bluuebunny/crossref_metadata_2025 huggingface dataset:
PS1 Affects the Pathology of Alzheimer’s Disease by Regulating BACE1 Distribution in the ER and BACE1 Maturation in the Golgi Apparatus
Authors: Li Nuomin , Qiu Yunjie , Wang Hao , Zhao Juan , Qing Hong
Published: December 2022

Neuritic plaques are one of the major pathological hallmarks of Alzheimer’s disease. They are formed by the aggregation of extracellular amyloid-β protein (Aβ), which is derived from the sequential cleavage of amyloid-β precursor protein (APP) by β- and γ-secretase. BACE1 is the main β-secretase in the pathogenic process of Alzheimer’s disease, which is believed to be a rate-limiting step of Aβ production. Presenilin 1 (PS1) is the active center of the γ-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene (PSEN1) are the most common cause of early onset familial Alzheimer’s disease (FAD). The PSEN1 mutations can alter the activity of γ-secretase on the cleavage of APP. Previous studies have shown that PSEN1 mutations increase the expression and activity of BACE1 and that BACE1 expression and activity are elevated in the brains of PSEN1 mutant knock-in mice, compared with wild-type mice, as well as in the cerebral cortex of FAD patients carrying PSEN1 mutations, compared with sporadic AD patients and controls. Here, we used a Psen1 knockout cell line and a PS1 inhibitor to show that PS1 affects the expression of BACE1 in vitro. Furthermore, we used sucrose gradient fractionation combined with western blotting to analyze the distribution of BACE1, combined with a time-lapse technique to show that PS1 upregulates the distribution and trafficking of BACE1 in the endoplasmic reticulum, Golgi, and endosomes. More importantly, we found that the PSEN1 mutant S170F increases the distribution of BACE1 in the endoplasmic reticulum and changes the ratio of mature BACE1 in the trans-Golgi network. The effect of PSEN1 mutations on BACE1 may contribute to determining the phenotype of early onset FAD.
Detection of the Omicron SARS-CoV-2 Lineage and Its BA.1 Variant with Multiplex RT-qPCR
Authors: Yolshin Nikita D. , Komissarov Andrey B. , Varchenko Kirill V. , Musaeva Tamila D. , Fadeev Artem V. , Lioznov Dmitry A.
Published: December 2022

Whole genome sequencing (WGS) is considered the best instrument to track both virus evolution and the spread of new, emerging variants. However, WGS still does not allow the analysis of as many samples as qPCR does. Epidemiological and clinical research needs to develop advanced qPCR methods to identify emerging variants of SARS-CoV-2 while collecting data on their spreading in a faster and cheaper way, which is critical for introducing public health measures. This study aimed at designing a one-step RT-qPCR assay for multiplex detection of the Omicron lineage and providing additional data on its subvariants in clinical samples. The RT-qPCR assay demonstrated high sensitivity and specificity on multiple SARS-CoV-2 variants and was cross-validated by WGS.
The Microbiome in Systemic Sclerosis: Pathophysiology and Therapeutic Potential
Authors: Kim Suhee , Park Hee Jin , Lee Sang-Il
Published: December 2022

Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease with unknown etiology characterized by multi-organ fibrosis. Despite substantial investigation on SSc-related cellular and molecular mechanisms, effective therapies are still lacking. The skin, lungs, and gut are the most affected organs in SSc, which act as physical barriers and constantly communicate with colonized microbiota. Recent reports have documented a unique microbiome signature, which may be the pathogenic trigger or driver of SSc. Since gut microbiota influences the efficacy and toxicity of oral drugs, evaluating drug–microbiota interactions has become an area of interest in disease treatment. The existing evidence highlights the potential of the microbial challenge as a novel therapeutic option in SSc. In this review, we have summarized the current knowledge about molecular mechanisms of SSc and highlighted the underlying role of the microbiome in SSc pathogenesis. We have also discussed the latest therapeutic interventions using microbiomes in SSc, including drug–microbiota interactions and animal disease models. This review aims to elucidate the pathophysiological connection and therapeutic potential of the microbiome in SSc. Insights into the microbiome will significantly improve our understanding of etiopathogenesis and developing therapeutics for SSc.
The Role of Tumor Microenvironment in Regulating the Plasticity of Osteosarcoma Cells
Authors: Tian Boren , Du Xiaoyun , Zheng Shiyu , Zhang Yan
Published: December 2022

Osteosarcoma (OS) is a malignancy that is becoming increasingly common in adolescents. OS stem cells (OSCs) form a dynamic subset of OS cells that are responsible for malignant progression and chemoradiotherapy resistance. The unique properties of OSCs, including self-renewal, multilineage differentiation and metastatic potential, 149 depend closely on their tumor microenvironment. In recent years, the likelihood of its dynamic plasticity has been extensively studied. Importantly, the tumor microenvironment appears to act as the main regulatory component of OS cell plasticity. For these reasons aforementioned, novel strategies for OS treatment focusing on modulating OS cell plasticity and the possibility of modulating the composition of the tumor microenvironment are currently being explored. In this paper, we review recent studies describing the phenomenon of OSCs and factors known to influence phenotypic plasticity. The microenvironment, which can regulate OSC plasticity, has great potential for clinical exploitation and provides different perspectives for drug and treatment design for OS.
Effect of Superovulation Treatment on Oocyte’s DNA Methylation
Authors: Lopes Jordana S. , Ivanova Elena , Ruiz Salvador , Andrews Simon , Kelsey Gavin , Coy Pilar
Published: December 2022

Controlled ovarian stimulation is a necessary step in some assisted reproductive procedures allowing a higher collection of female gametes. However, consequences of this stimulation for the gamete or the offspring have been shown in several mammals. Most studies used comparisons between oocytes from different donors, which may contribute to different responses. In this work, we use the bovine model in which each animal serves as its own control. DNA methylation profiles were obtained by single-cell whole-genome bisulfite sequencing of oocytes from pre-ovulatory unstimulated follicles compared to oocytes from stimulated follicles. Results show that the global percentage of methylation was similar between groups, but the percentage of methylation was lower for non-stimulated oocytes in the imprinted genes APEG3, MEG3, and MEG9 and higher in TSSC4 when compared to stimulated oocytes. Differences were also found in CGI of imprinted genes: higher methylation was found among non-stimulated oocytes in MEST (PEG1), IGF2R, GNAS (SCG6), KvDMR1 ICR UMD, and IGF2. In another region around IGF2, the methylation percentage was lower for non-stimulated oocytes when compared to stimulated oocytes. Data drawn from this study might help to understand the molecular reasons for the appearance of certain syndromes in assisted reproductive technologies-derived offspring.
The Influence of Novel, Biocompatible, and Bioresorbable Poly(3-hydroxyoctanoate) Dressings on Wound Healing in Mice
Authors: Seta Martyna , Haraźna Katarzyna , Kasarełło Kaja , Solarz-Keller Daria , Cudnoch-Jędrzejewska Agnieszka , Witko Tomasz , Rajfur Zenon , Guzik Maciej
Published: December 2022

The human body’s natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment.
Effects of Phytochelatin-like Gene on the Resistance and Enrichment of Cd2+ in Tobacco
Authors: Zheng Yilin , Li Mengyu , Liu Binman , Qin Yafei , Li Jinhua , Pan Yu , Zhang Xingguo
Published: December 2022

Phytochelatins (PCs) are class III metallothioneins in plants. They are low molecular-weight polypeptides rich in cysteine residues which can bind to metal ions and affect the physiological metabolism in plants. Unlike other types of metallothioneins, PCs are not the product of gene coding but are synthesized by phytochelatin synthase (PCS) based on glutathione (GSH). The chemical formula of phytochelatin is a mixture of (γ-Glu-Cys)n-Gly (n = 2–11) and is influenced by many factors during synthesis. Phytochelatin-like (PCL) is a gene-encoded peptide (Met-(α-Glu-Cys)11-Gly) designed by our laboratory whose amino acid sequence mimics that of a natural phytochelatin. This study investigated how PCL expression in transgenic plants affects resistance to Cd and Cd accumulation. Under Cd2+ stress, transgenic plants were proven to perform significantly better than the wild-type (WT), regarding morphological traits and antioxidant abilities, but accumulated Cd to higher levels, notably in the roots. Fluorescence microscopy showed that PCL localized in the cytoplasm and nucleus.
The Polyunsaturated Fatty Acid EPA, but Not DHA, Enhances Neurotrophic Factor Expression through Epigenetic Mechanisms and Protects against Parkinsonian Neuronal Cell Death
Authors: Ceccarini Maria Rachele , Ceccarelli Veronica , Codini Michela , Fettucciari Katia , Calvitti Mario , Cataldi Samuela , Albi Elisabetta , Vecchini Alba , Beccari Tommaso
Published: December 2022

ω-3 Polyunsaturated fatty acids (PUFAs) have been found to exert many actions, including neuroprotective effects. In this regard, the exact molecular mechanisms are not well understood. Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. Emerging evidence supports the hypothesis that PD is the result of complex interactions between genetic abnormalities, environmental toxins, mitochondrial dysfunction, and other cellular processes, such as DNA methylation. In this context, BDNF (brain-derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) have a pivotal role because they are both involved in neuron differentiation, survival, and synaptogenesis. In this study, we aimed to elucidate the potential role of two PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and their effects on BDNF and GDNF expression in the SH-SY5Y cell line. Cell viability was determined using the MTT assay, and flow cytometry analysis was used to verify the level of apoptosis. Transmission electron microscopy was performed to observe the cell ultrastructure and mitochondria morphology. BDNF and GDNF protein levels and mRNA were assayed by Western blotting and RT-PCR, respectively. Finally, methylated and hydroxymethylated DNA immunoprecipitation were performed in the BDNF and GDNF promoter regions. EPA, but not DHA, is able (i) to reduce the neurotoxic effect of neurotoxin 6-hydroxydopamine (6-OHDA) in vitro, (ii) to re-establish mitochondrial function, and (iii) to increase BNDF and GDNF expression via epigenetic mechanisms.
Synergistic Effects of the Combinational Use of Escitalopram Oxalate and 5-Fluorouracil on the Inhibition of Gastric Cancer SNU-1 Cells
Authors: Chen Vincent Chin-Hung , Huang Jing-Yu , Tzang Bor-Show , Hsu Tsai-Ching , McIntyre Roger S.
Published: December 2022

Owing to its high recurrence rate, gastric cancer (GC) is the leading cause of tumor-related deaths worldwide. Besides surgical treatment, chemotherapy is the most commonly used treatment against GC. However, the adverse events associated with chemotherapy use limit its effectiveness in GC treatment. In this study, we investigated the effects of using combinations of low-dose 5-fluorouracil (5-FU; 0.001 and 0.01 mM) with different concentrations of escitalopram oxalate (0.01, 0.02, 0.06, and 0.2 mM) to evaluate whether the assessed combination would have synergistic effects on SNU-1 cell survival. 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.06 mM) administered over 24 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Moreover, 5-FU (0.001 mM) + escitalopram oxalate (0.02 or 0.06 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.02, 0.06, or 0.2 mM) administered over 48 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Compared with controls, SNU-1 cells treated with 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) exhibited significantly increased levels of annexin V staining, reactive oxygen species, cleaved poly (ADP-ribose) polymerase, and caspase-3 proteins. Furthermore, 5-FU (12 mg/kg) + escitalopram oxalate (12.5 mg/kg) significantly attenuated xenograft SNU-1 cell proliferation in nude mice. Our study is the first to report the synergistic effects of the combinational use of low-dose 5-FU and escitalopram oxalate on inhibiting SNU-1 cell proliferation. These findings may be indicative of an alternative option for GC treatment.
Biodegradable and Non-Biodegradable Biomaterials and Their Effect on Cell Differentiation
Authors: Geevarghese Rency , Sajjadi Seyedeh Sara , Hudecki Andrzej , Sajjadi Samad , Jalal Nahid Rezvani , Madrakian Tayyebeh , Ahmadi Mazaher , Włodarczyk-Biegun Małgorzata K. , Ghavami Saeid , Likus Wirginia , Siemianowicz Krzysztof , Łos Marek J.
Published: December 2022

Biomaterials for tissue scaffolds are key components in modern tissue engineering and regenerative medicine. Targeted reconstructive therapies require a proper choice of biomaterial and an adequate choice of cells to be seeded on it. The introduction of stem cells, and the transdifferentiation procedures, into regenerative medicine opened a new era and created new challenges for modern biomaterials. They must not only fulfill the mechanical functions of a scaffold for implanted cells and represent the expected mechanical strength of the artificial tissue, but furthermore, they should also assure their survival and, if possible, affect their desired way of differentiation. This paper aims to review how modern biomaterials, including synthetic (i.e., polylactic acid, polyurethane, polyvinyl alcohol, polyethylene terephthalate, ceramics) and natural (i.e., silk fibroin, decellularized scaffolds), both non-biodegradable and biodegradable, could influence (tissue) stem cells fate, regulate and direct their differentiation into desired target somatic cells.
Melatonin as a Potential Approach to Anxiety Treatment
Authors: Repova Kristina , Baka Tomas , Krajcirovicova Kristina , Stanko Peter , Aziriova Silvia , Reiter Russel J. , Simko Fedor
Published: December 2022

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin’s benefit in anxiety may reside in its sympatholytic action, interaction with the renin–angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.
Identification of the Third Case of PSEN1 Tyr389His Variant in Early-Onset Alzheimer’s Disease in Korea
Authors: Shim Kyu Hwan , Kang Sangjoon , An Seong Soo A. , Kang Min Ju
Published: December 2022

Amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are associated with autosomal-dominant early-onset Alzheimer’s disease (AD). Most mutations have been identified in the PSEN1 gene. We discovered a PSEN1 mutation (Tyr389His) in a Korean patient with early-onset AD who presented memory decline at 41 years of age followed by language, memory, and visuospatial dysfunctions. As this is the third such patient identified in Korea, this mutation may be involved in AD pathogenesis, suggesting that routine screening is necessary in this population. Altered intra-molecular interactions with the mutated amino acid may result in the destabilization of γ-secretase. In the future, a panel incorporating genes with relatively high-frequency rare variants, along with the APOE4 gene, may predict the onset of AD and facilitate customized treatment.
Apicobasal Surfaceome Architecture Encodes for Polarized Epithelial Functionality and Depends on Tumor Suppressor PTEN
Authors: Koetemann Anika , Wollscheid Bernd
Published: December 2022

The loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hallmark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific intra- and extracellular functions. Epithelial transport and signaling capacities are thought to be determined largely by the quality, quantity, and nanoscale organization of proteins residing in these membrane domains, the apicobasal surfaceomes. Despite its implications for cancer, drug uptake, and infection, our current knowledge of how the polarized surfaceome is organized and maintained is limited. Here, we used chemoproteomic surfaceome scanning to establish proteotype maps of apicobasal surfaceomes and reveal quantitative distributions of, i.e., surface proteases, phosphatases, and tetraspanins as potential key regulators of polarized cell functionality. We show further that the tumor suppressor PTEN regulates polarized surfaceome architecture and uncover a potential role in collective cell migration. Our differential surfaceome analysis provides a molecular framework to elucidate polarized protein networks regulating epithelial functions and PTEN-associated cancer progression.
Anti-Inflammatory Drug Therapy in Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis of Prospective Randomized, Double-Blind and Placebo-Controlled Trials
Authors: Vychopen Martin , Güresir Erdem , Wach Johannes
Published: December 2022

Althoughanti-inflammatory drug therapy has been identified as potentially beneficial for patients suffering from chronic subdural hematoma (cSDH), contemporary literature presents contradictory results. In this meta-analysis, we aimed to investigate the impact of anti-inflammatory drug therapy on mortality and outcome. We searched for eligible randomized, placebo-controlled prospective trials (RTCs) on PubMed, Embase and Medline until July 2022. From 97 initially identified articles, five RTCs met the criteria and were included in our meta-analysis. Our results illustrate significantly lower rates of recurrent cSDH (OR: 0.35; 95% CI: 0.21–0.58, p = 0.0001) in patients undergoing anti-inflammatory therapy. In the subgroup of patients undergoing primary conservative treatment, anti-inflammatory therapy was associated with lower rates of “switch to surgery” cases (OR: 0.30; 95% CI: 0.14–0.63, p = 0.002). Despite these findings, anti-inflammatory drugs seemed to be associated with higher mortality rates in patients undergoing surgery (OR: 1.76; 95% CI: 1.03–3.01, p = 0.04), although in the case of primary conservative treatment, no effect on mortality has been observed (OR: 2.45; 95% CI: 0.35–17.15, p = 0.37). Further multicentric prospective randomized trials are needed to evaluate anti-inflammatory drugs as potentially suitable therapy for asymptomatic patients with cSDH to avoid the necessity of surgical hematoma evacuation on what are predominantly elderly, vulnerable, patients.
Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?
Authors: Seifalian Amelia , Kenyon Julian , Khullar Vik
Published: December 2022

Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.
Genome-Wide Identification of the CER Gene Family and Significant Features in Climate Adaptation of Castanea mollissima
Authors: Zhao Shuqing , Nie Xinghua , Liu Xueqing , Wang Biyao , Liu Song , Qin Ling , Xing Yu
Published: December 2022

The plant cuticle is the outermost layer of the aerial organs and an important barrier against biotic and abiotic stresses. The climate varies greatly between the north and south of China, with large differences in temperature and humidity, but Chinese chestnut is found in both regions. This study investigated the relationship between the wax layer of chestnut leaves and environmental adaptation. Firstly, semi-thin sections were used to verify that there is a significant difference in the thickness of the epicuticular wax layer between wild chestnut leaves in northwest and southeast China. Secondly, a whole-genome selective sweep was used to resequence wild chestnut samples from two typical regional populations, and significant genetic divergence was identified between the two populations in the CmCER1-1, CmCER1-5 and CmCER3 genes. Thirty-four CER genes were identified in the whole chestnut genome, and a series of predictive analyses were performed on the identified CmCER genes. The expression patterns of CmCER genes were classified into three trends—upregulation, upregulation followed by downregulation and continuous downregulation—when chestnut seedlings were treated with drought stress. Analysis of cultivars from two resource beds in Beijing and Liyang showed that the wax layer of the northern variety was thicker than that of the southern variety. For the Y-2 (Castanea mollissima genome sequencing material) cultivar, there were significant differences in the expression of CmCER1-1, CmCER1-5 and CmCER3 between the southern variety and the northern one-year-grafted variety. Therefore, this study suggests that the CER family genes play a role in environmental adaptations in chestnut, laying the foundation for further exploration of CmCER genes. It also demonstrates the importance of studying the adaptation of Chinese chestnut wax biosynthesis to the southern and northern environments.
Pharmaceutical Development of Nanostructured Vesicular Hydrogel Formulations of Rifampicin for Wound Healing
Authors: Wallenwein Chantal M. , Weigel Verena , Hofhaus Götz , Dhakal Namrata , Schatton Wolfgang , Gelperina Svetlana , Groeber-Becker Florian K. , Dressman Jennifer , Wacker Matthias G.
Published: December 2022

Chronic wounds exhibit elevated levels of inflammatory cytokines, resulting in the release of proteolytic enzymes which delay wound-healing processes. In recent years, rifampicin has gained significant attention in the treatment of chronic wounds due to an interesting combination of antibacterial and anti-inflammatory effects. Unfortunately, rifampicin is sensitive to hydrolysis and oxidation. As a result, no topical drug product for wound-healing applications has been approved. To address this medical need two nanostructured hydrogel formulations of rifampicin were developed. The liposomal vesicles were embedded into hydroxypropyl methylcellulose (HPMC) gel or a combination of hyaluronic acid and marine collagen. To protect rifampicin from degradation in aqueous environments, a freeze-drying method was developed. Before freeze-drying, two well-defined hydrogel preparations were obtained. After freeze-drying, the visual appearance, chemical stability, residual moisture content, and redispersion time of both preparations were within acceptable limits. However, the morphological characterization revealed an increase in the vesicle size for collagen–hyaluronic acid hydrogel. This was confirmed by subsequent release studies. Interactions of marine collagen with phosphatidylcholine were held responsible for this effect. The HPMC hydrogel formulation remained stable over 6 months of storage. Moving forward, this product fulfills all criteria to be evaluated in preclinical and clinical studies.
The Association of PLAUR Genotype and Soluble suPAR Serum Level with COVID-19-Related Lung Damage Severity
Authors: Nekrasova Ludmila A. , Shmakova Anna A. , Samokhodskaya Larisa M. , Kirillova Karina I. , Stoyanova Simona S. , Mershina Elena A. , Nazarova Galina B. , Rubina Kseniya A. , Semina Ekaterina V. , Kamalov Armais A.
Published: December 2022

Uncovering the risk factors for acute respiratory disease coronavirus 2019 (COVID-19) severity may help to provide a valuable tool for early patient stratification and proper treatment implementation, improving the patient outcome and lowering the burden on the healthcare system. Here we report the results of a single-center retrospective cohort study on 151 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected symptomatic hospitalized adult patients. We assessed the association of several blood test measurements, soluble urokinase receptor (uPAR) serum level and specific single nucleotide polymorphisms of ACE (I/D), NOS3 (rs2070744, rs1799983), SERPINE1 (rs1799768), PLAU (rs2227564) and PLAUR (rs344781, rs2302524) genes, with the disease severity classified by the percentage of lung involvement on computerized tomography scans. Our findings reveal that the T/C genotype of PLAUR rs2302524 was independently associated with a less severe lung damage (odds ratio 0.258 [0.071–0.811]). Along with high C-reactive protein, fibrinogen and soluble uPAR serum levels turned out to be independently associated with more severe lung damage in COVID-19 patients. The identified factors may be further employed as predictors of a possibly severe COVID-19 clinical course.
New Wolbachia pipientis Genotype Increasing Heat Stress Resistance of Drosophila melanogaster Host Is Characterized by a Large Chromosomal Inversion
Authors: Korenskaia Aleksandra E. , Shishkina Olga D. , Klimenko Alexandra I. , Andreenkova Olga V. , Bobrovskikh Margarita A. , Shatskaya Natalja V. , Vasiliev Gennady V. , Gruntenko Nataly E.
Published: December 2022

The maternally transmitted endocellular bacteria Wolbachia is a well-known symbiont of insects, demonstrating both negative and positive effects on host fitness. The previously found Wolbachia strain wMelPlus is characterized by a positive effect on the stress-resistance of its host Drosophila melanogaster, under heat stress conditions. This investigation is dedicated to studying the genomic underpinnings of such an effect. We sequenced two closely related Wolbachia strains, wMelPlus and wMelCS112, assembled their complete genomes, and performed comparative genomic analysis engaging available Wolbachia genomes from the wMel and wMelCS groups. Despite the two strains under study sharing very close gene-composition, we discovered a large (>1/6 of total genome) chromosomal inversion in wMelPlus, spanning through the region that includes the area of the inversion earlier found in the wMel group of Wolbachia genotypes. A number of genes in unique inversion blocks of wMelPlus were identified that might be involved in the induction of a stress-resistant phenotype in the host. We hypothesize that such an inversion could rearrange established genetic regulatory-networks, causing the observed effects of such a complex fly phenotype as a modulation of heat stress resistance. Based on our findings, we propose that wMelPlus be distinguished as a separate genotype of the wMelCS group, named wMelCS3.
Mitochondrial Aging and Senolytic Natural Products with Protective Potential
Authors: Deledda Andrea , Giordano Emanuele , Velluzzi Fernanda , Flore Giovanna , Franceschelli Sara , Speranza Lorenza , Ripari Patrizio
Published: December 2022

Living organisms do not disregard the laws of thermodynamics and must therefore consume energy for their survival. In this way, cellular energy exchanges, which aim above all at the production of ATP, a fundamental molecule used by the cell for its metabolisms, favor the formation of waste products that, if not properly disposed of, can contribute to cellular aging and damage. Numerous genes have been linked to aging, with some favoring it (gerontogenes) and others blocking it (longevity pathways). Animal model studies have shown that calorie restriction (CR) may promote longevity pathways, but given the difficult application of CR in humans, research is investigating the use of CR-mimetic substances capable of producing the same effect. These include some phytonutrients such as oleuropein, hydroxytyrosol, epigallo-catechin-gallate, fisetin, quercetin, and curcumin and minerals such as magnesium and selenium. Some of them also have senolytic effects, which promote the apoptosis of defective cells that accumulate over the years (senescent cells) and disrupt normal metabolism. In this article, we review the properties of these natural elements that can promote a longer and healthier life.
Cyberbullying in COVID-19 Pandemic Decreases? Research of Internet Habits of Croatian Adolescents
Authors: Vejmelka Lucija , Matkovic Roberta , Rajter Miroslav
Published: December 2022

Online contacts and other activities on the Internet came into focus given the increased use during the COVID-19 pandemic. The online environment is a setting for problematic Internet use, including cyberbullying, and research so far shows that inclusion in cyberbullying depends on the amount of screen time. Increases in screen time during the pandemic could affect the growth of the prevalence rates of children’s involvement in cyberbullying. The aim of this paper is to compare the Internet habits, cyberbullying and parental role in children’s online activities before and during the COVID-19 pandemic, when the use of the Internet increased due to online classes and implemented measures to prevent the spread of the infection. The Institute of Public Health of Split-Dalmatia County conducted a quantitative online survey of Internet habits and problematic Internet use in two waves in 2017 and 2020 with adolescents from 12–18 (N2017 = 536; N2020 = 284). Research included adherence to ethical standards of research with children. An online activity questionnaire for children, a questionnaire of parental behaviors and the European Cyberbullying Intervention Project Questionnaire—ECIPQ were used. The results of the research point out that cyberbullying rates in the pandemic decreased. The results show that the cumulative effect of parental monitoring is medium with approximately 5% of explained variance for experiencing and 6% for committing violence. The similar set of predictors is statistically significant in both regressions. Parental actions of monitoring applications, informing children and monitoring search history are identified as protective factors for committing or experiencing cyber violence. These findings are important for understanding the effect of the general digitization of society, which leads to an extensive increase in the use of online content and various digital tools, and the role of the parents, especially as protective potential for cyberbullying among children.
Yttrium and Lithium Complexes with Diamidophosphane Ligand Bearing 2,1,3-Benzothiazolyl Substituent: Polydentate Complexation and Reversible NH–PH Tautomery
Authors: Khisamov Radmir M. , Sukhikh Taisiya S. , Konchenko Sergey N. , Pushkarevsky Nikolay A.
Published: December 2022

Deprotonation of a bis(amino)phosphane H2L = PhP(HNBtd)2 bearing a heterocyclic Btd = 2,1,3-benzothiadiazol-4-yl substituents at nitrogen atoms by silylamides LiNTms2 and Y(NTms2)3 (Tms = trimethylsilylamide) results in lithium and yttrium complexes with the deprotonated HL– and L2– forms as κ2-N and κ4-N chelating ligands. A binuclear complex [LiHL]2 was crystallized from Et2O, and was shown to reversibly dissociate in thf (tetrahydrofuran) with the NH(soln)–PH(crystal) tautomeric shift; the compound [Li2L] was spectroscopically characterized. Yttrium readily forms stable bis-ligand complexes [YL2]– and [YL(HL)]. In the latter, the H atom in HL resides on phosphorus; the coordination sphere remains accessible to another ligands, and it was crystallized as [{YL(HL)}2(µ-dioxane)] species (YN8O coordination). In the former complex, the coordination sphere was saturated (YN8) by closer bound ligands; it was crystallized as a salt with [Li(thf)4]+. The monoligand complex could not be cleanly obtained in a 1:1 reaction of H2L and Y(NTms2)3, and was only crystallographically characterized as a dimer [YL(NTms)2]2. Partial oxidation of the central P atom with the formation of phosphine-oxide ligands PhP(O)(NBtd)2– was observed. They co-crystallize in the same position as non-oxidized ligands in [YL2]– and [YL(NTms2)]2 species and participate in bonding between two units in the latter. TD-DFT calculations reveal that main transitions in the visible region of electronic spectra correspond to the charge transfer bands mostly associated with the orbitals located on Btd fragments.
Genetic Structure of Apis cerana Populations from South Korea, Vietnam and the Russian Far East Based on Microsatellite and Mitochondrial DNA Polymorphism
Authors: Kaskinova Milyausha , Gaifullina Luisa , Ilyasov Rustem , Lelej Arkady , Kwon Hyung Wook , Thai Pham Hong , Saltykova Elena
Published: December 2022

In this article, we present the results of the genetic analysis of Apis cerana samples from the Russian Far East, South Korea and Vietnam. An analysis of the polymorphism of seven microsatellite loci and an assessment of the haplotype diversity of the mtDNA tRNAleu-COII locus were performed. A fragment of about 431 bp in tRNAleu-COII was sequenced. The analysis showed the presence of 14 haplotypes, while the predominant haplotype was Japan1. Microsatellite data revealed two differentiated clusters. The first cluster contained tropical climate A. cerana samples from Vietnam, and the second cluster combined temperate climate A. cerana samples from the Russian Far East and South Korea.
Review on the Genus Stylophoronychus (Acari: Tetranychidae), with Description of a New Species
Authors: Pan Xiaojuan , Ochoa Ronald , Jin Daochao , Yi Tianci
Published: December 2022

Only two species of the genus Stylophoronychus, S. baghensis (Prasad, 1975) and S. guangzhouensis (Ma and Yuan, 1980), have been recorded in China. Herein we describe a new species Stylophoronychus wangaePan, Jin & Yi sp. nov. based on characteristics of the deutonymphs and adults. The synonym of S. guangzhouensis (Ma and Yuan, 1980) and S. lalli (Prasad, 1975) with S. vannus (Rimando, 1968) is proposed. A redescription of S. vannus (Rimando, 1968) based on the adults of both sexes, deutonymphs and a protonymph is given. The ontogenetic changes of leg chaetotaxy in two species are given and discussed. The updated key to the species of Stylophoronychus of the world is provided.
Wheat-Bran-Based Artificial Diet for Mass Culturing of the Fall Armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae)
Authors: Ge Shishuai , Chu Bo , He Wei , Jiang Shan , Lv Chunyang , Gao Lingyun , Sun Xiaoting , Yang Xianming , Wu Kongming
Published: December 2022

Spodoptera frugiperda Smith (fall armyworm (FAW)) has invaded many countries in Africa and Asia in recent years, considerably restricting global agricultural production. In this study, we assessed the rearing performance of four artificial diets (D1: an artificial FAW diet based on wheat bran and soybean, maize, and yeast powders; D2: an artificial diet developed for Helicoverpa armigera (Hübner), based on wheat bran and soybean and yeast powders; D3: an artificial diet based on soybean powder; D4: an artificial diet based on wheat bran) for FAWs. We designed D4 based on a traditional diet (D2) but substituted the wheat bran for soybean and yeast powders. At 25 ± 1 °C, 75% ± 5% RH, and a 16:8 h L:D photoperiod, the larval stage of FAWs fed on D4 lasted 15.88 d, the pupal stage lasted 9.48 d, the pupal mass was 270.45 mg, the number of eggs deposited was 1364.78, and the mating rate was 89.53%. Most biological indicators of the larvae that were fed D4 were basically consistent with those of the larvae fed on the traditional diet (D2), but the intrinsic rate of increase (r), finite rate of increase (λ), and net reproduction rate (R0) of the D4 FAWs were lower than those of the D2 FAWs. The flight capacity (flight distance, duration, and velocity were 19.73 km, 6.91 h, and 2.90 km/h, respectively) of the D4 FAWs was comparable to that of the FAWs fed a traditional diet and maize leaves. Compared with the three other formulas, the cost of using D4 was lower by 26.42% on average. These results show that using cheap wheat bran instead of soybean flour and yeast powder as the basic material for an artificial diet for FAWs is feasible, which will substantially reduce rearing costs and promote the development of new controlling measures for FAWs. In addition, this study also has a reference value for reducing the cost of artificial diets for other insects.
A Single-Cell Atlas of the Atherosclerotic Plaque in the Femoral Artery and the Heterogeneity in Macrophage Subtypes between Carotid and Femoral Atherosclerosis
Authors: Wang Ping , Zheng Lin , Qiao Maolin , Zhao Tianliang , Zhang Ruijing , Dong Honglin
Published: December 2022

Atherosclerosis of femoral arteries can cause the insufficient blood supply to the lower limbs and lead to gangrenous ulcers and other symptoms. Atherosclerosis and inflammatory factors are significantly different from other plaques. Therefore, it is crucial to observe the cellular composition of the femoral atherosclerotic plaque and identify plaque heterogeneity in other arteries. To this end, we performed single-cell sequencing of a human femoral artery plaque. We identified 14 cell types, including endothelial cells, smooth muscle cells, monocytes, three macrophages with four different subtypes of foam cells, three T cells, natural killer cells, and B cells. We then downloaded single-cell sequencing data of carotid atherosclerosis from GEO, which were compared with the one femoral sample. We identified similar cell types, but the femoral artery had significantly more nonspecific immune cells and fewer specific immune cells than the carotid artery. We further compared the differences in the proportion of inflammatory macrophages, and resident macrophages, and the proportion of inflammatory macrophages was greater within the carotid artery. Through comparing one femoral sequencing sample with carotid samples from public datasets, our study reveals the single-cell map of the femoral artery and the heterogeneity of carotid and femoral arteries at the cellular level, laying the foundation for mechanistic and pharmacological studies of the femoral artery.
Prognostic Value of Combined Radiomic Features from Follow-Up DWI and T2-FLAIR in Acute Ischemic Stroke
Authors: Gerbasi Alessia , Konduri Praneeta , Tolhuisen Manon , Cavalcante Fabiano , Rinkel Leon , Kappelhof Manon , Wolff Lennard , Coutinho Jonathan M. , Emmer Bart J. , Costalat Vincent , Arquizan Caroline , Hofmeijer Jeannette , Uyttenboogaart Maarten , van Zwam Wim , Roos Yvo , Quaglini Silvana , Bellazzi Riccardo , Majoie Charles , Marquering Henk
Published: December 2022

The biological pathways involved in lesion formation after an acute ischemic stroke (AIS) are poorly understood. Despite successful reperfusion treatment, up to two thirds of patients with large vessel occlusion remain functionally dependent. Imaging characteristics extracted from DWI and T2-FLAIR follow-up MR sequences could aid in providing a better understanding of the lesion constituents. We built a fully automated pipeline based on a tree ensemble machine learning model to predict poor long-term functional outcome in patients from the MR CLEAN-NO IV trial. Several feature sets were compared, considering only imaging, only clinical, or both types of features. Nested cross-validation with grid search and a feature selection procedure based on SHapley Additive exPlanations (SHAP) was used to train and validate the models. Considering features from both imaging modalities in combination with clinical characteristics led to the best prognostic model (AUC = 0.85, 95%CI [0.81, 0.89]). Moreover, SHAP values showed that imaging features from both sequences have a relevant impact on the final classification, with texture heterogeneity being the most predictive imaging biomarker. This study suggests the prognostic value of both DWI and T2-FLAIR follow-up sequences for AIS patients. If combined with clinical characteristics, they could lead to better understanding of lesion pathophysiology and improved long-term functional outcome prediction.
Hemodynamic Instability during Surgery for Pheochromocytoma: A Retrospective Cohort Analysis
Authors: Senne Moritz , Wichmann Doerte , Pindur Pascal , Grasshoff Christian , Mueller Sven
Published: December 2022

Background: Perioperative hemodynamic instability is one of the most common adverse events in patients undergoing adrenalectomy for pheochromocytoma. The aim of this study was to analyze the impact of perioperative severe hemodynamic instability. Methods: We present a retrospective, single-center analysis in a major tertiary hospital of all consecutive patients undergoing elective adrenalectomy from 2005 to 2019 for pheochromocytoma. Severe perioperative hypertension and hypotension were evaluated, defined as changes in blood pressure larger than 30% of the preoperative patient-specific mean arterial pressure (MAP). Results: Unilateral adrenalectomy was performed in 67 patients. Intraoperative episodes of hemodynamic instability occurred in 97% of all patients (n = 65), severe hypertension occurred in 24 patients (36%), and severe hypotensive episodes occurred in 62 patients (93%). Patients with more than five severe hypotensive episodes (n = 29) received higher preoperative alpha-adrenergic blockades (phenoxybenzamine 51 ± 50 mg d−1 vs. 29 ± 27 mg d−1; p = 0.023) and had a longer mean ICU stay (39.6 ± 41.5 h vs. 20.6 ± 19.1 h, p = 0.015). Conclusion: Intraoperative hypotensive, rather than hypertensive, episodes occurred during adrenalectomy. The occurrence of more than five hypotensive episodes correlated well with a significantly longer hospital stay and ICU time.
Immune-Mediated Diseases Following COVID-19 Vaccination: Report of a Teaching Hospital-Based Case-Series
Authors: Liozon Eric , Filloux Matthieu , Parreau Simon , Gondran Guillaume , Bezanahary Holy , Ly Kim-Heang , Fauchais Anne-Laure
Published: December 2022

The occurrence and course of immune-mediated diseases (IMDs) following COVID-19 vaccination has been little explored so far. We retrieved, among adult patients hospitalized at the Internal Department of a French university hospital up to May 2022, all those who had developed, or relapsed to, an IMD less than 3 weeks following COVID-19 vaccination, without other triggers. Twenty-seven (24 new-onset) post-COVID-19 vaccine IMDs were recorded. They comprised giant cell arteritis or polymyalgia rheumatica (n = 16, HLA-DRB1*04 in 58% of 12 assessed GCA cases), immune-mediated necrotizing myositis or acute rhabdomyolysis, systemic vasculitis, immune thrombocytopenic purpura, rheumatoid arthritis, anti-synthetase syndrome, and adult-onset Still’s disease. The causative vaccines were mRNA-based (20 cases) or viral vector-based (7 cases). The IMD typically occurred after the first vaccine dose, with an average delay of 8 (5 SD) days. The patients’ mean age was 67 years, and 58% were women. The IMDs had protracted courses in all but three of the patients and typically required high-dose glucocorticoids, in combination with immunomodulators in 13 patients. One patient died of intractable rhabdomyolysis, whereas five suffered permanent damage from IMDs. Eleven patients with well-controlled IMDs completed their COVID-19 vaccination schedule, and two suffered mild IMD relapses. There is a risk of IMDs, notably GCA/PMR, and muscle disorders, following COVID-19 vaccination. Such adverse reactions typically occurred after the first dose, raising concern about subsequent COVID-19 vaccinations. However, early re-challenge in well-controlled IMDs appeared safe.