bluuebunny/crossref_metadata_2025 huggingface dataset:
PHILOSOPHICAL ANALYSIS OF INNOVATIVE AND CREATIVE FACTORS OF HUMAN CONSCIOUSNESS
Authors:   Donetsk National University of Economics and Trade named after Mykhailo Tugan-Baranovsky, Nikolenko K. V. , Melikova S. O. ,   Kryvyi Rih specialized school № 107 with in-depth study of English language
Published: June 2023

Objective. The objective of the article is to identify the problems of innovative and creative human activity in the field of consciousness as structural elements of transformative activity in order to improve and deepen the understanding of the creative process as such. Methods. The following methods are used to study the innovative and creative factors of human consciousness: natural-ontological and socio-ontological to analyze the peculiarities of the formation and development of consciousness, axiological — while assessing the importance of creativity and innovation as characteristics for the individual, moral and ethical methods in studying the consequences of creative and innovative process for humanity in general, as well as a constructive and destructive approaches to the interpretation of the welfare state. The scientific principles of the research are the principle of objectivity (in analyzing the results of the creative process and physiological features of consciousness), determinism (used to study the forms of manifestation of activity of consciousness), systematicity (general presentation of the material is based on a holistic perception of creativity in the system of individual, physiological, social and cultural norms). Results. The studied consciousness and spheres of social consciousness show that creativity is a necessary component of human consciousness. It appears in the mythological, religious and spiritual components. The innovative is a source of understanding the creative, it reveals the essential components of creation as such. Consciousness is a litmus test of various questions that do not have an unambiguous answer, manifesting itself as both the source and the result of solving these questions. The creative component of consciousness generates different types of reality, due to modern advances in science. Innovative and creative factors of human consciousness are due to psychological, anatomical and social factors. Creativity is understood as a characteristic creative activity of consciousness, a transformative force.
PECULIARITIES OF FRENCH YOUTH’S ARGOT
Authors:   Horlivka Institute for Foreign Languages HSEE “Donbass State Pedagogical University”, Potreba N. A.
Published: June 2023

Objective. The objective of the article is to determine the status of the youth’s argot and its role in modern French, as well as to identify the most productive models of the formation of the youth’s argot, which makes the language of young people more expressive and emotional. Methods. The work uses a complex of general scientific and special research methods, namely linguistic observation and description, analysis, systematization and generalization of scientific literature, which make it possible to understand the features of the French youth’s argot and its meaningful characteristics. Results. Young people’s language functions within any language and exists at all times, it changes only the quantitative composition and scope of application under the influence of both linguistic and non-linguistic factors. There are argots in the vocabulary of every modern young Frenchman, since they greatly simplify the understanding of any phenomena and increase the speed of assimilation of new information material. In recent decades there has been a constant evolution of the argot, which manifests itself in the growing penetration of argots into all spheres of life, it ceases to be a closed language and become part of the vocabulary of a significant number of French people. Global informatization has a particular impact on the French language. Over the past decades, the Internet has evolved from a specialized computer network into an open source of mass communication. And here, its own electronic youth culture is being formed, which is reflected in the emergence of new grammatical, syntactic, punctuation, lexical and other norms. The reasons for the formation of the modern youth’s argot is the saving of time and efforts, which gives rise to a huge number of different abbreviations of words and phrases; belonging of young people to a particular social group and classifying information from outsiders, which leads to a large number of argot; the desire to avoid the use of obscene expressions, in an abbreviated form lose the element of vulgarity; a desire to express their emotions and provide expressions of expressiveness and emotionality. Youth’s argot is not just a desire to rebel against generally accepted norms or lack of literary baggage for codified communication. It is a completely linguistic creativity, which develops especially rapidly during the period of social upheavals, cultural shifts. The author examines the content characteristics of youth’s argot.
Refugee Children’s Right to Education: Education of Syrian Refugee Children in Jordan – Reality and Prospects
Authors: Khater Maya
Published: June 2023

Background: Since the outbreak of political violence in Syria in 2011, vast numbers of Syrians have gone to the Jordanian border to escape one of the most devastating civil wars in recent times, and about one-third of the refugees fleeing their countries, i.e., about one million three hundred thousand Syrian refugees, have arrived. These refugees are distributed within the Zaatari, Azraq, Rakban, and Emirati-Jordanian camps. Some of them live outside the scope of these four camps, especially in the governorates of Irbid, Mafraq, Amman, and Zarqa. More than half of these refugees are children.
Methods: The research uses the descriptive analysis method, which is based on the detailed description and in-depth analysis of the topic of the study through gathering detailed data related to the research problem, analysing legal texts and relevant information as well as their clear interpretation, concluding with proposing appropriate solutions and recommendations aimed at supporting the right of Syrian refugee children in Jordan to obtain their right to education.
Results and Conclusions: The study concluded the importance of the efforts made by the Jordanian government, with the support of donors and humanitarian organisations, regarding assisting Syrian students in obtaining a quality education and its contribution to the steady increase in the percentage of children enrolled in education.
On the other hand, the study confirmed the many obstacles and difficulties that impede the education of Syrian refugees in Jordan, such as child labour and early marriage, the lack of appropriate educational infrastructure in light of the scarcity of essential financial resources, the lack of international funding; the limited availability of school, the shortage of qualified human resources to deal with refugee children, and the lack of the necessary documentation to enrol in education.
However, despite all the challenges and difficulties related to the education of Syrian refugees in Jordan, the opportunity remains to overcome the difficulties effectively, develop the educational reality, achieve an increase in the rates of absorption in the educational systems, and improve the quality of education provided to these students, which will contribute to the realisation of their dreams and aspirations and help them rebuild their society and host society alike.
Ectopic Thyroid Mimicking Lymph Node Metastasis of Thyroid Cancer
Authors: Cho Min Young , Kim Dong Young
Published: June 2023

Ectopic thyroid is a rare disease that occurs due to an error in the developmental stage of the embryo where the normal thyroid tissue is positioned at an area other than its normal site of the 2nd to 4th pretracheal area. Usually, the ectopic thyroid is discovered at the midline of a patient. We present this rare case of lateral ectopic thyroid mimicking the lymph node metastasis of thyroid cancer.
Enhancement of the technical and non-technical skills of nurse anesthesia students using the Anesthetic List Management Assessment Tool in Iran: a quasi-experimental study
Authors: Khalafi Ali , Kordnejad Maedeh , Saidkhani Vahid
Published: June 2023

Purpose: This study investigated the effect of evaluations based on the Anesthetic List Management Assessment Tool (ALMAT) form on improving the technical and non-technical skills of final-year nurse anesthesia students at Ahvaz Jundishapur University of Medical Sciences (AJUMS).Methods: This was a semi-experimental study with a pre-test and post-test design. It included 45 final-year nurse anesthesia students of AJUMS and lasted for 3 months. The technical and non-technical skills of the intervention group were assessed at 4 university hospitals using formative-feedback evaluation based on the ALMAT form, from induction of anesthesia until reaching mastery and independence. Finally, the students’ degree of improvement in technical and non-technical skills was compared between the intervention and control groups. Statistical tests (the independent t-test, paired t-test, and Mann-Whitney test) were used to analyze the data.Results: The rate of improvement in post-test scores of technical skills was significantly higher in the intervention group than in the control group (P˂0.0001). Similarly, the students in the intervention group received significantly higher post-test scores for non-technical skills than the students in the control group (P˂0.0001).Conclusion: The findings of this study showed that the use of ALMAT as a formative-feedback evaluation method to evaluate technical and non-technical skills had a significant effect on improving these skills and was effective in helping students learn and reach mastery and independence.
Quantifying regional feed utilization, production and nutrient waste emission of Norwegian salmon cage aquaculture
Authors: Wang CD , Olsen Y
Published: June 2023

We analyzed growth performance and waste emissions of cage aquaculture responding to biophysical conditions that vary along the coastline of Norway. The analysis is based on a published mass balance model predicting waste emissions and open quality-assured data from the Norwegian Directorate of Fisheries between 2016 and 2020. Results showed significant regional variation in feed conversion rate, with a steady increase from the Northern to Southern region (p < 0.001) and a co-occurring reduction in waste emission. The retention rate of feed carbon (C), nitrogen (N) and phosphorus (P) in tissues of farmed Atlantic salmon Salmo salar Linnaeus, 1758 varied from 39 to 43% of consumed nutrients across regions. The estimated defecation rate of C, N and P was 18% of consumption, whereas excretion or respiration varied from 39 to 43% across regions. This variability, along with farming methods and location characteristics, could potentially impact regional differences in benthic ecosystems. The regional differences in feed and environmental cost could potentially attract salmon farming to shift towards the Northern region, and this trend might become strengthened as water temperatures rise due to climate change. Additionally, salmon growth and feed intake rate interacted significantly with temperature (p < 0.001) and showed regular seasonal variation. The regulation of maximum allowed biomass restricts salmon farmers from increasing biomass beyond their maximum allowed level at any time. Nevertheless, the same biomass may cause higher waste in the summer. Therefore, we suggest an awareness of the seasonal increase in waste emissions and consideration of implementing environmental assessment for surface waters, which might be beneficial for decreasing the risk of reduced water quality.
SPOR YAPAN VE YAPMAYAN ÖĞRENCİLERİN ŞİDDET EĞİLİMİ VE SALDIRGANLIK DÜZEYLERİNİN İNCELENMESİ
Authors: ATATEKİN Burak , İSTANBULLU Aslihan
Published: June 2023

Bu araştırmada spor yapan ve yapmayan öğrencilerin şiddet eğilimi ve saldırganlık düzeylerinin incelenmesi amaçlanmıştır. Araştırmanın örneklemini 2022-2023 eğitim öğretim yılında devlete bağlı olan üç ortaokulda spor yapan (n=253) ve yapmayan (n=253) toplam 506 öğrenci oluşturmaktadır. Araştırmada nicel araştırma yöntemlerinden tarama modeli kullanılmıştır. Veriler “Kişisel Bilgi Formu”, “Şiddet Eğilimi Ölçeği” ve “Saldırganlık Ölçeği” kullanılarak elde edilmiştir. Verilerin analizinde bağımsız örneklem t testi ve Pearson korelasyon analizi kullanılmıştır. Araştırma sonuçlarına göre spor yapan ve yapmayan öğrencilerin şiddet eğilimi düzeyleri arasında spor yapan öğrenciler lehine istatistiki olarak anlamlı bir farklılığa rastlanmıştır ancak bu farkın düşük düzeyde anlamlı olduğu görülmüştür. Spor yapan ve yapmayan öğrencilerin saldırganlık düzeyleri arasında ise istatistiki olarak anlamlı bir farklılığa rastlanmamıştır. Spor yapan ve yapmayan öğrencilerin şiddet eğilimi düzeyi ile saldırganlık düzeyi arasındaki ilişkiye bakıldığında da pozitif yönde anlamlı ilişkiye rastlanmıştır. Bu sonuçlara göre spor yapmayan öğrencilerin spor yapan öğrencilere göre daha az şiddet ve saldırganlık düzeyine sahip olduğu ve şiddetin saldırganlığı ya da tam tersi olarak saldırganlığın da şiddeti arttırdığı görülmüştür. Literatürde yapılan araştırmaların farklı ve benzer sonuçlar taşıdığı düşünüldüğünde sporun şiddet eğilimi ve saldırganlık düzeyini azalttığını kesin olarak söylemek mümkün değildir. Buna rağmen çocukların kötü alışkanlık, bağımlılık, şiddet ve saldırganlık eğiliminden ayrı tutabilmek için spor etkinliklerine yöneltilmesi önerilmektedir.
Acute Dystonia Due to Pregabalin Abuse in an Adolescent
Authors: Çay Ezgi , Türker İkbal , Ekinci Faruk , Bilen Sevcan , Ozgur Horoz Ozden , Yılmaz Hayri , Yıldızdaş Dinçer
Published: June 2023

Pregabalin is a drug used to treat neuropathic pain, epilepsy, and fibromyalgia. However, the number of reported cases of pregabalin abuse is steadily growing. This case showed dystonia, an effect not previously documented as a consequence of pregabalin administration.
A 16-year-old male patient with no known pre-existing medical conditions was admitted to the pediatric emergency department for the first time, complaining of drowsiness caused by pregabalin abuse. During the patient's follow-up, dystonia was observed, and biperiden was administered at a repeating dose. Subsequently, he was moved to the pediatric intensive care unit (PICU) for further tests and treatment. After three days of follow-up, the patient was discharged due to the absence of complaints.
This case report presents dystonia resulting from pregabalin abuse, a condition that has not previously been documented in the literature.
Molecular and Phenotypic Characteristics of Short-Beaked Garfish Belone svetovidovi Collette and Parin, 1970 in a New Location, the Sea of Marmara
Authors: SEYHAN ÖZTÜRK Dilruba
Published: June 2023

There are two species of garfish belonging to the genus Belone (garfish B. belone and short-beaked garfish B. svetovidovi) in the coastal regions of Türkiye. It is known that Belone belone is distributed all around the Turkish coasts, and Belone svetovidovi is distributed only in the Mediterranean and Aegean coasts of Türkiye. These species’ morphological similarities and mainly overlapped morphological characters led to confusions for years. The present study represents the first detailed morphological and molecular analysis including twenty-two body portions and DNA barcode analysis of B. svetovidovi and reports the newly established populations in the Sea of Marmara with molecular and morphological evidences.
Financial Implications of the COVID-19 Pandemic on the Container Ship Time Charter Business
Authors: GENCER Hüseyin , TUZCUOĞLU Tolga
Published: June 2023

This study examines the financial implications of the COVID-19 pandemic on the container ship time charter business. In this context, the container charter transactions were derived from the Clarksons Research Database, which included the ship types, daily charter fees, ship ages, and total charter days. The empirical analysis employed the K-Means Algorithm to cluster the observations in which the elbow curves revealed three cluster centers in the pre-COVID period and four in the post-COVID era, respectively. Based on the industry-wide used threshold definitions, the clusters were then named according to the mean value of given features. In addition, the relative weight of each cluster was disclosed based on the number of transactions falling into the respective cluster. Accordingly, the pre-COVID period clusters were described as intermediate-rated middle-termed young-aged intermediate-TEU container ships; low-rated middle-termed middle-aged feeders; and intermediate-rated long-termed middle-aged upper intermediate-TEU container ships. As for the post-COVID era, the cluster definitions were determined as intermediate-rated middle-termed young-aged feeders; intermediate-rated middle-termed old-aged feeders; high-rated long-termed middle-aged intermediate-TEU container ships; and high-rated short-termed middle-aged intermediate-TEU container ships. The findings suggested that the pandemic boosted the demand for relatively lower TEU container ships such as the feeders in which the criterium of ship age lost its importance due to availability reasons in the market. In addition, the pandemic led to higher charter rates which was a prioritized factor over the charter period.
Evaluation of the red seaweed Mazzaella japonica as a feed additive for beef cattle
Authors: Terry Stephanie A. , Coates Trevor , Gruninger Robert , Abbott D. Wade , Beauchemin Karen A.
Published: June 2023

Supplementing ruminant diets with macroalgae is gaining interest globally because bromoform-containing seaweeds (e.g., Asparagopsis spp.) have been shown to be highly effective enteric methane (CH4) inhibitors. Some alternative seaweeds decrease in vitro CH4 production, but few have been evaluated in animals. This study examined the effects of including the red seaweed Mazzaella japonica in the diet of beef cattle on dry matter intake (DMI), rumen fermentation, digestibility, nitrogen (N) utilization, and enteric CH4 production. Six ruminally cannulated, mature beef heifers (824 ± 47.1 kg) were used in a double 3 × 3 Latin square with 35-d periods. The basal diet consisted of 52% barley silage, 44% barley straw, and 4% vitamin and mineral supplement [dry matter (DM) basis]. The treatments were (DM basis): 0% (control), 1%, and 2% M. japonica. The DMI increased quadratically (P = 0.025) with the inclusion of M. japonica, such that the DMI of heifers consuming 1% was greater (P < 0.05) than that of control heifers. The apparent total-tract digestibility of DM decreased linearly (P = 0.002) with the inclusion of M. japonica, but there were no treatment differences in the digestibility of organic matter, crude protein (CP), neutral detergent fiber, or starch. The level of M. japonica linearly (P < 0.001) increased the N intake of the heifers. Fecal N excretion linearly increased (P = 0.020) with M. japonica, but there were no differences in total urinary N excretion, N fractions (allantoin, uric acid), total purine derivatives, microbial purine derivatives absorbed, microbial N flow, or retained N. There were no treatment effects on rumen pH or total volatile fatty acids (VFAs); however, adding M. japonica to the diet quadratically (P = 0.023) decreased the proportion of acetate, whereas 1% inclusion decreased the acetate proportion. Methane production (g/day) decreased quadratically (P = 0.037), such that the heifers receiving 2% M. japonica produced 9.2% less CH4 than control animals; however, CH4 yield (g/kg DMI) did not differ among treatments. We conclude that supplementing a forage-based diet with up to 2% M. japonica failed to lower the enteric CH4 yield of beef heifers. M. japonica can be used in diets to help meet the CP requirements of cattle, but inclusion rates may be limited by high inorganic matter proportions. When comprising up to 2% of the diet, M. japonica cannot be recommended as a CH4 inhibitor for beef cattle fed on high-forage diets.
Zinc supplementation and ractopamine hydrochloride impact gene expression of zinc transporters in finishing beef steers
Authors: Rients Emma L. , Wyatt Remy N. , Deters Erin L. , Genther-Schroeder Olivia N. , Hansen Stephanie L.
Published: June 2023

Zinc is a trace mineral of interest for optimizing growth in feedlot cattle due to its roles in many physiological functions, including growth. Twenty-four Angus-cross steers (467 ± 13 kg) were used to assess the effects of supplemental Zn and ractopamine hydrochloride (RAC) on trace mineral concentrations and muscle gene expression. Four GrowSafe-equipped pens were randomly assigned to treatments (1 pen of six steers/treatment): 0 (CON), 60 (LOW), 120 (MED) or 180 (HI) mg supplemental Zn/kg DM (Availa-Zn, Zinpro). Dietary Zn treatments were initiated on d 0 and RAC supplementation (300 mg·steer·-1·d-1; Actogain45, Zoetis) began on d 53. Blood, liver and muscle (longissimus thoracis) samples were collected from all steers on d -4, 48, and 67. The LOW treatment was removed from gene expression analyses due to < 3 steers being represented for 14 of 22 genes. Data were analyzed using ProcMixed of SAS with the fixed effect of treatment and steer as the experimental unit; orthogonal linear and quadratic contrast statements were used to compare treatments. On d 48 and 67, there were linear and quadratic trends for plasma Zn to be greater in Zn-supplemented steers than CON (P ≤ 0.10). On d 48, there was a tendency for a quadratic decrease on the expression of SLC30A4 (P ≤ 0.07) but no other differences due to treatment. On d 67, several genes involved in Zn transport and storage (MTA1, SLC39A7, SLC39A8, SLC39A9, SLC39A10, SLC39A13) were decreased (P ≤ 0.08), suggesting increased growth influences intracellular Zn trafficking and demands.
Structure-based neural network protein–carbohydrate interaction predictions at the residue level
Authors: Canner Samuel W. , Shanker Sudhanshu , Gray Jeffrey J.
Published: June 2023

Carbohydrates dynamically and transiently interact with proteins for cell–cell recognition, cellular differentiation, immune response, and many other cellular processes. Despite the molecular importance of these interactions, there are currently few reliable computational tools to predict potential carbohydrate-binding sites on any given protein. Here, we present two deep learning (DL) models named CArbohydrate–Protein interaction Site IdentiFier (CAPSIF) that predicts non-covalent carbohydrate-binding sites on proteins: (1) a 3D-UNet voxel-based neural network model (CAPSIF:V) and (2) an equivariant graph neural network model (CAPSIF:G). While both models outperform previous surrogate methods used for carbohydrate-binding site prediction, CAPSIF:V performs better than CAPSIF:G, achieving test Dice scores of 0.597 and 0.543 and test set Matthews correlation coefficients (MCCs) of 0.599 and 0.538, respectively. We further tested CAPSIF:V on AlphaFold2-predicted protein structures. CAPSIF:V performed equivalently on both experimentally determined structures and AlphaFold2-predicted structures. Finally, we demonstrate how CAPSIF models can be used in conjunction with local glycan-docking protocols, such as GlycanDock, to predict bound protein–carbohydrate structures.
Preparation of photothermal responsive, antibacterial hydrogel by using PVA-Alg and silver nanofibers as building blocks
Authors: Ding Jiaxin , Gao Binbin , Mei Xifan
Published: June 2023

Introduction: Photothermal responsive, antimicrobial hydrogels are very attractive and have great potential in the field of tissue engineering. The defective wound environment and metabolic abnormalities in diabetic skin would lead to bacterial infections. Therefore, multifunctional composites with antimicrobial properties are urgently needed to improve the current therapeutic outcomes of diabetic wounds. We prepared an injectable hydrogel loaded with silver nanofibers for efficient and sustained bactericidal activity.

Methods: To construct this hydrogel with good antimicrobial activity, homogeneous silver nanofibers were first prepared by solvothermal method and then dispersed in PVA-lg solution. After homogeneous mixing and gelation, injectable hydrogels (Ag@H) wrapped with silver nanofibers were obtained.

Results: By virtue of Ag nanofibers, Ag@H exhibited good photothermal conversion efficiency and good antibacterial activity against drug-resistant bacteria, while the in vivo antibacterial also showed excellent performance. The results of antibacterial experiments showed that Ag@H had significant bactericidal effects on MRSA and E. coli with 88.4% and 90.3% inhibition rates, respectively.

Discussion: The above results indicate that Ag@H with photothermal reactivity and antibacterial activity is very promising for biomedical applications, such as wound healing and tissue engineering.
Nature-inspired Enzyme engineering and sustainable catalysis: biochemical clues from the world of plants and extremophiles
Authors: Chatterjee Anwesha , Puri Sonakshi , Sharma Pankaj Kumar , Deepa P. R. , Chowdhury Shibasish
Published: June 2023

The use of enzymes to accelerate chemical reactions for the synthesis of industrially important products is rapidly gaining popularity. Biocatalysis is an environment-friendly approach as it not only uses non-toxic, biodegradable, and renewable raw materials but also helps to reduce waste generation. In this context, enzymes from organisms living in extreme conditions (extremozymes) have been studied extensively and used in industries (food and pharmaceutical), agriculture, and molecular biology, as they are adapted to catalyze reactions withstanding harsh environmental conditions. Enzyme engineering plays a key role in integrating the structure-function insights from reference enzymes and their utilization for developing improvised catalysts. It helps to transform the enzymes to enhance their activity, stability, substrates-specificity, and substrate-versatility by suitably modifying enzyme structure, thereby creating new variants of the enzyme with improved physical and chemical properties. Here, we have illustrated the relatively less-tapped potentials of plant enzymes in general and their sub-class of extremozymes for industrial applications. Plants are exposed to a wide range of abiotic and biotic stresses due to their sessile nature, for which they have developed various mechanisms, including the production of stress-response enzymes. While extremozymes from microorganisms have been extensively studied, there are clear indications that plants and algae also produce extremophilic enzymes as their survival strategy, which may find industrial applications. Typical plant enzymes, such as ascorbate peroxidase, papain, carbonic anhydrase, glycoside hydrolases and others have been examined in this review with respect to their stress-tolerant features and further improvement via enzyme engineering. Some rare instances of plant-derived enzymes that point to greater exploration for industrial use have also been presented here. The overall implication is to utilize biochemical clues from the plant-based enzymes for robust, efficient, and substrate/reaction conditions-versatile scaffolds or reference leads for enzyme engineering.
Chemical profiling of Sanjin tablets and exploration of their effective substances and mechanism in the treatment of urinary tract infections
Authors: Li Meng-Yuan , Li Yang , Wang Li-Li , Xu Feng , Guo Xu-Yan , Zhang Jing , Lv Yang , Wang Peng-Pu , Wang Shun-Qi , Min Jian-Guo , Zou Xun , Cai Shao-Qing
Published: June 2023

Introduction: Sanjin tablets (SJT) are a well-known Chinese patent drug that have been used to treat urinary tract infections (UTIs) for the last 40 years. The drug consists of five herbs, but only 32 compounds have been identified, which hinders the clarification of its effective substances and mechanism.

Methods: The chemical constituents of SJT and their effective substances and functional mechanism involved in the treatment of UTIs were investigated by using high performance liquid chromatography-electrospray ionization-ion trap-time of flight-mass spectrometry (HPLC-ESI-IT-TOF-MSn), network pharmacology, and molecular docking.

Results: A total of 196 compounds of SJT (SJT-MS) were identified, and 44 of them were unequivocally identified by comparison with the reference compounds. Among 196 compounds, 13 were potential new compounds and 183 were known compounds. Among the 183 known compounds, 169 were newly discovered constituents of SJT, and 93 compounds were not reported in the five constituent herbs. Through the network pharmacology method, 119 targets related to UTIs of 183 known compounds were predicted, and 20 core targets were screened out. Based on the “compound–target” relationship analysis, 94 compounds were found to act on the 20 core targets and were therefore regarded as potential effective compounds. According to the literature, 27 of the 183 known compounds were found to possess antimicrobial and anti-inflammatory activities and were verified as effective substances, of which 20 were first discovered in SJT. Twelve of the 27 effective substances overlapped with the 94 potential effective compounds and were determined as key effective substances of SJT. The molecular docking results showed that the 12 key effective substances and 10 selected targets of the core targets have good affinity for each other.

Discussion: These results provide a solid foundation for understanding the effective substances and mechanism of SJT.
Antioxidant activity of lidocaine, bupivacaine, and ropivacaine in aqueous and lipophilic environments: an experimental and computational study
Authors: Kavčič H. , Jug U. , Mavri J. , Umek N.
Published: June 2023

Introduction: Local anesthetics are widely recognized pharmaceutical compounds with various clinical effects. Recent research indicates that they positively impact the antioxidant system and they may function as free radical scavengers. We hypothesize that their scavenging activity is influenced by the lipophilicity of the environment.

Methods: We assessed the free radical scavenging capacity of three local anesthetics (lidocaine, bupivacaine, and ropivacaine) using ABTS, DPPH, and FRAP antioxidant assays. We also employed quantum chemistry methods to find the most probable reaction mechanism. The experiments were conducted in an aqueous environment simulating extracellular fluid or cytosol, and in a lipophilic environment (n-octanol) simulating cellular membranes or myelin sheets.

Results: All local anesthetics demonstrated ABTS˙+ radical scavenging activity, with lidocaine being the most effective. Compared to Vitamin C, lidocaine exhibited a 200-fold higher half-maximal inhibitory concentration. The most thermodynamically favorable and only possible reaction mechanism involved hydrogen atom transfer between the free radical and the -C-H vicinal to the carbonyl group. We found that the antioxidant activity of all tested local anesthetics was negligible in lipophilic environments, which was further confirmed by quantum chemical calculations.

Conclusion: Local anesthetics exhibit modest free radical scavenging activity in aqueous environments, with lidocaine demonstrating the highest activity. However, their antioxidant activity in lipophilic environments, such as cellular membranes, myelin sheets, and adipose tissue, appears to be negligible. Our results thus show that free radical scavenging activity is influenced by the lipophilicity of the environment.
Phylogeny and diversity of Rigidoporus (Hymenochaetales, Basidiomycota), including three new species from Asia
Authors: Wang Chao-Ge , Vlasák Josef , Jin Can , Si Jing
Published: June 2023

Phylogenetic and morphological analyses on Rigidoporus were carried out. The genus Rigidoporus (Hymenochaetales, Basidiomycota), typified by R. microporus (Fr.) Overeem. (synonym Polyporus micromegas Mont.), was established by Murrill in 1905. The genus is mainly characterized by annual to perennial, resupinate, effused-reflexed to pileate or stipitate basidiomata with azonate or concentrically zonate and sulcate upper surface, a monomitic to pseudo-dimitic hyphal structure, simple-septate generative hyphae, and ellipsoid to globose basidiospores. Phylogeny on species of the genus is reconstructed with two loci DNA sequences including the internal transcribed spacer regions and the large subunit. Three new species in Rigidoporus are described and illustrated from Asia, and one new combination in the genus is proposed. The main morphological characteristics of the currently accepted species of Rigidoporus are provided.
Human and porcine aortic valve endothelial and interstitial cell isolation and characterization
Authors: Nehl D. , Goody P. R. , Maus K. , Pfeifer A. , Aikawa E. , Bakthiary F. , Zimmer S. , Nickenig G. , Jansen F. , Hosen M. R.
Published: June 2023

Background

Calcific aortic valve stenosis (AVS) is defined by pathological changes in the aortic valve (AV) and their predominant cell types: valvular interstitial (VICs) and endothelial cells (VECs). Understanding the cellular and molecular mechanisms of this disease is a prerequisite to identify potential pharmacological treatment strategies. In this study, we present a unique aortic valve cell isolation technique to acquire specific human and porcine cell populations and compared VICs and VECs of these species with each other for the first time.

Methods

AV cells were isolated from tissue obtained from human patients undergoing surgical aortic valve replacement (SAVR) or from porcine hearts. Functional analysis and in vitro experiments revealed that endothelial-to-mesenchymal transition (EndMT) can be induced in hVECs, leading to a significant increase in mesenchymal markers. In vitro calcification experiments of VICs demonstrated pronounced expression of calcification markers and visible calcific deposits in Alizarin Red staining in both species after incubation with pro-calcific media.

Results

Cells isolated from patient-derived AVs showed mesenchymal and endothelial-specific gene signatures (VIC and VEC, respectively). For instance, von Willebrand factor (vWF) and platelet endothelial adhesion molecule-1 (PECAM1) were upregulated in VECs, while the myofibroblastic markers alpha-smooth muscle actin (α-SMA) and vimentin (VIM) were downregulated in VECs compared to VICs. Analysis of cell function by migration revealed that VECs are more migratory than VICs. Induction of EndMT in vitro in VECs displayed increased expression of EndMT markers and decreased expression of endothelial markers, confirming their mesenchymal transdifferentiation ability. In vitro calcification of VICs revealed upregulation of alkaline phosphatase (ALPL), a hallmark of calcification. In addition, other calcification-related genes such as osteocalcin (BGLAP) and runt-related factor 2 (RUNX2) were upregulated. Alizarin red staining of calcified cells provided a further layer of confirmation that the isolated cells were VICs with osteoblastic differentiation capacity.

Conclusion

This study aims to take a first step towards standardizing a reproducible isolation technique for specific human and porcine VEC and VIC populations. A comparison of human and porcine aortic valve cells demonstrated that porcine cells may serve as an alternative cellular model system in settings where human tissue is difficult to obtain.
Is blue light exposure a cause of precocious puberty in male rats?
Authors: Uğurlu Aylin Kılınç , Bideci Aysun , Demirel Ayşe Mürşide , Kaplanoğlu Gülnur Take , Dayanır Duygu , Gülbahar Özlem , Bulut Tuba Saadet Deveci , Döğer Esra , Çamurdan Mahmut Orhun
Published: June 2023

Purpose

Our study aimed to examine the effects of blue light exposure on prepubertal male rats’ puberty and testis tissue.

Methods

Eighteen 21-day-old male Sprague Dawley rats were divided into three groups consisting of six rats in each group: Control Group (CG), Blue Light-6 hours (BL-6), and Blue Light-12 hours (BL-12). CG rats were maintained with 12/12-hour light-dark cycles. The rats of BL-6 and BL-12 were exposed to blue light (450-470nm/irradiance level 0.03uW/cm2) for 6 hours and 12 hours, respectively. Rats were exposed to blue light until the first signs of puberty. The ELISA method was used to analyze the serum levels of FSH, LH, testosterone, DHEA-S, leptin, ghrelin, melatonin, glutathione, glutathione peroxidase, and malondialdehyde. Testes were dissected for histomorphological examination.

Results

The medians of the pubertal entry days of the CG, BL-6, and BL-12 were 38th, 30th, and 28th days, respectively. (p:0.001) The FSH, LH, and testosterone concentrations of all groups were similar. The FSH concentration increased as the LH concentration increased (r: 0.82 p: 0.001). The serum LH concentration increased as serum testosterone, and DHEAS decreased, respectively (r: -0.561, p: 0.01) (r:-0.55 p:0.01). Testicular lengths and weights of the BL groups were smaller compared to CG (p: 0.03),(p: 0.04). GPx was higher for BL-6 and BL-12 than the CG (p:0.021, p:0.024). Testis tissue was compatible with the pubertal period in all groups. As the blue light exposure time increased, spermatogenesis was suppressed, and capillary dilatation and edema in the testis tissue increased.

Conclusion

Our study is the first to show the effects of blue light exposure on male rats’ puberty process. And we showed that exposure to blue light and the duration of exposure lead to precocious puberty in male rats. The blue light exposure suppressed spermatogenesis, marked vasodilatation in the interstitial area of the testis, and disrupted the integrity of the basement membrane. These findings intensified with increasing exposure time.
Alcohol-induced Cushing syndrome: report of eight cases and review of the literature
Authors: Surani Asif , Carroll Ty B. , Javorsky Bradley R. , Raff Hershel , Findling James W.
Published: June 2023

Introduction

Alcohol-induced hypercortisolism (AIH) is underrecognized and may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] obscuring its diagnosis.

Objective and methods

In order to characterize AIH, we performed a chart review of eight patients (4 males and 4 females; 2014-2022) referred for evaluation and treatment of neoplastic hypercortisolism — six for inferior petrosal sinus sampling, one due to persistent CS after unilateral adrenalectomy, and one for pituitary surgery for Cushing disease (CD). Five underwent dDAVP stimulation testing.

Results

All eight patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval confirming hypothalamic-pituitary mediation. All had abnormal low-dose dexamethasone suppression test and increased late-night salivary cortisol. Only one had increased urine cortisol excretion. In contrast to CD, the 5 patients tested had blunted or absent ACTH and cortisol responses to desmopressin. Two had adrenal nodules and one had abnormal pituitary imaging. Most patients underreported their alcohol consumption and one denied alcohol use. Elevated blood phosphatidyl ethanol (PEth) was required in one patient to confirm excessive alcohol use. All patients had elevations of liver function tests (LFTs) with AST>ALT.

Conclusion

AIH is an under-appreciated, reversible cause of non-neoplastic hypercortisolism that is indistinguishable from neoplastic CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption further confound the diagnosis. Measurement of PEth helps to confirm an alcohol use disorder. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP help to distinguish AIH from neoplastic hypercortisolism.
Induction of remission in diabetes by lowering blood glucose
Authors: Weir Gordon C. , Bonner-Weir Susan
Published: June 2023

As diabetes continues to grow as major health problem, there has been great progress in understanding the important role of pancreatic beta-cells in its pathogenesis. Diabetes develops when the normal interplay between insulin secretion and the insulin sensitivity of target tissues is disrupted. With type 2 diabetes (T2D), glucose levels start to rise when beta-cells are unable to meet the demands of insulin resistance. For type 1 diabetes (T1D) glucose levels rise as beta-cells are killed off by autoimmunity. In both cases the increased glucose levels have a toxic effect on beta-cells. This process, called glucose toxicity, has a major inhibitory effect on insulin secretion. This beta-cell dysfunction can be reversed by therapies that reduce glucose levels. Thus, it is becoming increasingly apparent that an opportunity exists to produce a complete or partial remission for T2D, both of which will provide health benefit.
Coastal nutrient enrichments facilitated reproductive output in exotic mangrove species over two decades
Authors: Huang Zijian , Li Zhen , Wang Minhuang , Zhu Dehuang , Yang Qiong , Yu Shixiao
Published: June 2023

Litterfall may facilitate the outperformance of exotic species by inducing better resource acquisition and reproductive performance. However, the drivers that determine litterfall patterns in exotic and native species have remained insufficiently investigated due to the lack of long-term observations. Here, we employed empirical dynamic modeling on a two-decade-long litterfall observation (1999–2019) in a subtropical mangrove forest in Shenzhen, China, to evaluate the relative importance of environmental drivers on different species. We found that mangrove leaf litterfall in both exotic and native species was strongly altered by temperature, and the causal relationship was stronger in the dominant exotic species Sonneratia apetala compared to native species. However, the main driver of reproductive output differed largely between exotic and native species; temperature was the main cause of native reproduction, whereas coastal nutrients drove the reproductive output of exotic species. Our study highlighted that high nutrient availability in Shenzhen Bay in the past decade allowed the exotic species S. apetala to gain better reproductive output than native species. We imply that enriched nutrients in coastal water likely contributed to exotic dominance in China’s coastal mangrove forest.
Umbilical cord-mesenchymal stem cells induce a memory phenotype in CD4+ T cells
Authors: Sengun Ezgi , Wolfs Tim G. A. M. , van Bruggen Valéry L. E. , van Cranenbroek Bram , Simonetti Elles R. , Ophelders Daan , de Jonge Marien I. , Joosten Irma , van der Molen Renate G.
Published: June 2023

Inflammation is a physiological state where immune cells evoke a response against detrimental insults. Finding a safe and effective treatment for inflammation associated diseases has been a challenge. In this regard, human mesenchymal stem cells (hMSC), exert immunomodulatory effects and have regenerative capacity making it a promising therapeutic option for resolution of acute and chronic inflammation. T cells play a critical role in inflammation and depending on their phenotype, they can stimulate or suppress inflammatory responses. However, the regulatory effects of hMSC on T cells and the underlying mechanisms are not fully elucidated. Most studies focused on activation, proliferation, and differentiation of T cells. Here, we further investigated memory formation and responsiveness of CD4+ T cells and their dynamics by immune-profiling and cytokine secretion analysis. Umbilical cord mesenchymal stem cells (UC-MSC) were co-cultured with either αCD3/CD28 beads, activated peripheral blood mononuclear cells (PBMC) or magnetically sorted CD4+ T cells. The mechanism of immune modulation of UC-MSC were investigated by comparing different modes of action; transwell, direct cell-cell contact, addition of UC-MSC conditioned medium or blockade of paracrine factor production by UC-MSC. We observed a differential effect of UC-MSC on CD4+ T cell activation and proliferation using PBMC or purified CD4+ T cell co-cultures. UC-MSC skewed the effector memory T cells into a central memory phenotype in both co-culture conditions. This effect on central memory formation was reversible, since UC-MSC primed central memory cells were still responsive after a second encounter with the same stimuli. The presence of both cell-cell contact and paracrine factors were necessary for the most pronounced immunomodulatory effect of UC-MSC on T cells. We found suggestive evidence for a partial role of IL-6 and TGFβ in the UC-MSC derived immunomodulatory function. Collectively, our data show that UC-MSCs clearly affect T cell activation, proliferation and maturation, depending on co-culture conditions for which both cell-cell contact and paracrine factors are needed.
Gene expression of peripheral blood mononuclear cells and CD8+ T cells from gilts after PRRSV infection
Authors: Lagumdzic Emil , Pernold Clara P. S. , Ertl Reinhard , Palmieri Nicola , Stadler Maria , Sawyer Spencer , Stas Melissa R. , Kreutzmann Heinrich , Rümenapf Till , Ladinig Andrea , Saalmüller Armin
Published: June 2023

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus, which emerged in Europe and U.S.A. in the late 1980s and has since caused huge economic losses. Infection with PRRSV causes mild to severe respiratory and reproductive clinical symptoms in pigs. Alteration of the host immune response by PRRSV is associated with the increased susceptibility to secondary viral and bacterial infections resulting in more serious and chronic disease. However, the expression profiles underlying innate and adaptive immune responses to PRRSV infection are yet to be further elucidated. In this study, we investigated gene expression profiles of PBMCs and CD8+ T cells after PRRSV AUT15-33 infection. We identified the highest number of differentially expressed genes in PBMCs and CD8+ T cells at 7 dpi and 21 dpi, respectively. The gene expression profile of PBMCs from infected animals was dominated by a strong innate immune response at 7 dpi which persisted through 14 dpi and 21 dpi and was accompanied by involvement of adaptive immunity. The gene expression pattern of CD8+ T cells showed a strong adaptive immune response to PRRSV, leading to the formation of highly differentiated CD8+ T cells starting from 14 dpi. The hallmark of the CD8+ T-cell response was the increased expression of effector and cytolytic genes (PRF1, GZMA, GZMB, GZMK, KLRK1, KLRD1, FASL, NKG7), with the highest levels observed at 21 dpi. Temporal clustering analysis of DEGs of PBMCs and CD8+ T cells from PRRSV-infected animals revealed three and four clusters, respectively, suggesting tight transcriptional regulation of both the innate and the adaptive immune response to PRRSV. The main cluster of PBMCs was related to the innate immune response to PRRSV, while the main clusters of CD8+ T cells represented the initial transformation and differentiation of these cells in response to the PRRSV infection. Together, we provided extensive transcriptomics data explaining gene signatures of the immune response of PBMCs and CD8+ T cells after PRRSV infection. Additionally, our study provides potential biomarker targets useful for vaccine and therapeutics development.