bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Senescence-Resumed Proliferation in Keloid Pathogenesis
Authors: Wang Ching-Yun , Wu Chieh-Wen , Lin Ting-Yi
Published: February 2023

Senescence-resumed proliferation (SRP) is proposed to be a mechanism associated with the escape of p21-mediated senescence and the activation of Wnt/β-catenin pathways that enhance malignancy. The keloid genomic landscape shows heavy intersections between TP53 and TGF-β signaling. The machinery to maintain cellular integrity through senescence, apoptosis, and autophagy is co-regulated with stemness, hedgehog, and immunomodulation. Our study demonstrated the presence of SRP and how, on the transcriptome level, TP53 and Wnt/β-catenin pathways are regulated to deliver the same cellular fate. Our study proves that SRP co-regulated with senescence-associated reprogramming (Wnt/β-catenin pathways) and TP53-p21 dysregulations originate from a common etiology and present a novel therapeutic target opportunity.
Effect of CUX1 on the Proliferation of Hu Sheep Dermal Papilla Cells and on the Wnt/β-Catenin Signaling Pathway
Authors: Zhou Hui , Huang Sainan , Lv Xiaoyang , Wang Shanhe , Cao Xiukai , Yuan Zehu , Getachew Tesfaye , Mwacharo Joram M. , Haile Aynalem , Quan Kai , Li Yutao , Reverter Antonio , Sun Wei
Published: February 2023

CUT-like homeobox 1 protein (CUX1), also called CUX, CUTL1, and CDP, is a member of the DNA-binding protein homology family. Studies have shown that CUX1 is a transcription factor that plays an important role in the growth and development of hair follicles. The aim of this study was to investigate the effect of CUX1 on the proliferation of Hu sheep dermal papilla cells (DPCs) to reveal the role of CUX1 in hair follicle growth and development. First, the coding sequence (CDS) of CUX1 was amplified by PCR, and then CUX1 was overexpressed and knocked down in DPCs. A Cell Counting Kit-8 (CCK8), 5-ethynyl-2-deoxyuridine (EdU), and cell cycle assays were used to detect the changes in the proliferation and cell cycle of DPCs. Finally, the effects of overexpression and knockdown of CUX1 in DPCs on the expression of WNT10, MMP7, C-JUN, and other key genes in the Wnt/β-catenin signaling pathway were detected by RT-qPCR. The results showed that the 2034-bp CDS of CUX1 was successfully amplified. Overexpression of CUX1 enhanced the proliferative state of DPCs, significantly increased the number of S-phase cells, and decreased the number of G0/G1-phase cells (p < 0.05). CUX1 knockdown had the opposite effects. It was found that the expression of MMP7, CCND1 (both p < 0.05), PPARD, and FOSL1 (both p < 0.01) increased significantly after overexpression of CUX1 in DPCs, while the expression of CTNNB1 (p < 0.05), C-JUN, PPARD, CCND1, and FOSL1 (all p < 0.01) decreased significantly. In conclusion, CUX1 promotes proliferation of DPCs and affects the expression of key genes of the Wnt/β-catenin signaling pathway. The present study provides a theoretical basis to elucidate the mechanism underlying hair follicle development and lambskin curl pattern formation in Hu sheep.
MiRNA Profiling and Its Potential Roles in Rapid Growth of Velvet Antler in Gansu Red Deer (Cervus elaphus kansuensis)
Authors: Zhang Zhenxiang , He Caixia , Bao Changhong , Li Zhaonan , Jin Wenjie , Li Changzhong , Chen Yanxia
Published: February 2023

A significant variety of cell growth factors are involved in the regulation of antler growth, and the fast proliferation and differentiation of various tissue cells occur during the yearly regeneration of deer antlers. The unique development process of velvet antlers has potential application value in many fields of biomedical research. Among them, the nature of cartilage tissue and the rapid growth and development process make deer antler a model for studying cartilage tissue development or rapid repair of damage. However, the molecular mechanisms underlying the rapid growth of antlers are still not well studied. MicroRNAs are ubiquitous in animals and have a wide range of biological functions. In this study, we used high-throughput sequencing technology to analyze the miRNA expression patterns of antler growth centers at three distinct growth phases, 30, 60, and 90 days following the abscission of the antler base, in order to determine the regulatory function of miRNA on the rapid growth of antlers. Then, we identified the miRNAs that were differentially expressed at various growth stages and annotated the functions of their target genes. The results showed that 4319, 4640, and 4520 miRNAs were found in antler growth centers during the three growth periods. To further identify the essential miRNAs that could regulate fast antler development, five differentially expressed miRNAs (DEMs) were screened, and the functions of their target genes were annotated. The results of KEGG pathway annotation revealed that the target genes of the five DEMs were significantly annotated to the “Wnt signaling pathway”, “PI3K-Akt signaling pathway”, “MAPK signaling pathway”, and “TGF-β signaling pathway”, which were associated with the rapid growth of velvet antlers. Therefore, the five chosen miRNAs, particularly ppy-miR-1, mmu-miR-200b-3p, and novel miR-94, may play crucial roles in rapid antler growth in summer.
Bonan Youang and Terrinalum: The Ethnogeology of Ballaarat’s Living Landscape
Authors: Jones David S.
Published: February 2023

Ethnogeology offers a longitudinal history of the formation of landscapes though the lens of First Nations Peoples. Significantly, it offers an insight into landscape change and geographical formation as consequence of geological events, climate shift (change), and consequential human resilience and adaptation strategies. This article considers a cultural landscape near Ballaarat (Ballarat) in Australia and its geological omnipresence in the eyes of the First Nations’ Wadawurrung People. The features, two extinct volcanoes—Bonan Youang (Mt Buninyong) and Terrinalum (Mt Elephant)—and a connection tract, offer high cultural values to the Wadawurrung People in addition to serving as key contemporary mental and orientation landmarks arising from their roles in the locality’s pastoral, goldmining, and suburbanisation colonisation phases.
The Impact of Multidrug-Resistant Acinetobacter baumannii Infection in Critically Ill Patients with or without COVID-19 Infection
Authors: Alenazi Thamer A. , Shaman Maryam S. Bin , Suliman Durria M. , Alanazi Turkiah A. , Altawalbeh Shoroq M. , Alshareef Hanan , Lahreche Doha I. , Al-Azzam Sayer , Araydah Mohammad , Karasneh Reema , Rebahi Faycal , Alharbi Marwah H. , Aldeyab Mamoon A.
Published: February 2023

This is a single-center, retrospective, cohort study aimed to evaluate the clinical outcomes of multi-drug resistance in Acinetobacter baumannii infections (MDR-AB) in intensive care unit (ICU) patients with or without a COVID-19 infection and risk factors for blood stream infection. A total of 170 patients with MDR-AB were enrolled in the study. Of these, 118 (70%) patients were admitted to the ICU due to a COVID-19 infection. Comparing the COVID-19 and non-COVID-19 groups, the use of mechanical ventilation (98.31% vs. 76.92%, p = 0.000), the presence of septic shock (96.61% vs. 82.69%, p = 0.002), and the use of steroid (99.15% vs. 71.15%, p = 0.000) and tocilizumab therapies (33.05% vs. 0%, p = 0.000) were more prevalent and statistically more significant in patients with COVID-19 infections. The average length of the ICU stay (21.2 vs. 28.33, p = 0.0042) was significantly lower in patients with COVID-19 infections. Survival rate was 21.19% for the COVID-19 group and 28.85% for non-COVID-19 group with a p-value = 0.0361. COVID-19 status was associated with significantly higher hazards of death (HR 1.79, CI 95% 1.02–3.15, p = 0.043). Higher SOFAB (15.07 vs. 12.07, p = 0.0032) and the placement of an intravascular device (97.06% vs. 89.71%, p = 0.046) were significantly associated with the development of a bloodstream infection. Our study has shown that critically ill patients with an MDR-AB infection, who were admitted due to a COVID-19 infection, had a higher hazard for death compared to non-COVID-19 infected patients.
Cardiotoxicity of Electronic Cigarettes and Heat-Not-Burn Tobacco Products—A Problem for the Modern Pediatric Cardiologist
Authors: Luca Alina-Costina , Curpăn Alexandrina-Ștefania , Iordache Alin-Constantin , Mîndru Dana Elena , Țarcă Elena , Luca Florin-Alexandru , Pădureț Ioana-Alexandra
Published: February 2023

Electronic nicotine delivery systems (ENDS) have become increasingly popular among adolescents, either as an alternative to conventional cigarettes (CCs) or as a newly acquired recreational habit. Although considered by most users as a safer option for nicotine intake, these devices pose significant health risks, resulting in multisystem damage. Heat-not-burn products, which, unlike ENDS, contain tobacco, are also alternatives to CCs that consumers use based on the idea that their safety profile is superior to that of cigarettes. Recent studies in the USA and EU show that adolescents are particularly prone to using these devices. Pediatric cardiologists, as well as other healthcare professionals, should be aware of the complications that may arise from acute and chronic consumption of these substances, considering the cardiovascular damage they elicit. This article summarized the known data about the impact of ENDS on the cardiovascular system, with emphasis on the pathophysiological and molecular changes that herald the onset of systemic lesions alongside the clinical cardiovascular manifestations in this scenario.
Association between Socioeconomic Status and Healthcare Utilization for Children with Allergic Diseases: Korean National Health and Nutritional Examination Survey (2015–2019)
Authors: Kim Jeoungmi , Kim Bomgyeol , Kim Do Hee , Kim Yejin , Rajaguru Vasuki
Published: February 2023

This study aimed to investigate the association between socioeconomic status (SES) and healthcare utilization by children with allergic diseases. We determined SES based on parental occupation and household income. A cross-sectional study was conducted using the Korean National Health and Nutritional Examination Survey (KNHANES) between 2015 and 2019 with participants who were under 18 years of age. The presence of allergic conditions was determined by a self-reported survey of parental response and healthcare utilization data (such as inpatient and outpatient visits). Moreover, we categorized SES into four quantiles (Q1–Q4) based on household income per annum. Then, the data were analyzed using chi-square tests and multivariate logistic regression analysis with confidence intervals (CIs) of 95%, and p < 0.05 was considered significant. A total of 3250 participants were involved in this study. The percentage of allergic diseases was 67.9% for allergic asthma and 32.1% for atopic dermatitis. It was found that the participants who were over 13 years old had atopic dermatitis and were more likely to visit the hospital than younger children. Additionally, the highest SES group in Q4 demonstrated higher healthcare utilization (OR = 1.58; 95% CI, 1.14–1.76) than other SES groups. Our study reveals that parental socioeconomic characteristics are related to the use of healthcare services for children with allergic disorders in Korea. These results highlight the need for public health actions and research to overcome the SES gap among children with allergic diseases.
Cultural Practices and Adoption of National Family Planning Communication Campaigns on Select Ethnic Groups in Nigeria
Authors: Ojih Success Emmanuel , Adeyeye Babatunde , Onoja Ibe Ben , Adesina Evaristus , Omole Funke , Kayode-Adedeji Tolulope
Published: February 2023

This study evaluated the extent to which married Idoma (Benue State) and Igala people (Kogi State) in North-Central Nigeria were exposed to the 2017 National Family Planning Communication Campaigns. The study also examined their level of knowledge, the extent to which they adopted the campaign messages, and how Alekwu/Ibegwu and other socio-cultural factors influenced their level of adoption of the campaign messages. The study adopted a quantitative (questionnaire survey) research method. The data were subjected to a descriptive analysis, correlation, ANOVA, Pearson Product Movement Correlation (PPMC), and Binary Logistics Regression. The findings showed that the majority of the people were exposed to information on condoms, implants, and Intrauterine Contraceptive Devices (IUCDs) (Cuppar T) in the course of the campaign; however, most of them were not exposed to information on Oral Pills, Vasectomies, Tubal ligation and Injections. Findings also revealed that knowledge of modern family planning in the study areas (51.2%) was below the 85.8% national family planning knowledge threshold and far below the expected 95% target of the 2017–2020 family planning communication campaign goal. Findings equally showed poor adoption of the campaign messages due to their cultural beliefs. The study concluded that family planning was often accepted among people whose ways of life have been significantly altered in favour of the idea.
A GDPR-Compliant Dynamic Consent Mobile Application for the Australasian Type-1 Diabetes Data Network
Authors: Wang Zhe , Stell Anthony , Sinnott Richard O. ,   the ADDN Study Group
Published: February 2023

Australia has a high prevalence of diabetes, with approximately 1.2 million Australians diagnosed with the disease. In 2012, the Australasian Diabetes Data Network (ADDN) was established with funding from the Juvenile Diabetes Research Foundation (JDRF). ADDN is a national diabetes registry which captures longitudinal information about patients with type-1 diabetes (T1D). Currently, the ADDN data are directly contributed from 42 paediatric and 17 adult diabetes centres across Australia and New Zealand, i.e., where the data are pre-existing in hospital systems and not manually entered into ADDN. The historical data in ADDN have been de-identified, and patients are initially afforded the opportunity to opt-out of being involved in the registry; however, moving forward, there is an increased demand from the clinical research community to utilise fully identifying data. This raises additional demands on the registry in terms of security, privacy, and the nature of patient consent. General Data Protection Regulation (GDPR) is an increasingly important mechanism allowing individuals to have the right to know about their health data and what those data are being used for. This paper presents a mobile application being designed to support the ADDN data collection and usage processes and aligning them with GDPR. The app utilises Dynamic Consent—an informed specific consent model, which allows participants to view and modify their research-driven consent decisions through an interactive interface. It focuses specifically on supporting dynamic opt-in consent to both the registry and to associated sub-projects requesting access to and use of the patient data for research purposes.
Effect of Intramuscular Tramadol on the Duration of Clinically Relevant Sciatic Nerve Blockade in Patients Undergoing Calcaneal Fracture Fixation: A Randomized Controlled Trial
Authors: Janiak Marek , Gorniewski Grzegorz , Kowalczyk Rafal , Wasilewski Piotr , Nowakowski Piotr , Trzebicki Janusz
Published: February 2023

Background: Calcaneal fracture fixation can generate severe postoperative pain and analgesia can be supported by a sciatic nerve block. However, following resolution of the sensory blockade, rebound pain may ensue. The aim of this study was to assess whether an incidental finding of two patients with an extension of the sciatic nerve block beyond 24 h following 100 mg of intramuscular tramadol administration could be confirmed. Methods: Thirty-seven patients scheduled for a calcaneal intramedullary fixation (Calcanail®) were randomly divided into two groups. The tramadol group (n = 19) received a sciatic nerve block with 20 mL of 0.25% bupivacaine and a concomitant dose of 100 mg of intramuscular tramadol, while the control group (n = 18) received an identical sciatic nerve block with concomitant injection of normal saline (placebo). All patients had a spinal anesthesia with light sedation for the procedure. The time to first analgesic request defined as appearance of any pain (NRS > 0) was assessed as the primary endpoint with a clinically relevant expected result of at least 50% elongation in sensory blockade. Results: The median time to first analgesic request from time of blockade in the tramadol group was 670 min compared with 578 min in the control group. The result was clinically not relevant and statistically not significant (p = 0.17). No statistical difference could be demonstrated in the time to first opioid request, although a trend for opioid sparing in the tramadol group could be seen. Total morphine consumption in the first 24 h was also statistically insignificant (the tramadol group 0.066 mg kg−1 compared with 0.125 mg kg−1 in the control group). In conclusion, intramuscular tramadol does not extend the duration of analgesia of a sciatic nerve block following a calcaneal fracture fixation beyond 2 h and an opioid sparing effect could not be demonstrated in this trial.
Systemic Review through Bibliometric Analysis with RStudio of Skills Learning to Favor the Employability of Its Graduates
Authors: Martin Gomez Sonia , Bartolome Muñoz de Luna Angel
Published: February 2023

Despite the fact that the member countries of the European Union initiated a reform of university education two decades ago to promote employability, giving importance to soft skills beyond the purely technical ones of each degree, there is still an important contrast between the demand for this type of skills on the part of the labor market and the educational offerings of universities. Therefore, it is necessary to analyze the impact that the concept of employability and soft skills really has on the scientific community and the patterns of collaboration between the European Union, the UK and Switzerland, among researchers in these matters, through a bibliometric study of the scientific publications in the area, collected in the databases Web of Science and Scopus during the period from 1996–2022, presenting the most significant bibliometric data through a descriptive and quantitative methodology. The main results allow us to detect, among other conclusions, an increase in scientific production from 2010 but minimal scientific collaboration, since 90% of the total number of works were signed by a single author. Two countries, the UK and Australia, have 80% more scientific production on these topics than Spain. This bibliometric study offers a descriptive and analytical panorama, from diachronic and synchronic perspectives, of the main bibliometric variables in two of the databases with the greatest impact among the scientific community (WOS and Scopus), allowing researchers and institutions to visualize the most developed study trends and the strongest emerging lines of research. The necessary rapprochement between the university and the company, in this way, will help the university to know its present situation but also to discover what learning strategy it should consider reducing the training gap in competences.
Reduction in Gingival Bleeding after Atelocollagen Injection in Patients with Hashimoto’s Disease—A Pilot Study
Authors: Klewin-Steinböck Sylwia , Wyganowska Marzena
Published: February 2023

Periodontal diseases are one of the main causes of tooth loss and the second most common oral disease after carries. Patients with autoimmune diseases, such as Hashimoto’s disease, are more often vulnerable to infection. In the study group of patients, despite the lack of other signs of gingivitis, bleeding occurred after tooth brushing or minor trauma. Bleeding on probing is the first objective sign of ongoing inflammation. The study was conducted on a group of 17 patients diagnosed with Hashimoto’s disease. The atelocollagen Linerase (100 mg) thinned with 5 mL 0.9% NaCl was used. A total of 0.05 mL of solution was injected into keratinized gingiva, two millimeters above the gingival papillae basement, four times in two-week intervals. The greatest decrease in the number of bleeding points was observed after the first and second injections of atelocollagen. After the third and fourth injections, the average BOP continued to decrease, but the decline was very slow. The use of atelocollagen made it possible to eliminate bleeding symptoms in the study group.
Enhancing Food Security through Digital Inclusive Finance: Evidence from Agricultural Enterprises in China
Authors: Huang Siqi , Nik Azman Nik Hadiyan
Published: February 2023

As a means of enhancing food security, efficient agricultural processing and the maintenance of a smooth supply chain are essential for ensuring food quality and reducing food wastage. Agricultural enterprises play a crucial role in the processing and transportation of food from farms to dinner tables. Operating income growth plays the vital role of ensuring that agricultural enterprises function in a stable manner while also indicating the quantity and quality of market food supply. Therefore, the objective of this study is to explore the impact of digital inclusive finance on food security by analyzing the effect of digital inclusive finance on the operating income of agricultural enterprises in China. By applying pooled OLS analysis to Chinese agricultural enterprises that are listed in the National Equities Exchange and Quotations, this study finds that digital inclusive finance can help improve agricultural operating income. The results reveal that digital inclusive finance can facilitate the promotion of agricultural operating income by increasing the supply of financing, accelerating inventory liquidity, and supporting investment in research and development. In addition, this study concludes that digital inclusive finance is more effective for increasing agricultural operating income as a result of its wider coverage and deeper utilization. Furthermore, the development of traditional finance is still necessary for the digitization of digital inclusive finance to be effective.
Multi-Temporal Sentinel-1 SAR and Sentinel-2 MSI Data for Flood Mapping and Damage Assessment in Mozambique
Authors: Nhangumbe Manuel , Nascetti Andrea , Ban Yifang
Published: February 2023

Floods are one of the most frequent natural disasters worldwide. Although the vulnerability varies from region to region, all countries are susceptible to flooding. Mozambique was hit by several cyclones in the last few decades, and in 2019, after cyclones Idai and Kenneth, the country became the first one in southern Africa to be hit by two cyclones in the same raining season. Aiming to provide the local authorities with tools to yield better responses before and after any disaster event, and to mitigate the impact and support in decision making for sustainable development, it is fundamental to continue investigating reliable methods for disaster management. In this paper, we propose a fully automated method for flood mapping in near real-time utilizing multi-temporal Sentinel-1 Synthetic Aperture Radar (SAR) data acquired in the Beira municipality and Macomia district. The procedure exploits the processing capability of the Google Earth Engine (GEE) platform. We map flooded areas by finding the differences of images acquired before and after the flooding and then use Otsu’s thresholding method to automatically extract the flooded area from the difference image. To validate and compute the accuracy of the proposed technique, we compare our results with the Copernicus Emergency Management Service (Copernicus EMS) data available in the study areas. Furthermore, we investigated the use of a Sentinel-2 multi-spectral instrument (MSI) to produce a land cover (LC) map of the study area and estimate the percentage of flooded areas in each LC class. The results show that the combination of Sentinel-1 SAR and Sentinel-2 MSI data is reliable for near real-time flood mapping and damage assessment. We automatically mapped flooded areas with an overall accuracy of about 87–88% and kappa of 0.73–0.75 by directly comparing our prediction and Copernicus EMS maps. The LC classification is validated by randomly collecting over 600 points for each LC, and the overall accuracy is 90–95% with a kappa of 0.80–0.94.
Loss of S1P Lyase Expression in Human Podocytes Causes a Reduction in Nephrin Expression That Involves PKCδ Activation
Authors: Imeri Faik , Stepanovska Tanturovska Bisera , Manaila Roxana , Pavenstädt Hermann , Pfeilschifter Josef , Huwiler Andrea
Published: February 2023

Sphingosine 1-phosphate (S1P) lyase (SPL, Sgpl1) is an ER-associated enzyme that irreversibly degrades the bioactive lipid, S1P, and thereby regulates multiple cellular functions attributed to S1P. Biallelic mutations in the human Sglp1 gene lead to a severe form of a particular steroid-resistant nephrotic syndrome, suggesting that the SPL is critically involved in maintaining the glomerular ultrafiltration barrier, which is mainly built by glomerular podocytes. In this study, we have investigated the molecular effects of SPL knockdown (kd) in human podocytes to better understand the mechanism underlying nephrotic syndrome in patients. A stable SPL-kd cell line of human podocytes was generated by the lentiviral shRNA transduction method and was characterized for reduced SPL mRNA and protein levels and increased S1P levels. This cell line was further studied for changes in those podocyte-specific proteins that are known to regulate the ultrafiltration barrier. We show here that SPL-kd leads to the downregulation of the nephrin protein and mRNA expression, as well as the Wilms tumor suppressor gene 1 (WT1), which is a key transcription factor regulating nephrin expression. Mechanistically, SPL-kd resulted in increased total cellular protein kinase C (PKC) activity, while the stable downregulation of PKCδ revealed increased nephrin expression. Furthermore, the pro-inflammatory cytokine, interleukin 6 (IL-6), also reduced WT1 and nephrin expression. In addition, IL-6 caused increased PKCδ Thr505 phosphorylation, suggesting enzyme activation. Altogether, these data demonstrate that nephrin is a critical factor downregulated by the loss of SPL, which may directly cause podocyte foot process effacement as observed in mice and humans, leading to albuminuria, a hallmark of nephrotic syndrome. Furthermore, our in vitro data suggest that PKCδ could represent a new possible pharmacological target for the treatment of a nephrotic syndrome induced by SPL mutations.
Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice
Authors: Gao Qingying , Luo Zhen , Ma Sheng , Yu Chengbing , Shen Cheng , Xu Weina , Zhang Jing , Zhang Hongcai , Xu Jianxiong
Published: February 2023

Obesity induces lipodystrophy and metabolic inflammation. Microbe-derived antioxidants (MA) are novel small-molecule nutrients obtained from microbial fermentation, and have anti-oxidation, lipid-lowering and anti-inflammatory effects. Whether MA can regulate obesity-induced lipodystrophy and metabolic inflammation has not yet been investigated. The aim of this study was to investigate the effects of MA on oxidative stress, lipid disorders, and metabolic inflammation in liver and epididymal adipose tissues (EAT) of mice fed with a high-fat diet (HFD). Results showed that MA was able to reverse the HFD-induced increase in body weight, body fat rate and Lee’s index in mice; reduce the fat content in serum, liver and EAT; and regulate the INS, LEP and resistin adipokines as well as free fatty acids to their normal levels. MA also reduced de novo synthesis of fat in the liver and EAT and promoted gene expression for lipolysis, fatty acid transport and β-oxidation. MA decreased TNF-α and MCP1 content in serum, elevated SOD activity in liver and EAT, induced macrophage polarization toward the M2 type, inhibited the NLRP3 pathway, increased gene expression of the anti-inflammatory factors IL-4 and IL-13 and suppressed gene expression of the pro-inflammatory factors IL-6, TNF-α and MCP1, thereby attenuating oxidative stress and inflammation induced by HFD. In conclusion, MA can effectively reduce HFD-induced weight gain and alleviate obesity-induced oxidative stress, lipid disorders and metabolic inflammation in the liver and EAT, indicating that MA shows great promise as a functional food.
The Effects of Mono- and Bivalent Linear Alkyl Interlayer Spacers on the Photobehavior of Mn(II)-Based Perovskites
Authors: Rakshit Soumyadipta , Medina Alicia Maldonado , Lezama Luis , Cohen Boiko , Douhal Abderrazzak
Published: February 2023

Mn(II)-based perovskite materials are being intensively explored for lighting applications; understanding the role of ligands regarding their photobehavior is fundamental for their development. Herein, we report on two Mn (II) bromide perovskites using monovalent (perovskite 1, P1) and bivalent (perovskite 2, P2) alkyl interlayer spacers. The perovskites were characterized with powder X-ray diffraction (PXRD), electron spin paramagnetic resonance (EPR), steady-state, and time-resolved emission spectroscopy. The EPR experiments suggest octahedral coordination in P1 and tetrahedral coordination for P2, while the PXRD results demonstrate the presence of a hydrated phase in P2 when exposed to ambient conditions. P1 exhibits an orange-red emission, while P2 shows a green photoluminescence, as a result of the different types of coordination of Mn(II) ions. Furthermore, the P2 photoluminescence quantum yield (26%) is significantly higher than that of P1 (3.6 %), which we explain in terms of different electron-phonon couplings and Mn-Mn interactions. The encapsulation of both perovskites into a PMMA film largely increases their stability against moisture, being more than 1000 h for P2. Upon increasing the temperature, the emission intensity of both perovskites decreases without a significant shift in the emission spectrum, which is explained in terms of an increase in the electron-phonon interactions. The photoluminescence decays fit two components in the microsecond regime—the shortest lifetime for hydrated phases and the longest one for non-hydrated phases. Our findings provide insights into the effects of linear mono- and bivalent organic interlayer spacer cations on the photophysics of these kinds of Mn (II)-based perovskites. The results will help in better designs of Mn(II)-perovskites, to increase their lighting performance.
The Role of Liquid–Liquid Phase Separation in Actin Polymerization
Authors: Povarova Olga , Antifeeva Iuliia , Fonin Alexander , Turoverov Konstantin , Kuznetsova Irina
Published: February 2023

To date, it has been shown that the phenomenon of liquid–liquid phase separation (LLPS) underlies many seemingly completely different cellular processes. This provided a new idea of the spatiotemporal organization of the cell. The new paradigm makes it possible to provide answers to many long-standing, but still unresolved questions facing the researcher. In particular, spatiotemporal regulation of the assembly/disassembly of the cytoskeleton, including the formation of actin filaments, becomes clearer. To date, it has been shown that coacervates of actin-binding proteins that arise during the phase separation of the liquid–liquid type can integrate G-actin and thereby increase its concentration to initiate polymerization. It has also been shown that the activity intensification of actin-binding proteins that control actin polymerization, such as N-WASP and Arp2/3, can be caused by their integration into liquid droplet coacervates formed by signaling proteins on the inner side of the cell membrane.
Concentration of Selected Adipokines and Factors Regulating Carbohydrate Metabolism in Patients with Head and Neck Cancer in Respect to Their Body Mass Index
Authors: Nuszkiewicz Jarosław , Czuczejko Jolanta , Dróżdż Wiktor , Woźniak Alina , Małkowski Bogdan , Szewczyk-Golec Karolina
Published: February 2023

Head and neck cancers (HNCs) are a group of tumors not common in European populations. So far, not much is known about the role of obesity, adipokines, glucose metabolism, and inflammation in the pathogenesis of HNC. The aim of the study was to determine the concentrations of ghrelin, omentin-1, adipsin, adiponectin, leptin, resistin, visfatin, glucagon, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), plasminogen activator inhibitor-1 (PAI-1), and gastric inhibitory peptide (GIP) in the blood serum of HNC patients depending on their body mass index (BMI). The study included 46 patients divided into two groups according to their BMI values: the normal BMI group (nBMI) included 23 patients with BMI < 25 kg/m2 and the increased BMI group (iBMI) included patients with BMI ≥ 25 kg/m2. A control group (CG) included 23 healthy people (BMI < 25 kg/m2). Statistically significant differences in the levels of adipsin, ghrelin, glucagon, PAI-1, and visfatin were shown between nBMI and CG. In the case of nBMI and iBMI, statistically significant differences were observed in the concentrations of adiponectin, C-peptide, ghrelin, GLP-1, insulin, leptin, omentin-1, PAI-1, resistin, and visfatin. The obtained results indicate a disruption of endocrine function of adipose tissue and impaired glucose metabolism in HNC. Obesity, which is not a typical risk factor for HNC, may aggravate the negative metabolic changes associated with this type of neoplasm. Ghrelin, visfatin, PAI-1, adipsin, and glucagon might be related to head and neck carcinogenesis. They seem to be promising directions for further research.
Proximity Labeling to Identify β-Arrestin1 Binding Partners Downstream of Ligand-Activated G Protein-Coupled Receptors
Authors: Zhuo Ya , Robleto Valeria L. , Marchese Adriano
Published: February 2023

β-arrestins are multifaceted adaptor proteins that regulate various aspects of G protein-coupled receptor (GPCR) signaling. β-arrestins are recruited to agonist-activated and phosphorylated GPCRs at the plasma membrane, thereby preventing G protein coupling, while also targeting GPCRs for internalization via clathrin-coated pits. In addition, β-arrestins can activate various effector molecules to prosecute their role in GPCR signaling; however, the full extent of their interacting partners remains unknown. To discover potentially novel β-arrestin interacting partners, we used APEX-based proximity labeling coupled with affinity purification and quantitative mass spectrometry. We appended APEX in-frame to the C-terminus of β-arrestin1 (βarr1-APEX), which we show does not impact its ability to support agonist-stimulated internalization of GPCRs. By using coimmunoprecipitation, we show that βarr1-APEX interacts with known interacting proteins. Furthermore, following agonist stimulation βarr1-APEX labeled known βarr1-interacting partners as assessed by streptavidin affinity purification and immunoblotting. Aliquots were prepared in a similar manner and analyzed by tandem mass tag labeling and high-content quantitative mass spectrometry. Several proteins were found to be increased in abundance following GPCR stimulation. Biochemical experiments confirmed two novel proteins that interact with β-arrestin1, which we predict are novel ligand-stimulated βarr1 interacting partners. Our study highlights that βarr1-APEX-based proximity labeling represents a valuable approach to identifying novel players involved in GPCR signaling.
Insight into the Structural Basis for Dual Nucleic Acid—Recognition by the Scaffold Attachment Factor B2 Protein
Authors: Korn Sophie M. , Von Ehr Julian , Dhamotharan Karthikeyan , Tants Jan-Niklas , Abele Rupert , Schlundt Andreas
Published: February 2023

The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately 100 kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA and RNA binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerize, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.
Transcriptomic Changes Following Induced De-Masculinisation of Australian Red Claw Crayfish Cherax quadricarinatus
Authors: Smith Grace , Glendinning Susan , Ventura Tomer
Published: February 2023

The Australian red claw crayfish Cherax quadricarinatus, an emerging species within the freshwater aquaculture trade, is not only an ideal species for commercial production due to its high fecundity, fast growth, and physiological robustness but also notoriously invasive. Investigating the reproductive axis of this species has been of great interest to farmers, geneticists, and conservationists alike for many decades; however, aside from the characterisation of the key masculinising insulin-like androgenic gland hormone (IAG) produced by the male-specific androgenic gland (AG), little remains known about this system and the downstream signalling cascade involved. This investigation used RNA interference to silence IAG in adult intersex C. quadricarinatus (Cq-IAG), known to be functionally male but genotypically female, successfully inducing sexual redifferentiation in all individuals. To investigate the downstream effects of Cq-IAG knockdown, a comprehensive transcriptomic library was constructed, comprised of three tissues within the male reproductive axis. Several factors known to be involved in the IAG signal transduction pathway, including a receptor, binding factor, and additional insulin-like peptide, were found to not be differentially expressed in response to Cq-IAG silencing, suggesting that the phenotypic changes observed may have occurred through post-transcriptional modifications. Many downstream factors displayed differential expression on a transcriptomic level, most notably related to stress, cell repair, apoptosis, and cell proliferation. These results suggest that IAG is required for sperm maturation, with necrosis of arrested tissue occurring in its absence. These results and the construction of a transcriptomic library for this species will inform future research involving reproductive pathways as well as biotechnological developments in this commercially and ecologically significant species.
Improvement of Therapeutic Value of Quercetin with Chitosan Nanoparticle Delivery Systems and Potential Applications
Authors: Lawson Michael Kenneth
Published: February 2023

This paper reviews recent studies investigating chitosan nanoparticles as drug delivery systems for quercetin. The therapeutic properties of quercetin include antioxidant, antibacterial and anti-cancer potential, but its therapeutic value is limited by its hydrophobic nature, low bioavailability and fast metabolism. Quercetin may also act synergistically with other stronger drugs for specific disease states. The encapsulation of quercetin in nanoparticles may increase its therapeutic value. Chitosan nanoparticles are a popular candidate in preliminary research, but the complex nature of chitosan makes standardisation difficult. Recent studies have used in-vitro, and in-vivo experiments to study the delivery of quercetin alone or in combination with another active pharmaceutical ingredient encapsulated in chitosan nanoparticles. These studies were compared with the administration of non-encapsulated quercetin formulation. Results suggest that encapsulated nanoparticle formulations are better. In-vivo or animal models simulated the type of disease required to be treated. The types of diseases were breast, lung, liver and colon cancers, mechanical and UVB-induced skin damage, cataracts and general oxidative stress. The reviewed studies included various routes of administration: oral, intravenous and transdermal routes. Although toxicity tests were often included, it is believed that the toxicity of loaded nanoparticles needs to be further researched, especially when not orally administered.
3D Characterization of the Molecular Neighborhood of •OH Radical in High Temperature Water by MD Simulation and Voronoi Polyhedra
Authors: Kazmierczak Lukasz , Szala-Rearick Joanna , Swiatla-Wojcik Dorota
Published: February 2023

Understanding the properties of the •OH radical in aqueous environments is essential for biochemistry, atmospheric chemistry, and the development of green chemistry technologies. In particular, the technological applications involve knowledge of microsolvation of the •OH radical in high temperature water. In this study, the classical molecular dynamics (MD) simulation and the technique based on the construction of Voronoi polyhedra were used to provide 3D characteristics of the molecular vicinity of the aqueous hydroxyl radical (•OHaq). The statistical distribution functions of metric and topological features of solvation shells represented by the constructed Voronoi polyhedra are reported for several thermodynamic states of water, including the pressurized high-temperature liquid and supercritical fluid. Calculations showed a decisive influence of the water density on the geometrical properties of the •OH solvation shell in the sub- and supercritical region: with the decreasing density, the span and asymmetry of the solvation shell increase. We also showed that the 1D analysis based on the oxygen–oxygen radial distribution functions (RDFs) overestimates the solvation number of •OH and insufficiently reflects the influence of transformations in the hydrogen-bonded network of water on the structure of the solvation shell.
Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
Authors: Kim Jung-Hwan , Jang Eui Hwa , Ryu Ji-Yeon , Lee Jiyong , Kim Jae Ho , Ryu Wonhyoung , Youn Young-Nam
Published: February 2023

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B–embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.
New Insights into the Biological Response Triggered by Dextran-Coated Maghemite Nanoparticles in Pancreatic Cancer Cells and Their Potential for Theranostic Applications
Authors: Balas Mihaela , Predoi Daniela , Burtea Carmen , Dinischiotu Anca
Published: February 2023

Iron oxide nanoparticles are one of the most promising tools for theranostic applications of pancreatic cancer due to their unique physicochemical and magnetic properties making them suitable for both diagnosis and therapy. Thus, our study aimed to characterize the properties of dextran-coated iron oxide nanoparticles (DIO-NPs) of maghemite (γ-Fe2O3) type synthesized by co-precipitation and to investigate their effects (low-dose versus high-dose) on pancreatic cancer cells focusing on NP cellular uptake, MR contrast, and toxicological profile. This paper also addressed the modulation of heat shock proteins (HSPs) and p53 protein expression as well as the potential of DIO-NPs for theranostic purposes. DIO-NPs were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering analyses (DLS), and zeta potential. Pancreatic cancer cells (PANC-1 cell line) were exposed to different doses of dextran-coated ɣ-Fe2O3 NPs (14, 28, 42, 56 μg/mL) for up to 72 h. The results revealed that DIO-NPs with a hydrodynamic diameter of 16.3 nm produce a significant negative contrast using a 7 T MRI scanner correlated with dose-dependent cellular iron uptake and toxicity levels. We showed that DIO-NPs are biocompatible up to a concentration of 28 μg/mL (low-dose), while exposure to a concentration of 56 μg/mL (high-dose) caused a reduction in PANC-1 cell viability to 50% after 72 h by inducing reactive oxygen species (ROS) production, reduced glutathione (GSH) depletion, lipid peroxidation, enhancement of caspase-1 activity, and LDH release. An alteration in Hsp70 and Hsp90 protein expression was also observed. At low doses, these findings provide evidence that DIO-NPs could act as safe platforms in drug delivery, as well as antitumoral and imaging agents for theranostic uses in pancreatic cancer.
The Adaptor Protein NumbL Is Involved in the Control of Glucolipotoxicity-Induced Pancreatic Beta Cell Apoptosis
Authors: Basavarajappa Halesha D. , Irimia Jose M. , Bauer Brandon M. , Fueger Patrick T.
Published: February 2023

Avoiding the loss of functional beta cell mass is critical for preventing or treating diabetes. Currently, the molecular mechanisms underlying beta cell death are partially understood, and there is a need to identify new targets for developing novel therapeutics to treat diabetes. Previously, our group established that Mig6, an inhibitor of EGF signaling, mediates beta cell death under diabetogenic conditions. The objective here was to clarify the mechanisms linking diabetogenic stimuli to beta cell death by investigating Mig6-interacting proteins. Using co-immunoprecipitation and mass spectrometry, we evaluated the binding partners of Mig6 under both normal glucose (NG) and glucolipotoxic (GLT) conditions in beta cells. We identified that Mig6 interacted dynamically with NumbL, whereas Mig6 associated with NumbL under NG, and this interaction was disrupted under GLT conditions. Further, we demonstrated that the siRNA-mediated suppression of NumbL expression in beta cells prevented apoptosis under GLT conditions by blocking the activation of NF-κB signaling. Using co-immunoprecipitation experiments, we observed that NumbL’s interactions with TRAF6, a key component of NFκB signaling, were increased under GLT conditions. The interactions among Mig6, NumbL, and TRAF6 were dynamic and context-dependent. We proposed a model wherein these interactions activated pro-apoptotic NF-κB signaling while blocking pro-survival EGF signaling under diabetogenic conditions, leading to beta cell apoptosis. These findings indicated that NumbL should be further investigated as a candidate anti-diabetic therapeutic target.