bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Surgical Cleavage Plane by Preoperative Magnetic Resonance Imaging Findings in Adult Intracranial Meningiomas
Authors: Ahmed Nazmin , Ferini Gianluca , Hossain Mosharef A. T. M. , Barua Kanak Kanti , Hossain Mohammad Nazrul , Umana Giuseppe Emmanuele , Shlobin Nathan A. , Scalia Gianluca , Palmisciano Paolo , Tomasi Ottavio S. , Chaurasia Bipin
Published: March 2022

(1) Background: Meningiomas are usually benign encapsulated intracranial tumors with well-defined borders that offer a high chance of cure with complete removal. The aim of this study was to evaluate the association between preoperative MRI features and surgical plane of cleavage. (2) Materials and Methods: This was a cross-sectional observational study conducted in the Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University. Data were recorded from 48 study participants with confirmed intracranial meningioma and analyzed by IBM SPSS (version 23). (3) Results: The highest incidence of intracranial meningioma was observed in the third decade of life of our study participants. The female to male ratio was 1.82:1. The most common location of meningiomas was convexity (29.16%), sphenoid wing (22.91%), parasagittal (20.83%), and falcine (14.58%). Most of the patients (68.8%) had medium-sized tumors, and 75.0% exhibited hyperintense signal change in the tumor parenchyma on T2-weighted imaging. One-third (33.3%) of patients were characterized as no edema, focal edema, and lobar/hemispheric edema. There was no statistically significant association between tumor size and types of surgical cleavage plane. Different signal intensities of tumor parenchyma, as well as types of peritumoral edema, showed no statistically significant association with surgical cleavage plane (p > 0.05). (4) Conclusion: There was no association among the size of the tumor, extent of peritumoral edema, the intensity of the tumor on T2-weighted images, and the types of surgical cleavage plane. Future studies with larger sample sizes are required to find out more precise findings.
6,6′-Di-(2″-thiophenol)-2,2′-bipyridine
Authors: Huang Yan , Tong Lianpeng
Published: March 2022

This short note describes the synthesis of compound 6,6′-di-(2″-thiophenol)-2,2′-bipyridine from its methyl phenyl sulfane precursor via deprotection of the methyl groups. The product as well as the intermediate in the synthetic route have been characterized by UV-Vis spectroscopy, 1H- and 13C-NMR spectroscopy, FT-IR spectroscopy, and HR-MS analysis. This work presents a rare example of tetradentate chelators that bears pyridyl backbones and thiophenol donors for the coordination with 3d-transition metal cations.
Bioinspired Topographic Surface Modification of Biomaterials
Authors: Arango-Santander Santiago
Published: March 2022

Physical surface modification is an approach that has been investigated over the last decade to reduce bacterial adhesion and improve cell attachment to biomaterials. Many techniques have been reported to modify surfaces, including the use of natural sources as inspiration to fabricate topographies on artificial surfaces. Biomimetics is a tool to take advantage of nature to solve human problems. Physical surface modification using animal and vegetal topographies as inspiration to reduce bacterial adhesion and improve cell attachment has been investigated in the last years, and the results have been very promising. However, just a few animal and plant surfaces have been used to modify the surface of biomaterials with these objectives, and only a small number of bacterial species and cell types have been tested. The purpose of this review is to present the most current results on topographic surface modification using animal and plant surfaces as inspiration to modify the surface of biomedical materials with the objective of reducing bacterial adhesion and improving cell behavior.
Tests and Numerical Study of Single-Lap Thermoplastic Composite Joints Bolted by Countersunk
Authors: Zhang Jian , Chen Xiuhua , Tian Aiqin , Fan Yin
Published: March 2022

Tensile tests were carried out to investigate the effect of stacking sequences on the bearing strength of single-lap thermoplastic composite countersunk bolted joints. A 3D elastoplastic model was built based on a plastic theory for numerical analysis. The damage initiation was judged based on LaRC05 criteria, and the damage propagation was described by using a nonlinear, gradual unloading method based on crack band theory. The accuracy of the present model was validated by comparing the numerical results to those from the tests. The test results showed that the effects of stacking sequences on the ultimate bearing strength and the 2% offset bearing strength are limited. Moreover, the numerical results depicted that the ultimate bearing strength and the 2% offset bearing strength reduce when the bolt-tightening torque or the bolt–hole clearance is increased.
Construction of Supramolecular Systems That Achieve Lifelike Functions
Authors: Banno Taisuke , Sawada Daichi , Toyota Taro
Published: March 2022

The Nobel Prize in Chemistry was awarded in 1987 and 2016 for research in supramolecular chemistry on the “development and use of molecules with structure-specific interactions of high selectivity” and the “design and production of molecular machines”, respectively. This confirmed the explosive development of supramolecular chemistry. In addition, attempts have been made in systems chemistry to embody the complex functions of living organisms as artificial non-equilibrium chemical systems, which have not received much attention in supramolecular chemistry. In this review, we explain recent developments in supramolecular chemistry through four categories: stimuli-responsiveness, time evolution, dissipative self-assembly, and hierarchical expression of functions. We discuss the development of non-equilibrium supramolecular systems, including the use of molecules with precisely designed properties, to achieve functions found in life as a hierarchical chemical system.
Highly Photostable Carbon Dots from Citric Acid for Bioimaging
Authors: Fiori Federico , Moukham Hind , Olia Federico , Piras Davide , Ledda Sergio , Salis Andrea , Stagi Luigi , Malfatti Luca , Innocenzi Plinio
Published: March 2022

Bioimaging supported by nanoparticles requires low cost, highly emissive and photostable systems with low cytotoxicity. Carbon dots (C-dots) offer a possible solution, even if controlling their properties is not always straightforward, not to mention their potentially simple synthesis and the fact that they do not exhibit long-term photostability in general. In the present work, we synthesized two C-dots starting from citric acid and tris (hydroxymethyl)-aminomethane (tris) or arginine methyl ester dihydrochloride. Cellular uptake and bioimaging were tested in vitro using murine neuroblastoma and ovine fibroblast cells. The C-dots are highly biocompatible, and after 24 h of incubation with the cells, 100% viability was still observed. Furthermore, the C-dots synthesized using tris have an average dimension of 2 nm, a quantum yield of 37%, high photostability and a zeta potential (ζ) around −12 mV. These properties favor cellular uptake without damaging cells and allow for very effective bioimaging.
Programming Soft Shape-Morphing Systems by Harnessing Strain Mismatch and Snap-Through Bistability: A Review
Authors: Wu Yi , Guo Gang , Wei Zhuxuan , Qian Jin
Published: March 2022

Multi-modal and controllable shape-morphing constitutes the cornerstone of the functionalization of soft actuators/robots. Involving heterogeneity through material layout is a widely used strategy to generate internal mismatches in active morphing structures. Once triggered by external stimuli, the entire structure undergoes cooperative deformation by minimizing the potential energy. However, the intrinsic limitation of soft materials emerges when it comes to applications such as soft actuators or load-bearing structures that require fast response and large output force. Many researchers have explored the use of the structural principle of snap-through bistability as the morphing mechanisms. Bistable or multi-stable mechanical systems possess more than one local energy minimum and are capable of resting in any of these equilibrium states without external forces. The snap-through motion could overcome energy barriers to switch among these stable or metastable states with dramatically distinct geometries. Attributed to the energy storage and release mechanism, such snap-through transition is quite highly efficient, accompanied by fast response speed, large displacement magnitude, high manipulation strength, and moderate driving force. For example, the shape-morphing timescale of conventional hydrogel systems is usually tens of minutes, while the activation time of hydrogel actuators using the elastic snapping instability strategy can be reduced to below 1 s. By rationally embedding stimuli-responsive inclusions to offer the required trigger energy, various controllable snap-through actuations could be achieved. This review summarizes the current shape-morphing programming strategies based on mismatch strain induced by material heterogeneity, with emphasis on how to leverage snap-through bistability to broaden the applications of the shape-morphing structures in soft robotics and mechanical metamaterials.
Comparative Study on Electrical Conductivity of CeO2-Doped AlN Ceramics Sintered by Hot-Pressing and Spark Plasma Sintering
Authors: Coëffe-Desvaux Mickael , Pradeilles Nicolas , Marchet Pascal , Vandenhende Marion , Joinet Mickael , Maître Alexandre
Published: March 2022

Aluminum nitride (AlN) ceramics were prepared by both Hot-pressing (HP) and Spark-Plasma-Sintering (SPS) using cerium oxide as the sintering aid. The characterization of AlN raw powder denoted the presence of an amorphous layer that led to the formation of aluminum oxide. During the sintering process, CeO2 introduced as a sintering aid was reduced into Ce2O3. The latter reacted with aluminum oxide to form a transient liquid phase that promotes sintering by both HP and SPS. A reactional path leading to the formation of secondary phases, such as CeAlO3 and CeAl11O18, has been proposed according to the pseudo-binary Al2O3 – Ce2O3. Ceramics obtained from HP and SPS are presented as similar, except for the secondary-phase distribution. The influences of secondary phase composition and distribution on electrical conductivity were evaluated by leakage current measurements. The mechanism of DC conduction and the global conductivity of ceramics were discussed according to the sintering process and the number of secondary phases.
Intelligent Optimization Based on a Virtual Marine Diesel Engine Using GA-ICSO Hybrid Algorithm
Authors: Chen Ximing , Liu Long , Du Jingtao , Liu Dai , Huang Li , Li Xiannan
Published: March 2022

Considering the trade-off relationship between brake specific fuel consumption (BSFC), combustion noise (CN) and NOx emission, it is a difficult task to optimize them simultaneously in a marine diesel engine. In order to overcome this problem, a novel genetic algorithm and improved chicken swarm optimization (GA-ICSO) hybrid algorithm was proposed, where the enhanced Levy flight and adaptive self-learning factor were introduced in this algorithm. Computational comparisons between GA-ICSO and other effective optimization algorithms were performed using four standard test functions, validating the improvements in both accuracy and stability for GA-ICSO. Furthermore, a predictive engine model based on a phenomenological approach was developed and validated. This model coupled the proposed algorithm for the optimization of a marine diesel engine. In the optimization process, five control parameters were selected as design variables, including injection timing (IT), intake cam phasing (ICP), intake valve closing (IVC), intake temperature and pressure. Results show that, a lower objective value can be obtained by GA-ICSO than other widely used optimization algorithms for all the operating conditions. Besides, by comparing the results between the optimal generations and baselines, it could be found that, under the condition of 50%, 75% and 100%load, CN is reduced by 10.7%, 4.9% and 3.9%, NOx is decreased by 15%, 31% and 33%, and BSFC is suppressed by 10.8%, 13.3% and 9.5%, respectively. Finally, heat release rates, noise spectrums, cylinder pressures and temperatures were all employed to discuss the optimization results of a marine diesel engine under different working conditions.
Optimal Classifier to Detect Unit of Measure Inconsistency in Gas Turbine Sensors
Authors: Manservigi Lucrezia , Venturini Mauro , Losi Enzo , Bechini Giovanni , Artal de la Iglesia Javier
Published: March 2022

Label noise is a harmful issue that arises when data are erroneously labeled. Several label noise issues can occur but, among them, unit of measure inconsistencies (UMIs) are inexplicably neglected in the literature. Despite its relevance, a general and automated approach for UMI detection suitable to gas turbines (GTs) has not been developed yet; as a result, GT diagnosis, prognosis, and control may be challenged since collected data may not reflect the actual operation. To fill this gap, this paper investigates the capability of three supervised machine learning classifiers, i.e., Support Vector Machine, Naïve Bayes, and K-Nearest Neighbors, that are tested by means of challenging analyses to infer general guidelines for UMI detection. Classification accuracy and posterior probability of each classifier is evaluated by means of an experimental dataset derived from a large fleet of Siemens gas turbines in operation. Results reveal that Naïve Bayes is the optimal classifier for UMI detection, since 88.5% of data are correctly labeled with 84% of posterior probability when experimental UMIs affect the dataset. In addition, Naïve Bayes proved to be the most robust classifier also if the rate of UMIs increases.
Estimating X¯ Statistical Control Limits for Any Arbitrary Probability Distribution Using Re-Expressed Truncated Cumulants
Authors: Braden Paul , Matis Timothy , Benneyan James C. , Chen Binchao
Published: March 2022

Shewhart X¯ control charts commonly used for monitoring the mean of a process may be inaccurate or perform poorly when the subgroup size is small or the distribution of the process variable is skewed. Truncated saddlepoint distributions can increase the accuracy of estimated control limits by including higher order moments/cumulants in their approximation, yet this distribution may not exist in the lower tail, and thus the lower control limit may not exist. We introduce a novel modification in which some usually truncated higher-order cumulants are re-expressed as functions of lower-order cumulants estimated from data in a manner that ensures the existence of the truncated saddlepoint distribution over the complete domain of the random variable. The accuracy of this approach is tested in cases where the cumulants are assumed either known or estimated from sample data, and demonstrated in a healthcare application.
Utilizing a Long Short-Term Memory Algorithm Modified by Dwarf Mongoose Optimization to Predict Thermal Expansion of Cu-Al2O3 Nanocomposites
Authors: Sadoun Ayman M. , Najjar Ismail R. , Alsoruji Ghazi S. , Wagih Ahmed , Abd Elaziz Mohamed
Published: March 2022

This paper presents a machine learning model to predict the effect of Al2O3 nanoparticle content on the coefficient of thermal expansion in Cu-Al2O3 nanocomposites prepared using an in situ chemical technique. The model developed is a modification of Long Short-Term Memory (LSTM) using dwarf mongoose optimization (DMO), which mimics the behavior of DMO to find its food for predicting the behavior of the composite. The swarm of DMO consists of three groups, namely the alpha group, scouts, and babysitters. Each group has its own behavior to capture the food. The preparation of the nanocomposite was performed using aluminum nitrate that was added to a solution containing scattered copper nitrate. After that, the powders of CuO and Al2O3 were obtained, and the leftover liquid was removed using thermal treatment at 850 °C for 1 h. The powders were consolidated using compaction and sintering processes. The impact of Al2O3 contents on the thermal properties of the Cu-Al2O3 nanocomposite was investigated. The results showed that the Thermal Expansion Coefficient (TEC) decreases with increasing Al2O3 content due to the increased precipitation of Al2O3 nanoparticles at the grain boundaries of the Cu matrix. Moreover, the good interfacial bonding between Al2O3 and the Cu may participate in this decrease in TEC. The proposed machine learning model was able to predict the TEC of all the produced composites with different Al2O3 content and was tested at different temperatures with very good accuracy, reaching 99%.
Analytical Model for Concentration (Pressure) Impedance of a Low-Pt PEM Fuel Cell Oxygen Electrode
Authors: Kulikovsky Andrei
Published: March 2022

In this study, a model for concentration/pressure impedance ζ of the cathode catalyst layer of a low-Pt PEM fuel cell is developed. The model is based on transient oxygen mass transport equations through the cathode catalyst layer modeled as a single pore with a thin Nafion film covering the pore surface. This structure is used to simulate oxygen transport through the catalyst layer depth and through the ionomer film covering Pt/C agglomerates in low-Pt cells. Analytical solution for zeta-impedance at high cell current is derived; this solution can be used for fast fitting of experimental zeta-spectra. Optimal conditions for measuring the zeta-spectra of a low-Pt cell are discussed. Zeta impedance is not affected by faradaic processes in the cell, which makes this technique a useful alternative to standard EIS.
Homochiral Metal-Organic Framework Based Mixed Matrix Membrane for Chiral Resolution
Authors: Choi Hwa-Jin , Koh Dong-Yeun
Published: March 2022

Efficient separation of enantiomers is critical in the chemical, pharmaceutical, and food industries. However, conventional separation methods, such as chromatography, crystallization, and enzymatic kinetic resolution, require high energy costs and specific reaction conditions for the efficient purification of one enantiomer. In contrast, membrane-based processes are continuous processes performed with less energy than conventional separation processes. Enantioselective polymer membranes have been developed for the chiral resolution of pharmaceuticals; however, it is difficult to generate sufficient enantiomeric excess (ee) with polymer membranes. In this work, a homochiral filler of L-His-ZIF-8 was synthesized by the ligand substitution method and mixed with polyamide(imide) (i.e., Torlon®) to fabricate an enantioselective mixed-matrix membrane (MMM). The enantio-selective separation of R-1-phenylethanol over S-1-phenylethanol was demonstrated with a 25 wt% loaded L-His-ZIF-8/Torlon® MMM in an organic solvent nanofiltration (OSN) mode.
Application of Machine Learning Solutions to Optimize Parameter Prediction to Enhance Automatic NMR Metabolite Profiling
Authors: Cañueto Daniel , Salek Reza M. , Bulló Mònica , Correig Xavier , Cañellas Nicolau
Published: March 2022

The quality of automatic metabolite profiling in NMR datasets from complex matrices can be affected by the numerous sources of variability. These sources, as well as the presence of multiple low-intensity signals, cause uncertainty in the metabolite signal parameters. Lineshape fitting approaches often produce suboptimal resolutions to adapt them in a complex spectrum lineshape. As a result, the use of software tools for automatic profiling tends to be restricted to specific biological matrices and/or sample preparation protocols to obtain reliable results. However, the analysis and modelling of the signal parameters collected during initial iteration can be further optimized to reduce uncertainty by generating narrow and accurate predictions of the expected signal parameters. In this study, we show that, thanks to the predictions generated, better profiling quality indicators can be outputted, and the performance of automatic profiling can be maximized. Our proposed workflow can learn and model the sample properties; therefore, restrictions in the biological matrix, or sample preparation protocol, and limitations of lineshape fitting approaches can be overcome.
Characterisation of Waterborne Psychrophilic Massilia Isolates with Violacein Production and Description of Massilia antarctica sp. nov.
Authors: Sedláček Ivo , Holochová Pavla , Busse Hans-Jürgen , Koublová Vendula , Králová Stanislava , Švec Pavel , Sobotka Roman , Staňková Eva , Pilný Jan , Šedo Ondrej , Smolíková Jana , Sedlář Karel
Published: March 2022

A group of seven bacterial strains producing blue-purple pigmented colonies on R2A agar was isolated from freshwater samples collected in a deglaciated part of James Ross Island and Eagle Island, Antarctica, from 2017–2019. The isolates were psychrophilic, oligotrophic, resistant to chloramphenicol, and exhibited strong hydrolytic activities. To clarify the taxonomic position of these isolates, a polyphasic taxonomic approach was applied based on sequencing of the 16S rRNA, gyrB and lepA genes, whole-genome sequencing, rep-PCR, MALDI-TOF MS, chemotaxonomy analyses and biotyping. Phylogenetic analysis of the 16S rRNA gene sequences revealed that the entire group are representatives of the genus Massilia. The closest relatives of the reference strain P8398T were Massilia atriviolacea, Massilia violaceinigra, Massilia rubra, Massilia mucilaginosa, Massilia aquatica, Massilia frigida, Massilia glaciei and Massilia eurypsychrophila with a pairwise similarity of 98.6–100% in the 16S rRNA. The subsequent gyrB and lepA sequencing results showed the novelty of the analysed group, and the average nucleotide identity and digital DNA–DNA hybridisation values clearly proved that P8398T represents a distinct Massilia species. After all these results, we nominate a new species with the proposed name Massilia antarctica sp. nov. The type strain is P8398T (= CCM 8941T = LMG 32108T).
Associations between Sociodemographic Factors, Lifestyle Behaviors, Pregnancy-Related Determinants, and Mediterranean Diet Adherence among Pregnant Women: The GESTAFIT Project
Authors: Flor-Alemany Marta , Nestares Teresa , Jiménez Nuria Marín , Baena-García Laura , Aparicio Virginia A.
Published: March 2022

We examined sociodemographic factors, lifestyle behaviors, and pregnancy-related determinants associated with adherence to the Mediterranean diet (MD) during pregnancy. A total of 152 Caucasian pregnant women were included in this cross-sectional study. Dietary habits and MD adherence were assessed with a food frequency questionnaire. Physical activity (PA) levels and physical fitness (PF) components (cardiorespiratory fitness, relative muscle strength, and flexibility) were objectively measured. A clustered overall PF index was calculated. Participants with a high MD adherence were older, had a lower body mass index (BMI), spent more time in moderate–vigorous PA, had a greater overall PF, cardiorespiratory fitness, and relative muscle strength compared to participants with low MD adherence (all, p < 0.05). When we explored factors associated with improved MD adherence with logistic regression analysis, we found that the following factors: lower pre-pregnancy BMI (OR = 2.337; p = 0.026), meeting PA recommendations (OR = 2.377; p = 0.045), higher relative muscle strength (OR = 2.265; p = 0.016), and higher overall PF (OR = 5.202; p = 0.004) increased the chances to adhere to the MD. Older age, lower BMI, greater PF, and meeting PA recommendations were associated with higher MD adherence. These factors should be considered for a better design of educational programs and guidelines focused on improving materno–fetal health status during pregnancy.
Role of Beta-Carotene in Lung Cancer Primary Chemoprevention: A Systematic Review with Meta-Analysis and Meta-Regression
Authors: Kordiak Jacek , Bielec Filip , Jabłoński Sławomir , Pastuszak-Lewandoska Dorota
Published: March 2022

Lung cancer is one of the most common neoplasms globally, with about 2.2 million new cases and 1.8 million deaths annually. Although the most important factor in reducing lung cancer risk is lifestyle change, most patients favour the use of supplements, for example, rather than quitting smoking or following a healthy diet. To better understand the efficacy of such interventions, a systematic review was performed of data from randomized controlled trials concerning the influence of beta-carotene supplementation on lung cancer risk in subjects with no lung cancer before the intervention. The search corpus comprised a number of databases and eight studies involving 167,141 participants, published by November 2021. The findings indicate that beta-carotene supplementation was associated with an increased risk of lung cancer (RR = 1.16, 95% CI = 1.06–1.26). This effect was even more noticeable among smokers and asbestos workers (RR = 1.21, 95% CI = 1.08–1.35) and non-medics (RR = 1.18, 95% CI = 1.07–1.29). A meta-regression found no relationship between the beta-carotene supplementation dose and the size of the negative effect associated with lung cancer risk. Our findings indicate that beta-carotene supplementation has no effect on lung cancer risk. Moreover, when used as the primary chemoprevention, beta-carotene may, in fact, increase the risk of lung cancer.
Both Neisseria gonorrhoeae and Neisseria sicca Induce Cytokine Secretion by Infected Human Cells, but Only Neisseria gonorrhoeae Upregulates the Expression of Long Non-Coding RNAs
Authors: Płaczkiewicz Jagoda , Adamczyk-Popławska Monika , Kozłowska Ewa , Kwiatek Agnieszka
Published: March 2022

Bacteria of the Neisseria genus are Gram-negative diplococci including both pathogenic and commensal species. We focused on pathogenic Neisseria gonorrhoeae and commensal Neisseria sicca. We have demonstrated that not only N. gonorrhoeae, but also N. sicca induce the secretion of pro-inflammatory cytokines IL-6, TNF-α, and chemokines CXCL8 and CCL20 by infected epithelial cells. However, N. sicca triggers a lesser effect than does N. gonorrhoeae. Furthermore, N. gonorrhoeae and N. sicca invoke distinct effects on the expression of genes (JUNB, FOSB, NFKB1, NFKBIA) encoding protein components of AP-1 and NF-κB transcription factors. We have also shown that the infection of epithelial cells by N. gonorrhoeae leads to significant overexpression of the long non-coding RNAs (lncRNAs), including MALAT1, ERICD, and RP11-510N19.5. This effect was not identified for N. sicca. In conclusion, data on the expression of lncRNAs and cytokine secretion in response to Neisseria spp. exposure indicate new directions for research on Neisseria-host interactions and can provide further insights into virulence of not only pathogenic, but also commensal Neisseria spp.
Depression and Autoimmune Hypothyroidism—Their Relationship and the Effects of Treating Psychiatric and Thyroid Disorders on Changes in Clinical and Biochemical Parameters Including BDNF and Other Cytokines—A Systematic Review
Authors: Kotkowska Zofia , Strzelecki Dominik
Published: March 2022

Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukins (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), and brain derived neurotrophic factor (BDNF). Disclosure of the relationship between the coexistence of depression and AHT indicates that the pathomechanism of depression may be related to the changes in the immune system, it is also possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly supported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid autoantibodies, and cytokine profile, which could bring us closer to understanding the interrelationships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psychiatric. We consider the above issues to be insufficiently investigated but of great importance. This article is an overview of the available literature as well as an introduction to our research project.
Encapsulation of Alpha-Lipoic Acid in Functional Hybrid Liposomes: Promising Tool for the Reduction of Cisplatin-Induced Ototoxicity
Authors: Curcio Manuela , Cirillo Giuseppe , Amato Rosario , Guidotti Lorenzo , Amantea Diana , De Luca Michele , Nicoletta Fiore Pasquale , Iemma Francesca , Garcia-Gil Mercedes
Published: March 2022

In this study, in order to address the drawback of cisplatin (CDDP)-induced ototoxicity, we propose a straightforward strategy based on the delivery of a sulfur-based antioxidant, such as lipoic acid (LA), to HEI-OC1 cells. To this aim, hybrid liposomes (LA@PCGC) with a spherical shape and a mean diameter of 25 nm were obtained by direct sonication of LA, phosphatidylcholine and a gelatin-curcumin conjugate in a physiological buffer. LA@PCGC were found to be stable over time, were quickly (i.e., by 1 h) taken up by HEI-OC1 cells, and guaranteed strong retention of the bioactive molecule, since LA release was less than 20%, even after 100 h. Cell viability studies showed the efficiency of LA@PCGC for stabilizing the protective activity of LA. Curcumin residues within the functional liposomes were indeed able to maintain the biological activity of LA, significantly improving (up to 2.19-fold) the viability of HEI-OC1 cells treated with 5 μM CDDP. Finally, LA@PCGC was incorporated within an alginate-based injectable hydrogel carrier to create a formulation with physical chemical features suitable for potential ear applications.
Natural Phaeosphaeride A Derivatives Overcome Drug Resistance of Tumor Cells and Modulate Signaling Pathways
Authors: Abzianidze Victoria , Moiseeva Natalia , Suponina Diana , Zakharenkova Sofya , Rogovskaya Nadezhda , Laletina Lidia , Holder Alvin A. , Krivorotov Denis , Bogachenkov Alexander , Garabadzhiu Alexander , Ukolov Anton , Kosorukov Vyacheslav
Published: March 2022

In the present study, natural phaeosphaeride A (PPA) derivatives are synthesized. Anti-tumor studies are carried out on the PC3, K562, HCT-116, THP-1, MCF-7, A549, NCI-H929, Jurkat, and RPMI8226 tumor cell lines, and on the human embryonic kidney (HEK293) cell line. All the compounds synthesized turned out to have better efficacy than PPA towards the tumor cell lines listed. Among them, three compounds exhibited an ability to overcome the drug resistance of tumor cells associated with the overexpression of the P-glycoprotein by modulating the work of this transporter. Luminex xMAP technology was used to assess the effect of five synthesized compounds on the activation of intracellular kinase cascades in A431 cells. MILLIPLEX MAP Multi-Pathway Magnetic Bead 9-Plex was used, which allowed for the simultaneous detection of the following nine phosphorylated protein markers of the main intracellular signaling pathways: a universal transcription factor that controls the expression of immune-response genes, apoptosis and cell cycle NFκB (pS536); cAMP-dependent transcription factor (CREB (pS133); mitogen-activated kinase p38 (pT180/pY182); stress-activated protein kinase JNK (pT183/pY185); ribosomal SK; transcription factors STAT3 (pS727) and STAT5A/B (pY694/699); protein kinase B (Akt) (pS473); and kinase regulated by extracellular signals ERK1/2 (pT185/pY187). The effect of various concentrations of PPA derivatives on the cell culture was studied using xCelligence RTCA equipment. The compounds were found to modulate JNK, ERK1/2, and p38 signaling pathways. The set of activated kinase cascades suggests that oxidative stress is the main probable mechanism of the toxic action of PPA derivatives.
Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects
Authors: Gao Lifang , Zhang Shuang-Qing
Published: March 2022

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis.
Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction
Authors: Ribeiro Viviana P. , Costa João B. , Carneiro Sofia M. , Pina Sandra , Veloso Ana C. A. , Reis Rui L. , Oliveira Joaquim M.
Published: March 2022

Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) hydrogels containing ZnSr-doped β-tricalcium phosphate (ZnSr-β-TCP) particles, as promising bone tunnel fillers to be used in ACL grafts (ACLGs) implantation. For comparative purposes, plain HRP-cross-linked SF hydrogels (PTGs) were fabricated. Sonication and freeze-drying methodologies capable of inducing crystalline β-sheet conformation were carried out to produce both the CTGs and PTGs. A homogeneous microstructure was achieved from microporous to nanoporous scales. The mechanical properties were dependent on the inorganic powder’s incorporation, with a superior tensile modulus observed on the CTGs (12.05 ± 1.03 MPa) as compared to the PTGs (5.30 ± 0.93 MPa). The CTGs presented adequate swelling properties to fill the space in the bone structure after bone tunnel enlargement and provide a stable degradation profile under low concentration of protease XIV. The in vitro studies revealed that SaOs-2 cells adhered, proliferated and remained viable when cultured into the CTGs. In addition, the bioactive CTGs supported the osteogenic activity of cells in terms of alkaline phosphatase (ALP) production, activity, and relative gene expression of osteogenic-related markers. Therefore, this study is the first evidence that the developed CTGs hold adequate structural, chemical, and biological properties to be used as bone tunnel fillers capable of connecting to the ACL tissue while stimulating bone tissue regeneration for a faster osteointegration.
Mucin-Protected Caco-2 Assay to Study Drug Permeation in the Presence of Complex Biorelevant Media
Authors: Ye Dong , López Mármol Álvaro , Lenz Verena , Muschong Patricia , Wilhelm-Alkubaisi Anita , Weinheimer Manuel , Koziolek Mirko , Sauer Kerstin A. , Laplanche Loic , Mezler Mario
Published: March 2022

The poor solubility and permeability of compounds beyond Lipinski’s Rule of Five (bRo5) are major challenges for cell-based permeability assays. Due to their incompatibility with gastrointestinal components in biorelevant media, the exploration of important questions addressing food effects is limited. Thus, we established a robust mucin-protected Caco-2 assay to allow the assessment of drug permeation in complex biorelevant media. To do that, the assay conditions were first optimized with dependence of the concentration of porcine mucin added to the cells. Mucin-specific effects on drug permeability were evaluated by analyzing cell permeability values for 15 reference drugs (BCS class I–IV). Secondly, a sigmoidal relationship between mucin-dependent permeability and fraction absorbed in human (fa) was established. A case study with venetoclax (BCS class IV) was performed to investigate the impact of medium complexity and the prandial state on drug permeation. Luminal fluids obtained from the tiny-TIM system showed a higher solubilization capacity for venetoclax, and a better read-out for the drug permeability, as compared to FaSSIF or FeSSIF media. In conclusion, the mucin-protected Caco-2 assay combined with biorelevant media improves the mechanistic understanding of drug permeation and addresses complex biopharmaceutical questions, such as food effects on oral drug absorption.
Activation of the VQ Motif-Containing Protein Gene VQ28 Compromised Nonhost Resistance of Arabidopsis thaliana to Phytophthora Pathogens
Authors: Lan Xingjie , Wang Xiaoxia , Tao Quandan , Zhang Haotian , Li Jinyang , Meng Yuling , Shan Weixing
Published: March 2022

Nonhost resistance refers to resistance of a plant species to all genetic variants of a non-adapted pathogen. Such resistance has the potential to become broad-spectrum and durable crop disease resistance. We previously employed Arabidopsis thaliana and a forward genetics approach to identify plant mutants susceptible to the nonhost pathogen Phytophthora sojae, which resulted in identification of the T-DNA insertion mutant esp1 (enhanced susceptibility to Phytophthora). In this study, we report the identification of VQ motif-containing protein 28 (VQ28), whose expression was highly up-regulated in the mutant esp1. Stable transgenic A. thaliana plants constitutively overexpressing VQ28 compromised nonhost resistance (NHR) against P. sojae and P. infestans, and supported increased infection of P. parasitica. Transcriptomic analysis showed that overexpression of VQ28 resulted in six differentially expressed genes (DEGs) that are involved in the response to abscisic acid (ABA). High performance liquid chromatography-mass spectrometry (HPLC-MS) detection showed that the contents of endogenous ABA, salicylic acid (SA), and jasmonate (JA) were enriched in VQ28 overexpression lines. These findings suggest that overexpression of VQ28 may lead to an imbalance in plant hormone homeostasis. Furthermore, transient overexpression of VQ28 in Nicotiana benthamiana rendered plants more susceptible to Phytophthora pathogens. Deletion mutant analysis showed that the C-terminus and VQ-motif were essential for plant susceptibility. Taken together, our results suggest that VQ28 negatively regulates plant NHR to Phytophthora pathogens.
In Vitro Oxidative Stress Threatening Maize Pollen Germination and Cytosolic Ca2+ Can Be Mitigated by Extracts of Emmer Wheatgrass Biofortified with Selenium
Authors: Del Pino Alberto Marco , Falcinelli Beatrice , D’Amato Roberto , Businelli Daniela , Benincasa Paolo , Palmerini Carlo Alberto
Published: March 2022

In this work, we studied the effects of in vitro oxidative stress applied by H2O2 to maize pollen germination and cytosolic Ca2+, taken as an experimental model to test the biological activity of extracts of emmer (Triticum turgidum L. spp. dicoccum (Schrank ex Shubler) Thell.) wheatgrass obtained from grains sprouted with distilled water, or salinity (50 mM) or selenium (45 mg L−1 of Na2SeO3). Wheatgrass extracts were obtained in two ways: by direct extraction in methanol, which represented the free phenolic fraction of extracts (Ef), and by residual content after alkaline digestion, which made it possible to obtain extracts with the bound fraction (Eb). Comparative tests on maize pollen were carried out by differently combining H2O2 and either wheatgrass extracts or pure phenolic acids (4-HO benzoic, caffeic, p-coumaric and salicylic). The cytosolic Ca2+ of maize pollen was influenced by either H2O2 or pure phenolic acids or Ef, but not by Eb. The negative effect of H2O2 on maize pollen germination and cytosolic Ca2+ was mitigated by Ef and, slightly, by Eb. The extent of the biological response of Ef depended on the sprouting conditions (i.e., distilled water, salinity or selenium). The extracts of Se-biofortified wheatgrass were the most effective in counteracting the oxidative stress.
Metabolic Diversity of Flavonoids and Antioxidant Potential for Characterization of Underutilized Citrus Species for Nutritional Security
Authors: Kumar Dinesh , Ladaniya Milind Shivratan , Gurjar Manju , Kumar Sunil , Mendke Sachin
Published: March 2022

Citrus fruits are grown commercially throughout the world. They are widely consumed due to their nutrients, use in energy supplements, and numerous health benefits. There is significant interest among consumers about this naturally available source, rich in flavonoids and antioxidants. However, underutilized citrus varieties remain unexplored due to the lack of information about the pool of nutritive properties they confer. Ten underutilized citrus varieties were collected from Nokrek Biosphere Reserve, West Garo Hills, Meghalaya, India, identified by UNESCO as a Biosphere reserve, to study the diversity in terms of limonin, ascorbic acid, carotenoids, browning, flavonoids, total phenol, and antioxidant activity, the contents of which varied significantly among different citrus cultivars. The results indicated that Citron and Pomelo were good sources of ascorbic acid (29.50 and 45.09 mg/100 mL), and that Khasi papeda was found to contain lower limonin content (9.21 ppm). However, in terms of flavonoids, Khasi papeda and Pomelo were found to exhibit a higher naringin content (189.13 ppm and 32.15 ppm), whereas the hesperidin content was highest in Kachai lemon, Khasi papeda, and Chinotto, at 199.51 ppm, 148.04 ppm, and 135.88 ppm, respectively. Antioxidant activity was assessed by three antioxidant assays (ABTS+ (radical cation azino-bis [3-ethylbenzthiazoline-6-sulfonic acid]) (ABTS), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), and Ferric Reducing Antioxidant Power (FRAP)). Khasi papeda (7.48 mM L−1 Trolox), Chinotto (7.48 mM L−1 Trolox), and Pomelo (7.48 mM L−1 Trolox) exhibited the highest reducing power with DPPH radical scavenging activity, and Khasi papeda (15.41 mg GAE L−1) possessed a higher phenolic content, whereas the antioxidant activity when assessed with ABTS and FRAP assays was highest among the underutilized species of Khasi papeda (4.84 mM L−1 Trolox, 1.93 mM L−1 Trolox) and Ada Jamir (4.96 mM L−1 Trolox, 2.03 mM L−1 Trolox), respectively. To the best of our knowledge, this is among the very few papers presenting comprehensive data on the metabolic diversity of flavonoids and antioxidant potential to characterize the underutilized citrus species. This study also demonstrated that Khasi papeda, Pomelo, Chinotto, and Kachai lemon can serve as potential sources of functional components, bioactive compounds, and antioxidants, which can be explored for further application in the processing industry for nutritional security.
Volatiles from Cotton Plants Infested by Agrotis segetum (Lep.: Noctuidae) Attract the Larval Parasitoid Microplitis mediator (Hym.: Braconidae)
Authors: Li Mengyu , Xia Shike , Zhang Tao , Williams Livy , Xiao Haijun , Lu Yanhui
Published: March 2022

Herbivore-induced plant volatiles (HIPVs), chemicals produced by plants infested by herbivorous insects, can act as kairomones that recruit natural enemies of the pest herbivore. Agrotis segetum (Denis and Schiffermüller) is a common, important pest of seedling cotton in Xinjiang Province, China, and the braconid Microplitis mediator (Haliday) is an important mortality factor of this pest’s larvae. In olfactometer tests, which included healthy foliage, infested foliage, or infested roots, M. mediator preferred A. segetum-infested cotton plants to healthy cotton plants. In GC-MS analyses of plant-emitted volatiles, we found that compounds emitted increased 14.9- and 13.3- fold after leaf infestation and root infestation, respectively, compared to healthy control plants. The volatiles were mainly p-xylene, nonanal, tetradecane, decanal, benzaldehyde, β-caryophyllene, and humulene, while linalool was only present in the leaf-infestation treatment. In addition, principal component analysis indicated that all 18 compounds were associated with the infested plants, especially β-caryophyllene, p-xylene, and decanal. Based on the above studies and previous functional evaluations of the volatile compounds, it can be demonstrated that these compounds play a crucial role in modulating the interactions between A. segetum and M. mediator and regulating parasitoid behavior. It may be possible to enhance the biological control of A. segetum by M. mediator through the application of HIPVs.
The Effect of Drying Methods and Extraction Techniques on Oleuropein Content in Olive Leaves
Authors: Cör Andrejč Darija , Butinar Bojan , Knez Željko , Tomažič Kaja , Knez Marevci Maša
Published: March 2022

Increased demand for olive oil has caused higher quantities of byproducts in olive processing, such as olive leaves, olive skins, and vegetation water. It is well known that olive leaves contain several phenolic compounds, including secoiridoids. Oleuropein is the major secoiridoid in olive leaves. Oleuropein has been found to exhibit antioxidative, antimicrobial, antiviral, and antiatherogenic activities. We studied the effect of extraction techniques and drying methods on oleuropein content in olive leaves of Istrska belica and Lecino cultivar. Three different procedures of drying were used: at room temperature, at 105 °C, and freeze drying. Ethanol-modified supercritical extraction with carbon dioxide, conventional methanol extraction, and ultrasonic extraction with deep eutectic solvent were performed. Antioxidant activity was determined, as well as methanolic and supercritical extracts. The presence of olive polyphenols was confirmed by the HPLC method.