bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Catalytic Co-Pyrolysis Characteristics and Synergistic Effect of Oily Sludge and Walnut Shell
Authors: Li Qinghong , Yang Huan , Chen Ping , Jiang Wenxue , Chen Fei , Yu Xiaorong , Su Gaoshen
Published: February 2023

The co-pyrolysis of oily sludge and walnut shell is a reliable method for solid waste treatment and waste recycling. In this paper, a thermogravimetric analysis was used to study the thermodynamics and synergy effect of oily sludge (OS) and walnut shell (WS) at four heating rates (10, 20, 30, and 40 °C/min) in the temperature range from 50–850 °C. Two model-free methods (FWO and KAS) were used to calculate the activation energy. The results showed that the heating rate had no significant effect on the pyrolysis process. The addition of walnut shell improved the pyrolysis process of the samples. Mixture 1OS3WS had a synergy effect, while other blends showed an inhibitory effect. The synergy effect of co-pyrolysis was strongest when the mass ratio of oily sludge was 25%. The activation energy of the Zn-ZSM-5/25 catalyst was the lowest, and the residual substances were the least, indicating that the Zn-ZSM-5/25 was beneficial to the co-pyrolysis of oily sludge and walnut shell. The analysis of catalytic pyrolysis products by Py-GC/MS found that co-pyrolysis was beneficial to the generation of aromatic hydrocarbons. This study provided a method for the resource utilization of hazardous waste and biomass waste, which was conducive to the production of aromatic chemicals with added value while reducing environmental pollution.
Vertical Transmission of Coxsackievirus A6 with Severe Congenital Pneumonia/Sepsis
Authors: Nakasone Ruka , Ogi Miki , Kawamura Aoi , Miyake Osamu , Kido Takumi , Abe Shinya , Takahashi Naoto , Nozu Kandai , Fujioka Kazumichi
Published: February 2023

We report a case of vertical transmission of Coxsackievirus (CV)-A6 with severe congenital pneumonia/sepsis. A male infant presented with severe respiratory symptoms at birth and was treated with full cardiopulmonary support, including inhaled nitric oxide. Three days before delivery, his older brother was diagnosed with hand, foot, and mouth disease (HFMD). His mother developed transient fever 1 day before delivery and presented a blister on her thumb 2 days after delivery. A multiplex polymerase chain reaction test on day 2 was positive for human rhinovirus/enterovirus. CV-A6 was later detected in the serum, tracheal aspirate, and stool of the patient sampled on day 6, and in the maternal serum sampled on the day of delivery. He was diagnosed with congenital CV-A6 pneumonia/sepsis caused by vertical transmission, based on VP1 consensus sequences used for typing of the virus that demonstrated a 100% match between the mother and infant. Further, the strain was closely related to the lethal CV-A6-Changchun strains in the phylogenetic analysis of the P2 region, which contributes to the pathogenicity. In conclusion, congenital CV-A6 infection should be considered if a woman exhibits HFMD symptoms during the perinatal period. Detailed virologic examination is useful for understanding its pathogenesis.
Effects of Suryanamaskar, an Intensive Yoga Exercise Routine, on the Stress Levels and Emotional Intelligence of Indian Students
Authors: Stec Krzysztof , Kruszewski Marek , Ciechanowski Leon
Published: February 2023

The inability of an individual to identify, assess, and manage emotions and levels of stress has adverse individual and societal consequences. Previous studies have shown that yoga-based interventions can successfully treat stress, anxiety, and depression, and can enhance emotional control. The aim of the current study was to assess the effect of a specific, intensive, yoga-based intervention, Dynamic Suryanamaskar, on the levels of perceived stress and emotional intelligence in Indian male school students. One hundred and five students with a median age of 17.15 ± 1.42 years were assessed. Practice took place over 12 weeks (n = 70 workouts). The Perceived Stress Scale (PSS) questionnaire and the emotional intelligence (EQ) questionnaire, developed for the Indian population, were used to measure stress and emotional levels at the start and end of the study. The Solomon four-group design was used to ensure statistical reliability. The post-study univariate analysis of covariance ANOVA between groups (p < 0.001) and the t-test for independent samples (p < 0.05) indicated that, for those using the Dynamic Suryanamaskar protocol, there was a significant reduction in stress levels and a significant (p < 0.01) increase in the levels of emotional intelligence. This study thus provides further evidence of the benefits of the practice of Dynamic Suryanamaskar.
How Does Spatial Injustice Affect Residents’ Policy Acceptance of the Economic–Social–Ecological Objectives of Construction Land Reduction?
Authors: Wang Keqiang , Lu Jianglin , Liu Hongmei
Published: February 2023

Construction land reduction (CLR) is a policy innovation for Shanghai to explore high-quality economic development, but it will also lead to spatial injustice in the implementation process. Although the literature on spatial injustice and CLR is increasing, very little is known about the influence of spatial injustice in CLR on residents’ policy acceptance of the economic–social–ecological objectives of CLR. To fill the knowledge gap, this study uses micro-survey data to identify the factors that influence residents’ policy acceptance of the economic–social–ecological objectives of CLR. Results show that: (1) Spatial injustice in CLR significantly reduces residents’ policy acceptance of the social and ecological objectives of CLR. (2) The locational disadvantage of villages significantly reduces residents’ policy acceptance of the ecological objectives of CLR. (3) The more educated the residents are, the more they recognize the social and ecological objectives of CLR. (4) The higher the percentage of household workers, the more residents endorse the economic and social objectives of CLR. (5) Compared with ordinary residents, cadres are more accepting of the economic objectives of CLR. (6) Robustness tests support the findings of this study. The findings of this study provide insights for sustainable CLR policy reform.
Central Locations across Spatial Scales: A Quantitative Evaluation for Italy Using Census Enumeration District Indicators
Authors: Salvucci Gianluigi , Salvati Luca , Arezzo Maria Felice
Published: February 2023

‘Marginal’ urban settlements can be assumed as specific locations within a metropolitan area that are unable to attract (incoming) commuter flows. The official statistical system of Italy (headed by the National Statistical Institute, Istat) introduced a summary index of ‘urban marginality’ following the original definition proposed by a national, ad hoc Parliamentary Committee and assessing together social vulnerability and material deprivation at a sufficiently detailed spatial scale. More specifically, the index—intended as a composite indicator of territorial marginality with a normative meaning—was calculated as a specific elaboration of the commuting matrix derived from decadal population censuses considering a municipal-level resolution. In this perspective, the ability of a given municipality to attract bigger (or smaller) inflows than outflows, indicates a specific demand for services allowing the identification of (respectively) central places and peripheral locations. Starting from the index described above, our study generalizes this approach to a wider background context, investigating the roles of spatial scale and geographical coverage. By providing a novel (functional) approach to centrality and periphery, we analyzed commuting patterns at a submunicipal level, indirectly focusing on patterns and processes of local development. A spatial clustering of a standardized polarization index quantifying home-to-work daily travels delineated submunicipal (homogeneous) areas taken as sinks (centers) or sources (peripheries) of commuter flows. The empirical results also demonstrate that spatial neighborhoods (i.e., contiguity order) did not affect the functional classification of a given territory as derived from spatial clustering. Our approach provides a dynamic and innovative interpretation of metropolitan hierarchy using simplified data derived from population censuses.
Analyzing Geographic Questions Using Embedding-based Topic Modeling
Authors: Yang Jonghyeon , Jang Hanme , Yu Kiyun
Published: February 2023

Recently, open-domain question-answering systems have achieved tremendous progress because of developments in large language models (LLMs), and have successfully been applied to question-answering (QA) systems, or Chatbots. However, there has been little progress in open-domain question answering in the geographic domain. Existing open-domain question-answering research in the geographic domain relies heavily on rule-based semantic parsing approaches using few data. To develop intelligent GeoQA agents, it is crucial to build QA systems upon datasets that reflect the real users’ needs regarding the geographic domain. Existing studies have analyzed geographic questions using the geographic question corpora Microsoft MAchine Reading Comprehension (MS MARCO), comprising real-world user queries from Bing in terms of structural similarity, which does not discover the users’ interests. Therefore, we aimed to analyze location-related questions in MS MARCO based on semantic similarity, group similar questions into a cluster, and utilize the results to discover the users’ interests in the geographic domain. Using a sentence-embedding-based topic modeling approach to cluster semantically similar questions, we successfully obtained topic models that could gather semantically similar documents into a single cluster. Furthermore, we successfully discovered latent topics within a large collection of questions to guide practical GeoQA systems on relevant questions.
PDIA3 Expression Is Altered in the Limbic Brain Regions of Triple-Transgenic Mouse Model of Alzheimer’s Disease
Authors: Cassano Tommaso , Giamogante Flavia , Calcagnini Silvio , Romano Adele , Lavecchia Angelo Michele , Inglese Francesca , Paglia Giuliano , Bukke Vidyasagar Naik , Romano Antonino Davide , Friuli Marzia , Altieri Fabio , Gaetani Silvana
Published: February 2023

In the present study, we used a mouse model of Alzheimer’s disease (AD) (3×Tg-AD mice) to longitudinally analyse the expression level of PDIA3, a protein disulfide isomerase and endoplasmic reticulum (ER) chaperone, in selected brain limbic areas strongly affected by AD-pathology (amygdala, entorhinal cortex, dorsal and ventral hippocampus). Our results suggest that, while in Non-Tg mice PDIA3 levels gradually reduce with aging in all brain regions analyzed, 3×Tg-AD mice showed an age-dependent increase in PDIA3 levels in the amygdala, entorhinal cortex, and ventral hippocampus. A significant reduction of PDIA3 was observed in 3×Tg-AD mice already at 6 months of age, as compared to age-matched Non-Tg mice. A comparative immunohistochemistry analysis performed on 3×Tg-AD mice at 6 (mild AD-like pathology) and 18 (severe AD-like pathology) months of age showed a direct correlation between the cellular level of Aβ and PDIA3 proteins in all the brain regions analysed, even if with different magnitudes. Additionally, an immunohistochemistry analysis showed the presence of PDIA3 in all post-mitotic neurons and astrocytes. Overall, altered PDIA3 levels appear to be age- and/or pathology-dependent, corroborating the ER chaperone’s involvement in AD pathology, and supporting the PDIA3 protein as a potential novel therapeutic target for the treatment of AD.
Ant-Neointimal Formation Effects of SLC6A6 in Preventing Vascular Smooth Muscle Cell Proliferation and Migration via Wnt/β-Catenin Signaling
Authors: Rong Zhihua , Li Fengshi , Zhang Rui , Niu Shuai , Di Xiao , Ni Leng , Liu Changwei
Published: February 2023

Vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of vascular remolding, such as atherosclerosis and restenosis. Solute carrier family 6 member 6 (SLC6A6) is a transmembrane transporter that maintains a variety of physiological functions and is highly expressed in VSMCs. However, its role on VSMCs during neointimal formation remains unknown. In this study, mRNA and protein levels of SLC6A6 were examined using models of VSMC phenotype switching in vivo and in vitro and human artery samples with or without atherosclerosis. SLC6A6 gain- and loss-of-function approaches were performed by adenovirus infection or small interfering RNA (siRNA) transfection, respectively. Reactive oxygen species (ROS), proliferation, migration, and phenotype-related proteins of VSMCs were measured. Vascular stenosis rate and related genes were assessed in a rat vascular balloon injury model overexpressing SLC6A6. SLC6A6 was downregulated in dedifferentiated VSMCs, atherosclerotic vascular tissues, and injured vascular tissues. SLC6A6 suppressed VSMC proliferation and migration, while increasing contractile VSMC proteins. Mechanistically, SLC6A6 overexpression reduced ROS production and inhibited the Wnt/β-catenin pathway. Furthermore, SLC6A6 overexpression suppressed neointimal formation in vivo. Collectively, overexpression of SLC6A6 suppresses neointimal formation by inhibiting VSMC proliferation and migration via Wnt/β-catenin signaling and maintaining the VSMC contractile phenotype.
Phosphorylation of Thymidylate Synthase and Dihydrofolate Reductase in Cancer Cells and the Effect of CK2α Silencing
Authors: Wińska Patrycja , Sobiepanek Anna , Pawlak Katarzyna , Staniszewska Monika , Cieśla Joanna
Published: February 2023

Our previous research suggests an important regulatory role of CK2-mediated phosphorylation of enzymes involved in the thymidylate biosynthesis cycle, i.e., thymidylate synthase (TS), dihydrofolate reductase (DHFR), and serine hydroxymethyltransferase (SHMT). The aim of this study was to show whether silencing of the CK2α gene affects TS and DHFR expression in A-549 cells. Additionally, we attempted to identify the endogenous kinases that phosphorylate TS and DHFR in CCRF-CEM and A-549 cells. We used immunodetection, immunofluorescence/confocal analyses, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), in-gel kinase assay, and mass spectrometry analysis. Our results demonstrate that silencing of the CK2α gene in lung adenocarcinoma cells significantly increases both TS and DHFR expression and affects their cellular distribution. Additionally, we show for the first time that both TS and DHFR are very likely phosphorylated by endogenous CK2 in two types of cancer cells, i.e., acute lymphoblastic leukaemia and lung adenocarcinoma. Moreover, our studies indicate that DHFR is phosphorylated intracellularly by CK2 to a greater extent in leukaemia cells than in lung adenocarcinoma cells. Interestingly, in-gel kinase assay results indicate that the CK2α’ isoform was more active than the CK2α subunit. Our results confirm the previous studies concerning the physiological relevance of CK2-mediated phosphorylation of TS and DHFR.
Genomics, Proteomics, and Metabolomics Approaches to Improve Abiotic Stress Tolerance in Tomato Plant
Authors: Naik Bindu , Kumar Vijay , Rizwanuddin Sheikh , Chauhan Mansi , Choudhary Megha , Gupta Arun Kumar , Kumar Pankaj , Kumar Vivek , Saris Per Erik Joakim , Rather Muzamil Ahmad , Bhuyan Shuvam , Neog Panchi Rani , Mishra Sadhna , Rustagi Sarvesh
Published: February 2023

To explore changes in proteins and metabolites under stress circumstances, genomics, proteomics, and metabolomics methods are used. In-depth research over the previous ten years has gradually revealed the fundamental processes of plants’ responses to environmental stress. Abiotic stresses, which include temperature extremes, water scarcity, and metal toxicity brought on by human activity and urbanization, are a major cause for concern, since they can result in unsustainable warming trends and drastically lower crop yields. Furthermore, there is an emerging reliance on agrochemicals. Stress is responsible for physiological transformations such as the formation of reactive oxygen, stomatal opening and closure, cytosolic calcium ion concentrations, metabolite profiles and their dynamic changes, expression of stress-responsive genes, activation of potassium channels, etc. Research regarding abiotic stresses is lacking because defense feedbacks to abiotic factors necessitate regulating the changes that activate multiple genes and pathways that are not properly explored. It is clear from the involvement of these genes that plant stress response and adaptation are complicated processes. Targeting the multigenicity of plant abiotic stress responses caused by genomic sequences, transcripts, protein organization and interactions, stress-specific and cellular transcriptome collections, and mutant screens can be the first step in an integrative approach. Therefore, in this review, we focused on the genomes, proteomics, and metabolomics of tomatoes under abiotic stress.
Advanced Materials for Electrochemical Energy Storage: Lithium-Ion, Lithium-Sulfur, Lithium-Air and Sodium Batteries
Authors: Julien Christian M.
Published: February 2023

The intention behind this Special Issue was to assemble high-quality works focusing on the latest advances in the development of various materials for rechargeable batteries, as well as to highlight the science and technology of devices that today are one of the most important and efficient types of energy storage, namely, lithium-ion, lithium–sulfur, lithium–air and sodium-ion batteries [...]
Role of Transcription Factor EB in Mitochondrial Dysfunction of Cisplatin-Induced Acute Kidney Injury
Authors: Wang Shujun , Chen Yanse , Wu Hongluan , Li Xiaoyu , Xiao Haiyan , Pan Qingjun , Liu Hua-Feng
Published: February 2023

Cisplatin, a widely used anticancer agent, can cause nephrotoxicity, including both acute kidney injury (AKI) and chronic kidney diseases, by accumulating in renal tubular epithelial cells (TECs). Mitochondrial pathology plays an important role in the pathogenesis of AKI. Based on the regulatory role of transcription factor EB (TFEB) in mitochondria, we investigated whether TFEB is involved in cisplatin-induced TEC damage. The results show that the expression of TFEB decreased in a concentration-dependent manner in both mouse kidney tissue and HK-2 cells when treated with cisplatin. A knockdown of TFEB aggravated cisplatin-induced renal TEC injury, which was partially reversed by TFEB overexpression in HK-2 cells. It was further observed that the TFEB knockdown also exacerbated cisplatin-induced mitochondrial damage in vitro, and included the depolarization of membrane potential, mitochondrial fragmentation and swelling, and the production of reactive oxygen species. In contrast, TFEB overexpression alleviated cisplatin-induced mitochondrial damage in TECs. These findings suggest that decreased TFEB expression may be a key mechanism of mitochondrial dysfunction in cisplatin-induced AKI, and that upregulation of TFEB has the potential to act as a therapeutic target to alleviate mitochondrial dysfunction and cisplatin-induced TEC injury. This study is important for developing therapeutic strategies to manipulate mitochondria through TFEB to delay AKI progression.
Functional Characterization of Lobularia maritima LmTrxh2 Gene Involved in Cold Tolerance in Tobacco through Alleviation of ROS Damage to the Plasma Membrane
Authors: Ben Saad Rania , Ben Romdhane Walid , Baazaoui Narjes , Bouteraa Mohamed Taieb , Chouaibi Yosra , Mnif Wissem , Ben Hsouna Anis , Kačániová Miroslava
Published: February 2023

Cold stress is a key environmental factor affecting plant growth and development, crop productivity, and geographic distribution. Thioredoxins (Trxs) are small proteins that are ubiquitously expressed in all organisms and implicated in several cellular processes, including redox reactions. However, their role in the regulation of cold stress in the halophyte plant Lobularia maritima remains unknown. We recently showed that overexpression of LmTrxh2, which is the gene that encodes the h-type Trx protein previously isolated from L. maritima, led to an enhanced tolerance to salt and osmotic stress in transgenic tobacco. This study functionally characterized the LmTrxh2 gene via its overexpression in tobacco and explored its cold tolerance mechanisms. Results of the RT-qPCR and western blot analyses indicated differential temporal and spatial regulation of LmTrxh2 in L. maritima under cold stress at 4 °C. LmTrxh2 overexpression enhanced the cold tolerance of transgenic tobacco, as evidenced by increased germination rate, fresh weight and catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD) activities; reduced malondialdehyde levels, membrane leakage, superoxide anion (O2−), and hydrogen peroxide (H2O2) levels; and higher retention of chlorophyll than in non-transgenic plants (NT). Furthermore, the transcript levels of reactive oxygen species (ROS)-related genes (NtSOD and NtCAT1), stress-responsive late embryogenis abundant protein 5 (NtLEA5), early response to dehydration 10C (NtERD10C), DRE-binding proteins 1A (NtDREB1A), and cold-responsive (COR) genes (NtCOR15A, NtCOR47, and NtKIN1) were upregulated in transgenic lines compared with those in NT plants under cold stress, indicating that LmTrxh2 conferred cold stress tolerance by enhancing the ROS scavenging ability of plants, thus enabling them to maintain membrane integrity. These results suggest that LmTrxh2 promotes cold tolerance in tobacco and provide new insight into the improvement of cold-stress resistance to cold stress in non-halophyte plants and crops.
SARS-CoV-2 Spike Protein Activates Human Lung Macrophages
Authors: Palestra Francesco , Poto Remo , Ciardi Renato , Opromolla Giorgia , Secondo Agnese , Tedeschi Valentina , Ferrara Anne Lise , Di Crescenzo Rosa Maria , Galdiero Maria Rosaria , Cristinziano Leonardo , Modestino Luca , Marone Gianni , Fiorelli Alfonso , Varricchi Gilda , Loffredo Stefania
Published: February 2023

COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells. The virus uses the protease TMPRSS2 as an entry activator. Human lung macrophages (HLMs) are the most abundant immune cells in the lung and fulfill a variety of specialized functions mediated by the production of cytokines and chemokines. The aim of this project was to investigate the effects of spike protein on HLM activation and the expression of ACE2 and TMPRSS2 in HLMs. Spike protein induced CXCL8, IL-6, TNF-α, and IL-1β release from HLMs; promoted efficient phagocytosis; and induced dysfunction of intracellular Ca2+ concentration by increasing lysosomal Ca2+ content in HLMs. Microscopy experiments revealed that HLM tracking was affected by spike protein activation. Finally, HLMs constitutively expressed mRNAs for ACE2 and TMPRSS2. In conclusion, during SARS-CoV-2 infection, macrophages seem to play a key role in lung injury, resulting in immunological dysfunction and respiratory disease.
Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism
Authors: Ogawa Chie , Tsuchiya Ken , Maeda Kunimi
Published: February 2023

The production of erythropoietin (EPO), the main regulator of erythroid differentiation, is regulated by hypoxia-inducible factor (HIF). HIF2α seems to be the principal regulator of EPO transcription, but HIF1α and 3α also may have additional influences on erythroid maturation. HIF is also involved in the regulation of iron, an essential component in erythropoiesis. Iron is essential for the organism but is also highly toxic, so its absorption and retention are strictly controlled. HIF also induces the synthesis of proteins involved in iron regulation, thereby ensuring the availability of iron necessary for hematopoiesis. Iron is a major component of hemoglobin and is also involved in erythrocyte differentiation and proliferation and in the regulation of HIF. Renal anemia is a condition in which there is a lack of stimulation of EPO synthesis due to decreased HIF expression. HIF prolyl hydroxylase inhibitors (HIF-PHIs) stabilize HIF and thereby allow it to be potent under normoxic conditions. Therefore, unlike erythropoiesis-stimulating agents, HIF-PHI may enhance iron absorption from the intestinal tract and iron supply from reticuloendothelial macrophages and hepatocytes into the plasma, thus facilitating the availability of iron for hematopoiesis. The only HIF-PHI currently on the market worldwide is roxadustat, but in Japan, five products are available. Clinical studies to date in Japan have also shown that HIF-PHIs not only promote hematopoiesis, but also decrease hepcidin, the main regulator of iron metabolism, and increase the total iron-binding capacity (TIBC), which indicates the iron transport capacity. However, concerns about the systemic effects of HIF-PHIs have not been completely dispelled, warranting further careful monitoring.
Comprehensive Insight into Lichen Planus Immunopathogenesis
Authors: Vičić Marijana , Hlača Nika , Kaštelan Marija , Brajac Ines , Sotošek Vlatka , Prpić Massari Larisa
Published: February 2023

Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral illness is up to five times more prevalent; still, both forms equally impair the patient’s quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.
Modulation of the Circulating Extracellular Vesicles in Response to Different Exercise Regimens and Study of Their Inflammatory Effects
Authors: Maggio Serena , Canonico Barbara , Ceccaroli Paola , Polidori Emanuela , Cioccoloni Andrea , Giacomelli Luca , Ferri Marini Carlo , Annibalini Giosuè , Gervasi Marco , Benelli Piero , Fabbri Francesco , Del Coco Laura , Fanizzi Francesco Paolo , Giudetti Anna Maria , Lucertini Francesco , Guescini Michele
Published: February 2023

Exercise-released extracellular vesicles (EVs) are emerging as a novel class of exerkines that promotes systemic beneficial effects. However, slight differences in the applied exercise protocols in terms of mode, intensity and duration, as well as the need for standardized protocols for EV isolation, make the comparison of the studies in the literature extremely difficult. This work aims to investigate the EV amount and EV-associated miRNAs released in circulation in response to different physical exercise regimens. Healthy individuals were subjected to different exercise protocols: acute aerobic exercise (AAE) and training (AT), acute maximal aerobic exercise (AMAE) and altitude aerobic training (AAT). We found a tendency for total EVs to increase in the sedentary condition compared to trained participants following AAE. Moreover, the cytofluorimetric analysis showed an increase in CD81+/SGCA+/CD45− EVs in response to AAE. Although a single bout of moderate/maximal exercise did not impact the total EV number, EV-miRNA levels were affected as a result. In detail, EV-associated miR-206, miR-133b and miR-146a were upregulated following AAE, and this trend appeared intensity-dependent. Finally, THP-1 macrophage treatment with exercise-derived EVs induced an increase of the mRNAs encoding for IL-1β, IL-6 and CD163 using baseline and immediately post-exercise EVs. Still, 1 h post-exercise EVs failed to stimulate a pro-inflammatory program. In conclusion, the reported data provide a better understanding of the release of circulating EVs and their role as mediators of the inflammatory processes associated with exercise.
Finding the Needle in the Haystack: Serological and Urinary Biomarkers in Behçet’s Disease: A Systematic Review
Authors: Arbrile Marta , Radin Massimo , Medica Davide , Miraglia Paolo , Rilat Letizia , Cecchi Irene , Foddai Silvia Grazietta , Barinotti Alice , Menegatti Elisa , Roccatello Dario , Sciascia Savino
Published: February 2023

Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for diagnosing Behçet’s disease (BD) are still lacking, negatively affecting the management of these patients. To analyze the currently available literature on serological and urinary BD biomarkers investigated in the last 25 years, we performed a systematic literature review using the Population, Intervention, Comparison, and Outcomes (PICO) strategy. One hundred eleven studies met the eligibility criteria (6301 BD patients, 5163 controls). Most of them were retrospective, while five (5%) were prospective. One hundred ten studies (99%) investigated serological biomarkers and only two (2%) focused on urinary biomarkers. One hundred three studies (93%) explored the diagnostic potential of the biomolecules, whereas sixty-two (56%) tested their effect on disease activity monitoring. Most articles reported an increase in inflammatory markers and pro-oxidant molecules, with a decrease in antioxidants. Promising results have been shown by the omics sciences, offering a more holistic approach. Despite the vast number of investigated markers, existing evidence indicates a persistent gap in BD diagnostic/prognostic indices. While new steps have been taken in the direction of pathogenesis and disease monitoring, international efforts for the search of a diagnostic marker for BD are still needed.
Substituent Effects of the Nitrogen Heterocycle on Indole and Quinoline HDN Performance: A Combination of Experiments and Theoretical Study
Authors: Jiang Shujiao , Ding Sijia , Zhou Yasong , Yuan Shenghua , Geng Xinguo , Cao Zhengkai
Published: February 2023

Hydrodenitrogenation (HDN) experiments and density functional theory (DFT) calculations were combined herein to study the substituent effects of the nitrogen heterocycle on the HDN behaviors of indole and quinoline. Indole (IND), 2-methyl-indole (2-M-IND), 3-methyl-indole (3-M-IND), quinoline (QL), 2-methyl-quinoline (2-M-QL) and 3-methyl-quinoline (3-M-QL) were used as the HDN reactant on the NiMo/γ-Al2O3 catalyst. Some key elementary reactions in the HDN process of these nitrogen compounds on the Ni-Mo-S active nanocluster were calculated. The notable difference between IND and QL in the HDN is that dihydro-indole (DHI) can directly convert to O-ethyl aniline via the C–N bond cleavage, whereas tetrahydro-quinoline (THQ) can only break the C–N single bond via the full hydrogenation saturation of the aromatic ring. The reason for this is that the –NH and C=C groups of DHI can be coplanar and well adsorbed on the Ni-Mo-edge simultaneously during the C–N bond cleavage. In comparison, those of THQ cannot stably simultaneously adsorb on the Ni-Mo-edge because of the non-coplanarity. Whenever the methyl group locates on the α-C or the β-C atom of indole, the hydrogenation ability of the nitrogen heterocycle will be evidently weakened because the methyl group increases the space requirement of the sp3 carbon, and the impaction of the C=C groups on the Ni-S-edge cannot provide enough space. When the methyl groups are located on the α-C of quinoline, the self-HDN behavior of 2-M-QL is similar to quinoline, whereas the competitive HDN ability of 2-M-QL in the homologs is evidently weakened because the methyl group on the α-C hinders the contact between the N atom of 2-M-QL and the exposed metal atom of the coordinatively unsaturated active sites (CUS). When the methyl group locates on the β-C of quinoline, the C–N bond cleavage of 3-methyl-quinoline becomes more difficult because the methyl group on the β-C increases the steric hindrance of the C=C group. However, the competitive HDN ability of 3-M-QL is not evidently influenced because the methyl group on the β-C does not evidently hinder the adsorption of 3-M-QL on the active sites.
Prunus Knotted-like Genes: Genome-Wide Analysis, Transcriptional Response to Cytokinin in Micropropagation, and Rootstock Transformation
Authors: Testone Giulio , Caboni Emilia , D’Angeli Simone , Altamura Maria Maddalena , Giannino Donato
Published: February 2023

Knotted1-like homeobox (KNOX) transcription factors are involved in plant development, playing complex roles in aerial organs. As Prunus species include important fruit tree crops of Italy, an exhaustive investigation of KNOX genes was performed using genomic and RNA-seq meta-analyses. Micropropagation is an essential technology for rootstock multiplication; hence, we investigated KNOX transcriptional behavior upon increasing 6-benzylaminopurine (BA) doses and the effects on GF677 propagules. Moreover, gene function in Prunus spp. was assessed by Gisela 6 rootstock transformation using fluorescence and peach KNOX transgenes. Based on ten Prunus spp., KNOX proteins fit into I-II-M classes named after Arabidopsis. Gene number, class member distribution, and chromosome positions were maintained, and exceptions supported the diversification of Prunus from Cerasus subgenera, and that of Armeniaca from the other sections within Prunus. Cytokinin (CK) cis-elements occurred in peach and almond KNOX promoters, suggesting a BA regulatory role in GF677 shoot multiplication as confirmed by KNOX expression variation dependent on dose, time, and interaction. The tripled BA concentration exacerbated stress, altered CK perception genes, and modified KNOX transcriptions, which are proposed to concur in in vitro anomalies. Finally, Gisela 6 transformation efficiency varied (2.6–0.6%) with the genetic construct, with 35S:GFP being more stable than 35S:KNOPE1 lines, which showed leaf modification typical of KNOX overexpression.
A Cross-Species Analysis Reveals Dysthyroidism of the Ovaries as a Common Trait of Premature Ovarian Aging
Authors: Colella Marco , Cuomo Danila , Nittoli Valeria , Amoresano Angela , Porciello Alfonsina , Reale Carla , Roberto Luca , Russo Filomena , Russo Nicola Antonino , De Felice Mario , Mallardo Massimo , Ambrosino Concetta
Published: February 2023

Although the imbalance of circulating levels of Thyroid Hormones (THs) affects female fertility in vertebrates, its involvement in the promotion of Premature Ovarian Aging (POA) is debated. Therefore, altered synthesis of THs in both thyroid and ovary can be a trait of POA. We investigated the relationship between abnormal TH signaling, dysthyroidism, and POA in evolutionary distant vertebrates: from zebrafish to humans. Ovarian T3 signaling/metabolism was evaluated by measuring T3 levels, T3 responsive transcript, and protein levels along with transcripts governing T3 availability (deiodinases) and signaling (TH receptors) in distinct models of POA depending on genetic background and environmental exposures (e.g., diets, pesticides). Expression levels of well-known (Amh, Gdf9, and Inhibins) and novel (miR143/145 and Gas5) biomarkers of POA were assessed. Ovarian dysthyroidism was slightly influenced by genetics since very few differences were found between C57BL/6J and FVB/NJ females. However, diets exacerbated it in a strain-dependent manner. Similar findings were observed in zebrafish and mouse models of POA induced by developmental and long-life exposure to low-dose chlorpyrifos (CPF). Lastly, the T3 decrease in follicular fluids from women affected by diminished ovarian reserve, as well as of the transcripts modulating T3 signaling/availability in the cumulus cells, confirmed ovarian dysthyroidism as a common and evolutionary conserved trait of POA.
The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating E6/E7-HPV Oncogenes and KCNH1 Gene Expression
Authors: Díaz Lorenza , Bernadez-Vallejo Samantha V. , Vargas-Castro Rafael , Avila Euclides , Gómez-Ceja Karla A. , García-Becerra Rocío , Segovia-Mendoza Mariana , Prado-Garcia Heriberto , Lara-Sotelo Galia , Camacho Javier , Larrea Fernando , García-Quiroz Janice
Published: February 2023

Cervical cancer is the fourth most common cancer among women worldwide. The main factor associated with the onset and progression of this neoplasia is the human papillomavirus (HPV) infection. The HPV-oncogenes E6 and E7 are critical drivers of cellular transformation, promoting the expression of oncogenes such as KCNH1. The phytochemical α-mangostin (AM) is a potent antineoplastic and antiviral compound. However, its effects on HPV oncogenes and KCNH1 gene expression remain unknown. This study evaluated the effects of AM on cell proliferation, cell cycle distribution and gene expression, including its effects on tumor growth in xenografted mice. AM inhibited cell proliferation in a concentration-dependent manner, being the most sensitive cell lines those with the highest number of HPV16 copies. In addition, AM promoted G1-cell cycle arrest in CaSki cells, while led to cell death in SiHa and HeLa cells. Of interest was the finding of an AM-dependent decreased gene expression of E6, E7 and KCNH1 both in vitro and in vivo, as well as the modulation of cytokine expression, Ki-67, and tumor growth inhibition. On these bases, we suggest that AM represents a good option as an adjuvant for the treatment and prevention of cervical cancer.
Fine Mapping and Identification of SmAPRR2 Regulating Rind Color in Eggplant (Solanum melongena L.)
Authors: Fang Huarong , Wang Peng , Wang Wanhao , Peng Jiechun , Zheng Jieming , Zhu Guangwei , Zhong Chuan , Yu Wenjin
Published: February 2023

Rind color is an economically important agronomic trait in eggplant that impacts consumer preferences. In this study, bulked segregant analysis and competitive allele-specific PCR were employed to identify the candidate gene for eggplant rind color through constructing a 2794 F2 population generated from a cross between “BL01” (green pericarp) and “B1” (white pericarp). Genetic analysis of rind color revealed that a single dominant gene controls green color of eggplant peel. Pigment content measurement and cytological observations demonstrated that chlorophyll content and chloroplast number in BL01 were higher than in B1. A candidate gene (EGP19168.1) was fine-mapped to a 20.36 Kb interval on chromosome 8, which was predicted to encode the two-component response regulator-like protein Arabidopsis pseudo-response regulator2 (APRR2). Subsequently, allelic sequence analysis revealed that a SNP deletion (ACT→AT) in white-skinned eggplant led to a premature termination codon. Genotypic validation of 113 breeding lines using the Indel marker closely linked to SmAPRR2 could predict the skin color (green/white) trait with an accuracy of 92.9%. This study will be valuable for molecular marker-assisted selection in eggplant breeding and provides theoretical foundation for analyzing the formation mechanism of eggplant peel color.
The Roles of Exosomal Proteins: Classification, Function, and Applications
Authors: Li Xin-Xin , Yang Lu-Xuan , Wang Chuang , Li Hui , Shi De-Shun , Wang Jian
Published: February 2023

Exosome, a subpopulation of extracellular vesicles, plays diverse roles in various biological processes. As one of the most abundant components of exosomes, exosomal proteins have been revealed to participate in the development of many diseases, such as carcinoma, sarcoma, melanoma, neurological disorders, immune responses, cardiovascular diseases, and infection. Thus, understanding the functions and mechanisms of exosomal proteins potentially assists clinical diagnosis and targeted delivery of therapies. However, current knowledge about the function and application of exosomal proteins is still limited. In this review, we summarize the classification of exosomal proteins, and the roles of exosomal proteins in exosome biogenesis and disease development, as well as in the clinical applications.
Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML
Authors: Meddi Elisa , Savi Arianna , Moretti Federico , Mallegni Flavia , Palmieri Raffaele , Paterno Giovangiacinto , Buzzatti Elisa , Del Principe Maria Ilaria , Buccisano Francesco , Venditti Adriano , Maurillo Luca
Published: February 2023

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal post-remission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint.
Ran GTPase and Its Importance in Cellular Signaling and Malignant Phenotype
Authors: El-Tanani Mohamed , Nsairat Hamdi , Mishra Vijay , Mishra Yachana , Aljabali Alaa A. A. , Serrano-Aroca Ángel , Tambuwala Murtaza M.
Published: February 2023

Ran is a member of the Ras superfamily of proteins, which primarily regulates nucleocytoplasmic trafficking and mediates mitosis by regulating spindle formation and nuclear envelope (NE) reassembly. Therefore, Ran is an integral cell fate determinant. It has been demonstrated that aberrant Ran expression in cancer is a result of upstream dysregulation of the expression of various factors, such as osteopontin (OPN), and aberrant activation of various signaling pathways, including the extracellular-regulated kinase/mitogen-activated protein kinase (ERK/MEK) and phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) pathways. In vitro, Ran overexpression has severe effects on the cell phenotype, altering proliferation, adhesion, colony density, and invasion. Therefore, Ran overexpression has been identified in numerous types of cancer and has been shown to correlate with tumor grade and the degree of metastasis present in various cancers. The increased malignancy and invasiveness have been attributed to multiple mechanisms. Increased dependence on Ran for spindle formation and mitosis is a consequence of the upregulation of these pathways and the ensuing overexpression of Ran, which increases cellular dependence on Ran for survival. This increases the sensitivity of cells to changes in Ran concentration, with ablation being associated with aneuploidy, cell cycle arrest, and ultimately, cell death. It has also been demonstrated that Ran dysregulation influences nucleocytoplasmic transport, leading to transcription factor misallocation. Consequently, patients with tumors that overexpress Ran have been shown to have a higher malignancy rate and a shorter survival time compared to their counterparts.
Relationship between Hypoxic and Immune Pathways Activation in the Progression of Neuroinflammation: Role of HIF-1α and Th17 Cells
Authors: Arias Consuelo , Sepúlveda Paulina , Castillo Rodrigo L. , Salazar Luis A.
Published: February 2023

Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. This review propounds the relationship between the deregulation of T helper cells and hypoxia, mainly Th17 and HIF-1α molecular pathways, events that are involved in the occurrence of the neuroinflammation. The clinical expression of neuroinflammation is included in prevalent pathologies such as multiple sclerosis, Guillain–Barré syndrome, and Alzheimer’s disease, among others. In addition, therapeutic targets are analyzed in relation to the pathways that induced neuroinflammation.
Group V Chitin Deacetylases Influence the Structure and Composition of the Midgut of Beet Armyworm, Spodoptera exigua
Authors: Wu Han , Zhao Dan , Guo Xiao-Chang , Liu Zhao-Rui , Li Rui-Jun , Lu Xiu-Jun , Guo Wei
Published: February 2023

Chitin deacetylase (CDA) can accelerate the conversion of chitin to chitosan, influencing the mechanical properties and permeability of the cuticle structures and the peritrophic membrane (PM) in insects. Putative Group V CDAs SeCDA6/7/8/9 (SeCDAs) were identified and characterized from beet armyworm Spodoptera exigua larvae. The cDNAs of SeCDAs contained open reading frames of 1164 bp, 1137 bp, 1158 bp and 1152 bp, respectively. The deduced protein sequences showed that SeCDAs are synthesized as preproteins of 387, 378, 385 and 383 amino acid residues, respectively. It was revealed via spatiotemporal expression analysis that SeCDAs were more abundant in the anterior region of the midgut. The SeCDAs were down-regulated after treatment with 20-hydroxyecdysone (20E). After treatment with a juvenile hormone analog (JHA), the expression of SeCDA6 and SeCDA8 was down-regulated; in contrast, the expression of SeCDA7 and SeCDA9 was up-regulated. After silencing SeCDAV (the conserved sequences of Group V CDAs) via RNA interference (RNAi), the layer of intestinal wall cells in the midgut became more compact and more evenly distributed. The vesicles in the midgut were small and more fragmented or disappeared after SeCDAs were silenced. Additionally, the PM structure was scarce, and the chitin microfilament structure was loose and chaotic. It was indicated in all of the above results that Group V CDAs are essential for the growth and structuring of the intestinal wall cell layer in the midgut of S. exigua. Additionally, the midgut tissue and the PM structure and composition were affected by Group V CDAs.
Transfer of Galectin-3-Binding Protein via Epididymal Extracellular Vesicles Promotes Sperm Fertilizing Ability and Developmental Potential in the Domestic Cat Model
Authors: Rowlison Tricia , Comizzoli Pierre
Published: February 2023

Key proteins transferred by epididymal extracellular vesicles (EVs) to the transiting sperm cells contribute to their centrosomal maturation and developmental potential. Although not reported in sperm cells yet, galectin-3-binding protein (LGALS3BP) is known to regulate centrosomal functions in somatic cells. Using the domestic cat model, the objectives of this study were to (1) detect the presence and characterize the transfer of LGALS3BP via EVs between the epididymis and the maturing sperm cells and (2) demonstrate the impact of LGALS3BP transfer on sperm fertilizing ability and developmental potential. Testicular tissues, epididymides, EVs, and spermatozoa were isolated from adult individuals. For the first time, this protein was detected in EVs secreted by the epididymal epithelium. The percentage of spermatozoa with LGALS3BP in the centrosome region increased as cells progressively incorporated EVs during the epididymal transit. When LGALS3BP was inhibited during in vitro fertilization with mature sperm cells, less fertilized oocytes and slower first cell cycles were observed. When the protein was inhibited in epididymal EVs prior to incubation with sperm cells, poor fertilization success further demonstrated the role of EVs in the transfer of LGALS3BP to the spermatozoa. The key roles of this protein could lead to new approaches to enhance or control fertility in clinical settings.