bluuebunny/crossref_metadata_2025 huggingface dataset:
Tropical Free‐Tropospheric Humidity Differences and Their Effect on the Clear‐Sky Radiation Budget in Global Storm‐Resolving Models
Authors: Lang Theresa , Naumann Ann Kristin , Stevens Bjorn , Buehler Stefan A.
Published: October 2021

Reducing the model spread in free‐tropospheric relative humidity (RH) and its response to warming is a crucial step toward reducing the uncertainty in clear‐sky climate sensitivity, a step that is hoped to be taken with recently developed global storm‐resolving models (GSRMs). In this study we quantify the inter‐model differences in tropical present‐day RH across GSRMs, making use of DYAMOND, a first 40‐day intercomparison. We find that the inter‐model spread in tropical mean free‐tropospheric RH is reduced compared to conventional atmospheric models, except from the tropopause region and the transition to the boundary layer. We estimate the reduction to ∼50%–70% in the upper troposphere and 25%–50% in the mid troposphere. However, the remaining RH differences still result in a spread of 1.2  in tropical mean clear‐sky outgoing longwave radiation (OLR). This spread is mainly caused by RH differences in the lower and mid free troposphere, whereas RH differences in the upper troposphere have a minor impact. By examining model differences in moisture space we identify two regimes with a particularly large contribution to the spread in tropical mean clear‐sky OLR: rather moist regimes at the transition from deep convective to subsidence regimes and very dry subsidence regimes. Particularly for these regimes a better understanding of the processes controlling the RH biases is needed.
Spatial Slip Rate Distribution Along the SE Xianshuihe Fault, Eastern Tibet, and Earthquake Hazard Assessment
Authors: Bai Mingkun , Chevalier Marie‐Luce , Leloup Philippe Hervé , Li Haibing , Pan Jiawei , Replumaz Anne , Wang Shiguang , Li Kaiyu , Wu Qiong , Liu Fucai , Zhang Jinjiang
Published: October 2021

The Xianshuihe (XSH) fault in eastern Tibet is one of the most active faults in China, with the next large earthquake most likely to occur along its SE part, where the fault splits into three parallel branches: Yalahe, Selaha and Zheduotang (ZDT). Precisely quantifying their slip rates at various timescales is essential to evaluate regional earthquake hazard. Here, we expand our previous work on the Selaha fault to the nearby ZDT and Moxi (MX) faults, and add observations on the Yalahe fault and on the newly discovered Mugecuo South fault zone. Using tectonic‐geomorphology approaches with10Be dating, we had previously determined average late Quaternary slip rates of 9.75 ± 0.15 and 4.4 ± 0.5 mm/yr along the NW and SE Selaha fault, respectively. Using the same methods here, we determine a slip rate of 3.4–4.8 mm/yr on the ZDT fault and of 9.6–13.4 mm/yr on the MX fault. This is consistent with the southeastward slip rate increase we had proposed along the XSH fault system from 6‐8 mm/yr (Ganzi fault) to ∼10 mm/yr (Selaha fault), and >9.6 mm/yr (MX fault). We propose a new model for the SE XSH fault, where the large‐scale Mugecuo pull‐apart basin lies within an even larger scale compressive uplift zone in a restraining bend of the XSH fault, where the highest peak in eastern Tibet is located (Gongga Shan, 7,556 m). Our slip rate determination helps to constrain a relatively high regional Mw ∼ 7 earthquake hazard at present on the SE XSH fault.
GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer
Authors: Song Jun-Wei , Zhu Jing , Wu Xing-Xuan , Tu Ting , Huang Jing-Qiang , Chen Guan-Zi , Liang Li-Yin , Zhou Chun-Hui , Xu XingZhi , Gong Li-Yun
Published: October 2021

Cancer metastasis is the main cause of mortality associated with non-small-cell lung cancer (NSCLC), accounting for up to 70% of deaths among patients. The mechanisms underlying distal metastasis remain largely unknown. Golgi phosphoprotein 3 (GOLPH3) correlates negatively with overall survival in multiple tumors. In this study, we evaluated the function of GOLPH3 in NSCLC distal metastasis. GOLPH3 was expressed at high levels in samples from patients with NSCLC and was positively associated with clinicopathologic characteristics including clinical stage (P < 0.001), T (P = 0.001), N (P = 0.007), and M (P = 0.001) classification. Functionally, Transwell and wound-healing assays suggested that GOLPH3 overexpression enhances NSCLC cell migration and invasion abilities. Tumor-sphere formation and flow cytometry assays demonstrated that GOLPH3 overexpression enhances a stem cell-like phenotype of NSCLC cells. Metastasis models established by tail vein and intracardiac injection confirmed the pro-metastatic function of GOLPH3 in vivo. A subcutaneous tumor formation model confirmed that GOLPH3 overexpression increased the tumorigenicity of NSCLC cells. Mechanistically, gene set enrichment analysis revealed a positive association of GOLPH3 mRNA expression with WNT-activated gene signatures. Luciferase-reporter and nuclear extract assays showed that GOLPH3 overexpression enhances metastasis and tumorigenicity through activation of the WNT/β-catenin pathway. Immunoprecipitation-mass spectrometry and gene ontology analysis demonstrated that GOLPH3 interacts with cytoskeleton-associated protein 4 (CKAP4) in exosome-mediated distal metastasis. We found that GOLPH3 decreased the amount of plasma membrane-localized CKAP4 and increased the amount of exosome-localized CKAP4 to promote the formation of CKAP4-containing exosomes. Furthermore, we demonstrated that CKAP4 binds exosomal WNT3A to enhance its secretion. Therefore, the GOLPH3/CKAP4 axis plays a crucial role in promoting exosomal-WNT3A secretion to enhance and maintain the stem-like phenotype and metastasis in NSCLC, thus indicating the therapeutic potential of GOLPH3 in patients with NSCLC metastasis.
Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery
Authors: Wu Qiuji , Xiang Ziyue , Ying Yibo , Huang Zhiyang , Tu Yurong , Chen Min , Ye Jiahui , Dou Haicheng , Sheng Sunren , Li Xiaoyang , Ying Weiyang , Zhu Sipin
Published: October 2021

The ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.
Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics
Authors: Gordillo-Marañón María , Zwierzyna Magdalena , Charoen Pimphen , Drenos Fotios , Chopade Sandesh , Shah Tina , Engmann Jorgen , Chaturvedi Nishi , Papacosta Olia , Wannamethee Goya , Wong Andrew , Sofat Reecha , Kivimaki Mika , Price Jackie F. , Hughes Alun D. , Gaunt Tom R. , Lawlor Deborah A. , Gaulton Anna , Hingorani Aroon D. , Schmidt Amand F. , Finan Chris
Published: October 2021

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target’s expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process.
Light-triggered and phosphorylation-dependent 14-3-3 association with NON-PHOTOTROPIC HYPOCOTYL 3 is required for hypocotyl phototropism
Authors: Reuter Lea , Schmidt Tanja , Manishankar Prabha , Throm Christian , Keicher Jutta , Bock Andrea , Droste-Borel Irina , Oecking Claudia
Published: October 2021

NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) is a key component of the auxin-dependent plant phototropic growth response. We report that NPH3 directly binds polyacidic phospholipids, required for plasma membrane association in darkness. We further demonstrate that blue light induces an immediate phosphorylation of a C-terminal 14-3-3 binding motif in NPH3. Subsequent association of 14-3-3 proteins is causal for the light-induced release of NPH3 from the membrane and accompanied by NPH3 dephosphorylation. In the cytosol, NPH3 dynamically transitions into membraneless condensate-like structures. The dephosphorylated state of the 14-3-3 binding site and NPH3 membrane recruitment are recoverable in darkness. NPH3 variants that constitutively localize either to the membrane or to condensates are non-functional, revealing a fundamental role of the 14-3-3 mediated dynamic change in NPH3 localization for auxin-dependent phototropism. This regulatory mechanism might be of general nature, given that several members of the NPH3-like family interact with 14-3-3 via a C-terminal motif.
Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins
Authors: Fusco Claudia M. , Desch Kristina , Dörrbaum Aline R. , Wang Mantian , Staab Anja , Chan Ivy C. W. , Vail Eleanor , Villeri Veronica , Langer Julian D. , Schuman Erin M.
Published: October 2021

Owing to their morphological complexity and dense network connections, neurons modify their proteomes locally, using mRNAs and ribosomes present in the neuropil (tissue enriched for dendrites and axons). Although ribosome biogenesis largely takes place in the nucleus and perinuclear region, neuronal ribosomal protein (RP) mRNAs have been frequently detected remotely, in dendrites and axons. Here, using imaging and ribosome profiling, we directly detected the RP mRNAs and their translation in the neuropil. Combining brief metabolic labeling with mass spectrometry, we found that a group of RPs rapidly associated with translating ribosomes in the cytoplasm and that this incorporation was independent of canonical ribosome biogenesis. Moreover, the incorporation probability of some RPs was regulated by location (neurites vs. cell bodies) and changes in the cellular environment (following oxidative stress). Our results suggest new mechanisms for the local activation, repair and/or specialization of the translational machinery within neuronal processes, potentially allowing neuronal synapses a rapid means to regulate local protein synthesis.
Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases
Authors: Raman Vishnu , Van Dessel Nele , Hall Christopher L. , Wetherby Victoria E. , Whitney Samantha A. , Kolewe Emily L. , Bloom Shoshana M. K. , Sharma Abhinav , Hardy Jeanne A. , Bollen Mathieu , Van Eynde Aleyde , Forbes Neil S.
Published: October 2021

Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors.
Stroboscopic operando spectroscopy of the dynamics in heterogeneous catalysis by event-averaging
Authors: Knudsen Jan , Gallo Tamires , Boix Virgínia , Strømsheim Marie Døvre , D’Acunto Giulio , Goodwin Christopher , Wallander Harald , Zhu Suyun , Soldemo Markus , Lömker Patrick , Cavalca Filippo , Scardamaglia Mattia , Degerman David , Nilsson Anders , Amann Peter , Shavorskiy Andrey , Schnadt Joachim
Published: October 2021

Heterogeneous catalyst surfaces are dynamic entities that respond rapidly to changes in their local gas environment, and the dynamics of the response is a decisive factor for the catalysts’ action and activity. Few probes are able to map catalyst structure and local gas environment simultaneously under reaction conditions at the timescales of the dynamic changes. Here we use the CO oxidation reaction and a Pd(100) model catalyst to demonstrate how such studies can be performed by time-resolved ambient pressure photoelectron spectroscopy. Central elements of the method are cyclic gas pulsing and software-based event-averaging by image recognition of spectral features. A key finding is that at 3.2 mbar total pressure a metallic, predominantly CO-covered metallic surface turns highly active for a few seconds once the O2:CO ratio becomes high enough to lift the CO poisoning effect before mass transport limitations triggers formation of a √5 oxide.
A class of organic cages featuring twin cavities
Authors: Yang Zhenyu , Yu Chunyang , Ding Junjie , Chen Lihua , Liu Huiyu , Ye Yangzhi , Li Pan , Chen Jiaolong , Wu Kim Jiayi , Zhu Qiang-Yu , Zhao Yu-Quan , Liu Xiaoning , Zhuang Xiaodong , Zhang Shaodong
Published: October 2021

A variety of organic cages with different geometries have been developed during the last decade, most of them exhibiting a single cavity. In contrast, the number of organic cages featuring a pair of cavities remains scarce. These structures may pave the way towards novel porous materials with emergent properties and functions.We herein report on rational design of a three-dimensional hexaformyl precursor 1, which exhibits two types of conformers, i.e. Conformer-1 and -2, with different cleft positions and sizes. Aided by molecular dynamics simulations, we select two triamino conformation capturers (denoted CC). Small-sized CC-1 selectively capture Conformer-1 by matching its cleft size, while the large-sized CC-2 is able to match and capture both conformers. This strategy allows the formation of three compounds with twin cavities, which we coin diphane. The self-assembly of diphane units results in superstructures with tunable proton conductivity, which reaches up to 1.37×10-5 S cm-1.
Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance
Authors: Qin Yongli , Jia Lina , Liu Huijiao , Ma Wenqiang , Ren Xinmin , Li Haifeng , Liu Yuanwu , Li Haiwen , Ma Shuoqian , Liu Mei , Li Pingping , Yan Jinghua , Zhang Jiyan , Guo Yangdong , You Hua , Guo Yan , Rahman Nafis A. , Wołczyński Sławomir , Kretowski Adam , Li Dangsheng , Li Xiru , Ren Fazheng , Li Xiangdong
Published: October 2021

In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.
Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients
Authors: Watanabe Fumiaki , Suzuki Koichi , Tamaki Sawako , Abe Iku , Endo Yuhei , Takayama Yuji , Ishikawa Hideki , Kakizawa Nao , Saito Masaaki , Futsuhara Kazushige , Noda Hiroshi , Konishi Fumio , Rikiyama Toshiki
Published: October 2021

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.
Bayesian inference of ion velocity distribution function from laser-induced fluorescence spectra
Authors: Tokuda S. , Kawachi Y. , Sasaki M. , Arakawa H. , Yamasaki K. , Terasaka K. , Inagaki S.
Published: October 2021

The velocity distribution function is a statistical description that connects particle kinetics and macroscopic parameters in many-body systems. Laser-induced fluorescence (LIF) spectroscopy is utilized to measure the local velocity distribution function in spatially inhomogeneous plasmas. However, the analytic form of such a function for the system of interest is not always clear under the intricate factors in non-equilibrium states. Here, we propose a novel approach to select the valid form of the velocity distribution function based on Bayesian statistics. We formulate the Bayesian inference of ion velocity distribution function and apply it to LIF spectra locally observed at several positions in a linear magnetized plasma. We demonstrate evaluating the spatial inhomogeneity by verifying each analytic form of the local velocity distribution function. Our approach is widely applicable to experimentally establish the velocity distribution function in plasmas and fluids, including gases and liquids.
Enhanced hyperspectral tomography for bioimaging by spatiospectral reconstruction
Authors: Warr Ryan , Ametova Evelina , Cernik Robert J. , Fardell Gemma , Handschuh Stephan , Jørgensen Jakob S. , Papoutsellis Evangelos , Pasca Edoardo , Withers Philip J.
Published: October 2021

Here we apply hyperspectral bright field imaging to collect computed tomographic images with excellent energy resolution (~ 1 keV), applying it for the first time to map the distribution of stain in a fixed biological sample through its characteristic K-edge. Conventionally, because the photons detected at each pixel are distributed across as many as 200 energy channels, energy-selective images are characterised by low count-rates and poor signal-to-noise ratio. This means high X-ray exposures, long scan times and high doses are required to image unique spectral markers. Here, we achieve high quality energy-dispersive tomograms from low dose, noisy datasets using a dedicated iterative reconstruction algorithm. This exploits the spatial smoothness and inter-channel structural correlation in the spectral domain using two carefully chosen regularisation terms. For a multi-phase phantom, a reduction in scan time of 36 times is demonstrated. Spectral analysis methods including K-edge subtraction and absorption step-size fitting are evaluated for an ex vivo, single (iodine)-stained biological sample, where low chemical concentration and inhomogeneous distribution can affect soft tissue segmentation and visualisation. The reconstruction algorithms are available through the open-source Core Imaging Library. Taken together, these tools offer new capabilities for visualisation and elemental mapping, with promising applications for multiply-stained biological specimens.
Multi-drug resistance and high mortality associated with community-acquired bloodstream infections in children in conflict-affected northwest Nigeria
Authors: Chukwumeze Frederick , Lenglet Annick , Olubiyo Ruth , Lawal Abdulhakeem Mohammed , Oluyide Bukola , Oloruntuyi Gbemisola , Ariti Cono , Gomez Diana , Roggeveen Harriet , Nwankwo Chijioke , Augustine Nwogu Ahamba , Egwuenu Abiodun , Maloba Guy , Sherlock Mark , Muhammad Shoaib , Wertheim Heiman , Hopman Joost , Clezy Kate
Published: October 2021

Pediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistantStaphylococcus aureus(MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.
Enhancement of Campylobacter hepaticus culturing to facilitate downstream applications
Authors: Phung Canh , Wilson Timothy B. , Quinteros José A. , Scott Peter C. , Moore Robert J. , Van Thi Thu Hao
Published: October 2021

Campylobacter hepaticus causes Spotty Liver Disease (SLD) in chickens. C. hepaticus is fastidious and slow-growing, presenting difficulties when growing this bacterium for the preparation of bacterin vaccines and experimental disease challenge trials. This study applied genomic analysis and in vitro experiments to develop an enhanced C. hepaticus liquid culture method. In silico analysis of the anabolic pathways encoded by C. hepaticus revealed that the bacterium is unable to biosynthesise l-cysteine, l-lysine and l-arginine. It was found that l-cysteine added to Brucella broth, significantly enhanced the growth of C. hepaticus, but l-lysine or l-arginine addition did not enhance growth. Brucella broth supplemented with l-cysteine (0.4 mM), l-glutamine (4 mM), and sodium pyruvate (10 mM) gave high-density growth of C. hepaticus and resulted in an almost tenfold increase in culture density compared to the growth in Brucella broth alone (log10 = 9.3 vs 8.4 CFU/mL). The type of culture flask used also significantly affected C. hepaticus culture density. An SLD challenge trial demonstrated that C. hepaticus grown in the enhanced culture conditions retained full virulence. The enhanced liquid culture method developed in this study enables the efficient production of bacterial biomass and therefore facilitates further studies of SLD biology and vaccine development.
Changes in the profile properties and chemical weathering characteristics of cultivated soils affected by anthropic activities
Authors: Li Jiangwen , Du Jing , Zhong Shouqin , Ci En , Wei Chaofu
Published: October 2021

The study of the pedogenic process in response to natural evolution, gradual anthropogenic shifts and engineering upheavals is of great significance for understanding, utilizing and transforming nature in the future. Although scholars have considered anthropic activities to be an important factor affecting pedogenesis, research on how and how much anthropic activities influence the soil-forming process is scant. This paper was conducted to analyse pedogenic characteristics dominated by anthropic activities. In this study, the parent materials and soils undergoing natural evolution (NE), tillage perturbation (TP) and engineering perturbation (EP) were selected as research objects. The genetic characteristics of soils undergoing NE, TP and EP are investigated mainly from three aspects: soil profile macromorphological characteristics, soil physical and chemical properties and chemical weathering characteristics. The results indicated that the influence of anthropic activities (TP and EP) on the process of pedogenesis is complicated. First, compared with NE, TP decreases the thickness of topsoil from 22.2 to 21.2 cm, while EP increases the thickness of topsoil from 22.2 to 23.2 cm, and EP causes the soil to have a high profile development index. Second, compared with TP, EP can improve bulk density (BD), soil organic carbon (SOC), total nitrogen (TN) and cation exchange capacity (CEC), Finally, the chemical weathering intensity differed among NE, TP and EP and followed the order of TP > NE > EP. Therefore, in the future, the genetic characteristics of soils dominated by anthropic activities should be considered. This will help us systematically understand the genesis and evolutionary characteristics of soil and lay a foundation for further perfecting the diagnostic horizon and diagnostic characteristics of the Soil Taxonomy and World Reference Base.
Characteristics of serum metabolites in sporadic amyotrophic lateral sclerosis patients based on gas chromatography-mass spectrometry
Authors: Jia Rui , Chen Qiaoyi , Zhou Qingqing , Zhang Ronghua , Jin Jiaoting , Hu Fangfang , Liu Xiao , Qin Xing , Kang Li , Zhao Songzhen , Dang Yonghui , Dang Jingxia
Published: October 2021

To identify differential metabolites and metabolic pathways and provide guidance for the novel biomarkers for diagnosis and prognosis of amyotrophic lateral sclerosis (ALS). ALS patients and people without nervous diseases were recruited. Metabolomic analysis was performed using gas chromatography-mass spectrometry (GC/MS). The orthogonal projections to latent structures discriminant analysis (OPLS-DA) were used to identify differential metabolites. Kyoto Encyclopedia of Genes and Genomes and MetaboAnalyst were used to identify metabolic pathways. 75 metabolites were detected and aligned. The OPLS-DA showed the metabolomic profile of ALS patients and those in the fast-progression and slow-progression ALS groups differed from that of CTRL (p < 0.05). The levels of maltose, glyceric acid, lactic acid, beta-alanine, phosphoric acid, glutamic acid, ethanolamine and glycine in ALS were significantly higher, while 2,4,6-tri-tert-butylbenzenethiol was lower. Glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, alanine, aspartate, and glutamate metabolism, beta-alanine metabolism, and pyruvate metabolism were significantly altered metabolic pathways in ALS. ROC was used to discriminate ALS from CTRL with an AUC of 0.898 (p < 0.001) using 2,4,6-tri-tert-butylbenzenethiol, beta-alanine, glycine, and ethanolamine. The serum metabolites and metabolic pathways in ALS patients are significantly altered compared with CTRL. These findings may contribute to the early diagnosis of ALS.
Nanobody-based CTLA4 inhibitors for immune checkpoint blockade therapy of canine cancer patients
Authors: Marable Jonathan , Ruiz Damien , Jaiswal Anil K. , Bhattacharya Ritankar , Pantazes Robert , Agarwal Payal , Suryawanshi Amol S. , Bedi Deepa , Mishra Amarjit , Smith Bruce F. , Sandey Maninder
Published: October 2021

Cancer is the leading cause of death in the geriatric dog population. Currently, the use of immune checkpoint inhibitors (ICIs) such as anti-CTLA4 antibodies has markedly improved the prognosis of several cancers in their advanced stages. However, ICIs targeting CTLA4 blockade to treat canine cancer patients are yet to define. In this study, we sought to develop, characterize and assess whether chimeric heavy chain only antibodies (cHcAbs) against CTLA4 are viable therapeutic candidates for the treatment of canine cancers. Anti-CTLA4 nanobodies (Nbs) were identified from a yeast nanobody (Nb) library using magnetic-assisted cell sorting (MACS) and flow cytometry. cHcAbs were engineered by genetically fusing the DNA sequences coding for anti-CTLA4 Nbs with the Fc domain of the subclass B of canine IgG. Recombinant cHcAbs were purified from ExpiCHO-S cells. Stable cell lines expressing canine CTLA4 and FcγRI were used to elucidate the binding ability and specificity of cHcAbs. PBMCs isolated from healthy dogs were used to evaluate the ability of cHcAbs to activate canine PBMCs (cPBMCs). Novel Nbs were identified using the extracellular domain of canine CTLA4 protein to screen a fully synthetic yeast nanobody library. Purified Nbs bind specifically to natïve canine CTLA4. We report that chimeric HcAbs, which were engineered by fusing the anti-CTLA4 Nbs and Fc region of subclass B of canine IgG, were half the size of a conventional mAb and formed dimers. The chimeric HcAbs specifically binds both with canine CTLA4 and Fcγ receptors. As the binding of Nbs overlapped with the MYPPPY motif of canine CTLA4, these Nbs were expected to sterically disrupt the interaction of canine CTLA4 to B-7s. Like their human counterpart, canine CTLA4 was expressed on helper T cells and a small subset of cytotoxic T cells. Canine Tregs also constitutively expressed CTLA4, and stimulation with PMA/Ionomycin dramatically increased expression of CTLA4 on the cell surface. Stimulation of cPBMCs in the presence of agonistic anti-CD3 Ab and cHcAb6 significantly increased the expression of IFN-γ as compared to the isotype control. This study identifies a novel nanobody-based CTLA4 inhibitor for the treatment of canine cancer patients.
Fabrication of clay soil/CuFe2O4 nanocomposite toward improving energy and shielding efficiency of buildings
Authors: Keykavous-Amand Shabnam , Peymanfar Reza
Published: October 2021

In this research, the energy and shielding efficiency of brick, fabricated by clay soil, as a practical building material was reinforced using CuFe2O4 nanoparticles. Initially, the nanoparticles were fabricated using the sol–gel method and then loaded in the brick matrix as a guest. The architected samples were characterized by X-ray powder diffraction (XRD), Fourier transform infrared (FTIR), diffuse reflection spectroscopy (DRS), field emission scanning electron microscopy (FE-SEM), High-resolution transmission electron microscopy (HRTEM), vibrating-sample magnetometer (VSM), differential scanning calorimetry (DSC) thermograms, and vector network analyzer (VNA) analyses. IR absorption of the tailored samples was monitored under an IR source using an IR thermometer. IR absorption and energy band gap attested that inserting the nanoparticles in brick medium led to the acceleration of a warming brick, desirable for energy efficiency in cold climates. It is worth noting that the brick/CuFe2O4 nanocomposite achieved a strong reflection loss (RL) of 58.54 dB and gained an efficient bandwidth as wide as 4.22 GHz (RL > 10 dB) with a thickness of 2.50 mm, meanwhile it shielded more than 58% of the electromagnetic waves at X-band by only a filler loading of 10 wt%. The microwave absorbing and shielding characteristics of the composite are mainly originated from conductive loss, electron hopping, natural and exchange resonance, relaxation loss, secondary fields, as well as eddy current loss. Interestingly, the shielding property of the nanocomposite was significantly generated from its absorbing features, reducing the secondary electromagnetic pollutions produced by the shielding materials applying the impedance mismatching mechanism.
Effect of prewarming on body temperature in short-term bladder or prostatic transurethral resection under general anesthesia: A randomized, double-blind, controlled trial
Authors: Becerra Ángel , Valencia Lucía , Saavedra Pedro , Rodríguez-Pérez Aurelio , Villar Jesús
Published: October 2021

Perioperative hypothermia causes postoperative complications. Prewarming reduces body temperature decrease in long-term surgeries. We aimed to assess the effect of different time-periods of prewarming on perioperative temperature in short-term transurethral resection under general anesthesia. Randomized, double-blind, controlled trial in patients scheduled for bladder or prostatic transurethral resection under general anesthesia. Eligible patients were randomly assigned to receive no-prewarming or prewarming during 15, 30, or 45 min using a forced-air blanket in the pre-anesthesia period. Tympanic temperature was used prior to induction of anesthesia and esophageal temperature intraoperatively. Primary outcome was the difference in core temperature among groups from the induction of general anesthesia until the end of surgery. Repeated measures multivariate analysis of covariance modeled the temperature response at each observation time according to prewarming. We examined modeled contrasts between temperature variables in subjects according to prophylaxis. We enrolled 297 patients and randomly assigned 76 patients to control group, 74 patients to 15-min group, 73 patients to 30-min group, and 74 patients to the 45-min group. Temperature in the control group before induction was 36.5 ± 0.5 °C. After prewarming, core temperature was significantly higher in 15- and 30-min groups (36.8 ± 0.5 °C, p = 0.004; 36.7 ± 0.5 °C, p = 0.041, respectively). Body temperature at the end of surgery was significantly lower in the control group (35.8 ± 0.6 °C) than in the three prewarmed groups (36.3 ± 0.6 °C in 15-min, 36.3 ± 0.5 °C in 30-min, and 36.3 ± 0.6 °C in 45-min group) (p < 0.001). Prewarming prior to short-term transurethral resection under general anesthesia reduced the body temperature drop during the perioperative period. These time-periods of prewarming also reduced the rate of postoperative complications.

Study Registration Registered at ClinicalTrials.gov (Identifier: NCT03630887).
Silica fertilization improved wheat performance and increased phosphorus concentrations during drought at the field scale
Authors: Schaller Jörg , Scherwietes Eric , Gerber Lukas , Vaidya Shrijana , Kaczorek Danuta , Pausch Johanna , Barkusky Dietmar , Sommer Michael , Hoffmann Mathias
Published: October 2021

Drought and the availability of mineable phosphorus minerals used for fertilization are two of the important issues agriculture is facing in the future. High phosphorus availability in soils is necessary to maintain high agricultural yields. Drought is one of the major threats for terrestrial ecosystem performance and crop production in future. Among the measures proposed to cope with the upcoming challenges of intensifying drought stress and to decrease the need for phosphorus fertilizer application is the fertilization with silica (Si). Here we tested the importance of soil Si fertilization on wheat phosphorus concentration as well as wheat performance during drought at the field scale. Our data clearly showed a higher soil moisture for the Si fertilized plots. This higher soil moisture contributes to a better plant performance in terms of higher photosynthetic activity and later senescence as well as faster stomata responses ensuring higher productivity during drought periods. The plant phosphorus concentration was also higher in Si fertilized compared to control plots. Overall, Si fertilization or management of the soil Si pools seem to be a promising tool to maintain crop production under predicted longer and more serve droughts in the future and reduces phosphorus fertilizer requirements.
Deformation understanding in the Upper Paleozoic of Ventana Ranges at Southwest Gondwana Boundary
Authors: Arzadún Guadalupe , Tomezzoli Renata Nela , Fortunatti Natalia , Cesaretti Nora Noemi , Febbo María Belén , Calvagno Juan Martin
Published: October 2021

At the east of the Ventana Ranges, Buenos Aires, Argentina, outcrops the Carboniferous-Permian Pillahuincó Group (Sauce Grande, Piedra Azul, Bonete and Tunas Formation). We carried out an Anisotropy of Magnetic Susceptibility (AMS) study on Sauce Grande, Piedra Azul and Bonete Formation that displays ellipsoids with constant Kmax axes trending NW–SE, parallel to the fold axes. The Kmin axes are orientated in the NE–SW quadrants, oscillating from horizontal (base of the sequence-western) to vertical (top of the sequence-eastern) positions, showing a change from tectonic to almost sedimentary fabric. This is in concordance with the type and direction of foliation measured in petrographic thin sections which is continuous and penetrative to the base and spaced and less developed to the top. We integrated this study with previous Tunas Formation results (Permian). Similar changes in the AMS pattern (tectonic to sedimentary fabric), as well as other characteristics such as the paleo-environmental and sharp curvature in the apparent polar wander path of Gondwana, marks a new threshold in the evolution of the basin. Those changes along the Pillahuincó deposition indicate two different spasm in the tectonic deformation that according to the ages of the rocks are 300–290 Ma (Sauce Grande to Bonete Formation deposition) and 290–276 Ma (Tunas Formation deposition). This Carboniferous-Permian deformation is locally assigned to the San Rafael (Hercinian) orogenic phase, interpreted as the result of rearrangements of the microplates that collided previously with Gondwana, and latitudinal movements of Gondwana toward north and Laurentia toward south to reach the Triassic Pangea.
Acute hyperoxia reveals tonic influence of peripheral chemoreceptors on systemic vascular resistance in heart failure patients
Authors: Tubek Stanislaw , Niewinski Piotr , Paleczny Bartlomiej , Langner-Hetmanczuk Anna , Banasiak Waldemar , Ponikowski Piotr
Published: October 2021

Peripheral chemoreceptors’ (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.
A panel of urine-derived biomarkers to identify sepsis and distinguish it from systemic inflammatory response syndrome
Authors: Tang Yao , Ling Ning , Li Shiying , Huang Juan , Zhang Wenyue , Zhang An , Ren Hong , Yang Yixuan , Hu Huaidong , Wang Xiaohao
Published: October 2021

Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. Hence, highly sensitive and specific biomarkers are needed to differentiate sepsis from SIRS. Urine samples were collected and segregated by group (a sepsis group, a SIRS group, and a healthy control group). iTRAQ was used to identify the differentially expressed proteins among the three groups. The identified proteins were measured by ELISA in urine samples. Finally, all the acquired data were analyzed in SPSS. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. The adjusted median concentrations of urinary C-reactive protein were 1337.6, 358.7, and 2.4 in the sepsis, SIRS, and healthy control groups, respectively. The urinary leucine-rich alpha glycoprotein-1 levels in these three groups were 1614.4, 644.5, and 13.6, respectively, and the levels of SAA were 6.3, 2.9, and 0.07, respectively. For all three of these measures, the sepsis group had higher levels than the SIRS group (P < 0.001), and the SIRS group had higher levels than the healthy control group. When combined, the three biomarkers had a sensitivity of 0.906 and a specificity of 0.896 in distinguishing sepsis from SIRS. Urinary C-reactive protein, urinary leucine-rich alpha glycoprotein-1 and urinary SAA have diagnostic value in cases of sepsis. This initial study suggests the possibility of improved differential diagnosis between sepsis and systemic inflammatory response syndrome; additional confirmation is necessary to corroborate the findings.
Design, synthesis, biological evaluation, and molecular modeling studies of pyrazole-benzofuran hybrids as new α-glucosidase inhibitor
Authors: Azimi Fateme , Azizian Homa , Najafi Mohammad , Khodarahmi Ghadamali , Saghaei Lotfollah , Hassanzadeh Motahareh , Ghasemi Jahan B. , Faramarzi Mohammad Ali , Larijani Bagher , Hassanzadeh Farshid , Mahdavi Mohammad
Published: October 2021

In this work, new derivatives of biphenyl pyrazole-benzofuran hybrids were designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 μM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 μM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features, used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.
Successful captive breeding of a Malayan pangolin population to the third filial generation
Authors: Yan Dingyu , Zeng Xiangyan , Jia Miaomiao , Guo Xiaobing , Deng Siwei , Tao Li , Huang Xiaolu , Li Baocai , Huang Chang , Que Tengcheng , Li Kaixiang , Liang Wenhui , Zhao Yao , Liang Xingxing , Zhong Yating , Platto Sara , Choo Siew Woh
Published: October 2021

Pangolins are threatened placental mammals distributed in Africa and Asia. Many efforts have been undertaken in the last century to maintain pangolins in captivity, but only a few of them succeeded in maintaining and keeping this species in a controlled environment. This study reports the first systematic breeding of the Critically Endangered Malayan pangolin (Manis javanica) in captivity. Our captive breeding approach successfully improved the reproductive rate for both wild and captive-born female pangolins. From 2016 to 2020, we had 33 wild pangolins and produced 49 captive-born offspring spanning three filial generations. The female offspring further bred 18 offspring, of which 14 (78%) were conceived during the first time of cohabitation with males, and four offspring were conceived during the second cohabitation event, suggesting that they may practice copulation-induced ovulation. We observed that captive-born female pangolins could reach sexual maturity at 7–9 months (n = 4), and male pangolins could mate and successfully fertilise females at nine months age (n = 1). We also observed a female pangolin conceiving on the eighth day after parturition (the fifth day after the death of its pup). Our captive pangolins had a female-biased sex ratio of 1:0.5 at birth, unlike other known captive-born mammals. Also, captive-born pangolins were generally more viable after successful weaning and had a similar gestation length (~185 days) to wild pangolins. Most importantly, we report the first self-sustaining captive population of Malayan pangolins, and this species has an efficient reproduction strategy. These advances provide more comprehensive information for people to understand pangolins, and have implications for conserving endangered Malayan pangolins and providing scientific guidance to the management of other pangolin species.