bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of pulp and acid leaching operations in zinc ingot production process with the data mining approach
Authors: Bamdad Shahrooz
Published: April 2021

This study presents a data mining approach to optimize the chemical processes. Typically, these processes are affected by a variety of interactive variables. So, their quality monitoring and detection usually emphasize changing main variables and their interaction effects. Sometimes, the input to the chemical processes lacks access to the raw materials, which causes the manufacturers to use residue instead of high-quality materials. The use of residue has flaws, most notably the low quality of the process output. In this paper, calculating the optimum points of process variables using residue with the data mining approach is suggested. As a real case, one of the operations of the zinc ingot production process, i.e., pulp and acid leaching operations, are studied. In this way, first, by studying the operation in detail, the required data are collected, and key input and output variables are distinguished. Then, by data pre-processing, the optimum points of the process are determined using data mining algorithms. Therefore, the input variable settings of the operation are extracted to optimize the output variables. To validate the results, a set of test data are used to examine the two periods before and after the variable settings. The results show that the operation output is improved significantly. According to the robustness of the proposed method, it can be used as a benchmark for other chemical processes.
Flexible welding of SiOx nanowire to macroporous carbon film and underlying new insights
Authors: Su Jiangbin , Wang Zhiwei , Ma Ji , He Zuming , Tang Bin , Jiang Meiping , Zhu Xianfang
Published: April 2021

With the continuous decreasing in sizes of functional materials and devices, people are being asked to perform a flexible, accurate, in-situ and non-thermal welding of nanowires at the nanoscale. In this work, a well deliberated procedure including three typical stages: sharpening, hooking and welding, was carried out in sequence by in-situ TEM to realize the high demand welding of SiOx nanowire to macroporous carbon film. It was found that the brittle SiOx nanowire was non-thermally softened under energetic e-beam irradiation, and the flexibility and accuracy of welding could be achieved by adjusting the beam spot size, irradiation location and irradiation time. It was demonstrated that the nanocurvature effect of SiOx nanowire and the ultra-fast energy deposition effect induced by energetic e-beam irradiation dominated the diffusion, evaporation and plastic flow of atoms and the resulting nanowire re-shaping and nanowelding processes. In contrast, the traditional knock-on mechanism and e-beam heating effect are inadequate to explain these phenomena. Therefore, such a study is crucial not only to the flexible technical controlling but also to the profound fundamental understanding of energetic e-beam-induced nanowire re-shaping and nanowelding.
Examining the Deferred Effects of Gaming Platform and Game Speed of Advergames on Memory, Attitude, and Purchase Intention
Authors: Ghosh Tathagata , Sreejesh S. , Dwivedi Yogesh K.
Published: April 2021

Advergames are digital games through which advertisers promote their brands. While many studies have explored the influence of the gamification of advertising, little is known about the effects of important advergame attributes such as gaming platform (device used to play games) and game speed (overall pace of games) on consumers’ immediate and delayed memory, delayed attitude, and delayed intention to purchase the advertised brands. We address these gaps by conducting two experiments with fictitious brands (Study 1) and real brands that vary in the degree of familiarity (Study 2). Results reveal that a PC-based advergame generates better delayed memory than a mobile-based advergame, while gaming platform does not affect immediate memory. Also, it interacts with game speed only in the delayed situation. Brand familiarity moderates the effects of gaming platform and game speed on brand attitude and purchase intention in such a way that unfamiliar brands are more effective than familiar ones.
Editorial
Authors: Barrett Steve
Published: April 2021

Emergency vehicles serve a variety of critical functions, and have certain operational requirements that can potentially be better met by the use of fuel cell power.
Paleowind directions from the magnetic fabric of loess deposits in the western Chinese Loess Plateau and implications for dust provenance
Authors: Gao Xinbo , Hao Qingzhen , Ge Junyi , Han Long , Fu Yu , Wu Xuechao , Deng Chenglong , Marković Slobodan B. , Guo Zhengtang
Published: April 2021

The aeolian loess-paleosol sequences in the Chinese Loess Plateau (CLP) are an excellent archive of variations in atmospheric circulation in the geological past. However, there is no consensus regarding the roles of the East Asian winter monsoon and westerly winds in transporting the dust responsible for loess deposition during glacial and interstadial periods. We conducted detailed measurements of the anisotropy of magnetic susceptibility (AMS) on two parallel loess profiles covering the most recent 130 ka in the western CLP to determine paleowind directions. Results show that the magnetic lineations of the loess and paleosol units in both sections are significantly clustered along the northwest to southeast direction. These observations demonstrate that the prevailing wind system responsible for dust transport in the western CLP was the northwesterly winter monsoon, rather than the westerly winds. The AMS-derived dust-bearing wind direction was relatively stable during the last glacial and interglacial cycle in the western CLP, consistent with sedimentary and AMS evidence from the eastern CLP. Accordingly, it is reasonable to conclude that large areas of deserts and Gobi deserts areas located in the upwind direction were the dominant sources for the aeolian deposits of the Loess Plateau.
Establishing a New Role for Antidumping Policy: Protection of an Unestablished Industry (Morocco–Hot-Rolled Steel (Turkey))
Authors: Crowley Meredith A. , Ortino Federico
Published: April 2021

This article analyses economic and legal issues in the WTO dispute between Morocco and Turkey over hot-rolled steel. Over 2013–2014, the Moroccan government conducted an antidumping investigation against two Turkish steel producers. Morocco's investigation concluded that Turkish dumping was retarding the establishment of a new domestic industry; antidumping duties were imposed against both Turkish producers. Turkey filed a complaint at the WTO in 2016, asserting procedural and substantive violations. The Panel found that Morocco had acted inconsistently with a number of WTO obligations, including those regarding its injury investigation. Although Morocco initially appealed the Panel's decision, it withdrew its appeal after the antidumping duties expired in September 2019. This case is unusual and important in that it was the first antidumping case in which a country sought to use antidumping duties to protect a newly developing industry. The Panel may have missed an opportunity to explore the definition of an ‘unestablished’ industry for purposes of determining injury in an antidumping investigation.
Lernwerkstätten in der Pflegeausbildung
Authors: Oehmen Ulrike , Schöppner Friederike , Wurm Sabrina
Published: April 2021

Zusammenfassung. Lernwerkstätten sind primär bekannt aus Kitas und Schulen – auch institutionenübergreifend im Sinne einer gemeinsamen Übergangsgestaltung. Darüber hinaus sind sie an zahlreichen Universitäten und pädagogischen Ausbildungsstätten zu finden. Vor allem angehende Pädagoginnen und Pädagogen können auf diese Weise das forschende Lernen für sich entdecken, um es später erfolgreich in Kitas und Schulen umzusetzen. In der Pflegeausbildung aber wird eher selten damit gearbeitet. Der folgende Artikel zeigt eine Möglichkeit auf, wie eine (mobile) Lernwerkstatt in der Pflegeausbildung aussehen kann.
Technikunterstützte Didaktik im Dementia Care-Bereich
Authors: Schnelli Angela , Hirt Julian , Gruber Christine , Beer Thomas
Published: April 2021

Zusammenfassung. Technologien nehmen in der Pflegepädagogik und -praxis einen immer höheren Stellenwert ein. Dieser Artikel bietet einen Überblick über technikunterstützte Didaktik, die in der Aus-, Fort- und Weiterbildung im Dementia Care-Bereich zum Einsatz kommt.
Precipitation Type Distribution and Microphysical Processes During the 1998 Ice Storm Simulated Under Pseudo‐Warmer Conditions
Authors: Cholette Mélissa , Thériault Julie Mireille
Published: April 2021

In the future, the intensity, phases, and frequency of precipitation are expected to change due to global warming, in particular during colder seasons when temperatures are near 0°C. To investigate the impacts of warmer atmospheric conditions on the microphysical processes that lead to several precipitation types, the extreme 1998 Ice Storm was simulated using the Weather Research and Forecasting (WRF) model, with and without a pseudo‐global warming. The pseudo‐global warming approach simulates similar large‐scale conditions but in warmer conditions, which allows for the assessment of thermodynamic feedback from cloud and precipitation microphysics. For both simulations, WRF was coupled with the Predicted Particle Properties (P3) bulk microphysics scheme that predicts the liquid fraction of mixed‐phase particles. Results of the pseudo‐global warming simulation show an increase of ∼828 m in the upper 0°C level and a northeastward migration (∼60 km) of the rain‐snow transition region. The results also show a 20% decrease in domain‐averaged freezing rain amounts, but with an increased maximum amount of 50%. The horizontal distance associated with a melting aloft and a refreezing layer near the surface is 105 km longer in southern Quebec due to the combined effects of the pseudo‐warming and the presence of the Appalachian Mountains. The microphysical processes that lead to precipitation are impacted as well; the increased ice mass and riming conditions aloft in warmer temperatures result in higher liquid precipitation rates. This study contributes to our understanding of the changes in the fine‐scale processes of an extreme storm, simulated with pseudo‐global warming conditions.
A Large Impact of Cooking Organic Aerosol (COA) on Particle Hygroscopicity and CCN Activity in Urban Atmosphere
Authors: Liu Jieyao , Zhang Fang , Xu Weiqi , Chen Lu , Ren Jingye , Jiang Sihui , Sun Yele , Li Zhanqing
Published: April 2021

Cooking organic aerosol (COA) constitutes a considerable proportion of fine particles in populated area, while there is a lack of understanding on its impact on climate. Using a data set from field observations in Beijing, we characterize the variations of COA in fine particulate matter (PM) and its effect on aerosols hygroscopicity and cloud condensation nuclei (CCN) activity. The observed mass concentrations of COA from two campaigns of winter 2016 and summer 2017 were 5.5 ± 5.6 µg m−3 and 1.9 ± 2.1 µg m−3, respectively, corresponding to mass fraction of COA to PM1 and total OA of 8% ± 9% and 17% ± 13% in winter, 10% ± 9% and 19% ± 13% in summer. The strong COA sources are evidenced by apparent peak values in mass concentrations at lunch and dinner times. With increase of volume fraction of COA from ∼10% during noncooking time to ∼40% during dinner time, hygroscopic parameter of OA (κorg) is decreased from ∼0.21 to ∼0.06 (corresponding to a decrease of overall hygroscopic parameter of aerosols, κ, from ∼0.25 to ∼0.20), showing a critical role of COA in altering aerosols hygroscopicity. Further evaluation shows that the decrease in aerosols hygroscopicity caused by COA will reduce its CCN activity significantly (characterized by critical supersaturation, Sc, increasing from ∼0.25%–0.5% to ∼0.4%–0.7%). The current circumstance, which presents no apparent downward trends of COA in Beijing during last decades but much greater levels of COA in China than those in other regions around the world, suggests the great significance to account for the effect of COA on regional climate in models.
CD8+ T cells inhibit metastasis and CXCL4 regulates its function
Authors: Joseph Robiya , Soundararajan Rama , Vasaikar Suhas , Yang Fei , Allton Kendra L. , Tian Lin , den Hollander Petra , Isgandarova Sevinj , Haemmerle Monika , Mino Barbara , Zhou Tieling , Shin Crystal , Martinez-Paniagua Melisa , Sahin Aysegul A. , Rodriguez-Canales Jaime , Gelovani Juri , Chang Jeffrey T. , Acharya Ghanashyam , Sood Anil K. , Wistuba Ignacio I. , Gibbons Don L. , Solis Luisa M. , Barton Michelle C. , Varadarajan Navin , Rosen Jeffrey M. , Zhang Xiang H. , Mani Sendurai A.
Published: April 2021

Background

The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.

Methods

We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as well.

Results

We reveal that intratumoral immune infiltration differs between metastatic and non-metastatic tumours. The non-metastatic tumours harbour high levels of CD8+ T cells and low levels of platelets, which is reverse in metastatic tumours. During tumour progression, platelets and CXCL4 induce differentiation of monocytes into myeloid-derived suppressor cells (MDSCs), which inhibit CD8+ T-cell function. TCGA pan-cancer data confirmed that CD8lowPlatelethigh patients have a significantly lower survival probability compared to CD8highPlateletlow.

Conclusions

CD8+ T cells inhibit metastasis. When the balance between CD8+ T cells and platelets is disrupted, platelets produce CXCL4, which induces MDSCs thereby inhibiting the CD8+ T-cell function.
Regulated cell death pathways in doxorubicin-induced cardiotoxicity
Authors: Christidi Effimia , Brunham Liam R.
Published: April 2021

Doxorubicin is a chemotherapeutic drug used for the treatment of various malignancies; however, patients can experience cardiotoxic effects and this has limited the use of this potent drug. The mechanisms by which doxorubicin kills cardiomyocytes has been elusive and despite extensive research the exact mechanisms remain unknown. This review focuses on recent advances in our understanding of doxorubicin induced regulated cardiomyocyte death pathways including autophagy, ferroptosis, necroptosis, pyroptosis and apoptosis. Understanding the mechanisms by which doxorubicin leads to cardiomyocyte death may help identify novel therapeutic agents and lead to more targeted approaches to cardiotoxicity testing.
Linking the YTH domain to cancer: the importance of YTH family proteins in epigenetics
Authors: Shi Rongkai , Ying Shilong , Li Yadan , Zhu Liyuan , Wang Xian , Jin Hongchuan
Published: April 2021

N6-methyladenosine (m6A), the most prevalent and reversible modification of mRNA in mammalian cells, has recently been extensively studied in epigenetic regulation. YTH family proteins, whose YTH domain can recognize and bind m6A-containing RNA, are the main “readers” of m6A modification. YTH family proteins perform different functions to determine the metabolic fate of m6A-modified RNA. The crystal structure of the YTH domain has been completely resolved, highlighting the important roles of several conserved residues of the YTH domain in the specific recognition of m6A-modified RNAs. Upstream and downstream targets have been successively revealed in different cancer types and the role of YTH family proteins has been emphasized in m6A research. This review describes the regulation of RNAs by YTH family proteins, the structural features of the YTH domain, and the connections of YTH family proteins with human cancers.
TFEB regulates pluripotency transcriptional network in mouse embryonic stem cells independent of autophagy–lysosomal biogenesis
Authors: Tan Anderson , Prasad Renuka , Jho Eek-hoon
Published: April 2021

Transcription factor EB (TFEB), a well-known master regulator of autophagy and lysosomal biogenesis, is a member of the microphthalmia family of transcription factors (MiT family). Over the years, TFEB has been shown to have diverse roles in various physiological processes such as clearance for intracellular pathogenic factors and having developmental functions such as dendritic maturation, as well as osteoclast, and endoderm differentiation. However, in the present study, we propose a novel mechanism for TFEB governing pluripotency of mouse ESCs (mESCs) by regulating the pluripotency transcriptional network (PTN) in these cells. We observed high levels of TFEB mRNA and protein levels in undifferentiated mESCs. Interestingly, we found a reduction of Nanog and Sox2 levels in TFEB knockout (KO) mESCs while pluripotency was maintained as there was an upregulation of TFE3, a potent stem cell maintenance factor. In consistent, double knockout of TFEB/TFE3 (TFEB/3 DKO) reduced mESC pluripotency, as indicated by the loss of ESC morphology, reduction of ESC markers, and the emergence of differentiation markers. We further discovered that Nanog was a TFEB target gene in undifferentiated mESCs. TFEB also promoted sex-determining region Y-box2 (Sox2) transcription by forming a heterodimer with Sox2 in mESCs. Notably, Sox2, Oct4, and Nanog were also binding to the TFEB promoter and thus generating a feed-forward loop in relation to TFEB. Although high levels of nuclear TFEB are expected to enhance autophagy–lysosomal activity, undifferentiated mESC remarkably displayed low basal autophagy–lysosomal activity. Overexpression or knockout of TFEB did not affect the expression of TFEB lysosomal–autophagy target genes and TFEB also had a lesser binding affinity to its own lysosomal promoter-target genes in mESCs compared to differentiated cells. Collectively, these findings define a newly incorporative, moonlighting function for TFEB in regulating PTN, independent of its autophagy–lysosomal biogenesis roles.
RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis
Authors: Liang Qian , Wang Yun , Lu Yingsi , Zhu Qingqing , Xie Wenlin , Tang Nannan , Huang Lifen , An Tailai , Zhang Di , Yan Anqi , Liu Shaoyu , Ye Liping , Zhu Chengming
Published: April 2021

The tumor necrosis factor (TNF) receptor superfamily member 11a (TNFRSF11a, also known as RANK) was demonstrated to play an important role in tumor metastasis. However, the specific function of RANK in colorectal cancer (CRC) metastasis and the underlying mechanism are unknown. In this study, we found that RANK expression was markedly upregulated in CRC tissues compared with that in matched noncancerous tissues. Increased RANK expression correlated positively with metastasis, higher TNM stage, and worse prognosis in patients with CRC. Overexpression of RANK promoted CRC cell metastasis in vitro and in vivo, while knockdown of RANK decreased cell migration and invasion. Mechanistically, RANK overexpression significantly upregulated the expression of tartrate-resistant acid phosphatase 5 (TRAP/ACP5) in CRC cells. Silencing of ACP5 in RANK-overexpressing CRC cells attenuated RANK-induced migration and invasion, whereas overexpression of ACP5 increased the migration and invasion of RANK-silencing cells. The ACP5 expression was transcriptionally regulated by calcineurin/nuclear factor of activated T cells c1 (NFATC1) axis. The inhibition of calcineurin/NFATC1 significantly decreased ACP5 expression, and attenuated RANK-induced cell migration and invasion. Furthermore, RANK induced phospholipase C-gamma (PLCγ)-mediated inositol-1,4,5-trisphosphate receptor (IP3R) axis and stromal interaction molecule 1 (STIM1) to evoke calcium (Ca2+) oscillation. The RANK-mediated intracellular Ca2+ mobilization stimulated calcineurin to dephosphorylate NFATC1 and induce NFATC1 nuclear translocation. Both blockage of PLCγ-IP3R axis and STIM1 rescued RANK-induced NFATC1 nuclear translocation, ACP5 expression, and cell metastasis. Our study revealed the functional expression of RANK in human CRC cells and demonstrated that RANK induced the Ca2+-calcineurin/NFATC1-ACP5 axis in the regulation of CRC metastasis, that might be amenable to therapeutic targeting.
Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria
Authors: Nishad Rajkishor , Mukhi Dhanunjay , Singh Ashish Kumar , Motrapu Manga , Chintala Kumaraswami , Tammineni Prasad , Pasupulati Anil K.
Published: April 2021

Glomerular podocytes are integral members of the glomerular filtration barrier in the kidney and are crucial for glomerular permselectivity. These highly differentiated cells are vulnerable to an array of noxious stimuli that prevail in several glomerular diseases. Elevated circulating growth hormone (GH) levels are associated with podocyte injury and proteinuria in diabetes. However, the precise mechanism(s) by which excess GH elicits podocytopathy remains to be elucidated. Previous studies have shown that podocytes express GH receptor (GHR) and induce Notch signaling when exposed to GH. In the present study, we demonstrated that GH induces TGF-β1 signaling and provokes cell cycle reentry of otherwise quiescent podocytes. Though differentiated podocytes reenter the cell cycle in response to GH and TGF-β1, they cannot accomplish cytokinesis, despite karyokinesis. Owing to this aberrant cell cycle event, GH- or TGF-β1-treated cells remain binucleated and undergo mitotic catastrophe. Importantly, inhibition of JAK2, TGFBR1 (TGF-β receptor 1), or Notch prevented cell cycle reentry of podocytes and protected them from mitotic catastrophe associated with cell death. Inhibition of Notch activation prevents GH-dependent podocyte injury and proteinuria. Similarly, attenuation of GHR expression abated Notch activation in podocytes. Kidney biopsy sections from patients with diabetic nephropathy (DN) show activation of Notch signaling and binucleated podocytes. These data indicate that excess GH induced TGF-β1-dependent Notch1 signaling contributes to the mitotic catastrophe of podocytes. This study highlights the role of aberrant GH signaling in podocytopathy and the potential application of TGF-β1 or Notch inhibitors, as a therapeutic agent for DN.
Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity
Authors: Sogkas Georgios , Atschekzei Faranaz , Adriawan Ignatius Ryan , Dubrowinskaja Natalia , Witte Torsten , Schmidt Reinhold Ernst
Published: April 2021

In addition to susceptibility to infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases, such as arthritis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome (SjS). Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic mechanisms. Here, we explore the interconnected pathogenic pathways of autoimmunity and primary immunodeficiency, highlighting the mechanisms breaking the different layers of immune tolerance to self-antigens in selected IEI.
Selective reaction of conjugated polymers with basic proteins for broad-spectrum antivirulence therapy
Authors: Sun Han , Liu Jing , Lv Fengting , Liu Libing , Gu Qi , Hu Baoyang , Wang Shu
Published: April 2021

Antivirulence therapy has proven to be an attractive method for the treatment of bacterial infections and venomous injuries; however, the approaches for neutralizing multiple types of virulence through one platform are limited. To address this challenge, we have developed a reactive conjugated polymer, PPV–NHS, which functions as a broad-spectrum antidote for directly inactivating basic toxins. The antivirulence is achieved via multivalent electrostatic recognition and subsequent amidation reactions between PPV–NHS and toxins. The resultant bioconjugates significantly reduced neurotoxicity and cytotoxicity. In the mouse model, PPV–NHS effectively inhibited the toxicity of cardiotoxin (CTX) and improved the survival rate of toxin-challenged mice. This work represents the rational design of functionalized conjugated polymers for antivirulence therapy with both high efficiency and broad applicability.
Electrospun nanofiber-based soft electronics
Authors: Wang Yan , Yokota Tomoyuki , Someya Takao
Published: April 2021

Electrospun nanofibers have received considerable attention in the field of soft electronics owing to their promising advantages and superior properties in flexibility and/or stretchability, conductivity, and transparency; furthermore, their one-dimensional nanostructure, high surface area, and diverse fibrous morphologies are also desirable. Herein, we provide an overview of electrospun nanofiber-based soft electronics. A brief introduction of the unique structure and properties of electrospun nanofiber materials is provided, and assembly strategies for flexible/stretchable electronics are highlighted. We then summarize the latest progress in the design and fabrication of representative flexible/stretchable electronic devices utilizing electrospun nanofibers, such as flexible/stretchable conductors, sensors, energy harvesting and storage devices, and transistors. Finally, a conclusion and several future research directions for electrospun nanofiber-based soft electronics are proposed.
Electrochemically active materials and wearable biosensors for the in situ analysis of body fluids for human healthcare
Authors: Park Heun , Park Woohyun , Lee Chi Hwan
Published: April 2021

The increasing demand for minimal to noninvasive in situ analysis of body fluids, such as sweat, interstitial fluid, and tears, has driven rapid development of electrochemically active materials and wearable biosensors. The mechanically soft and deformable nature of these biosensors enables them to efficiently adapt to the geometric nonlinearity of a specific part of the human body. The integration of these biosensors with a fully miniaturized wireless telemetry system enables displaying real-time data in a mobile device and/or reporting to an encrypted server for post analysis. These features are essential for the long-term, unobtrusive monitoring of biochemical activity in ambulatory care settings for improved management of many chronic diseases, such as diabetes, gout, and Parkinson’s disease. Herein, we present the latest innovations of wearable electrochemical sensors tailored for human skin or eyes with a focus on their materials, designs, sensing mechanisms, and clinical implications.
NIR-responsive MXene nanobelts for wound healing
Authors: Jin Lin , Guo Xiaoqing , Gao Di , Wu Cui , Hu Bin , Tan Guangxuan , Du Nannan , Cai Xiaolu , Yang Zhe , Zhang Xingcai
Published: April 2021

Effectively achieving wound healing is a great challenge. Herein, we facilely prepared temperature-responsive MXene nanobelt fibers (T-RMFs) carrying vitamin E with a controllable release ability for wound healing. These T-RMFs were composed of MXene nanosheets spread along polyacrylonitrile and polyvinylpyrrolidone composite nanobelts together with a thermosensitive PAAV- coating layer. The high mass loading and high surface area of the MXene nanosheets endow the T-RMFs with excellent photothermal properties. The temperature could be easily controlled by near-infrared (NIR) irradiation exposure, and then the thermoresponsive polymeric coating layer relaxed the interface to dissolve vitamin E and promote vitamin E release. The T-RMFs demonstrated excellent biocompatibility and wound-healing functions in cellular and animal tests. The facile method, high mass loading, high surface area, excellent wound-healing functions, interesting nanosheet/nanobelt structure, mass production potential, and NIR responsive properties of these T-RMFs indicate the great potential of our nanobelts for wound healing, tissue engineering, and much broader application areas. This facile nanosheet/nanobelt preparation strategy paves a new way for nanomaterial fabrication and applications.
Evolution of DNA methylation in the human brain
Authors: Jeong Hyeonsoo , Mendizabal Isabel , Berto Stefano , Chatterjee Paramita , Layman Thomas , Usui Noriyoshi , Toriumi Kazuya , Douglas Connor , Singh Devika , Huh Iksoo , Preuss Todd M. , Konopka Genevieve , Yi Soojin V.
Published: April 2021

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.
Monocyte progenitors give rise to multinucleated giant cells
Authors: Lösslein Anne Kathrin , Lohrmann Florens , Scheuermann Lisa , Gharun Kourosh , Neuber Jana , Kolter Julia , Forde Aaron James , Kleimeyer Christian , Poh Ying Yee , Mack Matthias , Triantafyllopoulou Antigoni , Dunlap Micah D. , Khader Shabaana A. , Seidl Maximilian , Hölscher Alexandra , Hölscher Christoph , Guan Xue Li , Dorhoi Anca , Henneke Philipp
Published: April 2021

The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.
A polymer controlled nucleation route towards the generalized growth of organic-inorganic perovskite single crystals
Authors: Ma Lin , Yan Zhengguang , Zhou Xiaoyuan , Pi Yiqun , Du Yiping , Huang Jie , Wang Kaiwen , Wu Ke , Zhuang Chunqiang , Han Xiaodong
Published: April 2021

Recently, there are significant progresses in the growth of organic-inorganic lead halide perovskite single crystals, however, due to their susceptible nucleation and growth mechanisms and solvent requirements, the efficient and generalized growth for these single crystals is still challenging. Here we report the work towards this target with a polymer-controlled nucleation process for the highly efficient growth of large-size high-quality simple ternary, mixed-cations and mixed-halide perovskite single crystals. Among them, the carrier lifetime of FAPbBr3 single crystals is largely improved to 10199 ns. Mixed MA/FAPbBr3 single crystals are synthesized. The crucial point in this process is suggested to be an appropriate coordinative interaction between polymer oxygen groups and Pb2+, greatly decreasing the nuclei concentrations by as much as 4 orders of magnitudes. This polymer-controlled route would help optimizing the solution-based OIHPs crystal growth and promoting applications of perovskite single crystals.
Systems serology detects functionally distinct coronavirus antibody features in children and elderly
Authors: Selva Kevin J. , van de Sandt Carolien E. , Lemke Melissa M. , Lee Christina Y. , Shoffner Suzanne K. , Chua Brendon Y. , Davis Samantha K. , Nguyen Thi H. O. , Rowntree Louise C. , Hensen Luca , Koutsakos Marios , Wong Chinn Yi , Mordant Francesca , Jackson David C. , Flanagan Katie L. , Crowe Jane , Tosif Shidan , Neeland Melanie R. , Sutton Philip , Licciardi Paul V. , Crawford Nigel W. , Cheng Allen C. , Doolan Denise L. , Amanat Fatima , Krammer Florian , Chappell Keith , Modhiran Naphak , Watterson Daniel , Young Paul , Lee Wen Shi , Wines Bruce D. , Mark Hogarth P. , Esterbauer Robyn , Kelly Hannah G. , Tan Hyon-Xhi , Juno Jennifer A. , Wheatley Adam K. , Kent Stephen J. , Arnold Kelly B. , Kedzierska Katherine , Chung Amy W.
Published: April 2021

The hallmarks of COVID-19 are higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive immunological responses, induced by circulating human coronaviruses (hCoVs), is needed to understand such divergent clinical outcomes. Here we show analysis of coronavirus antibody responses of pre-pandemic healthy children (n = 89), adults (n = 98), elderly (n = 57), and COVID-19 patients (n = 50) by systems serology. Moderate levels of cross-reactive, but non-neutralizing, SARS-CoV-2 antibodies are detected in pre-pandemic healthy individuals. SARS-CoV-2 antigen-specific Fcγ receptor binding accurately distinguishes COVID-19 patients from healthy individuals, suggesting that SARS-CoV-2 infection induces qualitative changes to antibody Fc, enhancing Fcγ receptor engagement. Higher cross-reactive SARS-CoV-2 IgA and IgG are observed in healthy elderly, while healthy children display elevated SARS-CoV-2 IgM, suggesting that children have fewer hCoV exposures, resulting in less-experienced but more polyreactive humoral immunity. Age-dependent analysis of COVID-19 patients, confirms elevated class-switched antibodies in elderly, while children have stronger Fc responses which we demonstrate are functionally different. These insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.
Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration
Authors: Ding Xin , Wang Jin , Huang Miaoxin , Chen Zhangpeng , Liu Jing , Zhang Qipeng , Zhang Chenyu , Xiang Yang , Zen Ke , Li Liang
Published: April 2021

Microglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.
Giant gauge factor of Van der Waals material based strain sensors
Authors: Yan Wenjie , Fuh Huei-Ru , Lv Yanhui , Chen Ke-Qiu , Tsai Tsung-Yin , Wu Yuh-Renn , Shieh Tung-Ho , Hung Kuan-Ming , Li Juncheng , Zhang Duan , Ó Coileáin Cormac , Arora Sunil K. , Wang Zhi , Jiang Zhaotan , Chang Ching-Ray , Wu Han-Chun
Published: April 2021

There is an emergent demand for high-flexibility, high-sensitivity and low-power strain gauges capable of sensing small deformations and vibrations in extreme conditions. Enhancing the gauge factor remains one of the greatest challenges for strain sensors. This is typically limited to below 300 and set when the sensor is fabricated. We report a strategy to tune and enhance the gauge factor of strain sensors based on Van der Waals materials by tuning the carrier mobility and concentration through an interplay of piezoelectric and photoelectric effects. For a SnS2 sensor we report a gauge factor up to 3933, and the ability to tune it over a large range, from 23 to 3933. Results from SnS2, GaSe, GeSe, monolayer WSe2, and monolayer MoSe2 sensors suggest that this is a universal phenomenon for Van der Waals semiconductors. We also provide proof of concept demonstrations by detecting vibrations caused by sound and capturing body movements.
Nectin-4 and p95-ErbB2 cooperatively regulate Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation
Authors: Kedashiro Shin , Kameyama Takeshi , Mizutani Kiyohito , Takai Yoshimi
Published: April 2021

Nectin-4, upregulated in various cancer cells, cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, p95-ErbB2 and ErbB2∆Ex16, enhancing DNA synthesis through the PI3K-AKT signaling in human breast cancer T47D cells in an adherent culture. We found here that nectin-4 and p95-ErbB2, but not nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced SOX2 gene expression and cell proliferation in a suspension culture. This enhancement of T47D cell proliferation in a suspension culture by nectin-4 and p95-ErbB2 was dependent on the SOX2 gene expression. In T47D cells, nectin-4 and any one of p95-ErbB2, ErbB2, or ErbB2∆Ex16 cooperatively activated the PI3K-AKT signaling, known to induce the SOX2 gene expression, to similar extents. However, only a combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively enhanced the SOX2 gene expression. Detailed studies revealed that only nectin-4 and p95-ErbB2 cooperatively activated the Hippo signaling. YAP inhibited the SOX2 gene expression in this cell line and thus the MST1/2-LATS1/2 signaling-mediated YAP inactivation increased the SOX2 gene expression. These results indicate that only the combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and either ErbB2 or ErbB2∆Ex16, cooperatively regulates the Hippo signaling-dependent SOX2 gene expression, enhancing anchorage-independent T47D cell proliferation.
Motor learning deficits in cervical dystonia point to defective basal ganglia circuitry
Authors: Loens Sebastian , Verrel Julius , Herrmann Vera-Maria , Kienzle Amrei , Tzvi Elinor , Weissbach Anne , Junker Johanna , Münchau Alexander , Bäumer Tobias
Published: April 2021

Dystonia is conceptualized as a network disorder involving basal ganglia, thalamus, sensorimotor cortex and the cerebellum. The cerebellum has been implicated in dystonia pathophysiology, but studies testing cerebellar function in dystonia patients have provided equivocal results. This study aimed to further elucidate motor network deficits in cervical dystonia with special interest in the role of the cerebellum. To this end we investigated motor learning tasks, that differ in their dependence on cerebellar and basal ganglia functioning. In 18 cervical dystonia patients and 18 age matched healthy controls we measured implicit motor sequence learning using a 12-item serial reaction time task mostly targeting basal ganglia circuitry and motor adaptation and eyeblink conditioning as markers of cerebellar functioning. ANOVA showed that motor sequence learning was overall impaired in cervical dystonia (p = 0.01). Moreover, unlike healthy controls, patients did not show a learning effect in the first part of the experiment. Visuomotor adaptation and eyeblink conditioning were normal. In conclusion, these data lend support to the notion that motor learning deficits in cervical dystonia relate to basal ganglia-thalamo-cortical loops rather than being a result of defective cerebellar circuitry.
Proton beam quality enhancement by spectral phase control of a PW-class laser system
Authors: Ziegler T. , Albach D. , Bernert C. , Bock S. , Brack F.-E. , Cowan T. E. , Dover N. P. , Garten M. , Gaus L. , Gebhardt R. , Goethel I. , Helbig U. , Irman A. , Kiriyama H. , Kluge T. , Kon A. , Kraft S. , Kroll F. , Loeser M. , Metzkes-Ng J. , Nishiuchi M. , Obst-Huebl L. , Püschel T. , Rehwald M. , Schlenvoigt H.-P. , Schramm U. , Zeil K.
Published: April 2021

We report on experimental investigations of proton acceleration from solid foils irradiated with PW-class laser-pulses, where highest proton cut-off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto-optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state-of-the-art high-repetition rate PW laser system.
Skeletal muscle fibers play a functional role in host defense during sepsis in mice
Authors: Laitano Orlando , Robinson Gerard P. , Murray Kevin O. , Garcia Christian K. , Mattingly Alex J. , Morse Deborah , King Michelle A. , Iwaniec John D. , Alzahrani Jamal M. , Clanton Thomas L.
Published: April 2021

Skeletal muscles secrete a wide variety of immunologically active cytokines, but the functional significance of this response to in vivo innate immunity is not understood. We addressed this by knocking out the toll receptor adapter protein, Myd88, only in skeletal muscle fibers (skmMyd88KO), and followed male and female mice at 6 and 12 h after peritoneal injection of cecal slurry (CS), a model of polymicrobial sepsis. Because of a previously identified increase in mortality to CS injection, males received ~ 30% lower dose. At 12 h, skmMyd88KO caused significant reductions in a wide variety of pro- and anti-inflammatory plasma cytokines, e.g. TNFα, IL-1β and IL-10, compared to strain-matched controls in both males and females. Similar reductions were observed at 6 h in females. SkmMyd88KO led to ~ 40–50% elevations in peritoneal neutrophils at 6 and 12 h post CS in females. At 12 h post CS, skmMyd88KO increased peritoneal monocytes/macrophages and decreased %eosinophils and %basophils in females. SkmMyd88KO also led to significantly higher rates of mortality in female mice but not in males. In conclusion, the results suggest that skeletal muscle Myd88-dependent signal transduction can play functionally important role in normal whole body, innate immune inflammatory responses to peritoneal sepsis.
Programmable nonreciprocal meta-prism
Authors: Taravati Sajjad , Eleftheriades George V.
Published: April 2021

Optical prisms are made of glass and map temporal frequencies into spatial frequencies by decomposing incident white light into its constituent colors and refract them into different directions. Conventional prisms suffer from their volumetric bulky and heavy structure and their material parameters are dictated by the Lorentz reciprocity theorem. Considering various applications of prisms in wave engineering and their growing applications in the invisible spectrum and antenna applications, there is a demand for compact apparatuses that are capable of providing prism functionality in a reconfigurable manner, with a nonreciprocal/reciprocal response. Here, we propose a nonreciprocal metasurface-based prism constituted of an array of phase- and amplitude-gradient frequency-dependent spatially variant radiating super-cells. In conventional optical prisms, nonreciprocal devices and metamaterials, the spatial decomposition and nonreciprocity functions are fixed and noneditable. Here, we present a programmable metasurface integrated with amplifiers to realize controllable nonreciprocal spatial decomposition, where each frequency component of the incident polychromatic wave can be transmitted under an arbitrary and programmable angle of transmission with a desired transmission gain. Such a polychromatic metasurface prism is constituted of frequency-dependent spatially variant transistor-based phase shifters and amplifiers for the spatial decomposition of the wave components. Interesting features include three-dimensional prism functionality with programmable angles of refraction, power amplification, and directive and diverse radiation beams. Furthermore, the metasurface prism can be digitally controlled via a field- programmable gate array (FPGA), making the metasurface a suitable solution for radars, holography applications, and wireless telecommunication systems.
Molecular diversity of Mycobacterium tuberculosis complex in Sikkim, India and prediction of dominant spoligotypes using artificial intelligence
Authors: Devi Kangjam Rekha , Pradhan Jagat , Bhutia Rinchenla , Dadul Peggy , Sarkar Atanu , Gohain Nitumoni , Narain Kanwar
Published: April 2021

In India, tuberculosis is an enormous public health problem. This study provides the first description of molecular diversity of the Mycobacterium tuberculosis complex (MTBC) from Sikkim, India. A total of 399 Acid Fast Bacilli sputum positive samples were cultured on Lőwenstein–Jensen media and genetic characterisation was done by spoligotyping and 24-loci MIRU-VNTR typing. Spoligotyping revealed the occurrence of 58 different spoligotypes. Beijing spoligotype was the most dominant type constituting 62.41% of the total isolates and was associated with Multiple Drug Resistance. Minimum Spanning tree analysis of 249 Beijing strains based on 24-loci MIRU-VNTR analysis identified 12 clonal complexes (Single Locus Variants). The principal component analysis was used to visualise possible grouping of MTBC isolates from Sikkim belonging to major spoligotypes using 24-MIRU VNTR profiles. Artificial intelligence-based machine learning (ML) methods such as Random Forests (RF), Support Vector Machines (SVM) and Artificial Neural Networks (ANN) were used to predict dominant spoligotypes of MTBC using MIRU-VNTR data. K-fold cross-validation and validation using unseen testing data set revealed high accuracy of ANN, RF, and SVM for predicting Beijing, CAS1_Delhi, and T1 Spoligotypes (93–99%). However, prediction using the external new validation data set revealed that the RF model was more accurate than SVM and ANN.