bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifungal Activity of the Frog Skin Peptide Temporin G and Its Effect on Candida albicans Virulence Factors
Authors: D’Auria Felicia Diodata , Casciaro Bruno , De Angelis Marta , Marcocci Maria Elena , Palamara Anna Teresa , Nencioni Lucia , Mangoni Maria Luisa
Published: June 2022

The increasing resistance to conventional antifungal drugs is a widespread concern, and a search for new compounds, active against different species of fungi, is demanded. Antimicrobial peptides (AMPs) hold promises in this context. Here we investigated the activity of the frog skin AMP Temporin G (TG) against a panel of fungal strains, by following the Clinical and Laboratory Standards Institute protocols. TG resulted to be active against (i) Candida species and Cryptococcus neoformans, with MIC50 between 4 µM and 64 µM after 24 h of incubation; (ii) dermatophytes with MIC80 ranging from 4 to 32 µM, and (iii) Aspergillus strains with MIC80 of 128 µM. In addition, our tests revealed that TG reduced the metabolic activity of Candida albicans cells, with moderate membrane perturbation, as proven by XTT and Sytox Green assays, respectively. Furthermore, TG was found to be effective against some C. albicans virulence factors; indeed, at 64 µM it was able to inhibit ~90% of yeast–mycelial switching, strongly prevented biofilm formation, and led to a 50% reduction of metabolic activity in mature biofilm cells, and ~30–35% eradication of mature biofilm biomass. Even though further studies are needed to deepen our knowledge of the mechanisms of TG antifungal activity, our results suggest this AMP as an attractive lead compound for treatment of fungal diseases.
Impact of N-Terminal Tags on De Novo Vimentin Intermediate Filament Assembly
Authors: Usman Saima , Aldehlawi Hebah , Nguyen Thuan Khanh Ngoc , Teh Muy-Teck , Waseem Ahmad
Published: June 2022

Vimentin, a type III intermediate filament protein, is found in most cells along with microfilaments and microtubules. It has been shown that the head domain folds back to associate with the rod domain and this association is essential for filament assembly. The N-terminally tagged vimentin has been widely used to label the cytoskeleton in live cell imaging. Although there is previous evidence that EGFP tagged vimentin fails to form filaments but is able to integrate into a pre-existing network, no study has systematically investigated or established a molecular basis for this observation. To determine whether a tag would affect de novo filament assembly, we used vimentin fused at the N-terminus with two different sized tags, AcGFP (239 residues, 27 kDa) and 3 × FLAG (22 residues; 2.4 kDa) to assemble into filaments in two vimentin-deficient epithelial cells, MCF-7 and A431. We showed that regardless of tag size, N-terminally tagged vimentin aggregated into globules with a significant proportion co-aligning with β-catenin at cell–cell junctions. However, the tagged vimentin aggregates could form filaments upon adding untagged vimentin at a ratio of 1:1 or when introduced into cells containing pre-existing filaments. The resultant filament network containing a mixture of tagged and untagged vimentin was less stable compared to that formed by only untagged vimentin. The data suggest that placing a tag at the N-terminus may create steric hinderance in case of a large tag (AcGFP) or electrostatic repulsion in case of highly charged tag (3 × FLAG) perhaps inducing a conformational change, which deleteriously affects the association between head and rod domains. Taken together our results shows that a free N-terminus is essential for filament assembly as N-terminally tagged vimentin is not only incapable of forming filaments, but it also destabilises when integrated into a pre-existing network.
Anti-Growth, Anti-Angiogenic, and Pro-Apoptotic Effects by CX-4945, an Inhibitor of Casein Kinase 2, on HuCCT-1 Human Cholangiocarcinoma Cells via Control of Caspase-9/3, DR-4, STAT-3/STAT-5, Mcl-1, eIF-2α, and HIF-1α
Authors: Wang Saini , Yadav Anil Kumar , Han Jin-Yi , Ahn Keun Soo , Jang Byeong-Churl
Published: June 2022

Overexpression of casein kinase 2 (CK2) has an oncogenic and pro-survival role in many cancers. CX-4945 (Silmitasertib) is a CK2 inhibitor with anti-cancerous and anti-angiogenic effects. Up to date, the anti-cancer effect and mechanism of CX-4945 on human cholangiocarcinoma (CCA) remain unclear. This study investigated whether CX-4945 inhibits growth and induces apoptosis of HuCCT-1 cells, a human CCA cell line. Of note, treatment with CX-4945 at 20 μM markedly reduced survival and induced apoptosis of HuCCT-1 cells, as evidenced by nuclear DNA fragmentation, PARP cleavage, activation of caspase-9/3, and up-regulation of DR-4. Although CX-4945 did not affect the phosphorylation and expression of CK2, it vastly inhibited the phosphorylation of CK2 substrates, supporting the drug’s efficacy in inhibiting CK2 and its downstream pathway. Importantly, knockdown of CK2 that partially suppressed the phosphorylation of CK2 substrates resulted in a significant reduction of HuCCT-1 cell survival. In addition, CX-4945 reduced the phosphorylation and expression of STAT-3 and STAT-5 in HuCCT-1 cells, and pharmacological inhibition or respective knockdown of these proteins resulted in significant growth suppression of HuCCT-1 cells. CX-4945 also had abilities to decrease Mcl-1 expression while increasing eIF-2α phosphorylation in HuCCT-1 cells. Furthermore, there was a time-differential negative regulation of HIF-1α expression by CX-4945 in HuCCT-1 cells, and knockdown of HIF-1α caused a significant reduction of the cell survival. In summary, these results demonstrated that CX-4945 has anti-growth, anti-angiogenic, and pro-apoptotic effects on HuCCT-1 cells, which are mediated through control of CK2, caspase-9/3, DR-4, STAT-3/5, Mcl-1, eIF-2α, and HIF-1α.
Artemisinin Attenuates Amyloid-Induced Brain Inflammation and Memory Impairments by Modulating TLR4/NF-κB Signaling
Authors: Zhao Xia , Huang Xiaosu , Yang Chao , Jiang Yizhou , Zhou Wenshu , Zheng Wenhua
Published: June 2022

The abnormal immune response is an early change in the pathogenesis of Alzheimer’s disease (AD). Microglial activation is a crucial regulator of the immune response, which contributes to progressive neuronal injury by releasing neurotoxic products. Therefore, finding effective drugs to regulate microglial homeostasis and neuroinflammation has become a new AD treatment strategy. Artemisinin has potent anti-inflammatory and immune activities. However, it is unclear whether Artemisinin contributes to the regulation of microglial activation, thereby improving AD pathology. This study found that Artemisinin significantly reduced amyloid beta-peptide 1–42 (Aβ1–42)-induced increases in nitric oxide and reactive oxygen species and inflammatory factors in BV2 cells. In addition, Artemisinin inhibited the migration of microglia and prevented the expansion of the inflammatory cascade. The mechanical studies showed Artemisinin inhibited neuroinflammation and exerted neuroprotective effects by regulating the Toll-like receptor 4 (TLR4)/Nuclear factor-kappa B (NF-κB) signaling pathway. Similar results were obtained in AD model mice, in which Artemisinin administration attenuated Aβ1–42-induced neuroinflammation and neuronal injury, reversing spatial learning and memory deficits. The anti-inflammatory effect of Artemisinin is also accompanied by the activation of the TLR4/NF-κB signaling pathway in the animal model. Our results indicate that Artemisinin attenuated Aβ1–42-induced neuroinflammation and neuronal injury by stimulating the TLR4/NF-κB signaling pathway. These findings suggest that Artemisinin is a potential therapeutic agent for AD.
Bis(μ-iodo)-tetrakis(O-methyl N-phenylthiocarbamate)-tetraiodo-dibismuth
Authors: Arar Wafa , Khatyr Abderrahim , Knorr Michael , Strohmann Carsten , Schmidt Annika
Published: June 2022

In order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, BiI3 was reacted with two equivalents of MeOC(=S)N(H)Ph in MeCN solution to afford the dinuclear title compound complexes [{I2Bi(μ2-I)2BiI2}{κ1-MeOC(=S)N(H)Ph}4] 1. Compound 1 was characterized by IR, UV and NMR spectroscopy, the formation of a dinuclear framework is ascertained by a single-crystal X-ray diffraction study performed at 100 K.
Chemical Composition and Related Properties of Lime (Tilia cordata Mill.) Bark and Wood as Affected by Tree Growth Conditions
Authors: Kusiak Władysław , Majka Jerzy , Zborowska Magdalena , Ratajczak Izabela
Published: June 2022

Tilia cordata Mill. is a favourite tree used in urban spaces. For this reason, it is important to know its sensitivity to environmental stress, which is particularly burdensome for vegetation in urban spaces. The aim of the study was to investigate the properties necessary to control the growth of these trees and their subsequent use, i.e., chemical properties (percentage contents of cellulose, holocellulose, lignin, pentosans and substances soluble in NaOH and EtOH) as well as the chemical elements (K, Na, Mg, Ca and Fe, Zn, Cu, Pb, Cd, B, Ni, Cr, Al, As and Hg) and selected hygroscopic properties (hysteresis and sorption isotherms). Trees of Tilia cordata Mill. growing in environments exposed to environmental stress of varying severity were examined. Regardless of the growth conditions, in terms of its chemical composition, bark differs significantly from wood, showing twice the contents of soluble substances in NaOH and lignin and half the content of polysaccharides. Growth conditions clearly affect the range of selected chemical components in bark, e.g., substances soluble in ethanol, cellulose, or lignin. The main inorganic elements in bark and wood are Na, K, Ca, Mg and Zn. In bark, a relationship was found between the content of most chemical elements and differing environmental growth conditions. It was shown that environmental stress influenced the hygroscopic properties of wood and bark, which are a consequence of the percentage of chemical components.
Stability Results of Quadratic-Additive Functional Equation Based on Hyers Technique in Matrix Paranormed Spaces
Authors: Tamilvanan Kandhasamy , Almalki Yahya , Mohiuddine Syed Abdul , Agarwal Ravi P.
Published: June 2022

In this work, we introduce a mixed type of quadratic-additive (QA) functional equation and obtain its general solution. The objective of this work is to investigate the Ulam–Hyers stability of this quadratic-additive (QA) functional equation in matrix paranormed spaces (briefly, MP spaces) using the Hyers method for the factor sum of norms.
Wind Speed Prediction via Collaborative Filtering on Virtual Edge Expanding Graphs
Authors: Ying Xiang , Zhao Keke , Liu Zhiqiang , Gao Jie , He Dongxiao , Li Xuewei , Xiong Wei
Published: June 2022

Accurate and stable wind speed prediction is crucial for the safe operation of large-scale wind power grid connections. Existing methods are typically limited to a certain fixed area when learning the information of the wind speed sequence, which cannot make full use of the spatiotemporal correlation of the wind speed sequence. To address this problem, in this paper we propose a new wind speed prediction method based on collaborative filtering against a virtual edge expansion graph structure in which virtual edges enrich the semantics that the graph can express. It is an effective extension of the dataset, connecting wind turbines of different wind farms through virtual edges to ensure that the spatial correlation of wind speed sequences can be effectively learned and utilized. The new collaborative filtering on the graph is reflected in the processing of the wind speed sequence. The wind speed is preprocessed from the perspective of pattern mining to effectively integrate various information, and the k-d tree is used to match the wind speed sequence to achieve the purpose of collaborative filtering. Finally, a model with long short-term memory (LSTM) as the main body is constructed for wind speed prediction. By taking the wind speed of the actual wind farm as the research object, we compare the new approach with four typical wind speed prediction methods. The mean square error is reduced by 16.40%, 11.78%, 9.57%, and 18.36%, respectively, which demonstrates the superiority of the proposed new method.
Symmetric Diffeomorphic Image Registration with Multi-Label Segmentation Masks
Authors: Cai Chenwei , Wang Lvda , Ying Shihui
Published: June 2022

Image registration aims to align two images through a spatial transformation. It plays a significant role in brain imaging analysis. In this research, we propose a symmetric diffeomorphic image registration model based on multi-label segmentation masks to solve the problems in brain MRI registration. We first introduce the similarity metric of the multi-label masks to the energy function, which improves the alignment of the brain region boundaries and the robustness to the noise. Next, we establish the model on the diffeomorphism group through the relaxation method and the inverse consistent constraint. The algorithm is designed through the local linearization and least-squares method. We then give spatially adaptive parameters to coordinate the descent of the energy function in different regions. The results show that our approach, compared with the mainstream methods, has better accuracy and noise resistance, and the transformations are more smooth and more reasonable.
Ćirić-Type Operators and Common Fixed Point Theorems
Authors: Mihiţ Claudia Luminiţa , Moţ Ghiocel , Petruşel Gabriela
Published: June 2022

In the context of a complete metric space, we will consider the common fixed point problem for two self operators. The operators are assumed to satisfy a general contraction type condition inspired by the Ćirić fixed point theorems. Under some appropriate conditions we establish existence, uniqueness and approximation results for the common fixed point. In the same framework, the second problem is to study various stability properties. More precisely, we will obtain sufficient conditions assuring that the common fixed point problem is well-posed and has the Ulam–Hyers stability, as well as the Ostrowski property for the considered problem. Some examples and applications are finally given in order to illustrate the abstract theorems proposed in the first part of the paper. Our results extend and complement some theorems in the recent literature.
Older Adults Get Lost in Virtual Reality: Visuospatial Disorder Detection in Dementia Using a Voting Approach Based on Machine Learning Algorithms
Authors: Bayahya Areej Y. , Alhalabi Wadee , Alamri Sultan H.
Published: June 2022

As the age of an individual progresses, they are prone to more diseases; dementia is one of these age-related diseases. Regarding the detection of dementia, traditional cognitive testing is currently one of the most accurate tests. Nevertheless, it has many disadvantages, e.g., it does not measure the extent of the brain damage and does not take the patient’s intelligence into consideration. In addition, traditional assessment does not measure dementia under real-world conditions and in daily tasks. It is therefore advisable to investigate the newest, more powerful applications that combine cognitive techniques with computerized techniques. Virtual reality worlds are one example, and allow patients to immerse themselves in a controlled environment. This study created the Medical Visuospatial Dementia Test (referred to as the “MVD Test”) as a non-invasive, semi-immersive, and cognitive computerized test. It uses a 3D virtual environment platform based on medical tasks combined with AI algorithms. The objective is to evaluate two cognitive domains: visuospatial assessment and memory assessment. Using multiple machine learning algorithms (MLAs), based on different voting approaches, a 3D system classifies patients into three classes: patients with normal cognition, patients with mild cognitive impairment (MCI), and patients with severe cognitive impairment (dementia). The model with the highest performance was derived from voting approach named Ensemble Vote, where accuracy was 97.22%. Cross-validation accuracy of Extra Tree and Random Forest classifiers, which was greater than 99%, indicated a greater discriminate capacity than that of other classes.
Predictors of Noninvasive Respiratory Support Failure in COVID-19 Patients: A Prospective Observational Study
Authors: Zablockis Rolandas , Šlekytė Goda , Mereškevičienė Rūta , Kėvelaitienė Karolina , Zablockienė Birutė , Danila Edvardas
Published: June 2022

Background and Objective: Respiratory assistance tactic that is best for COVID-19-associated acute hypoxemic respiratory failure (AHRF) individuals has yet to be determined. Patients with AHRF may benefit from the use of a high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The goals of this prospective observational research were to estimate predictive factors for HFNC and NIV failure in COVID-19-related AHRF subjects. Materials and Methods: The research enlisted the participation of 124 patients. A stepwise treatment approach was used. HFNC and NIV were used on 124 (100%) and 64 (51.6%) patients, respectively. Thirty (24.2%) of 124 patients were intubated and received invasive mechanical ventilation. Results: 85 (68.5%) patients were managed successfully. Patients who required NIV exhibited a higher prevalence of treatment failure (70.3% vs. 51.6%, p = 0.019) and had higher mortality (59.4% vs. 31.5%, p = 0.001) than patients who received HFNC. Using logistic regression, the respiratory rate oxygenation (ROX) index at 24 h (odds ratio (OR) = 0.74, p = 0.018) and the Charlson Comorbidity Index (CCI) (OR = 1.60, p = 0.003) were found to be predictors of HFNC efficacy. It was the ROX index at 24 h and the CCI optimum cut-off values for HFNC outcome that were 6.1 (area under the curve (AUC) = 0.73) and 2.5 (AUC = 0.68), respectively. Serum ferritin level (OR = 0.23, p = 0.041) and lymphocyte count (OR = 1.03, p = 0.01) were confirmed as predictors of NIV failure. Serum ferritin level at a cut-off value of 456.2 ng/mL (AUC = 0.67) and lymphocyte count lower than 0.70 per mm3, (AUC = 0.70) were associated with NIV failure with 70.5% sensitivity, 68.7% specificity and sensitivity of 84.1%, specificity of 56.2%, respectively. Conclusion: The ROX index at 24 h, CCI, as well as serum ferritin level, and lymphocyte count can be used as markers for HFNC and NIV failure, respectively, in SARS-CoV-2-induced AHRF patients.
Utilization of Bayesian Optimization and KWN Modeling for Increased Efficiency of Al-Sc Precipitation Strengthening
Authors: Deane Kyle , Yang Yang , Licavoli Joseph J. , Nguyen Vu , Rana Santu , Gupta Sunil , Venkatesh Svetha , Sanders Paul G.
Published: June 2022

The Kampmann and Wagner numerical model was adapted in MATLAB to predict the precipitation and growth of Al3Sc precipitates as a function of starting concentration and heat-treatment steps. This model was then expanded to predict the strengthening in alloys using calculated average precipitate number density, radius, etc. The calibration of this model was achieved with Bayesian optimization, and the model was verified against experimentally gathered hardness data. An analysis of the outputs from this code allowed the development of optimal heat treatments, which were validated experimentally and proven to result in higher final strengths than were previously observed. Bayesian optimization was also used to predict the optimal heat-treatment temperatures in the case of limited heat-treatment times.
Identification of the Parameter Values of the Constitutive and Friction Models in Machining Using EGO Algorithm: Application to Ti6Al4V
Authors: Kugalur Palanisamy Nithyaraaj , Rivière Lorphèvre Edouard , Gobert Maxime , Briffoteaux Guillaume , Tuyttens Daniel , Arrazola Pedro-José , Ducobu François
Published: June 2022

The application of artificial intelligence and increasing high-speed computational performance is still not fully explored in the field of numerical modeling and simulation of machining processes. The efficiency of the numerical model to predict the observables depends on various inputs. The most important and challenging inputs are the material behavior of the work material and the friction conditions during the cutting operation. The parameters of the material model and the friction model have a decisive impact on the simulated results. To reduce the expensive experimentation cost that gives limited data for the parameters, an inverse methodology to identify the parameter values of those inputs is suggested to potentially have data of better quality. This paper introduces a novel approach for the inverse identification of model parameters by implementing the Efficient Global Optimization algorithm. In this work, a method relying on a complete automated Finite Element simulation-based optimization algorithm is implemented to inversely identify the value of the Johnson–Cook (JC) parameters and Coulomb’s friction coefficient correlatively, where the objective function is defined as minimizing the error difference between experimental and numerical results. The Ti6Al4V Grade 5 alloy material is considered as a work material, and the identified parameters sets are validated by comparing the simulated results with experimental results. The developed automation process reduces the computation time and eliminating human errors. The identified model parameters value predicts the cutting force as 169 N/mm (2% deviation from experiments), feed force as 55 N/mm (7% deviation from experiments), and chip thickness as 0.150 mm (11% deviation from experiments). Overall, the identified model parameters set improves the prediction accuracy of the finite element model by 32% compared with the best-identified parameters set in the literature.
Associations of Cord Blood Lipids with Childhood Adiposity at the Age of Three Years: A Prospective Birth Cohort Study
Authors: Ye Qi-Qing , Kong Shao-Min , Yin Xin , Gao Chang , Lu Min-Shan , Ramakrishnan Rema , Guo Cheng , Yao Wang , Zeng Ji-Yuan , Kuang Ya-Shu , Lu Jin-Hua , He Jian-Rong , Qiu Xiu
Published: June 2022

We aimed to examine the associations between cord blood lipids and childhood adiposity and to investigate whether these associations vary across birth weight categories (small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA)) in 1306 infants in the Born in Guangzhou Cohort Study, China. Adiposity outcomes at the age of three years included z-scores of weight-for-length/height (WFLZ), body mass index (BMIZ), subscapular (SSTZ) and triceps skinfold thickness (TSTZ), and the sum of skinfold thicknesses (SSFTZ). Cord blood triglycerides (TG) levels were negatively associated with WFLZ and BMIZ, whereas high density lipoprotein (HDL) levels were positively associated with WFLZ, BMIZ, TSTZ and SSFTZ. These associations were attenuated after adjustment for birth weight. Stratified analyses revealed that total cholesterol (TC) and low-density lipoprotein (LDL) levels were positively associated with childhood adiposity indicators among AGA infants but tended to be negatively associated with the adiposity indicators among LGA infants (p values for interaction <0.05). Furthermore, TG levels appeared to be positively associated with adiposity indicators among SGA infants but negatively associated with the outcomes among LGA infants (p values for interaction <0.05). Cord blood lipids levels might be associated with childhood adiposity, and these associations appear to differ across different birth weight categories. If confirmed in future studies, our findings suggest that individualized management plans might be warranted in preventing obesity.
Structural and Functional Characterization of the Holliday Junction Resolvase RuvC from Deinococcus radiodurans
Authors: Qin Chen , Han Wanchun , Xu Ying , Zhao Ye , Xu Hong , Tian Bing , Wang Liangyan , Hua Yuejin
Published: June 2022

Holliday junctions (HJs) are four-way DNA structures, which are an important intermediate in the process of homologous recombination. In most bacteria, HJs are cleaved by specific nucleases called RuvC resolvases at the end of homologous recombination. Deinococcus radiodurans is an extraordinary radiation-resistant bacterium and is known as an ideal model organism for elucidating DNA repair processes. Here, we described the biochemical properties and the crystal structure of RuvC from D. radiodurans (DrRuvC). DrRuvC exhibited an RNase H fold that belonged to the retroviral integrase family. Among many DNA substrates, DrRuvC specifically bound to HJ DNA and cleaved it. In particular, Mn2+ was the preferred bivalent metal co-factor for HJ cleavage, whereas high concentrations of Mg2+ inhibited the binding of DrRuvC to HJ. In addition, DrRuvC was crystallized and the crystals diffracted to 1.6 Å. The crystal structure of DrRuvC revealed essential amino acid sites for cleavage and binding activities, indicating that DrRuvC was a typical resolvase with a characteristic choice for metal co-factor.
Targeting Persistent Biofilm Infections: Reconsidering the Topography of the Infection Site during Model Selection
Authors: Kolodkin-Gal Ilana , Cohen-Cymberknoh Malena , Zamir Gideon , Tsesis Igor , Rosen Eyal
Published: June 2022

The physiology of an organism in the environment reflects its interactions with the diverse physical, chemical, and biological properties of the surface. These principles come into consideration during model selection to study biofilm–host interactions. Biofilms are communities formed by beneficial and pathogenic bacteria, where cells are held together by a structured extracellular matrix. When biofilms are associated with a host, chemical gradients and their origins become highly relevant. Conventional biofilm laboratory models such as multiwall biofilm models and agar plate models poorly mimic these gradients. In contrast, ex vivo models possess the partial capacity to mimic the conditions of tissue-associated biofilm and a biofilm associated with a mineralized surface enriched in inorganic components, such as the human dentin. This review will highlight the progress achieved using these settings for two models of persistent infections: the infection of the lung tissue by Pseudomonas aeruginosa and the infection of the root canal by Enterococcus faecalis. For both models, we conclude that the limitations of the conventional in vitro systems necessitate a complimentary experimentation with clinically relevant ex vivo models during therapeutics development.
Antifungal Volatilomes Mediated Defense Mechanism against Fusarium oxysporum f. sp. lycopersici, the Incitant of Tomato Wilt
Authors: Thangaraj Praveen , Balamurali Akshaya Subbaih , Subbiah Krishnamoorthy Akkanna , Sevugapperumal Nakkeeran , Gurudevan Thiribhuvanamala , Uthandi Sivakumar , Shanmugam Haripriya
Published: June 2022

In this study, the volatilomes of naturally growing plant leaves were immobilized in a suitable substrate to enhance vapors’ diffusion in the soil to eradicate the Fusarium wilt pathogens in Tomato. Volatilomes produced by Mentha spicata leaves immobilized in vermiculite ball was found to be effective and exhibit 92.35 percent inhibition on the mycelial growth of Fusarium oxysporum f. sp. lycopersici (FOL). Moreover, the volatilomes of M. spicata immobilized vermiculite balls were tested based on the distance traveled by the diffused volatilomes from the ball and revealed that the volatilomes of M. spicata traveled up to 20 cm distance from the center of PVC (Polyvinly chloride) chamber showed maximum reduction in colony growth of FOL at 12th day after inoculation. Tomato plants inoculated with FOL revealed increased expressions of defense gene, pathogenesis related protein (PR1) with 2.63-fold after 72 h and the gene, transcription factor (WRKY) increased with 2.5-fold after 48 h on exposure to the volatilomes of M. spicata vermiculite balls. To the best of our knowledge, this is the first report on development of volatilomes based vermiculite ball formulations. This result indicated that the volatilomes of M. spicata are promising phyto-fumigants for management of Tomato Fusarial wilt.
Mass Defect Filtering-Oriented Identification of Resin Glycosides from Root of Convolvulus scammonia Based on Quadrupole-Orbitrap Mass Spectrometer
Authors: Yin Qiang , Abdulla Rahima , Kahar Gulmira , Aisa Haji Akber , Li Chunting , Xin Xuelei
Published: June 2022

This work aimed to develop and evaluate a post-acquisition data processing strategy, referred to as a mass defect filter (MDF), for rapid target the resin glycosides in root of Convolvulus scammonia by setting mass rang and mass defect range from high-resolution MS data. The full-scan mass data were acquired by high-performance liquid chromatography coupled with Q Exactive Plus hybrid quadrupole-orbitrap mass spectrometer that featured high resolution, mass accuracy, and sensitivity. To screen resin glycosides, three parent filter m/z 871, m/z 853, and m/z 869 combined with diagnostic fragment ions (DFIs) approach were applied to remove the interference from complex herbal extract. The targeted components were characterized based on detailed fragment ions. Using this approach, 80 targeted components, including 22 glycosidic acids and 58 resin glycosides were tentatively identified. The present results suggested that the proposed MDF strategy would be adaptable to the analysis of complex system in relevant filed.
Biocompatibility Assessment of Polylactic Acid (PLA) and Nanobioglass (n-BG) Nanocomposites for Biomedical Applications
Authors: Castro Jorge Iván , Valencia Llano Carlos Humberto , Tenorio Diego López , Saavedra Marcela , Zapata Paula , Navia-Porras Diana Paola , Delgado-Ospina Johannes , Chaur Manuel N. , Hernández José Hermínsul Mina , Grande-Tovar Carlos David
Published: June 2022

Scaffolds based on biopolymers and nanomaterials with appropriate mechanical properties and high biocompatibility are desirable in tissue engineering. Therefore, polylactic acid (PLA) nanocomposites were prepared with ceramic nanobioglass (PLA/n-BGs) at 5 and 10 wt.%. Bioglass nanoparticles (n-BGs) were prepared using a sol–gel methodology with a size of ca. 24.87 ± 6.26 nm. In addition, they showed the ability to inhibit bacteria such as Escherichia coli (ATCC 11775), Vibrio parahaemolyticus (ATCC 17802), Staphylococcus aureus subsp. aureus (ATCC 55804), and Bacillus cereus (ATCC 13061) at concentrations of 20 w/v%. The analysis of the nanocomposite microstructures exhibited a heterogeneous sponge-like morphology. The mechanical properties showed that the addition of 5 wt.% n-BG increased the elastic modulus of PLA by ca. 91.3% (from 1.49 ± 0.44 to 2.85 ± 0.99 MPa) and influenced the resorption capacity, as shown by histological analyses in biomodels. The incorporation of n-BGs decreased the PLA crystallinity (from 7.1% to 4.98%) and increased the glass transition temperature (Tg) from 53 °C to 63 °C. In addition, the n-BGs increased the thermal stability due to the nanoparticle’s intercalation between the polymeric chains and the reduction in their movement. The histological implantation of the nanocomposites and the cell viability with HeLa cells higher than 80% demonstrated their biocompatibility character with a greater resorption capacity than PLA. These results show the potential of PLA/n-BGs nanocomposites for biomedical applications, especially for long healing processes such as bone tissue repair and avoiding microbial contamination.
Systematic Qualitative and Quantitative Analyses of Wenxin Granule via Ultra-High Performance Liquid Chromatography Coupled with Ion Mobility Quadrupole Time-of-Flight Mass Spectrometry and Triple Quadrupole–Linear Ion Trap Mass Spectrometry
Authors: Mi Yueguang , Hu Wandi , Li Weiwei , Wan Shiyu , Xu Xiaoyan , Liu Meiyu , Wang Hongda , Mei Quanxi , Chen Qinhua , Yang Yang , Chen Boxue , Jiang Meiting , Li Xue , Yang Wenzhi , Guo Dean
Published: June 2022

Wenxin granule (WXG) is a popular traditional Chinese medicine (TCM) preparation for the treatment of arrhythmia disease. Potent analytical technologies are needed to elucidate its chemical composition and assess the quality differences among multibatch samples. In this work, both a multicomponent characterization and quantitative assay of WXG were conducted using two liquid chromatography–mass spectrometry (LC-MS) approaches. An ultra-high performance liquid chromatography–ion mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) approach combined with intelligent peak annotation workflows was developed to characterize the multicomponents of WXG. A hybrid scan approach enabling alternative data-independent and data-dependent acquisitions was established. We characterized 205 components, including 92 ginsenosides, 53 steroidal saponins, 14 alkaloids, and 46 others. Moreover, an optimized scheduled multiple reaction monitoring (sMRM) method was elaborated, targeting 24 compounds of WXG via ultra-high performance liquid chromatography–triple quadrupole linear ion trap mass spectrometry (UHPLC/QTrap-MS), which was validated based on its selectivity, precision, stability, repeatability, linearity, sensitivity, recovery, and matrix effect. By applying this method to 27 batches of WXG samples, the content variations of multiple markers from Notoginseng Radix et Rhizoma (21) and Codonopsis Radix (3) were depicted. Conclusively, we achieved the comprehensive multicomponent characterization and holistic quality assessment of WXG by targeting the non-volatile components.
Field Electron Emission from Crumpled CVD Graphene Patterns Printed via Laser-Induced Forward Transfer
Authors: Komlenok Maxim , Kurochitsky Nikolay , Pivovarov Pavel , Rybin Maxim , Obraztsova Elena
Published: June 2022

A new approach to the fabrication of graphene field emitters on a variety of substrates at room temperature and in an ambient environment is demonstrated. The required shape and orientation of the graphene flakes along the field are created by the blister-based laser-induced forward transfer of CVD high-quality single-layer graphene. The proposed technique allows the formation of emitting crumpled graphene patterns without losing the quality of the initially synthesized graphene, as shown by Raman spectroscopy. The electron field emission properties of crumpled graphene imprints 1 × 1 mm2 in size were studied. The transferred graphene flakes demonstrated good adhesion and emission characteristics.
Promising Colloidal Rhenium Disulfide Nanosheets: Preparation and Applications for In Vivo Breast Cancer Therapy
Authors: Song Yiwan , Yuan Yufeng , Peng Xiao , Peng Zheng , Liu Hao , Zhou Yingxin , Zhang Xiaoying , Zhou Feifan , Song Jun , Qu Junle
Published: June 2022

Photothermal therapy (PTT) has become an important therapeutic strategy in the treatment of cancer. However, exploring novel photothermal nanomaterials with satisfactory biocompatibility, high photothermal conversion efficiency, and efficient theranostic outcomes, remains a major challenge for satisfying clinical application. In this study, poly-ethylene glycol modified rhenium disulfide (PEG-ReS2) nanosheets are constructed by a simple-liquid phase exfoliation method. The PEG-ReS2 nanosheets were demonstrated to have good solubility, good biocompatibility, low toxicity, and strong capability of accumulating near-infrared (NIR) photons. Under 808 nm laser irradiation, the PEG-ReS2 nanosheets were found to have an excellent photothermal conversion efficiency (PTCE) of 42%. Moreover, the PEG-ReS2 nanosheets were demonstrated to be ideal photothermal transduction agents (PTAs), which promoted rapid cancer cell death in vitro and efficiently ablated tumors in vivo. Interestingly, the potential utility of up-regulation or down-regulation of miRNAs was proposed to evaluate the therapeutic outcomes of PEG-ReS2 nanosheets. The expression levels of a set of miRNAs in tumor-bearing mice were restored to normal levels after PTT therapy with PEG-ReS2 nanosheets. Both down-regulation miRNAs (miR-125a-5p, miR-34a-5p, miR-132-3p, and miR-148b-3p) and up-regulation miRNAs (miR-133a-3p, miR-200c-5p, miR-9-3p, and miR-150-3p) were suggested to be important clinical biomarkers for evaluating therapeutic outcomes of breast cancer-related PTT. This work highlights the great significance of PEG-ReS2 nanosheets as therapeutic nanoagents for cancer therapy.
Suppression of Anti-Inflammatory Mediators in Metabolic Disease May Be Driven by Overwhelming Pro-Inflammatory Drivers
Authors: Sajid Sehar , Zariwala Mohammed Gulrez , Mackenzie Richard , Turner Mark , Nell Theo , Bellary Srikanth , Renshaw Derek
Published: June 2022

Obesity is a multifactorial disease and is associated with an increased risk of developing metabolic syndrome and co-morbidities. Dysregulated expansion of the adipose tissue during obesity induces local tissue hypoxia, altered secretory profile of adipokines, cytokines and chemokines, altered profile of local tissue inflammatory cells leading to the development of low-grade chronic inflammation. Low grade chronic inflammation is considered to be the underlying mechanism that increases the risk of developing obesity associated comorbidities. The glucocorticoid induced protein annexin A1 and its N-terminal peptides are anti-inflammatory mediators involved in resolving inflammation. The aim of the current study was to investigate the role of annexin A1 in obesity and associated inflammation. To achieve this aim, the current study analysed data from two feasibility studies in clinical populations: (1) bariatric surgery patients (Pre- and 3 months post-surgery) and (2) Lipodystrophy patients. Plasma annexin A1 levels were increased at 3-months post-surgery compared to pre-surgery (1.2 ± 0.1 ng/mL, n = 19 vs. 1.6 ± 0.1 ng/mL, n = 9, p = 0.009) and positively correlated with adiponectin (p = 0.009, r = 0.468, n = 25). Plasma annexin A1 levels were decreased in patients with lipodystrophy compared to BMI matched controls (0.2 ± 0.1 ng/mL, n = 9 vs. 0.97 ± 0.1 ng/mL, n = 30, p = 0.008), whereas CRP levels were significantly elevated (3.3 ± 1.0 µg/mL, n = 9 vs. 1.4 ± 0.3 µg/mL, n = 31, p = 0.0074). The roles of annexin A1 were explored using an in vitro cell based model (SGBS cells) mimicking the inflammatory status that is observed in obesity. Acute treatment with the annexin A1 N-terminal peptide, AC2-26 differentially regulated gene expression (including PPARA (2.8 ± 0.7-fold, p = 0.0303, n = 3), ADIPOQ (2.0 ± 0.3-fold, p = 0.0073, n = 3), LEP (0.6 ± 0.2-fold, p = 0.0400, n = 3), NAMPT (0.4 ± 0.1-fold, p = 0.0039, n = 3) and RETN (0.1 ± 0.03-fold, p < 0.0001, n = 3) in mature obesogenic adipocytes indicating that annexin A1 may play a protective role in obesity and inflammation. However, this effect may be overshadowed by the continued increase in systemic inflammation associated with rapid tissue expansion in obesity.
Diurnal Variations of the Count Rates from Dark Photons in PHELEX
Authors: Kopylov Anatoly , Orekhov Igor , Petukhov Valery
Published: June 2022

This paper reports the PHELEX experiment, i.e., PHoton–ELectron EXperiment, to search for the dark photons (DPs) of cold dark matter using a multicathode counter technique specifically developed for this purpose by the authors. The paper presents new data, a novel upper limit for the constant of kinetic mixing, and the first results of measurements of the diurnal variations in solar and stellar frames. The perspectives of this method are outlined in terms of the search for DPs.
Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury
Authors: Du Zaizhi , Liu Han , Huang Xie , Li Yang , Wang Liting , Liu Jing , Long Shuang , Li Rong , Xiang Qiang , Luo Shenglin
Published: June 2022

Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endogenous ROS, and in this work a mitochondria-targeting radioprotectant (CY-TMP1) is reported for radiation injury-combined wound repair. It was designed, synthesized and screened out from different conjugates between mitochondria-targeting heptamethine cyanine dyes and a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (TEMPO). CY-TMP1 specifically accumulated in mitochondria, efficiently mitigated mitochondrial ROS and total intracellular ROS induced by 6 Gy of X-ray ionizing irradiation, thereby exhibiting a notable radioprotective effect. The mechanism study further demonstrated that CY-TMP1 protected mitochondria from radiation-induced injury, including maintaining mitochondrial membrane potential (MMP) and ATP generation, thereby reducing the ratio of cell apoptotic death. Particularly, an in vivo experiment showed that CY-TMP1 could effectively accelerate wound closure of mice after 6 Gy of whole-body ionizing radiation. Immunohistochemical staining further indicated that CY-TMP1 may improve wound repair through angiogenesis and re-epithelialization. Therefore, mitochondria-targeting ROS scavengers may present a feasible strategy to conquer refractory wound combined with radiation injury.
Polymeric Micelles with pH-Responsive Cross-Linked Core Enhance In Vivo mRNA Delivery
Authors: Yang Wenqian , Chen Pengwen , Boonstra Eger , Hong Taehun , Cabral Horacio
Published: June 2022

Messenger RNA (mRNA) is emerging as a promising therapeutic modality for a variety of diseases. Because of the fragility and limited intracellular access of mRNA, the development of delivery technologies is essential for promoting the applicability of mRNA-based treatments. Among effective nanocarriers, polymeric micelles loading mRNA by polyion complex (PIC) formation with block catiomers have the potential to meet the delivery needs. Since PICs are relatively unstable in in vivo settings, herein, we constructed mRNA-loaded micelles having pH-responsive cross-linked cores by complexing mRNA with cis-aconitic anhydride-modified poly(ethylene glycol)-poly(l-lysine) (PEG-pLL(CAA)) block copolymers. The micelles were stable at physiological pH (pH 7.4) but achieved the complete release of the mRNA at endosomal pH (pH 5.5–4.5). The cross-linking also enhanced the stability of the micelles against disassembly from polyanions and protected the loaded mRNA from degradation by nucleases. Thus, the cross-linked micelles increased the delivery of mRNA to cancer cells, promoting protein expression both in vitro and in vivo. Our results highlight the potential of PEG-pLL(CAA)-based micelles for mRNA delivery.
Influence of Acoustic Parameters and Sonication Schemes on Transcranial Blood–Brain Barrier Disruption Induced by Pulsed Weakly Focused Ultrasound
Authors: Hsu Yu-Hone , Lee Wei-Chung , Chu Shing-Shung , Chao Meng-En , Wu Kuo-Sheng , Liu Ren-Shyan , Wong Tai-Tong
Published: June 2022

Pulsed ultrasound combined with microbubbles use can disrupt the blood–brain barrier (BBB) temporarily; this technique opens a temporal window to deliver large therapeutic molecules into brain tissue. There are published studies to discuss the efficacy and safety of the different ultrasound parameters, microbubble dosages and sizes, and sonication schemes on BBB disruption, but optimal the paradigm is still under investigation. Our study is aimed to investigate how different sonication parameters, time, and microbubble dose can affect BBB disruption, the dynamics of BBB disruption, and the efficacy of different sonication schemes on BBB disruption. Method: We used pulsed weakly focused ultrasound to open the BBB of C57/B6 mice. Evans blue dye (EBD) was used to determine the degree of BBB disruption. With a given acoustic pressure of 0.56 MPa and pulse repetitive frequency of 1 Hz, burst lengths of 10 ms to 50 ms, microbubbles of 100 μL/kg to 300 μL/kg, and sonication times of 60 s to 150 s were used to open the BBB for parameter study. Brain EBD accumulation was measured at 1, 4, and 24 h after sonication for the time–response relationship study; EBD of 100 mg/kg to 200 mg/kg was administered for the dose–response relationship study; EBD injection 0 to 6 h after sonication was performed for the BBB disruption dynamic study; brain EBD accumulation induced by one sonication and two sonications was investigated to study the effectiveness on BBB disruption; and a histology study was performed for brain tissue damage evaluation. Results: Pulsed weakly focused ultrasound opens the BBB extensively. Longer burst lengths and a larger microbubble dose result in a higher degree of BBB disruption; a sonication time longer than 60 s did not increase BBB disruption; brain EBD accumulation peaks 1 h after sonication and remains 81% of the peak level 24 h after sonication; the EBD dose administered correlates with brain EBD accumulation; BBB disruption decreases as time goes on after sonication and lasts for 6 h at least; and brain EBD accumulation induced by two sonication increases 74.8% of that induced by one sonication. There was limited adverse effects associated with sonication, including petechial hemorrhages and mild neuronal degeneration. Conclusions: BBB can be opened extensively and reversibly by pulsed weakly focused ultrasound with limited brain tissue damage. Since EBD combines with albumin in plasma to form a conjugate of 83 kDa, these results may simulate ultrasound-induced brain delivery of therapeutic molecules of this size scale. The result of our study may contribute to finding the optimal paradigm of focused ultrasound-induced BBB disruption.
Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems
Authors: Pinto Bárbara , Novais Pedro , Henriques Ana C. , Carvalho-Tavares Juliana , Silva Patrícia M. A. , Bousbaa Hassan
Published: June 2022

The efficacy of antimitotics is limited by slippage, whereby treated cells arrested in mitosis exit mitosis without cell division and, eventually, escape apoptosis, constituting a serious resistance mechanism to antimitotics. Strategies to overcome slippage should potentiate the cancer cell killing activity of these antimitotics. Such strategies should accelerate cell death in mitosis before slippage. Here, we undertook a mechanistic analysis to test whether the apoptosis activator Navitoclax potentiates apoptosis triggered by the antimitotic BI2536, a potent inhibitor of Polo-like kinase 1 (PLK1) with the goal of overcoming slippage. We found that cancer cells in 2D cultures treated with BI2536 alone accumulate in mitosis, but a significant fraction of arrested cells undergo slippage and survive. Remarkably, combining BI2536 with Navitoclax dramatically reduces slippage, shifting the cell fate to accelerated death in mitosis. The results are confirmed in 3D spheroids, a preclinical system that mimics in vivo tumor drug responses. Importantly, in 3D spheroids, the effect of the BI2536/Navitoclax combination requires a lower therapeutic dosage of each drug, underlying its potential to improve the therapeutic index. Our results highlight the relevance of apoptosis potentiators to circumvent slippage associated with antimitotics. The combination of BI2536 with Navitoclax shows in vitro synergy/additive effect, which warrants further clinical research.