bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone marrow mesenchymal stem cells inhibit cardiac hypertrophy by enhancing FoxO1 transcription
Authors: Qiu Jiantao , Xiao Huaiteng , Zhou Shunchang , Du Weimin , Mu Xiang , Shi Guangjun , Tan Xueying
Published: October 2020

Bone marrow–derived mesenchymal stem cells (BMSCs) have therapeutic potential for certain heart diseases. Previous studies have shown that stem cells inhibit cardiac hypertrophy; however, it is necessary to explore the mechanisms underlying this effect. This study aimed to investigate the possible mechanism underlying the inhibitory effect of BMSCs on cardiomyocyte hypertrophy. We induced cardiomyocyte hypertrophy in cultured rat cells through isoproterenol (ISO) treatment with or without BMSC coculture. A microarray was performed to analyze messenger RNA expression in response to ISO treatment and BMSC coculture. Pathway enrichment analysis showed that the expression of differential genes was closely related to the 5′‐adenosine monophosphate‐activated protein kinase (AMPK) signaling pathway and that the expression of forkhead box O 1 (FoxO1) was significantly increased in the presence of BMSCs. Furthermore, we determined the expression levels of p‐AMPK/AMPK and p‐FoxO1/FoxO1 by western blot analysis. The expression of p‐AMPK/AMPK was upregulated, whereas that of p‐FoxO1/FoxO1 was downregulated upon coculturing with BMSCs. The AMPK‐specific antagonist Compound C inhibited the downregulation of p‐FoxO1/FoxO1 induced by the BMSC coculture. Furthermore, treatment with the specific FoxO1 antagonist AS1842856 reduced the inhibitory effects of BMSCs on cardiomyocyte hypertrophy in vivo and in vitro. Our present study demonstrates the inhibition of cardiomyocyte hypertrophy by BMSCs, which occurs partly through the AMPK–FoxO1 signaling pathway.
Advances and Fundamental Understanding of Electrocatalytic Methane Oxidation
Authors: Abdelkader Mohamed Aya Gomaa , Zahra Naqviab Syeda Andleeb , Wang Yaobing
Published: October 2020

Methane utilization is one of the promising energy‐efficient conversions which can potentially control its emissions as an additional benefit. In this regard, electrochemically methane conversion is particularly attractive as a fossil‐free and sustainable strategy to generate power and fuels of global importance. However, it is relatively less explored. This review aims to highlight the feasibility of the electro‐conversion approach via electrocatalytic methane oxidation (EMO) reaction. The recent progress regarding power generation as well as value‐added fuel/chemical production, such as hydrocarbons, alcohols, acids, and ketones, is summarized. Additional mechanistic insights to increase the fundamental understanding of the EMO reaction pathways underlying various catalytic modes and their challenges are provided. Theoretical modeling focusing on the reactivity trends and performance kinetics is also presented, along with key recommendations for the material design that need to be addressed. Suggesting some insights on catalysts‐related developing directions and chances in the EMO field is concluded.
Ordered Mesoporous Carbon Nitrides with Tuneable Nitrogen Contents and Basicity for Knoevenagel Condensation
Authors: Ruban Sujanya Maria , Sathish C. I. , Ramadass Kavitha , Joseph Stalin , Kim Sungho , Dasireddy Venkata D. B. C. , Young Kim In , Al‐Muhtaseb Ala'a H. , Sugi Yoshihiro , Vinu Ajayan
Published: October 2020

We report on the preparation of ordered mesoporous carbon nitrides (MCN) with a 3D porous structure, tuneable nitrogen contents and basicity and their basic catalytic activities on the Knoevenagel condensation of benzaldehyde with malononitrile. The chemical structure and the nitrogen contents of the materials are finely tuned with the simple adjustment of the calcination temperature from 350 to 550 °C. The samples prepared at 350 and 400 °C exhibit C3N5 structures with 1‐amino/imino‐1,2,4‐triazole moieties, whereas the samples synthesised at 450, 500, and 550 °C possess C3N4 structures with 2‐amino/imino‐1,3,5‐triazine moieties. The materials prepared at the temperature lower than 400 °C show much higher activity than those of the samples prepared at 450, 500 and 550 °C. The change in the catalytic activities of these materials is linked with the change of the structure, nitrogen contents and the functional groups on the surface of the materials prepared at different temperatures. CO2 temperature programme desorption study reveals that 1‐amino/imino‐1,2,4‐triazole moieties in C3N5 samples provide high basicity due to the strain in 5‐membered 1,2,4‐triazole rings; however, the samples with 1,3,5‐triazine moieties have limited basicity which significantly affects the catalytic activity of the material. The optimised C3N5 catalyst shows an enhanced catalytic activity when compared to other mesoporous basic catalysts and C3N4. It is also found that the optimised catalysts are highly stable and can be recycled several times and no major change in the activity is observed.
Experimental and Computational Studies towards Chemoselective C−F over C−Cl Functionalisation: Reversible Oxidative Addition is the Key
Authors: Jacobs Emily , Keaveney Sinead T.
Published: October 2020

Catalytic cross‐coupling is a valuable tool for forming new carbon‐carbon and carbon‐heteroatom bonds, allowing access to a variety of structurally diverse compounds. However, for this methodology to reach its full potential, precise control over all competing cross‐coupling sites in poly‐functionalised building blocks is required. Carbon‐fluorine bonds are one of the most stable bonds in organic chemistry, with oxidative addition at C−F being much more difficult than at other C‐halide bonds. As such, the development of methods to chemoselectively functionalise the C−F position in poly‐halogenated arenes would be very challenging if selectivity was to be induced at the oxidative addition step. However, metal‐halide complexes exhibit different trends in reactivity to the parent haloarenes, with metal‐fluoride complexes known to be very reactive towards transmetalation. In this current work we sought to exploit the divergent reactivity of Ni−Cl and Ni−F intermediates to develop a chemoselective C−F functionalisation protocol, where selectivity is controlled by the transmetalation step. Our experimental studies highlight that such an approach is feasible, with a number of nickel catalysts shown to facilitate Hiyama cross‐coupling of 1‐fluoronapthalene under base free conditions, while no cross‐coupling with 1‐chloronapthalene occurred. Computational and experimental studies revealed the importance of reversible C−Cl oxidative addition for the development of selective C−F functionalisation, with ligand effects on the potential for reversibility also presented.
Interface Amorphization of Two‐Dimensional Black Phosphorus upon Treatment with Diazonium Salts
Authors: Mitrović Aleksandra , Wild Stefan , Lloret Vicent , Fickert Michael , Assebban Mhamed , Márkus Bence G. , Simon Ferenc , Hauke Frank , Abellán Gonzalo , Hirsch Andreas
Published: October 2020

Two‐dimensional (2D) black phosphorus (BP) represents one of the most appealing 2D materials due to its electronic, optical, and chemical properties. Many strategies have been pursued to face its environmental instability, covalent functionalization being one of the most promising. However, the extremely low functionalization degrees and the limitations in proving the nature of the covalent functionalization still represent challenges in many of these sheet architectures reported to date. Here we shine light on the structural evolution of 2D‐BP upon the addition of electrophilic diazonium salts. We demonstrated the absence of covalent functionalization in both the neutral and the reductive routes, observing in the latter case an unexpected interface conversion of BP to red phosphorus (RP), as characterized by Raman, 31P‐MAS NMR, and X‐ray photoelectron spectroscopies (XPS). Furthermore, thermogravimetric analysis coupled to gas chromatography and mass spectrometry (TG‐GC‐MS), as well as electron paramagnetic resonance (EPR) gave insights into the potential underlying radical mechanism, suggesting a Sandmeyer‐like reaction.
Mimicking Biological Recognition: Lessons in Binding Hydrophilic Guests in Water
Authors: Ferguson Johns Hannah P. , Harrison Emily E. , Stingley Kyla J. , Waters Marcey L.
Published: October 2020

Selective molecular recognition of hydrophilic guests in water plays a fundamental role in a vast number of biological processes, but synthetic mimicry of biomolecular recognition in water still proves challenging both in terms of achieving comparable affinities and selectivities. This Review highlights strategies that have been developed in the field of supramolecular chemistry to selectively and non‐covalently bind three classes of biologically relevant molecules: nucleotides, carbohydrates, and amino acids. As several groups have systematically modified receptors for a specific guest, an evolutionary perspective is also provided in some cases. Trends in the most effective binding forces for each class are described, providing insight into selectivity and potential directions for future work.
A Promising Approach for Controlling the Second Coordination Sphere of Biomimetic Metal Complexes: Encapsulation in a Dynamic Hydrogen‐Bonded Capsule
Authors: Zhang Tongtong , Le Corre Laurent , Reinaud Olivia , Colasson Benoit
Published: October 2020

The design of biomimetic models of metalloenzymes needs to take into account many factors and is therefore a challenging task. We propose in this work an original strategy to control the second coordination sphere of a metal centre and its distal environment. A biomimetic complex, reproducing the first coordination sphere, is encapsulated in a self‐assembled hydrogen‐bonded capsule. The cationic complex is co‐encapsulated with its counter‐anion or with solvent molecules. The capsule is dynamic, allowing a fast in/out exchange of the co‐encapsulated species. It also provides both a hydrogen‐bonding site in the second coordination sphere and a source of proton as it can be deprotonated in the presence of the complex, providing a globally neutral host‐guest assembly. This simple and broad scope strategy is unprecedented in biomimetic studies. The approach appears to be a very promising method for the stabilisation of reactive species and for the study of their reactivity.
Reappraisal of Empirical Solvent Polarity Scales for Organic Solvents
Authors: Spange Stefan , Weiß Nadine , Schmidt Caroline H. , Schreiter Katja
Published: October 2020

Correlations of Reichardt'sET(30), the CatalánSdP(solvent dipolarity),SP(solvent polarizability),SA(solvent acidity),SB(solvent basicity), Kamlet‐Taftπ* (dipolarity/polarizability),α(hydrogen bond donating ability) andβ(hydrogen bond accepting ability) polarity parameters with the molar concentration of 161 pure organic solvents are presented. Mostly, linear relationships of the polarity parameter as a function of molar concentration are obtained as long as each individual solvent class is considered separately. A physically different interpretation of theET(30), Kamlet‐Taftπ* andαas well as CatalánSAandSBparameters has been proposed. Furthermore, the Hildebrand solubility parameter in combination with the diffraction index is used for the correlation analysis with the above‐mentioned solvent parameters. It can be concluded that empirical polarity parameters derived from solvatochromic UV/Vis measurements are inherently a function of the molecular structure of the probe.
Color difference classification of dyed fabrics via a kernel extreme learning machine based on an improved grasshopper optimization algorithm
Authors: Li Jianqiang , Shi Weimin , Yang Donghe
Published: October 2020

Conventional artificial color difference detection is error prone and inefficient. Herein, a novel color difference classification model is proposed for dyed fabrics via a kernel extreme learning machine based on an improved grasshopper optimization algorithm. First, in order to prevent the grasshopper optimization algorithm from succumbing to local optimality, it is proposed to optimize the initial population of the algorithm using differential evolution, resulting in a better solution direction at the outset. Then, this novel grasshopper algorithm is used to adjust the kernel bandwidth and penalty parameters of the learning maching model, thereby forming a color difference classification model for dyed fabrics based on the differential evolution grasshopper optimization algorithm kernel extreme learning machine. Finally, the key indicator values representing color difference are extracted from the printed and dyed product images collected under the standard light source. The color difference calculated by substituting these values into the color difference formula generates a color difference dataset, which is used to train and test the color difference classification model. Experimental results show that the proposed differential evolution grasshopper optimization algorithm kernel extreme learning machine model has high classification accuracy and impressive stability. The average classification accuracy of the proposed model is 98.89%, whereas the accuracy of kernel extreme learning machine is only 91.08%.
More Sustainable Chemical Activation Strategies for the Production of Porous Carbons
Authors: Sevilla Marta , Díez Noel , Fuertes Antonio B.
Published: October 2020

The preparation of porous carbons attracts a great deal of attention given the importance of these materials in many emerging applications, such as hydrogen storage, CO2 capture, and energy storage in supercapacitors and batteries. In particular, porous carbons produced by applying chemical activation methods are preferred because of the high pore development achieved. However, given the environmental risks associated with conventional activating agents such as KOH, the development of greener chemical activation methodologies is an important objective. This Review summarizes recent progress in the production of porous carbons by using more sustainable strategies based on chemical activation. The use of less‐corrosive chemical agents as an alternative to KOH is thoroughly reviewed. In addition, progress achieved to date by using emerging self‐activation methodologies applied to organic salts and biomass products is also discussed.
The “sugar‐coated bullets” of cancer: Tumor‐derived exosome surface glycosylation from basic knowledge to applications
Authors: Lin Shanyi , Zhou Shumin , Yuan Ting
Published: October 2020

Scientific interest in exosomes has exploded in recent decades. In 1990 only three articles were published on exosomes, while over 1,700 have already been published half‐way into 2020.1 While researchers have shown much interest in exosomes since being discovered in 1981, an appreciation of the potential role of glycans in exosome structure and function has emerged only recently. Glycosylation is one of the most common post‐translational modification, which functions in many physiological and pathological aspects of cellular function. Many components of exosomes are heavily glycosylated including proteins, lipids, among others. Thus, glycosylation undoubtedly has a great impact on exosome biosynthesis and function. Despite the importance of glycosylation in exosomes and the recent recognition of them as biomarkers for not only malignancies but also other system dysfunction and disease, the characterization of exosome glycans remains understudied. In this review, we discuss glycosylation patterns of exosomes derived from various tissues, their biological features, and potential for various clinical applications. We highlight state‐of‐the‐art knowledge about the fine structure of exosomes, which will allow researchers to reconstruct them by surface modification. These efforts will likely lead to novel disease‐related biomarker discovery, purification tagging, and targeted drug transfer for clinical applications in the future.
Scientism, creationism or category error? A cross‐age survey of secondary school students’ perceptions of the relationships between science and religion
Authors: Billingsley Berry , Taber Keith S. , Nassaji Mehdi
Published: October 2020

We report on a survey of 1717 students at two different points of their secondary school education. This survey is designed to discover their reasoning about scientific and religious accounts of the origins of the universe and life. The study was motivated by a concern, based on previous research, that factors such as the compartmentalised curriculum may limit students’ progression in interdisciplinary reasoning and their capacities to appreciate why science and religion are not necessarily incompatible. To investigate these matters, we gathered data in seven secondary schools in England. The findings indicated that a significant proportion of students are working with a poor understanding of the limits of science and of the range of scholarly positions on the nature of religious explanation. The implications of the results for educational theory and practice are discussed.
Using LiDAR to assess transitions in riparian vegetation structure along a rural‐to‐urban land use gradient in western North America
Authors: Grijseels Noortje H. , Buchert Martin , Brooks Paul D. , Pataki Diane E.
Published: October 2020

Riparian forests are essential for stream ecological processes in arid and semiarid regions, however, they are often highly altered by the rapid expansion of urban areas. To maintain riparian ecosystems services, it is important to better understand the effects of urbanization on riparian forests. We quantified the three‐dimensional (3D) structure and woody species composition of a riparian corridor in Utah, USA, to evaluate patterns of vegetation along stream reaches that flow through distinct hydrologic domains (with gaining and losing reaches) and through a rapid rural‐to‐urban gradient. By using LiDAR imaging and field observations, we explore the extent to which the riparian vegetation structure follows patterns of topography linked to energy and water subsidies and patterns of human influence along the stream. Whereas natural reaches of Red Butte Creek were characterized by native vegetation and typical riparian species (e.g., Betula occidentalis), urbanized reaches had higher numbers of introduced plants (e.g., Acer platanoides) and more upland species (e.g., Quercus gambelii). Urban reaches were also characterized by exceptionally high trees (>18 m) in older residential neighbourhoods. In the natural area, canopy height was negatively correlated with height above the river (HAR). Additionally, we found higher cover and taller canopies on north‐facing aspects. These results show that LiDAR data, in combination with ground observations, can reveal strong influences of hydrology as well as land use in different canopy layers of riparian forests. We suggest that the decision making of individual landowners shapes vegetation beyond natural hydrological patterns, with implications for riparian forest management and restoration.
Polycentric to monocentric governance: Power dynamics in Lake Victoria's fisheries
Authors: Mudliar Pranietha
Published: October 2020

In theory, polycentric governance arrangements are better able to respond to complex, uncertain, and multiscale challenges. Research on polycentric governance challenges these normative assumptions to find that the functionality of polycentric systems is constrained because different kinds of power influence not only the emergence and design of polycentric systems, but also decisions about policy choices and outcomes. This study uses a polycentric power typology to provide insights into the power dynamics underpinning the polycentric fisheries system of Lake Victoria through qualitative case study methods. The study reveals that power by design creates a polycentric structure that could potentially provide opportunities for power‐sharing between higher and lower decision centers. However, pragmatic and framing power erode power away from lower‐level authorities by either taking over or dismantling lower‐level decision centers and institutions. Without a genuine intent to share power among decision centers, cross‐level linkages are deliberately nonfunctional or have high transaction costs, creating and intensifying conflicts and competitions between the state and local governments. In the absence of functional cross‐linkages, information‐sharing, accountability, and conflict‐resolution mechanisms are hampered as is the inclusion of lower‐level actors in management. Higher‐level actors justify taking over functions of lower‐level actors by deploying frames of the lower‐level's “lack of capacity.” In combination, these factors concentrate power at the center, resulting in maladaptive outcomes in Lake Victoria's fisheries. The findings suggest that improving understanding of contextual conditions that are more suited to polycentric governance is important for refining theory and improving governance.
Proteomic exploration of common pathophysiological pathways in diabetes and cardiovascular disease
Authors: Molvin John , Jujić Amra , Melander Olle , Pareek Manan , Råstam Lennart , Lindblad Ulf , Daka Bledar , Leósdóttir Margrét , Nilsson Peter M. , Olsen Michael H. , Magnusson Martin
Published: October 2020

Aims

The epidemiological association between diabetes and cardiovascular disease is well established, but the pathophysiological link is complex and multifactorial. We investigated seven proteins, previously linked to incident diabetes mellitus, and their association with cardiovascular disease and mortality.

Methods and results

Plasma samples from 1713 individuals from the Swedish population‐based Malmö Preventive Project (mean age 67.4 ± 6.0 years; 29.1% women) were analysed with a proximity extension assay panel. Seven proteins [scavenger receptor cysteine rich type 1 protein M130 (CD163), fatty acid‐binding protein 4 (FABP4), plasminogen activator inhibitor 1 (PAI), insulin‐like growth factor‐binding protein 2 (IGFB2), cathepsin D (CTSD), galectin‐4 (GAL4), and paraoxonase‐3 (PON3)] previously shown to be associated with incident diabetes were analysed for associations with all‐cause mortality (ACM), cardiovascular mortality (CVM), incident coronary events (CEs), and incident heart failure (HF). After exclusion of prevalent cases of respective outcome, proteins that met Bonferroni‐corrected significance were analysed in multivariable Cox regression models. Significant associations were identified between five proteins [GAL4 (hazard ratio; 95% confidence interval: 1.17–1.41), CTSD (1.15–1.37), CD163 (1.09–1.30), IGFBP2 (1.05–1.30), and FABP4 (1.04–1.29)] and ACM and four proteins [GAL4 (1.38–1.56), CTSD (1.14–1.43), CD163 (1.09–1.36), and IGFBP2 (1.03–1.35)] with CVM. Three proteins [GAL4 (1.14–1.57), CTSD (1.12–1.50), and FABP4 (1.05–1.55)] were significantly associated with incident CE and two [GAL4 (1.03–1.54) and CTSD (1.01–1.46)] were associated with incident HF after adjusting for traditional risk factors including N‐terminal pro‐brain natriuretic peptide.

Conclusions

In a general Swedish population, four proteins previously shown to be associated with diabetes were associated with ACM and CVM. Three proteins were associated with incident CE. Finally, GAL4 and CTSD displayed novel associations with incident HF and were the only proteins associated with all outcomes.
Parent of origin gene expression in the bumblebee,Bombus terrestris, supports Haig's kinship theory for the evolution of genomic imprinting
Authors: Marshall Hollie , van Zweden Jelle S. , Van Geystelen Anneleen , Benaets Kristof , Wäckers Felix , Mallon Eamonn B. , Wenseleers Tom
Published: October 2020

Genomic imprinting is the differential expression alleles in diploid individuals, with the expression being dependent on the sex of the parent from which it was inherited. Haig's kinship theory hypothesizes that genomic imprinting is due to an evolutionary conflict of interest between alleles from the mother and father. In social insects, it has been suggested that genomic imprinting should be widespread. One recent study identified parent-of-origin expression in honey bees and found evidence supporting the kinship theory. However, little is known about genomic imprinting in insects and multiple theoretical predictions must be tested to avoid single-study confirmation bias. We, therefore, tested for parent-of-origin expression in a primitively eusocial bee. We found equal numbers of maternally and paternally biased expressed genes. The most highly biased genes were maternally expressed, offering support for the kinship theory. We also found low conservation of potentially imprinted genes with the honey bee, suggesting rapid evolution of genomic imprinting in Hymenoptera.
Alterations of brain activity and functional connectivity in transition from acute to chronic tinnitus
Authors: Lan Liping , Li Jiahong , Chen Yanhong , Chen Wan , Li Wenrui , Zhao Fei , Chen Guisheng , Liu Jiahao , Chen Yuchen , Li Yuanqing , Wang Chang‐Dong , Zheng Yiqing , Cai Yuexin
Published: October 2020

The objective of this study was to investigate alterations to brain activity and functional connectivity in patients with tinnitus, exploring neural features in the transition from acute to chronic phantom perception. Twenty‐four patients with acute tinnitus, 23 patients with chronic tinnitus, and 32 healthy controls were recruited. High‐density electroencephalography (EEG) was used to explore changes in brain areas and functional connectivity in different groups. When compared with healthy subjects, acute tinnitus patients had a significant reduction in superior frontal cortex activity across all frequency bands, whereas chronic tinnitus patients had a significant reduction in the superior frontal cortex at beta 3 and gamma frequency bands as well as a significant increase in the inferior frontal cortex at delta‐band and superior temporal cortex at alpha 1 frequency band. When compared to the chronic tinnitus group, the acute tinnitus group activity was significantly increased in the middle frontal and parietal gyrus at the gamma‐band. Functional connectivity analysis showed that the chronic tinnitus group had increased connections between the parahippocampus gyrus, posterior cingulate cortex, and precuneus when compared with the healthy group. Alterations of local brain activity and connections between the parahippocampus gyrus and other nonauditory areas appeared in the transition from acute to chronic tinnitus. This indicates that the appearance and development of tinnitus is a dynamic process involving aberrant local neural activity and abnormal connectivity in multifunctional brain networks.
Modelling the impact of audit/remuneration committee overlap on debtholders' perceptions of accounting information quality: The role of CEO power
Authors: Al‐Dhamari Redhwan , Alquhaif Abdulsalam Saad , Al‐Gamrh Bakr Ali
Published: October 2020

This study examines how debtholders perceive accounting information quality of firms with audit committee members who are also on the remuneration committee, and whether strong CEO power enhances or undermines the governance role of overlapping committees. Using 841 observations of Malaysian firms over the period 2013–2015, we find that firms with overlapping audit and remuneration committees are perceived by debtholders to be transparent and of lower operating risk and, consequently, be associated with lower cost of debt. We also find that the beneficial effect of the presence of overlapping committees is weakened by the level of CEO power. Our results are robust to concerns of endogeneity and alternative measurers of the key variables. This study is timely in light of recently increasing call for the broadening of audit committee members' understanding of business strategies, risks and incentives provided by firms' executive compensation structures. Our study also contributes to the ongoing debate surrounding CEO power by suggesting that debtholders perceive potent CEO power as detrimental to their investments and thus charge higher interest rates from firms with powerful CEOs and overlapping directors.
Comparison of toxicity of Ti3C2 and Nb2C Mxene quantum dots (QDs) to human umbilical vein endothelial cells
Authors: Gu Manyu , Dai Zhiqi , Yan Xiang , Ma Junfei , Niu Yingchun , Lan Wenjie , Wang Xin , Xu Quan
Published: October 2020

Recently, we developed highly fluorescent Ti3C2 and Nb2C Mxene quantum dots (QDs) for labeling of in vitro models. However, the mechanism of the toxicity of the prepared QDs was not explored before. In this study, we addressed the possible mechanism associated with cytotoxicity of the QDs to human umbilical vein endothelial cells (HUVECs). Exposure to up to 100 μg/ml Ti3C2 but not Nb2C QDs for 24 h significantly induced cytotoxicity. The exposure also increased intracellular Ti and Nb elements, indicating the internalization of both types of QDs. None of the QDs promoted interleukin 6 (IL‐6) and IL‐8 releases. Rather, Ti3C2 QDs significantly reduced IL‐6 and IL‐8 release, indicating that the toxicity of Ti3C2 QDs was not due to elevated inflammatory responses. Exposure to Ti3C2 but not Nb2C QDs resulted in increased LC3B‐II/I ratio and beclin‐1 proteins, biomarkers of autophagy, as well as the accumulation of autophagic substance p62. Ti3C2 QDs also more effectively promoted pro‐caspase 3 but not pro‐caspase 8 compared with Nb2C QDs. Furthermore, pre‐treatment with autophagic modulators altered the cytotoxicity of Ti3C2 QDs, which further confirmed the role of autophagic dysfunction in Ti3C2 QD‐induced toxicity to HUVECs. In conclusion, the results from this study suggested that high levels of Ti3C2 QDs could induce cytotoxicity to HUVECs by inducing the dysfunction of autophagy. Nb2C QDs appeared to be more biocompatible to HUVECs compared with Ti3C2 QDs at the same mass concentrations, which suggested a role of composition of Mxene QDs to determine their toxicity to human endothelial cells.
SERS‐based sensor for direct L‐selectin level determination in plasma samples as alternative method of tumor detection
Authors: Kowalska Aneta Aniela , Nowicka Ariadna B. , Szymborski Tomasz , Piecyk Patrycja , Kamińska Agnieszka
Published: October 2020

Selectin ligands are present on the surface of tumor cells, for this reason lowering the L‐selectin level in the blood and lymph can indicate presence of the tumor. Therefore the selectin level in the plasma are potential targets for anticancer therapy. We demonstrate the surface enhanced Raman spectroscopy (SERS)‐based sensor for the determination of L‐selectin level in biological samples that can be used in medical diagnosis. The combination of SERS with the method of multivariate analysis as principle component analysis (PCA) allows to strengthen the presented data analysis. The loadings of PCA permit to indicate those vibration modes, that are the most important for the assumed identification (bands at 1574, 1450, 1292 cm−1). Two bands at 1286 and 1580 cm−1 were selected for the determination of the calibration curve (bands intensities I1286/I1580 ratio). The L‐selectin level of biological samples can be read, directly from the calibration curve. The presented sensor is as a sensitive tool with good specificity and selectivity of L‐selectin, even in the case of coexistence of P‐ and E‐selectin.
Bioenergetic signature as a target of zinc oxide nanoparticles in Ehrlich ascitic carcinoma‐bearing mice
Authors: Morsy Sara , Abd‐Ellatif Rania N. , Soliman Nema A. , Ibrahim Wafaa M.
Published: October 2020

The current study aims to evaluate the modulatory effect of zinc oxide nanoparticles (ZnO NPs) on the bioenergetic signature biomarkers in the Ehrlich ascitic carcinoma (EAC) model. To achieve this goal, 90 female albino mice were included in this study and were divided into six equal groups (n   =15 per group): saline‐treated group, ZnO NP‐treated, EACs‐bearing mice, and three groups of EACs‐bearing mice treated with ZnO NPs at a dose of 20 mg/kg every other day, 10 mg/kg every other day, 10 mg/kg every day, respectively, for 14 days. The tissues from treated groups and control groups were homogenized and used for the assay of glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) and F1 beta subunit of adenosine triphosphate (ATP) synthase levels, as well as the determination of lactate level. The survival time of mice was improved in all ZnO NP‐treated groups, especially in EACs‐bearing mice treated with ZnO NPs at a dose of 10  mg/kg every other day. This improvement was associated with an increased F1 beta subunit of ATP synthase level and a decreased GAPDH level. Also, the lactate level was significantly decreased in all treated groups when compared with the untreated group. The overall effect was the increased bioenergetic signature as compared with EC.These results implied that ZnO NPs have a significant efficacy against cancer cells and they significantly increased the bioenergetic signature.
Generation and initial characterization of novel tumour organoid models to study human pancreatic cancer‐induced cachexia
Authors: Vaes Rianne D.W. , van Dijk David P.J. , Welbers Tessa T.J. , Blok Marinus J. , Aberle Merel R. , Heij Lara , Boj Sylvia F. , Olde Damink Steven W.M. , Rensen Sander S.
Published: October 2020

Background

The majority of patients with pancreatic cancer develops cachexia. The mechanisms underlying cancer cachexia development and progression remain elusive, although tumour‐derived factors are considered to play a major role. Pancreatic tumour organoids are in vitro three‐dimensional organ‐like structures that retain many pathophysiological characteristics of the in vivo tumour. We aimed to establish a pancreatic tumour organoid biobank from well‐phenotyped cachectic and non‐cachectic patients to enable identification of tumour‐derived factors driving cancer cachexia.

Methods

Organoids were generated from tumour tissue of eight pancreatic cancer patients. A comprehensive pre‐operative patient assessment of cachexia‐related parameters including nutritional status, physical performance, body composition, and inflammation was performed. Tumour‐related and cachexia‐related characteristics of the organoids were analysed using histological stainings, targeted sequencing, and real‐time–quantitative PCR. Cachexia‐related factors present in the circulation of the patients and in the tumour organoid secretome were analysed by enzyme‐linked immunosorbent assay.

Results

The established human pancreatic tumour organoids presented typical features of malignancy corresponding to the primary tumour (i.e. nuclear enlargement, multiple nucleoli, mitosis, apoptosis, and mutated KRAS and/or TP53). These tumour organoids also expressed variable levels of many known cachexia‐related genes including interleukin‐6 (IL‐6), TNF‐α, IL‐8, IL‐1α, IL‐1β, Mcp‐1, GDF15, and LIF. mRNA expression of IL‐1α and IL‐1β was significantly reduced in organoids from cachectic vs. non‐cachectic patients (IL‐1α: −3.8‐fold, P = 0.009, and IL‐1β: −4.7‐fold, P = 0.004). LIF, IL‐8, and GDF15 mRNA expression levels were significantly higher in organoids from cachectic vs. non‐cachectic patients (LIF: 1.6‐fold, P = 0.003; IL‐8: 1.4‐fold, P = 0.01; GDF15: 2.3‐fold, P < 0.001). In line with the GDF15 and IL‐8 mRNA expression levels, tumour organoids from cachectic patients secreted more GDF15 and IL‐8 compared with organoids from non‐cachectic patients (5.4 vs. 1.5 ng/mL, P = 0.01, and 7.4 vs. 1.3 ng/mL, P = 0.07, respectively).

Conclusions

This novel human pancreatic tumour organoid biobank provides a valuable tool to increase our understanding of the mechanisms driving cancer cachexia. Our preliminary characterization of the secretome of these organoids supports their application in functional studies including conditioned medium approaches and in vivo transplantation models.
The role of blocking circulation and emerging open water feedbacks on Greenland cold‐season air temperature variability over the last century
Authors: Ballinger Thomas J. , Hanna Edward , Hall Richard J. , Carr J. Rachel , Brasher Saber , Osterberg Erich C. , Cappelen John , Tedesco Marco , Ding Qinghua , Mernild Sebastian H.
Published: October 2020

Substantial marine, terrestrial, and atmospheric changes have occurred over the Greenland region during the last century. Several studies have documented record‐levels of Greenland Ice Sheet (GrIS) summer melt extent during the 2000s and 2010s, but relatively little work has been carried out to assess regional climatic changes in other seasons. Here, we focus on the less studied cold‐season (i.e., autumn and winter) climate, tracing the long‐term (1873–2013) variability of Greenland's air temperatures through analyses of coastal observations and model‐derived outlet glacier series and their linkages with North Atlantic sea ice, sea surface temperature (SST), and atmospheric circulation indices. Through a statistical framework, large amounts of west and south Greenland temperature variance (up to r2 ~ 50%) can be explained by the seasonally‐contemporaneous combination of the Greenland Blocking Index (GBI) and the North Atlantic Oscillation (NAO; hereafter the combination of GBI and NAO is termed GBI). Lagged and concomitant regional sea‐ice concentration (SIC) and the Atlantic Multidecadal Oscillation (AMO) seasonal indices account for small amounts of residual air temperature variance (r2 < ~10%) relative to the GBI. The correlations between GBI and cold‐season temperatures are predominantly positive and statistically‐significant through time, while regional SIC conditions emerge as a significant covariate from the mid‐20th century through the conclusion of the study period. The inclusion of the cold‐season Pacific Decadal Oscillation (PDO) in multivariate analyses bolsters the air temperature variance explained by the North Atlantic regional predictors, suggesting the remote, background climate state is important to long‐term Greenland temperature variability. These findings imply that large‐scale tropospheric circulation has a strong control on surface temperature over Greenland through dynamic and thermodynamic impacts and stress the importance of understanding the evolving two‐way linkages between the North Atlantic marine and atmospheric environment in order to more accurately predict Greenland seasonal climate variability and change through the 21st century.
Soil drought and circulation types in a longitudinal transect over central Europe
Authors: Řehoř Jan , Brázdil Rudolf , Trnka Miroslav , Lhotka Ondřej , Balek Jan , Možný Martin , Štěpánek Petr , Zahradníček Pavel , Mikulová Katarína , Turňa Maroš
Published: October 2020

Among the variables that can be employed to characterize agricultural drought, soil drought is of particular importance. This contribution uses gridded soil‐drought values calculated from the SoilClim model for the 1961–2019 period to analyse soil drought episodes (based on the 10th percentile) in four lowlands, relatively homogeneous regions in central Europe that provide a longitudinal transect over central Europe. These areas are predominantly located at altitudes of below 400 m asl and include central Bohemia, southern Moravia and an adjacent part of Slovakia, southern Slovakia and eastern Slovakia. The results indicate that, after 1990, such episodes occurred largely in the summer half‐year (April–September), accompanied by an increasing linear trend in the 1961–2019 period, while the situation was reversed in the winter half‐year (October–March). Selected drought episodes are further divided into three phases (Phase I – origin, Phase II – course, Phase III – end) and investigated separately in terms of precipitation and objective classification of circulation types based on flow strength, direction and vorticity. Decreases in the frequency of precipitation‐rich cyclonic and the directional types associated with higher daily precipitation totals, together with increases in precipitation‐poor anticyclonic types, were responsible for soil‐drought Phases I and II, with the opposite pertaining to Phase III. Differences in the effects of circulation types on precipitation and soil‐drought occurrence were considerable, particularly for central Bohemia compared with the other three regions. The results obtained are also discussed with respect to data uncertainty and their broader spatiotemporal context.
Metaplastic breast cancer: Prognostic and therapeutic considerations
Authors: Corso Giovanni , Frassoni Samuele , Girardi Antonia , De Camilli Elisa , Montagna Emilia , Intra Mattia , Bottiglieri Luca , Margherita De Scalzi Alessandra , Fanianos Denise Mattar , Magnoni Francesca , Invento Alessandra , Toesca Antonio , Conforti Fabio , Bagnardi Vincenzo , Viale Giuseppe , Colleoni Marco Angelo , Veronesi Paolo
Published: October 2020

Introduction

Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting.

Methods

We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic‐pathological factors, number and type of events during follow‐up were considered to evaluate overall survival (OS) and invasive disease‐free survival (IDFS).

Results

The majority of MBC was triple‐negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki‐67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple‐negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5‐fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting.

Conclusion

Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease‐free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.
Metastatic renal cell carcinoma to the pancreas: Clinical features and treatment outcome
Authors: Shin Teak Jun , Song Cheryn , Jeong Chang Wook , Kwak Cheol , Seo Seongil , Kang Minyong , Chung Jinsoo , Hong Sung‐Hoo , Hwang Eu Chang , Park Jae Young , Lee Hakmin
Published: October 2020

Background and Objectives

Metastatic renal cell carcinoma to the pancreas (PM‐RCC) is infrequent; we sought to describe the characteristics of PM‐RCC and analyze the outcome following treatment.

Methods

Data of 3107 mRCC patients treated between 1992 and 2007 from the Korean Renal Cancer Study Group database were obtained to identify 300 (9.7%) PM‐RCC patients. Characteristics and survival were analyzed and compared to the rest of the mRCC, according to the timing of metastasis and surgical treatments received.

Results

PM‐RCC was younger at initial diagnosis (55.0 vs. 58.2 years), more frequently in women (30.3% vs. 22.3%), and metachronous (65.3% vs. 41.9%) with a longer disease‐free period (82.0 vs. 33.0 months). Overall survival (OS) was significantly better in PM‐RCC but pancreas metastasectomy was associated with improved OS only among metachronous PM‐RCC. In the 132 metachronous PM‐RCC with pancreas metastasectomy, median recurrence‐free survival was 17.2 months and we found Heng risk group (hazard ratio [HR] = 2.384, 95% confidence interval [CI] = 1.213–4.684), younger age (HR = 0.965, 95% CI = 0.945–0.987), shorter interval to pancreas metastasis (HR = 0.993, 95% CI = 0.986–0.999), and Eastern Cooperative Oncology Group performance status to be predictive of early progression following pancreas metastasectomy.

Conclusion

Compared to the other mRCC, PM‐RCC demonstrated a favorable prognosis. Pancreas metastasectomy was associated with prolonged survival in the metachronous PM‐RCC with a long progression‐free period.
Predictive value of tumor‐infiltrating lymphocytes for response to neoadjuvant chemotherapy and breast cancer prognosis
Authors: Li Xiaomin , Tan Qiuwen , Li Hongjiang , Yang Xiaoqin
Published: October 2020

Background

Tumor‐infiltrating lymphocytes (TILs) are predictive for the response to neoadjuvant chemotherapy (NAC) of breast cancer. However, little is known about the predictive value of TILs for axillary lymph node involvement after NAC.

Methods

We analyzed 282 breast cancer patients who were operated following NAC and curative surgery from 2008 to 2018. TILs were assessed in core needle biopsies before NAC, and the biopsies were divided into three groups: low (0%–10% immune cells in stromal tissue within the tumor), intermediate (11%–59%), and high (≥60%). The patients were followed for an average of 63 months (range, 2–116 months). We analyzed retrospectively the predictive value of TILs for the response to NAC, including pathological complete response (pCR) and axillary lymph node involvement (positive lymph node ratio (LNR; the ratio of the number of nodes involved to the total number of nodes dissected)). The prognostic values of TILs and LNR were assessed.

Results

A pCR was achieved in 27 of 188 patients (14.4%) in the low‐TIL group, in 14 of 57 patients (24.6%) in the intermediate‐TIL group, and in 13 of 37 (35.1%) in the high‐TIL group (p = .007). Among patients who underwent axillary lymph node dissection after NAC, patients with high TILs had lower LNR (p = 0021) compared with the other groups. Kaplan‐Meier analysis showed that overall survival (OS; p < .001) and disease‐free survival (p < .001) were significantly longer for patients with low LNR (≤0.2). TILs were positively correlated with disease‐free survival (p = .028), but TILs did not correlate with OS (p = .171). Moreover, by multivariable analysis, LNR independently affected disease‐free survival (p < .001).

Conclusions

TILs may be predictive for pCR rate, postoperative residual lymph node involvement, and disease‐free survival of breast cancer patients. High TILs may suggest favorable outcomes.
Modeling the role of riverine organic matter in hypoxia formation within the coastal transition zone off the Pearl River Estuary
Authors: Yu Liuqian , Gan Jianping , Dai Minhan , Hui Chiwing Rex , Lu Zhongming , Li Dou
Published: October 2020

Globally expanding hypoxia in estuaries and coastal oceans has largely been attributed to the elevated river nutrient inputs, whereas the role of river‐delivered terrestrial organic matter (OMterr) in hypoxia formation has been less investigated. This study uses a coupled physical‐biogeochemical model and observations to investigate how OMterr directly (via remineralization) and indirectly (via the nutrients released from OMterr remineralization) promotes hypoxia development in the coastal transition zone off the Pearl River Estuary. Results show that direct contribution of OMterr remineralization to total oxygen consumption by terrestrial and marine organic matter negatively correlates with salinity, decreasing from over 60% in the upper estuary to nearly 0% in the far reaches of the river plume, and is higher in the upstream (average 30%) than the downstream region (average 18%). Nevertheless, the nutrients released from OMterr remineralization greatly sustain an indirect contribution to oxygen depletion and hypoxia formation downstream. The increasing relative importance of indirect over the direct effect of OMterr to hypoxia along the plume path is a combined result of the wind‐driven eastward shelf current and the OMterr‐released nutrients being advected farther downstream than the sinking OMterr. This highlights that without including the indirect effect of OMterr may underestimate the role of OMterr in hypoxia formation in aquatic systems. Examinations of the hypoxia response to varying riverine loads further suggest that reducing the nutrient and OMterr loads is required for hypoxia mitigation in the upstream region while reducing the nutrient load alone is more effective in mitigating hypoxia in the downstream.