bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Simulations Suggest SARS-CoV-2 3CLpro Mutations in Beta and Omicron Variants Do Not Alter Binding Affinities for Cleavage Sites of Non-Structural Proteins
Authors: de Freitas Amorim Vitor Martins , de Souza Robson Francisco , Guzzo Cristiane Rodrigues , de Souza Anacleto Silva
Published: April 2023

In the course of SARS-CoV-2 infection, the 3CL or nsp5 protease plays a pivotal role as the most important viral protease required for the maturation of viral proteins during host infection. Herein, we simulated for 500 ns 3CLproWT, 3CLproH41A, 3CLproBeta, and 3CLproOmicron, in complex with the substrates nsp 4|5 and nsp 5|6. Our results show that mutations in the 3CLpro present in the SARS-CoV-2 variants of concern (VOCs) did not lead to significant conformational changes or changes in substrate binding affinities. However, significantly high cleavage rates for the boundary between nsp4 and nsp5 were obtained for 3CLproBeta and 3CLproOmicron and may play a key role in viral replication and virus fitness gain. Our molecular dynamics data suggest that the cleavage rate of nsp4|5 may be related to the increased amount of viral load observed for these VOCs, releasing more nsp4 than other non-structural proteins. This study is limited by being fully computational. However, our results suggest that the cleavage rate may be affected by mutations. Based on our hydrogen bonding analyses, we also discovered that Gly143 and Glu166 are key residues in substrate recognition, suggesting that these residues may be incorporated as pharmacophoric centers for Beta and Omicron variants in drug design. Our results suggest that Gly143 and Glu166 are essential residues to interact with Gln6 of the different substrates and, therefore, are potential broad-spectrum pharmacophoric centers of SARS-CoV-2 3CLpro.
Anonymous Homomorphic IBE with Application to Anonymous Aggregation
Authors: Clear Michael , Tewari Hitesh
Published: April 2023

All anonymous identity-based encryption (IBE) schemes that are group homomorphic (to the best of our knowledge) require knowledge of the identity to compute the homomorphic operation. This paper is motivated by this open problem, namely to construct an anonymous group-homomorphic IBE scheme that does not sacrifice anonymity to perform homomorphic operations. Note that even when strong assumptions, such as indistinguishability obfuscation (iO), are permitted, no schemes are known. We succeed in solving this open problem by assuming iO and the hardness of the DBDH problem over rings (specifically, ZN2 for RSA modulus N). We then use the existence of such a scheme to construct an IBE scheme with re-randomizable anonymous encryption keys, which we prove to be IND-ID-RCCA secure. Finally, we use our results to construct identity-based anonymous aggregation protocols.
The Importance and Impact of Francisella-like Endosymbionts in Hyalomma Ticks in the Era of Climate Change
Authors: Sesmero-García Celia , Cabanero-Navalon Marta Dafne , Garcia-Bustos Victor
Published: April 2023

Ticks are obligatory hematophagous parasites that serve as vectors for a large amount of important human and livestock pathogens around the world, and their distribution and incidence of tick-associated diseases are currently increasing because of environmental biomass being modified by both climate change and other human activities. Hyalomma species are of major concern for public health, due to their important role as vectors of several diseases such as the Crimea–Congo hemorrhagic fever (CCHF) virus in humans or theileriosis in cattle. Characterizing the Hyalomma-associated microbiota and delving into the complex interactions between ticks and their bacterial endosymbionts for host survival, development, and pathogen transmission are fundamental, as it may provide new insights and spawn new paradigms to control tick-borne diseases. Francisella-like endosymbionts (FLEs) have recently gained importance, not only as a consequence of the public health concerns of the highly transmissible Francisella tularensis, but for the essential role of FLEs in tick homeostasis. In this comprehensive review, we discuss the growing importance of ticks associated with the genus Hyalomma, their associated tick-borne human and animal diseases in the era of climate change, as well as the role of the microbiome and the FLE in their ecology. We compile current evidence from around the world on FLEs in Hyalomma species and examine the impact of new molecular techniques in the study of tick microbiomes (both in research and in clinical practice). Lastly, we also discuss different endosymbiont-directed strategies for the control of tick populations and tick-borne diseases, providing insights into new evidence-based opportunities for the future.
Fatty Acid, Carotenoid and Fat-Soluble Vitamin Composition of Multispecies Swards Grown in Ireland—Implications for a Sustainable Feed in Dairy Farming
Authors: Rapisarda Samuel , O’Neill Graham , Abu-Ghannam Nissreen
Published: April 2023

Although traditional ryegrass pastures are still commonly used, they require intense management and input and do not perform well during the summer months. Multispecies systems have been recognised as more sustainable, needing less fertiliser and being tolerant to drought and heat. While data on monoculture system fat composition exist, information for multispecies is scarce. The present study compared the fatty acid (FA), carotenoid and fat-soluble composition of a multispecies system (consisting of perennial ryegrass, timothy, white clover, red clover, chicory and plantain) (MULTI) with two other conventional grazing systems (monoculture perennial ryegrass (PRG) and a binary mixture of perennial ryegrass and white clover (PRG+WC)) over the Irish late-summer grazing season of dairy cattle (July–September). The results showed that the three systems had similar levels of FAs (p > 0.05), with mean α-linolenic acid values of 20.00 mg/g in PRG, 18.51 mg/g in PRG+WC, and 17.90 mg/g in MULTI and mean linoleic acid values of 3.84 mg/g in PRG, 4.16 mg/g in PRG+WC, and 4.39 mg/g in MULTI. Fourfold and twofold increases in the concentrations of α-linolenic acid and linoleic acid, respectively, were observed throughout July–September. Variations in stearic acid concentrations were not significant (p > 0.05), and palmitic acid concentrations increased over time (p < 0.05). The average values of lutein (36.68 mg/kg in PRG, 31.26 mg/kg in PRG+WC, and 35.75 mg/kg in MULTI) and α-tocopherol (2.28 mg/kg in PRG, 1.49 mg/kg in PRG+WC, and 1.83 mg/kg in MULTI) were similar among the grazing systems (p > 0.05), and the average β-carotene value was 25% higher in monoculture ryegrass (140.74 mg/kg) than in the multispecies (102.51 mg/kg) (p < 0.05). Nonetheless, the levels of β-carotene found in the multispecies were still above the recommended intake required for ruminants. In conclusion, multispecies pastures could be included in dairy cattle production systems as a sustainable alternative to traditional pastures while also providing typically adequate sources of fats for animal diets.
An Axiomatic Characterization of Mutual Information
Authors: Fullwood James
Published: April 2023

We characterize mutual information as the unique map on ordered pairs of discrete random variables satisfying a set of axioms similar to those of Faddeev’s characterization of the Shannon entropy. There is a new axiom in our characterization, however, which has no analog for Shannon entropy, based on the notion of a Markov triangle, which may be thought of as a composition of communication channels for which conditional entropy acts functorially. Our proofs are coordinate-free in the sense that no logarithms appear in our calculations.
IMF: Interpretable Multi-Hop Forecasting on Temporal Knowledge Graphs
Authors: Du Zhenyu , Qu Lingzhi , Liang Zongwei , Huang Keju , Cui Lin , Gao Zhiyang
Published: April 2023

Temporal knowledge graphs (KGs) have recently attracted increasing attention. The temporal KG forecasting task, which plays a crucial role in such applications as event prediction, predicts future links based on historical facts. However, current studies pay scant attention to the following two aspects. First, the interpretability of current models is manifested in providing reasoning paths, which is an essential property of path-based models. However, the comparison of reasoning paths in these models is operated in a black-box fashion. Moreover, contemporary models utilize separate networks to evaluate paths at different hops. Although the network for each hop has the same architecture, each network achieves different parameters for better performance. Different parameters cause identical semantics to have different scores, so models cannot measure identical semantics at different hops equally. Inspired by the observation that reasoning based on multi-hop paths is akin to answering questions step by step, this paper designs an Interpretable Multi-Hop Reasoning (IMR) framework based on consistent basic models for temporal KG forecasting. IMR transforms reasoning based on path searching into stepwise question answering. In addition, IMR develops three indicators according to the characteristics of temporal KGs and reasoning paths: the question matching degree, answer completion level, and path confidence. IMR can uniformly integrate paths of different hops according to the same criteria; IMR can provide the reasoning paths similarly to other interpretable models and further explain the basis for path comparison. We instantiate the framework based on common embedding models such as TransE, RotatE, and ComplEx. While being more explainable, these instantiated models achieve state-of-the-art performance against previous models on four baseline datasets.
Semi-Empirical Satellite-to-Ground Quantum Key Distribution Model for Realistic Receivers
Authors: Khmelev Aleksandr V. , Ivchenko Egor I. , Miller Alexander V. , Duplinsky Alexey V. , Kurochkin Vladimir L. , Kurochkin Yury V.
Published: April 2023

Satellite-based link analysis is valuable for efficient and secure quantum communication, despite seasonal limits and restrictions on transmission times. A semi-empirical quantum key distribution model for satellite-based systems was proposed that simplifies simulations of communication links. Unlike other theoretical models, our approach was based on the experimentally-determined atmospheric extinction coefficient typical for mid-latitude ground stations. The parameter was measured for both clear and foggy conditions, and it was validated using published experimental data from the Micius satellite. Using this model, we simulated secure QKD between the Micius satellite and ground stations with 300 mm and 600 mm aperture telescopes.
Detecting, Monitoring and Foreseeing Wildland Fire Requires Similar Multiscale Viewpoints as Meteorology and Climatology
Authors: Bowman David M. J. S.
Published: April 2023

Achieving sustainable coexistence with wildfires in the Anthropocene requires skilful integrated fire observations, fire behaviour predictions, forecasts of fire risk, and projections of change to fire climates. The diverse and multiscale approaches used by the atmospheric sciences, to understand geographic patterns, temporal trends and likely trajectories of weather and climate, provide a role model for how multiscale assessments of fire danger can be formulated and delivered to fire managers, emergency responders and at-risk communities. Adaptation to escalating risk of fire disasters requires specialised national agencies, like weather services, that provide to provide a diverse range of products to enable detection and near and longer-range prediction of landscape fire activity.
Experimental Investigation of the Hydrodynamic Characteristics of Longline Aquaculture Facilities under Current and Wave Conditions
Authors: Wang Xinxin , Xie Junyi , Luo Yan , Wang Xiao , Guo Gaobo , You Xinxing
Published: April 2023

In this study, a longline aquaculture facility with lantern nets off the coast of northern China was modelled to conduct hydrodynamic tests starting from the culture unit to the entire facility under various current and wave conditions. The experimental results indicated that the drag coefficients of the lantern net model with weights of 0.5, 0.75, and 1.0 kg were 0.75, 0.83, and 0.91, respectively, in the Reynolds number range of 1 × 104–1 × 106. The current-driven upstream mooring line was more dominant than the wave-driven tension, and a simplified model of the longline facility accurately predicted the mooring line tension under the current conditions. The scope of the mooring line (defined as the length of the mooring line related to the water depth) played an important role in eliminating an order of magnitude difference in mooring tension under the wave conditions. The amplitudes of the vertical movement of the longline facility were smaller than the wave height when L/Lm was less than 1.5. Therefore, detailed information is needed to better understand the hydrodynamic characteristics and motion response of longline aquaculture facilities for the safe operation of longline structures in offshore environments, in order to process high-quality oyster products.
Effects of Incorporation of Porous Tapioca Starch on the Quality of White Salted (Udon) Noodles
Authors: Pokharel Anju , Jaidka Randhir Kumar , Sruthi N. U. , Bhattarai Rewati Raman
Published: April 2023

White salted (udon) noodles are one of the major staple foods in Asian countries, particularly in Japan. Noodle manufacturers prefer the Australian noodle wheat (ANW) varieties to produce high-quality udon noodles. However, the production of this variety has reduced significantly in recent years, thus affecting the Japanese noodle market. Noodle manufacturers often add tapioca starch to compensate for the flour scarcity; however, the noodle-eating quality and texture are significantly reduced. This study, therefore, investigated the effect of the addition of porous tapioca starch on the cooking quality and texture of udon noodles. For this, tapioca starch was initially subjected to enzyme treatment, ultrasonication, and a combination of both to produce a porous starch where a combined enzyme (0.4% alpha amylase)–ultrasound treatment (20 kHz) yielded a porous starch with increased specific surface area and better absorbent properties which are ideal for udon noodle manufacturing, Later, udon noodles were prepared using three varieties of ANW, a hard Mace variety, and commercial wheat flour by incorporating the prepared porous tapioca starch at a concentration of 5% and 10% of dry ingredients. Adding this porous starch resulted in a lower cooking time with higher water absorption and desirable lower cooking loss compared to the control sample with 5% of the porous starch chosen as the optimum formulation. Increasing the level of the porous starch reduced the hardness of the noodles whilst maintaining the desired instrumental texture. Additionally, a multivariate analysis indicated a good correlation between responses’ optimum cooking time and water absorption capacity as well as turbidity and cooking loss, and a cluster analysis grouped noodle samples prepared from different varieties into the same clusters based on the porous starch added, indicating the possibility of different market strategies to improve the quality of the udon noodles produced from different wheat varieties.
A Numerical Solution of Generalized Caputo Fractional Initial Value Problems
Authors: Saadeh Rania , A. Abdoon Mohamed , Qazza Ahmad , Berir Mohammed
Published: April 2023

In this article, the numerical adaptive predictor corrector (Apc-ABM) method is presented to solve generalized Caputo fractional initial value problems. The Apc-ABM method was utilized to establish approximate series solutions. The presented technique is considered to be an extension to the original Adams–Bashforth–Moulton approach. Numerical simulations and figures are presented and discussed, in order to show the efficiency of the proposed method. In the future, we anticipate that the provided generalized Caputo fractional derivative and the suggested method will be utilized to create and simulate a wide variety of generalized Caputo-type fractional models. We have included examples to demonstrate the accuracy of the present method.
Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease
Authors: Franco Gianluca Antonio , Interdonato Livia , Cordaro Marika , Cuzzocrea Salvatore , Di Paola Rosanna
Published: April 2023

Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress, and neuronal depletion. They include selective malfunction and progressive loss of neurons, glial cells, and neural networks in the brain and spinal cord. There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases because, today, there is no treatment that can cure degenerative diseases; however, we have many symptomatic treatments. Current nutritional approaches are beginning to reflect a fundamental change in our understanding of health. The Mediterranean diet may have a protective effect on the neurodegenerative process because it is rich in antioxidants, fiber, and omega-3 polyunsaturated fatty acids. Increasing knowledge regarding the impact of diet on regulation at the genetic and molecular levels is changing the way we consider the role of nutrition, resulting in new dietary strategies. Natural products, thanks to their bioactive compounds, have recently undergone extensive exploration and study for their therapeutic potential for a variety of diseases. Targeting simultaneous multiple mechanisms of action and a neuroprotection approach with the diet could prevent cell death and restore function to damaged neurons. For these reasons, this review will be focused on the therapeutic potential of natural products and the associations between the Mediterranean-style diet (MD), neurodegenerative diseases, and markers and mechanisms of neurodegeneration.
Creation of New Oregano Genotypes with Different Terpene Chemotypes via Inter- and Intraspecific Hybridization
Authors: Sun Meiyu , Liu Ningning , Miao Jiahui , Zhang Yanan , Hao Yuanpeng , Zhang Jinzheng , Li Hui , Bai Hongtong , Shi Lei
Published: April 2023

Oregano is a medicinal and aromatic plant of value in the pharmaceutical, food, feed additive, and cosmetic industries. Oregano breeding is still in its infancy compared with traditional crops. In this study, we evaluated the phenotypes of 12 oregano genotypes and generated F1 progenies by hybridization. The density of leaf glandular secretory trichomes and the essential oil yield in the 12 oregano genotypes varied from 97–1017 per cm2 and 0.17–1.67%, respectively. These genotypes were divided into four terpene chemotypes: carvacrol-, thymol-, germacrene D/β-caryophyllene-, and linalool/β-ocimene-type. Based on phenotypic data and considering terpene chemotypes as the main breeding goal, six oregano hybrid combinations were performed. Simple sequence repeat (SSR) markers were developed based on unpublished whole-genome sequencing data of Origanum vulgare, and 64 codominant SSR primers were screened on the parents of the six oregano combinations. These codominant primers were used to determine the authenticity of 40 F1 lines, and 37 true hybrids were identified. These 37 F1 lines were divided into six terpene chemotypes: sabinene-, β-ocimene-, γ-terpinene-, thymol-, carvacrol-, and p-cymene-type, four of which (sabinene-, β-ocimene-, γ-terpinene-, and p-cymene-type) were novel (i.e., different from the chemotypes of parents). The terpene contents of 18 of the 37 F1 lines were higher than those of their parents. The above results lay a strong foundation for the creating of new germplasm resources, constructing of genetic linkage map, and mapping quantitative trait loci (QTLs) of key horticultural traits, and provide insights into the mechanism of terpenoid biosynthesis in oregano.
The Overlap of Kidney Failure in Extrapulmonary Sarcoidosis in Children—Case Report and Review of Literature
Authors: Mocanu Adriana , Bogos Roxana , Trandafir Laura , Cojocaru Elena , Ioniuc Ileana , Alecsa Mirabela , Lupu Vasile , Miron Lucian , Lazaruc Tudor , Lupu Ancuta , Miron Ingrith , Starcea Iuliana
Published: April 2023

Sarcoidosis is a non-necrotizing granulomatous inflammatory multisystemic disorder of unknown etiology. In children, as in adults, it can involve a few or all organ systems to a varying extent and degree, entailing multisystemic manifestations. Kidney involvement in pediatric-onset adult-type sarcoidosis is rare, with a wide range of renal manifestations, most of them related to calcium metabolism. Children with renal sarcoidosis tend to be more symptomatic than adults, although male patients have a higher prevalence. We present the case of a 10-year-old boy who presented with advanced renal failure with nephrocalcinosis and important hepatosplenomegaly. The diagnosis was established by histopathological examination, with consequent cortisone therapy and hemodialysis. This review emphasizes that sarcoidosis should be considered in the differential diagnosis of pediatric patients with acute kidney insufficiency or chronic kidney disease of an unknown etiology. As far as we know, this is the first study regarding extrapulmonary sarcoidosis in children from Romania.
Evaluating the Transition from Targeted to Exome Sequencing: A Guide for Clinical Laboratories
Authors: Yauy Kevin , Van Goethem Charles , Pégeot Henri , Baux David , Guignard Thomas , Thèze Corinne , Ardouin Olivier , Roux Anne-Françoise , Koenig Michel , Bergougnoux Anne , Cossée Mireille
Published: April 2023

The transition from targeted to exome or genome sequencing in clinical contexts requires quality standards, such as targeted sequencing, in order to be fully adopted. However, no clear recommendations or methodology have emerged for evaluating this technological evolution. We developed a structured method based on four run-specific sequencing metrics and seven sample-specific sequencing metrics for evaluating the performance of exome sequencing strategies to replace targeted strategies. The indicators include quality metrics and coverage performance on gene panels and OMIM morbid genes. We applied this general strategy to three different exome kits and compared them with a myopathy-targeted sequencing method. After having achieved 80 million reads, all-tested exome kits generated data suitable for clinical diagnosis. However, significant differences in the coverage and PCR duplicates were observed between the kits. These are two main criteria to consider for the initial implementation with high-quality assurance. This study aims to assist molecular diagnostic laboratories in adopting and evaluating exome sequencing kits in a diagnostic context compared to the strategy used previously. A similar strategy could be used to implement whole-genome sequencing for diagnostic purposes.
A Practical Method for Amino Acid Analysis by LC-MS Using Precolumn Derivatization with Urea
Authors: Zhao Runjin , Huang Biling , Lu Gang , Fu Songsen , Ying Jianxi , Zhao Yufen
Published: April 2023

Amino acid (AA) analysis is important in biochemistry, food science, and clinical medicine. However, due to intrinsic limitations, AAs usually require derivatization to improve their separation and determination. Here, we present a liquid chromatography-mass spectrometry (LC-MS) method for the derivatization of AAs using the simple agent urea. The reactions proceed quantitatively under a wide range of conditions without any pretreatment steps. Urea-derivatized products (carbamoyl amino acids) of 20 AAs exhibit better separation on reversed-phase columns and increased response in a UV detector compared to underivatized ones. We applied this approach to AA analysis in complex samples using a cell culture media as a model, and it showed potential for the determination of oligopeptides. This fast, simple, and inexpensive method should be useful for AA analysis in complex samples.
Simultaneous Inhibition of Thrombosis and Inflammation Is Beneficial in Treating Acute Myocardial Infarction
Authors: Vargas Ian , Grabau Ryan P. , Chen Junjie , Weinheimer Carla , Kovacs Attila , Dominguez-Viqueira William , Mitchell Adam , Wickline Samuel A. , Pan Hua
Published: April 2023

Myocardial ischemia reperfusion injury (IRI) in acute coronary syndromes is a condition in which ischemic/hypoxic injury to cells subtended by the occluded vessel continues despite successful resolution of the thrombotic obstruction. For decades, most efforts to attenuate IRI have focused on interdicting singular molecular targets or pathways, but none have successfully transitioned to clinical use. In this work, we investigate a nanoparticle-based therapeutic strategy for profound but local thrombin inhibition that may simultaneously mitigate both thrombosis and inflammatory signaling pathways to limit myocardial IRI. Perfluorocarbon nanoparticles (PFC NP) were covalently coupled with an irreversible thrombin inhibitor, PPACK (Phe[D]-Pro-Arg-Chloromethylketone), and delivered intravenously to animals in a single dose prior to ischemia reperfusion injury. Fluorescent microscopy of tissue sections and 19F magnetic resonance images of whole hearts ex vivo demonstrated abundant delivery of PFC NP to the area at risk. Echocardiography at 24 h after reperfusion demonstrated preserved ventricular structure and improved function. Treatment reduced thrombin deposition, suppressed endothelial activation, inhibited inflammasome signaling pathways, and limited microvascular injury and vascular pruning in infarct border zones. Accordingly, thrombin inhibition with an extraordinarily potent but locally acting agent suggested a critical role for thrombin and a promising therapeutic strategy in cardiac IRI.
Epoxide Hydrolases: Multipotential Biocatalysts
Authors: Bučko Marek , Kaniaková Katarína , Hronská Helena , Gemeiner Peter , Rosenberg Michal
Published: April 2023

Epoxide hydrolases are attractive and industrially important biocatalysts. They can catalyze the enantioselective hydrolysis of epoxides to the corresponding diols as chiral building blocks for bioactive compounds and drugs. In this review article, we discuss the state of the art and development potential of epoxide hydrolases as biocatalysts based on the most recent approaches and techniques. The review covers new approaches to discover epoxide hydrolases using genome mining and enzyme metagenomics, as well as improving enzyme activity, enantioselectivity, enantioconvergence, and thermostability by directed evolution and a rational design. Further improvements in operational and storage stabilization, reusability, pH stabilization, and thermal stabilization by immobilization techniques are discussed in this study. New possibilities for expanding the synthetic capabilities of epoxide hydrolases by their involvement in non-natural enzyme cascade reactions are described.
Novel Functionalized Spiro [Indoline-3,5′-pyrroline]-2,2′dione Derivatives: Synthesis, Characterization, Drug-Likeness, ADME, and Anticancer Potential
Authors: Asif Mohd , Alvi Sahir Sultan , Azaz Tazeen , Khan Abdul Rahman , Tiwari Bhoopendra , Hafeez Bilal Bin , Nasibullah Malik
Published: April 2023

A highly stereo-selective, one-pot, multicomponent method was chosen to synthesize the novel functionalized 1, 3-cycloaddition spirooxindoles (SOXs) (4a–4h). Synthesized SOXs were analyzed for their drug-likeness and ADME parameters and screened for their anticancer activity. Our molecular docking analysis revealed that among all derivatives of SOXs (4a–4h), 4a has a substantial binding affinity (∆G) −6.65, −6.55, −8.73, and −7.27 Kcal/mol with CD-44, EGFR, AKR1D1, and HER-2, respectively. A functional study demonstrated that SOX 4a has a substantial impact on human cancer cell phenotypes exhibiting abnormality in cytoplasmic and nuclear architecture as well as granule formation leading to cell death. SOX 4a treatment robustly induced reactive oxygen species (ROS) generation in cancer cells as observed by enhanced DCFH-DA signals. Overall, our results suggest that SOX (4a) targets CD-44, EGFR, AKR1D1, and HER-2 and induces ROS generation in cancer cells. We conclude that SOX (4a) could be explored as a potential chemotherapeutic molecule against various cancers in appropriate pre-clinical in vitro and in vivo model systems.
Lichen-Derived Actinomycetota: Novel Taxa and Bioactive Metabolites
Authors: Yang Qingrong , Song Zhiqiang , Li Xinpeng , Hou Yage , Xu Tangchang , Wu Shaohua
Published: April 2023

Actinomycetes are essential sources of numerous bioactive secondary metabolites with diverse chemical and bioactive properties. Lichen ecosystems have piqued the interest of the research community due to their distinct characteristics. Lichen is a symbiont of fungi and algae or cyanobacteria. This review focuses on the novel taxa and diverse bioactive secondary metabolites identified between 1995 and 2022 from cultivable actinomycetota associated with lichens. A total of 25 novel actinomycetota species were reported following studies of lichens. The chemical structures and biological activities of 114 compounds derived from the lichen-associated actinomycetota are also summarized. These secondary metabolites were classified into aromatic amides and amines, diketopiperazines, furanones, indole, isoflavonoids, linear esters and macrolides, peptides, phenolic derivatives, pyridine derivatives, pyrrole derivatives, quinones, and sterols. Their biological activities included anti-inflammatory, antimicrobial, anticancer, cytotoxic, and enzyme-inhibitory actions. In addition, the biosynthetic pathways of several potent bioactive compounds are summarized. Thus, lichen actinomycetes demonstrate exceptional abilities in the discovery of new drug candidates.
Double Mutation of Days to Heading 2 and CONSTANS 3 Improves Agronomic Performance of Japonica Rice under Short Daylight Conditions in Southern China
Authors: Wang Hongmei , Zhu Yue , Wang Linlin , Xiao Chujian , Yuan Jianming , Liu Yao-Guang , Zhang Qunyu
Published: April 2023

Some progress has been made in understanding the pathways related to rice heading, but their applications to breeding japonica rice varieties adapted to grow in low-latitude areas (“indica to japonica”) are limited. We edited eight adaptation-related genes via a lab-established CRISPR/Cas9 system in a japonica variety, Shennong265 (SN265). All T0 plants and their progeny bearing random mutation permutations were planted in southern China and screened for changes in heading date. We found that the double mutant of Days to heading 2 (DTH2) and CONSTANS 3 (OsCO3) (dth2-osco3), two CONSTANS-like (COL) genes, showed significantly delayed heading under both short-day (SD) and long-day (LD) conditions in Guangzhou and manifested great yield increase under SD conditions. We further demonstrated that the heading-related Hd3a-OsMADS14 pathway was down-regulated in the dth2-osco3 mutant lines. The editing of the COL genes DTH2 and OsCO3 greatly improves the agronomic performance of japonica rice in Southern China.
Metabolic Rewiring in Adult-Type Diffuse Gliomas
Authors: Park Jong-Whi
Published: April 2023

Multiple metabolic pathways are utilized to maintain cellular homeostasis. Given the evidence that altered cell metabolism significantly contributes to glioma biology, the current research efforts aim to improve our understanding of metabolic rewiring between glioma’s complex genotype and tissue context. In addition, extensive molecular profiling has revealed activated oncogenes and inactivated tumor suppressors that directly or indirectly impact the cellular metabolism that is associated with the pathogenesis of gliomas. The mutation status of isocitrate dehydrogenases (IDHs) is one of the most important prognostic factors in adult-type diffuse gliomas. This review presents an overview of the metabolic alterations in IDH-mutant gliomas and IDH-wildtype glioblastoma (GBM). A particular focus is placed on targeting metabolic vulnerabilities to identify new therapeutic strategies for glioma.
Discovering the Mechanisms of Oleodaphnone as a Potential HIV Latency-Reversing Agent by Transcriptome Profiling
Authors: Li Shifei , Wang Xiuyi , Yang Yuqin , Wu Xingkang , Zhang Liwei
Published: April 2023

Latent HIV is a key factor that makes AIDS difficult to cure. Highly effective and specific latent HIV activators can effectively activate latent HIV, and then combined with antiretroviral therapy to achieve a functional cure of AIDS. Here, four sesquiterpenes (1–4) including a new one (1), five flavonoids (5–9) including three biflavonoid structures, and two lignans (10 and 11) were obtained from the roots of Wikstroemia chamaedaphne. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configuration of 1 was determined by experimental electronic circular dichroism. NH2 cell model was used to test the activity of these 11 compounds in activating latent HIV. Oleodaphnone (2) showed the latent HIV activation effect as well as the positive drug prostratin, and the activation effect was time- and concentration-dependent. Based on transcriptome analysis, the underlying mechanism was that oleodaphnone regulated the TNF, C-type lectin receptor, NF-κB, IL-17, MAPK, NOD-like receptor, JAK-Stat, FoxO, and Toll-like receptor signaling pathways. This study provides the basis for the potential development of oleodaphnone as an effective HIV latency-reversing agent.
Is the In Vitro Observed NETosis the Favored Physiological Death of Neutrophils or Mainly Induced by an Isolation Bias?
Authors: Rimboeck Julia , Gruber Michael , Wittmann Sigrid
Published: April 2023

Centrifugation steps are regularly used for neutrophil isolation. Thereby, the influences of applied g-forces on the functionality of PMNs have hardly been analyzed and could consequently have been overlooked or led to biased results. We now hypothesize that blood PMNs—when gently isolated—can be long-lived cells and they physiologically become apoptotic rather than NETotic. Neutrophils were isolated from whole blood without centrifugation using a sedimentation enhancer (gelafundin). PMNs were analyzed via live-cell imaging for migratory activity and vitality condition by fluorescent staining. Native neutrophils showed still relevant migratory activity after more than 6 days ex vivo. The percentage of cells that were annexin V+ or PI+ increased successively with increasing ex vivo time. In addition, the characteristics of DAPI staining of gently isolated granulocytes differed markedly from those obtained by density gradient separation (DGS). We conclude that NETosis occurring after DGS is the consequence of applied g-forces and not a physiological phenomenon. Future studies on neutrophils should be performed with most native cells (applied g-time load as low as possible).
Shear-Mediated Platelet Microparticles Demonstrate Phenotypic Heterogeneity as to Morphology, Receptor Distribution, and Hemostatic Function
Authors: Roka-Moiia Yana , Ammann Kaitlyn R. , Miller-Gutierrez Samuel , Sheriff Jawaad , Bluestein Danny , Italiano Joseph E. , Flaumenhaft Robert C. , Slepian Marvin J.
Published: April 2023

Implantable Cardiovascular Therapeutic Devices (CTD), while lifesaving, impart supraphysiologic shear stress to platelets, resulting in thrombotic and bleeding coagulopathy. We previously demonstrated that shear-mediated platelet dysfunction is associated with downregulation of platelet GPIb-IX-V and αIIbβ3 receptors via generation of Platelet-Derived MicroParticles (PDMPs). Here, we test the hypothesis that sheared PDMPs manifest phenotypical heterogeneity of morphology and receptor surface expression and modulate platelet hemostatic function. Human gel-filtered platelets were exposed to continuous shear stress. Alterations of platelet morphology were visualized using transmission electron microscopy. Surface expression of platelet receptors and PDMP generation were quantified by flow cytometry. Thrombin generation was quantified spectrophotometrically, and platelet aggregation was measured by optical aggregometry. Shear stress promotes notable alterations in platelet morphology and ejection of distinctive types of PDMPs. Shear-mediated microvesiculation is associated with the remodeling of platelet receptors, with PDMPs expressing significantly higher levels of adhesion receptors (αIIbβ3, GPIX, PECAM-1, P-selectin, and PSGL-1) and agonist receptors (P2Y12 and PAR1). Sheared PDMPs promote thrombin generation and inhibit platelet aggregation induced by collagen and ADP. Sheared PDMPs demonstrate phenotypic heterogeneity as to morphology and defined patterns of surface receptors and impose a bidirectional effect on platelet hemostatic function. PDMP heterogeneity suggests that a range of mechanisms are operative in the microvesiculation process, contributing to CTD coagulopathy and posing opportunities for therapeutic manipulation.
A Pilot Study on the Role of Computed Tomography in the Management of Patients with Coronary Artery Anomalies in Romania
Authors: Capisizu Adriana Sorina , Cuzino Dragos , Stanciu Silviu Marcel
Published: April 2023

Coronary artery anomalies may occur during embryogenesis and can lead to changes in the vascularization of the heart, possible ischemia, and an increased risk of sudden death. A retrospective study was conducted with the aim of assessing the prevalence of coronary anomalies in a Romanian sample of patients, investigated with computed tomography angiography for coronary artery disease. The objectives of the study were to identify the anomalies of the coronary arteries and to conduct an anatomical classification according to Angelini. The study also consisted of evaluations regarding coronary artery calcification in the sample of patients by the Agatston calcium score and assessments regarding the presence of cardiac symptoms and their association with coronary abnormalities. The results showed a prevalence of coronary anomalies of 8.7%, of which 3.8% were origin and course anomalies and 4.9% were coronary anomalies with intramuscular bridging of the left anterior descending artery. Recommendations for practice include the widespread use of coronary computed tomography angiography for the diagnosis of coronary artery anomalies and coronary artery disease in larger patient groups and encouraging this investigation across the country.
Green Nanocomposite Electrodes/Electrolytes for Microbial Fuel Cells—Cutting-Edge Technology
Authors: Kausar Ayesha , Ahmad Ishaq , Zhao Tingkai , Maaza Malik , Bocchetta Patrizia
Published: April 2023

Fuel cell efficiency can be improved by using progressive electrodes and electrolytes. Green nanomaterials and green technologies have been explored for the manufacturing of high-performance electrode and electrolyte materials for fuel cells. Platinum-based electrodes have been replaced with green materials and nanocomposites using green fabrication approaches to attain environmentally friendly fuel cells. In this regard, ecological and sustainable electrode- and electrolyte-based membrane electrode assemblies have also been designed. Moreover, green nanocomposites have been applied to form the fuel cell electrolyte membranes. Among fuel cells, microbial fuel cells have gained research attention for the incorporation of green and sustainable materials. Hence, this review essentially focuses on the potential of green nanocomposites as fuel cell electrode and electrolyte materials and application of green synthesis techniques to attain these materials. The design of and interactions with nanocomposites have led to synergistic effects on the morphology, impedance, resistance, power density, current density, electrochemical features, proton conductivity, and overall efficiency. Moreover, we deliberate the future significance and challenges of the application of green nanocomposites in electrodes and electrolytes to attain efficient fuel cells.
α-Manganese Dioxide (α-MnO2) Coated with Polyaniline (PANI) and Reduced Graphene Oxide (rGO)-Based Nanocomposite for Supercapacitor Application
Authors: Patil Pranoti H. , Kulkarni Vidya V. , Dongale Tukaram D. , Jadhav Sushilkumar A.
Published: April 2023

This work reports the preparation and testing of a composite material composed of α-Manganese dioxide (α-MnO2) coated with polyaniline (PANI) and reduced graphene oxide (rGO) for supercapacitor application. The structure and morphology of the materials were characterized by using X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and Raman spectroscopy. The electrochemical performances of the materials were investigated by using cyclic voltammetry (CV), Galvanostatic charge–discharge (GCD), cyclic stability and electrochemical impedance spectroscopy (EIS). The α-MnO2-coated PANI/rGO nanocomposite exhibited a specific capacitance of 261 F g−1 at the scan rate of 5 mV s−1 with 75% capacitance retention after 2000 cycles at 5 A g−1. It showed a specific energy of 11 W h kg−1 and specific power of 1250 W kg−1.
Gambierone and Sodium Channel Specific Bioactivity Are Associated with the Extracellular Metabolite Pool of the Marine Dinoflagellate Coolia palmyrensis
Authors: Leynse Alexander K. , Mudge Elizabeth M. , Turner Andrew D. , Maskrey Benjamin H. , Robertson Alison
Published: April 2023

Tropical epibenthic dinoflagellate communities produce a plethora of bioactive secondary metabolites, including the toxins ciguatoxins (CTXs) and potentially gambierones, that can contaminate fishes, leading to ciguatera poisoning (CP) when consumed by humans. Many studies have assessed the cellular toxicity of causative dinoflagellate species to better understand the dynamics of CP outbreaks. However, few studies have explored extracellular toxin pools which may also enter the food web, including through alternative and unanticipated routes of exposure. Additionally, the extracellular exhibition of toxins would suggest an ecological function and may prove important to the ecology of the CP-associated dinoflagellate species. In this study, semi-purified extracts obtained from the media of a Coolia palmyrensis strain (DISL57) isolated from the U.S. Virgin Islands were assessed for bioactivity via a sodium channel specific mouse neuroblastoma cell viability assay and associated metabolites evaluated by targeted and non-targeted liquid chromatography tandem and high-resolution mass spectrometry. We found that extracts of C. palmyrensis media exhibit both veratrine enhancing bioactivity and non-specific bioactivity. LC-HR-MS analysis of the same extract fractions identified gambierone and multiple undescribed peaks with mass spectral characteristics suggestive of structural similarities to polyether compounds. These findings implicate C. palmyrensis as a potential contributor to CP and highlight extracellular toxin pools as a potentially significant source of toxins that may enter the food web through multiple exposure pathways.
Reactive Hyperemia and Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Patients: A Systematic Review of Randomized and Nonrandomized Clinical Trials
Authors: López-Galán Erislandis , Montoya-Pedrón Arquímedes , Barrio-Deler Rafael , Sánchez-Hechavarría Miguel Enrique , Muñoz-Bustos Mario Eugenio , Muñoz-Bustos Gustavo Alejandro
Published: April 2023

Objective: This work aimed to determine the relationship between the autonomic nervous system and reactive hyperemia (RH) in type 2 diabetes patients with and without cardiovascular autonomic neuropathy (CAN). Methodology: A systematic review of randomized and nonrandomized clinical studies characterizing reactive hyperemia and autonomic activity in type 2 diabetes patients with and without CAN was performed. Results: Five articles showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy, while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia between normal subjects and non-smoking diabetic patients. Four studies measured reactive hyperemia using peripheral arterial tonometry (PAT); only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients than in those without CAN. Four studies measured reactive hyperemia using flow-mediated dilation (FMD), but no significant differences were reported between diabetic patients with and without CAN. Two studies measured RH using laser Doppler techniques; one of them found significant differences in the blood flow of calf skin after stretching between diabetic non-smokers and smokers. The diabetic smokers had neurogenic activity at baseline that was significantly lower than that of the normal subjects. The greatest evidence revealed that the differences in RH between diabetic patients with and without CAN may depend on both the method used to measure hyperemia and that applied for the ANS examination as well as the type of autonomic deficit present in the patients. Conclusions: In diabetic patients, there is a deterioration in the vasodilator response to the reactive hyperemia maneuver compared to healthy subjects, which depends in part on endothelial and autonomic dysfunction. Blood flow alterations in diabetic patients during RH are mainly mediated by sympathetic dysfunction. The greatest evidence suggests a relationship between ANS and RH; however, there are no significant differences in RH between diabetic patients with and without CAN, as measured using FMD. When the flow of the microvascular territory is measured, the differences between diabetics with and without CAN become evident. Therefore, RH measured using PAT may reflect diabetic neuropathic changes with greater sensitivity compared to FMD.
Intrauterine Growth Restriction—Prediction and Peripartum Data on Hospital Care
Authors: Dinu Marina , Stancioi-Cismaru Andreea Florentina , Gheonea Mihaela , Luciu Elinor Dumitru , Aron Raluca Maria , Pana Razvan Cosmin , Marinas Cristian Marius , Degeratu Stefan , Sorop-Florea Maria , Carp-Veliscu Andreea , Hodorog Andreea Denisa , Tudorache Stefania
Published: April 2023

Background and Objectives: We aimed to prospectively obtain data on pregnancies complicated with intrauterine growth restriction (IUGR) in the Prenatal Diagnosis Unit of the Emergency County Hospital of Craiova. We collected the demographic data of mothers, the prenatal ultrasound (US) features, the intrapartum data, and the immediate postnatal data of newborns. We aimed to assess the detection rates of IUGR fetuses (the performance of the US in estimating the actual neonatal birth weight), to describe the prenatal care pattern in our unit, and to establish predictors for the number of total hospitalization days needed postnatally. Materials and Methods: Data were collected from cases diagnosed with IUGR undergoing prenatal care in our hospital. We compared the percentile of estimated fetal weight (EFW) using the Hadlock 4 technique with the percentile of weight at birth. We retrospectively performed a regression analysis to correlate the variables predicting the number of hospitalization days. Results: Data on 111 women were processed during the period of 1 September 2019–1 September 2022. We confirmed the significant differences in US features between early- (Eo) and late-onset (Lo) IUGR cases. The detection rates were higher if the EFW was lower, and Eo-IUGR was associated with a higher number of US scans. We obtained a mathematical formula for estimating the total number of hospitalization days needed postnatally. Conclusion: Early- and late-onset IUGR have different US features prenatally and different postnatal outcomes. If the US EFW percentile is lower, a prenatal diagnosis is more likely to be made, and a closer follow-up is offered in our hospital. The total number of hospitalization days may be predicted using intrapartum and immediate postnatal data in both groups, having the potential to optimize the final financial costs and to organize the neonatal department efficiently.