bluuebunny/crossref_metadata_2025 huggingface dataset:
High moon brightness and low ambient temperatures affect sloth predation by harpy eagles
Authors: Miranda Everton B.P. de , Kenup Caio F. , Campbell-Thompson Edwin , Vargas Felix H. , Muela Angel , Watson Richard , Peres Carlos A. , Downs Colleen T.
Published: August 2020

Background

Climate plays a key role in the life histories of tropical vertebrates. However, tropical forests are only weakly seasonal compared with temperate and boreal regions. For species with limited ability to control core body temperature, even mild climatic variation can determine major behavioural outcomes, such as foraging and predator avoidance. In tropical forests, sloths are the arboreal vertebrate attaining the greatest biomass density, but their capacity to regulate body temperature is limited, relying on behavioural adaptations to thermoregulate. Sloths are largely or strictly nocturnal, and depend on crypsis to avoid predation. The harpy eagle (Harpia harpyja) is a sloth-specialist and exerts strong top-down control over its prey species. Yet the role of environmental variables on the regulation of predator–prey interactions between sloths and harpy eagles are unknown. The harpy eagle is considered Near Threatened. This motivated a comprehensive eﬀort to reintroduce this species into parts of Mesoamerica. This eﬀort incidentally enabled us to understand the prey profile of harpy eagles over multiple seasons.

Methods

Our study was conducted between 2003 and 2009 at Soberanía National Park, Panamá. Telemetered harpy eagles were seen hunting and feeding on individual prey species. For each predation event, field assistants systematically recorded the species killed. We analysed the effects of climatic conditions and vegetation phenology on the prey species profile of harpy eagles using generalised linear mixed models.

Results

Here we show that sloth predation by harpy eagles was negatively aﬀected by nocturnal ambient light (i.e. bright moonshine) and positively aﬀected by seasonally cool temperatures. We suggest that the first ensured low detectability conditions for sloths foraging at night and the second posed a thermally unsuitable climate that forced sloths to forage under riskier daylight. We showed that even moderate seasonal variation in temperature can influence the relationship between a keystone tropical forest predator and a dominant prey item. Therefore, predator–prey ecology in the tropics can be modulated by subtle changes in environmental conditions. The seasonal eﬀects shown here suggest important demographic consequences for sloths, which are under top-down regulation from harpy eagle predation, perhaps limiting their geographic distribution at higher latitudes.
Association analysis between chronic obstructive pulmonary disease and polymorphisms in circadian genes
Authors: Chen Guo , Zhang Jingwei , Zhang Lijuan , Xiong Xuan , Yu Dongke , Zhang Yuan
Published: August 2020

Background

Circadian genes have been suggested to play an important role in lung pathology. However, it remains unknown whether polymorphisms of these genes are associated with chronic obstructive pulmonary disease (COPD). Here, we aimed to investigate the association of circadian genes polymorphisms with COPD in a case-control study of 477 COPD patient and 323 control Han Chinese persons.

Methods

Genotyping assays were carried out for nine single nucleotide polymorphisms (SNPs) from five circadian genes (PER3, CLOCK, RORB, BMAL1 and CRY2) that were previously identified in lung pathology. Age, sex, BMI and smoking status and comorbidities were recorded for all subjects.

Results

No significant association was found in all SNP sites in overall subjects and no significant difference was found in age, sex, smoking status stratification analysis.

Discussion

The findings of this investigation indicated the effect of circadian genes polymorphisms on COPD susceptibility may only be small and possibly dependent on the subject factors, such as age and sex.
Upregulation of CIP2A in estrogen depletion‐resistant breast cancer cells treated with low‐dose everolimus
Authors: Nishio Eiji , Hayashi Takanori , Akaza Mao , Hisatomi Yukiko , Hikichi Masahiro , Fujii Takuma , Utsumi Toshiaki , Harada Nobuhiro , Shimono Yohei
Published: August 2020

Everolimus (EVE), an inhibitor of mammalian target of rapamycin, is an emerging second‐line therapeutic option for hormone therapy‐resistant breast cancers. However, some patients do not respond to EVE, whereas in others it exacerbates the disease. Cellular inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that can promote cancer cell growth and apoptosis resistance. Although CIP2A is upregulated in hormone‐related cancers, such as breast cancer, little is known about potential anti‐tumor effects of downregulating CIP2A. As a model to study the resistance of breast cancer cells to hormone treatment, we previously established clones of long‐term estrogen depletion‐resistant MCF‐7 (LTED) cells. Here, we selected three clones highly responsive to EVE and three clones poorly responsive to EVE. When cells were treated with EVE, CIP2A mRNA expression was decreased in highly responsive EVE clones (DC‐cells) whereas it was increased in poorly responsive EVE clones (IC‐cells). Using Kaplan–Meier survival plots, we report that high expression of CIP2A was associated with significantly reduced overall survival in patients with luminal A breast cancer. In IC‐cells, cell growth was enhanced upon EVE treatment whereas an EVE range of 0.1–100 nm decreased growth in DC‐cells. The mRNA expression of genes involved in epithelial–mesenchymal transition (EMT) such as CDH1, CLDN3, and CK19 was significantly decreased in IC‐cells, but remained unchanged in DC‐cells. These findings highlight a relationship between CIP2A and EMT in the intrinsic resistance of hormone therapy‐resistant breast cancers to EVE.
Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma
Authors: Li Anmao , Chen Xuanxin , Jing Zizi , Chen Jianbin
Published: August 2020

Multiple myeloma (MM) is the second most common hematologic malignancy of immunoglobulin‐secreting plasma cells. Recent modern combination therapies have improved survival rates, but many patients develop resistance to novel drugs, leading to relapse. Trifluoperazine (TFP), a typical antipsychotic drug, has been reported to exert antitumor effects by targeting various pathways. Thus far, the role of TFP in MM has not been elucidated. In the current study, we demonstrated that TFP inhibited cell growth and autophagy activity but induced apoptosis of U266 and RPMI 8226 MM cells. Furthermore, cotreatment of these cell lines with TFP and rapamycin, a potent autophagy inducer, reduced cell apoptosis compared with TFP treatment alone. We also found that TFP inhibited nuclear protein 1 (NUPR1) expression. In the presence of TFP, cells stably overexpressing NUPR1 showed a higher viability than cells treated with the nonspecific control. Autophagy suppression and apoptosis induction caused by TFP were also reversed in MM cells upon NUPR1 overexpression. Overall, our results indicate that in the context of MM, TFP targets NUPR1, inhibiting cell growth and inducing apoptosis by autophagy inhibition. Our results could contribute toward efforts for the development of more effective therapies for MM to be tested in future clinical trials.
Neurological manifestations of coronavirus infections – a systematic review
Authors: Almqvist Jesper , Granberg Tobias , Tzortzakakis Antonios , Klironomos Stefanos , Kollia Evangelia , Öhberg Claes , Martin Roland , Piehl Fredrik , Ouellette Russell , Ineichen Benjamin V.
Published: August 2020

To optimize diagnostic workup of the current severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, we systematically reviewed neurological and neuroradiological manifestations of SARS‐CoV‐2 and all other known human coronavirus species (HCoV). Which lessons can we learn? We identified relevant publications (until 26 July 2020) using systematic searches in PubMed, Web of Science, and Ovid EMBASE with predefined search strings. A total of 4571 unique publications were retrieved, out of which 378 publications were selected for in‐depth analysis by two raters, including a total of 17549 (out of which were 14418 SARS‐CoV‐2) patients. Neurological complications and associated neuroradiological manifestations are prevalent for all HCoVs (HCoV‐229E, HKU1, NL63, OC43, Middle East respiratory syndrome (MERS)‐CoV, SARS‐CoV‐1, and SARS‐CoV‐2). Moreover there are similarities in symptomatology across different HCoVs, particularly between SARS‐CoV‐1 and SARS‐CoV‐2. Common neurological manifestations include fatigue, headache, and smell/taste disorders. Additionally, clinicians need to be attentive for at least five classes of neurological complications: (1) Cerebrovascular disorders including ischemic stroke and macro/micro‐hemorrhages, (2) encephalopathies, (3) para‐/postinfectious immune‐mediated complications such as Guillain‐Barré syndrome and acute disseminated encephalomyelitis, (4) (meningo‐)encephalitis, potentially with concomitant seizures, and (5) neuropsychiatric complications such as psychosis and mood disorders. Our systematic review highlights the need for vigilance regarding neurological complications in patients infected by SARS‐CoV‐2 and other HCoVs, especially since some complications may result in chronic disability. Neuroimaging protocols should be designed to specifically screen for these complications. Therefore, we propose practical imaging guidelines to facilitate the diagnostic workup and monitoring of patients infected with HCoVs.
Site‐Specific MicroRNA‐33 Antagonism by pH‐Responsive Nanotherapies for Treatment of Atherosclerosis via Regulating Cholesterol Efflux and Adaptive Immunity
Authors: Li Chenwen , Dou Yin , Chen Yidan , Qi Yuantong , Li Lanlan , Han Songling , Jin Taotao , Guo Jiawei , Chen Jianhong , Zhang Jianxiang
Published: August 2020

Atherosclerosis remains the leading cause of a broad spectrum of deadliest cardiovascular diseases. MicroRNA‐33 is a new therapeutic target for atherosclerosis due to its diverse functions. However, it remains a great challenge in clinical translation of nucleic acid‐based microRNA‐targeting therapeutics. Considering lesional acidosis, herein cyclodextrin‐derived pH‐responsive and integrin‐targeting nanoparticles containing an antisense oligonucleotide against microRNA‐33 (anti‐miR33) are engineered for precision therapy of atherosclerosis. A desirable anti‐miR33 nanotherapy (AAM NP) is initially developed by screening carrier materials. AAM NP is further decorated with a peptide ligand cRGDfK for integrin to afford an active targeting nanotherapy RAAM NP, to achieve more effective delivery of anti‐miR33 to plaques and target cells. Both nanotherapies can be efficiently internalized by different cells relevant to atherosclerosis. After intravenous delivery, AAM NP passively accumulates in atherosclerotic plaques and related cells in apolipoprotein E‐deficient mice. Correspondingly, AAM NP treatment significantly attenuates atherosclerosis in mice and notably reduces vulnerable plaques. Decoration with cRGDfK considerably enhances the targeting capability and therapeutic effects of RAAM NP. Mechanistically, anti‐miR33 nanotherapies significantly promote reverse cholesterol transport and notably regulate adaptive immunity via modulating macrophage polarization and regulatory T cell differentiation. Consequently, the pH‐responsive anti‐miR33 nanotherapies are promising for targeted treatment of atherosclerosis.
Highly Tunable Ferroelectricity in Hybrid Improper Ferroelectric Sr3Sn2O7
Authors: Xu Xianghan , Wang Yazhong , Huang Fei‐Ting , Du Kai , Nowadnick Elizabeth A. , Cheong Sang‐Wook
Published: August 2020

The successful theoretical prediction and experimental demonstration of hybrid improper ferroelectricity (HIF) provides a new pathway to couple octahedral rotations, ferroelectricity, and magnetism in complex materials. To enable technological applications, an HIF with a small coercive field is desirable. Sr3Sn2O7 single crystals are successfully grown, and it is discovered that they exhibit the smallest electric coercive field at room temperature among all known HIFs. Furthermore, it is demonstated that a small external stress can repeatedly erase and re‐generate ferroelastic domains. In addition, using in‐plane piezo‐response force microscopy, abundant charged and neutral domain walls are charaterized. The observed small electrical and mechanical coercive field values are in accordance with the results of the first‐principles calculations on Sr3Sn2O7, which show low energy barriers for both 90° and 180° polarization switching compared to those in other experimentally demonstrated HIFs. The findings represent an advancement towards the possible technological implemetation of functional HIFs.
Gas Foaming Guided Fabrication of 3D Porous Plasmonic Nanoplatform with Broadband Absorption, Tunable Shape, Excellent Stability, and High Photothermal Efficiency for Solar Water Purification
Authors: Wang Hui , Zhang Ruijuan , Yuan Di , Xu Suying , Wang Leyu
Published: August 2020

Solar steam generation is an efficient way for water purification. However, it is still challenging to establish a steam generation system possessing high evaporation efficiency under natural sunlight condition with good durability. Herein a novel, free‐floating nanoplatform is constructed by a gas foaming strategy, embedding plasmonic Cu7S4‐MoS2‐Au nanoparticles (CMA NPs) in porous polydimethylsiloxane (PDMS) matrix. The gas diffusion process creates 3D porous PDMS matrix with low thermal conductivity and open channels, which allows for efficient energy confinement and fast water supply in an integral matrix, beneficial to mechanical strength of the system. By taking advantage of broadband absorption and high photothermal efficiency of CMA NPs and structural design of the matrix, the nanoplatform achieves a high evaporation rate (3.824 kg m−2 h−1) and photothermal conversion efficiency (96.6%) under one‐sun illumination (1 kW m−2). Moreover, such performance maintains stable even under harsh conditions in the presence of strong acid, strong base, strong oxidants, and high salinity, suggesting a broad prospect in seawater desalination, sewage treatment, sterilization and so on.
Comparison of Ionic Liquids and Chemical Permeation Enhancers for Transdermal Drug Delivery
Authors: Qi Qin M. , Duffy Miya , Curreri Alex M. , Balkaran Joel P. R. , Tanner Eden E. L. , Mitragotri Samir
Published: August 2020

Transdermal delivery offers a patient‐friendly method of drug administration. An ideal formulation for transdermal drug delivery should have high potency to enhance skin permeation and low tendency to induce skin irritation. Ionic liquids (ILs) and deep eutectic solvents (DESs) have recently been proposed to serve as an excellent platform to enable transdermal delivery of various therapeutics including proteins and siRNA. In spite of their success, general safety‐efficacy behavior of ILs/DESs is not reported. Using safety and efficacy as two design criteria, a Fourier transform infrared (FTIR) spectroscopy study is conducted to compare the performance of 31 ammonium‐based ILs/DESs and 44 conventional chemical permeation enhancer (CPE) molecules. FTIR analysis of skin stratum corneum exposed to ILs/DESs and CPEs is performed to extract features indicative of their safety and efficacy. ILs/DESs, as a class, outperformed conventional CPEs in terms of both potency and safety. Analysis of ILs/DESs and CPEs based on Hansen solubility parameters indicates that ILs/DESs possess solubility parameters close to those of skin, which may explain their superiority over CPEs. These studies support ILs/DESs as promising materials for novel drug delivery systems.
TGase‐Enhanced Microtissue Assembly in 3D‐Printed‐Template‐Scaffold (3D‐MAPS) for Large Tissue Defect Reparation
Authors: Yu Hongsheng , You Zhifeng , Yan Xiaojun , Liu Wei , Nan Zhirui , Xing Dan , Huang Chenyu , Du Yanan
Published: August 2020

Engineering large and functional tissue constructs with complex structures (e.g., external ear or nose) for reparation and reconstruction of tissue defects remains one of the major challenges in regenerative medicine, which demands abundant cell sources, advanced biofabrication schemes, and satisfactory integration with the host for long‐term efficacy post implantation. Here the ‘Microtissue Assembly in 3D‐Printed‐template‐Scaffold’ (3D‐MAPS), as a platform technology to rapidly fabricate centimeter‐sized functional tissue constructs with complex structures, is developed. 3D‐MAPS facilitates bottom‐up assembly of large‐scale manufactured microtissues within the 3D‐printed hollow polymeric templates with pre‐defined architectures. The assembly and fusion of 2×106mesenchymal stem cell–based microtissues within the defined 3D‐printed template is further enhanced by addition of a natural protein crosslinker (i.e., transglutaminase (TGase)), and thereby achieves construction of centimeter‐sized tissue with high cell viability and mechanical stability in vitro within 30 min. Further in vivo implantation of the 3D‐MAPS‐fabricated ear‐like tissue construct in rabbit models assisted by flap prefabrication technique results in increased structural vascular support and strengthened functional survival. Thus, the TGase‐enhanced 3D‐MAPS demonstrates its potential and feasibility as a powerful biofabrication platform for tissue engineering application.
Stretch‐Healable Molecular Nanofibers
Authors: Han Yanxiao , Langer Michal , Medved’ Miroslav , Otyepka Michal , Král Petr
Published: August 2020

Ultrastretchable nanofibers formed by covalently linked molecular flakes are introduced. Molecular dynamics simulations show that mixed coronene and perfluorocoronene molecular flakes in aqueous solutions form linear stacks having predominantly an alternating pattern. When such molecular flakes are covalently connected by short flexible molecular linkers into chains of various organizations, they can form stretchable and healable fibers with parameters dependent on humidity.
Combining Battery‐Type and Pseudocapacitive Charge Storage in Ag/Ti3C2Tx MXene Electrode for Capturing Chloride Ions with High Capacitance and Fast Ion Transport
Authors: Liang Mingxing , Wang Lei , Presser Volker , Dai Xiaohu , Yu Fei , Ma Jie
Published: August 2020

The recent advances in chloride‐ion capturing electrodes for capacitive deionization (CDI) are limited by the capacity, rate, and stability of desalination. This work introduces Ti3C2Tx/Ag synthesized via a facile oxidation‐reduction method and then uses it as an anode for chloride‐ion capture in CDI. Silver nanoparticles are formed successfully and uniformly distributed with the layered‐structure of Ti3C2Tx. All Ti3C2Tx/Ag samples are hydrophilic, which is beneficial for water desalination. Ti3C2Tx/Ag samples with a low charge transfer resistance exhibit both pseudocapacitive and battery behaviors. Herein, the Ti3C2Tx/Ag electrode with a reaction time of 3 h exhibits excellent desalination performance with a capacity of 135 mg Cl− g−1 at 20 mA g−1 in a 10 × 10−3 m NaCl solution. Furthermore, low energy consumption of 0.42 kWh kg−1 Cl− and a desalination rate of 1.5 mg Cl− g−1 min−1 at 50 mA g−1 is achieved. The Ti3C2Tx/Ag system exhibits fast rate capability, high desalination capacity, low energy consumption, and excellent cyclability, which can be ascribed to the synergistic effect between the battery and pseudocapacitive behaviors of the Ti3C2Tx/Ag hybrid material. This work provides fundamental insight into the coupling of battery and pseudocapacitive behaviors during Cl− capture for electrochemical desalination.
Microscopic Chromosomal Structural and Dynamical Origin of Cell Differentiation and Reprogramming
Authors: Chu Xiakun , Wang Jin
Published: August 2020

As an essential and fundamental process of life, cell development involves large‐scale reorganization of the 3D genome architecture, which forms the basis of gene regulation. Here, a landscape‐switching model is developed to explore the microscopic chromosomal structural origin of embryonic stem cell (ESC) differentiation and somatic cell reprogramming. It is shown that chromosome structure exhibits significant compartment‐switching in the unit of topologically associating domain. It is found that the chromosome during differentiation undergoes monotonic compaction with spatial repositioning of active and inactive chromosomal loci toward the chromosome surface and interior, respectively. In contrast, an overexpanded chromosome, which exhibits universal localization of loci at the chromosomal surface with erasing the structural characteristics formed in the somatic cells, is observed during reprogramming. An early distinct differentiation pathway from the ESC to the terminally differentiated cell, giving rise to early bifurcation on the Waddington landscape for the ESC differentiation is suggested. The theoretical model herein including the non‐equilibrium effects, draws a picture of the highly irreversible cell differentiation and reprogramming processes, in line with the experiments. The predictions provide a physical understanding of cell differentiation and reprogramming from the chromosomal structural and dynamical perspective and can be tested by future experiments.
An early (pre‐1500 BP) fishhook assemblage from Ofu and Olosega islands, Manu‘a Group, American Samoa: implications for technological evolution and cultural interaction
Authors: QUINTUS SETH , CLARK JEFFREY T.
Published: August 2020

Marine resources are integral to the subsistence of coastal populations in Oceania and have been since the islands were first settled. While items of fishing gear, most notably fishhooks, are found throughout the Pacific, they are not as common as one might think. Fishhooks are in fact noticeably uncommon in the Central Pacific, for example. Consequently, the various types of analyses of fishhook morphology, particularly the types of line attachment devices, that have been carried out on East Polynesian assemblages have not been possible for West Polynesian sites. Using a large collection of fishhooks from three sites on Ofu and Olosega islands in the Manu‘a Group of American Samoa, we present a detailed analysis of a large combined assemblage and compare the data collected to those from other islands and island groups in the region. We show that the hooks reflect exploitation emphasising inshore environments, and that angling as a fish capture method is likely to vary in intensity based on local environmental variability. Moreover, we illustrate how these fishhooks constitute a means of assessing both early cultural contacts and cultural variability in the Central Pacific.
Highly efficient detection of Cu2+and B4O72−based on a recyclable asymmetric salamo‐based probe in aqueous medium
Authors: Xu Xin , Li Ya‐Juan , Feng Tao , Dong Wen‐Kui , Ding Yu‐Jie
Published: August 2020

An asymmetric salamo‐based probe molecule (H2L) was synthesized and characterized structurally. When DMF/H2O (9:1) was used as the solvent, it was shown probeH2Lhas high sensitivity to Cu2+. Using high‐resolution mass spectrometry and theoretical calculation, it was found that probeH2Lcould form a more stable complex (1:1) with Cu2+, the minimum limit of detection (LOD) ofH2Lfor Cu2+was calculated as 9.95 × 10−8M. In addition, probeH2Lcould also be used to identify B4O72−under the same detection conditions and the minimum LOD ofH2Lfor B4O72−was calculated as 4.98 × 10−7M. At the same time, density functional theory theoretical calculation further proved the flexibility of probeH2L. Through the action of EDTA, probeH2Lhad a cyclic ability to recognize Cu2+, and showed a better response in the physiological pH range; probeH2Lhad the characteristics of fast recognition speed and high efficiency. In addition, with probeH2Ltest paper for Cu2+and B4O72−, the effect was more obvious. Meanwhile, probeH2Lcan be used to quantitatively detect Cu2+in water samples.
The FTO/miR‐181b‐3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer
Authors: Xu Yuanyuan , Ye Shuang , Zhang Nan , Zheng Shuhui , Liu Huatao , Zhou Kewen , Wang Ling , Cao Yue , Sun Peng , Wang Tinghuai
Published: August 2020

Background

N6‐methyladenosine (m6A) RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors, including breast cancer. Fat mass and obesity‐associated (FTO) enzyme, initially known as the obesity‐related protein, is the first identified m6A demethylase. However, the relationship between FTO and breast cancer remains controversial. In this study, we aimed to elucidate the role and clinical significance of FTO in breast cancer and to explore the underlying mechanism.

Methods

We first investigated the expression of FTO in breast cancer cell lines and tissues by quantitative reverse transcription‐PCR (qRT‐PCR), Western blotting, and immunohistochemistry. Wound healing assay and Transwell assay were performed to determine the migration and invasion abilities of SKBR3 and MDA‐MB453 cells with either knockdown or overexpression of FTO. RNA sequencing (RNA‐seq) was conducted to decipher the downstream targets of FTO. qRT‐PCR, luciferase reporter assay, and Western blotting were employed to confirm the existence of the FTO/miR‐181b‐3p/ARL5B axis. The biological function of ADP ribosylation factor like GTPase 5B (ARL5B) in breast cancer cells was evaluated by wound healing assay and Transwell invasion assay.

Results

High FTO expression was observed in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer, predicting advanced progression (tumor size [P < 0.001], nuclear grade [P = 0.001], peritumoral lymphovascular invasion [P < 0.001), lymph node metastasis [P = 0.002], and TNM stage [P = 0.001]) and poor prognosis. Moreover, FTO promoted cell invasion and migration in vitro. Mechanistically, RNA‐seq and further confirmation studies suggested that FTO up‐regulated ARL5B by inhibiting miR‐181b‐3p. We further verified that ARL5B also displayed carcinogenic activity in breast cancer cells.

Conclusion

Our work demonstrated the carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR‐181b‐3p/ARL5B signaling pathway.
Towards Responsive Single‐Molecule Device
Authors: Chen Yaorong , Huang Longfeng , Chen Hang , Chen Zhixin , Zhang Hewei , Xiao Zongyuan , Hong Wenjing
Published: August 2020

Single‐molecule devices, which are fabricated by the single molecule bridged through electrodes, provide a promising approach to investigate the intrinsic chemical or physical properties of individual molecules. Beyond the studies of single‐molecule wires, a large number of responsive single‐molecule junctions or devices with unique chemical or physical properties have been designed and fabricated by introducing the external field, which further offers the chance to explore conductive materials at the molecular level. Here, we summarized the latest studies on the behaviors of single‐molecule devices based on the photon, thermal, electric, or magnetic responses, and discussed the development of responsive single‐molecule devices in prospect.
Eleven‐marker 10‐color flow cytometric assessment of measurable residual disease for T‐cell acute lymphoblastic leukemia using an approach of exclusion
Authors: Tembhare Prashant R. , Chatterjee Gaurav , Khanka Twinkle , Ghogale Sitaram , Badrinath Yajamanam , Deshpande Nilesh , Panda Devasis , Patkar Nikhil V. , Narula Gaurav , Girase Karishma , Verma Shefali , Sanyal Mahima , Sriram Harshini N. , Banavali Shripad , Gujral Sumeet , Subramanian Papagudi G.
Published: August 2020

Measurable/minimal residual disease (MRD) status has been suggested as a powerful indicator of clinical‐outcome in T‐cell lymphoblastic leukemia/lymphoma (T‐ALL). Multicolor flow cytometric (MFC)‐based T‐ALL MRD reports are limited and traditionally based on the utilization of markers‐of‐immaturity like TdT and CD99. Moreover, studies demonstrating the multicolor flow cytometric (MFC) approach for the assessment of T‐ALL MRD are sparse. Herein, we describe an 11‐marker, 10‐color MFC‐based T‐ALL MRD method using an “approach of exclusion.”

Methods

The study included 269 childhood T‐ALL patients treated with a modified‐MCP841 protocol. An 11‐marker, 10‐color MFC‐based MRD was performed in bone marrow (BM) samples at the end‐of‐induction (EOI) and end‐of‐consolidation (EOC) time‐points using Kaluza‐version‐1.3 software.

Results

We studied EOI‐MRD in 269 and EOC‐MRD in 105 childhood T‐ALL patients. EOI‐MRD was detectable in 125 (46.5%) samples (median, 0.3%; range, 0.0007–66.3%), and EOC‐MRD was detectable in 34/105 (32.4%) samples (median, 0.055%; range, 0.0008–27.6%). Leukemia‐associated immunophenotypes (LAIPs) found useful for MRD assessment were dual‐negative CD4/CD8 (40.9%), dual‐positive CD4/CD8 (23.3%) and only CD4 or CD8 expression (35.8%); dim/subset/dim‐negative surface‐CD3 (39%), dim/subset/dim‐negative/negative CD5 (28.3%), dim/dim‐negative/negative/heterogeneous CD45 (44.7%) and co‐expression of CD5/CD56 (7.5%). EOI‐MRD‐positive status was found to be the most‐relevant independent factor in the prediction of inferior relapse‐free and overall survival.

Conclusion

We described an 11‐marker 10‐color MFC‐based highly sensitive MRD assay in T‐ALL using an approach of exclusion. The addition of CD4 and CD8 to the pan‐T‐cell markers in a 10‐color assay is highly useful in T‐ALL MRD assessment and extends its applicability to almost all T‐ALL patients.
High‐throughput liquid chromatography tandem mass spectrometry assay as initial testing procedure for analysis of total urinary fraction
Authors: Sobolevsky Tim , Ahrens Brian
Published: August 2020

In the recent years, a lot of effort was put into the development of multiclass initial testing procedures (ITP) to streamline analytical workflow in antidoping laboratories. Here, a high‐throughput assay based on liquid chromatography–triple quadrupole mass spectrometry suitable for use as initial testing procedure covering multiple classes of compounds prohibited in sports is described. Employing a 96‐well plate packed with 10 mg of weak cation exchange polymeric sorbent, up to 94 urine samples and their associated positive and negative controls can be processed in less than 3 h with minimal labor. The assay requires a 0.5‐ml urine aliquot, which is subjected to enzymatic hydrolysis followed by solid phase extraction, evaporation, and reconstitution in a 96‐well collection plate. With a 10‐min run time, more than 100 analytes can be detected using electrospray ionization with polarity switching. The assay can be run nearly 24/7 with minimal downtime for instrument maintenance while detecting picogram amounts for the majority of analytes. Having analyzed approximately 28,000 samples, nearly 400 adverse analytical findings were found of which only one tenth were at or above 50% of the minimum required performance level established by the World Anti‐Doping Agency. Compounds most often identified were stanozolol, GW1516, ostarine, LGD4033, and clomiphene, with median estimated concentrations in the range of 0.02–0.09 ng/ml (either as parent drug or a metabolite). Our data demonstrate the importance of using a highly sensitive ITP to ensure efficient antidoping testing.
Experimental study of the influence of structural planes on the mechanical properties of sandstone specimens under cyclic dynamic disturbance
Authors: Du Han , Song Danqing , Chen Zhuo , Guo Zizheng
Published: August 2020

Discontinuity‐controlled slopes constitute potentially fatal risks during exploitation activities in open‐pit mines and severely threaten the safe mining of collieries. To investigate the dynamic mechanical properties of rock with structural planes under periodic cyclic dynamic disturbance, this study took the north side of the Anjialing open‐pit mine as an example. Uniaxial compression tests were carried out on rock samples containing structural planes with different dip angles (θ). The impacts of θ on the strength, deformation characteristics, energy dissipation characteristics, and fracture rules of rock samples under different disturbance stress amplitudes (Δσ) are studied. The test results show that the structural plane affects the mechanical properties of rocks under dynamic perturbation. A closed hysteresis loop curve of rock is formed in each loading and unloading cycle, thus forming three stages: a sparse stage, a dense stage, and another sparse stage. θ, Δσ, and the number of disturbance cycles (n) impact the rock hysteresis loop curve and deformation modulus. The plastic deformation of rock mainly includes an initial deformation stage, an isokinetic deformation stage, and an accelerated deformation and overall failure stage. Moreover, there is a disturbance threshold for Δσ′ of the rock failure, and the evolution law of plastic strain accumulation and n near the disturbance threshold conform to the negative exponential function and the inverse function of the Langevin function, respectively. Based on damage theory, a constitutive model of the structural plane considering a disturbance threshold is proposed.
Quantum computing inspired framework of student performance assessment in smart classroom
Authors: Bhatia Munish , Kaur Avneet
Published: August 2020

Internet of Things (IoT) technology, merged with fog‐cloud computing, has provided efficient services in the education industry. Inspired by this aspect, this paper presents an effective framework of the smart classroom for optimal evaluation of the performance of students and teachers based on quantum game‐theoretic (QGT) decision making. Specifically, IoT technology is incorporated inside the classroom to acquire data about students and teachers for determining the academic enhancement of students. The acquired data is evaluated over the fog‐cloud computing platform to estimate a quantifiable measure of probability of performance using the Bayesian modeling technique. Moreover, to analyze the student and teacher performance over the temporal scale, student performance indicator and teacher performance indicator are calculated. Finally, student‐teacher performance is assessed using the effective two‐player quantum gametic decision‐making. The experimental simulation on four challenging datasets namely student performance (7029 instances), student academic performance (3585 instances), student performance prediction (2120 instances), and student performance analysis (6507 instances) shows the effectiveness of the proposed framework. The simulation results are contrasted with various state‐of‐the‐art techniques to estimate the overall efficiency of the proposed system. Moreover, mathematical analysis has been carried out to depict the performance of the proposed framework.
Hybridization and introgression between toads with different sex chromosome systems
Authors: Dufresnes Christophe , Litvinchuk Spartak N , Rozenblut-Kościsty Beata , Rodrigues Nicolas , Perrin Nicolas , Crochet Pierre-André , Jeffries Daniel L
Published: August 2020

The growing interest in the lability of sex determination in non-model vertebrates such as amphibians and fishes has revealed high rates of sex chromosome turnovers among closely related species of the same clade. Can such lineages hybridize and admix with different sex-determining systems, or could the changes have precipitated their speciation? We addressed these questions in incipient species of toads (Bufonidae), where we identified a heterogametic transition and characterized their hybrid zone with genome-wide markers (RADseq). Adult and sibship data confirmed that the common toad B. bufo is female heterogametic (ZW), while its sister species the spined toad B. spinosus is male heterogametic (XY). Analysis of a fine scale transect across their parapatric ranges in southeastern France unveiled a narrow tension zone (∼10 km), with asymmetric mitochondrial and nuclear admixture over hundreds of kilometers southward and northward, respectively. The geographic extent of introgression is consistent with an expansion of B. spinosus across B. bufo’s former ranges in Mediterranean France, as also suggested by species distribution models. However, widespread cyto-nuclear discordances (B. spinosus backrosses carrying B. bufo mtDNA) run against predictions from the dominance effects of Haldane's rule, perhaps because Y and W heterogametologs are not degenerated. Common and spined toads can thus successfully cross-breed despite fundamental differences in their sex determination mechanisms, but remain partially separated by reproductive barriers. Whether and how the interactions of their XY and ZW genes contribute to these barriers shall provide novel insights on the debated role of labile sex chromosomes in speciation.
Forecasting negative yield‐curve distributions
Authors: Jun Jae‐Yun , Lebreton Victor , Rakotondratsimba Yves
Published: August 2020

Negative interest rates have been present in various marketplaces since mid‐2014, following the negative interest rate policy (NIRP) adopted by the European Central Bank to raise economic growth. The well‐known historical approach (HA) appears to be a good resource. By tweaking the HA, we derive a very tractable data‐driven tool that allows practitioners to generate yield‐curve distributions at future discrete time horizons. We thereby provide a robust and easy‐to‐understand forecasting model, suitable for the NIRP context, allowing an appreciation of its predictive power. Besides the methodological development herein, various numerical illustrations are presented to shed light on the benefits (and limitations) of this forecasting approach.
Research progress on exosomes derived from mesenchymal stem cells in hematological malignancies
Authors: Lyu Tianxin , Zhang Binglei , Li Mengjia , Jiao Xueli , Song Yongping
Published: August 2020

Mesenchymal stem cells (MSCs) are a subset of multifunctional stem cells with self‐renewal and multidirectional differentiation properties that play a pivotal role in tumor progression. MSCs are reported to exert biological functions by secreting specialized vesicles, known as exosomes, with tumor cells. Exosomes participate in material and information exchange between cells and are crucial in multiple physiological and pathological processes. This study provides a comprehensive overview of the roles, mechanisms of action and sources of MSC exosomes in hematological malignancies, and different tumor types.
Sclerostin-Neutralizing Antibody Treatment Rescues Negative Effects of Rosiglitazone on Mouse Bone Parameters
Authors: Farrell Mariah , Fairfield Heather , Costa Samantha , D'Amico Anastasia , Falank Carolyne , Brooks Daniel J , Reagan Michaela R
Published: August 2020

Obesity, a growing pandemic, is a risk factor for many cancers and causes increased bone marrow adipose tissue (BMAT). in vitro studies and obese animal models suggest that BMAT contributes to cancer progression, but there is a lack of preclinical models to directly test BMAT's role in cancer. Overactivation of peroxisome-proliferator-activated receptor-γ (PPARγ) can skew bone formation and resorption rates, resulting in increased BMAT and trabecular bone loss. Thiazolidinediones (eg, rosiglitazone) are anti-diabetic therapies that promote adipogenesis through PPARγ activation. We investigated if rosiglitazone increases BMAT in an immunocompromised model, commonly used in cancer research, and if these effects could be reversed by co-administering a bone anabolic agent (sclerostin-neutralizing antibody [Scl-Ab]), which has been shown to inhibit adipogenesis, using DXA, μCT, OsO4 μCT, and dynamic histomorphometry. Four weeks of rosiglitazone in female SCID Beige mice (cohort 1) significantly decreased trabecular bone volume (BV/TV) by about one-half, through increased osteoclast and suppressed osteoblast activity, and significantly increased BMAT. In cohort 2, mice were administered rosiglitazone ± Scl-Ab for 4 weeks, and then rosiglitazone was discontinued and Scl-Ab or vehicle were continued for 6 weeks. Scl-Ab significantly increased bone parameters (eg, BV/TV, N.Ob/B.Pm, and MS/BS) in both groups. Scl-Ab also overcame many negative effects of rosiglitazone (eg, effects on trabecular bone parameters, increased mineralization lag time [MLT], and decreased bone formation rate [BFR]). Interestingly, Scl-Ab significantly decreased rosiglitazone-induced BMAT in the femur, mostly due to a reduction in adipocyte size, but had a much weaker effect on tibial BMAT. These data suggest targeting sclerostin can prevent rosiglitazone-induced bone loss and reduce BM adiposity, in some, but not all BMAT locations. Collectively, our data demonstrate that rosiglitazone increases BMAT in SCID Beige mice, but concomitant changes in bone may confound its use to specifically determine BMAT's role in tumor models. © 2020 American Society for Bone and Mineral Research (ASBMR).
Double‐filtration plasmapheresis combined with immunosuppressive treatment for severe pemphigus: 10 years' experience of a single center in China
Authors: Liu Yan , Zhang Bingjie , Ma Jie , Wang Haiyun , Fan Xiaohong , Zheng Ke , Chen Limeng , Li Xuewang , Qin Yan , Li Li , Li Xuemei
Published: August 2020

Background

Pemphigus is a group of rare and severe autoimmune blistering disease mediated by pathogenic autoantibodies against desmogleins. Plasmapheresis can directly remove autoantibodies from circulation, which has been applied to the treatment of pemphigus as an adjuvant therapy. But the results of the researches are controversial. This study aims to evaluate the efficacy and safety of double filtration plasmapheresis (DFPP) combined with immunosuppressive treatment for patients with severe pemphigus in our single center.

Methods

We retrospectively analyzed 17 patients with severe pemphigus who were unresponsive to high‐dose corticosteroid and received DFPP treatment between January 2010 and January 2020. The information on demographic characteristics, clinical and laboratory data, treatment regimens, and clinical outcomes were collected.

Results

All the patients were diagnosed as severe pemphigus and had a period of at least 1 week of high‐dose prednisone (1‐1.5 mg/kg/day), but they were unresponsive to corticosteroid and immunosuppressants treatment. They received DFPP treatment as an adjuvant therapy. After DFPP treatment, the titers of desmogleins antibodies significantly decreased (P < .001), Nikolsky's sign became negative and no new blisters appeared. The dosage of corticosteroid could begin to taper down rapidly in 9 ± 4 days. On discharge, the dosage of prednisone decreased significantly (51 ± 3 mg/day, P < .001). No major adverse events happened that could lead to the termination of DFPP treatment.

Conclusion

Double filtration plasmapheresis combined with immunosuppressive treatment is an effective and safe therapeutic regimen for severe pemphigus. DFPP can also contribute to the dosage reduction of steroid to avoid more drug‐related side effect.
Synthesis and pancreatic lipase inhibitory activities of some 1,2,4‐triazol‐5(3)‐one derivatives
Authors: Ozdemir Yusuf , Bekircan Olcay , Baltaş Nimet , Menteşe Emre
Published: August 2020

In this study, starting from 4‐amino‐5‐(4‐chlorobenzyl)‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐one (1), the 4‐Amino‐5‐(4‐chlorobenzyl)‐2‐undecyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one (2) was first synthesized and this compound was converted to Schiff base derivatives (3a‐e). In the second step of the study, the 2‐[3‐(4‐chlorobenzyl)‐5‐oxo‐1‐undecyl‐1,5‐dihydro‐4H‐1,2,4‐triazole‐4‐yl]‐acetohydrazide (6), which was used as a key product in the synthesis of many heterocyclic compounds was synthesized in four steps, and then this compound was converted into methylidene acetohydrazide (7a‐e), thiosemicarbazide (8a‐e), and 1,2,4‐triazole‐5‐thione (9a‐e) derivatives. Also, in the last part of the study, 1,2,4‐triazole‐5‐thione derivatives were changed into Mannich bases (10a‐b) bearing a 4‐phenylpiperazine ring. These new compounds were tested with regard to pancreatic lipase (PL) inhibition activity, and compound 3b, 3d, 7d, 8d, and 9d showed a considerable anti‐lipase activity at various concentrations. The activity of compounds 7b (IC50 = 1.45 ± 0.12 μM) was the highest in terms of IC50, comparable to that of orlistat, a well‐known PL inhibitor used as an antiobesity drug.
Adaptations for matrotrophy in the female reproductive system in the pseudoscorpion Chelifer cancroides (Chelicerata: Pseudoscorpiones, Cheliferidae)
Authors: Jędrzejowska Izabela , Garbiec Arnold
Published: August 2020

Pseudoscorpiones (pseudoscorpions, false scorpions) is an order of small terrestrial chelicerates. While most chelicerates are lecithotrophic, that is, embryos develop due to nutrients (mostly yolk) deposited in the oocyte cytoplasm, pseudoscorpions are matrotrophic, that is, embryos are nourished by the female. Pseudoscorpion oocytes contain only a small amount of yolk. The embryos develop within a brood sac carried on the abdominal site of the female and absorb nutrients by a pumping organ. It is believed that in pseudoscorpions nutrients for developing embryos are produced in the ovary during a postovulatory (secretory) phase of the ovarian cycle. The goal of our study was to analyze the structure of the female reproductive system during the secretory phase in the pseudoscorpion Chelifer cancroides, a representative of the family Cheliferidae, considered to be one of the most advanced pseudoscorpion taxa. We use diverse microscopic techniques to document that the nutritive fluid is produced not only in the ovaries but also by the epithelial cells in the oviducts. The secretory active epithelial cells are hypertrophic and polyploid and release their content by fragmentation of apical parts. Our observations also indicate that fertilization occurs in the oviducts. Moreover, in contrast to previous findings, we show that secretion of the nutritive material starts when the fertilized oocytes reach the brood sac and thus precedes formation of the pumping organ. Summing up, we show that C. cancroides exhibits traits of advanced adaptations for matrotrophy due to coordinated secretion of the nutritive fluid by the ovarian and oviductal epithelial cells, which substantially increases the efficiency of nutritive fluid formation. Since the secretion of nutrients starts before formation of the pumping organ, we suggest that the embryos are able to absorb the nutritive fluid also in the early embryonic stages.