bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphologic, Steroidogenic, and Transcriptomic Assessment of the Corpus Luteum in Holstein Cows after Spontaneous or Hormone-Induced Ovulation
Authors: Ponce-Barajas Patricio , Colazo Marcos G. , Behrouzi Amir , Ree Todd O. , Kastelic John P. , Ambrose Divakar J.
Published: July 2023

There is evidence that replacing the gonadotropin-releasing hormone (GnRH) with porcine luteinizing hormone (pLH) to synchronize ovulation prior to artificial insemination (AI) increased pregnancy per AI in dairy cows without affecting blood progesterone (P4) concentrations. Whether morphologic, steroidogenic, and transcriptomic differences exist among corpora lutea (CL) formed after ovulation induced by GnRH and pLH is unclear. Our main objective, therefore, was to compare CL characteristics between GnRH- and pLH-induced CL. In 24 non-lactating Holstein cows, ovulations were spontaneous (Spont-Ov) or induced with 100 µg GnRH, 25 mg pLH, or 1 mg estradiol benzoate (EB), with CL excised 12 d after ovulation. In pLH- versus GnRH-treated cows, the duration of elevated LH (above baseline) was prolonged (10 versus 6 h, respectively, p < 0.01), but CL dimensions, pixel intensity of CL images, proportions of steroidogenic and non-steroidogenic luteal cells, and mean plasma LH did not significantly differ. Post-ovulation mean plasma P4 (ng/mL) did not differ among Spont-Ov (3.0) pLH (3.1) or GnRH (3.0) cows but were lower in EB cows (2.0). In vitro P4 concentration was greater in luteal explants of pLH-treated cows than in all other groups (combined means, 16.0 vs. 12.3 µg/mL, p < 0.02). Relative abundance of mRNA for oxytocin receptor (OXTR) was 2-fold higher (p < 0.01) in CL of pLH vs. GnRH cows and highest in Spont-Ov CL. In summary, pLH-treated cows had a longer LH peak, and greatest luteal tissue concentrations and in vitro production of P4. We inferred that increased P4 concentrations at the ovarian–uterine level in pLH-treated cows could have promoted embryo development and increased pregnancy per AI.
Influence of Equilibration Time and Bull-Specific Extender for Cryopreservation on Semen Quality and Fertility in German Holstein Friesian Bulls: A Controlled Field Trial
Authors: Pieper Laura , Meschede Tristan , Jung Markus , Janowitz Ulrich , Schulze Martin
Published: July 2023

Equilibration with an extender is necessary to allow cryopreservation of bovine sperm. The aim of trial 1 was to assess the effect of 24 h versus 4 h equilibration time with three different extenders on sperm quality and to select the preferred extender for each bull. The aim of trial 2 was to investigate the effect of using a 24 h equilibration time with a bull-specific extender on field fertility. For trial 1, three ejaculates each from eight Holstein Friesian breeding bulls were used as the split-sample, including two equilibration times (4 h and 24 h) and three extenders (BioXcell, Triladyl, and OptiXcell). For trial 2, from 5 to 10 ejaculates from the same bulls were collected and treated (split-sample) as BioXcell with 4 h equilibration and either Triladyl or OptiXcell, both with 24 h equilibration. A total of 11,059 straws were used for insemination of cows and heifers. For Triladyl, progressive sperm motility, acrosome defects, and plasma membrane and acrosome integrity improved with a 24 h compared to a 4 h equilibration time. Four bulls each were used with Triladyl and OptiXcell for trial 2. In trial 2, non-return rates did not differ among groups. Therefore, using a 24 h equilibration time might improve in vitro sperm parameters, depending on the extender used. Moreover, it would be possible to change from 4 h to 24 h equilibration time without impairing field fertility.
Simulated Gastrointestinal Digestion of Chestnut (Castanea sativa Mill.) Shell Extract Prepared by Subcritical Water Extraction: Bioaccessibility, Bioactivity, and Intestinal Permeability by In Vitro Assays
Authors: Pinto Diana , Silva Ana Margarida , Dall’Acqua Stefano , Sut Stefania , Vallverdú-Queralt Anna , Delerue-Matos Cristina , Rodrigues Francisca
Published: July 2023

Chestnut shells (CSs) are an appealing source of bioactive molecules, and constitute a popular research topic. This study explores the effects of in vitro gastrointestinal digestion and intestinal permeability on the bioaccessibility and bioactivity of polyphenols from CS extract prepared by subcritical water extraction (SWE). The results unveiled higher phenolic concentrations retained after gastric and intestinal digestion. The bioaccessibility and antioxidant/antiradical properties were enhanced in the following order: oral < gastric ≤ intestinal digests, attaining 40% of the maximum bioaccessibility. Ellagic acid was the main polyphenol in the digested and undigested extract, while pyrogallol–protocatechuic acid derivative was only quantified in the digests. The CS extract revealed potential mild hypoglycemic (<25%) and neuroprotective (<75%) properties before and after in vitro digestion, along with upmodulating the antioxidant enzymes’ activities and downregulating the lipid peroxidation. The intestinal permeation of ellagic acid achieved 22.89% after 240 min. This study highlighted the efficacy of the CS extract on the delivery of polyphenols, sustaining its promising use as nutraceutical ingredient.
Internet Wizard for Enhancing Open-Domain Question-Answering Chatbot Knowledge Base in Education
Authors: Mzwri Kovan , Turcsányi-Szabo Márta
Published: July 2023

Chatbots have gained widespread popularity for their task automation capabilities and consistent availability in various domains, including education. However, their ability to adapt to the continuously evolving and dynamic nature of knowledge is limited. This research investigates the implementation of an internet wizard to enhance the knowledge base of an open-domain question-answering chatbot. The proposed approach leverages search engines, particularly Google, and its features, including feature snippets, knowledge graph, and organic search, in conjunction with data science and natural language models. This mechanism empowers the chatbot to dynamically access the extensive and up-to-date knowledge available on the web, enabling the provision of real time and pertinent answers to user queries sourced from web documents. A pilot study in a higher education context evaluated the chatbot’s mechanism and features, confirming its proficiency in generating responses across a broad range of educational and non-educational topics. Positive feedback and high user satisfaction validate these findings. Notably, the chatbot’s dynamic feature of retrieving related or follow-up questions from search engines significantly enhances student engagement and facilitates exploration of supplementary information beyond the curriculum.
Whole Rock, Mineral Chemistry during Skarn Mineralization-Case Study from Tongshan Cu-Mo Skarn Profile
Authors: Bi Ran , Wang Fangyue , Zhang Wenqi
Published: July 2023

Studying the activation, migration and precipitation processes of ore-forming elements is essential for understanding the genesis and mechanisms of skarn deposits. A typical skarn profile formed by the intrusion of Yanshanian granodiorite into the Carboniferous carbonate strata was studied. The profile is highly consistent with the classic skarn profile, ranging from the intrusion, weak alteration belt, skarn belt (inner and outer skarn belt) and mineralization belt (mainly characterized by Cu mineralization) to the surrounding marble without being affected by late-stage low-temperature or supergene weathering alteration. Whole-rock data show that the major and trace elements exhibit relatively small changes in the granodiorite and inner skarn, but huge variation in the boundary between the inner and outer skarn; Na, Al, Ti and Sr show significant decreases, while Fe, Mg, Zn, V and Ni show significant increases. The elemental content in the outer skarn is 10–100 times or more higher than that in the marble, but the elements such as Ca, Sr and Cs diluted from the marble. During the migration process from the inner skarn to the outer skarn, some elements (such as K, Rb and Ba) were depleted in the inner, but not enriched in the outer, indicating that they may migrate to farther locations. Grossularite developed in the inner skarn, with light rare earth element (LREE) depletion and heavy REE enrichment, as well as positive and negative anomalies of Eu (δEu = 0.42–3.95). Andradite developed in the outer skarn, with zonation development, light REE enrichment, and heavy REE depletion and a positive Eu anomaly (δEu = 0.36–46.83). Some negative Eu anomalies appear at the edges of garnets in the outer skarn, indicating fluctuations in fO2 during the late skarn process. A positive correlation between Fe3+ and REE3+ in the garnets from the inner skarn, as well as between Al3+ and REE3+ from the outer skarn indicated that there are different YAG substitution mechanisms of REE between the inner and outer skarn. Low garnet REE contents and highly variable Y/Ho ratios in outer skarn suggest that the significant fluctuations in REEs may be primarily controlled by water-rock interactions. Considering the whole-rock major and trace element contents, as well as the trace element features of garnet, we found that whole-rock Na, Al, Ti and Sr elements, garnet Ti, Zr and Nb elements exhibit significant differences between the inner and outer skarn. These characteristics can be used to distinguish the boundary between the rock body and carbonate during the skarnification process.
K-Means Clustering of 51 Geospatial Layers Identified for Use in Continental-Scale Modeling of Outdoor Acoustic Environments
Authors: Pedersen Katrina , Jensen Ryan R. , Hall Lucas K. , Cutler Mitchell C. , Transtrum Mark K. , Gee Kent L. , Lympany Shane V.
Published: July 2023

Applying machine learning methods to geographic data provides insights into spatial patterns in the data as well as assists in interpreting and describing environments. This paper investigates the results of k-means clustering applied to 51 geospatial layers, selected and scaled for a model of outdoor acoustic environments, in the continental United States. Silhouette and elbow analyses were performed to identify an appropriate number of clusters (eight). Cluster maps are shown and the clusters are described, using correlations between the geospatial layers and clusters to identify distinguishing characteristics for each cluster. A subclustering analysis is presented in which each of the original eight clusters is further divided into two clusters. Because the clustering analysis used geospatial layers relevant to modeling outdoor acoustics, the geospatially distinct environments corresponding to the clusters may aid in characterizing acoustically distinct environments. Therefore, the clustering analysis can guide data collection for the problem of modeling outdoor acoustic environments by identifying poorly sampled regions of the feature space (i.e., clusters which are not well-represented in the training data).
A Wasserstein Generative Adversarial Network–Gradient Penalty-Based Model with Imbalanced Data Enhancement for Network Intrusion Detection
Authors: Lee Gwo-Chuan , Li Jyun-Hong , Li Zi-Yang
Published: July 2023

In today’s network intrusion detection systems (NIDS), certain types of network attack packets are sparse compared to regular network packets, making them challenging to collect, and resulting in significant data imbalances in public NIDS datasets. With respect to attack types with rare data, it is difficult to classify them, even by using various algorithms such as machine learning and deep learning. To address this issue, this study proposes a data augmentation technique based on the WGAN-GP model to enhance the recognition accuracy of sparse attacks in network intrusion detection. The enhanced performance of the WGAN-GP model on sparse attack classes is validated by evaluating three sparse data generation methods, namely Gaussian noise, WGAN-GP, and SMOTE, using the NSL-KDD dataset. Additionally, machine learning algorithms, including KNN, SVM, random forest, and XGBoost, as well as neural network models such as multilayer perceptual neural networks (MLP) and convolutional neural networks (CNN), are applied to classify the enhanced NSL-KDD dataset. Experimental results revealed that the WGAN-GP generation model is the most effective for detecting sparse data probes. Furthermore, a two-stage fine-tuning algorithm based on the WGAN-GP model is developed, fine-tuning the classification algorithms and model parameters to optimize the recognition accuracy of the sparse data probes. The final experimental results demonstrate that the MLP classifier significantly increases the accuracy rate from 74% to 80% after fine tuning, surpassing all other classifiers. The proposed method exhibits a 10%, 7%, and 13% improvement over untuned Gaussian noise enhancement, untuned SMOTE enhancement, and no enhancement.
Sound Wave Absorption Coefficient and Sound Velocity in Thermally Modified Wood
Authors: Mania Przemysław , Flach Artur , Pilarska Marta
Published: July 2023

The present work analyses the absorption coefficient of sound waves and the speed of sound propagation in thermally modified wood. The high resistance to weathering, fungi, and better dimensional stability, and therefore the broad physical properties of this material, are well known. However, the literature lacks numerous analyses of its acoustic characteristics. During the study, high-density species, such as oak, red oak, and beech were used, in contrast to pine. Pine wood during this test was characterised by a most rapid increase in the sound absorption coefficient value, in the range of 1000–6300 Hz, and reached the highest value from all wood species. Among all species, the highest value of the examined parameter was obtained for beech wood and pine wood, which were 0.213 (at frequency 3 kHz) and 0.183 (at 6.3 kHz), respectively. The sound velocity decreased for all species only in the tangential direction.
Characterizing the As-Fabricated State of Additively Fabricated IN718 Using Ultrasonic Nondestructive Evaluation
Authors: Miles Zebadiah , Aydogan Beytullah , Huanes-Alvan Guillermo , Sahasrabudhe Himanshu , Chakrapani Sunil Kishore
Published: July 2023

This article reports on the characterization of the “as-fabricated” state of Inconel 718 samples fabricated using laser directed energy deposition (DED). Laser-DED is known to produce complex metastable microstructures that can significantly influence the baseline ultrasonic response compared to conventional processing methods. The present work uses three parameters to characterize the samples: (a) ultrasonic velocity, (b) an attenuation coefficient, and (c) a backscatter coefficient. The baseline ultrasonic response from the DED sample was compared against the ultrasonic properties of conventional IN718 samples reported in the literature. The results suggest that strong grain boundary scattering from large macrograins can lead to attenuation and backscatter values that are significantly higher than conventional samples. Additionally, the results including velocities, attenuation and backscatter coefficients were found to be dependent on the fabrication direction, with the build direction being different from the transverse directions. Finally, destructive analysis was used to develop conjectures to explain the experimentally observed ultrasonic response.
Sugar-Induced Cell Death in the Yeast S. cerevisiae Is Accompanied by the Release of Octanoic Acid, Which Does Not Originate from the Fatty Acid Synthesis Type II Mitochondrial System
Authors: Avtukh Alexander , Baskunov Boris , Keshelava Varlam , Valiakhmetov Airat
Published: July 2023

Incubation of the yeast S. cerevisiae with glucose, in the absence of other nutrients, leads to Sugar-Induced Cell Death (SICD), accompanied by the accumulation of Reactive Oxygen Species (ROS). Yeast acidifies the environment during glucose metabolism not only as a result of the activity of the H+-ATPase of the plasma membrane but also due to the release of carboxylic acids. Acetic acid is known to induce apoptosis in growing yeast. We analyzed the composition of the incubation medium and found octanoic acid (OA) but no other carboxylic acids. Its concentration (0.675 µM) was significantly lower than the one at which OA had a toxic effect on the cell. However, the theoretically calculated concentration of OA inside the cell (about 200 μM) was found to be high enough to lead to cell necrosis. To test the hypothesis that OA might cause SICD, we used a ΔACP1 strain incapable of synthesizing OA in the yeast mitochondrial Fatty Acid Synthesis type II system (FAS-II). The deletion of the ACP1 gene did not affect the OA content in the medium. But, on the other hand, OA is a precursor of lipoic acid, which has antioxidant properties. However, strains with deleted genes for lipoic acid biosynthesis from OA (ΔPPT2, ΔLIP2, ΔLIP5, and ΔSGV3) showed no change in ROS and SICD levels. Thus, lipoic acid synthesized in FAS-II does not protect cells from ROS accumulated during SICD. We conclude that OA synthesized in the mitochondrial FAS-II system and its derivative lipoic acid are not involved in SICD in yeast S. cerevisiae.
Exploring the Opportunities of Haptic Technology in the Practice of Visually Impaired and Blind Sound Creatives
Authors: Harrison Jacob , Lucas Alex , Cunningham James , McPherson Andrew P. , Schroeder Franziska
Published: July 2023

Visually impaired and blind (VIB) people as a community face several access barriers when using technology. For users of specialist technology, such as digital audio workstations (DAWs), these access barriers become increasingly complex—often stemming from a vision-centric approach to user interface design. Haptic technologies may present opportunities to leverage the sense of touch to address these access barriers. In this article, we describe a participant study involving interviews with twenty VIB sound creatives who work with DAWs. Through a combination of semi-structured interviews and a thematic analysis of the interview data, we identify key issues relating to haptic audio and accessibility from the perspective of VIB sound creatives. We introduce the technical and practical barriers that VIB sound creatives encounter, which haptic technology may be capable of addressing. We also discuss the social and cultural aspects contributing to VIB people’s uptake of new technology and access to the music technology industry.
New Results on the Sequence Spaces Inclusion Equations of the Form F⊂E+Fx′ Where F, F′ ∈ {w0, w, w∞}
Authors: de Malafosse Bruno , Malkowsky Eberhard , Rakočević Vladimir
Published: July 2023

We determine the multipliers M(X,Y) where X, Y∈{w0,w,w∞}, and we apply these results to the solvability of both the (SSIE) of the form F⊂E+wx, where F∈{w0,w,w∞}, and the (SSIE) w⊂E+Wx0 and w⊂E+Wx.
Clodronate Liposome-Mediated Phagocytic Hemocyte Depletion Affects the Regeneration of the Cephalic Tentacle of the Invasive Snail, Pomacea canaliculata
Authors: Bergamini Giulia , Sacchi Sandro , Ferri Anita , Franchi Nicola , Montanari Monica , Ahmad Mohamad , Losi Chiara , Nasi Milena , Cocchi Marina , Malagoli Davide
Published: July 2023

After amputation, granular hemocytes infiltrate the blastema of regenerating cephalic tentacles of the freshwater snail Pomacea canaliculata. Here, the circulating phagocytic hemocytes were chemically depleted by injecting the snails with clodronate liposomes, and the effects on the cephalic tentacle regeneration onset and on Pc-Hemocyanin, Pc-transglutaminase (Pc-TG) and Pc-Allograft Inflammatory Factor-1 (Pc-AIF-1) gene expressions were investigated. Flow cytometry analysis demonstrated that clodronate liposomes targeted large circulating hemocytes, resulting in a transient decrease in their number. Corresponding with the phagocyte depletion, tentacle regeneration onset was halted, and it resumed at the expected pace when clodronate liposome effects were no longer visible. In addition to the regeneration progress, the expressions of Pc-Hemocyanin, Pc-TG, and Pc-AIF-1, which are markers of hemocyte-mediated functions like oxygen transport and immunity, clotting, and inflammation, were modified. After the injection of clodronate liposomes, a specific computer-assisted image analysis protocol still evidenced the presence of granular hemocytes in the tentacle blastema. This is consistent with reports indicating the large and agranular hemocyte population as the most represented among the professional phagocytes of P. canaliculata and with the hypothesis that different hemocyte morphologies could exert diverse biological functions, as it has been observed in other invertebrates.
Single-Cell Atlas Reveals the Hemocyte Subpopulations and Stress Responses in Asian Giant Softshell Turtle during Hibernation
Authors: Hong Xiaoyou , Wang Yakun , Wang Kaikuo , Wei Chengqing , Li Wei , Yu Lingyun , Xu Haoyang , Zhu Junxian , Zhu Xinping , Liu Xiaoli
Published: July 2023

Hibernation in turtle species is an adaptive survival strategy to colder winter conditions or food restrictions. However, the mechanisms underlying seasonal adaptions remain unclear. In the present study, we collected hemocytes from Pelochelys cantorii and compared the molecular signature of these cells between the active state and hibernation period based on single-cell RNA sequencing (scRNA-seq) analysis. We found six cell types and identified a list of new marker genes for each cell subpopulation. Moreover, several heat shock genes, including the Hsp40 family chaperone gene (DNAJ) and HSP temperature-responsive genes (HSPs), were upregulated during the hibernation period, which predicted these genes may play crucial roles in the stress response during hibernation. Additionally, compared to hemocytes in the active state, several upregulated differentially expressed immune-related genes, such as stat1, traf3, and socs6, were identified in hemocytes during the hibernation period, thus indicating the important immune function of hemocytes. Therefore, our findings provide a unified classification of P. cantorii hemocytes and identify the genes related to the stress response, thereby providing a better understanding of the adaptive mechanisms of hibernation.
Targeting Endothelial HIF2α/ARNT Expression for Ischemic Heart Disease Therapy
Authors: Ullah Karim , Ai Lizhuo , Humayun Zainab , Wu Rongxue
Published: July 2023

Ischemic heart disease (IHD) is a major cause of mortality and morbidity worldwide, with novel therapeutic strategies urgently needed. Endothelial dysfunction is a hallmark of IHD, contributing to its development and progression. Hypoxia-inducible factors (HIFs) are transcription factors activated in response to low oxygen levels, playing crucial roles in various pathophysiological processes related to cardiovascular diseases. Among the HIF isoforms, HIF2α is predominantly expressed in cardiac vascular endothelial cells and has a key role in cardiovascular diseases. HIFβ, also known as ARNT, is the obligate binding partner of HIFα subunits and is necessary for HIFα’s transcriptional activity. ARNT itself plays an essential role in the development of the cardiovascular system, regulating angiogenesis, limiting inflammatory cytokine production, and protecting against cardiomyopathy. This review provides an overview of the current understanding of HIF2α and ARNT signaling in endothelial cell function and dysfunction and their involvement in IHD pathogenesis. We highlight their roles in inflammation and maintaining the integrity of the endothelial barrier, as well as their potential as therapeutic targets for IHD.
An N-Cyanoamide Derivative of Lithocholic Acid Co-Operates with Lysophosphatidic Acid to Promote Human Osteoblast (MG63) Differentiation
Authors: Mansell Jason P. , Tanatani Aya , Kagechika Hiroyuki
Published: July 2023

Less-calcaemic vitamin D receptor (VDR) agonists have the potential to promote osteoblast maturation in a bone regenerative setting. The emergence of lithocholic acid (LCA) as a bona fide VDR agonist holds promise as an adjunct for arthroplasty following reports that it was less calcaemic than calcitriol (1,25D). However, LCA and some earlier derivatives, e.g., LCA acetate, had to be used at much higher concentrations than 1,25D to elicit comparable effects on osteoblasts. However, recent developments have led to the generation of far more potent LCA derivatives that even outperform the efficacy of 1,25D. These new compounds include the cyanoamide derivative, Dcha-150 (also known as AY2-79). In light of this significant development, we sought to ascertain the ability of Dcha-150 to promote human osteoblast maturation by monitoring alkaline phosphatase (ALP) and osteocalcin (OC) expression. The treatment of MG63 cells with Dcha-150 led to the production of OC. When Dcha-150 was co-administered with lysophosphatidic acid (LPA) or an LPA analogue, a synergistic increase in ALP activity occurred, with Dcha-150 showing greater potency compared to 1,25D. We also provide evidence that this synergy is likely attributed to the actions of myocardin-related transcription factor (MRTF)–serum response factor (SRF) gene transcription following LPA-receptor-induced cytoskeletal reorganisation.
The Novel MDM4 Inhibitor CEP-1347 Activates the p53 Pathway and Blocks Malignant Meningioma Growth In Vitro and In Vivo
Authors: Mitobe Yuta , Suzuki Shuhei , Nakagawa-Saito Yurika , Togashi Keita , Sugai Asuka , Sonoda Yukihiko , Kitanaka Chifumi , Okada Masashi
Published: July 2023

A significant proportion of meningiomas are clinically aggressive, but there is currently no effective chemotherapy for meningiomas. An increasing number of studies have been conducted to develop targeted therapies, yet none have focused on the p53 pathway as a potential target. In this study, we aimed to determine the in vitro and in vivo effects of CEP-1347, a small-molecule inhibitor of MDM4 with known safety in humans. The effects of CEP-1347 and MDM4 knockdown on the p53 pathway in human meningioma cell lines with and without p53 mutation were examined by RT-PCR and Western blot analyses. The growth inhibitory effects of CEP-1347 were examined in vitro and in a mouse xenograft model of meningioma. In vitro, CEP-1347 at clinically relevant concentrations inhibited MDM4 expression, activated the p53 pathway in malignant meningioma cells with wild-type p53, and exhibited preferential growth inhibitory effects on cells expressing wild-type p53, which was mostly mimicked by MDM4 knockdown. CEP-1347 effectively inhibited the growth of malignant meningioma xenografts at a dose that was far lower than the maximum dose that could be safely given to humans. Our findings suggest targeting the p53 pathway with CEP-1347 represents a novel and viable approach to treating aggressive meningiomas.
A Comparative Analysis of Strain and 2D Shear Wave Elastography in the Diagnosis of Autoimmune Thyroiditis in Pediatric Patients
Authors: Roi Cristina Mihaela , Borlea Andreea , Mihuta Monica Simina , Paul Corina , Stoian Dana
Published: July 2023

This paper aims to assess the usefulness of shear-wave elastography (SWE) and strain elastography (SE) for identifying and monitoring thyroid gland changes in children diagnosed with chronic autoimmune thyroiditis (CAT). Our study included 77 children between the ages of six and eighteen. Of these, 45 were diagnosed with CAT, while 32 had no thyroid pathology. Following a clinical examination and laboratory tests, an ultrasound was carried out, and then a SE (using a Hitachi Preirus machine) and SWE (using an Aixplorer Mach 30, Supersonic imagine, France) were performed in the same session. The median thyroid elastic index (EI) in the CAT group was 13.8 (13.3–17) kPa compared to 10.1 (9.3–11.2) kPa in healthy children (p < 0.0001). We found a median strain ratio (SR) of 1.2 (1.2–1.3) for CAT compared to 0.7 (0.6–0.9) for healthy thyroid tissue (p < 0.0001). The optimal cut-off value for predicting the presence of CAT in children using SR was >1 (Se = 82.2%, Sp = 87.5%, PPV = 90.2%, and NPV = 77.8%, AUROC = 0.850), while using SWE, the optimal cut-off value for predicting the presence of CAT in children was >12 kPa (Se = 88.9%, Sp = 93.7%, PPV = 95.2%, and NPV = 85.5%, AUROC = 0.943). Both techniques are useful for measuring thyroid tissue elasticity, and their diagnostic accuracy and reliability are comparable.
Cell-Penetrating Peptide-Based Delivery of Macromolecular Drugs: Development, Strategies, and Progress
Authors: Sun Zhe , Huang Jinhai , Fishelson Zvi , Wang Chenhui , Zhang Sihe
Published: July 2023

Cell-penetrating peptides (CPPs), developed for more than 30 years, are still being extensively studied due to their excellent delivery performance. Compared with other delivery vehicles, CPPs hold promise for delivering different types of drugs. Here, we review the development process of CPPs and summarize the composition and classification of the CPP-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers. We also summarize the optimization routes of CPP-based macromolecular drug delivery from stability and targeting perspectives. Strategies for enhanced endosomal escape, which prolong its half-life in blood, improved targeting efficiency and stimuli-responsive design are comprehensively summarized for CPP-based macromolecule delivery. Finally, after concluding the clinical trials of CPP-based drug delivery systems, we extracted the necessary conditions for a successful CPP-based delivery system. This review provides the latest framework for the CPP-based delivery of macromolecular drugs and summarizes the optimized strategies to improve delivery efficiency.
Evaluation of Cx43 Gap Junction Inhibitors Using a Quantitative Structure-Activity Relationship Model
Authors: Matusevičiūtė Ramona , Ignatavičiūtė Eglė , Mickus Rokas , Bordel Sergio , Skeberdis Vytenis Arvydas , Raškevičius Vytautas
Published: July 2023

Gap junctions (GJs) made of connexin-43 (Cx43) are necessary for the conduction of electrical impulses in the heart. Modulation of Cx43 GJ activity may be beneficial in the treatment of cardiac arrhythmias and other dysfunctions. The search for novel GJ-modulating agents using molecular docking allows for the accurate prediction of binding affinities of ligands, which, unfortunately, often poorly correlate with their potencies. The objective of this study was to demonstrate that a Quantitative Structure-Activity Relationship (QSAR) model could be used for more precise identification of potent Cx43 GJ inhibitors. Using molecular docking, QSAR, and 3D-QSAR, we evaluated 16 known Cx43 GJ inhibitors, suggested the monocyclic monoterpene d-limonene as a putative Cx43 inhibitor, and tested it experimentally in HeLa cells expressing exogenous Cx43. The predicted concentrations required to produce 50% of the maximal effect (IC50) for each of these compounds were compared with those determined experimentally (pIC50 and eIC50, respectively). The pIC50ies of d-limonene and other Cx43 GJ inhibitors examined by our QSAR and 3D-QSAR models showed a good correlation with their eIC50ies (R = 0.88 and 0.90, respectively) in contrast to pIC50ies obtained from molecular docking (R = 0.78). However, molecular docking suggests that inhibitor potency may depend on their docking conformation on Cx43. Searching for new potent, selective, and specific inhibitors of GJ channels, we propose to perform the primary screening of new putative compounds using the QSAR model, followed by the validation of the most suitable candidates by patch-clamp techniques.
Effects of Sleep Deprivation on Performance during a Change Signal Task with Adaptive Dynamics
Authors: Honn Kimberly A. , Morris Megan B. , Jackson Melinda L. , Van Dongen Hans P. A. , Gunzelmann Glenn
Published: July 2023

Augmented cognition, which refers to real-time modifications to a human–system interface to improve performance and includes dynamic task environments with automated adaptations, can serve to protect against performance impairment under challenging work conditions. However, the effectiveness of augmented cognition as a countermeasure for performance impairment due to sleep loss is unknown. Here, in a controlled laboratory study, an adaptive version of a Change Signal task was administered repeatedly to healthy adults randomized to 62 h of total sleep deprivation (TSD) or a rested control condition. In the computerized task, a left- or right-facing arrow was presented to start each trial. In a subset of trials, a second arrow facing the opposite direction was presented after a delay. Subjects were to respond within 1000 ms of the trial start by pressing the arrow key corresponding to the single arrow (Go trials) or to the second arrow when present (Change trials). The Change Signal Delay (CSD)—i.e., the delay between the appearance of the first and second arrows—was shortened following incorrect responses and lengthened following correct responses so that subsequent Change trials became easier or harder, respectively. The task featured two distinct CSD dynamics, which produced relatively stable low and high error rates when subjects were rested (Low and High Error Likelihood trials, respectively). During TSD, the High Error Likelihood trials produced the same, relatively high error rate, but the Low Error Likelihood trials produced a higher error rate than in the rested condition. Thus, sleep loss altered the effectiveness of the adaptive dynamics in the Change Signal task. A principal component analysis revealed that while subjects varied in their performance of the task along a single dominant dimension when rested, a second inter-individual differences dimension emerged during TSD. These findings suggest a need for further investigation of the interaction between augmented cognition approaches and sleep deprivation in order to determine whether and how augmented cognition can be relied upon as a countermeasure to performance impairment in operational settings with sleep loss.
Schizophrenia: A Review of Social Risk Factors That Affect Women
Authors: González-Rodríguez Alexandre , Natividad Mentxu , Seeman Mary V. , Paolini Jennipher Paola , Balagué Ariadna , Román Eloïsa , Izquierdo Eduard , Pérez Anabel , Vallet Anna , Salvador Mireia , Monreal José Antonio
Published: July 2023

Social risk factors are long-term or repeated environmental exposures in childhood and youth that change the brain and may, via epigenetic effects, change gene expression. They thus have the power to initiate or aggravate mental disorders. Because these effects can be mediated via hormonal or immune/inflammatory pathways that differ between men and women, their influence is often sex-specific. The goal of this narrative review is to explore the literature on social risk factors as they affect women with schizophrenia. We searched the PubMed and Scopus databases from 2000 to May 2023 using terms referring to the various social determinants of health in conjunction with “women” and with “schizophrenia”. A total of 57 studies fulfilled the inclusion criteria. In the domains of childhood and adult abuse or trauma, victimization, stigma, housing, and socioeconomics, women with schizophrenia showed greater probability than their male peers of suffering negative consequences. Interventions targeting appropriate housing, income support, social and parenting support, protection from abuse, violence, and mothering-directed stigma have, to different degrees, yielded success in reducing stress levels and alleviating the many burdens of schizophrenia in women.
Improvement Strategies for Enhancing User Satisfaction with Spatial Publicness in Privately Owned Public Open Space in Post COVID-19: A Case from Italy
Authors: Shan Jingwen , Cai Gangwei , Lin Alin , Xu Binyan
Published: July 2023

In the past five decades, privately owned public open spaces (POPOS) have become increasingly prevalent and significant in urban areas. However, the COVID-19 pandemic has led to significant changes in the performance and utilization of these spaces as the internal functions of adjacent buildings were shut down. This offers an opportunity to address the research gap in the theory of publicness—one of the most crucial attributes in these places due to their ownership and management—by assessing user satisfaction with spatial publicness in POPOS independently of adjacent commercial and corporate functions. This study aims to identify key environmental factors that significantly affect user satisfaction during a pandemic and develop adaptive strategies to enhance user satisfaction and resilience in such contexts. Based on a comprehensive literature review of previous assessment criteria for spatial publicness, the study proposes 30 vital indicators. Importance-performance analysis (IPA) is employed to analyze changes in user satisfaction regarding these vital indicators. Data from 386 users of Plaza Gae Aulenti in Milan, Italy were collected via an online questionnaire. The findings reveal that optimizing physical facilities and visual permeability are crucial environmental factors for promoting a higher degree of publicness during pandemics, as evidenced by a comparison of pre-COVID-19 and post-COVID-19 feedback. This study addresses the research gap by assessing the spatial publicness of POPOS independently of adjacent commercial and corporate functions. These findings have practical implications for the design and regulation of future projects in the post-COVID-19 era.
Circulating Natural Killer Cells as Prognostic Value for Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: Correlation with Sarcopenia
Authors: Tenuta Marta , Pandozzi Carla , Sciarra Francesca , Campolo Federica , Gelibter Alain J. , Sirgiovanni Grazia , Cortesi Enrico , Lenzi Andrea , Isidori Andrea M. , Sbardella Emilia , Venneri Mary Anna
Published: July 2023

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of tumors. Natural killer (NK) cells can play an important role in cancer immune surveillance. The aim of this prospective observational study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with advanced non-small-cell lung cancer (NSCLC) receiving ICIs in order to identify predictive factors for better survival outcomes. Methods: Forty-seven stage IV NSCLC patients were enrolled. Patients underwent baseline (T0) and longitudinal (T1) evaluations after ICIs. Peripheral immune blood cell counts were analyzed using flow cytometry. Results: Basal levels of CD3−CD56+ NK cells were higher in patients with controlled disease (DC) compared to progression disease (PD) patients (127 cells/µL vs. 27.8 cells/µL, p < 0.001). Lower NK cell values were independent prognostic factors for shorter overall survival (OS) (HR 0.992; 95% CI 0.987–0.997, p < 0.001) and progression-free survival (PFS) (HR 0.988; 95% CI 0.981–0.994, p < 0.001). During the longitudinal evaluation, CD3−CD56+ NK cells (138.1 cells/µL vs. 127 cells/µL, p = 0.025) and CD56bright NK cells (27.4 cells/µL vs. 18.1 cells/µL, p = 0.034) significantly increased in the DC group. Finally, lower values of CD3−CD56+ NK cells (28.3 cells/µL vs. 114.6 cells/µL, p = 0.004) and CD56dim NK cells (13.2 cells/µL vs. 89.4 cells/µL, p < 0.001) were found in sarcopenic patients compared to patients without sarcopenia. Conclusions: Peripheral NK cells could represent a non-invasive and useful tool to predict ICI therapy response in NSCLC patients, and the association of low NK cell levels with sarcopenia deserves even more attention in clinical evaluation.
Innovative Synthetic Approaches for Sulphate-Promoted Catalysts for Biomass Valorisation
Authors: Giordana Alessia , Pizzolitto Cristina , Ghedini Elena , Signoretto Michela , Operti Lorenza , Cerrato Giuseppina
Published: July 2023

In the present research, we report on an innovative and quick procedure for the synthesis of metal oxides: a sol-gel procedure which is followed by two steps that are assisted by microwaves (MW) heating. First, MW heating promotes gel drying and successively permits the calcination of the xerogel in a few minutes, using a susceptor that rapidly reaches high temperatures. The procedure was employed for the synthesis of zirconium dioxide (ZrO2), and MW-assisted calcination enables the collection of tetragonal ZrO2, as confirmed by different experimental techniques (PXRD, HR-TEM and Raman spectroscopy). Using this MW-assisted sol-gel procedure, a promoted sulphated zirconia (SZ) has been obtained. Both the nature and strength of SZ surface acidity have been investigated with FTIR spectroscopy using CO and 2,6-dimethylpyridine (2,6-DMP) as probe molecules. The obtained materials were tested as catalysts in acid hydrolysis of glucose to give 5-(hydroxymethyl)furfural (5-HMF). One of the obtained catalysts exhibited a better selectivity towards 5-HMF with respect to SZ material prepared by a classical precipitation route, suggesting that this procedure could be employed to obtain a well-known catalyst with a less energy-consuming procedure. Catalytic results also suggest that good selectivity to 5-HMF can be achieved in aqueous media in the presence of weak Lewis and Brønsted sites.
“Mens Sana in Cute Sana”—A State of the Art of Mutual Etiopathogenetic Influence and Relevant Pathophysiological Pathways between Skin and Mental Disorders: An Integrated Approach to Contemporary Psychopathological Scenarios
Authors: Papa Vincenzo , Li Pomi Federica , Borgia Francesco , Genovese Sara , Pioggia Giovanni , Gangemi Sebastiano
Published: July 2023

The negative socioeconomic impact of mental health disorders and skin diseases has increased in part due to the conflict between Russia and Ukraine, which has been a fertile ground for the emergence of psychopathologies. It is firmly established that there is a direct thread of etiopathogenetic communication between skin diseases and neuropsychiatric disorders, and the literature has tried to reveal the pathophysiological mechanisms governing such bidirectionality. This paper discusses this complex network of molecular pathways that are targeted by conventional and biological pharmacological agents that appear to impact two pathological spheres that previously seemed to have little connection. This molecular discussion is supplemented with a literature review, from a clinical viewpoint, regarding skin–brain etiopathogenetic bidirectionality. We focus on post-traumatic stress disorder (PTSD), which can be considered for all intents and purposes a systemic inflammatory disease that also affects the skin. A brief overview is also provided on the diagnostic–therapeutic and follow-up potential of oxidative and inflammatory markers potentially involved in the pathophysiological mechanisms treated. The aim is to clarify how these mechanisms may be useful in defining different stress-coping strategies and thus individual phenotypes of stress sensitivity/resistance in order to promote personalized medicine in the field of psychodermatology.
Structural and Kinetic Characterization of the SpeG Spermidine/Spermine N-acetyltransferase from Methicillin-Resistant Staphylococcus aureus USA300
Authors: Tsimbalyuk Sofiya , Shornikov Aleksander , Srivastava Parul , Le Van Thi Bich , Warren Imani , Khandokar Yogesh B. , Kuhn Misty L. , Forwood Jade K.
Published: July 2023

Polyamines are simple yet critical molecules with diverse roles in numerous pathogenic and non-pathogenic organisms. Regulating polyamine concentrations affects the transcription and translation of genes and proteins important for cell growth, stress, and toxicity. One way polyamine concentrations are maintained within the cell is via spermidine/spermine N-acetyltransferases (SSATs) that acetylate intracellular polyamines so they can be exported. The bacterial SpeG enzyme is an SSAT that exhibits a unique dodecameric structure and allosteric site compared to other SSATs that have been previously characterized. While its overall 3D structure is conserved, its presence and role in different bacterial pathogens are inconsistent. For example, not all bacteria have speG encoded in their genomes; in some bacteria, the speG gene is present but has become silenced, and in other bacteria, it has been acquired on mobile genetic elements. The latter is the case for methicillin-resistant Staphylococcus aureus (MRSA) USA300, where it appears to aid pathogenesis. To gain a greater understanding of the structure/function relationship of SpeG from the MRSA USA300 strain (SaSpeG), we determined its X-ray crystal structure in the presence and absence of spermine. Additionally, we showed the oligomeric state of SaSpeG is dynamic, and its homogeneity is affected by polyamines and AcCoA. Enzyme kinetic assays showed that pre-incubation with polyamines significantly affected the positive cooperativity toward spermine and spermidine and the catalytic efficiency of the enzyme. Furthermore, we showed bacterial SpeG enzymes do not have equivalent capabilities to acetylate aminopropyl versus aminbutyl ends of spermidine. Overall, this study provides new insight that will assist in understanding the SpeG enzyme and its role in pathogenic and non-pathogenic bacteria at a molecular level.
Immunochemical Identification of the Main Cell Wall Polysaccharides of the Early Land Plant Marchantia polymorpha
Authors: Kolkas Hasan , Burlat Vincent , Jamet Elisabeth
Published: July 2023

Plant primary cell walls are composite structures surrounding the protoplast and containing pectins, hemicelluloses, and cellulose polysaccharides, as well as proteins. Their composition changed during the evolution of the green lineage from algae to terrestrial plants, i.e., from an aquatic to a terrestrial environment. The constraints of life in terrestrial environments have generated new requirements for the organisms, necessitating adaptations, such as cell wall modifications. We have studied the cell wall polysaccharide composition of thalli of Marchantia polymorpha, a bryophyte belonging to one of the first land plant genera. Using a collection of specific antibodies raised against different cell wall polysaccharide epitopes, we were able to identify in polysaccharide-enriched fractions: pectins, including low-methylesterified homogalacturonans; rhamnogalacturonan I with arabinan side-chains; and hemicelluloses, such as xyloglucans with XXLG and XXXG modules, mannans, including galactomannans, and xylans. We could also show the even distribution of XXLG xyloglucans and galactomannans in the cell walls of thalli by immunocytochemistry. These results are discussed with regard to the cell wall proteome composition and in the context of the evolution of the green lineage. The cell wall polysaccharides of M. polymorpha illustrate the transition from the charophyte ancestors of terrestrial plants containing xyloglucans, xylans and mannans as hemicelluloses, and embryophytes which do not exhibit mannans as major primary cell wall polysaccharides.
One-Dimensional Modeling of Mass Transfer Processes in an Annular Centrifugal Contactor
Authors: Ritzler Peter M. , Weiss Clemens K. , Seyfang Bernhard C.
Published: July 2023

Due to the importance of process intensification, modeling of Annular Centrifugal Contactors (ACCs) is becoming of increasing interest. By the current state of scientific knowledge, universal modeling without high computing power of these complex apparatuses is not possible to a satisfactory degree. In this article, a one-dimensional model to describe the mass transfer during a physical extraction process in an ACC is presented. The model is based on solely geometrical data and operating conditions of the ACC, as well as physical properties of the components. Regarding the selection of physical properties, only physical properties that are easily accessible were used. With this model, mass transfer calculations are possible and therefore, the output concentrations can be predicted. Simulations of an ACC based on the model were done by creating and running a python code. Validation of the model was conducted by varying and comparing operating conditions in both the simulation and the experiments. Validation was completed successfully for a representative system of components and showed good agreement over a range of rotational frequencies and temperatures.