bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Toxicity Associated with Cancer Immunotherapy and Biological Drugs
Authors: Montisci Andrea , Vietri Maria Teresa , Palmieri Vittorio , Sala Silvia , Donatelli Francesco , Napoli Claudio
Published: September 2021

Cancer immunotherapy significantly contributed to an improvement in the prognosis of cancer patients. Immunotherapy, including human epidermal growth factor receptor 2 (HER2)-targeted therapies, immune checkpoint inhibitors (ICI), and chimeric antigen receptor-modified T (CAR-T), share the characteristic to exploit the capabilities of the immune system to kill cancerous cells. Trastuzumab is a monoclonal antibody against HER2 that prevents HER2-mediated signaling; it is administered mainly in HER2-positive cancers, such as breast, colorectal, biliary tract, and non-small-cell lung cancers. Immune checkpoint inhibitors (ICI) inhibit the binding of CTLA-4 or PD-1 to PDL-1, allowing T cells to kill cancerous cells. ICI can be used in melanomas, non-small-cell lung cancer, urothelial, and head and neck cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and chimeric antigen receptor-modified T (CAR-T) cell therapy, mainly applied for B-cell lymphoma and leukemia and mantle-cell lymphoma. HER2-targeted therapies, mainly trastuzumab, are associated with left ventricular dysfunction, usually reversible and rarely life-threatening. PD/PDL-1 inhibitors can cause myocarditis, rare but potentially fulminant and associated with a high fatality rate. CAR-T therapy is associated with several cardiac toxic effects, mainly in the context of a systemic adverse effect, the cytokines release syndrome.
Colorectal Tumour Mucosa Microbiome Is Enriched in Oral Pathogens and Defines Three Subtypes That Correlate with Markers of Tumour Progression
Authors: Zwinsová Barbora , Petrov Vyacheslav A. , Hrivňáková Martina , Smatana Stanislav , Micenková Lenka , Kazdová Natálie , Popovici Vlad , Hrstka Roman , Šefr Roman , Bencsiková Beatrix , Zdražilová-Dubská Lenka , Brychtová Veronika , Nenutil Rudolf , Vídeňská Petra , Budinská Eva
Published: September 2021

Long-term dysbiosis of the gut microbiome has a significant impact on colorectal cancer (CRC) progression and explains part of the observed heterogeneity of the disease. Even though the shifts in gut microbiome in the normal-adenoma-carcinoma sequence were described, the landscape of the microbiome within CRC and its associations with clinical variables remain under-explored. We performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually normal mucosa and stool swabs of 178 patients with stage 0–IV CRC to describe the tumour microbiome and its association with clinical variables. We identified new genera associated either with CRC tumour mucosa or CRC in general. The tumour mucosa was dominated by genera belonging to oral pathogens. Based on the tumour microbiome, we stratified CRC patients into three subtypes, significantly associated with prognostic factors such as tumour grade, sidedness and TNM staging, BRAF mutation and MSI status. We found that the CRC microbiome is strongly correlated with the grade, location and stage, but these associations are dependent on the microbial environment. Our study opens new research avenues in the microbiome CRC biomarker detection of disease progression while identifying its limitations, suggesting the need for combining several sampling sites (e.g., stool and tumour swabs).
Minimally Invasive versus Open Liver Resection for Stage I/II Hepatocellular Carcinoma
Authors: Birgin Emrullah , Kaslow Sarah R. , Hetjens Svetlana , Correa-Gallego Camilo , Rahbari Nuh N.
Published: September 2021

Minimally invasive liver resection (MILR) is increasingly used as a surgical treatment for patients with hepatocellular carcinoma (HCC). However, there is no large scale data to compare the effectiveness of MILR in comparison to open liver resection (OLR). We identified patients with stage I or II HCC from the National Cancer Database using propensity score matching techniques. Overall, 1931 (66%) and 995 (34%) patients underwent OLR or MILR between 2010 and 2015. After propensity matching, 5-year OS was similar in the MILR and OLR group (51.7% vs. 52.8%, p = 0.766). MILR was associated with lower 90-day mortality (5% vs. 7%, p = 0.041) and shorter length of stay (4 days vs. 5 days, p < 0.001), but higher rates of positive margins (6% vs. 4%, p = 0.001). An operation at an academic institution was identified as an independent preventive factor for a positive resection margin (OR 0.64: 95% CI 0.43–0.97) and 90-day mortality (OR 0.61; 95% CI 0.41–0.91). MILR for HCC is associated with similar overall survival to OLR, with the benefit of improved short term postoperative outcomes. The increased rate of positive margins after MILR requires further investigation, as do the differences in perioperative outcomes between academic and nonacademic institutions.
Precision Medicine for Colorectal Cancer with Liquid Biopsy and Immunotherapy
Authors: Nagayama Satoshi , Low Siew-Kee , Kiyotani Kazuma , Nakamura Yusuke
Published: September 2021

In the field of colorectal cancer (CRC) treatment, diagnostic modalities and chemotherapy regimens have progressed remarkably in the last two decades. However, it is still difficult to identify minimal residual disease (MRD) necessary for early detection of recurrence/relapse of tumors and to select and provide appropriate drugs timely before a tumor becomes multi-drug-resistant and more aggressive. We consider the leveraging of in-depth genomic profiles of tumors as a significant breakthrough to further improve the overall prognosis of CRC patients. With the recent technological advances in methodologies and bioinformatics, the genomic profiles can be analyzed profoundly without delay by blood-based tests—‘liquid biopsies’. From a clinical point of view, a minimally-invasive liquid biopsy is thought to be a promising method and can be implemented in routine clinical settings in order to meet unmet clinical needs. In this review, we highlighted clinical usefulness of liquid biopsies in the clinical management of CRC patients, including cancer screening, detection of MRD, selection of appropriate molecular-targeted drugs, monitoring of the treatment responsiveness, and very early detection of recurrence/relapse of the disease. In addition, we addressed a possibility of adoptive T cell therapies and a future personalized immunotherapy based on tumor genome information.
Cancer Stem Cell for Tumor Therapy
Authors: Huang Binjie , Yan Xin , Li Yumin
Published: September 2021

Tumors pose a significant threat to human health. Although many methods, such as operations, chemotherapy and radiotherapy, have been proposed to eliminate tumor cells, the results are unsatisfactory. Targeting therapy has shown potential due to its specificity and efficiency. Meanwhile, it has been revealed that cancer stem cells (CSCs) play a crucial role in the genesis, development, metastasis and recurrence of tumors. Thus, it is feasible to inhibit tumors and improve prognosis via targeting CSCs. In this review, we provide a comprehensive understanding of the biological characteristics of CSCs, including mitotic pattern, metabolic phenotype, therapeutic resistance and related mechanisms. Finally, we summarize CSCs targeted strategies, including targeting CSCs surface markers, targeting CSCs related signal pathways, targeting CSC niches, targeting CSC metabolic pathways, inducing differentiation therapy and immunotherapy (tumor vaccine, CAR-T, oncolytic virus, targeting CSCs–immune cell crosstalk and immunity checkpoint inhibitor). We highlight the potential of immunity therapy and its combinational anti-CSC therapies, which are composed of different drugs working in different mechanisms.
Development of Population-Based Cancer Indicators and a Measurement of Cancer Care Continuum Using a Modified Delphi Method
Authors: Rajaguru Vasuki , Jang Jieun , Kim JaeHyun , Kwon JeoungA , Cho Oyeon , Chung SeungYeun , Ahn MiSun , Park JinHee , Won YoungJoo , Jung KyuWon , Shin Jaeyong , Chun Mison
Published: September 2021

To identify population-based cancer indicators and construct monitoring systems for the entire lifecycle of cancer patients using a modified Delphi method. A modified Delphi method was used to identify the cancer indicators and measurement by scoping review and gray literature. The final list of cancer indicators was developed by consensus of 11 multidisciplinary experts over multiple rounds and rating scored the importance of each indicator on a 10-point scale. Frequency analysis was performed to rate with median scores ≥7 and finalized the list of indicators according to the priority. Initially, 254 indicators were identified, of which 94 were considered important and feasible. After two rounds of rating by the experts and panel discussions, 26 indicators were finalized in six domains: primary prevention (n = 7), secondary prevention (n = 11), treatment (n = 2), quality of life (n = 4), survivor management (n = 1), and end-of-life care (n = 1). The Donabedian model used for examining health services and the Institute of Medicine quality of healthcare domains were applied to the measurement system. Panel experts identified cancer indicators based on priorities with a high level of consensus, providing a scrupulous foundation for community-based monitoring of cancer patients.
Molecular and Clinical Implications of Somatostatin Receptor Profile and Somatostatin Analogues Treatment in Oral Cavity Squamous Cell Carcinoma
Authors: Sanjuan-Sanjuan Alba , Alors-Perez Emilia , Sanchez-Frías Marina , Dean-Ferrer Alicia , Gahete Manuel D. , Heredero-Jung Susana , Luque Raúl M.
Published: September 2021

Oral squamous cell carcinoma (OSCC) incidence has increased by 50% over the last decade. Unfortunately, surgery and adjuvant radiotherapy and chemotherapy are still the mainstream modality of treatment, underscoring the need for alternative therapies. Somatostatin-analogues (SSA) are efficacious and safe treatments for a variety of tumors, but the presence of somatostatin-receptors (SSTs) and pharmacological effects of SSA on OSCC are poorly known. In this study, we demonstrated that SST2 and SST3 levels were significantly higher in OSCC, compared to adjacent healthy control tissues. SST2 expression was associated with less regional metastasis and a lower recurrence rate. Moreover, SST2 was elevated in OSCC and associated with histopathological good prognosis factors, such as high peritumoral inflammation, smaller depth of invasion, and expansive vs. infiltrative front of tumor invasion. Importantly, treatment with different SSA (octreotide, lanreotide, and pasireotide) significantly reduced cell-proliferation in OSCC primary cell cultures. Altogether, this study demonstrated that SST2 is overexpressed in OSCC vs. healthy tissues and could represent a novel prognostic biomarker, since its expression is associated with tumors that show better prognostic factors and less recurrent rate. Moreover, our data unveil clear antitumoral effects of SSAs on OSCC, opening new avenues to explore their potential as targeting therapy to OSCC.
Proteomic Landscape of Prostate Cancer: The View Provided by Quantitative Proteomics, Integrative Analyses, and Protein Interactomes
Authors: Sadeesh Nithin , Scaravilli Mauro , Latonen Leena
Published: September 2021

Prostate cancer is the second most frequent cancer of men worldwide. While the genetic landscapes and heterogeneity of prostate cancer are relatively well-known already, methodological developments now allow for studying basic and dynamic proteomes on a large scale and in a quantitative fashion. This aids in revealing the functional output of cancer genomes. It has become evident that not all aberrations at the genetic and transcriptional level are translated to the proteome. In addition, the proteomic level contains heterogeneity, which increases as the cancer progresses from primary prostate cancer (PCa) to metastatic and castration-resistant prostate cancer (CRPC). While multiple aspects of prostate adenocarcinoma proteomes have been studied, less is known about proteomes of neuroendocrine prostate cancer (NEPC). In this review, we summarize recent developments in prostate cancer proteomics, concentrating on the proteomic landscapes of clinical prostate cancer, cell line and mouse model proteomes interrogating prostate cancer-relevant signaling and alterations, and key prostate cancer regulator interactomes, such as those of the androgen receptor (AR). Compared to genomic and transcriptomic analyses, the view provided by proteomics brings forward changes in prostate cancer metabolism, post-transcriptional RNA regulation, and post-translational protein regulatory pathways, requiring the full attention of studies in the future.
CuO-In2O3 Catalysts Supported on Halloysite Nanotubes for CO2 Hydrogenation to Dimethyl Ether
Authors: Pechenkin Alexey , Potemkin Dmitry , Rubtsova Maria , Snytnikov Pavel , Plyusnin Pavel , Glotov Aleksandr
Published: September 2021

Hydrogenation of CO2 relative to valuable chemical compounds such as methanol or dimethyl ether (DME) is an attractive route for reducing CO2 emissions in the atmosphere. In the present work, the hydrogenation of CO2 into DME over CuO-In2O3, supported on halloysite nanotubes (HNT) was investigated in the temperature range 200–300 °C at 40 atm. HNT appears to be novel promising support for bifunctional catalysts due to its thermal stability and the presence of acidic sites on its surface. CuO-In2O3/HNT catalysts demonstrate higher CO2 conversion and DME selectivity compared to non-indium CuO/HNT catalysts. The catalysts were investigated by N2 adsorption, X-ray diffraction, hydrogen-temperature programmed reduction and transition electron microscopy. The acid sites were analyzed by temperature programmed desorption of ammonia. It was shown that CuO/HNT was unstable under reaction conditions in contrast to CuO-In2O3/HNT. The best CuO-In2O3/HNT catalyst provided CO2 conversion of 7.6% with 65% DME selectivity under P = 40 atm, T = 250 °C, gas hour space velocity 12,000 h−1 and H2:CO2 = 3:1.
Reply to Inoue et al. Comment on “Weber et al. Mayenite-Based Electride C12A7e−: A Reactivity and Stability Study. Catalysts 2021, 11, 334”
Authors: Weber Sebastian , Schunk Stephan A.
Published: September 2021

With gratitude, we would like to thank Yasunori Inoue, Masaaki Kitano and Hideo Hosono for their comments on our recently published article and express our appreciation for the critical discussion of our results [...]
Impact of Doping and Additive Applications on Photocatalyst Textural Properties in Removing Organic Pollutants: A Review
Authors: Mohtar Safia Syazana , Aziz Farhana , Ismail Ahmad Fauzi , Sambudi Nonni Soraya , Abdullah Hamidah , Rosli Ahmad Nazrul , Ohtani Bunsho
Published: September 2021

The effect of ion doping and the incorporation of additives on photocatalysts’ textural properties have been reviewed. Generally, it can be summarised that ion doping and additives have beneficial effects on photocatalytic efficiency and not all have an increase in the surface area. The excessive amount of dopants and additives will produce larger aggregated particles and also cover the mesoporous structures, thereby increasing the pore size (Pd) and pore volume (Pv). An excessive amount of dopants also leads to visible light shielding effects, thus influence photocatalytic performance. Ion doping also shows some increment in the surface areas, but it has been identified that synergistic effects of the surface area, porosity, and dopant amount contribute to the photocatalytic performance. It is therefore important to understand the effect of doping and the application of additives on the textural properties of photocatalysts, thus, their performance. This review will provide an insight into the development of photocatalyst with better performance for wastewater treatment applications.
Remediation of Diethyl Phthalate in Aqueous Effluents with TiO2-Supported Rh0 Nanoparticles as Multicatalytic Materials
Authors: Denicourt-Nowicki Audrey , Pélisson Carl-Hugo , Soutrel Isabelle , Favier Lidia , Roucoux Alain
Published: September 2021

An innovative “domino” process, based on an arene hydrogenation followed by a photocatalytic step, was designed for the remediation of endocrine disrupting compounds, in highly concentrated aqueous effluents. The novelty relies on the use of TiO2-supported zerovalent Rh nanoparticles as multicatalytic materials (MCMs) for this two-step treatment, applied on diethyl phthalate, which is a model aromatic pollutant frequently present in aquatic environments. This nanocomposite advanced material, which was easily prepared by a green, wet impregnation methodology, proved to be active in the successive reactions, the reduction in the aromatic ring, and the photodegradation step. This sustainable approach offers promising alternatives in the case of photoresistive compounds.
Biostimulants for the Regulation of Reactive Oxygen Species Metabolism in Plants under Abiotic Stress
Authors: Hasanuzzaman Mirza , Parvin Khursheda , Bardhan Kirti , Nahar Kamrun , Anee Taufika Islam , Masud Abdul Awal Chowdhury , Fotopoulos Vasileios
Published: September 2021

Global food security for a growing population with finite resources is often challenged by multiple, simultaneously occurring on-farm abiotic stresses (i.e., drought, salinity, low and high temperature, waterlogging, metal toxicity, etc.) due to climatic uncertainties and variability. Breeding for multiple stress tolerance is a long-term solution, though developing multiple-stress-tolerant crop varieties is still a challenge. Generation of reactive oxygen species in plant cells is a common response under diverse multiple abiotic stresses which play dual role of signaling molecules or damaging agents depending on concentration. Thus, a delicate balance of reactive oxygen species generation under stress may improve crop health, which depends on the natural antioxidant defense system of the plants. Biostimulants represent a promising type of environment-friendly formulation based on natural products that are frequently used exogenously to enhance abiotic stress tolerance. In this review, we illustrate the potential of diverse biostimulants on the activity of the antioxidant defense system of major crop plants under stress conditions and their other roles in the management of abiotic stresses. Biostimulants have the potential to overcome oxidative stress, though their wider applicability is tightly regulated by dose, crop growth stage, variety and type of biostimulants. However, these limitations can be overcome with the understanding of biostimulants’ interaction with ROS signaling and the antioxidant defense system of the plants.
Recent Advances in Cardiac Tissue Engineering for the Management of Myocardium Infarction
Authors: Sharma Vineeta , Dash Sanat Kumar , Govarthanan Kavitha , Gahtori Rekha , Negi Nidhi , Barani Mahmood , Tomar Richa , Chakraborty Sudip , Mathapati Santosh , Bishi Dillip Kumar , Negi Poonam , Dua Kamal , Singh Sachin Kumar , Gundamaraju Rohit , Dey Abhijit , Ruokolainen Janne , Thakur Vijay Kumar , Kesari Kavindra Kumar , Jha Niraj Kumar , Gupta Piyush Kumar , Ojha Shreesh
Published: September 2021

Myocardium Infarction (MI) is one of the foremost cardiovascular diseases (CVDs) causing death worldwide, and its case numbers are expected to continuously increase in the coming years. Pharmacological interventions have not been at the forefront in ameliorating MI-related morbidity and mortality. Stem cell-based tissue engineering approaches have been extensively explored for their regenerative potential in the infarcted myocardium. Recent studies on microfluidic devices employing stem cells under laboratory set-up have revealed meticulous events pertaining to the pathophysiology of MI occurring at the infarcted site. This discovery also underpins the appropriate conditions in the niche for differentiating stem cells into mature cardiomyocyte-like cells and leads to engineering of the scaffold via mimicking of native cardiac physiological conditions. However, the mode of stem cell-loaded engineered scaffolds delivered to the site of infarction is still a challenging mission, and yet to be translated to the clinical setting. In this review, we have elucidated the various strategies developed using a hydrogel-based system both as encapsulated stem cells and as biocompatible patches loaded with cells and applied at the site of infarction.
Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA
Authors: Piano Mortari Eva , Russo Cristina , Vinci Maria Rosaria , Terreri Sara , Fernandez Salinas Ane , Piccioni Livia , Alteri Claudia , Colagrossi Luna , Coltella Luana , Ranno Stefania , Linardos Giulia , Agosta Marilena , Albano Christian , Agrati Chiara , Castilletti Concetta , Meschi Silvia , Romania Paolo , Roscilli Giuseppe , Pavoni Emiliano , Camisa Vincenzo , Santoro Annapaola , Brugaletta Rita , Magnavita Nicola , Ruggiero Alessandra , Cotugno Nicola , Amodio Donato , Ciofi Degli Atti Marta Luisa , Giorgio Daniela , Russo Nicoletta , Salvatori Guglielmo , Corsetti Tiziana , Locatelli Franco , Perno Carlo Federico , Zaffina Salvatore , Carsetti Rita
Published: September 2021

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.
Sterol Glucosyltransferases Tailor Polysaccharide Accumulation in Arabidopsis Seed Coat Epidermal Cells
Authors: Berger Adeline , Ralet Marie-Christine , Akary Elodie , Sallé Christine , Grandjean Olivier , Debeaujon Isabelle , North Helen M.
Published: September 2021

The conjugation of sterols with a Glc moiety is catalyzed by sterol glucosyltransferases (SGTs). A portion of the resulting steryl glucosides (SG) are then esterified with a long-chain fatty acid to form acyl-SG (ASG). SG and ASG are prevalent components of plant cellular membranes and influence their organization and functional properties. Mutant analysis had previously inferred that two Arabidopsis SGTs, UGT80A2 and UGT80B1/TT15, could have specialized roles in the production of SG in seeds, despite an overlap in their enzymatic activity. Here, we establish new roles for both enzymes in the accumulation of polysaccharides in seed coat epidermal cells (SCEs). The rhamnogalacturonan-I (RG-I) content of the inner layer of seed mucilage was higher in ugt80A2, whereas RG-I accumulation was lower in mutants of UGT80B1, with double mutant phenotypes indicating that UGT80A2 acts independently from UGT80B1. In contrast, an additive phenotype was observed in double mutants for increased galactoglucomannan (GGM) content. Double mutants also exhibited increased polymer density within the inner mucilage layer. In contrast, cell wall defects were only observed in mutants defective for UGT80B1, while more mucilage cellulose was only observed when UGT80A2 was mutated. The generation of a range of phenotypic effects, simultaneously within a single cell type, demonstrates that the adjustment of the SG and ASG composition of cellular membranes by UGT80A2 and UGT80B1 tailors polysaccharide accumulation in Arabidopsis seeds.
miR-21-3p/IL-22 Axes Are Major Drivers of Psoriasis Pathogenesis by Modulating Keratinocytes Proliferation-Survival Balance and Inflammatory Response
Authors: Abdallah Florence , Henriet Elodie , Suet Amandine , Arar Ali , Clemençon Rudy , Malinge Jean-Marc , Lecellier Gaël , Baril Patrick , Pichon Chantal
Published: September 2021

Psoriasis is a chronic inflammatory skin disease that is mediated by complex crosstalk between immune cells and keratinocytes (KCs). Emerging studies have showed a specific psoriatic microRNAs signature, in which miR-21 is one of the most upregulated and dynamic miRNAs. In this study, we focused our investigations on the passenger miR-21-3p strand, which is poorly studied in skin and in psoriasis pathogenesis. Here, we showed the upregulation of miR-21-3p in an IMQ-induced psoriasiform mouse model. This upregulation was correlated with IL-22 expression and functionality, both in vitro and in vivo, and it occurred via STAT3 and NF-κB signaling. We identified a network of differentially expressed genes involved in abnormal proliferation control and immune regulatory genes implicated in the molecular pathogenesis of psoriasis in response to miR-21-3p overexpression in KCs. These results were confirmed by functional assays that validated the proliferative potential of miR-21-3p. All these findings highlight the importance of miR-21-3p, an underestimated miRNA, in psoriasis and provide novel molecular targets for therapeutic purposes.
Intermittent High Glucose Elevates Nuclear Localization of EZH2 to Cause H3K27me3-Dependent Repression of KLF2 Leading to Endothelial Inflammation
Authors: Thakar Sumukh , Katakia Yash T , Ramakrishnan Shyam Kumar , Pandya Thakkar Niyati , Majumder Syamantak
Published: September 2021

Epigenetic mechanisms have emerged as one of the key pathways promoting diabetes-associated complications. Herein, we explored the role of enhancer of zeste homolog 2 (EZH2) and its product histone 3 lysine 27 trimethylation (H3K27me3) in high glucose-mediated endothelial inflammation. To examine this, we treated cultured primary endothelial cells (EC) with different treatment conditions—namely, constant or intermittent or transient high glucose. Intermittent high glucose maximally induced endothelial inflammation by upregulating transcript and/or protein-level expression of ICAM1 and P-selectin and downregulating eNOS, KLF2, and KLF4 protein levels. We next investigated the underlining epigenetic mechanisms responsible for intermittent hyperglycemia-dependent endothelial inflammation. Compared with other high glucose treatment groups, intermittent high glucose-exposed EC exhibited an increased level of H3K27me3 caused by reduction in EZH2 threonine 367 phosphorylation and nuclear retention of EZH2. Intermittent high glucose also promoted polycomb repressive complex-2 (PRC2) assembly and EZH2′s recruitment to histone H3. Abrupt enrichment of H3K27me3 on KLF2 and KLF4 gene promoters caused repression of these genes, further supporting endothelial inflammation. In contrast, reducing H3K27me3 through small molecule and/or siRNA-mediated inhibition of EZH2 rescued KLF2 level and inhibited endothelial inflammation in intermittent high glucose-challenged cultured EC and isolated rat aorta. These findings indicate that abrupt chromatin modifications cause high glucose-dependent inflammatory switch of EC.
Arginine Regulates TOR Signaling Pathway through SLC38A9 in Abalone Haliotis discus hannai
Authors: Liu Yue , Yu Haixia , Guo Yanlin , Huang Dong , Liu Jiahuan , Pan Mingzhu , Wang Liu , Zhang Wenbing , Mai Kangsen
Published: September 2021

Arginine plays an important role in the regulation of the target of the rapamycin (TOR) signaling pathway, and Solute Carrier Family 38 Member 9 (SLC38A9) was identified to participate in the amino acid-dependent activation of TOR in humans. However, the regulations of arginine on the TOR signaling pathway in abalone are still unclear. In this study, slc38a9 of abalone was cloned, and the slc38a9 was knocked down and overexpressed to explore its function in the regulation of the TOR signaling pathway. The results showed that knockdown of slc38a9 decreased the expression of tor, ribosomal s6 protein kinase (s6k) and eukaryotic translation initiation factor 4e (eif4e) and inhibited the activation of the TOR signaling pathway by arginine. Overexpression of slc38a9 up-regulated the expression of TOR-related genes. In addition, hemocytes of abalone were treated with 0, 0.2, 0.5, 1, 2 and 4 mmol/L of arginine, and abalones were fed diets with 1.17%, 1.68% and 3.43% of arginine, respectively, for 120 days. Supplementation of arginine (0.5–4 mmol/L) increased the expressions of slc38a9, tor, s6k and eif4e in hemocytes, and abalone fed with 1.68% of dietary arginine showed higher mRNA levels of slc38a9, tor, s6k and eif4e and phosphorylation levels of TOR, S6 and 4E-BP. In conclusion, the TOR signaling pathway of abalone can be regulated by arginine, and SLC38A9 plays an essential role in this regulation.
Treatment with Autophagy Inducer Trehalose Alleviates Memory and Behavioral Impairments and Neuroinflammatory Brain Processes in db/db Mice
Authors: Korolenko Tatiana , Dubrovina Nina , Ovsyukova Marina , Bgatova Nataliya , Tenditnik Michael , Pupyshev Alexander , Akopyan Anna , Goncharova Natalya , Lin Chih-Li , Zavjalov Evgeny , Tikhonova Maria , Amstislavskaya Tamara
Published: September 2021

Autophagy attenuation has been found in neurodegenerative diseases, aging, diabetes mellitus, and atherosclerosis. In experimental models of neurodegenerative diseases, the correction of autophagy in the brain reverses neuronal and behavioral deficits and hence seems to be a promising therapy for neuropathologies. Our aim was to study the effect of an autophagy inducer, trehalose, on brain autophagy and behavior in a genetic model of diabetes with signs of neuronal damage (db/db mice). A 2% trehalose solution was administered as drinking water during 24 days of the experiment. Expressions of markers of autophagy (LC3-II), neuroinflammation (IBA1), redox state (NOS), and neuronal density (NeuN) in the brain were assessed by immunohistochemical analysis. For behavioral phenotyping, the open field, elevated plus-maze, tail suspension, pre-pulse inhibition, and passive avoidance tests were used. Trehalose caused a slight reduction in increased blood glucose concentration, considerable autophagy activation, and a decrease in the neuroinflammatory response in the brain along with improvements of exploration, locomotor activity, anxiety, depressive-like behavior, and fear learning and memory in db/db mice. Trehalose exerted some beneficial peripheral and systemic effects and partially reversed behavioral alterations in db/db mice. Thus, trehalose as an inducer of mTOR-independent autophagy is effective at alleviating neuronal and behavioral disturbances accompanying experimental diabetes.
Cell Transdifferentiation and Reprogramming in Disease Modeling: Insights into the Neuronal and Cardiac Disease Models and Current Translational Strategies
Authors: Kalra Rajkumar Singh , Dhanjal Jaspreet Kaur , Das Mriganko , Singh Birbal , Naithani Rajesh
Published: September 2021

Cell transdifferentiation and reprogramming approaches in recent times have enabled the manipulation of cell fate by enrolling exogenous/artificial controls. The chemical/small molecule and regulatory components of transcription machinery serve as potential tools to execute cell transdifferentiation and have thereby uncovered new avenues for disease modeling and drug discovery. At the advanced stage, one can believe these methods can pave the way to develop efficient and sensitive gene therapy and regenerative medicine approaches. As we are beginning to learn about the utility of cell transdifferentiation and reprogramming, speculations about its applications in translational therapeutics are being largely anticipated. Although clinicians and researchers are endeavoring to scale these processes, we lack a comprehensive understanding of their mechanism(s), and the promises these offer for targeted and personalized therapeutics are scarce. In the present report, we endeavored to provide a detailed review of the original concept, methods and modalities enrolled in the field of cellular transdifferentiation and reprogramming. A special focus is given to the neuronal and cardiac systems/diseases towards scaling their utility in disease modeling and drug discovery.
Influence of Confinement Due to COVID-19 on Physical Activity and Mediterranean Diet Adherence and Its Relationship with Self-Esteem in Pre-Adolescent Students
Authors: Villodres Gracia Cristina , García-Pérez Laura , Corpas Juan Miguel , Muros José Joaquín
Published: September 2021

Regular physical activity and good adherence to the Mediterranean diet are important for improving physical and mental health. Confinement due to the COVID-19 pandemic has led to a lack of exercise and poor nutrition. Preadolescent mental health, specifically regarding self-esteem, may have been affected. This is particularly relevant between the ages of 10 and 14. The influence of total confinement due to COVID-19 on physical activity and Mediterranean diet adherence, and its relationship with self-esteem was studied in third-year primary school students and first-year secondary school students in the provinces of Granada and Malaga, Spain. Validated questionnaires were administered to evaluate physical activity (PAQ-C), Mediterranean diet adherence (KIDMED) and self-esteem (Rosenberg Scale). In the same way, the FAS III test was used to evaluate socioeconomic status and an ad-hoc questionnaire was developed to collect sociodemographic data and evaluate screen time. Data were analyzed using IBM SPSS 25.0 statistical software. During the period of total confinement, statistically significant differences were found between examined variables, according to sex, school year, school type, socioeconomic status and whether or not the participant had contracted COVID-19. These data were compared with those collected during a previous time period. Those with a low socioeconomic status and girls were most affected.
Anthropometric Phenotype of Patients with PMM2-CDG
Authors: Lipiński Patryk , Różdżyńska-Świątkowska Agnieszka , Bogdańska Anna , Tylki-Szymańska Anna
Published: September 2021

Background: Growth failure is commonly reported in children with PMM2-CDG. The aim of the study was to delineate the longitudinal anthropometric phenotype of patients with PMM2-CDG and attempt to find some correlations between the genotype and anthropometric phenotype. Materials and methods: Retrospective chart review of PMM2-CDG patients’ medical records was performed regarding the anthropometric measurements (head circumference, body length/height, body weight, body mass index) and PMM2 variants. Results: A negative tendency of growth evolution was observed. Patients found to be heterozygous for R141H grew slower than other patients. Body weight was correlated with body height. A negative tendency of the growth rate of head circumference was observed. Patients found to be heterozygous for R141H experienced slower growth than other patients. Conclusions: Long-term observational studies are essential to characterize the anthropometric phenotype. The body growth failure, as well as head circumference growth failure, were more severe in patients found to be heterozygous for R141H.
Management and Outcome of Traumatic Intracerebral Hemorrhage in 79 Infants and Children from a Single Level 1 Trauma Center
Authors: Binder Harald , Majdan Marek , Leitgeb Johannes , Payr Stephan , Breuer Robert , Hajdu Stefan , Tiefenboeck Thomas M.
Published: September 2021

Objective: Traumatic brain injury is a leading form of pediatric trauma and a frequent cause of mortality and acquired neurological impairment in children. The aim of this study was to present the severity and outcomes of traumatic intracerebral bleeding in children and adolescence. Methods: Seventy-nine infants and children with intracerebral bleedings were treated between 1992 and 2020 at a single level 1 trauma center. Data regarding accident, treatment and outcomes were collected retrospectively. The Glasgow Outcome Scale was used to classify the outcome at hospital discharge and at follow-up visits. CT scans of the brain were classified according to the Rotterdam score. Results: In total, 41 (52%) patients with intracerebral bleedings were treated surgically, and 38 (48%) patients were treated conservatively; in 15% of the included patients, delayed surgery was necessary. Patients presenting multiple trauma (p < 0.04), higher ISS (p < 0.01), poor initial neurological status (p < 0.001) and a higher Rotterdamscore (p = 0.038) were significantly more often treated surgically. Eighty-three percent of patients were able to leave the hospital, and out of these patients, about 60% showed good recovery at the latest follow-up visit. Overall, 11 patients (14%) died. Conclusion: The findings in this study verified intracerebral bleeding as a rare but serious condition. Patients presenting with multiple traumas, higher initial ISS, poor initial neurological status and a higher Rotterdamscore were more likely treated by surgery. Trial registration: (researchregistry 2686).
Low Electron Temperature Plasma Diagnosis: Revisiting Langmuir Electrostatic Probes
Authors: Regodón Guillermo Fernando , Díaz-Cabrera Juan Manuel , Fernández Palop José Ignacio , Ballesteros Jerónimo
Published: September 2021

This article describes a method of measurement of the current-to-probe voltage characteristic curve of a Langmuir electrostatic probe immersed in a plasma characterized by a low electron temperature that is only one order of magnitude higher than room temperature. These plasmas are widely used in industrial processes related to surface technology, polymers, cleaning, nanostructures, etc. The measurement method complies with the strict requirements to perform representative plasma diagnosis, particularly in the ion saturation zone when the probe is polarized much more negatively that the potential of the plasma bulk surrounding the probe and allows to diagnose the plasma very quickly and locally, making it possible to better monitor and control the plasma discharge uniformity and time drift. The requirements for the Langmuir probe design, the data acquisition and data treatment are thoroughly explained and their influence on the measurement method is also described. Subsequently, the article describes different diagnostic methods of the magnitudes that characterize the plasma, based on theoretical models of that characteristic curve. Each of these methods is applied to different zones of the measured characteristic curve, the obtained results being quite similar, which guarantees the quality of the measurements. The advantages and disadvantages of each method are discussed. A series of measurements of the plasma density for different plasma conditions shows that the method is sensitive enough that the temperature of the ions needs to be taken into account in the data processing. Finally, a Virtual Instrument is included in the LabView environment that performs the diagnosis process with sufficient speed and precision, which allows the scientist to control the parameters that characterize the plasma to increase the quality and performance of the industrial processes in which the plasma diagnosis is to be used. The Virtual Instrument can be downloaded for free from a link that is included, in order to be easily adapted to the usual devices in a plasma laboratory.
P System–Based Clustering Methods Using NoSQL Databases
Authors: Lehotay-Kéry Péter , Tarczali Tamás , Kiss Attila
Published: September 2021

Models of computation are fundamental notions in computer science; consequently, they have been the subject of countless research papers, with numerous novel models proposed even in recent years. Amongst a multitude of different approaches, many of these methods draw inspiration from the biological processes observed in nature. P systems, or membrane systems, make an analogy between the communication in computing and the flow of information that can be perceived in living organisms. These systems serve as a basis for various concepts, ranging from the fields of computational economics and robotics to the techniques of data clustering. In this paper, such utilization of these systems—membrane system–based clustering—is taken into focus. Considering the growing number of data stored worldwide, more and more data have to be handled by clustering algorithms too. To solve this issue, bringing these methods closer to the data, their main element provides several benefits. Database systems equip their users with, for instance, well-integrated security features and more direct control over the data itself. Our goal is if the type of the database management system is given, e.g., NoSQL, but the corporation or the research team can choose which specific database management system is used, then we give a perspective, how the algorithms written like this behave in such an environment, so that, based on this, a more substantiated decision can be made, meaning which database management system should be connected to the system. For this purpose, we discover the possibilities of a clustering algorithm based on P systems when used alongside NoSQL database systems, that are designed to manage big data. Variants over two competing databases, MongoDB and Redis, are evaluated and compared to identify the advantages and limitations of using such a solution in these systems.
Novel LaAOx/g-C3N4 (A = V, Fe, Co) Heterojunctions with Enhanced Photocatalytic Degradation of Norfloxacin under Visible Light
Authors: Jiang Jiwen , Li Yonghua
Published: September 2021

In this study, novel photocatalysts LaAOx/g-C3N4 (A = V, Fe, Co) were prepared by the hydrothermal method, through which LaAOx and g-C3N4 were mixed and ultrasonically oscillated to gain heterojunction catalysts. All the samples were characterized by XRD, SEM, FT-IR, XPS, DRS, and PL to ensure the successful integration of LaAOx with g-C3N4. The obtained results showed that LaAOx/g-C3N4 (A = V, Fe, Co) could effectually improve the separation efficiency of photogenerated carriers during the photodegradation process, thus improving the photodegradation efficiency, while among them, LaFeO3/g-C3N4 showed the best photocatalytic performance and degradation of norfloxacin under visible light, reaching up to 95% in 180 min, which was 9.32 times higher than pristine g-C3N4. From the discussed results above, the possible mechanism of the photodegradation process was put forward. This study supplies a promising method to gain g-C3N4-based photocatalysts for antibiotics removal.
Mitogenomes of Three Satyrid Butterfly Species (Nymphalidae: Lepidoptera) and Reconstructed Phylogeny of Satyrinae
Authors: Dan Zhicuo , Duan Lei , Chen Zhenning , Guan Delong , Xu Shengquan
Published: September 2021

Satyrinae is a 3000-species butterfly subfamily of Nymphalidae. The higher-level classification of this family is still controversial. In this research, we sequenced the complete mitogenomes of three satyrid butterfly species, Hipparchia autonoe, Paroeneis palaearctica, and Oeneis buddha, and studied the phylogeny of Satyrinae with all known complete mitogenomes. The results showed that the lengths of the three satyrid butterfly mitogenomes are 15,435 bp (H. Autonoe), 15,942 bp (P. palaearctica), and 15,259 bp (O. buddha). Gene content and arrangement of newly sequenced mitogenomes are highly conserved and are typical of Lepidoptera. These three mitogenomes were found to have a typical set of 37 genes and an A + T-rich region. The tRNA genes in these three mitogenomes showed a typical clover leaf structure, but the stem of tRNASer (AGN) was lacking dihydroacridine. In these three species, the lengths of the A + T-rich regions were different, which led to differences in mitochondrial genome sizes. The characterizations of the three mitogenomes enrich our knowledge on the Lepidopteran mitogenome and provide us genetic information to reconstruct the phylogenetic tree. Finally, the phylogenetic results confirmed the position of the genus Davidina in the subfamily Satyrini, had a closer phylogenetic relationship with Oeneis, and the phylogenetic analysis supported the formation of Oeneis buddha as an independent taxon in Oeneis.
The LiverTox Paradox-Gaps between Promised Data and Reality Check
Authors: Teschke Rolf , Danan Gaby
Published: September 2021

The LiverTox database compiles cases of idiosyncratic drug-induced liver injury (iDILI) with the promised aims to help identify hepatotoxicants and provide evidence-based information on iDILI. Weaknesses of this approach include case selection merely based on published case number and not on a strong causality assessment method such as the Roussel Uclaf Causality Assessment Method (RUCAM). The aim of this analysis was to find out whether the promised aims have been achieved by comparison of current iDILI case data with those promised in 2012 in LiverTox. First, the LiverTox criteria of likelihood categories applied to iDILI cases were analyzed regarding robustness. Second, the quality was analyzed in LiverTox cases caused by 46 selected drugs implicated in iDILI. LiverTox included iDILI cases of insufficient quality because most promised details were not fulfilled: (1) Standard liver injury definition; (2) incomplete narratives or inaccurate for alternative causes; and (3) not a single case was assessed for causality with RUCAM, as promised. Instead, causality was arbitrarily judged on the iDILI case number presented in published reports with the same drug. All of these issues characterize the paradox of LiverTox, requiring changes in the method to improve data quality and database reliability. In conclusion, establishing LiverTox is recognized as a valuable effort, but the paradox due to weaknesses between promised data quality and actual data must be settled by substantial improvements, including, for instance, clear definition and identification of iDILI cases after evaluation with RUCAM to establish a robust causality grading.
Evaluation of the New Beckmann Coulter Analyzer DxH 900 Compared to Sysmex XN20: Analytical Performance and Flagging Efficiency
Authors: Serrando Querol Maite , Nieto-Moragas Javier , Marull Arnall Anna , Figueras Meritxell Deulofeu , Jiménez-Romero Orlando
Published: September 2021

Efficiency and accuracy in automated hematology analyzers are very important for clinical laboratories. The purpose was to evaluate the flags and results reported by the newest Beckman Coulter analyzer DxH 900 compared to the Sysmex XN20 system. Samples were analyzed on the XN20 (Sysmex, Kobe, Japan) and on the Beckman Coulter DxH 900 (Beckman Coulter, Miami, Florida, USA). Slide reviews were performed microscopically. Morphologic criteria were used to identify abnormal cells as recommended by International Consensus Group for Hematology (ICSH): blasts, immature granulocytes (IG%), abnormal lymphocytes (ALs) and plasma cells. Results: there was a strong correlation between the analyzers in almost all clinical parameters tested. Both DxH 900 and XN20 showed an excellent degree of association for the leukocyte differential compared to the reference method (manual microscopy). When it comes to IG%, XN20 showed a positive bias for higher results. Related to platelets, there are no differences between the two methods for PLT count. For mean platelet volume (MPV), DxH 900 provided 100% results of the samples analyzed while XN20 while in the XN20 analyzer, 16% of the results were missing. From our results we came to the conclusion that both analyzers, DxH 900 and XN20 were clinically accurate and efficient. Abnormal Lymphocyte detection highlighted the differences between the two technologies as only minimal agreement was obtained. DxH 900 demonstrated higher sensitivity in detecting IG with good correlation with microscopic review. The DxH 900 for platelet clumps identification provides an excellent flag (PLT Clumps) with the highest sensitivity observed in our evaluation.