bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual role of the miR‐146 family in rhinovirus‐induced airway inflammation and allergic asthma exacerbation
Authors: Laanesoo Anet , Urgard Egon , Periyasamy Kapilraj , Laan Martti , Bochkov Yury A. , Aab Alar , Magilnick Nathaniel , Pooga Margus , Gern James E. , Johnston Sebastian L. , Coquet Jonathan M. , Boldin Mark P. , Wengel Jesper , Altraja Alan , Bochenek Grazyna , Jakiela Bogdan , Rebane Ana 
Published: May 2021

AbstractRhinovirus (RV) infections are associated with asthma exacerbations. MicroRNA‐146a and microRNA‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that suppress signaling through the nuclear factor kappa B (NF‐κB) pathway and inhibit pro‐inflammatory chemokine production in primary human bronchial epithelial cells (HBECs). In the current study, we aimed to explore whether miR‐146a/b could regulate cellular responses to RVs in HBECs and airways during RV‐induced asthma exacerbation. We demonstrated that expression of miR‐146a/b and pro‐inflammatory chemokines was increased in HBECs and mouse airways during RV infection. However, transfection with cell‐penetrating peptide (CPP)‐miR‐146a nanocomplexes before infection with RV significantly reduced the expression of the pro‐inflammatory chemokines CCL5, IL‐8 and CXCL1, increased interferon‐λ production, and attenuated infection with the green fluorescent protein (GFP)‐expressing RV‐A16 in HBECs. Concordantly, compared to wild‐type (wt) mice, Mir146a/b−/− mice exhibited more severe airway neutrophilia and increased T helper (Th)1 and Th17 cell infiltration in response to RV‐A1b infection and a stronger Th17 response with a less prominent Th2 response in house dust mite extract (HDM)‐induced allergic airway inflammation and RV‐induced exacerbation models. Interestingly, intranasal administration of CPP‐miR‐146a nanocomplexes reduced HDM‐induced allergic airway inflammation without a significant effect on the Th2/Th1/Th17 balance in wild‐type mice. In conclusion, the overexpression of miR‐146a has a strong anti‐inflammatory effect on RV infection in HBECs and a mouse model of allergic airway inflammation, while a lack of miR‐146a/b leads to attenuated type 2 cell responses in mouse models of allergic airway inflammation and RV‐induced exacerbation of allergic airway inflammation. Furthermore, our data indicate that the application of CPP‐miR‐146a nanocomplexes has therapeutic potential for targeting airway inflammation.
Aging affects cognition and hippocampal ultrastructure in male Wistar rats
Authors: Lomidze Nino , Zhvania Mzia G. , Tizabi Yousef , Japaridze Nadezhda , Pochkhidze Nino , Rzayev Fuad , Lordkipanidze Tamar 
Published: May 2021

AbstractIt is now well established that aging is associated with emotional and cognitive changes. Although the basis of such changes is not fully understood, ultrastructural alterations in key brain areas are likely contributing factors. Recently, we reported that aging‐related anxiety in male Wistar rats is associated with ultrastructural changes in the central nucleus of amygdala, an area that plays important role in emotional regulation. In this study, we evaluated the cognitive performance of adolescent, adult, and aged male Wistar rats in multi‐branch maze (MBM) as well as in Morris water maze (MWM). We also performed ultrastructural analysis of the CA1 region of the hippocampus, an area intimately involved in cognitive function. The behavioral data indicate significant impairments in few indices of cognitive functions in both tests in aged rats compared to the other two age groups. Concomitantly, a total number of presynaptic vesicles as well as vesicles in the resting pool were significantly lower, whereas postsynaptic mitochondrial area was significantly higher in aged rats compared to the other age groups. No significant differences in presynaptic terminal area or postsynaptic mitochondrial number were detected between the three age groups. These results indicate that selective ultrastructural changes in specific hippocampal region may accompany cognitive decline in aging rats.
Stereoelectronic Characterization and Catalytic Potential of a 1,3‐Bis(2,6‐terphenyl)‐Substituted N‐Heterocyclic Carbene
Authors: Twycross Daniel , Davey Christopher J. , Cole Marcus L. , McKay Alasdair I. 
Published: May 2021

AbstractThe preparation of a 1,3‐bis(2,6‐terphenyl)imidazol‐2‐ylidene, IDitop (Ditop=2,6‐bis(4‐tolyl)phenyl‐) is reported. Several late transition metal complexes as well as the selenium adduct of IDitop were prepared to study and compare the stereoelectronic properties of IDitop to other well‐known N‐heterocyclic carbenes (NHCs). A study of the steric character of IDitop taken from crystal structure data of the complexes and adducts reveals a high degree of flexibility. Preliminary application to challenging Suzuki coupling reactions was undertaken.
Direct C3 Carbamoylation of 2H‐Indazoles
Authors: Bhat Vighneshwar Shridhar , Lee Anna 
Published: May 2021

AbstractWe developed a novel method for direct C3 carbamoylation of 2H‐indazoles using oxamic acids as carbamoyl radical sources. In the presence of ammonium persulfate, carbamoyl radicals were generated from oxamic acids, then used for further reactions with 2H‐indazoles to afford the desired products. The reaction proceeds under metal‐ and catalyst‐free conditions. This simple process allows for the efficient synthesis of C3 carbamoylated 2H‐indazoles, which are important scaffolds in organic synthesis.
Mechanistic Study of Domino Processes Involving the Bidentate Lewis Acid Catalyzed Inverse Electron‐Demand Diels−Alder Reaction
Authors: Strauss Marcel A. , Kohrs Daniel , Ruhl Julia , Wegner Hermann A. 
Published: May 2021

AbstractThe detailed understanding of mechanisms is the basis to design new reactions. Herein, we studied the domino bidentate Lewis acid catalyzed inverse electron‐demand Diels−Alder (IEDDA) reaction developed in our laboratory computationally as well as by synthetic experiments, to characterize different pathways. A quinodimethane intermediate was identified as key structure, which is the basis for all subsequent transformations: Elimination to an aromatic naphthalene, rearrangement to a dihydroaminonaphthalene and a photo‐induced ring opening. These insights allow to optimize the reaction conditions, such as catalytic utilization of amine, as well as to advance new reactions in the future.
Oxonium Ylides Generated from 1,4‐Disubstituted α‐Diazo Glutaconimides: a Rich Source of Diverse Oxygen Heterocyclic Frameworks
Authors: Guranova Natalia , Dar'in Dmitry , Kantin Grigory , Krasavin Mikhail 
Published: May 2021

AbstractAn underexplored type of heterocyclic α‐diazocarbonyl compounds, α‐diazo glutaconimides was involved in the generation of oxonium ylide species by Rh(II) catalysis in the presence of tetrahydrofuran and 1,4‐dioxane. The formation of a spirocycle through a formal Stevens‐type O→C [1,2]‐shift within the oxonium ylide species in the case of THF was low‐yielding and was accompanied by the known formal O→O [1,4]‐shift to give fused bicyclic products. Reactions with 1,4‐dioxane proved noticeably higher‐yielding with respect to the target spirocycle. In this case, however, the observed by‐products resulted from hitherto not described alternative formal O→C [1,4]‐shift accompanied by the transposition of the double bond. The latter fate of the oxonium ylide species, although minor, is likely attributable to the unique nature of α‐diazo glutaconimides as precursors to Rh(II) carbenes and subsequently formed oxonium ylide.
System behavior prediction by artificial neural network algorithm of a methanol steam reformer for polymer electrolyte fuel cell stack use
Authors: Qi Yuanxin , Andersson Martin , Wang Lei , Wang Jingyu 
Published: May 2021

AbstractIn this paper, a novel membrane reactor (MR) for methanol steam reforming is modeled to produce fuel cell grade hydrogen, which can be used as the inlet fuel for a later developed 500‐W horizon polymer electrolyte fuel cell (PEFC) stack. The backpropagation (BP) neural network algorithm is employed to develop the mapping relation model between the MR's prime operational parameters and fuel cell output performance for future integration system design and control application. Simulation results showed that the MR model performs well for hydrogen production and the developed PEFC system presents good agreement with experimental results. Finally, the BP method captures an accurate mapping relation model between the MR inputs and PEFC output, for example, predicts the system's behavior well.
Are We in a De‐Globalization Process? The Evidence from Global Trade During 2007–2017
Authors: Li Xiaomeng , Shen Chen , Cai Hongbo , Chen Qinghua 
Published: May 2021

AbstractThrough the analysis of statistical data, some scholars believe that the globalization of trade is declining, and de‐globalization has become a trend, even since the financial crisis in 2008. However, the superficial decline of global trade volume cannot be taken as a corollary of the de‐globalization. It needs go deep into the structural analysis, and “globalization or de‐globalization” should be discussed by analyzing whether the global trade structure has changed. This paper finds that during 2007–2017, the global trade resistances are clearly classified, and trade resistance in the global community has increased significantly. Second, an expectation maximization (EM) algorithm is applied to divide global trade relations into two categories: intimate trade relations, whose barriers are mainly related to geographical distance; and unfriendly trade relations with high artificial barriers. Third, the trade purity indicator (TPI) is introduced to describe the trade environment of countries, and its evolution indicates after the financial crisis and for quite a long time, the structure of global trade has not changed much. And it shows some deterioration trend and structural adjustment after 2015, which indicates an opportunity for the emergence of de‐globalization in such an international environment full of uncertainty and challenges.
Clinical Course and Risk Factors for Infection in Severe Forms of Alcohol‐Associated Liver Disease
Authors: Otero Sanchez Lukas , Karakike Eleni , Njimi Hassane , Putignano Antonella , Degré Delphine , Hites Maya , Jacobs Frédérique , Moreno Christophe , Trepo Eric , Gustot Thierry 
Published: May 2021

Background and Aims
Infection is a major driver of mortality in patients with advanced alcohol‐associated liver disease (ALD). The epidemiology and clinical course of patients infected with life‐threatening forms of ALD, including severe alcohol‐associated hepatitis (sAH) and decompensated alcohol‐associated cirrhosis (DAC), and specific risk factors for infection remain mostly unknown.

Approach and Results
In this observational study, we assessed all infectious episodes occurring within a 90‐day period from diagnosis in all consecutive patients with biopsy‐proven sAH (modified Maddrey’s discriminant function ≥ 32, Model for End‐Stage Liver Disease [MELD] ≥ 18) and DAC (MELD ≥ 18) without alcohol‐associated hepatitis in our tertiary hospital between 2003 and 2016. A total of 207 patients were included: 139 with sAH and 68 with DAC. One hundred seventeen (84%) patients with sAH and 41 (60%) patients with DAC experienced at least one infection episode at 90 days (P < 0.001). In multivariable analysis, factors associated with the development of infection were the presence of sAH and baseline MELD score. Bacterial infections represented the most common infection in the two groups, and only the MELD score was independently associated with the occurrence of bacterial infection. In both groups, pneumonia was the most prevalent bacterial infection, and gram‐negative bacilli were the main pathogens. Invasive fungal infections (IFI) occurred in 20 (14.5%) patients with sAH and 3 (4.5%) with patients with DAC (P < 0.05). Multivariable regression showed that younger age, higher MELD, and corticosteroid therapy were independently associated with IFI. The 90‐day cumulative incidence of death in patients infected with sAH and patients infected with DAC was 46% and 41.5%, respectively (P = 0.43).

Conclusions
Patients with sAH are more susceptible to develop infection than those with DAC. In life‐threatening forms of ALD, patients who were infected share a similar mortality rate. Corticosteroid treatment, not sAH, seems to be the main risk factor triggering IFI.
Nitrergic modulation of neuronal excitability in the mouse hippocampus is mediated via regulation of Kv2 and voltage‐gated sodium channels
Authors: Scheiblich Hannah , Steinert Joern R. 
Published: May 2021

AbstractRegulation of neuronal activity is a necessity for communication and information transmission. Many regulatory processes which have been studied provide a complex picture of how neurons can respond to permanently changing functional requirements. One such activity‐dependent mechanism involves signaling mediated by nitric oxide (NO). Within the brain, NO is generated in response to neuronal NO synthase (nNOS) activation but NO‐dependent pathways regulating neuronal excitability in the hippocampus remain to be fully elucidated. This study was set out to systematically assess the effects of NO on ion channel activities and intrinsic excitabilities of pyramidal neurons within the CA1 region of the mouse hippocampus. We characterized whole‐cell potassium and sodium currents, both involved in action potential (AP) shaping and propagation and determined NO‐mediated changes in excitabilities and AP waveforms. Our data describe a novel signaling by which NO, in a cGMP‐independent manner, suppresses voltage‐gated Kv2 potassium and voltage‐gated sodium channel activities, thereby widening AP waveforms and reducing depolarization‐induced AP firing rates. Our data show that glutathione, which possesses denitrosylating activity, is sufficient to prevent the observed nitrergic effects on potassium and sodium channels, whereas inhibition of cGMP signaling is also sufficient to abolish NO modulation of sodium currents. We propose that NO suppresses both ion channel activities via redox signaling and that an additional cGMP‐mediated component is required to exert effects on sodium currents. Both mechanisms result in a dampened excitability and firing ability providing new data on nitrergic activities in the context of activity‐dependent regulation of neuronal function following nNOS activation.
Syringic acid, a novel thyroid hormone receptor‐β agonist, ameliorates propylthiouracil‐induced thyroid toxicity in rats
Authors: Panda Sunanda , Kar Anand , Singh Meenakshi , Singh Ram Kumar , Ganeshpurkar Ankit 
Published: May 2021

AbstractThe aim of this study was to evaluate the potential of syringic acid (SA) against propylthiouracil (PTU)‐induced hypothyroidism in rats. SA at a prestandardized dose, 50 mg/kg/day, was orally administered to PTU‐induced hypothyroid rats for 30 days, and alterations in the levels of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), alanine transaminase (ALT), and aspartate transaminase (AST); tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6); total cholesterol (CHOL) and triglycerides (TG); hepatic lipid peroxidation (LPO) and antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione content), as well as histological changes in liver and thyroid were examined. The molecular interactions of the ligand, SA, with thyroid‐related protein targets, such as human thyroid hormone receptor β (hTRβ), and thyroid peroxidase (TPO) protein, were studied using molecular docking. Whereas in hypothyroid animals, T4, T3, and antioxidants were decreased, there was an increase in TSH, TNF‐α, IL‐6, ALT, AST, and hepatic LPO; administration of SA in PTU‐induced animals reversed all these indices to near normal levels. SA also improved the histological features of liver and thyroid gland. Our study clearly demonstrates SA as a novel thyroid agonist for augmenting the thyroid functions in rats. Molecular docking analysis reveals that SA possesses good binding affinity toward both the targets, hTRβ and TPO. Through this approach, for the first time we provide the evidence for SA as a novel thyroid agonist and suggest a receptor‐mediated mechanism for its thyroid stimulatory potential.
Pseudogene ANXA2P2 knockdown shows tumor‐suppressive function by inhibition of the PI3K/PKB pathway in glioblastoma cells
Authors: Ni Hongzao , Zhi Rongrong , Zuo Jiandong , Liu Wenguang , Xie Peng , Zhi Zhongwen 
Published: May 2021

AbstractThe pseudogene annexin A2 pseudogene 2 (ANXA2P2) is highly expressed in glioblastoma (GBM). However, its role and mechanism involved in the progression of GBM remain poorly understood. ANXA2P2 messenger RNA expression was measured by quantitative reverse transcription‐polymerase chain reaction. The protein levels were detected by Western blot. Cell viability was evaluated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide and lactate dehydrogenase (LDH) release assays. Cell invasive ability was investigated by the transwell assay and by epithelial–mesenchymal transition (EMT). Cell apoptosis was examined by flow cytometry. The results showed that ANXA2P2 expression was increased in GBM tissues and cells. Silencing of ANXA2P2 inhibited the activation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (PKB) pathway in GBM cells. Knockdown of ANXA2P2 decreased cell viability, promoted LDH release, suppressed cell invasive ability, and EMT, and induced cell apoptosis in GBM cells. The addition of the PI3K/PKB activator 740Y‐P abrogated the effects of ANXA2P2 knockdown on cell viability, LDH release, invasive ability, and apoptosis. In conclusion, knockdown of ANXA2P2 inhibited cell viability and invasion but promoted the apoptotic rate by suppressing the PI3K/PKB pathway in GBM cells. ANXA2P2 may represent a new target for the treatment of GBM.
Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF‐κB intricate network in experimentally doxorubicin‐induced cardiotoxicity in rats: The role of curcumin
Authors: Soliman Nema A. , Abo El Gheit Rehab E. , Abdel Ghafar Muhammad T. , AbuoHashish Norhan A. , Ibrahim Marwa A. A. , Abo Safia Hend S. , El‐Saka Mervat H. , Elshamy Amira M. 
Published: May 2021

AbstractDoxorubicin (DOX) is an important chemotherapeutic drug. Cardiotoxicity diminishes its clinical efficacy. We aimed to focus on the mechanism of DOX‐induced cardiotoxicity, in addition, to evaluate curcumin's protective effect against it. Twenty‐eight rats were divided into the normal control group I, curcumin‐treated (200 mg/kg body weight [b.w.]) group II,DOX‐treated (4 mg/kg b.w.) group III, and DOX + curcumin group IV. Cardiac injury markers, heart tissue oxidative stress indices, interferon‐gamma (INF‐γ), tumor necrosis factor‐like weak inducer of apoptosis (TWEAK), upregulated modulator of apoptosis (PUMA), p53 and nuclear factor kappa‐B p65 (NF‐κB p65) levels as well as messenger RNA gene expression ofRac1 and fibroblast growth factor‐inducible protein 14(Fn14) were assayed,besides the assay of DNA damage, histopathological changes, survivin immunohistochemistry and electron microscopic examination. Curcumin significantly downregulatedRac1andFn14gene expression and significantly decreased p53, NF‐κB p65, INF‐γ, and PUMA levels in the cardiac tissue. In addition, curcumin improved oxidative stress indices, DNA damage, and cardiac toxicity markers in the form of lactate dehydrogenase (LD), creatine kinase isoenzyme‐MB (CK‐MB), and cardiac troponin‐I (cTn‐I). Meanwhile, upregulated antiapoptotic marker survivin was observed. Light and electron microscopic findings confirmed our biochemical and molecular outcomes. The current study established the antioxidant, anti‐inflammatory, and antiapoptotic roles of curcumin against DOX cardiotoxicity.
Response to comment on “Superposition of waves or densities: Which is the nature of chemical resonance?”
Authors: Wang Yang 
Published: May 2021

AbstractI reply to the comment by Weinhold and Glendening on the article (J. Comput. Chem. 2021, 42, 412). I provide further explanation and an additional numerical example to support my previous assertion that the present form of natural resonance theory is fundamentally flawed, at least within the DFT framework.
Microscopic analysis of plant‐mediated silver nanoparticle toxicity in rainbow trout fish (Oncorhynchus mykiss)
Authors: Ali Ihsan , Khan Shuaib , Shah Khadim , Haroon  , Kalimullah  
Published: May 2021

AbstractOver the years, nanoscience and the application of nanomaterials have gained the attention of researchers due to their enormous application history. Especially, the application of AgNPs providing innovative solutions to a wide range of environmental issues, for instance, wastewater treatment, bioremediations, and environmental sensing. Besides all these, the environmental application of silver nanomaterials causes severe problems in the terrestrial and aquatic ecosystems. For their concern, the present study was conducted to expose rainbow trout fish (Oncorhynchus mykiss) to different concentrations of silver nanoparticles for 25 days. In the current study, mortality (LC50), accumulation, and histopathological changes were analyzed. The results have revealed that the silver nanoparticles were mostly accumulated in the liver followed by the intestine, gill, and muscles. The microscopic analysis has shown that the accumulation of silver nanoparticles led to histological changes in gill and intestinal tissues. Necrosis, degeneration, mucus substance on the surface of gill lamella, cell lysis, and gill lamella atrophy were found at (0.04 mg/L) and (0.06 mg/L). The findings in the current study showed less toxicity in the sense of mortality and accumulation of AgNPs. Therefore, further systematic studies are needed to access the influence of silver nanoparticles on the aquatic ecosystem.
A narrative review of evidence to guide deprescribing among older adults
Authors: Ie Kenya , Aoshima Shuichi , Yabuki Taku , Albert Steven M. 
Published: May 2021

AbstractPotentially inappropriate prescription and polypharmacy are well‐known risk factors for morbidity and mortality among older adults. However, recent systematic reviews have failed to demonstrate the overall survival benefits of deprescribing. Thus, it is necessary to synthesize the current evidence to provide a practical direction for future research and clinical practice. This review summarizes the existing body of evidence regarding deprescribing to identify useful intervention elements. There is evidence that even simple interventions, such as direct deprescribing targeted at risky medications and explicit criteria‐based approaches, effectively reduce inappropriate prescribing. On the other hand, if the goal is to improve clinical outcomes such as hospitalization and emergency department visits, patient‐centered multimodal interventions such as a combination of medication review, multidisciplinary collaboration, and patient education are likely to be more effective. We also consider the opportunities and challenges for deprescribing within the Japanese healthcare system.
A step further in the theory of regional integration: A look at the South American integration strategy
Authors: Bonilla‐Bolaños Andrea 
Published: May 2021

AbstractAlthough literature about regional integration is substantial, its definition remains controversial. Indeed, it is common nowadays for the terms regional integration and regional economic integration to be used interchangeably in spite of the importance accorded by literature to non‐economic factors. Inspired on the South American integration strategy—the Union of South American Nations (UNASUR), this paper revisits the theory of regional integration and proposes to analyse regional integration projects from three complementary angles: economic integration, political integration and physical integration. Moreover, it asserts that political and physical integration constitute a preliminary, or contemporaneous, step towards economic integration and not a final stage, as the current debate suggests.