bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolating Large‐Scale Smoke Impacts on Cloud and Precipitation Processes Over the Amazon With Convection Permitting Resolution
Authors: Herbert Ross , Stier Philip , Dagan Guy 
Published: June 2021

AbstractAbsorbing aerosol from biomass burning impacts the hydrological cycle and radiation fluxes both directly and indirectly via modifications to convective processes and cloud development. Using the ICOsahedral Non‐hydrostatic modelling framework in a regional configuration with 1,500 m convection‐permitting resolution, we isolate the response of the Amazonian atmosphere to biomass burning smoke via enhanced cloud droplet number concentrations Nd (aerosol‐cloud interactions; ACI) and changes to radiative fluxes (aerosol‐radiation interactions; ARI) over a period of 8 days. We decompose ARI into contributions from reduced shortwave radiation and localized heating of the smoke. We show ARI influences the formation and development of convective cells: surface cooling below the smoke drives suppression of convection that increases with smoke optical depth, while the elevated heating promotes initial suppression and subsequent intensification of convection overnight; a corresponding diurnal response (repeating temporal response day‐after‐day) from high precipitation rates is shown. Enhanced Nd (ACI) perturbs the bulk cloud properties and suppresses low‐to‐moderate precipitation rates. Both ACI and ARI result in enhanced high‐altitude ice clouds that have a strong positive longwave radiative effect. Changes to low‐cloud coverage (ARI) and albedo (ACI) drive an overall negative shortwave radiative effect, that slowly increases in magnitude due to a moistening of the boundary layer. The overall net radiative effect is dominated by the enhanced high‐altitude clouds, and is sensitive to the plume longevity. The considerable diurnal responses that we simulate cannot be observed by polar orbiting satellites widely used in previous work, highlighting the potential of geostationary satellites to observe large‐scale impacts of aerosols on clouds.
ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron
Authors: Lu Shan , Wang Xuan-zhong , He Chuan , Wang Lei , Liang Shi-peng , Wang Chong-cheng , Li Chen , Luo Tian-fei , Feng Chun-sheng , Wang Zhen-chuan , Chi Guang-fan , Ge Peng-fei 
Published: June 2021

AbstractFerroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 μM) or improved by ferric ammonium citrate (500 μM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 μM) or liproxstatin-1 (30 μM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.
SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target
Authors: Xia Bingqing , Shen Xurui , He Yang , Pan Xiaoyan , Liu Feng-Liang , Wang Yi , Yang Feipu , Fang Sui , Wu Yan , Duan Zilei , Zuo Xiaoli , Xie Zhuqing , Jiang Xiangrui , Xu Ling , Chi Hao , Li Shuangqu , Meng Qian , Zhou Hu , Zhou Yubo , Cheng Xi , Xin Xiaoming , Jin Lin , Zhang Hai-Lin , Yu Dan-Dan , Li Ming-Hua , Feng Xiao-Li , Chen Jiekai , Jiang Hualiang , Xiao Gengfu , Zheng Yong-Tang , Zhang Lei-Ke , Shen Jingshan , Li Jia , Gao Zhaobing 
Published: June 2021

AbstractCytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics
Authors: Yang Boguang , Wei Kongchang , Loebel Claudia , Zhang Kunyu , Feng Qian , Li Rui , Wong Siu Hong Dexter , Xu Xiayi , Lau Chunhon , Chen Xiaoyu , Zhao Pengchao , Yin Chao , Burdick Jason A. , Wang Yi , Bian Liming 
Published: June 2021

Abstract3D culture of cells in designer biomaterial matrices provides a biomimetic cellular microenvironment and can yield critical insights into cellular behaviours not available from conventional 2D cultures. Hydrogels with dynamic properties, achieved by incorporating either degradable structural components or reversible dynamic crosslinks, enable efficient cell adaptation of the matrix and support associated cellular functions. Herein we demonstrate that given similar equilibrium binding constants, hydrogels containing dynamic crosslinks with a large dissociation rate constant enable cell force-induced network reorganization, which results in rapid stellate spreading, assembly, mechanosensing, and differentiation of encapsulated stem cells when compared to similar hydrogels containing dynamic crosslinks with a low dissociation rate constant. Furthermore, the static and precise conjugation of cell adhesive ligands to the hydrogel subnetwork connected by such fast-dissociating crosslinks is also required for ultra-rapid stellate spreading (within 18 h post-encapsulation) and enhanced mechanosensing of stem cells in 3D. This work reveals the correlation between microscopic cell behaviours and the molecular level binding kinetics in hydrogel networks. Our findings provide valuable guidance to the design and evaluation of supramolecular biomaterials with cell-adaptable properties for studying cells in 3D cultures.
Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum
Authors: Cai Shenglin , Pataillot-Meakin Thomas , Shibakawa Akifumi , Ren Ren , Bevan Charlotte L. , Ladame Sylvain , Ivanov Aleksandar P. , Edel Joshua B. 
Published: June 2021

AbstractMicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 μl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.
Promiscuous molecules for smarter file operations in DNA-based data storage
Authors: Tomek Kyle J. , Volkel Kevin , Indermaur Elaine W. , Tuck James M. , Keung Albert J. 
Published: June 2021

AbstractDNA holds significant promise as a data storage medium due to its density, longevity, and resource and energy conservation. These advantages arise from the inherent biomolecular structure of DNA which differentiates it from conventional storage media. The unique molecular architecture of DNA storage also prompts important discussions on how data should be organized, accessed, and manipulated and what practical functionalities may be possible. Here we leverage thermodynamic tuning of biomolecular interactions to implement useful data access and organizational features. Specific sets of environmental conditions including distinct DNA concentrations and temperatures were screened for their ability to switchably access either all DNA strands encoding full image files from a GB-sized background database or subsets of those strands encoding low resolution, File Preview, versions. We demonstrate File Preview with four JPEG images and provide an argument for the substantial and practical economic benefit of this generalizable strategy to organize data.
Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia
Authors: Ecker Veronika , Stumpf Martina , Brandmeier Lisa , Neumayer Tanja , Pfeuffer Lisa , Engleitner Thomas , Ringshausen Ingo , Nelson Nina , Jücker Manfred , Wanninger Stefan , Zenz Thorsten , Wendtner Clemens , Manske Katrin , Steiger Katja , Rad Roland , Müschen Markus , Ruland Jürgen , Buchner Maike 
Published: June 2021

AbstractCurrent therapeutic approaches for chronic lymphocytic leukemia (CLL) focus on the suppression of oncogenic kinase signaling. Here, we test the hypothesis that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT (PI3K/AKT)-signaling pathway may be leveraged to trigger CLL cell death. Though counterintuitive, our data show that genetic hyperactivation of PI3K/AKT-signaling or blocking the activity of the inhibitory phosphatase SH2-containing-inositol-5′-phosphatase-1 (SHIP1) induces acute cell death in CLL cells. Our mechanistic studies reveal that increased AKT activity upon inhibition of SHIP1 leads to increased mitochondrial respiration and causes excessive accumulation of reactive oxygen species (ROS), resulting in cell death in CLL with immunogenic features. Our results demonstrate that CLL cells critically depend on mechanisms to fine-tune PI3K/AKT activity, allowing sustained proliferation and survival but avoid ROS-induced cell death and suggest transient SHIP1-inhibition as an unexpectedly promising concept for CLL therapy.
Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance
Authors: Yamazaki Chisato M. , Yamaguchi Aiko , Anami Yasuaki , Xiong Wei , Otani Yoshihiro , Lee Jangsoon , Ueno Naoto T. , Zhang Ningyan , An Zhiqiang , Tsuchikama Kyoji 
Published: June 2021

AbstractBreast tumors generally consist of a diverse population of cells with varying gene expression profiles. Breast tumor heterogeneity is a major factor contributing to drug resistance, recurrence, and metastasis after chemotherapy. Antibody-drug conjugates (ADCs) are emerging chemotherapeutic agents with striking clinical success, including T-DM1 for HER2-positive breast cancer. However, these ADCs often suffer from issues associated with intratumor heterogeneity. Here, we show that homogeneous ADCs containing two distinct payloads are a promising drug class for addressing this clinical challenge. Our conjugates show HER2-specific cell killing potency, desirable pharmacokinetic profiles, minimal inflammatory response, and marginal toxicity at therapeutic doses. Notably, a dual-drug ADC exerts greater treatment effect and survival benefit than does co-administration of two single-drug variants in xenograft mouse models representing intratumor HER2 heterogeneity and elevated drug resistance. Our findings highlight the therapeutic potential of the dual-drug ADC format for treating refractory breast cancer and perhaps other cancers.
Giant phonon anomalies in the proximate Kitaev quantum spin liquid α-RuCl3
Authors: Li Haoxiang , Zhang T. T. , Said A. , Fabbris G. , Mazzone D. G. , Yan J. Q. , Mandrus D. , Halász Gábor B. , Okamoto S. , Murakami S. , Dean M. P. M. , Lee H. N. , Miao H. 
Published: June 2021

AbstractThe Kitaev quantum spin liquid epitomizes an entangled topological state, for which two flavors of fractionalized low-energy excitations are predicted: the itinerant Majorana fermion and the Z2 gauge flux. It was proposed recently that fingerprints of fractional excitations are encoded in the phonon spectra of Kitaev quantum spin liquids through a novel fractional-excitation-phonon coupling. Here, we detect anomalous phonon effects in α-RuCl3 using inelastic X-ray scattering with meV resolution. At high temperature, we discover interlaced optical phonons intercepting a transverse acoustic phonon between 3 and 7 meV. Upon decreasing temperature, the optical phonons display a large intensity enhancement near the Kitaev energy, JK~8 meV, that coincides with a giant acoustic phonon softening near the Z2 gauge flux energy scale. These phonon anomalies signify the coupling of phonon and Kitaev magnetic excitations in α-RuCl3 and demonstrates a proof-of-principle method to detect anomalous excitations in topological quantum materials.
Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis
Authors: Huan Leitao , Shu Xiaomin , Zu Weisai , Zhong De , Huo Haohua 
Published: June 2021

AbstractAsymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.
Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients
Authors: Paoletti Costanza , Regan Meredith M. , Niman Samuel M. , Dolce Emily M. , Darga Elizabeth P. , Liu Minetta C. , Marcom P. Kelly , Hart Lowell L. , Smith John W. , Tedesco Karen L. , Amir Eitan , Krop Ian E. , DeMichele Angela M. , Goodwin Pamela J. , Block Margaret , Aung Kimberly , Brown Martha E. , McCormack Robert T. , Hayes Daniel F. 
Published: June 2021

AbstractCirculating tumor cells (CTC) are prognostic in metastatic breast cancer (MBC). The CTC-endocrine therapy index (CTC-ETI), consisting of CTC-ER (estrogen receptor), BCL2, human epidermal growth factor receptor (HER2), and Ki67 expression, might predict resistance to endocrine therapy (ET) in patients with ER-positive MBC. One hundred twenty-one patients with ER-positive/HER2-negative MBC initiating a new ET after ≥1 lines of ET were enrolled in a prospective, multi-institutional clinical trial. CTC-ETI and clinical/imaging follow-up were performed at baseline and serial time points. Progression-free survival (PFS) and rapid progression (RP; determined at the 3-month time point) were primary endpoints. Associations with clinical outcomes used logrank and Fisher’s exact tests. At baseline, 36% (38/107) of patients had ≥5 CTC/7.5 ml whole blood (WB). Patients with ≥5 vs. <5 CTC/7.5 ml WB had significantly worse PFS (median 3.3 vs. 5.9 months, P = 0.03). Elevated CTC at 1 month was associated with even worse PFS (1.9 vs. 5.0 months from the 1-month sample, P < 0.001). Low, intermediate, and high CTC-ETI were observed in 71 (66%), 8 (8%), and 28 (26%) patients, with median PFS of 6.9, 8.5, and 2.8 months, respectively (P = 0.008). Patients with high vs. low CTC and CTC-ETI more frequently experienced RP (CTC: 66% vs. 41%; P = 0.03; CTC-ETI: 79% vs. 40%; P = 0.002). In conclusion, CTC enumeration and the CTC-ETI assay are prognostic at baseline and follow-up in patients with ER-positive/HER2-negative MBC starting new ET. CTC at first follow-up might identify a group of patients with ER-positive MBC that could forego ET, but CTC-ETI did not contribute further.
Senolytics improve bone forming potential of bone marrow mesenchymal stem cells from aged mice
Authors: Zhou Yueying , Xin Xiaonan , Wang Lichao , Wang Binsheng , Chen Li , Liu Ousheng , Rowe David W. , Xu Ming 
Published: June 2021

AbstractThe osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) declines dramatically with aging. By using a calvarial defect model, we showed that a senolytic cocktail (dasatinib+quercetin; D + Q) improved osteogenic capacity of aged BMSC both in vitro and in vivo. The study presented a model to assess strategies to improve bone-forming potential on aged BMSCs. D + Q might hold promise for improving BMSC function in aged populations.
The effect of endurance and endurance-strength training on body composition and cardiometabolic markers in abdominally obese women: a randomised trial
Authors: Jamka Małgorzata , Mądry Edyta , Krzyżanowska-Jankowska Patrycja , Skrypnik Damian , Szulińska Monika , Mądry Radosław , Lisowska Aleksandra , Batyrova Gulnara , Duś-Żuchowska Monika , Gotz-Więckowska Anna , Bogdański Paweł , Walkowiak Jarosław 
Published: June 2021

AbstractStudies comparing the effect of endurance and endurance-strength training on cardiometabolic markers provided inconsistent results. Therefore, the study aimed to compare the effect of endurance and endurance-strength training on body composition and cardiometabolic parameters in abdominally obese women. In this randomised trial, 101 subjects were included and divided into endurance (n = 52) and endurance-strength (n = 49) training. During the 12-week intervention, participants performed supervised one-hour training three times a week. Body composition, blood pressure (BP), markers of glucose and lipid homeostasis, and myoglobin levels were measured before and after the intervention. In total, 85 subjects completed the trial. Both interventions decreased fat mass and visceral adipose tissue and increased free fat mass, appendicular lean mass index and lean mass index. Neither endurance training nor endurance-strength training affected glucose and lipid metabolism. However, only endurance training significantly decreased paraoxonase and myoglobin levels. Both training programmes significantly decreased BP, with a more reduction of diastolic BP noted in the endurance group. In conclusion, both training programmes had a favourable effect on body composition but did not improve glucose and lipid homeostasis. Besides, endurance training decreased paraoxonase activity and myoglobin levels and was more effective in reducing BP.The study was registered with the German Clinical Trials Register (DRKS) within the number: DRKS00019832 (retrospective registration), date of registration: 26/02/2020.
Vertical and seasonal changes in soil carbon pools to vegetation degradation in a wet meadow on the Qinghai-Tibet Plateau
Authors: Wu Jiangqi , Wang Haiyan , Li Guang , Wu Jianghua , Ma Weiwei 
Published: June 2021

AbstractWet meadows provide opportunities to decrease carbon dioxide (CO2) and methane (CH4) released into the atmosphere by increasing the soil organic carbon (SOC) stored in wetland systems. Although wet meadows serve as the most important and stable C sinks, there has been very few investigations on the seasonal distributions of SOC fractions in high-altitude wet meadows. Here, we studied the effects of four vegetation degradation levels, non-degraded (ND), lightly degraded (LD), moderately degraded (MD), and heavily degraded (HD), on the measured vertical and seasonal changes of SOC and its different fractions. Among these vegetation degradation levels, 0–10 and 10–20 cm soil depths in ND plots had significantly higher SOC contents than the other degradation levels had throughout the year. This is attributed to the relatively greater inputs of aboveground plant litter and richer fine-root biomass in ND plots. Particulate organic carbon (POC) and light fraction organic carbon (LFOC) showed similar vertical and seasonal variations in autumn, reaching a minimum. Moreover, microbial biomass (MBC) and easily oxidizable organic carbon (EOC) contents were highest in summer and the smallest in winter, while dissolved organic carbon (DOC) content was highest in spring and lowest in summer, and were mainly concentrated in the 0–20 cm layer. Pearson correlation analysis indicated that soil properties and aboveground biomass were significantly related to different SOC fractions. The results indicate that vegetation degradation reduces the accumulation of total SOC and its different fractions, which may reduce carbon sink capacity and soil quality of alpine wet meadows, and increase atmospheric environmental pressure. In addition, vegetation biomass and soil characteristics play a key role in the formation and transformation of soil carbon. These results strengthen our understanding of soil C dynamics, specifically related to the different C fractions as affected by vegetation degradation levels and soil depth, in wet meadow systems.