≥ 3; n=71) and low CCI (CCI < 3; n=107) groups for comparative analyses of differences in their short- and long-term outcomes., Results: Postoperative 30-day complications were more frequent in the high CCI group than in the low CCI group. Logistic regression analysis revealed that a high CCI was significantly predictive of postoperative 30-day complications. The 5-year overall survival (OS) rates were 65% and 54% for the low and high CCI groups, respectively (p=0.034) and their 5-year disease-free survival (DFS) rates were 60% and 47%, respectively (p=0.030)., Conclusion: CCI predicted the likelihood of postoperative 30-day complications and long-term survival outcomes of elderly patients who underwent laparoscopic surgery for colon cancer with radical intent.

Aloperine is a quinolizidine alkaloid extracted from the leaves of Sophora plants. It has been recognized with the potential to treat inflammatory and allergic diseases as well as tumors. In this report, we demonstrate that pretreatment with aloperine provided protection for mice against ischemia-reperfusion (IR)-induced acute renal injury as manifested by the attenuated inflammatory infiltration, reduced tubular apoptosis, and well-preserved renal function. Mechanistic studies revealed that aloperine selectively repressed IL-1β and IFN-γ expression by regulating PI3K/Akt/mTOR signaling and NF-κB transcriptional activity. However, aloperine did not show a perceptible impact on IL-6 and TGF-β expression and the related Jak2/Stat3 signaling. It was also noted that aloperine regulates AP-1 activity, through which it not only enhances SOD expression to increase reactive oxygen species (ROS) detoxification but also promotes the expression of antiapoptotic Bcl-2, thereby preventing tubular cells from IR-induced apoptosis. Collectively, our data suggest that administration of aloperine prior to IR insults, such as renal transplantation, could be a viable approach to prevent IR-induced injuries.

Background: Human telomeres, tandem repeats of TTAGGG nucleotides at the ends of chromosomes, are essential for maintaining genomic integrity and stability. Results of previous epidemiologic studies about the association of telomere length with risk of colorectal cancer (CRC) have been conflicting., Methods: A case-control study was conducted in a Han population in Wuhan, central China. The relative telomere length (RTL) was measured in peripheral blood leukocytes (PBLs) using quantitative real-time polymerase chain reaction (PCR) in 628 CRC cases and 1,256 age and sex frequency matched cancer-free controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression models to evaluate the association between RTL and CRC risk., Results: Using median RTL in the controls as the cutoff, individuals with shorter RTL were associated with a significantly increased risk of CRC (adjusted OR = 1.27, 95%CI: 1.05-1.55). When participants were further categorized into 3 and 4 groups according to the tertile and quartile RTL values of controls, significant relationships were still observed between shorter RTL and increased CRC risk (OR per tertile = 1.13, 95%CI: 1.00-1.28, P(trend) = 0.045; OR per quartile = 1.12, 95%CI: 1.03-1.23, P(trend) = 0.012). In stratified analyses, significant association between shorter RTL and increased CRC risk was found in females, individuals younger than 60 years old, never smokers and never drinkers., Conclusions: This study suggested that short telomere length in PBLs was significantly associated with an increased risk of CRC in Chinese Han population. Further validation in large prospective studies and investigation of the biologic mechanisms are warranted.

Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell lines. In this study, we investigate how oleuropein strongly induces apoptotic cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells apoptosis as demonstrated by induction of a sub-G(1) peak in flow cytometry and apoptosis-related morphological changes observed by fluorescence microscopy after being stained by Hoechst 33324. The results also showed that 150 - 200 μM oleuropein&ndash;treated HeLa cells were arrested at the G(2)/M phase. Western blot analysis revealed that the phosphorylated ATF-2, c-Jun NH(2)-terminal kinase (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm significantly increased in a dose-dependent manner after treatment of oleuropein for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK signaling, which formed mitochondrial membrane channels, accounted for releasing of cytochrome c and activation of caspase-9 and -3. SP600125 (20 μM), a JNK(1/2) inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by oleuropein at 200 μM. Thus, oleuropein-induced apoptosis was activated by the JNK/SPAK signal pathway. The result shows that oleuropein holds promise as a potential chemotherapeutic agent for the treatment of HeLa cells.

Cancer stem cells (CSCs) are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.

The murine double minute 2 protein (MDM2) and TP53 interact in regulating cell cycle, DNA repair and apoptosis process, which is crucial in carcinogenesis. Since functional variations in these two genes were shown to change gene expression and function, we hypothesized that potentially functional polymorphisms in these genes may contribute to colorectal cancer (CRC) susceptibility. A hospital-based case-control study consisting of 444 patients and 569 controls was conducted to explore the associations between TP53 Arg72Pro and MDM2 T309G and CRC risk in Chinese. The combined effect of TP53 Arg72Pro and MDM2 T309G was significant in a gene dose-response increasing CRC risk (trend test: P = 0.02). Individuals carrying 3 or more potential risk alleles had 1.78 times risk (95 % CI: 1.13-2.80) to develop CRC compared with individuals without potential risk allele. This increased cancer risk was more pronounced in smokers who carried 3-4 potential risk alleles (OR = 2.75, 95 % CI: 1.14-6.60) and in young subjects (OR = 2.05, 95 % CI: 1.08-3.88). The gene-gene interaction between TP53 Arg72Pro and MDM2 T309G may interact in carcinogenesis of CRC in Chinese, especially in smokers, and this kind of interaction is associated with onset age of CRC.

Abstract Cellular redox homeostasis is the first line of defense against diverse stimuli and is crucial for various biological processes. Reactive oxygen species (ROS), byproducts of numerous cellular events, may serve in turn as signaling molecules to regulate cellular processes such as proliferation, differentiation, and apoptosis. However, when overproduced ROS fail to be scavenged by the antioxidant system, they may damage cellular components, giving rise to senescent, degenerative, or fatal lesions in cells. Accordingly, this review not only covers general mechanisms of ROS production under different conditions, but also focuses on various types of ROS-involved diseases, including atherosclerosis, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, and cancer. In addition, potentially therapeutic agents and approaches are reviewed in a relatively comprehensive manner. However, due to the complexity of ROS and their cellular impacts, we believe that the goal to design more effective approaches or agents may require a better understanding of mechanisms of ROS production, particularly their multifaceted impacts in disease at biochemical, molecular, genetic, and epigenetic levels. Thus, it requires additional tools of omics in systems biology to achieve such a goal. Antioxid. Redox Signal. 15, 2867-2908.

Cisplatin, as a first-line drug in the chemotherapy of ovarian cancer, poses significant problems in its toxicity to normal tissue and drug resistance. Here, we report that Tetrandrine, with potent anti-cancer effect, significantly enhances the cytotoxicity of cisplatin in ovarian cancer. The in vitro assay indicates that Tetrandrine can markedly increase growth suppression and apoptosis induced by cisplatin and cause redistribution of the cell cycle. Further assay indicates that modulation of Wnt/cadherin signaling pathway contributes to the chemosensitizing effect of Tetrandrine on the cytotoxicity of cisplatin in ovarian cancer. In vivo, the combination of Tetrandrine and cisplatin exhibits the strongest anti-cancer effect compared with each drug alone, with no obvious additional toxicity. These results provide rational evidence supporting the application of Tetrandrine as an adjunct to cisplatin in improvement of chemotherapy in ovarian cancer., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

In this paper, we present a direct method to characterize a piezoelectric film that is sandwiched with two electrodes and deposited on a substrate to form a four-layer thickness extension mode composite resonator (also known as over-moded resonator). Based on the parallel and series resonant frequency spectra of a composite resonator, the electromechanical coupling factor, the density and the elastic constant of the piezoelectric film can be evaluated directly. Experimental results on samples consisting of ZnO films on fused quartz substrates with different thickness are presented. They show good agreement with theoretical prediction. The mechanical effect of the electrode on the method is investigated, and numerical simulation shows that the effect of the electrodes can be properly corrected by the modified formulae presented in this paper. The effect of mechanical loss in piezoelectric film and in substrate on this method also has been investigated. It is proven that the method is insensitive to the losses.

Objective: The purpose of this study is to compare the fracture strengths of custom-fabricated Celay all-ceramic post-core, custom cast metal post-core, and prefabricated stainless steel post (Parapost) plus composite resin core with or without a 2.0 mm dentine ferrule., Methods: A total of 60 recently extracted human maxillary central incisors were endodontically treated and divided into five groups of 12. They were given the following treatments: Group A: Celay ceramic post-core with 2.0 mm dentine ferrule, Group B: Celay ceramic post-core with no dentine ferrule, Group C: cast metal post-core with 2.0 mm dentine ferrule, Group D: cast metal post-core with no dentine ferrule, and Group E: prefabricated post and composite core with 2.0 mm dentine ferrule. All specimens were stored at 100% humidity at room temperature for 30 days before testing. Each specimen was in a special jig at a 45 degrees angle to the long axis and subjected to a load on MTS 810 universal material testing machine until failure, with crosshead speed of 0.02 cm/min. Analysis of variance followed by the Newman-Keuls pairwise multiple comparison test was used to compare the results of the groups tested., Results: There was a statistically significant difference between five groups (P < 0.01). Celay ceramic post-core with 2.0 mm dentine ferrule (758.35 N +/- 119.26 N) and cast metal post-core with 2.0 mm dentine ferrule (756.63 N +/- 166.22 N) had a significantly larger mean failure threshold for fracture than the other three groups which had no significant difference between each other. There was a statistically significant difference between the fracture resistance of Celay post-core restored teeth with and without 2.0 mm dentine ferrule., Conclusion: The custom-fabricated Celay post-core could be a choice for clinical use in endodontically treated tooth when the final restoration is an all-ceramic crown and the preparation has a 2.0 mm dentine ferrule.

Objective: To investigate the influence of post-core structure on the strength of endodontically treated and crowned teeth with or without a 2.0 mm dentine ferrule., Methods: A total of 60 recently extracted human maxillary central incisors were endodontically treated and randomly divided into five groups of 12. They were given following treatments: Group A, endodontically treated; Group B, endodontically treated and crowned (PFM); Group C, cast metal post-core with 2.0 mm dentine ferrule and crowned (PFM); Group D, cast metal post-core with no dentine ferrule and crowned (PFM); Group E, prefabricated post and composite core with 2.0 mm dentine ferrule and crowned (PFM). All specimens were stored at 100% humidity at room temperature for 30 days before testing. Each specimen was in a special jig on the MTS 810 universal material testing machine and subjected to a load at a 135-degree angle to the long axis until failure, with crosshead speed of 0.02 cm/minute. Analysis of variance followed by the Newman-Keuls pairwise multiple comparison tests was used to compare the results., Results: There was a statistically significant difference between different restorative methods. The cast metal post-core with 2.0 mm dentine ferrule and crowned teeth had the highest fracture strength (1793.59 +/- 387.93N), followed by endodontically treated intact teeth (1466.68 +/- 240.11N). No significant difference in the fracture strength was found among the other three groups (958.49 +/- 286.02N; 992.98 +/- 291.00N; 994.94 +/- 285.04 N). There was a statistically significant difference in the fracture resistance between crowned teeth with and without 2.0 mm dentine ferrule (P < 0.01)., Conclusions: Not all post-core structure could improve the strength of endodontically treated teeth. The dentine ferrule can effectively improve the fracture resistance of endodontically treated and crowned teeth.