bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal neuronal damage and inflammation in the hippocampus of kainic acid‐induced epilepsy mice
Authors: Li Xiaoying , Yang Ciqing , Shi Yaping , Guan Lihong , Li Han , Li Shuanqing , Li Yunxiao , Zhang Yong , Lin Juntang
Published: May 2021

In this study, we established a mouse model of epilepsy and analysed abnormal neuronal damage and inflammation in the hippocampus of mice with kainic acid (KA)‐induced epilepsy to provide the basis for the pathogenesis of epilepsy. C57 mice, aged 4 weeks, were injected intraperitoneally in the KA group with 20 mg/kg of KA and in the sham experimental group with normal saline. The whole brain and hippocampus of mice in the sham experimental group and KA epilepsy model group were collected on days 7, 14, 21 and 28 after injection. The difference in the protein expression in the hippocampus was detected using fluorescence immunohistochemistry. The hippocampal tissue was also collected and frozen to detect protein expression by western blot. The results of the haematoxylin and eosin (HE) and Nissl staining showed that the mouse model of temporal lobe epilepsy could be established by intraperitoneal injection of KA, and the success rate of the model was 53.8%. The expression of DCX‐, β‐catenin‐, GFAP‐ and Iba‐1‐labelled glial cells in the KA‐induced epilepsy model group were higher than those in the sham group. The results of western blotting showed that the expression of DCX and β‐catenin in the KA‐induced epilepsy model group was higher than that in the sham experimental group, while the expression of N‐cadherin and Iba‐1 on days 14 and 28 was significantly (P < .05) higher than that in the sham experimental group. In KA‐induced epilepsy model group, the expression of Bcl‐2 was decreased, while the expression of Bad and PUMA was increased.
Impact of a micro‐net mesh technology covering stent on coronary microvascular dysfunction in patients with high thrombus burden
Authors: Noirclerc Nathalie , Marliere Stephanie , Bakhti Akader , Mangin Lionel , Cassar Emmanuel , Vautrin Estelle , Piliero Nicolas , Ormezzano Olivier , Bouvaist Helene , Riou Laurent , Vanzetto Gerald , Belle Loic , Barone‐Rochette Gilles
Published: May 2021

Background

Highly thrombotic coronary lesions continue to be a serious and clinically significant problem that is not effectively and completely addressed by current technology.

Objectives

We aimed to investigate whether a micro‐net mesh (MNM) technology covering stent could preserve the index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) in patients with high thrombus burden.

Methods and Results

Fifty‐two patients with non‐ST elevation myocardial infarction or ST Elevation Myocardial Infarction and high thrombus burden (TIMI thrombus grade ≥ 3) were randomized into two groups, PCI with a MNM covering stent (MNM group, n = 25) and PCI with any commercially available stent (DES group, n = 27). As the primary endpoint, IMR was measured immediately after PCI using a pressure–temperature sensor‐tipped coronary wire. The secondary endpoint was left ventricular ejection fraction (LVEF) at 6 months of follow‐up. The IMR in the MNM group was significantly lower in comparison to the DES group (33.2 [21.3, 48.9] vs. 57.2 [39.9, 98.0], p = 0.005). No significant differences were observed in baseline LVEF (54.5 ± 10.2% vs. 53.1 ± 6.87%, p = .57), while LVEF was significantly improved at follow‐up in the MNM group (61.1 ± 7.1% vs. 53.9 ± 6.35%, p = .0001).

Conclusion

MNM technology significantly improved coronary microvascular dysfunction after PCI in patient with acute coronary syndrome and appears as a useful technological option for thrombus management.
Suitability of the current breadmaking quality test to predict the breadmaking potential of healthy bread formulations
Authors: Hernández‐Espinosa Nayelli , Guzmán Carlos , Morales‐Dorantes Anayeli Sarai , Crespo‐Herrera Leonardo , Mondal Suchismita , Singh Ravi , Ibba Maria Itria
Published: May 2021

Background and objectives

Selection for high breadmaking quality is mostly conducted using tests employing refined flour and added salt which may not be adequate for selecting lines with high wholemeal or low‐sodium breadmaking potential. The objective of this study was thus to evaluate the suitability of the current breadmaking quality tests for the selection of wheat lines intended for high‐quality healthier breads.

Findings

A set of common wheat lines was analyzed for its breadmaking quality using three bread formulations: refined flour and 1% salt (RF); refined flour and no added salt (RNa); and reconstituted flour and 1% salt (WM). The RNa bread quality was accurately predicted using the RF formulation (r > 0.90) and was highly correlated with protein content and dough properties. Differently, the WM breadmaking quality was less predictable using the RF formulation (r = 0.64) and was highly correlated with grain hardness and dough properties but less with protein content.

Conclusions

The current methods used for evaluating wheat breadmaking quality are effective to predict low‐sodium bread quality but not wholemeal bread quality.

Significance and novelty

Results of this study highlighted the need of using wholemeal rather than refined flour for the selection of wheat lines with high wholemeal breadmaking potential and suggested that traits such as grain hardness and SDS‐sedimentation volume could be useful to predict high wholemeal breadmaking quality.
Analysis of Updated Literature Data up to 2019 on the Oxidative Coupling of Methane Using an Extrapolative Machine‐Learning Method to Identify Novel Catalysts
Authors: Mine Shinya , Takao Motoshi , Yamaguchi Taichi , Toyao Takashi , Maeno Zen , Hakim Siddiki S. M. A. , Takakusagi Satoru , Shimizu Ken‐ichi , Takigawa Ichigaku
Published: May 2021

We have constructed and analyzed an updated dataset consisting of 4759 experimental datapoints for the oxidative coupling of methane (OCM) reaction based on literature data reported before 2020 (∼2019) using machine learning (ML) methods. Several ML methods, including random forest regression (RFR), extra trees regression (ETR), and gradient boosting regression with XGBoost (XGB), were used in conjunction with our proposed approach, in which elemental features are used as input representations rather than inputting the catalyst compositions directly. A recent research trend, namely, the extensive exploration of Mn/Na2WO4/SiO2 catalyst systems in recent years due to their high activity and durability, was clearly reflected in the dataset analysis. An ML model for the prediction of the reaction outcome (C2 yield) was successfully developed, and feature importance scores and SHapley Additive exPlanations (SHAP) values were calculated based on ETR and XGB, respectively, to identify the input variables with the greatest influence on the catalyst performance and observe how these important variables affect the C2 yield in the OCM. The discovery and optimization of catalytic processes using ML as a “surrogate” model were explored, and promising catalytic system candidates for the OCM reaction were identified. Notably, the developed ML model predicted catalysts containing elements that do not appear in the OCM dataset. This clearly demonstrates desirably high potential of our ML model to enable extrapolative predictions for ML‐aided future catalysis research.
Hydrogenation of a Benzene‐Toluene Mixture Using Metal Nanoparticles Stabilized by a Hyper‐Crosslinked Aromatic Polymer
Authors: Bykov Alexey V. , Demidenko Galina N. , Nikoshvili Linda Zh. , Sulman Mikhail G. , Kiwi-Minsker Lioubov
Published: May 2021

Hydrogenation of aromatic compounds is a widely used catalytic process in modern industry. Selective hydrogenation of benzene (BZ)‐toluene (TL) mixtures is an important industrial process as it allows the purification of BZ for further synthetic purposes. In this work, the hydrogenation of a BZ‐TL mixture (at a molar ratio close to 1) was studied for varying reaction parameters (temperature in the range of 100–180 °C and pressure in the range of 1–7 MPa) using Pt‐, Pd‐, and Ru‐containing nanoparticles stabilized by an amino‐functionalized hyper‐crosslinked aromatic polymer (HAP). Among the synthesized catalytic systems, Ru/HAP containing ruthenium(IV) oxide was shown to be the most active and selective one, allowing 44 % selectivity with respect to cyclohexane at nearly 100 % of BZ conversion.
Non‐Parallel Photo‐Assisted Electrocatalysis Mechanism of SnS2/NiO Heterojunction for Efficient Electrocatalytic Oxygen Evolution Reaction
Authors: Gao Yidan , Bai Ling , Zhang Xin , Yang Fengchun
Published: May 2021

Developing high activity electrocatalysts for OER with low cost materials has remained a great challenge in electrochemical water splitting. As a clean and renewable energy source, light energy is becoming increasingly important as a driving force to improve the performance of catalyst. Herein, we investigate the electrocatalytic activity of SnS2/NiO heterojunction under visible light irradiation. The p‐n junction structure promotes the production of more high‐valence Ni (Ni3+) on NiO after illumination as the active site of OER. SnS2/NiO shows superior electrocatalytic activity, small overpotential of 310 mV for OER to afford a current density of 10 mA cm−2 and a significant current density. Moreover, a photo‐assisted non‐parallel catalytic mechanism is proposed according to the mode of action of light. At low potentials, light is the dominant player to reduce the initial potential of the OER reaction, and at high potentials, the applied potential acts as the dominant player to further increase OER performance. This work provides an efficient strategy to manipulate the electronic environment, optical energy and energy band of semiconductors for improved electrocatalytic OER activity.
Surface Diffusion of Underpotential‐Deposited Lead Adatoms on Gold Nanoelectrodes
Authors: Zhang Baodan , Wang Wei , Liu Cheng , Han Lianhuan , Peng Juan , Oleinick Alexander , Svir Irina , Amatore Christian , Tian Zhong‐Qun , Zhan Dongping
Published: May 2021

A simple and readily applicable voltammetric approach is described to characterize and measure the site‐hopping surface diffusion of underpotential‐deposited (UPD) metal adatoms at nanoelectrodes. UPD refers to the deposition of atoms on foreign metal supports at potentials lower than those predicted by Nernst law for a bulk deposition. Despite its importance in several fields of catalysis, advanced nanofabrication or even atomic nanoengineering by atomic layer epitaxy, diffusion of UPD adatoms is difficult to observe at micro‐ and macroelectrodes. In fact, at electrodes of usual dimensions, UPD adatoms surface diffusion is masked by other electrochemical phenomena of greater relative amplitudes. Conversely, at nanowires electrodes sealed in glass, only an extremely small fraction of the surface of the wires is exposed to the electrolyte solution and is rapidly loaded. This allows the spillage of UPD adatoms onto the much larger area of the nanowire rod which is immune to Faradaic reactions due to its isolation from the electrochemical solution by the glass casing. Therefore, surprisingly for a UPD process, voltammetric peaks currents and integral desorption charges primarily reflect these diffusional surface processes so that the integral charges vary linearly with the inverse of the square root of the scan rate. This is easily observable and measurable with usual bench‐level electrochemical instrumentation. In this work, by using nanoelectrodes with diameters between 90 and 260 nm, we were able to establish the major involvement of this site‐hopping surface diffusion of UPD Pb adatoms on polycrystalline gold (Au) and characterize it quantitatively. The equivalent surface diffusion coefficient of UPD Pb adatoms was determined to be ∼4.4×10−11 cm2 s−1 at room temperature, corresponding to a Gibbs free energy activation barrier of ca. 18.72 kJ mol−1 (i. e., 0.19 eV per Pb adatom) for the reaction of inter‐sites exchange of Pb adatoms on a polycrystalline Au surface.
Spatiotemporal Resolved Live Cell Membrane Tracking through Photo‐click Reactions Enriched in Lipid Phase
Authors: Wu Xueting , Deng Jiajie , Guo Guiling , Zheng Yuanqin , Xiong Qin , Zheng Tingting , Zhao Xiaohu , Yu Zhipeng
Published: May 2021

A set of photo‐switchable monopeptides derived from cis‐β‐dibenzodiazocine‐l‐alanine (cis‐DBDAA) have been designed and synthesized, which are capable of photo‐click reacting with diaryltetrazoles or diarylsydnones in a hydrophobic phospholipid bilayer environment. The DBDAA monopeptides include both a hydrophobic tail on C‐terminal, providing high affinity toward lipid membrane, and a modularized functional moiety on N‐terminal, enabling rapid optimization of the self‐assembly strength to form multifunctional supramolecules. With the cis‐DBDAA monopeptides photo‐switched into trans‐configuration, we were able to disrupt the supramolecular assembly through an efficient photo‐click reaction across the lipid bilayer of liposomes. We reveal that the performance of the photo‐click reactions between the monopeptides and photo‐generated nitrile imine intermediates is significantly enhanced by enrichment of both reactants in the hydrophobic membrane lamel of liposomes. Enrichment of the DBDAA monopeptide in lipid phase serves as a convenient method to introduce bioorthogonal chemical handles on live cell membranes, which enables fluorescence labelling of single cell's membrane with high spatiotemporal resolution to facilitate the studies on cell membrane dynamics.
Super Na+ Half/Full Batteries and Ultrafast Na+ Diffusion Kinetics of Cobalt‐Nickel Selenide from Assembling Co0.5Ni0.5Se2@NC Nanosheets into Cross‐Stacked Architecture
Authors: Li Zhiyong , Peng Zilin , Sun Rui , Qin Zhaoxia , Liu Xinlong , Wang Caihong , Fan Haosen , Lu Shengjun
Published: May 2021

Main observation and conclusion

Exploration of advanced anode materials for sodium‐ion batteries (SIBs) is still a big challenge due to the large radius of sodium. In this work, the hierarchical architectures assembled from N‐doped carbon‐coated Co0.5Ni0.5Se2 (Co0.5Ni0.5Se2@NC) nanoparticles encapsulated into cross‐stacked nanosheets have been successfully prepared from the cobalt‐nickel binary‐metal organic frameworks (CoNi‐MOF) by two steps of the solid‐state selenization and carbon coating processes. Importantly, the resultant hierarchical Co0.5Ni0.5Se2@NC architecture can achieve a satisfactory electrochemical performance, maintaining a high‐rate capacity of 330 mA·h·g–1 at 3 A·g–1 and a stable cyclability of 100 cycles without obvious capacity decay at 0.2 A·g–1. The design of distinct superstructure can not only be applied to other electrode materials but also boost the forward development of energy storage systems.
QoS for best‐effort batch jobs in container‐based cloud
Authors: Yim Yin‐Goo , Jang Hyeon‐Jun , Jin Hyun‐Wook
Published: May 2021

The resource orchestrators in the cloud provide different QoS classes. Existing studies have mainly focused on resource guarantee for high‐priority class jobs, but yet to consider delicate QoS control of low‐priority jobs in the cloud. In this paper, we propose the differentiated shares that provide weighted CPU scheduling for low‐priority batch jobs in container‐based cloud. To implement the differentiated shares, we extend resource reservation interfaces provided by Kubernetes and suggest an algorithm that maps the resource management attributes of Kubernetes into those of Linux. The proposed differentiated shares can avoid worsening interference with high‐priority containers by exploiting the hierarchical resource sharing of task groups in Linux. In addition, we suggest a node scoring policy to provide efficient inter‐node job scheduling with the consideration of the differentiated shares. The performance measurement results show that the differentiated shares can provide weighted CPU scheduling for best‐effort batch containers without interference with high‐priority containers (less than 3% with respect to application‐level performance).
The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes
Authors: Cherkaoui Sanae , Pinnow Ellen , Bulatao Ilynn , Day Brendan , Kalaria Manish , Brajovic Sonja , Dal Pan Gerald
Published: May 2021

We characterized the size of the premarket safety population for 278 small‐molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.04), orphan products than nonorphan products (393 vs. 1,606, P < 0.001), and for products with fast‐track designation (617 vs. 1,455, P < 0.001), priority review (630 vs. 1,735, P < 0.001), and accelerated approval (475 vs. 1,164, P < 0.001), than products without that designation. The median number of postmarket safety label updates and issues added to the label were higher with larger premarket exposure among nonorphan products, but not among orphan products. Products with accelerated approval using a surrogate end point had a higher median number of safety issues added to the label than those with full approval, but this did not vary with the size of the safety population; fast‐track and priority review were not associated with the number of safety issues added to the label. A smaller safety population size was associated with a longer time to first safety outcome for nonorphan products but not orphan products. For orphan and nonorphan products combined, smaller premarket safety population size is not associated with the number or timing of postmarket safety outcomes, regardless of expedited program participation.
Effects of extended pharmacological disruption of zebrafish embryonic heart biomechanical environment on cardiac function, morphology, and gene expression
Authors: Foo Yoke Yin , Motakis Efthymios , Tiang Zenia , Shen Shuhao , Lai Jason Kuan Han , Chan Wei Xuan , Wiputra Hadi , Chen Nanguang , Chen Ching Kit , Winkler Christoph , Foo Roger Sik Yin , Yap Choon Hwai
Published: May 2021

Background

Biomechanical stimuli are known to be important to cardiac development, but the mechanisms are not fully understood. Here, we pharmacologically disrupted the biomechanical environment of wild‐type zebrafish embryonic hearts for an extended duration and investigated the consequent effects on cardiac function, morphological development, and gene expression.

Results

Myocardial contractility was significantly diminished or abolished in zebrafish embryonic hearts treated for 72 hours from 2 dpf with 2,3‐butanedione monoxime (BDM). Image‐based flow simulations showed that flow wall shear stresses were abolished or significantly reduced with high oscillatory shear indices. At 5 dpf, after removal of BDM, treated embryonic hearts were maldeveloped, having disrupted cardiac looping, smaller ventricles, and poor cardiac function (lower ejected flow, bulboventricular regurgitation, lower contractility, and slower heart rate). RNA sequencing of cardiomyocytes of treated hearts revealed 922 significantly up‐regulated genes and 1,698 significantly down‐regulated genes. RNA analysis and subsequent qPCR and histology validation suggested that biomechanical disruption led to an up‐regulation of inflammatory and apoptotic genes and down‐regulation of ECM remodeling and ECM–receptor interaction genes. Biomechanics disruption also prevented the formation of ventricular trabeculation along with notch1 and erbb4a down‐regulation.

Conclusions

Extended disruption of biomechanical stimuli caused maldevelopment, and potential genes responsible for this are identified.
Construction of a Highly Selective and Sensitive Dopamine Enzyme‐free Biosensor Based on Carbon Nanomaterials
Authors: Liu Chong , Xie Yuchen , Hou Yingjiao , Wang Ziyi , Pan Xiaoyu , Zhu Hong , Li Hongna
Published: May 2021

A selective and sensitive electrochemical enzyme‐free sensor for dopamine (DA) was prepared, containing carbon nanomaterials, gold nanoparticles (GNPs) and room‐temperature ionic liquid of 1‐butyl‐3‐methylimidazolium tetrafluor (BmimBF4). The peaks of DA, ascorbic acid (AA) and uric acid (UA) can be well separated by optimization of pH condition and carbon nanomaterials.Multi‐walled carbon nanotubes (MWCNTs), single‐walled carbon nanotubes (SWCNTs), single‐walled carbon nanohorns (SWCNHs), carboxylated graphene (C‐GR), were chosen to compare the affection to DA detection. The catalytic effect was SWCNTs>MWCNTs>C‐GR≈SWCNHs. It showed carbon nanotube materials with electron acceleration channels play the key role in catalytic performance. The pH condition also influenced detection, all the redox peak potentials of DA, UA, and AA had a negative shift as the pH changed from low to high, but the amplitude of the shift was different. At pH 1, the three anodic peaks are separated ca.0.24 V and 0.20 V. Under optimum conditions linear calibration graphs were obtained over the DA concentration range 0.2 to 20 μM.The modified electrode was applied for the assay of spiked DA in blood serum and human urine.This work studied the influence of carbon nanomaterials on DA detection and provided a simple approach to selectively detect dopamine in the presence of AA and UA.
Study on the pressure relief effect in gob‐side coal body during mining an inclined longwall panel
Authors: Zhou Ruoqian , Wang Hongtu , Shu Cai , Chu Tao
Published: May 2021

This study combined multi‐field coupled numerical calculations and field measurements to analyze the gas pressure relief and the outburst elimination range of the coal body in the lower side of a gob induced by excavating an inclined seam. A coal seam gas flow solid‐gas coupled model allowing for elastoplastic damage was established based on an inclined longwall panel of the Hongyan Coal Mine in Chongqing, China. To inspect the gas depressurization effect, this study simulated the collapse and damage of strata surrounding the longwall panel after mining by using a constitutive model of the interlayer weak plane, the changes in the damage, gas pressure, and stress concentration in the gob‐side coal seam were analyzed numerically. Besides, variation in gas pressure within 10‐23 m away from the panel margin was measured on‐site during the advancement of the longwall face to validate and modify the results of modeling. The simulation results showed that the advancing of the panel is highly effective in releasing gas from the gob‐side coal body. The rupture penetration, stress concentration, and original elastic zone will be formed in the gob‐side coal body with increasing distance away from the gob after mining the 3603‐2 panel. The permeability increased dramatically and the gas was almost exhausted in the rupture penetration zone. The field measurement results indicated that gas pressure decreased in three stages with advancement. After completion of excavation activities, the drop rates of gas pressure and gas content within 10‐23 m from the gob were 26.55%‐73.58% and 34%‐71%, respectively. Additionally, it was proved that the numerical simulation results were instructive for predicting the range of gas outburst‐proneness elimination belt by comparing simulation and field results, and the outburst elimination range of the inclined longwall panel of the Hongyan Coal Mine was determined to be 10 m.
We Are Not Immune: Racial and Ethnic Disparities in Autoimmune Liver Diseases
Authors: Lee Brian T. , Tana Michele M. , Kahn Jeffrey A. , Dara Lily
Published: May 2021

Autoimmune liver diseases are attributed to a complex interplay of biologic, acquired, and environmental factors. Increased prevalence, later stage at presentation, worse response to standard therapy, and transplant‐related disparities have all been reported in racial and ethnic minorities such as Black and Latinx patients with autoimmune liver diseases. While biology and inherited genetic predispositions may partly explain these disparities, definitive and universal genetic variations underlying these differences in outcomes have not been defined. Nonetheless, socioeconomic status, access to health care, environmental and societal factors, and implicit provider bias can all contribute to poor patient outcomes. There remains an unmet need to understand and mitigate the factors contributing to health inequity in autoimmune liver diseases. In this review, we summarize the data on racial and ethnic disparities in presentation, treatment response, and outcomes pertaining to autoimmune liver diseases in minority populations, on the premise that understanding disparities is the first step toward reaching health equity.
Nanoscale energy transport of inclined magnetized 3D hybrid nanofluid with Lobatto IIIA scheme
Authors: Ayub Assad , Darvesh Adil , Altamirano Gilder C. , Sabir Zulqurnain
Published: May 2021

Key developments in the field of nanotechnology have drawn the attention of many scholars toward the interaction of nanoparticles due to their capturing applications in solar energy systems and thermal engineering. Larger consumption of energy posed a challenge for thermal science, so thermal engineering is trying to solve this issue by increasing the thermal conductivity of the fluid. The thermal conductivity of conventional fluid is increased by incorporating the nanoparticles in the base fluid. Keeping this in mind, the present research project addresses the utilization of nanoparticles in a steady three‐dimensional rotating flow of magnetohydrodynamic water‐based hybrid fluid over an extending sheet. Nanoparticles of aluminum oxide (Al2O3) and silver (Ag) are being used with water (H2O) as base fluid. The velocity of nanoparticles is being captured under the influence of an inclined magnetic field and the transport of heat is scrutinized through thermal radiation. The physical model generates partial differential equations and then transported into an equivalent set of a nonlinear ordinary differential equations. The purpose of numerical computation is made by the Lobatto IIIA method, which is a type of Matlab scheme bvp4c and based on the finite difference method. Geometry of velocity profile is explained with different parameters in presence and absence of magnetic field and energy of hybrid nanofluid is explained under the influence of the inclined and perpendicular magnetic field. Gradual increment inϑbothfandgprofiles because strengthen the magnetic field results lower velocity. An increment in nanoparticle concentration of Al2O3andAggives a larger magnitude of velocity. The rotation parameter shows the rotation of nanoparticles; due to these rotations both linear and angular components of velocity increase in the presence and absence of a magnetic effect.
TMEM88 exhibits an antiproliferative and anti‐invasive effect in bladder cancer by downregulating Wnt/β‐catenin signaling
Authors: Zhao Xu , Li Gang , Chong Tie , Xue Li , Luo Qidong , Tang Xiaoshuang , Zhai Xiaoqiang , Chen Juan , Zhang Xin
Published: May 2021

Transmembrane protein 88 (TMEM88) acts as a novel tumor‐associated protein. The dysregulation of TMEM88 has been observed in several tumor types. However, the relevance of TMEM88 in tumorigenesis is still contradictory. This study assessed the relevance of TMEM88 in bladder cancer. TMEM88 levels were found to be significantly lower in bladder cancer tissue. Upregulation of TMEM88 resulted in a dramatic decrease in the cellular proliferative and invasive abilities of bladder cancer. Upregulation of TMEM88 decreased the level of active β‐catenin and prohibited the activation of the Wnt/β‐catenin pathway, an effect that was associated with downregulation of glycogen synthase kinase‐3β (GSK‐3β) phosphorylation. Suppression of GSK‐3β or overexpression of β‐catenin reversed the TMEM88‐induced tumor‐inhibiting effects in bladder cancer. Overexpression of TMEM88 prohibited the tumor formation and growth of bladder cancer cells in nude mice. In conclusion, this study demonstrates that TMEM88 exerts an antitumor function in bladder cancer through downregulation of Wnt/β‐catenin signaling.
Mesenchymal stem cells support delivery and boost the efficacy of oncolytic reoviruses in TC‐1 tumor cells
Authors: Banijamali Razieh S. , Soleimanjahi Hoorieh , Soudi Sara , Karimi Hesam
Published: May 2021

Cancer has remained a major health problem around the world. Mesenchymal stem cells (MSCs)‐based therapy exhibits a therapeutic effect via different mechanisms. By using MSCs as carrier cells, the major problem of clearance of oncolytic viruses is resolved by neutralizing antibodies before they react with cancer cells. The aim of this study was to characterize the effect of infected MSCs by reovirus type‐3 Dearing (T3D) for in vitro cancer therapy. Adipose‐derived MSCs (AD‐MSCs) were infected with reovirus T3D and its biological properties were evaluated. Then, the effects of reovirus‐infected AD‐MSCs on cytokine profile, nitric oxide (NO) production, and apoptosis induction in TC‐1 cells were assessed. Our results indicated that the differentiation potential of AD‐MSCs was affected by reovirus. However, phenotypes were not affected after infection. Then, the effects of reovirus‐infected AD‐MSCs in TC‐1 cells showed an increased amount of tumor necrosis factor‐alpha (TNF‐α) and NO production and a decreased amount of transforming growth factor‐beta 1 (TGF‐β1) and interleukin‐10 (IL‐10). Moreover, apoptosis significantly increased via coculturing of TC‐1 cells with infected AD‐MSCs, compared with control, and both internal and external apoptosis pathways are activated in experimental groups. In conclusion, the data showed that with increasing TNF‐α and NO production and reducing IL‐10 and TGF‐β production, AD‐MSCs can enhance the oncolytic effect of reovirus in cancer cells. Furthermore, the results suggested that AD‐MSCs can be used as effective carrier cells candidate for reovirus T3D to maximize their anticancer cell activity.
Drug discovery for X‐linked adrenoleukodystrophy: An unbiased screen for compounds that lower very long‐chain fatty acids
Authors: Moser Ann B. , Liu Yanqiu , Shi Xiaohai , Schrifl Ulrike , Hiebler Shandi , Fatemi Ali , Braverman Nancy E. , Steinberg Steven J. , Watkins Paul A.
Published: May 2021

X‐linked adrenoleukodystrophy (XALD) is a genetic neurologic disorder with multiple phenotypic presentations and limited therapeutic options. The childhood cerebral phenotype (CCALD), a fatal demyelinating disorder affecting about 35% of patients, and the adult‐onset adrenomyeloneuropathy (AMN), a peripheral neuropathy affecting 40%–45% of patients, are both caused by mutations in the ABCD1 gene. Both phenotypes are characterized biochemically by elevated tissue and plasma levels of saturated very long‐chain fatty acids (VLCFA), and an increase in plasma cerotic acid (C26:0), along with the clinical presentation, is diagnostic. Administration of oils containing monounsaturated fatty acids, for example, Lorenzo's oil, lowers patient VLCFA levels and reduced the frequency of development of CCALD in presymptomatic boys. However, this therapy is not currently available. Hematopoietic stem cell transplant and gene therapy remain viable therapies for boys with early progressive cerebral disease. We asked whether any existing approved drugs can lower VLCFA and thus open new therapeutic possibilities for XALD. Using SV40‐transformed and telomerase‐immortalized skin fibroblasts from an XALD patient, we conducted an unbiased screen of a library of approved drugs and natural products for their ability to decrease VLCFA, using measurement of C26:0 in lysophosphatidyl choline (C26‐LPC) by tandem mass spectrometry as the readout. While several candidate drugs were initially identified, further testing in primary fibroblast cell lines from multiple CCALD and AMN patients narrowed the list to one drug, the anti‐hypertensive drug irbesartan. In addition to lowering C26‐LPC, levels of C26:0 and C28:0 in total fibroblast lipids were reduced. The effect of irbesartan was dose dependent between 2 and 10 μM. When male XALD mice received orally administered irbesartan at a dose of 10 mg/kg/day, there was no reduction in plasma C26‐LPC. However, irbesartan failed to lower mouse fibroblast C26‐LPC consistently. The results of these studies indicate a potential therapeutic benefit of irbesartan in XALD that should be validated by further study.
Development of a cell‐free protein synthesis protocol to rapidly screenL‐asparaginaseproteoforms by enzymatic activity
Authors: Lima Guilherme M , Menezes Milene C , Costa Iris M , Serrano Solange MT , Monteiro Gisele
Published: May 2021

BACKGROUND

Cell‐free protein synthesis (CFPS) technology has emerged as a powerful tool for a variety of biotechnological applications, including the expression of different classes of biopharmaceutical products. L‐Asparaginase (E.C. Number: 3.5.1.1, L‐asparagine amidohydrolase) (L‐ASNase) is an important biopharmaceutical used to treat leukemia, but expression of multiple proteoforms in CFPS systems and rapid characterization using standard colorimetric methods has not yet been fully exploited. Herein, recombinant expression and characterization of an L‐ASNase fromErwinia chrysanthemi(Erwinase) using a new CFPS protocol is reported.

RESULTS

Expression and quantification of the enzymatic activity of a soluble his‐tagged L‐ASNase directly from a CFPS reaction was successfully achieved. Purification of the protein was not required in order to assess its biological activity. Activity of L‐ASNase was significantly higher than the control reaction (7.07 ± 0.68 U mL–1vs. 1.83 ± 0.14 U mL–1, respectively). Expression of a mutant Erwinase proteoform – V293M – was also achieved and it presented a similar enzymatic activity. No significant loss in L‐ASNase enzymatic activity was noticed after removal of cyclic AMP, spermidine, transfer RNA, T7 RNA polymerase and, especially, ammonium acetate (a common interference in ASNase enzymatic assays) from the CFPS reaction.

CONCLUSION

The protocol developed in this work will facilitate the screening of novel clinically‐relevant L‐ASNase proteoforms. © 2021 Society of Chemical Industry (SCI).
Uniform hypergraphs with many edge‐colorings avoiding a fixed rainbow expanded complete graph
Authors: Contiero Lucas de Oliveira , Hoppen Carlos , Lefmann Hanno , Odermann Knut
Published: May 2021

For fixed positive integers and , and a fixed ‐uniform hypergraph , we look for ‐vertex hypergraphs that admit the maximum number of ‐edge‐colorings with the property that there is no copy of for which all hyperedges are assigned different colors. We consider , the ‐uniform expanded complete graph, and we prove that the Turán hypergraph , the balanced ‐partite ‐uniform hypergraph on vertices, is the only extremal configuration for any and large .
Inflammasome regulation in driving COVID-19 severity in humans and immune tolerance in bats
Authors: Nagaraja Sahana , Jain Disha , Kesavardhana Sannula
Published: May 2021

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host–virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.
The Swiss Alpine zero degree line: Methods, past evolution and sensitivities
Authors: Scherrer Simon C. , Gubler Stefanie , Wehrli Kathrin , Fischer Andreas M. , Kotlarski Sven
Published: May 2021

The near‐surface zero degree line (ZDL) is a key isotherm in mountain regions worldwide, but a detailed analysis of methods for the ZDL determination, their properties and applicability in a changing climate is missing. We here test different approaches to determine the near‐surface ZDL on a monthly scale in the Swiss Alps. A non‐linear profile yields more robust and more realistic ZDLs than a linear profile throughout the year and especially in the winter‐half year when frequent inversions disqualify a linear assumption. In the period 1871–2019, the Swiss ZDL has risen significantly in every calendar month: In northern Switzerland, the monthly ZDL increases generally amount to 300–400 m with smaller values in April and September (200–250 m) and a larger value in October (almost 500 m). The largest increases of 600–700 m but also very large uncertainties (±400 m, 95% confidence interval) are found in December and January. The increases have accelerated in the last decades, especially in spring and summer. The ZDL is currently increasing by about 160 m·°C−1 warming in the summer‐half year and by up to 340 ± 45 m·°C−1 warming in winter months. In southern Switzerland, ZDL trends and temperature scalings are somewhat smaller, especially in winter. Sensitivity analyses using a simple shift of the non‐linear temperature profile suggest that the winter ZDL‐temperature scalings are at a record high today or will reach it in the near future, and are expected to decrease with a strong future warming. Nevertheless, the cumulative ZDL increase for strong warming is considerably larger in winter than in summer. Based on a few key criteria, we also present best practises to determine the ZDL in mountain regions worldwide. The outlined methods lay a foundation for the analysis of further isotherms and to study the future ZDL evolution based on climate scenario data.
Timing, pace and controls on ice sheet retreat: an introduction to the BRITICE‐CHRONO transect reconstructions of the British–Irish Ice Sheet
Authors: Clark Chris D. , Chiverrell Richard C. , Fabel Derek , Hindmarsh Richard C. A. , Ó Cofaigh Colm , Scourse James D.
Published: May 2021

Motivated to help improve the robustness of predictions of sea level rise, the BRITICE‐CHRONO project advanced knowledge of the former British–Irish Ice Sheet, from 31 to 15 ka, so that it can be used as a data‐rich environment to improve ice sheet modelling. The project comprised over 40 palaeoglaciologists, covering expertise in terrestrial and marine geology and geomorphology, geochronometric dating and the modelling of ice sheets and oceans. A systematic and directed campaign, organised across eight transects from the continental shelf edge to a short distance (10s of kilometres) onshore, was used to collect 914 samples which yielded 639 new ages, tripling the number of dated sites constraining the timing and rates of change of the collapsing ice sheet. This special issue synthesises these findings of ice advancing to the maximum extent and its subsequent retreat for each of the eight transects to produce definitive palaeogeographic reconstructions of ice margin positions across the marine to terrestrial transition. These results are used to understand the controls that drove or modulated ice sheet retreat. A further paper reports on how ice sheet modelling experiments and empirical data can be used in combination, and another probes the glaciological meaning of ice‐rafted debris.
Survival of the thickest? Impacts of extreme wave‐forcing on marsh seedlings are mediated by species morphology
Authors: Schoutens Ken , Reents Svenja , Nolte Stefanie , Evans Ben , Paul Maike , Kudella Matthias , Bouma Tjeerd , Möller Iris , Temmerman Stijn
Published: May 2021

Although tidal marshes are known for their coastal defense function during storm surges, the impact of extreme wave forcing on tidal marsh development is poorly understood. Seedling survival in the first season after germination, which may involve exposure to extreme wave events, is crucial for the natural establishment and human restoration of marshes. We hypothesize that species‐specific plant traits plays a significant role in seedlings survival and response to wave induced stress, i.e., through stem bending and uprooting. To test this hypothesis, seedlings of pioneer species (Bolboschoenus maritimus, Schoenoplectus tabernaemontani, Spartina anglica, and Puccinellia maritima) with contrasting biophysical traits were placed in the Large Wave Flume in Hannover (Germany) and exposed to storm wave conditions. Seedlings of P. maritima and S. anglica experienced a lower loss rate and bending angle after wave exposure compared to S. tabernaemontani and especially B. maritimus. The higher loss rates of B. maritimus and S. tabernaemontani result from deeper scouring around the stem base. Scouring depth was larger around stems of greater diameter and higher resistance to bending. Here, B. maritimus and S. tabernaemontani have both thicker and stiffer stems than S. anglica and P. maritima. Our results show that especially seedlings with thicker stems suffer from erosion and scouring, and have the highest risk of being lost during extreme wave events. This implies that for successful seedling establishment and eventually the establishment of a mature tidal marsh vegetation, the species composition and their capacity to cope with storm wave disturbances is crucial.
Stoichiometric imbalances complicate prediction of phytoplankton biomass in U.S. lakes: Implications for nutrient criteria
Authors: Moon David L. , Scott J. Thad , Johnson Tom R.
Published: May 2021

Using National Lakes Assessment data, we evaluated the influence of total N (TN), total P (TP), and other variables on lake chlorophyll‐a concentrations. With simple linear regressions, high TN/TP samples biased predictions based on TN, and low TN/TP samples biased predictions based on TP. The bias problem was corrected, and correlation was improved, by splitting the dataset at the TN/TP ratio we estimated to be indicative of a balanced supply and developing separate regressions that predict chlorophyll‐a based on TP, TN, dissolved inorganic N (DIN), dissolved organic carbon (DOC), nonalgal light attenuation, depth, area, latitude, elevation, and conductivity. Both nutrients were excellent predictors, and nonalgal light attenuation was the next most influential predictor. The regression analysis suggested that a potential for P only limitation (high TN/TP, 17% of samples) or N only limitation (low TN/TP, 14% of samples) can be inferred at the extremes of the TN/TP range. However, 69% of samples had an intermediate TN/TP ratio where it is difficult to infer anything about potential nutrient limitations (biomass could be N limited, P limited, N and P co‐limited, or not limited by nutrients at all). Our results show that when developing phytoplankton response relationships using cross‐lake datasets that span a wide range of trophic states, it is important to consider whether and how biomass is influenced by confounding factors—such as differences in the relative supply of N and P—so that biomass is not underestimated or overestimated, and nutrient criteria are not under‐protective or over‐protective.
A Dual Physical Cross‐Linking Strategy to Construct Tough Hydrogels with High Strength, Excellent Fatigue Resistance, and Stretching‐Induced Strengthening Effect
Authors: Yang Qianyu , Gao Chen , Zhang Xuemei , Tsou Chihui , Zhao Xingyu , De Guzman Manuel Reyes , Pu Zejun , Li Xinyue , Lu Yue , Zeng Chunyan , Yuan Li , Xia Yiqing , Sheng Yuping , Fu Yiqing
Published: May 2021

Hydrogels with excellent stiffness, toughness, anti‐fatigue, and self‐recovery properties are regarded as promising water‐containing materials. In this work, a dual physically cross‐linked (DPC) sodium alginate (SA)/poly[acrylamide (AAm)‐acrylic acid (AAc)‐octadecyl methacrylate (OMA)]‐Fe3+ hydrogel is reported, which is constructed by hydrophobic association (HA) and ionic coordination (IC). The optimal DPC hydrogel demonstrates excellent mechanical performance: tensile modulus of 0.65 MPa, tensile strength of 3.31 MPa, elongation at break of 1547%, and toughness of 27.8 MJ m–3. SA/P(AAm‐AAc‐OMA)‐Fe3+ DPC hydrogels also exhibit prominent anti‐fatigue and self‐recovery performance (99.1–109.7% modulus recovery and 90.4–108.9% dissipated energy recovery after resting for 5 min without additional stimuli at ambient temperature) through the reconstruction of reversible physical cross‐linking. Some of the SA/P(AAm‐AAc‐OMA)‐Fe3+ DPC hydrogels even exhibit a stretching‐induced strengthening effect, which is similar to the performance of muscle—“the more training, the more strength.” Hence, the combination of HA and IC will provide an effective approach to design DPC hydrogels with desirable mechanical performances and a longer service life for wider applications of soft materials.
Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
Authors: Lertwilaiwittaya Pongtawat , Suktitipat Bhoom , Khongthon Phongphak , Pongsapich Warut , Limwongse Chanin , Pithukpakorn Manop
Published: May 2021

Background

Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra‐rare form of osteopetrosis.

Methods

The older brother and the younger sister presented with chronic mandibular osteomyelitis in their 20s. Since childhood, they had visual impairment, pathological fracture, and skeletal dysmorphism.

Quadruplet whole‐exome sequencing was performed and confirmed with Sanger sequencing. Novel mutation in TNFSF11 (RANKL) c.842T>G, p.Phe281Cys was identified in a homozygous state in both siblings.

Results

Surgical debridement, antibiotic, and hyperbaric oxygen therapy were used and discontinued over a 6‐month period with normalization of C‐reactive protein. Hematopoietic stem cell transplantation candidacy was excluded by molecular diagnosis.

Conclusion

We report a novel mutation in an ultra‐rare form of osteopetrosis. Our siblings manifested with a milder phenotype in comparison with nine cases previously published.