bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Injury Is Prevalent and Precedes Tobacco Use among Youth and Young Adults Experiencing Homelessness
Authors: Nemeth Julianna M. , Glasser Allison M. , Hinton Alice , Macisco Joseph M. , Wermert Amy , Smith Raya , Kemble Hannah , Sasser Georgia
Published: March 2023

70%+ of youth and young adults experiencing homelessness (YYEH; 14–24 years old) smoke combustible tobacco. Little is known about the prevalence of acquired brain injury (ABI) among youth and young adult smokers experiencing homelessness (YYSEH) and its impact on tobacco use progression—the aim of our study. Through an interviewer-administered survey, YYSEH were asked about timing of tobacco use; exposure to causes of ABI; including brain oxygen deprivation (BOD; strangulation; accidental; choking games) and blunt force head trauma (BFHT; intentional; shaken violently; accidental); and perpetrators of intentional assault. Participants (n = 96) were on average 22 years old and from populations who experience structural disparities; including those minoritized by race (84.4%) and gender/sexual orientation (26.0%). In total, 87% of participants reported at least one exposure to BFHT and 65% to BOD. Intentional injury was more common than accidental. Furthermore, 60.4% of participants (n = 59) were classified as having ABI using the Brain Injury Severity Assessment. A significant proportion of YYSEH living with ABI were exposed to both BFHT and BOD prior to trying (68.5%, p = 0.002) and to first regular use (82.8%, p < 0.001) of tobacco. Among YYSEH with ABI; injury exposure occurred a median of 1 and 5 years before age of first regular tobacco use, dependent on injury mechanism. ABI from intentional violence is prevalent and precedes tobacco use among YYSEH.
The Therapeutic Impact of Plant-Based and Nutritional Supplements on Anxiety, Depressive Symptoms and Sleep Quality among Adults and Elderly: A Systematic Review of the Literature
Authors: Kamat Darshan , Al-Ajlouni Yazan A. , Hall Ryan C. W.
Published: March 2023

Background: The emerging research in the literature continues to forecast a drastic and alarming increase in negative mental health and sleep health outcomes among populations, especially after the COVID-19 pandemic, which significantly influenced people’s way of life. With mental health pharmaceutical interventions continuing to be stigmatized and inaccessible among populations, natural supplements provide an opportunity for intervention. Objective: This study sought to conduct a systematic review of the literature on the most recent comprehensive evidence for which nutritional supplements have the greatest therapeutic impact on symptoms of anxiety, depression, and insomnia. Methods: A systematic search of the literature, utilizing several databases, including PubMed and Web of Science, was conducted on 29 April 2022. We used developed keywords and MeSH terms for the search. The study eligibility criteria included (1) a randomized control trial; (2) investigating a plant-based therapeutic or natural supplement as the intervention; (3) measuring at least one health outcome of the following: anxiety symptoms, depressive symptoms, or sleep health outcomes; (4) utilizing validated measurement tools to measure the outcome of interest; (5) written in the English language; (6) peer reviewed; and (7) focused on adults and elderly populations. Main Results: Following the PRISMA guidelines, 76 studies were included in this review. We used the revised Risk of Bias tool (RoB2) to assess the quality of all included randomized control trials. A qualitative data synthesis was conducted. Overall, we found several valuable insights from the evidence in the literature, including evidence that demonstrates the benefits of probiotics and vitamin B complexes on anxiety symptoms, depressive symptoms, and sleep quality. Implication of Key Findings: This review provides the most updated findings in the literature on the topic, including an abundance of research that was published in the past 5 years. Given the expected rise in negative mental and sleep health outcomes following the pandemic, the supplements and therapeutics identified in this study should be the target of intervention measures to increase their accessibility and affordability and allow them to be incorporated into clinical guidelines of treatment. PROSPERO registration number: CRD42022361130.
Spatial Correlation Network and Driving Factors of Urban Energy Eco-Efficiency from the Perspective of Human Well-Being: A Case Study of Shaanxi Province, China
Authors: Wang Meixia , Zheng Qingyun , Wang Yunxia
Published: March 2023

It is very important to seek a sustainable improvement in human well-being under a limited resource supply and to promote the scientific and coordinated development of urban economic development, ecological environment protection, and human well-being. This paper constructs a human well-being index that includes economic well-being, culture and education well-being, and social development well-being as factors, and it incorporates the human well-being index into the evaluation system for urban well-being energy eco-efficiency (WEE). It uses the super-slack-based measure (SBM) model, which considers undesirable output, to measure the WEE of 10 prefecture-level cities in Shaanxi Province, China, from 2005 to 2019. The social network analysis (SNA) is used to describe the characteristics of the spatial correlation network of WEE and its spatiotemporal evolutionary trend, and the quadratic assignment procedure (QAP) analysis method is used to identify the driving factors that affect the spatial correlation network. The results show that, first, the WEE in Shaanxi is relatively low as a whole and varies greatly among regions, with the highest level in northern Shaanxi, followed by Guanzhong; the lowest level is in southern Shaanxi. Second, in Shaanxi, WEE has transcended geographical proximity into a complex, multi-threaded spatial correlation network, and Yulin is at the center of the network. Third, the network shows four sectors: the net overflow, main benefit, two-way overflow, and broker. Members in each sector have not fully exploited their advantages, and the whole network can be improved. Fourth, the differences in the economic development level, openness, industrial structure, and population are the main driving factors influencing the formation of the spatial correlation network.
Using Solution-Focused Coaching in Social Work Practice with the Long-Term Unemployed to Promote Their Well-Being
Authors: Zatloukal Leoš , Matulayová Tatiana , Jurníčková Pavlína , Matulayová Nataša , Doležel Jakub , Šlechtová Hana
Published: March 2023

Long-term unemployment, one of the challenges social workers face, produces a variety of non-monetary and social consequences. The helping professionals understand that interventions towards unemployed clients do not cover just the pure fact of their unemployment but that a holistic approach to the clients’ living situations is needed. This paper aims to promote well-being while implementing solution-focused coaching in working with unemployed clients in social work practice. The Reteaming coaching model is supported by two detailed case studies describing three key areas covered in the Reteaming process. Working with clients in both cases contributed to various elements of the client’s psychological well-being: positive emotions, engagement, relationships, meaning, and achievement. The Reteaming coaching model can be used effectively as a suitable structured approach, mainly used in strength-based social work.
Synergistic Interaction of the Class IIa HDAC Inhibitor CHDI0039 with Bortezomib in Head and Neck Cancer Cells
Authors: Schrenk Christian , Bollmann Lukas M. , Haist Corinna , Bister Arthur , Wiek Constanze , Wecker Maria , Roth Dennis , Petzsch Patrick , Köhrer Karl , Hamacher Alexandra , Hanenberg Helmut , Fluegen Georg , Kassack Matthias U.
Published: March 2023

In contrast to class I/IIb/pan histone deacetylase inhibitors (HDACi), the role of class IIa HDACi as anti-cancer chemosensitizing agents is less well understood. Here, we studied the effects of HDAC4 in particular and the class IIa HDACi CHDI0039 on proliferation and chemosensitivity in Cal27 and cisplatin-resistant Cal27CisR head and neck squamous cell cancer (HNSCC). HDAC4 and HDAC5 overexpression clones were generated. HDAC4 overexpression (Cal27_HDAC4) increased proliferation significantly compared to vector control cells (Cal27_VC). Chicken chorioallantoic membrane (CAM) studies confirmed the in vitro results: Cal27_HDAC4 tumors were slightly larger than tumors from Cal27_VC, and treatment with CHDI0039 resulted in a significant decrease in tumor size and weight of Cal27_HDAC4 but not Cal27_VC. Unlike class I/pan-HDACi, treatment with CHDI0039 had only a marginal impact on cisplatin cytotoxicity irrespective of HDAC4 and HDAC5 expression. In contrast, the combination of CHDI0039 with bortezomib was synergistic (Chou–Talalay) in MTT and caspase 3/7 activation experiments. RNAseq indicated that treatment with CHDI0039 alters the expression of genes whose up- or downregulation is associated with increased survival in HNSCC patients according to Kaplan–Meier data. We conclude that the combination of class IIa HDACi with proteasome inhibitors constitutes an effective treatment option for HNSCC, particularly for platinum-resistant cancers.
OsαCA1 Affects Photosynthesis, Yield Potential, and Water Use Efficiency in Rice
Authors: He Yaqian , Duan Wen , Xue Baoping , Cong Xiaochen , Sun Peng , Hou Xin , Liang Yun-Kuan
Published: March 2023

Plant growth and crop yield are essentially determined by photosynthesis when considering carbon dioxide (CO2) availability. CO2 diffusion inside a leaf is one of the factors that dictate the CO2 concentrations in chloroplasts. Carbonic anhydrases (CAs) are zinc-containing enzymes that interconvert CO2 and bicarbonate ions (HCO3−), which, consequently, affect CO2 diffusion and thus play a fundamental role in all photosynthetic organisms. Recently, the great progress in the research in this field has immensely contributed to our understanding of the function of the β-type CAs; however, the analysis of α-type CAs in plants is still in its infancy. In this study, we identified and characterized the OsαCA1 gene in rice via the analysis of OsαCAs expression in flag leaves and the subcellular localization of its encoding protein. OsαCA1 encodes an α-type CA, whose protein is located in chloroplasts with a high abundance in photosynthetic tissues, including flag leaves, mature leaves, and panicles. OsαCA1 deficiency caused a significant reduction in assimilation rate, biomass accumulation, and grain yield. The growth and photosynthetic defects of the OsαCA1 mutant were attributable to the restricted CO2 supply at the chloroplast carboxylation sites, which could be partially rescued by the application of an elevated concentration of CO2 but not that of HCO3−. Furthermore, we have provided evidence that OsαCA1 positively regulates water use efficiency (WUE) in rice. In summary, our results reveal that the function of OsαCA1 is integral to rice photosynthesis and yield potential, underscoring the importance of α-type CAs in determining plant physiology and crop yield and providing genetic resources and new ideas for breeding high-yielding rice varieties.
Inhibitory Effects of 3-Methylcholanthrene Exposure on Porcine Oocyte Maturation
Authors: Zhang Mengya , Wang Xin , Liu Qiuchen , Yan Yelian , Xu Changzhi , Zhu Zhihua , Wu Sucheng , Zuo Xiaoyu , Zong Yanfeng , Li Chunxiao , Zhang Yunhai , Cao Zubing
Published: March 2023

3-methylcholanthrene (3-MC) is a highly toxic environmental pollutant that impairs animal health. 3-MC exposure can cause abnormal spermatogenesis and ovarian dysfunction. However, the effects of 3-MC exposure on oocyte maturation and embryo development remain unclear. This study revealed the toxic effects of 3-MC exposure on oocyte maturation and embryo development. 3-MC with different concentrations of 0, 25, 50, and 100 μM was applied for in vitro maturation of porcine oocytes. The results showed that 100 μM 3-MC significantly inhibited cumulus expansion and the first polar body extrusion. The rates of cleavage and blastocyst of embryos derived from 3-MC-exposed oocytes were significantly lower than those in the control group. Additionally, the rates of spindle abnormalities and chromosomal misalignments were higher than those in the control group. Furthermore, 3-MC exposure not only decreased the levels of mitochondria, cortical granules (CGs), and acetylated α-Tubulin, but also increased the levels of reactive oxygen species (ROS), DNA damage, and apoptosis. The expression of cumulus expansion and apoptosis-related genes was abnormal in 3-MC-exposed oocytes. In conclusion, 3-MC exposure disrupted the nuclear and cytoplasmic maturation of porcine oocytes through oxidative stress.
Co-Catalyzed Asymmetric Hydrogenation. The Same Enantioselection Pattern for Different Mechanisms
Authors: Gridnev Ilya D.
Published: March 2023

The mechanism of the recently reported catalyzed asymmetric hydrogenation of enyne 1 catalyzed by the Co-(R,R)-QuinoxP* complex was studied by DFT. Conceivable pathways for the Co(I)-Co(III) mechanism were computed together with a Co(0)-Co(II) catalytic cycle. It is commonly assumed that the exact nature of the chemical transformations taking place along the actually operating catalytic pathway determine the sense and level of enantioselection of the catalytic reaction. In this work, two chemically different mechanisms reproduced the experimentally observed perfect stereoselection of the same handedness. Moreover, the relative stabilities of the transition states of the stereo induction stages were controlled via exactly the same weak disperse interactions between the catalyst and the substrate.
Stereochemical Study of the Super Large Tetrakis Alkaloid Alasmontamine A by Means of an Advanced Computational NMR
Authors: Semenov Valentin A. , Krivdin Leonid B.
Published: March 2023

1H and 13C NMR chemical shifts of the tetrakis monoterpene indole alkaloid alasmontamine A, with a molecular formula of C84H91N8O12, have been calculated within the DFT framework. Six minimum energy conformers of this alkaloid were identified, and three key configurations that contribute to its NMR shielding constants were established. Several ambiguities in the reported assignment of the NMR chemical shifts of alasmontamine A have been resolved.
Aluminum Foil vs. Gold Film: Cost-Effective Substrate in Sandwich SERS Immunoassays of Biomarkers Reveals Potential for Selectivity Improvement
Authors: Bukasov Rostislav , Sultangaziyev Alisher , Kunushpayeva Zhanar , Rapikov Alisher , Dossym Dina
Published: March 2023

The first application of aluminum foil (Al F) as a low-cost/high-availability substrate for sandwich immunoassay using surface-enhanced Raman spectroscopy (SERS) is reported. Untreated and unmodified Al F and gold film are used as substrates for sandwich SERS immunoassay to detect tuberculosis biomarker MPT64 and human immunoglobulin (hIgG) in less than 24 h. The limits of detection (LODs) for tuberculosis (TB) biomarker MPT64 on Al foil, obtained with commercial antibodies, are about 1.8–1.9 ng/mL, which is comparable to the best LOD (2.1 ng/mL) reported in the literature for sandwich ELISA, made with fresh in-house antibodies. Not only is Al foil competitive with traditional SERS substrate gold for the sandwich SERS immunoassay in terms of LOD, which is in the range 18–30 pM or less than 1 pmol of human IgG, but it also has a large cost/availability advantage over gold film. Moreover, human IgG assays on Al foil and Si showed better selectivity (by about 30–70% on Al foil and at least eightfold on Si) and a nonspecific response to rat or rabbit IgG, in comparison to the selectivity in assays using gold film.
Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature
Authors: Phing Ang Hui , Makpol Suzana , Nasaruddin Muhammad Luqman , Wan Zaidi Wan Asyraf , Ahmad Nurul Saadah , Embong Hashim
Published: March 2023

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.
Genome-Wide Association Mapping of QTL Underlying Groat Protein Content of a Diverse Panel of Oat Accessions
Authors: Yan Honghai , Zhang Haixu , Zhou Pingping , Ren Changzhong , Peng Yuanying
Published: March 2023

Groat protein content (GPC) is a key quality trait attribute in oat. Understanding the variation of GPC in oat germplasms and identifying genomic regions associated with GPC are essential for improving this trait. In this study, the GPC of 174 diverse oat accessions was evaluated in three field trials. The results showed a wide variation in GPC, ranging from 6.97% to 22.24% in this panel. Hulless oats displayed a significantly higher GPC compared to hulled oats across all environments. A GWAS analysis was performed based on 38,313 high-quality SNPs, which detected 27 non-redundant QTLs with 41 SNPs significantly associated with GPC. Two QTLs on chromosome 6C (QTL16) and 4D (QTL11) were consistently detected in multiple environments, with QTL16 being the most significant and explaining the highest proportion of the phenotypical variation in all tested environments except in CZ20. Haplotype analysis showed that the favorable haplotypes for GPC are more prevalent in hulless oats. These findings provide a foundation for future efforts to incorporate favorable alleles into new cultivars through introgression, fine mapping, and cloning of promising QTLs.
Chromatin Remodeling Enzyme Cluster Predicts Prognosis and Clinical Benefit of Therapeutic Strategy in Breast Cancer
Authors: Kuo Chia-Yu , Moi Sin-Hua , Hou Ming-Feng , Luo Chi-Wen , Pan Mei-Ren
Published: March 2023

The treatment provided for breast cancer depends on the expression of hormone receptors, human epidermal growth factor receptor-2 (HER2), and cancer staging. Surgical intervention, along with chemotherapy or radiation therapy, is the mainstay of treatment. Currently, precision medicine has led to personalized treatment using reliable biomarkers for the heterogeneity of breast cancer. Recent studies have shown that epigenetic modifications contribute to tumorigenesis through alterations in the expression of tumor suppressor genes. Our aim was to investigate the role of epigenetic modifications in genes involved in breast cancer. A total of 486 patients from The Cancer Genome Atlas Pan-cancer BRCA project were enrolled in our study. Hierarchical agglomerative clustering analysis further divided the 31 candidate genes into 2 clusters according to the optimal number. Kaplan–Meier plots showed worse progression-free survival (PFS) in the high-risk group of gene cluster 1 (GC1). In addition, the high-risk group showed worse PFS in GC1 with lymph node invasion, which also presented a trend of better PFS when chemotherapy was combined with radiotherapy than when chemotherapy was administered alone. In conclusion, we developed a novel panel using hierarchical clustering that high-risk groups of GC1 may be promising predictive biomarkers in the clinical treatment of patients with breast cancer.
Pathogenesis of Pregnancy-Related Complications
Authors: Hromadnikova Ilona
Published: March 2023

In this special edition (closed on 31 October 2022), 4 reviews, 13 original papers, 1 communication, and 1 case report are published [...]
NAADP-Evoked Ca2+ Signaling Leads to Mutant Huntingtin Aggregation and Autophagy Impairment in Murine Astrocytes
Authors: Pereira Cássia Arruda de Souza , Medaglia Natalia de Castro , Ureshino Rodrigo Portes , Bincoletto Claudia , Antonioli Manuela , Fimia Gian Maria , Piacentini Mauro , Pereira Gustavo José da Silva , Erustes Adolfo Garcia , Smaili Soraya Soubhi
Published: March 2023

Huntington’s disease (HD) is a progressive neurodegenerative disease characterized by mutations in the huntingtin gene (mHtt), causing an unstable repeat of the CAG trinucleotide, leading to abnormal long repeats of polyglutamine (poly-Q) in the N-terminal region of the huntingtin, which form abnormal conformations and aggregates. Alterations in Ca2+ signaling are involved in HD models and the accumulation of mutated huntingtin interferes with Ca2+ homeostasis. Lysosomes are intracellular Ca2+ storages that participate in endocytic and lysosomal degradation processes, including autophagy. Nicotinic acid adenine dinucleotide phosphate (NAADP) is an intracellular second messenger that promotes Ca2+ release from the endo-lysosomal system via Two-Pore Channels (TPCs) activation. Herein, we show the impact of lysosomal Ca2+ signals on mHtt aggregation and autophagy blockade in murine astrocytes overexpressing mHtt-Q74. We observed that mHtt-Q74 overexpression causes an increase in NAADP-evoked Ca2+ signals and mHtt aggregation, which was inhibited in the presence of Ned-19, a TPC antagonist, or BAPTA-AM, a Ca2+ chelator. Additionally, TPC2 silencing revert the mHtt aggregation. Furthermore, mHtt has been shown co-localized with TPC2 which may contribute to its effects on lysosomal homeostasis. Moreover, NAADP-mediated autophagy was also blocked since its function is dependent on lysosomal functionality. Taken together, our data show that increased levels of cytosolic Ca2+ mediated by NAADP causes mHtt aggregation. Additionally, mHtt co-localizes with the lysosomes, where it possibly affects organelle functions and impairs autophagy.
Odorant-Binding Proteins and Chemosensory Proteins in Spodoptera frugiperda: From Genome-Wide Identification and Developmental Stage-Related Expression Analysis to the Perception of Host Plant Odors, Sex Pheromones, and Insecticides
Authors: Jia Chen , Mohamed Amr , Cattaneo Alberto Maria , Huang Xiaohua , Keyhani Nemat O. , Gu Maiqun , Zang Liansheng , Zhang Wei
Published: March 2023

Spodoptera frugiperda is a worldwide generalist pest with remarkable adaptations to environments and stresses, including developmental stage-related behavioral and physiological adaptations, such as diverse feeding preferences, mate seeking, and pesticide resistance. Insects’ odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are essential for the chemical recognition during behavioral responses or other physiological processes. The genome-wide identification and the gene expression patterns of all these identified OBPs and CSPs across developmental stage-related S. frugiperda have not been reported. Here, we screened for genome-wide SfruOBPs and SfruCSPs, and analyzed the gene expression patterns of SfruOBPs and SfruCSPs repertoires across all developmental stages and sexes. We found 33 OBPs and 22 CSPs in the S. frugiperda genome. The majority of the SfruOBP genes were most highly expressed in the adult male or female stages, while more SfruCSP genes were highly expressed in the larval or egg stages, indicating their function complementation. The gene expression patterns of SfruOBPs and SfruCSPs revealed strong correlations with their respective phylogenic trees, indicating a correlation between function and evolution. In addition, we analyzed the chemical-competitive binding of a widely expressed protein, SfruOBP31, to host plant odorants, sex pheromones, and insecticides. Further ligands binding assay revealed a broad functional related binding spectrum of SfruOBP31 to host plant odorants, sex pheromones, and insecticides, suggesting its potential function in food, mate seeking, and pesticide resistance. These results provide guidance for future research on the development of behavioral regulators of S. frugiperda or other environmentally friendly pest-control strategies.
Laser Cutting Coupled with Electro-Exfoliation to Prepare Versatile Planar Graphene Electrodes for Energy Storage
Authors: Wang Jianren , Yang Tianshuo , Vilà Neus , Walcarius Alain
Published: March 2023

The study of planar energy storage devices, characterized by low-cost, high capacity, and satisfactory flexibility, is becoming a valuable research hotspot. Graphene, monolayer sp2 hybrid carbon atoms with a large surface area, always acts as its active component, yet there is a tension between its high conductivity and ease of implementation. Although the difficult-to-assemble graphene can easily achieve planar assemblies in its highly oxidized form (GO), the undesirable conductivity, even after proper reduction, still restricts its further applications. Here, a facile “Top-down” method has been proposed to prepare the graphene planar electrode via in situ electro-exfoliation of graphite supported on a piece of laser-cutting patterned scotch tape. Detailed characterizations have been performed to study its physiochemical property evolution during electro-exfoliation. The obtained flexible graphene planar electrodes show decent energy storage performance, e.g., 40.8 mF cm−2 at a current density of 0.5 mA cm−2 and an 81% capacity retention at a current density of 8 mA cm−2 for the optimized sample G-240. Their high conductivity also makes it possible to couple them with other redox-active materials through electrodeposition to improve their performance, e.g., ferrocene-functionalized mesoporous silica film (Fc-MS), MnO2, and polyaniline (PANI). The highest capacity was achieved with the PANI functionalized sample, which achieved a 22-fold capacity increase. In a word, the versatility, practicality, and adaptability of the protocol to prepare the planar graphene electrode proposed in this work make it a potential candidate to meet the continuously growing energy storage demands.
A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms
Authors: Kalabusheva Ekaterina P. , Shtompel Anastasia S. , Rippa Alexandra L. , Ulianov Sergey V. , Razin Sergey V. , Vorotelyak Ekaterina A.
Published: March 2023

Keratins are a family of intermediate filament-forming proteins highly specific to epithelial cells. A combination of expressed keratin genes is a defining property of the epithelium belonging to a certain type, organ/tissue, cell differentiation potential, and at normal or pathological conditions. In a variety of processes such as differentiation and maturation, as well as during acute or chronic injury and malignant transformation, keratin expression undergoes switching: an initial keratin profile changes accordingly to changed cell functions and location within a tissue as well as other parameters of cellular phenotype and physiology. Tight control of keratin expression implies the presence of complex regulatory landscapes within the keratin gene loci. Here, we highlight patterns of keratin expression in different biological conditions and summarize disparate data on mechanisms controlling keratin expression at the level of genomic regulatory elements, transcription factors (TFs), and chromatin spatial structure.
Influence of HA on Release Process of Anionic and Cationic API Incorporated into Hydrophilic Gel
Authors: Wójcik-Pastuszka Dorota , Stawicka Karolina , Dryś Andrzej , Musiał Witold
Published: March 2023

The properties of sodium hyaluronate (HA), such as hygroscopicity, flexibility, the ability to form hydrogels, as well as biocompatibility and biodegradability, are beneficial for the applications in pharmaceutical technology, cosmetics industry, and aesthetic medicine. The aim of this study was to prepare HA-based hydrogels doped with active pharmaceutical ingredient (API): a cationic drug—lidocaine hydrochloride or anionic drug—sodium. The interaction between the carrier and the implemented active pharmaceutical substances was evaluated in prepared systems by applying viscometric measurements, performing release tests of the drug from the obtained formulations, and carrying out FTIR and DSC. The data from release studies were analyzed using the zero-, first-, and second-order kinetics and Higuchi, Korsmeyer-Peppas, and Hixon-Crowell models. The respective kinetic parameters: the release rate constants, the half-release time and, in the case of the Korsmeyer-Peppas equation, the n parameter were calculated. The variability between the obtained release profiles was studied by calculating the difference (f1) and the similarity factor (f2) as well as employing statistical methods. It was revealed that the incorporation of the drugs resulted in an increase in the viscosity of the hydrogels in comparison to the respective drug-free preparations. The dissolution study showed that not entire amount of the added drug was released from the formulation, suggesting an interaction between the carrier and the drug. The FTIR and DSC studies confirmed the bond formation between HA and both medicinal substances.
Rapid and Efficient Optimization Method for a Genetic Transformation System of Medicinal Plants Erigeron breviscapus
Authors: Zhao Yujun , Yu Yifan , Guo Juan , Zhang Yifeng , Huang Luqi
Published: March 2023

Erigeron breviscapus is an important medicinal plant with high medicinal and economic value. It is currently the best natural biological drug for the treatment of obliterative cerebrovascular disease and the sequela of cerebral hemorrhage. Therefore, to solve the contradiction between supply and demand, the study of genetic transformation of E. breviscapus is essential for targeted breeding. However, establishing an efficient genetic transformation system is a lengthy process. In this study, we established a rapid and efficient optimized protocol for genetic transformation of E. breviscapus using the hybrid orthogonal method. The effect of different concentrations of selection pressure (Hygromycin B) on callus induction and the optimal pre-culture time of 7 days were demonstrated. The optimal transformation conditions were as follows: precipitant agents MgCl2 + PEG, target tissue distance 9 cm, helium pressure 650 psi, bombardment once, plasmid DNA concentration 1.0 μg·μL−1, and chamber vacuum pressure 27 mmHg. Integration of the desired genes was verified by amplifying 1.02 kb of htp gene from the T0 transgenic line. Genetic transformation of E. breviscapus was carried out by particle bombardment under the optimized conditions, and a stable transformation efficiency of 36.7% was achieved. This method will also contribute to improving the genetic transformation rate of other medicinal plants.
Diversity-Generating Retroelements in Prokaryotic Immunity
Authors: Belalov Ilya S. , Sokolov Arseniy A. , Letarov Andrey V.
Published: March 2023

Adaptive immunity systems found in different organisms fall into two major types. Prokaryotes possess CRISPR-Cas systems that recognize former invaders using memorized (captured) pieces of their DNA as pathogen signatures. Mammals possess a vast repertoire of antibodies and T-cell receptor variants generated in advance. In this second type of adaptive immunity, a pathogen presentation to the immune system specifically activates the cells that express matching antibodies or receptors. These cells proliferate to fight the infection and form the immune memory. The principle of preemptive production of diverse defense proteins for future use can hypothetically take place in microbes too. We propose a hypothesis that prokaryotes employ diversity-generating retroelements to prepare defense proteins against yet-unknown invaders. In this study, we test this hypothesis with the methods of bioinformatics and identify several candidate defense systems based on diversity-generating retroelements.
Novel Strategies in the Development of New Therapies, Drug Substances, and Drug Carriers Volume II
Authors: Kutner Andrzej , Brown Geoffrey , Kallay Enikö
Published: March 2023

The highly successful previous Volume 1 [...]
Deep Learning-Based Semantic Segmentation Methods for Pavement Cracks
Authors: Zhang Yu , Gao Xin , Zhang Hanzhong
Published: March 2023

As road mileage continues to expand, the number of disasters caused by expanding pavement cracks is increasing. Two main methods, image processing and deep learning, are used to detect these cracks to improve the efficiency and quality of pavement crack segmentation. The classical segmentation network, UNet, has a poor ability to extract target edge information and small target segmentation, and is susceptible to the influence of distracting objects in the environment, thus failing to better segment the tiny cracks on the pavement. To resolve this problem, we propose a U-shaped network, ALP-UNet, which adds an attention module to each encoding layer. In the decoding phase, we incorporated the Laplacian pyramid to make the feature map contain more boundary information. We also propose adding a PAN auxiliary head to provide an additional loss for the backbone to improve the overall network segmentation effect. The experimental results show that the proposed method can effectively reduce the interference of other factors on the pavement and effectively improve the mIou and mPA values compared to the previous methods.
Fouling Community on Pinna nobilis Larval Collectors in the Adriatic—Impact of Invasive Species
Authors: Bakran-Petricioli Tatjana , Kujundžić Dajana , Naranđa Martina , Petricioli Donat , Petricioli Lucija , Kipson Silvija
Published: March 2023

In the last few years, the endemic Mediterranean bivalve Pinna nobilis has been exposed to dramatic mortality in its entire area, which could lead to the extinction of the species. Throughout the Mediterranean, a lot of effort is being put into finding ways of preserving it. One of the methods used to monitor recruitment and juveniles’ survival is the installation of collectors for bivalve larvae. We installed collectors at two locations: in Brijuni National Park (North Adriatic) and Luka Cove (central Adriatic). Our aim was to compare the fouling community on the collectors in two consecutive years (2019 and 2020), especially because the installation of collectors in 2020 coincided with mass mortality events of P. nobilis in the area. The number and size of juvenile P. nobilis and the qualitative and quantitative composition of the fouling communities were determined. The results show a reduction in the number and size of juvenile P. nobilis and an explosion of the invasive bivalve Anadara transversa population on collectors in the second year. In Luka Cove, another invasive species—the ascidian Styela plicata—also seriously affected other organisms on the collectors to the point of preventing analysis of the fouling community.
High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species
Authors: Losada Luiza Chaves de Miranda Leonhardt , Monteiro Ruan Campos , de Carvalho Jamile Ambrósio , Hagen Ferry , Fisher Matthew C. , Spruijtenburg Bram , Meis Jacques F. , de Groot Theun , Gonçalves Sarah Santos , Negroni Ricardo , Kano Rui , Bonifaz Alexandro , de Camargo Zoilo Pires , Rodrigues Anderson Messias
Published: March 2023

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140–143,912 SSR loci were identified (82,841–98,369 unique markers), with a 3651.55–3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.
Anti-Biofilm Activity of Phenyllactic Acid against Clinical Isolates of Fluconazole-Resistant Candida albicans
Authors: Maione Angela , Imparato Marianna , Buonanno Annalisa , Carraturo Federica , Schettino Antonetta , Schettino Maria Teresa , Galdiero Marilena , de Alteriis Elisabetta , Guida Marco , Galdiero Emilia
Published: March 2023

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region, and is responsible for 85% to 90% of vulvovaginal candidiasis (VVC) cases. The development of drug resistance in C. albicans isolates after long-term therapy with fluconazole is an important complication to solve and new therapeutic strategies are required to target this organism and its pathogenicity. In the present study, phenyllactic acid (PLA) an important broad-spectrum antimicrobial compound was investigated for its antifungal and antivirulence activities against clinical isolates of C. albicans. Previously characterized strains of C. albicans isolates from women with VVC and C. albicans ATCC90028 were used to evaluate the antimicrobial and time dependent killing assay activity of PLA showing a MIC 7.5 mg mL−1 and a complete reduction of viable Candida cells detected by killing kinetics after 4 h of treatment with PLA. Additionally, PLA significantly reduced the biomass and the metabolic activity of C. albicans biofilms and impaired biofilm formation also with changes in ERG11, ALS3, and HWP1 genes expression as detected by qPCR. PLA eradicated pre-formed biofilms as showed also with confocal laser scanning microscopy (CLSM) observations. Furthermore, the compound prolonged the survival rate of Galleria mellonella infected by C. albicans isolates. These results indicate that PLA is a promising candidate as novel and safe antifungal agents for the treatment of vulvovaginal candidiasis.
Silver(I) 1,10-Phenanthroline Complexes Are Active against Fonsecaea pedrosoi Viability and Negatively Modulate Its Potential Virulence Attributes
Authors: Sousa Ingrid S. , Vieira Tatiana D. P. , Menna-Barreto Rubem F. S. , Guimarães Allan J. , McCarron Pauraic , McCann Malachy , Devereux Michael , Santos André L. S. , Kneipp Lucimar F.
Published: March 2023

The genus Fonsecaea is one of the etiological agents of chromoblastomycosis (CBM), a chronic subcutaneous disease that is difficult to treat. This work aimed to evaluate the effects of copper(II), manganese(II) and silver(I) complexes coordinated with 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione (phendione) on Fonsecaea spp. Our results revealed that most of these complexes were able to inhibit F. pedrosoi, F. monophora and F. nubica conidial viability with minimum inhibitory concentration (MIC) values ranging from 0.6 to 100 µM. The most effective complexes against F. pedrosoi planktonic conidial cells, the main etiologic agent of CBM, were [Ag(phen)2]ClO4 and [Ag2(3,6,9-tdda)(phen)4].EtOH, (tdda: 3,6,9-trioxaundecanedioate), displaying MIC values equal to 1.2 and 0.6 µM, respectively. These complexes were effective in reducing the viability of F. pedrosoi biofilm formation and maturation. Silver(I)-tdda-phen, combined with itraconazole, reduced the viability and extracellular matrix during F. pedrosoi biofilm development. Moreover, both silver(I) complexes inhibited either metallo- or aspartic-type peptidase activities of F. pedrosoi as well as its conidia into mycelia transformation and melanin production. In addition, the complexes induced the production of intracellular reactive oxygen species in F. pedrosoi. Taken together, our data corroborate the antifungal action of metal-phen complexes, showing they represent a therapeutic option for fungal infections, including CBM.
Closed-End Fund Discounts and Economic Policy Uncertainty
Authors: Durmaz Nazif
Published: March 2023

This paper empirically tests the determinants of closed-end fund (CEF) prices by employing cointegration and error-correction modeling with an advanced ARDL framework. Since CEF shares generally trade at discounts to their net asset value (NAV), we modeled CEF prices, including volatility and economic policy indices along with their NAVs. The present study consists of 31 monthly frequency CEF discount data from January 1999 to April 2018 and economic policy uncertainty (EPU) with ten subindices. This paper finds evidence for cointegration in many of the series and statistically significant coefficients in the short- and long-run estimates of the included subindices.
The Impact and Mechanism of the Increased Integration of Urban Agglomerations on the Eco-Efficiency of Cities in the Region—Taking the Chengdu–Chongqing Urban Agglomeration in China as an Example
Authors: Jian Yuting , Yang Yongchun , Xu Jing
Published: March 2023

China is attaching increasing importance to the creation of regional integration, high-quality economic development and ecological civilization. An accurate grasp of the traction effect of the increased level of integration of urban agglomerations on the eco-efficiency (EE) of cities in the region will help to promote the steady improvement of urban economic development and the ecological environment. This paper constructs an index system to measure the level of integration of the Chengdu–Chongqing urban agglomeration (CCUA) and the EE of each city within it from 2011 to 2020 and explores the impact of regional integration on urban EE and its mechanism of action. The study presents the follow findings: (1) The level of integration of the CCUA increased nearly 10 times from 2011 to 2020, with the government playing a significant leading role. (2) The positive and negative effects of the level of integration of the CCUA on urban EE depend on factors such as the level of economic development, the stage of development and the location. There are several relationships between the level of intra-regional integration and urban EE: first, a nearly linear increase, as in Chongqing and Chengdu; second, an increase in fluctuation, as in Dazhou, Guang’an and Leshan; and third, a fluctuation, decrease, flat or even no real increase, as in Luzhou, Ya’an and Zigong. (3) Based on this, this paper considers the mechanism of the level of integration within the region on urban EE in terms of both economic and eco-environmental effects, with a view to exploring the future green development path of the CCUA.
Automated Insulin Delivery (AID) Systems: Use and Efficacy in Children and Adults with Type 1 Diabetes and Other Forms of Diabetes in Europe in Early 2023
Authors: Bassi Marta , Franzone Daniele , Dufour Francesca , Strati Marina Francesca , Scalas Marta , Tantari Giacomo , Aloi Concetta , Salina Alessandro , d’Annunzio Giuseppe , Maghnie Mohamad , Minuto Nicola
Published: March 2023

Type 1 diabetes (T1D) patients’ lifestyle and prognosis has remarkably changed over the years, especially after the introduction of insulin pumps, in particular advanced hybrid closed loop systems (AHCL). Emerging data in literature continuously confirm the improvement of glycemic control thanks to the technological evolution taking place in this disease. As stated in previous literature, T1D patients are seen to be more satisfied thanks to the use of these devices that ameliorate not only their health but their daily life routine as well. Limited findings regarding the use of new devices in different age groups and types of patients is their major limit. This review aims to highlight the main characteristics of each Automated Insulin Delivery (AID) system available for patients affected by Type 1 Diabetes Mellitus. Our main goal was to particularly focus on these systems’ efficacy and use in different age groups and populations (i.e., children, pregnant women). Recent studies are emerging that demonstrate their efficacy and safety in younger patients and other forms of diabetes.
Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study
Authors: Tomita Noriko , Morino Eriko , Terada-Hirashima Junko , Uemura Yukari , Shimizu Yosuke , Saito Sho , Suzuki Tetsuya , Okumura Nobumasa , Iwasaki Haruka , Ebihara Hideki , Shimojima Masayuki , Sugiura Wataru , Ohmagari Norio , Ujiie Mugen
Published: March 2023

Monkeypox (mpox) is an acute exanthematous disease caused by the monkeypox virus (MPXV). Since May 2022, patients with mpox have been reported worldwide, mainly in Europe and the Americas. In Japan, LC16”KMB,” which is a smallpox vaccine derived from a dried cell culture, against mpox, has been approved. Although inoculation with a smallpox vaccine has been recommended to prevent MPXV infection, the immunogenicity of the smallpox vaccine against the MPXV is unclear, and information regarding postvaccination safety is scarce. We present the protocol for a single-arm open-label study to investigate the immunogenicity and safety of LC16”KMB” against the MPXV in healthy Japanese adults. The primary endpoint is the seroconversion rate of neutralizing antibodies against the MPXV on postvaccination day 28. The secondary endpoints are the seroconversion rates against the MPXV on postvaccination days 14 and 168; the seroconversion rates against the vaccinia virus on postvaccination days 14, 28, and 168; the incidence of mpox until day 168; and adverse and serious adverse events until postvaccination days 28 and 168. These results will pave the way for larger comparative studies using other smallpox vaccines to evaluate the test vaccine’s safety and efficacy in preventing mpox.