bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of UAV Monitoring to Identify Factors Limiting the Sustainability of Stream Restoration Projects
Authors: Langhammer Jakub , Lendzioch Theodora , Šolc Jakub
Published: February 2023

The detection and mapping of riverscapes with Unmanned Aerial Vehicles (UAVs, drones) provide detailed, reliable, and operable spatial information in hydrological sciences, enhancing conventional field survey techniques. In this study, we present the results of long-term, optical RGB (red, green, blue) UAV monitoring of stream restoration projects to identify the positive and negative features that affect their sustainability. We determined quantitative and qualitative aspects of restoration, such as the restoration effect, the dynamics of fluvial processes, hydrological connectivity, and riparian vegetation. The study was based on six years of UAV monitoring in three restored streams in Prague, Czech Republic. The multitemporal riverscape models from the photogrammetric reconstruction served as a basis for the visual assessment, compliant with the standard hydromorphological assessment. Such a combined approach extends the potential of UAV monitoring by allowing for the use of existing classification schemes and data and the objective detection of critical features. The study pointed to the significant discrepancies in channel geometry between the planned restorations and realized restorations in all assessed projects as a general phenomenon. Multitemporal, optical RGB UAV monitoring then detected issues in qualitative aspects that limit restoration quality, such as water overuse, extensive eutrophication, or inefficient riparian shading.
Assessing Hydrological Simulations with Machine Learning and Statistical Models
Authors: Rozos Evangelos
Published: February 2023

Machine learning has been used in hydrological applications for decades, and recently, it was proven to be more efficient than sophisticated physically based modelling techniques. In addition, it has been used in hybrid frameworks that combine hydrological and machine learning models. The concept behind the latter is the use of machine learning as a filter that advances the performance of the hydrological model. In this study, we employed such a hybrid approach but with a different perspective and objective. Machine learning was used as a tool for analyzing the error of hydrological models in an effort to understand the source and the attributes of systematic modelling errors. Three hydrological models were applied to three different case studies. The results of these models were analyzed with a recurrent neural network and with the k-nearest neighbours algorithm. Most of the systematic errors were detected, but certain types of errors, including conditional systematic errors, passed unnoticed, leading to an overestimation of the confidence of some erroneously simulated values. This is an issue that needs to be considered when using machine learning as a filter in hybrid networks. The effect of conditional systematic errors can be reduced by naively combining the simulations (mean values) of two or more hydrological models. This simple technique reduces the magnitude of conditional systematic errors and makes them more discoverable to machine learning models.
Self-Supervised Representation Learning for Geographical Data—A Systematic Literature Review
Authors: Corcoran Padraig , Spasić Irena
Published: February 2023

Self-supervised representation learning (SSRL) concerns the problem of learning a useful data representation without the requirement for labelled or annotated data. This representation can, in turn, be used to support solutions to downstream machine learning problems. SSRL has been demonstrated to be a useful tool in the field of geographical information science (GIS). In this article, we systematically review the existing research literature in this space to answer the following five research questions. What types of representations were learnt? What SSRL models were used? What downstream problems were the representations used to solve? What machine learning models were used to solve these problems? Finally, does using a learnt representation improve the overall performance?
Steroidogenic Factor 1, a Goldilocks Transcription Factor from Adrenocortical Organogenesis to Malignancy
Authors: Relav Lauriane , Doghman-Bouguerra Mabrouka , Ruggiero Carmen , Muzzi João C. D. , Figueiredo Bonald C. , Lalli Enzo
Published: February 2023

Steroidogenic factor-1 (SF-1, also termed Ad4BP; NR5A1 in the official nomenclature) is a nuclear receptor transcription factor that plays a crucial role in the regulation of adrenal and gonadal development, function and maintenance. In addition to its classical role in regulating the expression of P450 steroid hydroxylases and other steroidogenic genes, involvement in other key processes such as cell survival/proliferation and cytoskeleton dynamics have also been highlighted for SF-1. SF-1 has a restricted pattern of expression, being expressed along the hypothalamic-pituitary axis and in steroidogenic organs since the time of their establishment. Reduced SF-1 expression affects proper gonadal and adrenal organogenesis and function. On the other hand, SF-1 overexpression is found in adrenocortical carcinoma and represents a prognostic marker for patients’ survival. This review is focused on the current knowledge about SF-1 and the crucial importance of its dosage for adrenal gland development and function, from its involvement in adrenal cortex formation to tumorigenesis. Overall, data converge towards SF-1 being a key player in the complex network of transcriptional regulation within the adrenal gland in a dosage-dependent manner.
Paracrine Effects of Renal Proximal Tubular Epithelial Cells on Podocyte Injury under Hypoxic Conditions Are Mediated by Arginase-II and TGF-β1
Authors: Ma Yiqiong , Potenza Duilio Michele , Ajalbert Guillaume , Brenna Andrea , Zhu Cui , Ming Xiu-Fen , Yang Zhihong
Published: February 2023

Hypoxia is an important risk for renal disease. The mitochondrial enzyme arginase-II (Arg-II) is expressed and/or induced by hypoxia in proximal tubular epithelial cells (PTECs) and in podocytes, leading to cellular damage. Because PTECs are vulnerable to hypoxia and located in proximity to podocytes, we examined the role of Arg-II in the crosstalk of PTECs under hypoxic conditions with podocytes. A human PTEC cell line (HK2) and a human podocyte cell line (AB8/13) were cultured. Arg-ii gene was ablated by CRISPR/Case9 in both cell types. HK2 cells were exposed to normoxia (21% O2) or hypoxia (1% O2) for 48 h. Conditioned medium (CM) was collected and transferred to the podocytes. Podocyte injuries were then analyzed. Hypoxic (not normoxic) HK2-CM caused cytoskeletal derangement, cell apoptosis, and increased Arg-II levels in differentiated podocytes. These effects were absent when arg-ii in HK2 was ablated. The detrimental effects of the hypoxic HK2-CM were prevented by TGF-β1 type-I receptor blocker SB431542. Indeed, TGF-β1 levels in hypoxic HK2-CM (but not arg-ii−/−-HK2-CM) were increased. Furthermore, the detrimental effects of TGF-β1 on podocytes were prevented in arg-ii−/−-podocytes. This study demonstrates crosstalk between PTECs and podocytes through the Arg-II-TGF-β1 cascade, which may contribute to hypoxia-induced podocyte damage.
A DNA Finite-State Machine Based on the Programmable Allosteric Strategy of DNAzyme
Authors: Wang Jun , Zhang Xiaokang , Shi Peijun , Cao Ben , Wang Bin
Published: February 2023

Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development and design of nanodevices with the ability to process time-related information could facilitate the development of molecular information processing systems. Here, we proposed a DNA finite-state machine that can dynamically respond to sequential stimuli signals. To build this state machine, a programmable allosteric strategy of DNAzyme was developed. This strategy performs the programmable control of DNAzyme conformation using a reconfigurable DNA hairpin. Based on this strategy, we first implemented a finite-state machine with two states. Through the modular design of the strategy, we further realized the finite-state machine with five states. The DNA finite-state machine endows molecular information systems with the ability of reversible logic control and order detection, which can be extended to more complex DNA computing and nanomachines to promote the development of dynamic nanotechnology.
HER2 Amplification Level Predicts Pathological Complete Response in the Neoadjuvant Setting of HER2-Overexpressing Breast Cancer: A Meta-Analysis and Systematic Review
Authors: Gonullu Burak , Angeli Eurydice , Pamoukdjian Frédéric , Bousquet Guilhem
Published: February 2023

Anti-HER2 therapies have dramatically improved the prognosis of human epidermal growth factor receptor 2 (HER2)-overexpressing cancers. However, the correlation between the HER2 copy number and the response rate to anti-HER2 remains unclear. Here, following the PRISMA method, we performed a meta-analysis in the neoadjuvant setting in breast cancer to study the association between the HER2 amplification level and the pathological complete response (pCR) to anti-HER2 therapies. Nine articles (four clinical trials, five observational studies) were retrieved after full-text screening, involving 11,238 women with locally advanced breast cancer in the neoadjuvant setting. The median HER2/CEP17 ratio cut-off value was 5.0 ± 5.0 (min-max = 1.0–14.0). For the overall population, the median pCR rate was 48% using the random effect model. The studies were categorized in quartiles as follows: ≤2 (Class 1); 2.1 to 5.0 (Class 2); 5.1 to 7.0 (Class 3); and >7.0 (Class 4). After grouping, the pCR rates were 33%, 49%, 57%, and 79%, respectively. When we excluded the study by Greenwell et al., which accounted for 90% of the patients, using the same quartiles, we still observed an increasing rate of pCR as the HER2/CEP17 ratio increased. This is the first meta-analysis demonstrating the relationship between the HER2 amplification level and the percentage of pCR in the neoadjuvant setting among women with HER2-overexpressing breast cancer, with potential therapeutic applications.
Plasma N-Cleaved Galectin-9 Is a Surrogate Marker for Determining the Severity of COVID-19 and Monitoring the Therapeutic Effects of Tocilizumab
Authors: Iwasaki-Hozumi Hiroko , Maeda Yosuke , Niki Toshiro , Chagan-Yasutan Haorile , Bai Gaowa , Matsuba Takashi , Furushima Daisuke , Ashino Yugo , Hattori Toshio
Published: February 2023

Galectin-9 (Gal-9) is known to contribute to antiviral responses in coronavirus disease 2019 (COVID-19). Increased circulating Gal-9 in COVID-19 is associated with COVID-19 severity. In a while, the linker-peptide of Gal-9 is susceptible to proteolysis that can cause the change or loss of Gal-9 activity. Here, we measured plasma levels of N-cleaved-Gal9, which is Gal9 carbohydrate-recognition domain at the N-terminus (NCRD) with attached truncated linker peptide that differs in length depending on the type of proteases, in COVID-19. We also investigated the time course of plasma N-cleaved-Gal9 levels in severe COVID-19 treated with tocilizumab (TCZ). As a result, we observed an increase in plasma N-cleaved-Gal9 levels in COVID-19 and its higher levels in COVID-19 with pneumonia compared to the mild cases (healthy: 326.1 pg/mL, mild: 698.0 pg/mL, and with pneumonia: 1570 pg/mL). N-cleaved-Gal9 levels were associated with lymphocyte counts, C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R), D-dimer, and ferritin levels, and ratio of percutaneous oxygen saturation to fraction of inspiratory oxygen (S/F ratio) in COVID-19 with pneumonia and discriminated different severity groups with high accuracy (area under the curve (AUC): 0.9076). Both N-cleaved-Gal9 and sIL-2R levels were associated with plasma matrix metalloprotease (MMP)-9 levels in COVID-19 with pneumonia. Furthermore, a decrease in N-cleaved-Gal9 levels was associated with a decrease of sIL-2R levels during TCZ treatment. N-cleaved-Gal9 levels showed a moderate accuracy (AUC: 0.8438) for discriminating the period before TCZ from the recovery phase. These data illustrate that plasma N-cleaved-Gal9 is a potential surrogate marker for assessing COVID-19 severity and the therapeutic effects of TCZ.
Radiosensitization of Breast Cancer Cells with a 2-Methoxyestradiol Analogue Affects DNA Damage and Repair Signaling In Vitro
Authors: Nolte Elsie Magdalena , Joubert Anna Margaretha , Lafanechère Laurence , Mercier Anne Elisabeth
Published: February 2023

Radiation resistance and radiation-related side effects warrant research into alternative strategies in the application of this modality to cancer treatment. Designed in silico to improve the pharmacokinetics and anti-cancer properties of 2-methoxyestradiol, 2-ethyl-3-O-sulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16) disrupts microtubule dynamics and induces apoptosis. Here, we investigated whether pre-exposure of breast cancer cells to low-dose ESE-16 would affect radiation-induced deoxyribonucleic acid (DNA) damage and the consequent repair pathways. MCF-7, MDA-MB-231, and BT-20 cells were exposed to sub-lethal doses of ESE-16 for 24 h before 8 Gy radiation. Flow cytometric quantification of Annexin V, clonogenic studies, micronuclei quantification, assessment of histone H2AX phosphorylation and Ku70 expression were performed to assess cell viability, DNA damage, and repair pathways, in both directly irradiated cells and cells treated with conditioned medium. A small increase in apoptosis was observed as an early consequence, with significant repercussions on long-term cell survival. Overall, a greater degree of DNA damage was detected. Moreover, initiation of the DNA-damage repair response was delayed, with a subsequent sustained elevation. Radiation-induced bystander effects induced similar pathways and were initiated via intercellular signaling. These results justify further investigation of ESE-16 as a radiation-sensitizing agent since pre-exposure appears to augment the response of tumor cells to radiation.
Inhibition of Myeloperoxidase Pro-Fibrotic Effect by Noscapine in Equine Endometrium
Authors: Amaral Ana , Cebola Nélio , Szóstek-Mioduchowska Anna , Rebordão Maria Rosa , Kordowitzki Paweł , Skarzynski Dariusz , Ferreira-Dias Graça
Published: February 2023

Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (COL1) induced by myeloperoxidase in equine endometrial explants from follicular and mid-luteal phases, at 24 and 48 h of treatment. The transcription of collagen type 1 alpha 2 chain (COL1A2), and COL1 protein relative abundance were evaluated by qPCR and Western blot, respectively. The treatment with myeloperoxidase increased COL1A2 mRNA transcription and COL1 protein, whereas noscapine was able to reduce this effect with respect to COL1A2 mRNA transcription, in a time/estrous cycle phase-dependent manner (in explants from the follicular phase, at 24 h of treatment). Our study indicates that noscapine is a promising drug to be considered as an anti-fibrotic molecule to prevent endometrosis development, making noscapine a strong candidate to be applied in future endometrosis therapies.
Neutrophil Extracellular Traps Release following Hypoxic-Ischemic Brain Injury in Newborn Rats Treated with Therapeutic Hypothermia
Authors: Bernis Maria E. , Zweyer Margit , Maes Elke , Schleehuber Yvonne , Sabir Hemmen
Published: February 2023

The peripheral immune system plays a critical role in neuroinflammation of the central nervous system after an insult. Hypoxic-ischemic encephalopathy (HIE) induces a strong neuroinflammatory response in neonates, which is often associated with exacerbated outcomes. In adult models of ischemic stroke, neutrophils infiltrate injured brain tissue immediately after an ischemic insult and aggravate inflammation via various mechanisms, including neutrophil extracellular trap (NETs) formation. In this study, we used a neonatal model of experimental hypoxic-ischemic (HI) brain injury and demonstrated that circulating neutrophils were rapidly activated in neonatal blood. We observed an increased infiltration of neutrophils in the brain after exposure to HI. After treatment with either normothermia (NT) or therapeutic hypothermia (TH), we observed a significantly enhanced expression level of the NETosis marker Citrullinated H3 (Cit-H3), which was significantly more pronounced in animals treated with TH than in those treated with NT. NETs and NLR family pyrin domain containing 3 (NLRP-3) inflammasome assembly are closely linked in adult models of ischemic brain injury. In this study, we observed an increase in the activation of the NLRP-3 inflammasome at the time points analyzed, particularly immediately after TH, when we observed a significant increase in NETs structures in the brain. Together, these results suggest the important pathological functions of early arriving neutrophils and NETosis following neonatal HI, particularly after TH treatment, which is a promising starting point for the development of potential new therapeutic targets for neonatal HIE.
Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation
Authors: Ding Mina , Chen Zhihao , Cho Eunjin , Park Sang-Wook , Lee Tae-Hoon
Published: February 2023

Epigenetic regulators are involved in osteoclast differentiation. This study proposes that the inhibitors of epigenetic regulators could be effective in the treatment of osteoporosis. This study identified GSK2879552, a lysine-specific histone demethylase 1 (LSD1) inhibitor, as a candidate for the treatment of osteoporosis from epigenetic modulator inhibitors. We investigate the function of LSD1 during RANKL-induced osteoclast formation. LSD1 small-molecule inhibitors effectively inhibit the RANKL-induced osteoclast differentiation in a dose-dependent manner. LSD1 gene knockout in macrophage cell line Raw 264.7 also inhibits RANKL-mediated osteoclastogenesis. LSD1-inhibitor-treated primary macrophage cells and LSD1 gene knockout Raw 264.7 cells failed to show actin ring formation. LSD1 inhibitors prevent the expression of RANKL-induced osteoclast-specific genes. They also downregulated the protein expression of osteoclast-related markers in osteoclastogeneses, such as Cathepsin K, c-Src, and NFATc1. Although LSD1 inhibitors were shown to reduce the in vitro demethylation activity of LSD1, they did not modulate the methylation of Histone 3 K4 and K9 during osteoclastogenesis. The ovariectomy (OVX)-induced osteoporosis model revealed that GSK2879552 slightly restores OVX-induced cortical bone loss. LSD1 can be employed as a positive regulator to promote osteoclast formation. Hence, inhibition of LSD1 activities is a potential target for preventing bone diseases characterized by excessive osteoclast activities.
Synthesis of an Environmentally Friendly Modified Mulberry Branch-Derived Biochar Composite: High Degradation Efficiency of BPA and Mitigation of Toxicity in Silkworm Larvae
Authors: Qu Han , Chen Lin , Yang Fujian , Zhu Jiangwei , Qi Chengdu , Peng Guilong
Published: February 2023

In the present study, mulberry branch-derived biochar CuO (MBC/CuO) composite was successfully synthesized and used as a catalyst to activate persulfate (PS) for the degradation of bisphenol A (BPA). The MBC/CuO/PS system exhibited a high degradation efficiency (93%) of BPA, under the conditions of 0.1 g/L MBC/CuO, 1.0 mM PS, 10 mg/L BPA. Free radical quenching and electron spin-resonance spectroscopy (ESR) experiments confirmed that both free radicals •OH, SO4•− and O2•− and non-radicals 1O2 were involved in the MBC/CuO reaction system. Cl− and NOM displayed negligible influence on the degradation of BPA, while HCO3− promoted the removal of BPA. In addition, the toxicity tests of BPA, MBC/CuO and the degraded BPA solution were conducted by the 5th instar silkworm larvae. The toxicity of BPA was reduced after the treatment in the MBC/CuO/PS system, and no obvious toxicity of the synthesized MBC/CuO composite was found in the toxicity evaluation experiments. This work provides a new value-added utilization of mulberry branches as a cost-effective and environmentally friendly PS activator.
Selective α3β4 Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction
Authors: Kanasuwan Apinan , Deuther-Conrad Winnie , Chongruchiroj Sumet , Sarasamkan Jiradanai , Chotipanich Chanisa , Vajragupta Opa , Arunrungvichian Kuntarat
Published: February 2023

α3β4 Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α3β4 nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, (S)-QND8 and (S)-T2, for the development of an α3β4 nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a p-hydroxyl motif for ligand-receptor binding affinity. Four (R)- and (S)-quinuclidine-triazole (AK1-AK4) were synthesized and the binding affinity, together with selectivity to α3β4 nAChR subtype, were determined by competitive radioligand binding assay using [3H]epibatidine as a radioligand. Among all modified compounds, AK3 showed the highest binding affinity and selectivity to α3β4 nAChR with a Ki value of 3.18 nM, comparable to (S)-QND8 and (S)-T2 and 3069-fold higher affinity to α3β4 nAChR in comparison to α7 nAChR. The α3β4 nAChR selectivity of AK3 was considerably higher than those of (S)-QND8 (11.8-fold) and (S)-T2 (294-fold). AK3 was shown to be a promising α3β4 nAChR tracer for further development as a radiotracer for drug addiction.
High-Energy, Whole-Body Proton Irradiation Differentially Alters Long-Term Brain Pathology and Behavior Dependent on Sex and Alzheimer’s Disease Mutations
Authors: Hinshaw Robert G. , Schroeder Maren K. , Ciola Jason , Varma Curran , Colletti Brianna , Liu Bin , Liu Grace Geyu , Shi Qiaoqiao , Williams Jacqueline P. , O’Banion M. Kerry , Caldarone Barbara J. , Lemere Cynthia A.
Published: February 2023

Whole-body exposure to high-energy particle radiation remains an unmitigated hazard to human health in space. Ongoing experiments at the NASA Space Radiation Laboratory and elsewhere repeatedly show persistent changes in brain function long after exposure to simulations of this unique radiation environment, although, as is also the case with proton radiotherapy sequelae, how this occurs and especially how it interacts with common comorbidities is not well-understood. Here, we report modest differential changes in behavior and brain pathology between male and female Alzheimer’s-like and wildtype littermate mice 7–8 months after exposure to 0, 0.5, or 2 Gy of 1 GeV proton radiation. The mice were examined with a battery of behavior tests and assayed for amyloid beta pathology, synaptic markers, microbleeds, microglial reactivity, and plasma cytokines. In general, the Alzheimer’s model mice were more prone than their wildtype littermates to radiation-induced behavior changes, and hippocampal staining for amyloid beta pathology and microglial activation in these mice revealed a dose-dependent reduction in males but not in females. In summary, radiation-induced, long-term changes in behavior and pathology, although modest, appear specific to both sex and the underlying disease state.
Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors
Authors: Mahiat Cédric , Bihin Benoît , Duplaquet Fabrice , Stanciu Pop Claudia , Dupont Michael , Vander Borght Thierry , Rondelet Benoît , Vanderick Jean , André Bénédicte , Pirard Lionel , Ocak Sebahat
Published: February 2023

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.
Identification, Characterization and Functional Analysis of Fibroblast Growth Factors in Black Rockfish (Sebastes schlegelii)
Authors: Jin Chaofan , Yan Kai , Wang Mengya , Song Weihao , Kong Xiangfu , Zhang Zhengrui
Published: February 2023

Fibroblast growth factors (FGFs) are short polypeptides that play essential roles in various cellular biological processes, including cell migration, proliferation, and differentiation, as well as tissue regeneration, immune response, and organogenesis. However, studies focusing on the characterization and function of FGF genes in teleost fishes are still limited. In this study, we identified and characterized expression patterns of 24 FGF genes in various tissues of embryonic and adult specimens of the black rockfish (Sebates schlegelii). Nine FGF genes were found to play essential roles in myoblast differentiation, as well as muscle development and recovery in juvelines of S. schlegelii. Moreover, sex-biased expression pattern of multiple FGF genes was recorded in the species’ gonads during its development. Among them, expression of the FGF1 gene was recorded in interstitial and sertoli cells of testes, promoting germ-cell proliferation and differentiation. In sum, the obtained results enabled systematic and functional characterization of FGF genes in S. schlegelii, laying a foundation for further studies on FGF genes in other large teleost fishes.
The EphA1 and EphA2 Signaling Modulates the Epithelial Permeability in Human Sinonasal Epithelial Cells and the Rhinovirus Infection Induces Epithelial Barrier Dysfunction via EphA2 Receptor Signaling
Authors: Shin Jae Min , Han Moon Soo , Park Jae Hyung , Lee Seung Hyeok , Kim Tae Hoon , Lee Sang Hag
Published: February 2023

Deficiencies in epithelial barrier integrity are involved in the pathogenesis of chronic rhinosinusitis (CRS). This study aimed to investigate the role of ephrinA1/ephA2 signaling on sinonasal epithelial permeability and rhinovirus-induced epithelial permeability. This role in the process of epithelial permeability was evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to rhinovirus infection. EphrinA1 treatment increased epithelial permeability, which was associated with decreased expression of ZO-1, ZO-2, and occludin. These effects of ephrinA1 were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. Furthermore, rhinovirus infection upregulated the expression levels of ephrinA1 and ephA2, increasing epithelial permeability, which was suppressed in ephA2-deficient cells. These results suggest a novel role of ephrinA1/ephA2 signaling in epithelial barrier integrity in the sinonasal epithelium, suggesting their participation in rhinovirus-induced epithelial dysfunction.
The Formation of Morphologically Stable Lipid Nanocarriers for Glioma Therapy
Authors: Pavlov Rais , Romanova Elvira , Kuznetsov Denis , Lyubina Anna , Amerhanova Syumbelya , Voloshina Alexandra , Buzyurova Daina , Babaev Vasily , Zueva Irina , Petrov Konstantin , Lukashenko Svetlana , Gaynanova Gulnara , Zakharova Lucia
Published: February 2023

Cerasomes are a promising modification of liposomes with covalent siloxane networks on the surface that provide outstanding morphological stability while maintaining all the useful traits of liposomes. Herein, thin film hydration and ethanol sol injection methods were utilized to produce cerasomes of various composition, which were then evaluated for the purpose of drug delivery. The most promising nanoparticles obtained by the thin film method were studied closely using MTT assay, flow cytometry and fluorescence microscopy on T98G glioblastoma cell line and modified with surfactants to achieve stability and the ability to bypass the blood–brain barrier. An antitumor agent, paclitaxel, was loaded into cerasomes, which increased its potency and demonstrated increased ability to induce apoptosis in T98G glioblastoma cell culture. Cerasomes loaded with fluorescent dye rhodamine B demonstrated significantly increased fluorescence in brain slices of Wistar rats compared to free rhodamine B. Thin film hydration with Tween 80 addition was established as a more reliable and versatile method for cerasome preparation. Cerasomes increased the antitumor action of paclitaxel toward T98G cancer cells by a factor of 36 and were able to deliver rhodamine B over the blood–brain barrier in rats.
Optimization of Isolation and Transformation of Protoplasts from Uncaria rhynchophylla and Its Application to Transient Gene Expression Analysis
Authors: Shao Yingying , Mu Detian , Pan Limei , Wilson Iain W. , Zheng Yajie , Zhu Lina , Lu Zhiguo , Wan Lingyun , Fu Jine , Wei Shugen , Song Lisha , Qiu Deyou , Tang Qi
Published: February 2023

Protoplast-based engineering has become an important tool for basic plant molecular biology research and developing genome-edited crops. Uncaria rhynchophylla is a traditional Chinese medicinal plant with a variety of pharmaceutically important indole alkaloids. In this study, an optimized protocol for U. rhynchophylla protoplast isolation, purification, and transient gene expression was developed. The best protoplast separation protocol was found to be 0.8 M D-mannitol, 1.25% Cellulase R-10, and 0.6% Macerozyme R-10 enzymolysis for 5 h at 26 °C in the dark with constant oscillation at 40 rpm/min. The protoplast yield was as high as 1.5 × 107 protoplasts/g fresh weight, and the survival rate of protoplasts was greater than 90%. Furthermore, polyethylene glycol (PEG)-mediated transient transformation of U. rhynchophylla protoplasts was investigated by optimizing different crucial factors affecting transfection efficiency, including plasmid DNA amount, PEG concentration, and transfection duration. The U. rhynchophylla protoplast transfection rate was highest (71%) when protoplasts were transfected overnight at 24 °C with the 40 µg of plasmid DNA for 40 min in a solution containing 40% PEG. This highly efficient protoplast-based transient expression system was used for subcellular localization of transcription factor UrWRKY37. Finally, a dual-luciferase assay was used to detect a transcription factor promoter interaction by co-expressing UrWRKY37 with a UrTDC-promoter reporter plasmid. Taken together, our optimized protocols provide a foundation for future molecular studies of gene function and expression in U. rhynchophylla.
Small-Molecule Inhibition of MuRF1 Prevents Early Disuse-Induced Diaphragmatic Dysfunction and Atrophy
Authors: Ribeiro Fernando , Alves Paula K. N. , Bechara Luiz R. G. , Ferreira Julio C. B. , Labeit Siegfried , Moriscot Anselmo S.
Published: February 2023

In clinical conditions such as diaphragm paralysis or mechanical ventilation, disuse-induced diaphragmatic dysfunction (DIDD) is a condition that poses a threat to life. MuRF1 is a key E3-ligase involved in regulating skeletal muscle mass, function, and metabolism, which contributes to the onset of DIDD. We investigated if the small-molecule mediated inhibition of MuRF1 activity (MyoMed-205) protects against early DIDD after 12 h of unilateral diaphragm denervation. Wistar rats were used in this study to determine the compound’s acute toxicity and optimal dosage. For potential DIDD treatment efficacy, diaphragm contractile function and fiber cross-sectional area (CSA) were evaluated. Western blotting investigated potential mechanisms underlying MyoMed-205’s effects in early DIDD. Our results indicate 50 mg/kg bw MyoMed-205 as a suitable dosage to prevent early diaphragmatic contractile dysfunction and atrophy following 12 h of denervation without detectable signs of acute toxicity. Mechanistically, treatment did not affect disuse-induced oxidative stress (4-HNE) increase, whereas phosphorylation of (ser632) HDAC4 was normalized. MyoMed-205 also mitigated FoxO1 activation, inhibited MuRF2, and increased phospho (ser473) Akt protein levels. These findings may suggest that MuRF1 activity significantly contributes to early DIDD pathophysiology. Novel strategies targeting MuRF1 (e.g., MyoMed-205) have potential therapeutic applications for treating early DIDD.
Is CCL2 an Important Mediator of Mast Cell–Tumor Cell Interactions in Oral Squamous Cell Carcinoma?
Authors: Hemmerlein Bernhard , Reinhardt Luisa , Wiechens Bernhard , Khromov Tatjana , Schliephake Henning , Brockmeyer Phillipp
Published: February 2023

In this study, we aimed to evaluate the influence of interactions between mast cells (MCs) and oral squamous cell carcinoma (OSCC) tumor cells on tumor proliferation and invasion rates and identify soluble factors mediating this crosstalk. To this end, MC/OSCC interactions were characterized using the human MC cell line LUVA and the human OSCC cell line PCI-13. The influence of an MC-conditioned (MCM) medium and MC/OSCC co-cultures on the proliferative and invasive properties of the tumor cells was investigated, and the most interesting soluble factors were identified by multiplex ELISA analysis. LUVA/PCI-13 co-cultures increased tumor cell proliferation significantly (p = 0.0164). MCM reduced PCI-13 cell invasion significantly (p = 0.0010). CC chemokine ligand 2 (CCL2) secretion could be detected in PCI-13 monocultures and be significantly (p = 0.0161) increased by LUVA/PCI-13 co-cultures. In summary, the MC/OSCC interaction influences tumor cell characteristics, and CCL2 could be identified as a possible mediator.
Effect of Hyaluronic Acid and Mesenchymal Stem Cells Secretome Combination in Promoting Alveolar Regeneration
Authors: Della Sala Francesca , Longobardo Gennaro , Lista Gianluca , Messina Francesco , Borzacchiello Assunta
Published: February 2023

Pharmacological therapies in lung diseases are nowadays useful in reducing the symptomatology of lung injury. However, they have not yet been translated to effective treatment options able to restore the lung tissue damage. Cell-therapy based on Mesenchymal Stem Cells (MSCs) is an attractive, as well as new therapeutic approach, although some limitations can be ascribed for therapeutic use, such as tumorigenicity and immune rejection. However, MSCs have the capacity to secrete multiple paracrine factors, namely secretome, capable of regulating endothelial and epithelial permeability, decrease inflammation, enhancing tissue repair, and inhibiting bacterial growth. Furthermore, Hyaluronic acid (HA) has been demonstrated to have particularly efficacy in promoting the differentiation of MSCs in Alveolar type II (ATII) cells. In this frame, the combination of HA and secretome to achieve the lung tissue regeneration has been investigated for the first time in this work. Overall results showed how the combination of HA (low and medium molecular weight HA) plus secretome could enhance MSCs differentiation in ATII cells (SPC marker expression of about 5 ng/mL) compared to the only HA or secretome solutions alone (SPC about 3 ng/mL, respectively). Likewise, cell viability and cell rate of migration were reported to be improved for HA and secretome blends, indicating an interesting potentiality of such systems for lung tissue repair. Moreover, an anti-inflammatory profile has been revealed when dealing with HA and secretome mixtures. Therefore, these promising results can allow important advance in the accomplishment of the future therapeutic approach in respiratory diseases, up to date still missing.
Enhanced Resistance to Fungal and Bacterial Diseases Due to Overexpression of BSR1, a Rice RLCK, in Sugarcane, Tomato, and Torenia
Authors: Maeda Satoru , Ackley Wataru , Yokotani Naoki , Sasaki Katsutomo , Ohtsubo Norihiro , Oda Kenji , Mori Masaki
Published: February 2023

Sugarcane smut caused by Sporisorium scitamineum is one of the most devastating sugarcane diseases. Furthermore, Rhizoctonia solani causes severe diseases in various crops including rice, tomato, potato, sugar beet, tobacco, and torenia. However, effective disease-resistant genes against these pathogens have not been identified in target crops. Therefore, the transgenic approach can be used since conventional cross-breeding is not applicable. Herein, the overexpression of BROAD-SPECTRUM RESISTANCE 1 (BSR1), a rice receptor-like cytoplasmic kinase, was conducted in sugarcane, tomato and torenia. BSR1-overexpressing tomatoes exhibited resistance to the bacteria Pseudomonas syringae pv. tomato DC3000 and the fungus R. solani, whereas BSR1-overexpressing torenia showed resistance to R. solani in the growth room. Additionally, BSR1 overexpression conferred resistance to sugarcane smut in the greenhouse. These three BSR1-overexpressing crops exhibited normal growth and morphologies except in the case of exceedingly high levels of overexpression. These results indicate that BSR1 overexpression is a simple and effective tool for conferring broad-spectrum disease resistance to many crops.
Residual Amino Acid Imbalance in Rats during Recovery from Acute Thioacetamide-Induced Hepatic Encephalopathy Indicates Incomplete Healing
Authors: Shurubor Yevgeniya I. , Rogozhin Alexander E. , Isakova Elena P. , Deryabina Yulia I. , Krasnikov Boris F.
Published: February 2023

The delayed consequences of the influence of hepatic encephalopathy (HE) on the metabolism of animals have not been studied enough. We have previously shown that the development of acute HE under the influence of the thioacetamide (TAA) toxin is accompanied by pathological changes in the liver, an imbalance in CoA and acetyl CoA, as well as a number of metabolites of the TCA cycle. This paper discusses the change in the balance of amino acids (AAs) and related metabolites, as well as the activity of glutamine transaminase (GTK) and ω-amidase enzymes in the vital organs of animals 6 days after a single exposure to TAA. The balance of the main AAs in blood plasma, liver, kidney, and brain samples of control (n = 3) and TAA-induced groups (n = 13) of rats that received the toxin at doses of 200, 400, and 600 mg/kg was considered. Despite the apparent physiological recovery of the rats at the time of sampling, a residual imbalance in AA and associated enzymes persisted. The data obtained give an idea of the metabolic trends in the body of rats after their physiological recovery from TAA exposure and may be useful for prognostic purposes when choosing the necessary therapeutic agents.
Suppression of Rice Osa-miR444.2 Improves the Resistance to Sheath Blight in Rice Mediating through the Phytohormone Pathway
Authors: Feng Tao , Zhang Zhao-Yang , Gao Peng , Feng Zhi-Ming , Zuo Shi-Min , Ouyang Shou-Qiang
Published: February 2023

MicroRNAs (miRNAs) are a class of conserved small RNA with a length of 21–24 nucleotides in eukaryotes, which are involved in development and defense responses against biotic and abiotic stresses. By RNA-seq, Osa-miR444b.2 was identified to be induced after Rhizoctonia solani (R. solani) infection. In order to clarify the function of Osa-miR444b.2 responding to R. solani infection in rice, transgenic lines over-expressing and knocking out Osa-miR444b.2 were generated in the background of susceptible cultivar Xu3 and resistant cultivar YSBR1, respectively. Over-expressing Osa-miR444b.2 resulted in compromised resistance to R. solani. In contrast, the knocking out Osa-miR444b.2 lines exhibited improved resistance to R. solani. Furthermore, knocking out Osa-miR444b.2 resulted in increased height, tillers, smaller panicle, and decreased 1000-grain weight and primary branches. However, the transgenic lines over-expressing Osa-miR444b.2 showed decreased primary branches and tillers, but increased panicle length. These results indicated that Osa-miR444b.2 was also involved in regulating the agronomic traits in rice. The RNA-seq assay revealed that Osa-miR444b.2 mainly regulated the resistance to rice sheath blight disease by affecting the expression of plant hormone signaling pathways-related genes such as ET and IAA, and transcription factors such as WRKYs and F-boxes. Together, our results suggest that Osa-miR444b.2 negatively mediated the resistance to R. solani in rice, which will contribute to the cultivation of sheath blight resistant varieties.
A Proteomic Screen to Unravel the Molecular Pathways Associated with Warfarin-Induced or TNAP-Inhibited Arterial Calcification in Rats
Authors: Opdebeeck Britt , Neven Ellen , Maudsley Stuart , Leysen Hanne , Walter Deborah , Geryl Hilde , D’Haese Patrick C. , Verhulst Anja
Published: February 2023

Arterial media calcification refers to the pathological deposition of calcium phosphate crystals in the arterial wall. This pathology is a common and life-threatening complication in chronic kidney disease, diabetes and osteoporosis patients. Recently, we reported that the use of a TNAP inhibitor, SBI-425, attenuated arterial media calcification in a warfarin rat model. Employing a high-dimensionality unbiased proteomic approach, we also investigated the molecular signaling events associated with blocking arterial calcification through SBI-425 dosing. The remedial actions of SBI-425 were strongly associated with (i) a significant downregulation of inflammatory (acute phase response signaling) and steroid/glucose nuclear receptor signaling (LXR/RXR signaling) pathways and (ii) an upregulation of mitochondrial metabolic pathways (TCA cycle II and Fatty Acid β-oxidation I). Interestingly, we previously demonstrated that uremic toxin-induced arterial calcification contributes to the activation of the acute phase response signaling pathway. Therefore, both studies suggest a strong link between acute phase response signaling and arterial calcification across different conditions. The identification of therapeutic targets in these molecular signaling pathways may pave the way to novel therapies against the development of arterial media calcification.
How Nanoparticles Modify Adsorbed Proteins: Impact of Silica Nanoparticles on the Hemoglobin Active Site
Authors: Giraudon--Colas Gaël , Devineau Stéphanie , Marichal Laurent , Barruet Elodie , Zitolo Andrea , Renault Jean-Philippe , Pin Serge
Published: February 2023

The adsorption of proteins on surfaces has been studied for a long time, but the relationship between the structural and functional properties of the adsorbed protein and the adsorption mechanism remains unclear. Using hemoglobin adsorbed on silica nanoparticles, we have previously shown that hemoglobin’s affinity towards oxygen increases with adsorption. Nevertheless, it was also shown that there were no significant changes in the quaternary and secondary structures. In order to understand the change in activity, we decided in this work to focus on the active sites of hemoglobin, the heme and its iron. After measuring adsorption isotherms of porcine hemoglobin on Ludox silica nanoparticles, we analyzed the structural modifications of adsorbed hemoglobin by X-ray absorption spectroscopy and circular dichroism spectra in the Soret region. It was found that upon adsorption, there were modifications in the heme pocket environment due to changes in the angles of the heme vinyl functions. These alterations can explain the greater affinity observed.
Unveiling the Machinery behind Chromosome Folding by Polymer Physics Modeling
Authors: Conte Mattia , Esposito Andrea , Vercellone Francesca , Abraham Alex , Bianco Simona
Published: February 2023

Understanding the mechanisms underlying the complex 3D architecture of mammalian genomes poses, at a more fundamental level, the problem of how two or multiple genomic sites can establish physical contacts in the nucleus of the cells. Beyond stochastic and fleeting encounters related to the polymeric nature of chromatin, experiments have revealed specific, privileged patterns of interactions that suggest the existence of basic organizing principles of folding. In this review, we focus on two major and recently proposed physical processes of chromatin organization: loop-extrusion and polymer phase-separation, both supported by increasing experimental evidence. We discuss their implementation into polymer physics models, which we test against available single-cell super-resolution imaging data, showing that both mechanisms can cooperate to shape chromatin structure at the single-molecule level. Next, by exploiting the comprehension of the underlying molecular mechanisms, we illustrate how such polymer models can be used as powerful tools to make predictions in silico that can complement experiments in understanding genome folding. To this aim, we focus on recent key applications, such as the prediction of chromatin structure rearrangements upon disease-associated mutations and the identification of the putative chromatin organizing factors that orchestrate the specificity of DNA regulatory contacts genome-wide.
Molecular Assessment of Healthy Pathological Articular Cartilages in Physically Active People: A Scoping Review
Authors: Petrigna Luca , Trovato Bruno , Roggio Federico , Castorina Alessandro , Musumeci Giuseppe
Published: February 2023

Physiological aging triggers a cascade of negative effects on the human body and the human joint is only one of the several compartments affected by this irreversible and natural process. Osteoarthritis and cartilage degeneration can cause pain and disability; therefore, identifying the molecular processes underlying these phenomena and the biomarkers produced during physical activity is of critical importance. In the present review, the main goal was to identify and discuss the articular cartilage biomarkers analyzed in studies in which physical or sports activities were adopted and eventually to propose a standard operating procedure for the assessment. Articles collected from Pubmed, Web of Science, and Scopus were scrutinized to detect reliable cartilage biomarkers. The principal articular cartilage biomarkers detected in these studies were cartilage oligomeric matrix protein, matrix metalloproteinases, interleukins, and carboxy-terminal telopeptide. The articular cartilage biomarkers identified in this scoping review may aid in a better comprehension of where research on the topic is heading and offer a viable instrument for streamlining investigations on cartilage biomarker discovery.