bluuebunny/crossref_metadata_2025 huggingface dataset:
Learned Immobility Produces Enduring Impairment of the HPA Axis Reactivity in Mice without Replicating the Broad Spectrum of Depressive-Like Phenotype
Authors: Bullich Sébastien , Delcourte Sarah , Haddjeri Nasser , Guiard Bruno P.
Published: January 2021

The forced swim stress test (FST) is widely used for screening pharmacological or non-pharmacological strategies with potential antidepressant activities. Recent data have suggested that repeated FST for five consecutive days (i.e., 5d-RFSS) could be used to generate a robust depressive-like phenotype in mice. However, the face, construct, and predictive validities of 5d-RFSS have been recently challenged. This study took advantage of recent findings showing that mice vulnerability to anxiety is enhanced when animals are stressed during the dark phase, to provide new insight into the relevance of this model. Our results showed a progressive increase in time of immobility in 5d-RFSS mice relative to control non-stressed animals (sham). Three weeks later, we noticed that 5d-RFSS mice injected with the vehicle compound (Veh) still exhibited a high level of immobility in the FST whereas this behavior was reversed by the antidepressant drug amitriptyline (AMI). However, 5d-RFSS/Veh and 5d-RFSS mice/AMI mice showed normal performances in the open field, the novelty suppressed feeding and the tail suspension tests. Despite this lack of generalized behavioral deficits, an impairment of different parameters characterizing the hypothalamic-pituitary-adrenal (HPA) axis reactivity was evidenced in 5d-RFSS mice/Veh but not in 5d-RFSS mice/AMI. Despite anomalies in the HPA axis, the activity of the central serotonergic system remained unaffected in 5d-RFSS mice relative to controls. From our results, it is suggested that learned immobility does not replicate the broad spectrum of depressive symptoms observed in other chronic models of depression such as the unpredictable chronic mild stress (UCMS) model, the chronic social defeat stress (CSDS) model or chronic corticosterone (CORT) exposure but its influence on the HPA axis is remarkable. Further experiments are warranted to makes this model suitable for modelling depression and therefore refine its translational applicability.
A Calcium Guard in the Outer Membrane: Is VDAC a Regulated Gatekeeper of Mitochondrial Calcium Uptake?
Authors: Sander Paulina , Gudermann Thomas , Schredelseker Johann
Published: January 2021

Already in the early 1960s, researchers noted the potential of mitochondria to take up large amounts of Ca2+. However, the physiological role and the molecular identity of the mitochondrial Ca2+ uptake mechanisms remained elusive for a long time. The identification of the individual components of the mitochondrial calcium uniporter complex (MCUC) in the inner mitochondrial membrane in 2011 started a new era of research on mitochondrial Ca2+ uptake. Today, many studies investigate mitochondrial Ca2+ uptake with a strong focus on function, regulation, and localization of the MCUC. However, on its way into mitochondria Ca2+ has to pass two membranes, and the first barrier before even reaching the MCUC is the outer mitochondrial membrane (OMM). The common opinion is that the OMM is freely permeable to Ca2+. This idea is supported by the presence of a high density of voltage-dependent anion channels (VDACs) in the OMM, forming large Ca2+ permeable pores. However, several reports challenge this idea and describe VDAC as a regulated Ca2+ channel. In line with this idea is the notion that its Ca2+ selectivity depends on the open state of the channel, and its gating behavior can be modified by interaction with partner proteins, metabolites, or small synthetic molecules. Furthermore, mitochondrial Ca2+ uptake is controlled by the localization of VDAC through scaffolding proteins, which anchor VDAC to ER/SR calcium release channels. This review will discuss the possibility that VDAC serves as a physiological regulator of mitochondrial Ca2+ uptake in the OMM.
Combined Effects of Methylated Cytosine and Molecular Crowding on the Thermodynamic Stability of DNA Duplexes
Authors: Tsuruta Mitsuki , Sugitani Yui , Sugimoto Naoki , Miyoshi Daisuke
Published: January 2021

Methylated cytosine within CpG dinucleotides is a key factor for epigenetic gene regulation. It has been revealed that methylated cytosine decreases DNA backbone flexibility and increases the thermal stability of DNA. Although the molecular environment is an important factor for the structure, thermodynamics, and function of biomolecules, there are few reports on the effects of methylated cytosine under a cell-mimicking molecular environment. Here, we systematically investigated the effects of methylated cytosine on the thermodynamics of DNA duplexes under molecular crowding conditions, which is a critical difference between the molecular environment in cells and test tubes. Thermodynamic parameters quantitatively demonstrated that the methylation effect and molecular crowding effect on DNA duplexes are independent and additive, in which the degree of the stabilization is the sum of the methylation effect and molecular crowding effect. Furthermore, the effects of methylation and molecular crowding correlate with the hydration states of DNA duplexes. The stabilization effect of methylation was due to the favorable enthalpic contribution, suggesting that direct interactions of the methyl group with adjacent bases and adjacent methyl groups play a role in determining the flexibility and thermodynamics of DNA duplexes. These results are useful to predict the properties of DNA duplexes with methylation in cell-mimicking conditions.
Biological Activities of Some New Secondary Metabolites Isolated from Endophytic Fungi: A Review Study
Authors: Zheng Ruihong , Li Shoujie , Zhang Xuan , Zhao Changqi
Published: January 2021

Secondary metabolites isolated from plant endophytic fungi have been getting more and more attention. Some secondary metabolites exhibit high biological activities, hence, they have potential to be used for promising lead compounds in drug discovery. In this review, a total of 134 journal articles (from 2017 to 2019) were reviewed and the chemical structures of 449 new metabolites, including polyketides, terpenoids, steroids and so on, were summarized. Besides, various biological activities and structure-activity relationship of some compounds were aslo described.
Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data
Authors: Seidler Stephanie , Koual Meriem , Achen Guillaume , Bentivegna Enrica , Fournier Laure , Delanoy Nicolas , Nguyen-Xuan Huyên-Thu , Bats Anne-Sophie , Azaïs Henri
Published: January 2021

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter.
The Retrobulbar Spot Sign and Prominent Middle Limiting Membrane as Prognostic Markers in Non-Arteritic Retinal Artery Occlusion
Authors: Schnieder Marlena , Fischer-Wedi Charlotte V. , Bemme Sebastian , Kortleben Mai-Linh , Feltgen Nicolas , Liman Jan
Published: January 2021

Central retinal artery occlusion (CRAO) is characterized by the sudden, painless loss of vision. Typical sonographic and optic coherence tomography (OCT) findings are a retrobulbar spot sign and prominent middle limiting membrane (p-MLM) sign. It remains uncertain whether the retrobulbar spot sign alone or coinciding with the appearance of p-MLM sign is a prognostic marker for visual acuity and the development of secondary retinal ischemia after CRAO. In our prospective cohort study, we included patients with a non-arteritic central artery occlusion < 4 weeks. We examined the following parameters at prespecified time points: ultrasound examination of orbital cavity, Spectral Domain-OCT examination, visual acuity test, and fundoscopy and ultra-widefield angiography to diagnose retinal vascularization. The presence of p-MLM sign in SD-OCT after CRAO was accompanied by significantly better vision during the first four weeks (2.3 (IQR 0.75) vs. 2.6 (IQR 0.33); p = 0.006). Moreover, the spot sign seems to be a prognostic factor for developing secondary retinal ischemia (8 (100%) vs. 0 (0%); p = 0.036). A retrobulbar spot sign seems to be a negative prognostic factor and is associated with secondary retinal ischemia, whereas a p-MLM sign is a somewhat positive prognostic factor for visual acuity.
Early Pregnancy Outcomes in Fresh Versus Deferred Embryo Transfer Cycles for Endometriosis-Associated Infertility: A Retrospective Cohort Study
Authors: Tan Justin , Cerrillo Maria , Cruz Maria , Cecchino Gustavo Nardini , Garcia-Velasco Juan Antonio
Published: January 2021

Given the estrogen-dependence associated with endometriosis, hyper-stimulation associated with assisted reproduction treatment may exacerbate the disease process and adversely affect endometrial receptivity and subsequent implantation. In this way, a freeze-all deferred embryo transfer (ET) approach may benefit patients with endometriosis, although controversy exists regarding the mechanism of endometriosis-associated infertility and benefits of deferred ET on endometrial receptivity. Hence, the purpose of this study was to compare in vitro fertilization (IVF) outcomes in women with endometriosis, diagnosed by histology, undergoing fresh versus deferred-ET after elective cryopreservation. Of the 728 women included, no significant differences were observed in baseline patient characteristics and response to gonadotrophin stimulation between fresh and deferred ET groups. Furthermore, no significant differences in implantation rate (49.7 vs. 49.9%, p = 0.73), clinical pregnancy rate (40.9 vs. 39.9%, p = 0.49), and miscarriage rate (9.4 vs. 9.9%, p = 0.63) were observed between fresh and deferred ET groups, respectively. Hence, contrary to previous studies, our results suggest that a deferred ET “freeze-all” IVF strategy does not improve early pregnancy outcomes among women with endometriosis. However, prospective studies are required to validate these findings and further insight into the etiology and pathogenesis of endometriosis-associated infertility are necessary to optimize IVF protocols in this population.
Cardiovascular Risk Factors and Their Relationship with Vascular Dysfunction in South African Children of African Ancestry
Authors: Matjuda Edna N. , Engwa Godwill A. , Anye Samuel Nkeh Chungag , Nkeh-Chungag Benedicta N. , Goswami Nandu
Published: January 2021

Vascular dysfunction is known to be an initiator of the development and progression of cardiovascular diseases (CVDs). However, there is paucity of information on the relationship of vascular dysfunction with cardiovascular risk factors in children of African ancestry. This study investigated the relationship between cardiovascular risk factors and vascular function in South African children of African ancestry. A cross-sectional study on 6–9-year-old children in randomly selected rural and urban schools of the Eastern Cape Province of South Africa was conducted. General anthropometric indices were measured, followed by blood pressure (BP) measurements. The pulse wave velocity (PWV) was measured using a Vicorder. Albumin to creatinine ratio (ACR), asymmetric dimethylarginine (ADMA), 8-hydroxy-2deoxyguanosine (8-OHdG) and thiobarbituric acid reactive substance (TBARS) were assayed in urine. Children from urban settings (10.8%) had a higher prevalence of overweight/obesity than their rural counterparts (8.5%) while the prevalence of elevated/high blood pressure was higher in rural (23.2%) than urban children (19.0%). Mean arterial blood pressure (MAP) and diastolic blood pressure (DBP) increased with increasing PWV (p < 0.05). Body mass index (BMI), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) positively associated (p < 0.05) with PWV. Creatinine, albumin and ACR significantly (p < 0.005) increased with increasing ADMA. ADMA associated positively (p < 0.05) with creatinine and 8-OHdG. In conclusion, vascular dysfunction was associated with obesity, high blood pressure, oxidative stress and microalbuminuria in South African children of African ancestry.
The Association between Serum Hemoglobin and Renal Prognosis of IgA Nephropathy
Authors: Oh Tae Ryom , Song Su Hyun , Choi Hong Sang , Kim Chang Seong , Han Seung Hyeok , Kang Kyung Pyo , Kwon Young Joo , Kim Soo Wan , Ma Seong Kwon , Bae Eun Hui
Published: January 2021

Immunoglobin A (IgA) nephropathy causes chronic kidney disease worldwide. Therefore, identifying risk factors associated with the progression of IgA nephropathy is crucial. Anemia is a common complication of chronic kidney disease; however, few studies have investigated the effect of serum hemoglobin on the renal prognosis of IgA nephropathy. This study aimed to determine the effect of serum hemoglobin on the progression of IgA nephropathy. We retrospectively analyzed 4326 patients with biopsy-proven IgA nephropathy. We evaluated the effect of serum hemoglobin on IgA nephropathy progression using Kaplan–Meier survival analyses, the log-rank test, and the Cox proportional hazards model. The primary end-point was progression of IgA nephropathy, defined as dialysis initiation or kidney transplantation. Serum hemoglobin showed a nonlinear relationship with the progression of IgA nephropathy. The Cox proportional hazards model showed that the risk of progression of IgA nephropathy decreased 0.87 times for every 1.0 g/dL increase in serum hemoglobin. In subgroup analyses, reduced serum hemoglobin was an independent risk factor for IgA nephropathy progression only in women. There was no statistically significant interaction of serum hemoglobin between men and women (Pinteraction = 0.177). Results of Sensitivity analysis were robust and consistent. Serum hemoglobin at diagnosis was an independent predictor for IgA nephropathy progression.
Dermatological Manifestations in Inflammatory Bowel Diseases
Authors: Antonelli Elisabetta , Bassotti Gabrio , Tramontana Marta , Hansel Katharina , Stingeni Luca , Ardizzone Sandro , Genovese Giovanni , Marzano Angelo Valerio , Maconi Giovanni
Published: January 2021

Inflammatory bowel diseases (IBDs) may be associated with extra-intestinal manifestations. Among these, mucocutaneous manifestations are relatively frequent, often difficult to diagnose and treat, and may complicate the course of the underlying disease. In the present review, a summary of the most relevant literature on the dermatologic manifestations occurring in patients with inflammatory bowel diseases has been reviewed. The following dermatological manifestations associated with IBDs have been identified: (i) specific manifestations with the same histological features of the underlying IBD (occurring only in Crohn’s disease); (ii) cutaneous disorders associated with IBDs (such as aphthous stomatitis, erythema nodosum, psoriasis, epidermolysis bullosa acquisita); (iii) reactive mucocutaneous manifestations of IBDs (such as pyoderma gangrenosum, Sweet’s syndrome, bowel-associated dermatosis-arthritis syndrome, aseptic abscess ulcers, pyodermatitis–pyostomatitis vegetans, etc.); (iv) mucocutaneous conditions secondary to treatment (including injection site reactions, infusion reactions, paradoxical reactions, eczematous and psoriasis-like reactions, cutaneous infections, and cutaneous malignancies); (v) manifestations due to nutritional malabsorption (such as stomatitis, glossitis, angular cheilitis, pellagra, scurvy, purpura, acrodermatitis enteropathica, phrynoderma, seborrheic-type dermatitis, hair and nail abnormalities). An accurate dermatological examination is essential in all IBD patients, especially in candidates to biologic therapies, in whom drug-induced cutaneous reactions may assume marked clinical relevance.
The Impact of Air Pollution Exposure on the MicroRNA Machinery and Lung Cancer Development
Authors: Sima Michal , Rossnerova Andrea , Simova Zuzana , Rossner Pavel
Published: January 2021

Small non-coding RNA molecules (miRNAs) play an important role in the epigenetic regulation of gene expression. As these molecules have been repeatedly implicated in human cancers, they have been suggested as biomarkers of the disease. Additionally, miRNA levels have been shown to be affected by environmental pollutants, including airborne contaminants. In this review, we searched the current literature for miRNAs involved in lung cancer, as well as miRNAs deregulated as a result of exposure to air pollutants. We then performed a synthesis of the data and identified those molecules commonly deregulated under both conditions. We detected a total of 25 miRNAs meeting the criteria, among them, miR-222, miR-21, miR-126-3p, miR-155 and miR-425 being the most prominent. We propose these miRNAs as biomarkers of choice for the identification of human populations exposed to air pollution with a significant risk of developing lung cancer.
Land-Use Planning and the Public: Is There an Optimal Degree of Civic Participation?
Authors: Kopáček Miroslav
Published: January 2021

Civic participation has an irreplaceable role in the land-use planning process because it contributes a practical perspective to expert knowledge. This article discusses whether there is actually a level of civic participation that can be considered optimal, which would allow experts to effectively obtain information from everyday users of the territory, who have the best practical knowledge of it; experts may also gain sufficient feedback on intended developments, based on knowledge about civic participation from representatives of individual municipalities. The article also proposes measures that can promote an optimal degree of participation in the land-use planning process. The fieldwork was conducted in the form of semi-structured interviews with the mayors of municipalities with a population of up to 2000 inhabitants in selected districts of the Ústí Region (Czech Republic). The results suggest that the optimal degree of civic participation in land-use planning should have a representative extent, so it should not merely be a matter of individuals, but also one of groups of dozens of people, and such groups should encompass a balanced variety of characteristics; an optimal level of civic participation should also provide the maximum number of relevant impulses. Measures that may secure and foster an optimal degree of civic participation in land-use planning include (1) striving to avoid preferring purely voluntary participation; (2) simultaneously utilizing various tools to engage inhabitants; (3) educating inhabitants on a regular basis; and (4) consistently communicating and providing feedback, while also searching for informal means of communication and discussion.
Using Artificial Neural Network with Prey Predator Algorithm for Prediction of the COVID-19: The Case of Brazil and Mexico
Authors: Hamadneh Nawaf N. , Tahir Muhammad , Khan Waqar A.
Published: January 2021

The spread of the COVID-19 epidemic worldwide has led to investigations in various aspects, including the estimation of expected cases. As it helps in identifying the need to deal with cases caused by the pandemic. In this study, we have used artificial neural networks (ANNs) to predict the number of cases of COVID-19 in Brazil and Mexico in the upcoming days. Prey predator algorithm (PPA), as a type of metaheuristic algorithm, is used to train the models. The proposed ANN models’ performance has been analyzed by the root mean squared error (RMSE) function and correlation coefficient (R). It is demonstrated that the ANN models have the highest performance in predicting the number of infections (active cases), recoveries, and deaths in Brazil and Mexico. The simulation results of the ANN models show very well predicted values. Percentages of the ANN’s prediction errors with metaheuristic algorithms are significantly lower than traditional monolithic neural networks. The study shows the expected numbers of infections, recoveries, and deaths that Brazil and Mexico will reach daily at the beginning of 2021.
Coverability of Graphs by Parity Regular Subgraphs
Authors: Petruševski Mirko , Škrekovski Riste
Published: January 2021

A graph is even (resp. odd) if all its vertex degrees are even (resp. odd). We consider edge coverings by prescribed number of even and/or odd subgraphs. In view of the 8-Flow Theorem, a graph admits a covering by three even subgraphs if and only if it is bridgeless. Coverability by three odd subgraphs has been characterized recently [Petruševski, M.; Škrekovski, R. Coverability of graph by three odd subgraphs. J. Graph Theory 2019, 92, 304–321]. It is not hard to argue that every acyclic graph can be decomposed into two odd subgraphs, which implies that every graph admits a decomposition into two odd subgraphs and one even subgraph. Here, we prove that every 3-edge-connected graph is coverable by two even subgraphs and one odd subgraph. The result is sharp in terms of edge-connectivity. We also discuss coverability by more than three parity regular subgraphs, and prove that it can be efficiently decided whether a given instance of such covering exists. Moreover, we deduce here a polynomial time algorithm which determines whether a given set of edges extends to an odd subgraph. Finally, we share some thoughts on coverability by two subgraphs and conclude with two conjectures.
Alikhanov Legendre—Galerkin Spectral Method for the Coupled Nonlinear Time-Space Fractional Ginzburg–Landau Complex System
Authors: Zaky Mahmoud A. , Hendy Ahmed S. , De Staelen Rob H.
Published: January 2021

A finite difference/Galerkin spectral discretization for the temporal and spatial fractional coupled Ginzburg–Landau system is proposed and analyzed. The Alikhanov L2-1σ difference formula is utilized to discretize the time Caputo fractional derivative, while the Legendre-Galerkin spectral approximation is used to approximate the Riesz spatial fractional operator. The scheme is shown efficiently applicable with spectral accuracy in space and second-order in time. A discrete form of the fractional Grönwall inequality is applied to establish the error estimates of the approximate solution based on the discrete energy estimates technique. The key aspects of the implementation of the numerical continuation are complemented with some numerical experiments to confirm the theoretical claims.
Impact of Renewable Energy Sources into Multi Area Multi-Source Load Frequency Control of Interrelated Power System
Authors: Arora Krishan , Kumar Ashok , Kamboj Vikram Kumar , Prashar Deepak , Shrestha Bhanu , Joshi Gyanendra Prasad
Published: January 2021

There is an increasing concentration in the influences of nonconventional power sources on power system process and management, as the application of these sources upsurges worldwide. Renewable energy technologies are one of the best technologies for generating electrical power with zero fuel cost, a clean environment, and are available almost throughout the year. Some of the widespread renewable energy sources are tidal energy, geothermal energy, wind energy, and solar energy. Among many renewable energy sources, wind and solar energy sources are more popular because they are easy to install and operate. Due to their high flexibility, wind and solar power generation units are easily integrated with conventional power generation systems. Traditional generating units primarily use synchronous generators that enable them to ensure the process during significant transient errors. If massive wind generation is faltered due to error, it may harm the power system’s operation and lead to the load frequency control issue. This work proposes binary moth flame optimizer (MFO) variants to mitigate the frequency constraint issue. Two different binary variants are implemented for improving the performance of MFO for discrete optimization problems. The proposed model was evaluated and compared with existing algorithms in terms of standard testing benchmarks and showed improved results in terms of average and standard deviation.
Indistinguishability Operators via Yager t-norms and Their Applications to Swarm Multi-Agent Task Allocation
Authors: Bibiloni-Femenias Maria-del-Mar , Guerrero José , Miñana Juan-José , Valero Oscar
Published: January 2021

In this paper, we propose a family of indistinguishability operators, that we have called Yager Possibilitic Response Functions (YPRFs for short), as an appropriate tool for allocating tasks to a collective of agents. In order to select the best agent to carry out each task, we have used the so-called response threshold method, where each agent decides the next task to perform following a probabilistic Markov process and, in addition, involves a response function which models how appropriate the task is for the agent. In previous works, we developed a new response threshold method which incorporates the use of indistinguishability operators as response functions and possibility theory instead of probability, for task allocation from a very general perspective without taking into account the specific characteristics of the agents except their limitations to carry out a task. Such an allocation is modelled by means of possibilistic, instead of probabilisitic, Markov chains. We show that possibilistic Markov chains outperform its probabilistic counterparts for the aforementioned propose. All the indistinguishability operators considered in previous papers were not able to take into account the agents’ restrictions for moving from a task to another one, or equivalently to carry out a task instead of another one. In order to avoid this handicap, we introduce a new kind of response functions, YPRFs, which are modelled by means of indistinguishability operators obtained via Yager t-norms. This new type of response functions drops to zero when an agent, due to its limitations, is not able to execute a task and, therefore, is able to model a generic multi-agent system with restrictions. The performed simulation, under Matlab, allows us to compare the results obtained using the new YPRFs with those obtained applying celebrated response functions also generated via indistinguishability operators (that we call Original Possibilitic Response Functions, OPRFs for short). Moreover, the results confirm that the YPRFs are able to take into account agent’s restrictions while the OPRFs are not able. Finally, in the light of the experimental results, we can confirm that those systems modelled.
Cold-Active β-Galactosidases: Insight into Cold Adaptation Mechanisms and Biotechnological Exploitation
Authors: Mangiagalli Marco , Lotti Marina
Published: January 2021

β-galactosidases (EC 3.2.1.23) catalyze the hydrolysis of β-galactosidic bonds in oligosaccharides and, under certain conditions, transfer a sugar moiety from a glycosyl donor to an acceptor. Cold-active β-galactosidases are identified in microorganisms endemic to permanently low-temperature environments. While mesophilic β-galactosidases are broadly studied and employed for biotechnological purposes, the cold-active enzymes are still scarcely explored, although they may prove very useful in biotechnological processes at low temperature. This review covers several issues related to cold-active β-galactosidases, including their classification, structure and molecular mechanisms of cold adaptation. Moreover, their applications are discussed, focusing on the production of lactose-free dairy products as well as on the valorization of cheese whey and the synthesis of glycosyl building blocks for the food, cosmetic and pharmaceutical industries.
A Conantokin Peptide Con-T[M8Q] Inhibits Morphine Dependence with High Potency and Low Side Effects
Authors: Liu Zhuguo , Yu Zheng , Yu Shuo , Zhu Cui , Dong Mingxin , Mao Wenxiang , Hu Jie , Prorok Mary , Su Ruibin , Dai Qiuyun
Published: January 2021

N-methyl-D-aspartate receptor (NMDAR) antagonists have been found to be effective to inhibit morphine dependence. However, the discovery of the selective antagonist for NMDAR GluN2B with low side-effects still remains challenging. In the present study, we report a selective NMDAR GluN2B antagonist con-T[M8Q](a conantokin-T variant) that potently inhibits the naloxone-induced jumping and conditioned place preference of morphine-dependent mice at nmol/kg level, 100-fold higher than ifenprodil, a classical NMDAR NR2B antagonist. Con-T[M8Q] displays no significant impacts on coordinated locomotion function, spontaneous locomotor activity, and spatial memory mice motor function at the dose used. Further molecular mechanism experiments demonstrate that con-T[M8Q] effectively inhibited the transcription and expression levels of signaling molecules related to NMDAR NR2B subunit in hippocampus, including NR2B, p-NR2B, CaMKII-α, CaMKII-β, CaMKIV, pERK, and c-fos. The high efficacy and low side effects of con-T[M8Q] make it a good lead compound for the treatment of opiate dependence and for the reduction of morphine usage.
The Creep and Oxidation Behaviour of Pesting-Resistant (Mo,Ti)5Si3-Containing Eutectic-Eutectoid Mo-Si-Ti Alloys
Authors: Obert Susanne , Kauffmann Alexander , Pretzler Rupert , Schliephake Daniel , Hinrichs Frauke , Heilmaier Martin
Published: January 2021

In this study we present a series of light-weight (6.24 to 6.42 g/cm3), Ti-rich Mo-Si-Ti alloys (≥40 at.% nominal Ti content) with the hitherto best combination of pesting and creep resistance at 800 and 1200 °C, respectively. This has been achieved by fine-scaled eutectic-eutectoid microstructures with substantial fractions of primarily solidified (Mo,Ti)5Si3. (Mo,Ti)5Si3 was found to be oxidation-resistant in these alloys and also beneficial for the creep resistance. The enhanced solidus temperature is of specific relevance with respect to the latter point. The creep resistance is competitive to the non-pesting resistant, but most creep-resistant (among the Mo-Si-Ti alloys) eutectoid alloy Mo-21Si-34Ti developed by Schliephake et al. [Schliephake et al., in Intermetallics 104 (2019) pp. 133–142]. Moreover, it is favourably superior to the commercially applied Ni-based single crystal alloy CMSX-4 for the applied compressive loading conditions under vacuum.
Vertical–Horizontal Coupling Vibration of Hot Rolling Mill Rolls under Multi-Piecewise Nonlinear Constraints
Authors: Peng Rongrong , Zhang Xingzhong , Shi Peiming
Published: January 2021

This study establishes a vertical–horizontal coupling vibration model of hot rolling mill rolls under multi-piecewise nonlinear constraints considering the piecewise nonlinear spring force and piecewise nonlinear friction force constraints of the hydraulic cylinder in the vertical direction of the rolls, the piecewise stiffness constraints in the horizontal direction, and the influence of the nonlinear dynamic rolling force in the rolling process. Using the average method to solve the amplitude–frequency response equation of the coupled vibration system and taking the actual parameters of a 1780 mm hot rolling mill (Chengde Steel Co., Ltd., Chengde, China) as an example, we study the amplitude–frequency characteristics of the mill rolls under different parameter settings. The results show that the amplitude and resonance region can be reduced by appropriately reducing the external disturbance force and the nonlinear spring force of the hydraulic cylinder, appropriately increasing the nonlinear friction force, and eliminating the gap between the bearing seat and the mill housing, to avoid the amplitude jump phenomenon due to piecewise variation. Furthermore, using the singularity theory to study the static bifurcation characteristics of the coupled vibration system, we establish a relationship between the vibration parameters and the topological bifurcation solution of the coupled system. The transition sets and their corresponding bifurcation topological structure in three cases are given, and the steady and unsteady process parameter regions of the rolls are obtained. The dynamic behavior of the coupled vibration system can be controlled by varying the bifurcation parameter. This study provides a theoretical basis for restraining the vibration of hot rolling mill rolls and optimizing the process parameters.
Microstructures and Tensile Fracture Behavior of 2219 Wrought Al–Cu Alloys with Different Impurity of Fe
Authors: Xu Daofen , Zhu Changjun , Xu Chengfu , Chen Kanghua
Published: January 2021

The Fe-rich intermetallic phases have a broadly detrimental effect on the mechanical properties of Al–Cu alloy. In this paper, the continuous evolution of Fe-rich intermetallics and their effects on mechanical properties, especially the tensile fracture behavior of 2219 wrought Al–Cu alloys as a function of Fe content against different processing approaches (i.e., as-cast, homogenization, multidirectional forging, and solution-peak aging treatment) were investigated using optical microscopy, scanning electron microscopy, and tensile tests. The results indicated that needle-like Al7Cu2Fe or Al7Cu2(Fe, Mn) intermetallics mainly presented in the final microstructures of all alloys with various Fe contents. The size and number of Al7Cu2Fe/Al7Cu2(Fe, Mn) intermetallics increased with the increase of Fe content. The increase of Fe content had little influence on the ultimate tensile strength and yield strength, while obvious deterioration in the elongation, because fracture initiators mainly occurred at the Al7Cu2Fe/Al7Cu2(Fe, Mn) particles or particles–matrix interface. Therefore, the 2219 Al–Cu alloy with 0.2 wt.% Fe content presented relatively low tensile ductility. The tensile fracture mechanism has been discussed in detail.
Grafting of 18β-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity
Authors: Quan Wei-Yan , Kong Song-Zhi , Li Si-Dong , Liu Hua-Zhong , Ouyang Qian-Qian , Huang Yong-Mei , Luo Hui
Published: January 2021

Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18β-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18β-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 β-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.
Antifungal Activity of Melaleuca alternifolia Essential Oil (TTO) and Its Synergy with Itraconazole or Ketoconazole against Trichophyton rubrum
Authors: Roana Janira , Mandras Narcisa , Scalas Daniela , Campagna Paolo , Tullio Vivian
Published: January 2021

Over the past 20–30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.
Application of Pomegranate by-Products in Muscle Foods: Oxidative Indices, Colour Stability, Shelf Life and Health Benefits
Authors: Das Arun K. , Nanda Pramod Kumar , Chowdhury Nilabja Roy , Dandapat Premanshu , Gagaoua Mohammed , Chauhan Pranav , Pateiro Mirian , Lorenzo Jose M.
Published: January 2021

In recent years, considerable importance is given to the use of agrifood wastes as they contain several groups of substances that are useful for development of functional foods. As muscle foods are prone to lipid and protein oxidation and perishable in nature, the industry is in constant search of synthetic free additives that help in retarding the oxidation process, leading to the development of healthier and shelf stable products. The by-products or residues of pomegranate fruit (seeds, pomace, and peel) are reported to contain bioactive compounds, including phenolic and polyphenolic compounds, dietary fibre, complex polysaccharides, minerals, vitamins, etc. Such compounds extracted from the by-products of pomegranate can be used as functional ingredients or food additives to harness the antioxidant, antimicrobial potential, or as substitutes for fat, and protein in various muscle food products. Besides, these natural additives are reported to improve the quality, safety, and extend the shelf life of different types of food products, including meat and fish. Although studies on application of pomegranate by-products on various foods are available, their effect on the physicochemical, oxidative changes, microbial, colour stabilizing, sensory acceptability, and shelf life of muscle foods are not comprehensively discussed previously. In this review, we vividly discuss these issues, and highlight the benefits of pomegranate by-products and their phenolic composition on human health.
Spectroelectrochemical Behavior of Polycrystalline Gold Electrode Modified by Reverse Micelles
Authors: Rodríguez González Miriam C. , Luis-Sunga Maximina , Souto Ricardo M. , Hernández Creus Alberto , Pastor Elena , García Gonzalo
Published: January 2021

The increasing demand for raising the reliability of electronic contacts has led to the development of methods that protect metal surfaces against atmospheric corrosion agents. This severe problem implies an important economic cost annually but small amounts of corrosion inhibitors can control, decrease or avoid reactions between a metal and its environment. In this regard, surfactant inhibitors have displayed many advantages such as low price, easy fabrication, low toxicity and high inhibition efficiency. For this reason, in this article, the spectroelectrochemical behavior of polycrystalline gold electrode modified by reverse micelles (water/polyethyleneglycol-dodecylether (BRIJ 30)/n-heptane) is investigated by atomic force microscopy (AFM), potentiodynamic methods and electrochemical impedance spectroscopy (EIS). Main results indicate a strong adsorption of a monolayer of micelles on the gold substrate in which electron tunneling conduction is still possible. Therefore, this method of increasing the corrosion resistance of gold contacts is usable only in conditions of long-term storage but not in the operation of devices with such contacts. In this regard, the micelle coating must be removed from the surface of the gold contacts before use. Finally, the aim of the present work is to understand the reactions occurring at the surfactant/metal interface, which may help to improve the fabrication of novel electrodes.
New Antineoplastic Naphthohydroquinones Attached to Labdane and Rearranged Diterpene Skeletons
Authors: Hernández Ángela P. , Chamorro Pablo , Rodríguez Mª Lucena , Miguel del Corral José M. , García Pablo A. , Francesch Andrés , San Feliciano Arturo , Castro Mª Ángeles
Published: January 2021

Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI50 values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI50 at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.
A Review on Lithium-Ion Battery Separators towards Enhanced Safety Performances and Modelling Approaches
Authors: Li Ao , Yuen Anthony Chun Yin , Wang Wei , De Cachinho Cordeiro Ivan Miguel , Wang Cheng , Chen Timothy Bo Yuan , Zhang Jin , Chan Qing Nian , Yeoh Guan Heng
Published: January 2021

In recent years, the applications of lithium-ion batteries have emerged promptly owing to its widespread use in portable electronics and electric vehicles. Nevertheless, the safety of the battery systems has always been a global concern for the end-users. The separator is an indispensable part of lithium-ion batteries since it functions as a physical barrier for the electrode as well as an electrolyte reservoir for ionic transport. The properties of separators have direct influences on the performance of lithium-ion batteries, therefore the separators play an important role in the battery safety issue. With the rapid developments of applied materials, there have been extensive efforts to utilize these new materials as battery separators with enhanced electrical, fire, and explosion prevention performances. In this review, we aim to deliver an overview of recent advancements in numerical models on battery separators. Moreover, we summarize the physical properties of separators and benchmark selective key performance indicators. A broad picture of recent simulation studies on separators is given and a brief outlook for the future directions is also proposed.
ZnII and CuII-Based Coordination Polymers and Metal Organic Frameworks by the of Use of 2-Pyridyl Oximes and 1,3,5-Benzenetricarboxylic Acid
Authors: Mylonas-Margaritis Ioannis , Mayans Julia , McArdle Patrick , Papatriantafyllopoulou Constantina
Published: January 2021

The simultaneous use of 2-pyridyl oximes (pyridine-2 amidoxime, H2pyaox; 2-methyl pyridyl ketoxime, Hmpko) and 1,3,5-benzenetricarboxylic acid (H3btc) provided access to five new compounds, namely [Zn(H2btc)2(H2pyaox)2]•2H2O (1•2H2O), [Zn(Hbtc)(H2pyaox)2]n (2), [Cu(Hbtc)(H2pyaox)]n (3), [Cu(Hbtc)(HmpKo)]n (4) and [Cu2(Hbtc)2(Hmpko)2(H2O)2]•4H2O (5•4H2O). Among them, 3 is the first example of a metal-organic framework (MOF) containing H2pyaox. Its framework can be described as a 3-c uninodal net of hcb topology with the layers being parallel to the (1,0,1) plane. Furthermore, 3 is the third reported MOF based on a 2-pyridyl oxime in general. 2 and 4 are new members of a small family of coordination polymers containing an oximic ligand. 1–5 form 3D networks through strong intermolecular interactions. Dc magnetic susceptibility studies were carried out in a crystalline sample of 3 and revealed the presence of weak exchange interactions between the metal centres; the experimental data were fitted to a theoretical model with the fitting parameters being J = −0.16(1) cm−1 and g = 2.085(1). The isotropic g value was also confirmed by electronic paramagnetic resonance (EPR) spectroscopy. Reactivity studies were performed for 3 in the presence of metal ions; the reaction progress was studied and discussed for Fe(NO3)3 by the use of several characterization techniques, including single crystal X-ray crystallography and IR spectroscopy.
Analyzing the Carotenoid Composition of Melilot (Melilotus officinalis (L.) Pall.) Extracts and the Effects of Isolated (All-E)-lutein-5,6-epoxide on Primary Sensory Neurons and Macrophages
Authors: Horváth Györgyi , Csikós Eszter , Andres Eichertné Violetta , Bencsik Tímea , Takátsy Anikó , Gulyás-Fekete Gergely , Turcsi Erika , Deli József , Szőke Éva , Kemény Ágnes , Payrits Maja , Szente Lajos , Kocsis Marianna , Molnár Péter , Helyes Zsuzsanna
Published: January 2021

Melilotus officinalis is known to contain several types of secondary metabolites. In contrast, the carotenoid composition of this medicinal plant has not been investigated, although it may also contribute to the biological activities of the drug, such as anti-inflammatory effects. Therefore, this study focuses on the isolation and identification of carotenoids from Meliloti herba and on the effect of isolated (all-E)-lutein 5,6-epoxide on primary sensory neurons and macrophages involved in nociception, as well as neurogenic and non-neurogenic inflammatory processes. The composition of the plant extracts was analyzed by high performance liquid chromatography (HPLC). The main carotenoid was isolated by column liquid chromatography (CLC) and identified by MS and NMR. The effect of water-soluble lutein 5,6-epoxide-RAMEB (randomly methylated-β-cyclodextrin) was investigated on Ca2+-influx in rat primary sensory neurons induced by the activation of the transient receptor potential ankyrin 1 receptor agonist to mustard-oil and on endotoxin-induced IL-1β release from isolated mouse peritoneal macrophages. (all-E)-Lutein 5,6-epoxide significantly decreased the percent of responsive primary sensory neurons compared to the vehicle-treated stimulated control. Furthermore, endotoxin-evoked IL-1β release from macrophages was significantly decreased by 100 µM lutein 5,6-epoxide compared to the vehicle-treated control. The water-soluble form of lutein 5,6-epoxide-RAMEB decreases the activation of primary sensory neurons and macrophages, which opens perspectives for its analgesic and anti-inflammatory applications.