bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic loss assessment of curved bridges considering the effect of ground motion directionality
Authors: Feng Ruiwei , Yuan Wancheng , Sextos Anastasios
Published: August 2021

This study aims to assess, in a probabilistic manner, the effect of seismic excitation direction on the performance of a 638 m‐long, 12 span prestressed concrete bridge with significant curvature in plan on the basis of overall monetary repair loss. By means of a large number of nonlinear dynamic analyses, the optimum intensity measure (IM) was selected from a pool of twenty candidates considering the impact of seismic excitation direction. Next, the variability of bridge loss with respect to the seismic incidence angle under different groups of earthquake intensities was obtained. Finally, the applicability of combination rules for the seismic performance of curved bridges was evaluated based on the multidirectional loss assessment results. Meanwhile, the effects of seismic excitation direction and earthquake intensity on the evaluation of combination rules were also revealed. Results indicate that velocity‐related or/and structural‐dependent IMs are more appropriate for the probabilistic seismic demand analysis of curved bridges. It is also notable that the total bridge loss gradually turns out to be independent of the seismic excitation direction as the seismic intensity increases and the damage develops throughout the structure. Additionally, the widely used100/30and100/40rules may lead to an unconservative estimation for the loss of the curved bridge. The above findings highlight the necessity of addressing the issue of ground motion directionality in a rigorous probabilistic manner and pave the way for further research on qualifying the influences of geometric configuration, material parameters, soil type and the consequent soil‐structure interaction effect.
Soil erosion and sediment transport in Tanzania: Part I – sediment source tracing in three neighbouring river catchments
Authors: Wynants Maarten , Munishi Linus , Mtei Kelvin , Bodé Samuel , Patrick Aloyce , Taylor Alex , Gilvear David , Ndakidemi Patrick , Blake William H. , Boeckx Pascal
Published: August 2021

Water bodies in Tanzania are experiencing increased siltation, which is threatening water quality, ecosystem health, and livelihood security in the region. This phenomenon is caused by increasing rates of upstream soil erosion and downstream sediment transport. However, a lack of knowledge on the contributions from different catchment zones, land‐use types, and dominant erosion processes, to the transported sediment is undermining the mitigation of soil degradation at the source of the problem. In this context, complementary sediment source tracing techniques were applied in three Tanzanian river systems to further the understanding of the complex dynamics of soil erosion and sediment transport in the region. Analysis of the geochemical and biochemical fingerprints revealed a highly complex and variable soil system that could be grouped in distinct classes. These soil classes were unmixed against riverine sediment fingerprints using the Bayesian MixSIAR model, yielding proportionate source contributions for each catchment. This sediment source tracing indicated that hillslope erosion on the open rangelands and maize croplands in the mid‐zone contributed over 75% of the transported sediment load in all three river systems during the sampling time‐period. By integrating geochemical and biochemical fingerprints in sediment source tracing techniques, this study demonstrated links between land use, soil erosion and downstream sediment transport in Tanzania. This evidence can guide land managers in designing targeted interventions that safeguard both soil health and water quality.
Energy efficient resource allocation in cache‐enabled fog networks
Authors: Basir Rabeea , Qaisar Saad , Ali Mudassar , Naeem Muhammad , Anpalagan Alagan
Published: August 2021

To gain high energy efficiency and low latency, fog computing can be considered as a promising enabling technology for supporting future IoT networks. Exponentially increasing data rate demand of smart IoT devices in the fifth‐Generation (5G) networks require new resource management and power allocation schemes. Fog computing involves the deployment of data storage devices (fog nodes) near the proximity of IoT nodes. The fog nodes collaborate to process requests generated from users. These nodes can store data in their storage capacity and supports in achieving quality‐of‐service (QoS) requirements. A joint node association and energy efficiency maximization problem is formulated in this article. The proposed problem is a non‐linear concave programming problem under cache size, association, and optimal power allocation constraints. A mesh adaptive direct search algorithm (MADS) is used to solve the formulated problem to find the sub‐optimal results. The efficient performance of the algorithm can be seen in comparison with more complex algorithms namely, outer approximation algorithm and exhaustive search algorithm. Extensive simulations are done to observe the detailed performance analysis of the IoT‐Fog network. As a result, energy‐efficient resource allocation is done under cache and QoS constraints with very little complexity and low computational power and delays.
Predicting flammability limits through thermal theory and density theory of flame propagation
Authors: Nassimi Ali M.
Published: August 2021

Flammability limits are important safety parameters of each flammable material. Thermal theory of flame propagation suggests existence of a threshold temperature above which a flame propagates. Density theory of flame propagation suggests existence of a threshold density factor above which a flame propagates; density factor is defined as the ratio of before ignition to after ignition density. Based on a general version of thermal theory of flame propagation, constancy of values of adiabatic flame temperature at each flammability limit can be used to predict flammability limits. Similarly, based on a general version of the density theory of flame propagation, constancy of values of density factor at each flammability limit can be used to predict flammability limits. This work reports and compares predictions of general versions of both thermal theory and density theory of flame propagation for lower flammability limits and for upper flammability limits. This work shows that thermal theory and density theory both perform well at predicting the lower flammability limit while density theory performs far better than thermal theory at predicting the upper explosive limit.
Effect of calcium treatment on the browning of harvested eggplant fruits and its relation to the metabolisms of reactive oxygen species (ROS) and phenolics
Authors: Ban Qiuyan , Liu Tongjin , Ning Kun , Fan Junjun , Cui Qunxiang , Guo Yanle , Zai Xueming
Published: August 2021

Eggplant is a popular vegetable in Asia; however, it has a short storage life and considerable economic losses have resulted from eggplant browning. Calcium has been reported to play a key role in the postharvest storage of plants. Here, we found that exogenous calcium application could delay eggplant fruit browning and maintain higher storage quality. The increased browning index (BI), relative electrolytic leakage (REL), and water loss were suppressed by calcium treatment during storage. Delayed browning with calcium treatment might result from a higher phenolic level and suppressed the activity of polyphenol oxidase (PPO). Less H2O2 and O2‐ but more activated reactive oxygen species (ROS) scavenging enzymes accumulated in calcium‐treated fruits than in H2O‐treated fruits. Moreover, the nonenzymatic antioxidant, ascorbic acid (AsA), was accumulated more in calcium‐treated eggplant fruits. Taken together, our data demonstrated that exogenous calcium application delayed eggplant fruit browning by regulating phenol metabolism and enhancing antioxidant systems.
Microglia contributes to remyelination in cerebral but not spinal cord ischemia
Authors: Pavic Goran , Petzsch Patrick , Jansen Robin , Raba Katharina , Rychlik Nicole , Simiantonakis Ioannis , Küry Patrick , Göttle Peter , Köhrer Karl , Hartung Hans‐Peter , Meuth Sven G. , Jander Sebastian , Gliem Michael
Published: August 2021

Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in gray matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion. Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance.
Impacts of depression subcase and case on all‐cause mortality in older people: The findings from the multi‐centre community‐based cohort study in China
Authors: Chen Ruoling , Zhou Weiju , Ma Ying , Wan Yuhui , Qin Xia , Rodney Amanda , Ni Jindong , Thomas Erica , Gao Jian , Spira Adam P. , Hu Zhi , Copeland John R. M.
Published: August 2021

Objectives

It is unclear whether and to what extent depression subcases and cases in older age were associated with all‐cause mortality. Little is known about gender differences in the associations. We assess these in older Chinese.

Methods

We examined a random sample of 6124 participants aged ≥60 years across five provinces in China. They were interviewed using a standard method of the GMS‐AGECAT to diagnose depression subcase and case and record sociodemographic and disease risk factors at baseline, and to follow up their vital status. We employed Cox regression models to determine all‐cause mortality in relation to depression subcases and cases, with adjustment for important variables, including social support and co‐morbidities.

Results

Over the 10‐year follow‐up, 928 deaths occurred. Compared to those without depression at baseline, participants with depression subcase (n = 196) and case (n = 264) had increased risk of mortality; adjusted hazard ratios (HRs) were 1.46 (95% CI 1.07–2.00) and 1.45 (1.10–1.91). The adjusted HRs in men were 1.15 (0.72–1.81) and 1.85 (1.22–2.81), and in women 1.87 (1.22–2.87) and 1.22 (0.83–1.77) respectively. In participants aged ≥65 years, the adjusted HRs were 1.12 (0.68–1.84) and 1.99 (1.28–3.10) in men, and 2.06 (1.32–2.24) and 1.41 (0.94–2.10) in women. Increased HR in depression subcases was higher in women than man (ratio of HRs was 1.84, p = 0.034).

Conclusions

Older people with depression subcase could have increased all‐cause mortality to a similar extent to those with depression case. More attention should be paid to subcases of depression in women to tackle gender inequalities and improve survival.
Hepatitis E virus infection activates NOD‐like receptor family pyrin domain‐containing 3 inflammasome antagonizing interferon response but therapeutically targetable
Authors: Li Yang , Yu Peifa , Kessler Amy L. , Shu Jingyi , Liu Xiaoyan , Liang Zhaochao , Liu Jiaye , Li Yunlong , Li Pengfei , Wang Ling , Wang Yining , Ma Zhongren , Liu Aixia , Wang Ling , Bruno Marco J. , de Man Robert A. , Peppelenbosch Maikel P. , Buschow Sonja I. , Wang Lin , Wang Yijin , Pan Qiuwei
Published: August 2021

Background and Aims

HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting.

Approach and Results

We measured IL‐1β secretion, the hallmark of inflammasome activation, in serum of HEV‐infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte‐derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL‐1β production. A profound increase of IL‐1β secretion was further observed in HEV‐infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF‐κB signaling activation as a key upstream event of HEV‐induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross‐interference.

Conclusions

HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.
The geographic scope of conflict and HIV
Authors: Kim Yiyeon
Published: August 2021

Background

HIV affects 74.9 million people. While there is empirical inconsistency in the conflict and HIV literature, no previous studies have questioned the effects of geographic scope of conflict on HIV. This study aims to overcome past limitations by examining on the impact of geographic scope of conflict on HIV prevalence and women's HIV prevalence.

Methodology

This study analyzes 31 developing countries from 1990 to 2009 using fixed‐effects regression models with Driscoll and Kraay standard errors (DKSE). DKSE adjusts higher‐order autocorrelation, serial correlation, and spatial dependency.

Results

This study finds that as the scope of a conflict increases, so do both overall HIV and women's HIV prevalence rates. This is the first study that reveals the impact of conflict's scope on society.

Conclusion

For leaders who implement HIV policy, this study shows that international organisations and NGOs should consider expanding their efforts in fighting HIV to include areas that experience wide conflict. In addition, this study suggests for conflict literature that scope of conflict is a significant factor that should examined from the perspective of consequences of conflict.
Subarctic catchment water storage and carbon cycling – Leading the way for future studies using integrated datasets at Pallas, Finland
Authors: Marttila Hannu , Lohila Annalea , Ala‐Aho Pertti , Noor Kashif , Welker Jeffrey M. , Croghan Danny , Mustonen Kaisa , Meriö Leo‐Juhani , Autio Anna , Muhic Filip , Bailey Hannah , Aurela Mika , Vuorenmaa Jussi , Penttilä Timo , Hyöky Valtteri , Klein Eric , Kuzmin Anton , Korpelainen Pasi , Kumpula Timo , Rauhala Anssi , Kløve Bjørn
Published: August 2021

Subarctic ecohydrological processes are changing rapidly, but detailed and integrated ecohydrological investigations are not as widespread as necessary. We introduce an integrated research catchment site (Pallas) for atmosphere, ecosystems, and ecohydrology studies in subarctic conditions in Finland that can be used for a new set of comparative catchment investigations. The Pallas site provides unique observational data and high‐intensity field measurement datasets over long periods. The infrastructure for atmosphere‐ to landscape‐scale research in ecosystem processes in a subarctic landscape has recently been complemented with detailed ecohydrological measurements. We identify three dominant processes in subarctic ecohydrology: (a) strong seasonality drives ecohydrological regimes, (b) limited dynamic storage causes rapid stream response to water inputs (snowmelt and intensive storms), and (c) hydrological state of the system regulates catchment‐scale dissolved carbon dynamics and greenhouse (GHG) fluxes. Surface water and groundwater interactions play an important role in regulating catchment‐scale carbon balances and ecosystem respiration within subarctic peatlands, particularly their spatial variability in the landscape. Based on our observations from Pallas, we highlight key research gaps in subarctic ecohydrology and propose several ways forward. We also demonstrate that the Pallas catchment meets the need for sustaining and pushing the boundaries of critical long‐term integrated ecohydrological research in high‐latitude environments.
Genetic‐based adaptive momentum estimation for predicting mortality risk factors for COVID‐19 patients using deep learning
Authors: Elghamrawy Sally M. , Hassanien Aboul Ella , Vasilakos Athanasios V.
Published: August 2021

The mortality risk factors for coronavirus disease (COVID‐19) must be early predicted, especially for severe cases, to provide intensive care before they develop to critically ill immediately. This paper aims to develop an optimized convolution neural network (CNN) for predicting mortality risk factors for COVID‐19 patients. The proposed model supports two types of input data clinical variables and the computed tomography (CT) scans. The features are extracted from the optimized CNN phase and then applied to the classification phase. The CNN model's hyperparameters were optimized using a proposed genetic‐based adaptive momentum estimation (GB‐ADAM) algorithm. The GB‐ADAM algorithm employs the genetic algorithm (GA) to optimize Adam optimizer's configuration parameters, consequently improving the classification accuracy. The model is validated using three recent cohorts from New York, Mexico, and Wuhan, consisting of 3055, 7497,504 patients, respectively. The results indicated that the most significant mortality risk factors are: CD T Lymphocyte (Count), D‐dimer greater than 1 Ug/ml, high values of lactate dehydrogenase (LDH), C‐reactive protein (CRP), hypertension, and diabetes. Early identification of these factors would help the clinicians in providing immediate care. The results also show that the most frequent COVID‐19 signs in CT scans included ground‐glass opacity (GGO), followed by crazy‐paving pattern, consolidations, and the number of lobes. Moreover, the experimental results show encouraging performance for the proposed model compared with different predicting models.
Measuring the depth of reflection in reflective supervision/consultation sessions: Initial validation of the Reflective Interaction Observation Scale (RIOS)
Authors: Meuwissen Alyssa S. , Watson Christopher
Published: August 2021

Research on reflective supervision and reflective consultation (RS/C) is limited, and has primarily relied on self‐report measures and qualitative interviews. To our knowledge, no measures currently exist which provide a way to observationally measure what occurs during an RS/C session. Thus, the Reflective Interaction Observation Scale (RIOS) was created as a way to more objectively measure the quality of RS/C. This study sought to provide initial evidence around the reliability and validity of the RIOS through a sample of child welfare workers (N = 40) who participated in six online group reflective consultation sessions and completed self‐report surveys after their first and last session. The RIOS was used to code the first and last session each participant attended. Results showed that in this sample the RIOS Essential Elements had good variability and strong reliability. The data suggested that the five Elements could be condensed into three subscales, two of which showed significant change over time. The Self Openness subscale showed concurrent validity with existing self‐report measures of RS/C. Results suggest that the RIOS shows promise as a measure that could contribute to a more rigorous evidence base for the practice of RS/C.
On‐farm irrigation water management in India: Challenges and research gaps*
Authors: Gupta Ajita , Singh Ranjay kumar , Kumar Mukesh , Sawant Chetankumar Prakash , Gaikwad Bhaskar Bharat
Published: August 2021

The growing demand for food to feed the increasing population of India has made it necessary to bring more land under cultivation with assured irrigation facilities. The irrigation sector demands a high amount of the available freshwater resources of the country. Thus, the efficiency of its use is of utmost importance for sustainable agriculture. India is the second‐largest irrigated country and is one of the leading countries in terms of the expansion of irrigated areas in the world. Researchers and various agencies are working towards increasing the irrigation efficiency of the system and the water productivity of the crops. The formulation of any irrigation scheme and policy to be sustainable should be based on scientific inputs and supported by pertinent research studies. The effective communication between policymakers and the research community is the main key to the success of such formulated schemes and policies. This paper provides an overview of current challenges and problems associated with irrigation at the field level vis‐à‐vis research gaps for scientific management of irrigation water in the farmer's field. The apathy of farmers for adopting modern irrigation practices has also been reasoned in this review paper. This review paper would provide an insight into common irrigation‐related problems of farmers to researchers and policymakers.
Determining optimal values of performance indicators in different scenarios of on‐farm water management*
Authors: Moghimi Mohammad Mehdi , Niknejad Fatemeh , Mahmoudi Mohammad Reza , Moghaddam Atefeh
Published: August 2021

In order to save water in the agricultural sector, the efficient use of irrigation water should be considered seriously by using appropriate performance indicators. In this research, the impact of on‐farm water management factors (irrigation application efficiency [Ea] and water reduction fraction [WRF]) on the performance indicators net income (NI) and farm irrigation water productivity (WP) were assessed in different deficit irrigation scheduling scenarios (consists of deliberately applying irrigation depths smaller than those required), using response surface methodology. Pareto charts of the standardized effects showed that the factors of WRF and Ea were the most important predictors influencing NI and WP, respectively. Considering multiple response predictions for simultaneous optimization of NI and WP, the maximum optimal values of NI obtained were 62.1 million rials (WP = 1.12, WRF = 0.33), 113.2 (WP = 0.76, WRF = 0.02), 32.2 (WP = 0.8, WRF = 0.19), 65.5 (WP = 0.66, WRF = 0.17), and 84.0 (WP = 0.34, WRF = 0.48) for winter wheat, rapeseed, barley, maize, and cotton, respectively. These values were obtained in Ea = 90%, method 2 of deficit irrigation scheduling and sprinkler irrigation system. Using different deficit irrigation scheduling scenarios and irrigation systems resulted in on‐farm water management packages for different conditions of water availability.
Measuring real activity using a weekly economic index
Authors: Lewis Daniel J. , Mertens Karel , Stock James H. , Trivedi Mihir
Published: August 2021

This paper describes a weekly economic index (WEI) developed to track the rapid economic developments associated with the onset of and policy response to the novel coronavirus in the United States. The WEI is a weekly composite index of real economic activity, with eight of 10 series available the Thursday after the end of the reference week. In addition to being a weekly real activity index, the WEI has strong predictive power for output measures and provided an accurate nowcast of current‐quarter GDP growth in the first half of 2020, with weaker performance in the second half. We document how the WEI responded to key events and data releases during the first 10 months of the pandemic.
Single‐shot phase contrast microscopy using polarisation‐resolved differential phase contrast
Authors: Kalita Ranjan , Flanagan William , Lightley Jonathan , Kumar Sunil , Alexandrov Yuriy , Garcia Edwin , Hintze Mark , Barkoulas Michalis , Dunsby Chris , French Paul M. W.
Published: August 2021

We present a robust, low‐cost single‐shot implementation of differential phase microscopy utilising a polarisation‐sensitive camera to simultaneously acquire four images from which phase contrast images can be calculated. This polarisation‐resolved differential phase contrast (pDPC) microscopy technique can be easily integrated with fluorescence microscopy.
Semiautomated quantification of the fibrous tissue response to complex three‐dimensional filamentous scaffolds using digital image analysis
Authors: Barsch Friedrich , Mamilos Andreas , Babel Maximilian , Wagner Willi L. , Winther Hinrich B. , Schmitt Volker H. , Hierlemann Helmut , Teufel Andreas , Brochhausen Christoph
Published: August 2021

Fibrosis represents a relevant response to the implantation of biomaterials, which occurs not only at the tissue–material interface (fibrotic encapsulation) but also within the void fraction of complex three‐dimensional (3D) biomaterial constructions (fibrotic ingrowth). Usual evaluation of the biocompatibility mostly depicts fibrosis at the interface of the biomaterial using semiquantitative scores. Here, the relations between encapsulation and infiltrating fibrotic growth are poorly represented. Virtual pathology and digital image analysis provide new strategies to assess fibrosis in a more differentiated way. In this study, we adopted a method previously used to quantify fibrosis in visceral organs to the quantification of fibrosis to 3D biomaterials. In a proof‐of‐concept study, we transferred the “Collagen Proportionate Area” (CPA) analysis from hepatology to the field of biomaterials. As one task of an experimental animal study, we used CPA analysis to quantify the fibrotic ingrowth into a filamentous scaffold after subcutaneous implantation. We were able to demonstrate that the application of the CPA analysis is well suited as an additional fibrosis evaluation strategy for new biomaterial constructions. The CPA method can contribute to a better understanding of the fibrotic interactions between 3D scaffolds and the host tissue responses.
Conductive and injectable hyaluronic acid/gelatin/gold nanorod hydrogels for enhanced surgical translation and bioprinting
Authors: Kiyotake Emi A. , Thomas Emily E. , Homburg Hannah B. , Milton Camille K. , Smitherman Adam D. , Donahue Nathan D. , Fung Kar‐Ming , Wilhelm Stefan , Martin Michael D. , Detamore Michael S.
Published: August 2021

There is growing evidence indicating the need to combine the rehabilitation and regenerative medicine fields to maximize functional recovery after spinal cord injury (SCI), but there are limited methods to synergistically combine the fields. Conductive biomaterials may enable synergistic combination of biomaterials with electric stimulation (ES), which may enable direct ES of neurons to enhance axon regeneration and reorganization for better functional recovery; however, there are three major challenges in developing conductive biomaterials: (1) low conductivity of conductive composites, (2) many conductive components are cytotoxic, and (3) many conductive biomaterials are pre‐formed scaffolds and are not injectable. Pre‐formed, noninjectable scaffolds may hinder clinical translation in a surgical context for the most common contusion‐type of SCI. Alternatively, an injectable biomaterial, inspired by lessons from bioinks in the bioprinting field, may be more translational for contusion SCIs. Therefore, in the current study, a conductive hydrogel was developed by incorporating high aspect ratio citrate‐gold nanorods (GNRs) into a hyaluronic acid and gelatin hydrogel. To fabricate nontoxic citrate‐GNRs, a robust synthesis for high aspect ratio GNRs was combined with an indirect ligand exchange to exchange a cytotoxic surfactant for nontoxic citrate. For enhanced surgical placement, the hydrogel precursor solution (i.e., before crosslinking) was paste‐like, injectable/bioprintable, and fast‐crosslinking (i.e., 4 min). Finally, the crosslinked hydrogel supported the adhesion/viability of seeded rat neural stem cells in vitro. The current study developed and characterized a GNR conductive hydrogel/bioink that provided a refinable and translational platform for future synergistic combination with ES to improve functional recovery after SCI.
Exosomes derived from ADSCs containing miR‐378 promotes wound healing by targeting caspase‐3
Authors: Zheng Tianfeng , Shao Wenjun , Tian Jun
Published: August 2021

Pathological scars and chronic wounds caused by injury, aging, or surgery have always been important public health problems, and there is an urgent need to study the driving forces to find more effective treatments. In this study, we extracted and identified ADSCs exosomes and found that they have the ability to protect HaCat cells from oxidative damage, including promoting proliferation and migration and reducing apoptosis. Further studies determined that the expression of miR‐378 was significantly enriched in exosomes. Studies have found that miR‐378 mimic can produce protection similar to ADSCs‐exo. However, when miR‐378 inhibitors are used on ADSCs, the damage protection of the secreted exosomes disappears. This proves that miR‐378 enriched in exosomes can improve HaCat's oxidative stress damage. Luciferase experiments show that this effect is achieved by targeting caspase‐3. These results indicate that ADSCs play a protective role in wound healing by secreting miR‐378‐rich exosomes.
Activation of PI3K/PKB/GSK‐3β signaling by sciadopitysin protects cardiomyocytes against high glucose‐induced oxidative stress and apoptosis
Authors: Zhang Chujie , Yu Huimei , Yang Han , Liu Ben
Published: August 2021

Diabetic cardiomyopathy (DCM), a diabetes complication, accounts for diabetes‐associated morbidity, mortality, and heart failure. Biflavonoids have been demonstrated to possess extensive pharmacological properties, such as antidiabetic and antioxidant activities. Our study aimed to explore the effects of sciadopitysin, a type of biflavonoid, on DCM and the mechanism involved. An experimental cell model was established in AC16 cardiomyocytes by exposure to high glucose (HG). Cell injury was estimated by detecting cell viability and lactate dehydrogenase (LDH) release. Oxidative stress was determined by measuring malondialdehyde (MDA) level and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and catalase (CAT). Apoptosis was assessed by flow cytometry analysis, caspase‐3/7 activity assay, and Western blot analysis of cytochrome C (Cyt C) expression. Alternation of the phosphatidylinositol‐3 kinase (PI3K)/protein kinase B (PKB)/glycogen synthase kinase‐3β (GSK‐3β) pathway was detected by Western blot. Results showed that HG exposure reduced viability and increased LDH release in AC16 cells, which was abolished by sciadopitysin treatment. Sciadopitysin inhibited HG‐induced oxidative stress, as evidenced by the reduced MDA content, and the increased activities of SOD, CAT, and GSH‐Px. Sciadopitysin suppressed HG‐induced apoptosis, an increase of caspase‐3/7 activity, and Cyt C expression in AC16 cells. Mechanistically, sciadopitysin activated the PI3K/PKB/GSK‐3β pathway under HG stimulation in AC16 cells. Inhibition of PI3K/PKB/GSK‐3β pathway by LY294002 blocked the effects of sciadopitysin on HG‐induced injury, oxidative stress, and apoptosis in AC16 cells. Summarily, sciadopitysin alleviated HG‐caused oxidative stress and apoptosis in cardiomyocytes by activating the PI3K/PKB/GSK‐3β pathway.
Distribution and reference interval establishment of neutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) in Chinese healthy adults
Authors: Wang Junjun , Zhang Fan , Jiang Feng , Hu Lijuan , Chen Jian , Wang Yumin
Published: August 2021

Background

Neutral‐to‐lymphocyte ratio (NLR), lymphocyte‐to‐monocyte ratio (LMR), and platelet‐to‐lymphocyte ratio (PLR) are associated with coronavirus disease 2019 (COVID‐19) and many diseases, but there are few data about the reference interval (RI) of NLR, LMR, and PLR.

Methods

The neutrophil count, lymphocyte count, monocyte count, and platelet count of 404,272 Chinese healthy adults (>18 years old) were measured by Sysmex XE‐2100 automatic hematology analyzer, and NLR, LMR, and PLR were calculated. According to CLSI C28‐A3, the nonparametric 95% percentile interval is defined as the reference interval.

Results

The results of Mann‐Whitney U test showed that NLR (p < .001) in male was significantly higher than that in female; LMR (p < .001) and PLR (p < .001) in male were significantly lower than that in female. Kruskal‐Wallis H test showed that there were significant differences in NLR, LMR, and PLR among different genders and age groups (p < .001). The linear graph showed that the reference upper limit of NLR and PLR increased with age and the reference upper limit of LMR decreases with age in male population. In female population, the reference upper limit of NLR in 50–59 group, LMR in >80 group, and PLR in 70–79 group appeared a trough; the reference upper limit of NLR in >80 group, LMR in 50–59 group, and PLR in 40–49 group appeared peak.

Conclusion

The establishment of RI for NLR, LMR, and PLR in Chinese healthy adults according to gender and age will promote the standardization of clinical application.
Preparation of recyclable materials for removing heavy metal ions in aqueous solution and wastewater applications
Authors: Liang Shuaiyu , Li Yingli , Qu Guangfei , Yang Congqing , Yang Can , Zhou Junhong
Published: August 2021

BACKGROUND

Two functionalized nano‐adsorbents were prepared by modifying carbon nanotubes and graphene oxide with active carboxyl groups, and used to remove Pb(II) heavy metal ions in aqueous solutions. The adsorbent combines the advantages of the active groups that can easily capture heavy metal ions and the high specific surface area of nanomaterials, has high adsorption capacity and affinity and is easily separated from the sample solution by centrifugation.

RESULTS

Both scanning and transmission electron microscopy images show that the walls of the carbon tubes are oxidized and the ports at both ends are also opened, and the graphene oxide surface has more folds, producing more active groups such as carboxyl and hydroxyl groups, which provide suitable active sites for the attachment of heavy metals. X‐ray photoelectron spectroscopy shows that characteristic peak of lead appears in the energy spectrum after adsorption. Raman and infrared spectra show that the surface defects of the two materials have increased. The adsorption capacity calculated using the Langmuir equation was 118.82 and 178.23 mg g−1 at pH = 5, and equilibrium adsorption capacity was reached at 120 min. The adsorption capacity of the materials for Pb2+ reaches the equilibrium concentration value when the concentration is 50 mg L−1. Wastewater experiments were carried out to prove that the materials can meet the relevant national standards for lead ions in actual wastewater.

CONCLUSIONS

The adsorption results for the two materials demonstrated that the materials prepared in the optimum conditions exhibited strong adsorption ability and high stability and with promise for practical applications. © 2021 Society of Chemical Industry
In‐vivo toxicity and therapeutic efficacy of Paeonia emodi‐mediated zinc oxide nanoparticles: In‐vitro study
Authors: Shah Amreen , Tauseef Isfahan , Yameen Muhammad Arfat , Haleem Syed Kashif , Haq Sirajul , Shoukat Sabeena
Published: August 2021

This study was planned to explore the in‐vitro and in‐vivo therapeutic significance of Paeonia emodi‐mediated zinc oxide nanoparticles (ZnO NPs) against the Staphylococcus aureus and Escherichia coli. The texture parameters were derived from nitrogen adsorption–desorption data using Brunauer–Emmett–Teller (BET) and Barrett–Joyner–Halenda (BJH) methods, and the surface area (SBET) was found to be 214 m2/g with a pore size of 2.3 nm. The crystallographic parameters were investigated through X‐ray diffraction analysis, and the calculated crystallite size is 29.13 nm. The microstructure was examined through transmission and scanning electron microscopies (TEM and SEM, respectively), and the average particle size estimated from a TEM image is 44.40 nm. The chemical composition and attached function groups were identified through energy‐dispersive X‐ray and Fourier transform infrared spectroscopies. The in‐vitro minimum inhibitory concentration (MIC) for both bacterial species results was found less than 2 μg/ml. The tolerance limit of mouse models was evaluated by the inoculation of different concentrations of ZnO suspension where the concentration above 23 ppm was proved lethal. The maximum infection was caused in mouse models by inoculation of 3 × 107 CFUs (Colony forming unit) of the both bacterial species. The concentration higher than 3 × 107 CFUs led to the ultimate death of the mice. The histopathological and hematological studies reveal that the after simultaneous inoculation of both ZnO NPs and bacterial suspensions (tolerated amount), no/negligible infection was found in the mice model.
Slope stability of streambanks at saturated riparian buffer sites
Authors: Dickey Loulou C. , McEachran Andrea R. , Rutherford Cassandra J. , Rehmann Chris R. , Perez Michael A. , Groh Tyler A. , Isenhart Thomas M.
Published: August 2021

Saturated riparian buffers (SRBs) reduce nitrate export from agricultural tile drainage by infusing drainage water into carbon‐rich riparian soils where denitrification and plant uptake occur. The water quality benefits from SRBs are well documented, but uncertainties about their effect on streambank stability have led to design standards that limit the maximum bank height and minimum buffer width, thus reducing the number of suitable candidate sites. In this study, the relationship between SRB design and streambank stability was examined through numerical slope stability modeling and validated using field sites. At the study sites, the addition of SRB flow increased the probability of failure by less than 3% for both simulated dry and rainfall scenarios. Furthermore, the simulations provide no evidence to support excluding potential sites based on bank height alone. Multivariate analysis of dimensionless parameters developed for SRB flow conditions was used to predict the factor of safety as a function of the SRB site and design conditions. The equation presented allows designers to assess the stability of a potential site where bank failure poses a heightened risk. The results of this study alleviate the need for extensive geotechnical evaluations at future SRB sites and could increase SRB implementation by expanding the range of eligible sites.
Split‐nitrogen application with cover cropping reduces subsurface nitrate losses while maintaining corn yields
Authors: Preza‐Fontes Giovani , Pittelkow Cameron M. , Greer Kristin D. , Bhattarai Rabin , Christianson Laura E.
Published: August 2021

Artificial subsurface drainage is essential to sustain crop production in many areas but may also impair water quality by exacerbating nitrate (NO3)–nitrogen (N) delivery downstream. Cover crops and split‐N application have been promoted as key conservation practices for reducing NO3–N losses, but few studies have simultaneously assessed their effect on water quality and crop productivity. A field study was conducted to evaluate the effects of N application timing and cover crops on subsurface drainage NO3–N losses and grain yield in continuous corn (Zea mays L.). Treatments were preplant‐N: 224 kg N ha–1 split‐applied with 60% fall + 40% preplant in 2018, or as single preplant applications in 2019 and 2020; split‐N: 40% preplant + 60% side‐dress (V6–V7); split‐N + cover crop (CC): Split‐N + cereal rye (Secale cereale L.); and a zero N plot as the control. Across the 3‐yr study period, split‐N + CC significantly reduced flow‐weighted NO3–N concentration and NO3–N loss by 35 and 37%, respectively, compared with preplant‐N. However, flow‐weighted NO3–N concentration (4.3 mg L–1) and NO3–N loss (22.4 kg ha–1) with split‐N were not significantly different from either preplant‐N (4.8 mg L–1 and 26.4 kg ha–1, respectively) or split‐N + CC (3.1 mg L–1 and 16.7 kg ha–1, respectively). Corn yield was significantly lower in the control treatment but did not differ among N fertilized treatments in any year. These results indicate that combining split‐N application with cover crops holds promise for meeting the statewide interim milestone NO3–N reduction target of 15% by 2025 without negatively impacting crop productivity.
Robust sequential biophysical fractionation of blood plasma to study variations in the biomolecular landscape of systemically circulating extracellular vesicles across clinical conditions
Authors: Vergauwen Glenn , Tulkens Joeri , Pinheiro Cláudio , Avila Cobos Francisco , Dedeyne Sándor , De Scheerder Marie‐Angélique , Vandekerckhove Linos , Impens Francis , Miinalainen Ilkka , Braems Geert , Gevaert Kris , Mestdagh Pieter , Vandesompele Jo , Denys Hannelore , De Wever Olivier , Hendrix An
Published: August 2021

Separating extracellular vesicles (EV) from blood plasma is challenging and complicates their biological understanding and biomarker development. In this study, we fractionate blood plasma by combining size‐exclusion chromatography (SEC) and OptiPrep density gradient centrifugation to study clinical context‐dependent and time‐dependent variations in the biomolecular landscape of systemically circulating EV. Using pooled blood plasma samples from breast cancer patients, we first demonstrate the technical repeatability of blood plasma fractionation. Using serial blood plasma samples from HIV and ovarian cancer patients (n = 10) we next show that EV carry a clinical context‐dependent and/or time‐dependent protein and small RNA composition, including miRNA and tRNA. In addition, differential analysis of blood plasma fractions provides a catalogue of putative proteins not associated with systemically circulating EV. In conclusion, the implementation of blood plasma fractionation allows to advance the biological understanding and biomarker development of systemically circulating EV.
Itraconazole inhibits nuclear delivery of extracellular vesicle cargo by disrupting the entry of late endosomes into the nucleoplasmic reticulum
Authors: Santos Mark F. , Rappa Germana , Karbanová Jana , Fontana Simona , Bella Maria Antonietta Di , Pope Marshall R. , Parrino Barbara , Cascioferro Stella Maria , Vistoli Giulio , Diana Patrizia , Cirrincione Girolamo , Arena Goffredo O. , Woo Gyunghwi , Huang Kevin , Huynh Tony , Moschetti Marta , Alessandro Riccardo , Corbeil Denis , Lorico Aurelio
Published: August 2021

Extracellular vesicles (EVs) are mediators of intercellular communication under both healthy and pathological conditions, including the induction of pro‐metastatic traits, but it is not yet known how and where functional cargoes of EVs are delivered to their targets in host cell compartments. We have described that after endocytosis, EVs reach Rab7+ late endosomes and a fraction of these enter the nucleoplasmic reticulum and transport EV biomaterials to the host cell nucleoplasm. Their entry therein and docking to outer nuclear membrane occur through a tripartite complex formed by the proteins VAP‐A, ORP3 and Rab7 (VOR complex). Here, we report that the antifungal compound itraconazole (ICZ), but not its main metabolite hydroxy‐ICZ or ketoconazole, disrupts the binding of Rab7 to ORP3–VAP‐A complexes, leading to inhibition of EV‐mediated pro‐metastatic morphological changes including cell migration behaviour of colon cancer cells. With novel, smaller chemical drugs, inhibition of the VOR complex was maintained, although the ICZ moieties responsible for antifungal activity and interference with intracellular cholesterol distribution were removed. Knowing that cancer cells hijack their microenvironment and that EVs derived from them determine the pre‐metastatic niche, small‐sized inhibitors of nuclear transfer of EV cargo into host cells could find cancer therapeutic applications, particularly in combination with direct targeting of cancer cells.
Preclinical efficacy and clinical safety of clinical‐grade nebulized allogenic adipose mesenchymal stromal cells‐derived extracellular vesicles
Authors: Shi Meng‐meng , Yang Qing‐yuan , Monsel Antoine , Yan Jia‐yang , Dai Cheng‐xiang , Zhao Jing‐ya , Shi Guo‐chao , Zhou Min , Zhu Xue‐mei , Li Su‐ke , Li Ping , Wang Jing , Li Meng , Lei Ji‐gang , Xu Dong , Zhu Ying‐gang , Qu Jie‐ming
Published: August 2021

Mesenchymal stromal cell‐derived extracellular vesicles (MSC‐EVs) turn out to be a promising source of cell‐free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose‐derived MSC‐EVs (haMSC‐EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC‐EVs in healthy volunteers. DiR‐labelled haMSC‐EVs were used to explore the distribution of nebulized haMSC‐EVs in the murine model. Pseudomonas aeruginosa‐induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL‐6, TNF‐α and IL‐10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC‐EVs through the nebulized route. Twenty‐four healthy volunteers were involved and received the haMSC‐EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC‐EVs improved survival rate to 80% at 96 h in P. aeruginosa‐induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC‐EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC‐EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC‐EVs in lung injury diseases.