bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomics as an Important Tool for Determining the Mechanisms of Human Skeletal Muscle Deconditioning
Authors: Alldritt Isabelle , Greenhaff Paul L. , Wilkinson Daniel J.
Published: December 2021

Muscle deconditioning impairs both locomotor function and metabolic health, and is associated with reduced quality life and increased mortality rates. Despite an appreciation of the existence of phenomena such as muscle anabolic resistance, mitophagy, and insulin resistance with age and disease in humans, little is known about the mechanisms responsible for these negative traits. With the complexities surrounding these unknowns and the lack of progress to date in development of effective interventions, there is a need for alternative approaches. Metabolomics is the study of the full array of metabolites within cells or tissues, which collectively constitute the metabolome. As metabolomics allows for the assessment of the cellular metabolic state in response to physiological stimuli, any chronic change in the metabolome is likely to reflect adaptation in the physiological phenotype of an organism. This, therefore, provides a holistic and unbiased approach that could be applied to potentially uncover important novel facets in the pathophysiology of muscle decline in ageing and disease, as well as identifying prognostic markers of those at risk of decline. This review will aim to highlight the current knowledge and potential impact of metabolomics in the study of muscle mass loss and deconditioning in humans and will highlight key areas for future research.
A Novel Nano-Antimicrobial Polymer Engineered with Chitosan Nanoparticles and Bioactive Peptides as Promising Food Biopreservative Effective against Foodborne Pathogen E. coli O157-Caused Epithelial Barrier Dysfunction and Inflammatory Responses
Authors: Kuang Ming , Yu Haitao , Qiao Shiyan , Huang Tao , Zhang Jiaqi , Sun Mingchao , Shi Xiumei , Chen Han
Published: December 2021

For food quality and safety issues, the emergence of foodborne pathogenic bacteria has further accelerated the spread of antibiotic residues and drug resistance genes. To alleviate the harm caused by bacterial infections, it is necessary to seek novel antimicrobial agents as biopreservatives to prevent microbial spoilage. Nanoantimicrobials have been widely used in the direct treatment of bacterial infections. CNMs, formed by chitosan nanoparticles and peptides, are promising antibiotic alternatives for use as excellent new antibacterial drugs against pathogenic bacteria. Herein, the current study evaluated the function of CNMs in the protection of foodborne pathogen Escherichia coli (E. coli) O157 infection using an intestinal epithelial cell model. Antibacterial activity assays indicated that CNMs exerted excellent bactericidal activity against E. coli O157. Assessment of the cytotoxicity risks toward cells demonstrated that 0.0125–0.02% of CNMs did not cause toxicity, but 0.4% of CNMs caused cytotoxicity. Additionally, CNMs did not induced genotoxicity either. CNMs protected against E. coli O157-induced barrier dysfunction by increasing transepithelial electrical resistance, decreasing lactate dehydrogenase and promoting the protein expression of occludin. CNMs were further found to ameliorate inflammation via modulation of tumor factor α, toll-like receptor 4 and nuclear factor κB (NF-κB) expression via inhibition of mitogen-activated protein kinase and NF-κB activation and improved antioxidant activity. Taken together, CNMs could protect the host against E. coli O157-induced intestinal barrier damage and inflammation, showing that CNMs have great advantages and potential application as novel antimicrobial polymers in the food industry as food biopreservatives, bringing new hope for the treatment of bacterial infections.
Screening of Self-Assembling of Collagen IV Fragments into Stable Structures Potentially Useful in Regenerative Medicine
Authors: Kolasa Marcin , Galita Grzegorz , Majsterek Ireneusz , Kucharska Ewa , Czerczak Katarzyna , Wasko Joanna , Becht Angelika , Fraczyk Justyna , Gajda Anna , Pietrzak Lukasz , Szymanski Lukasz , Krakowiak Agnieszka , Draczynski Zbigniew , Kolesinska Beata
Published: December 2021

The aim of the research was to check whether it is possible to use fragments of type IV collagen to obtain, as a result of self-assembling, stable spatial structures that could be used to prepare new materials useful in regenerative medicine. Collagen IV fragments were obtained by using DMT/NMM/TosO− as a coupling reagent. The ability to self-organize and form stable spatial structures was tested by the CD method and microscopic techniques. Biological studies covered: resazurin assay (cytotoxicity assessment) on BJ, BJ-5TA and C2C12 cell lines; an alkaline version of the comet assay (genotoxicity), Biolegend Legendplex human inflammation panel 1 assay (SC cell lines, assessment of the inflammation activity) and MTT test to determine the cytotoxicity of the porous materials based on collagen IV fragments. It was found that out of the pool of 37 fragments (peptides 1–33 and 2.1–2.4) reconstructing the outer sphere of collagen IV, nine fragments (peptides: 2, 4, 5, 6, 14, 15, 25, 26 and 30), as a result of self-assembling, form structures mimicking the structure of the triple helix of native collagens. The stability of spatial structures formed as a result of self-organization at temperatures of 4 °C, 20 °C, and 40 °C was found. The application of the MST method allowed us to determine the Kd of binding of selected fragments of collagen IV to ITGα1β1. The stability of the spatial structures of selected peptides made it possible to obtain porous materials based on their equimolar mixture. The formation of the porous materials was found for cross-linked structures and the material stabilized only by weak interactions. All tested peptides are non-cytotoxic against all tested cell lines. Selected peptides also showed no genotoxicity and no induction of immune system responses. Research on the use of porous materials based on fragments of type IV collagen, able to form stable spatial structures as scaffolds useful in regenerative medicine, will be continued.
GSK3β Serine 389 Phosphorylation Modulates Cardiomyocyte Hypertrophy and Ischemic Injury
Authors: Vainio Laura , Taponen Saija , Kinnunen Sini M. , Halmetoja Eveliina , Szabo Zoltan , Alakoski Tarja , Ulvila Johanna , Junttila Juhani , Lakkisto Päivi , Magga Johanna , Kerkelä Risto
Published: December 2021

Prior studies show that glycogen synthase kinase 3β (GSK3β) contributes to cardiac ischemic injury and cardiac hypertrophy. GSK3β is constitutionally active and phosphorylation of GSK3β at serine 9 (S9) inactivates the kinase and promotes cellular growth. GSK3β is also phosphorylated at serine 389 (S389), but the significance of this phosphorylation in the heart is not known. We analyzed GSK3β S389 phosphorylation in diseased hearts and utilized overexpression of GSK3β carrying ser→ala mutations at S9 (S9A) and S389 (S389A) to study the biological function of constitutively active GSK3β in primary cardiomyocytes. We found that phosphorylation of GSK3β at S389 was increased in left ventricular samples from patients with dilated cardiomyopathy and ischemic cardiomyopathy, and in hearts of mice subjected to thoracic aortic constriction. Overexpression of either GSK3β S9A or S389A reduced the viability of cardiomyocytes subjected to hypoxia–reoxygenation. Overexpression of double GSK3β mutant (S9A/S389A) further reduced cardiomyocyte viability. Determination of protein synthesis showed that overexpression of GSK3β S389A or GSK3β S9A/S389A increased both basal and agonist-induced cardiomyocyte growth. Mechanistically, GSK3β S389A mutation was associated with activation of mTOR complex 1 signaling. In conclusion, our data suggest that phosphorylation of GSK3β at S389 enhances cardiomyocyte survival and protects from cardiomyocyte hypertrophy.
Three Component Composite Scaffolds Based on PCL, Hydroxyapatite, and L-Lysine Obtained in TIPS-SL: Bioactive Material for Bone Tissue Engineering
Authors: Korbut Aleksandra , Włodarczyk Marcin , Rudnicka Karolina , Szwed Aleksandra , Płociński Przemysław , Biernat Monika , Tymowicz-Grzyb Paulina , Michalska Martyna , Karska Natalia , Rodziewicz-Motowidło Sylwia , Szustakiewicz Konrad
Published: December 2021

In this research, we describe the properties of three-component composite foam scaffolds based on poly(ε-caprolactone) (PCL) as a matrix and hydroxyapatite whiskers (HAP) and L-Lysine as fillers (PCL/HAP/Lys with wt% ratio 50/48/2). The scaffolds were prepared using a thermally induced phase separation technique supported by salt leaching (TIPS-SL). All materials were precisely characterized: porosity, density, water uptake, wettability, DSC, and TGA measurements and compression tests were carried out. The microstructure of the obtained scaffolds was analyzed via SEM. It was found that the PCL/HAP/Lys scaffold has a 45% higher Young’s modulus and better wettability compared to the PCL/HAP system. At the same time, the porosity of the system was ~90%. The osteoblast hFOB 1.19 cell response was also investigated in osteogenic conditions (39 °C) and the cytokine release profile of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was determined. Modification of PCL scaffolds with HAP and L-Lysine significantly improved the proliferation of pre-osteoblasts cultured on such materials.
Three-Dimensional Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Promotes Matrix Metallopeptidase 13 (MMP13) Expression in Type I Collagen Hydrogels
Authors: Oliveros Anerillas Luis , Kingham Paul J. , Lammi Mikko J. , Wiberg Mikael , Kelk Peyman
Published: December 2021

Autologous bone transplantation is the principal method for reconstruction of large bone defects. This technique has limitations, such as donor site availability, amount of bone needed and morbidity. An alternative to this technique is tissue engineering with bone marrow-derived mesenchymal stem cells (BMSCs). In this study, our aim was to elucidate the benefits of culturing BMSCs in 3D compared with the traditional 2D culture. In an initial screening, we combined BMSCs with four different biogels: unmodified type I collagen (Col I), type I collagen methacrylate (ColMa), an alginate and cellulose-based bioink (CELLINK) and a gelatin-based bioink containing xanthan gum (GelXA-bone). Col I was the best for structural integrity and maintenance of cell morphology. Osteogenic, adipogenic, and chondrogenic differentiations of the BMSCs in 2D versus 3D type I collagen gels were investigated. While the traditional pellet culture for chondrogenesis was superior to our tested 3D culture, Col I hydrogels (i.e., 3D) favored adipogenic and osteogenic differentiation. Further focus of this study on osteogenesis were conducted by comparing 2D and 3D differentiated BMSCs with Osteoimage® (stains hydroxyapatite), von Kossa (stains anionic portion of phosphates, carbonates, and other salts) and Alizarin Red (stains Ca2+ deposits). Multivariate gene analysis with various covariates showed low variability among donors, successful osteogenic differentiation, and the identification of one gene (matrix metallopeptidase 13, MMP13) significantly differentially expressed in 2D vs. 3D cultures. MMP13 protein expression was confirmed with immunohistochemistry. In conclusion, this study shows evidence for the suitability of type I collagen gels for 3D osteogenic differentiation of BMSCs, which might improve the production of tissue-engineered constructs for treatment of bone defects.
Genome-Wide Analysis of Smad7-Mediated Transcription in Mouse Embryonic Stem Cells
Authors: Meng Guohua , Lauria Andrea , Maldotti Mara , Anselmi Francesca , Polignano Isabelle Laurence , Rapelli Stefania , Donna Daniela , Oliviero Salvatore
Published: December 2021

Smad7 has been identified as a negative regulator of the transforming growth factor TGF-β pathway by direct interaction with the TGF-β type I receptor (TβR-I). Although Smad7 has also been shown to play TGF-β unrelated functions in the cytoplasm and in the nucleus, a comprehensive analysis of its nuclear function has not yet been performed. Here, we show that in ESCs Smad7 is mainly nuclear and acts as a general transcription factor regulating several genes unrelated to the TGF-β pathway. Loss of Smad7 results in the downregulation of several key stemness master regulators, including Pou5f1 and Zfp42, and in the upregulation of developmental genes, with consequent loss of the stem phenotype. Integrative analysis of genome-wide mapping data for Smad7 and ESC self-renewal and pluripotency transcriptional regulators revealed that Smad7 co-occupies promoters of highly expressed key stemness regulators genes, by binding to a specific consensus response element NCGGAAMM. Altogether, our data establishes Smad7 as a new, integral component of the regulatory circuitry that controls ESC identity.
Magnesium and Morphine in the Treatment of Chronic Neuropathic Pain–A Biomedical Mechanism of Action
Authors: Kulik Kamila , Żyżyńska-Granica Barbara , Kowalczyk Agnieszka , Kurowski Przemysław , Gajewska Małgorzata , Bujalska-Zadrożny Magdalena
Published: December 2021

The effectiveness of opioids in the treatment of neuropathic pain is limited. It was demonstrated that magnesium ions (Mg2+), physiological antagonists of N-methyl-D-aspartate receptor (NMDAR), increase opioid analgesia in chronic pain. Our study aimed to determine the molecular mechanism of this action. Early data indicate the cross-regulation of µ opioid receptor (MOR) and NMDAR in pain control. Morphine acting on MOR stimulates protein kinase C (PKC), while induction of NMDAR recruits protein kinase A (PKA), leading to a disruption of the MOR-NMDAR complex and promoting functional changes in receptors. The mechanical Randall-Selitto test was used to assess the effect of chronic Mg2+ and morphine cotreatment on streptozotocin-induced hyperalgesia in Wistar rats. The level of phosphorylated NMDAR NR1 subunit (pNR1) and phosphorylated MOR (pMOR) in the periaqueductal gray matter was determined with the Western blot method. The activity of PKA and PKC was examined by standard enzyme immunoassays. The experiments showed a reduction in hyperalgesia after coadministration of morphine (5 mg/kg intraperitoneally) and Mg2+ (40 mg/kg intraperitoneally). Mg2+ administered alone significantly decreased the level of pNR1, pMOR, and activity of both tested kinases. The results suggest that blocking NMDAR signaling by Mg2+ restores the MOR-NMDAR complex and thus enables morphine analgesia in neuropathic rats.
GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression
Authors: Stemmler Albert , Symmank Judit , Steinmetz Julia , von Brandenstein Katrin , Hennig Christoph-Ludwig , Jacobs Collin
Published: December 2021

Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in P. gingivalis-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in GDF15 siRNA-treated HPdLF stimulated with P. gingivalis lipopolysaccharides alone and in combination with compressive force. GDF15 knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions.
Benzimidazole Derivatives as New and Selective Inhibitors of Arginase from Leishmania mexicana with Biological Activity against Promastigotes and Amastigotes
Authors: Betancourt-Conde Irene , Avitia-Domínguez Claudia , Hernández-Campos Alicia , Castillo Rafael , Yépez-Mulia Lilián , Oria-Hernández Jesús , Méndez Sara T. , Sierra-Campos Erick , Valdez-Solana Mónica , Martínez-Caballero Siseth , Hermoso Juan A. , Romo-Mancillas Antonio , Téllez-Valencia Alfredo
Published: December 2021

Leishmaniasis is a disease caused by parasites of the Leishmania genus that affects 98 countries worldwide, 2 million of new cases occur each year and more than 350 million people are at risk. The use of the actual treatments is limited due to toxicity concerns and the apparition of resistance strains. Therefore, there is an urgent necessity to find new drugs for the treatment of this disease. In this context, enzymes from the polyamine biosynthesis pathway, such as arginase, have been considered a good target. In the present work, a chemical library of benzimidazole derivatives was studied performing computational, enzyme kinetics, biological activity, and cytotoxic effect characterization, as well as in silico ADME-Tox predictions, to find new inhibitors for arginase from Leishmania mexicana (LmARG). The results show that the two most potent inhibitors (compounds 1 and 2) have an I50 values of 52 μM and 82 μM, respectively. Moreover, assays with human arginase 1 (HsARG) show that both compounds are selective for LmARG. According to molecular dynamics simulation studies these inhibitors interact with important residues for enzyme catalysis. Biological activity assays demonstrate that both compounds have activity against promastigote and amastigote, and low cytotoxic effect in murine macrophages. Finally, in silico prediction of their ADME-Tox properties suggest that these inhibitors support the characteristics to be considered drug candidates. Altogether, the results reported in our study suggest that the benzimidazole derivatives are an excellent starting point for design new drugs against leishmanisis.
Modelling of the Citrus CCD4 Family Members: In Silico Analysis of Membrane Binding and Substrate Preference
Authors: Cantero Jorge , Polticelli Fabio , Paulino Margot
Published: December 2021

Coloring is one of the most important characteristics in commercial flowers and fruits, generally due to the accumulation of carotenoid pigments. Enzymes of the CCD4 family in citrus intervene in the generation of β-citraurin, an apocarotenoid responsible for the reddish-orange color of mandarins. Citrus CCD4s enzymes could be capable of interacting with the thylakoid membrane inside chloroplasts. However, to date, this interaction has not been studied in detail. In this work, we present three new complete models of the CCD4 family members (CCD4a, CCD4b, and CCD4c), modeled with a lipid membrane. To identify the preference for substrates, typical carotenoids were inserted in the active site of the receptors and the protein–ligand interaction energy was evaluated. The results show a clear preference of CCD4s for xanthophylls over aliphatic carotenes. Our findings indicate the ability to penetrate the membrane and maintain a stable interaction through the N-terminal α-helical domain, spanning a contact surface of 2250 to 3250 Å2. The orientation and depth of penetration at the membrane surface suggest that CCD4s have the ability to extract carotenoids directly from the membrane through a tunnel consisting mainly of hydrophobic residues that extends up to the catalytic center of the enzyme.
Non-Opioid Peptides Targeting Opioid Effects
Authors: Kaczyńska Katarzyna , Wojciechowski Piotr
Published: December 2021

Opioids are the most potent widely used analgesics, primarily, but not exclusively, in palliative care. However, they are associated with numerous side effects, such as tolerance, addiction, respiratory depression, and cardiovascular events. This, in turn, can result in their overuse in cases of addiction, the need for dose escalation in cases of developing tolerance, and the emergence of dose-related opioid toxicity, resulting in respiratory depression or cardiovascular problems that can even lead to unintentional death. Therefore, a very important challenge for researchers is to look for ways to counteract the side effects of opioids. The use of peptides and their related compounds, which have been shown to modulate the effects of opioids, may provide such an opportunity. This short review is a compendium of knowledge about the most important and recent findings regarding selected peptides and their modulatory effects on various opioid actions, including cardiovascular and respiratory responses. In addition to the peptides more commonly reported in the literature in the context of their pro- and/or anti-opioid activity—such as neuropeptide FF (NPFF), cholecystokinin (CCK), and melanocyte inhibiting factor (MIF)—we also included in the review nociceptin/orphanin (N/OFQ), ghrelin, oxytocin, endothelin, and venom peptides.
KRAS Affects Adipogenic Differentiation by Regulating Autophagy and MAPK Activation in 3T3-L1 and C2C12 Cells
Authors: Yu Wenjie , Chen Cheng-Zhen , Peng Yanxia , Li Ze , Gao Yan , Liang Shuang , Yuan Bao , Kim Nam-Hyung , Jiang Hao , Zhang Jia-Bao
Published: December 2021

Kirsten rat sarcoma 2 viral oncogene homolog (Kras) is a proto-oncogene that encodes the small GTPase transductor protein KRAS, which has previously been found to promote cytokine secretion, cell survival, and chemotaxis. However, its effects on preadipocyte differentiation and lipid accumulation are unclear. In this study, the effects of KRAS inhibition on proliferation, autophagy, and adipogenic differentiation as well as its potential mechanisms were analyzed in the 3T3-L1 and C2C12 cell lines. The results showed that KRAS was localized mainly in the nuclei of 3T3-L1 and C2C12 cells. Inhibition of KRAS altered mammalian target of rapamycin (Mtor), proliferating cell nuclear antigen (Pcna), Myc, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein beta (C/ebp-β), diacylglycerol O-acyltransferase 1 (Dgat1), and stearoyl-coenzyme A desaturase 1 (Scd1) expression, thereby reducing cell proliferation capacity while inducing autophagy, enhancing differentiation of 3T3-L1 and C2C12 cells into mature adipocytes, and increasing adipogenesis and the capacity to store lipids. Moreover, during differentiation, KRAS inhibition reduced the levels of extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), p38, and phosphatidylinositol 3 kinase (PI3K) activation. These results show that KRAS has unique regulatory effects on cell proliferation, autophagy, adipogenic differentiation, and lipid accumulation.
Highly Active Thermophilic L-Asparaginase from Melioribacter roseus Represents a Novel Large Group of Type II Bacterial L-Asparaginases from Chlorobi-Ignavibacteriae-Bacteroidetes Clade
Authors: Dumina Maria , Zhgun Alexander , Pokrovskaya Marina , Aleksandrova Svetlana , Zhdanov Dmitry , Sokolov Nikolay , El’darov Michael
Published: December 2021

L-asparaginase (L-ASNase) is a biotechnologically relevant enzyme for the pharmaceutical, biosensor and food industries. Efforts to discover new promising L-ASNases for different fields of biotechnology have turned this group of enzymes into a growing family with amazing diversity. Here, we report that thermophile Melioribacter roseus from Ignavibacteriae of the Bacteroidetes/Chlorobi group possesses two L-ASNases—bacterial type II (MrAII) and plant-type (MrAIII). The current study is focused on a novel L-ASNase MrAII that was expressed in Escherichia coli, purified and characterized. The enzyme is optimally active at 70 °C and pH 9.3, with a high L-asparaginase activity of 1530 U/mg and L-glutaminase activity ~19% of the activity compared with L-asparagine. The kinetic parameters KM and Vmax for the enzyme were 1.4 mM and 5573 µM/min, respectively. The change in MrAII activity was not significant in the presence of 10 mM Ni2+, Mg2+ or EDTA, but increased with the addition of Cu2+ and Ca2+ by 56% and 77%, respectively, and was completely inhibited by Zn2+, Fe3+ or urea solutions 2–8 M. MrAII displays differential cytotoxic activity: cancer cell lines K562, Jurkat, LnCap, and SCOV-3 were more sensitive to MrAII treatment, compared with normal cells. MrAII represents the first described enzyme of a large group of uncharacterized counterparts from the Chlorobi-Ignavibacteriae-Bacteroidetes clade.
Prothrombotic Phenotype in COVID-19: Focus on Platelets
Authors: Barale Cristina , Melchionda Elena , Morotti Alessandro , Russo Isabella
Published: December 2021

COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.
Designing Red-Shifted Molecular Emitters Based on the Annulated Locked GFP Chromophore Derivatives
Authors: Sinenko Gregory D. , Farkhutdinova Dilara A. , Myasnyanko Ivan N. , Baleeva Nadezhda S. , Baranov Mikhail S. , Bochenkova Anastasia V.
Published: December 2021

Bioimaging techniques require development of a wide variety of fluorescent probes that absorb and emit red light. One way to shift absorption and emission of a chromophore to longer wavelengths is to modify its chemical structure by adding polycyclic aromatic hydrocarbon (PAH) fragments, thus increasing the conjugation length of a molecule while maintaining its rigidity. Here, we consider four novel classes of conformationally locked Green Fluorescent Protein (GFP) chromophore derivatives obtained by extending their aromatic systems in different directions. Using high-level ab initio quantum chemistry calculations, we show that the alteration of their electronic structure upon annulation may unexpectedly result in a drastic change of their fluorescent properties. A flip of optically bright and dark electronic states is most prominent in the symmetric fluorene-based derivative. The presence of a completely dark lowest-lying excited state is supported by the experimentally measured extremely low fluorescence quantum yield of the newly synthesized compound. Importantly, one of the asymmetric modes of annulation provides a very promising strategy for developing red-shifted molecular emitters with an absorption wavelength of ∼600 nm, having no significant impact on the character of the bright S-S1 transition.
Robust Complaint Processing in Portuguese
Authors: Lopes-Cardoso Henrique , Osório Tomás Freitas , Barbosa Luís Vilar , Rocha Gil , Reis Luís Paulo , Machado João Pedro , Oliveira Ana Maria
Published: December 2021

The Natural Language Processing (NLP) community has witnessed huge improvements in the last years. However, most achievements are evaluated on benchmarked curated corpora, with little attention devoted to user-generated content and less-resourced languages. Despite the fact that recent approaches target the development of multi-lingual tools and models, they still underperform in languages such as Portuguese, for which linguistic resources do not abound. This paper exposes a set of challenges encountered when dealing with a real-world complex NLP problem, based on user-generated complaint data in Portuguese. This case study meets the needs of a country-wide governmental institution responsible for food safety and economic surveillance, and its responsibilities in handling a high number of citizen complaints. Beyond looking at the problem from an exclusively academic point of view, we adopt application-level concerns when analyzing the progress obtained through different techniques, including the need to obtain explainable decision support. We discuss modeling choices and provide useful insights for researchers working on similar problems or data.
Using Machine Learning to Compare the Information Needs and Interactions of Facebook: Taking Six Retail Brands as an Example
Authors: Chen Yulin
Published: December 2021

This study explores the interactive characteristics of the public, referencing existing data mining methods. This research attempts to develop a community data mining and integration technology to investigate the trends of global retail chain brands. Using social media mining and ensemble learning, it examines key image cues to highlight the various reasons motivating participation by fans. Further, it expands the discussion on image and marketing cues to explore how various social brands induce public participation and the evaluation of information efficiency. This study integrates random decision forests, extreme gradient boost, and adaboost for statistical verification. From 1 January 2011 to 31 December 2019, the studied brands published a total of 25,538 posts. The study combines community information and participation in its research framework. The samples are divided into three categories: retail food brand, retail home improvement brand, and retail warehouse club brand. This research draws on brand image and information cue theory to design the theoretical framework, and then uses behavior response factors for the theoretical integration. This study contributes a model that classifies brand community posts and mines related data to analyze public needs and preferences. More specifically, it proposes a framework with supervised and ensemble learning to classify information users′ behavioral characteristics.
Parallel Particle Swarm Optimization Based on Spark for Academic Paper Co-Authorship Prediction
Authors: Yang Congmin , Zhu Tao , Zhang Yang , Ning Huansheng , Chen Liming , Liu Zhenyu
Published: December 2021

The particle swarm optimization (PSO) algorithm has been widely used in various optimization problems. Although PSO has been successful in many fields, solving optimization problems in big data applications often requires processing of massive amounts of data, which cannot be handled by traditional PSO on a single machine. There have been several parallel PSO based on Spark, however they are almost proposed for solving numerical optimization problems, and few for big data optimization problems. In this paper, we propose a new Spark-based parallel PSO algorithm to predict the co-authorship of academic papers, which we formulate as an optimization problem from massive academic data. Experimental results show that the proposed parallel PSO can achieve good prediction accuracy.
Sublethal Effects of Imidacloprid on Fecundity, Apoptosis and Virus Transmission in the Small Brown Planthopper Laodelphax striatellus
Authors: Zhang Yuanyuan , Xu Gang , Jiang Yu , Ma Chao , Yang Guoqing
Published: December 2021

Laodelphax striatellus damages plants directly through sucking plant sap and indirectly as a vector of rice stripe virus (RSV), resulting in serious losses of rice yield. It is one of the most destructive insects of rice in East Asia. Insecticides are primarily used for pest management, but the sublethal concentrations of insecticides may benefit several insects. The present research attempted to explore the effects of sublethal concentrations of imidacloprid on the fecundity, apoptosis and RSV transmission in the viruliferous SBPH. The results showed that the fecundity of SBPH was significantly increased after treatment with the LC10 dose of imidacloprid, while the LC30 dose of imidacloprid reduced the fecundity compared with the control. To further investigate the underlying mechanism of increased fecundity after exposure to the LC10 dose of imidacloprid, we examined the expression levels of vitellogenin (Vg), Vg receptor (VgR) and caspases in the ovaries of SBPH, and observed the apoptosis by terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL). qRT-PCR results indicated that the expression levels of Vg, VgR and four caspase genes were all significantly increased by the LC10 dose of imidacloprid, and TUNEL assays suggested that the frequency of apoptosis was significantly higher in the SBPH treated by the LC10 dose of imidacloprid, suggesting a potential correlation between the increased fecundity and the apoptosis of SBPH ovarioles. Additionally, the expression levels of RNA3 and capsid protein (CP) were both increased significantly by the LC10 dose of imidacloprid, whereas were decreased by the LC30 dose of imidacloprid compared to the control. Therefore, this study clarifies the mechanisms of sublethal effects of imidacloprid on viruliferous SBPH and could be used to optimize pest control strategies.
Functional Response and Predation Potential of Carabus elysii Adults against the Terrestrial Slug Agriolimax agrestis
Authors: Jiang Lin , Zhao Runa , Tian Hui , Wu Xuesan , Guo Feng , Chen Wenlong
Published: December 2021

Terrestrial slugs are a prominent agricultural pest worldwide. To mitigate the negative effects of chemical pest control, biological control involves the use of natural enemies to reduce the impact of target pests. Numerous insects are natural predators of slugs. This study evaluated potential of the predatory species, Carabus elysii Thomson (Coleoptera: Carabidae) to biologically control the terrestrial slug, Agriolimax agrestis. Laboratory experiments were conducted to investigate the functional response, searching efficiency, and interference effect of female and male C. elysii adults regarding adult, immature, and juvenile A. agrestis individuals. The results show that both female and male ground beetle adults are functionally capable of preying on different sizes of terrestrial slugs. C. elysii exhibited Holling type II functional responses when preying on A. agrestis. The maximum daily prey consumption was 35.5 juveniles, 25.1 immatures, and 17.1 adults for adult females and 26.9 juveniles, 20.3 immatures, and 11.6 adults for adult males. The searching efficiency of female C. elysii adults regarding A. agrestis was always higher than that of male adults for identical ages and densities of A. agrestis. Moreover, the predation of C. elysii on slugs was affected by predator density. The disturbance coefficient of male C. elysii were the highest on adult A. agrestis. The results of this study suggest that female C. elysii exhibit a high potential for the biological control of A. agrestis.
Ovarian Cancer: Latest Advances and Prospects
Authors: Dion Ludivine , Lavoué Vincent
Published: December 2021

The landscape of ovarian cancer therapeutics is experiencing an increase in new opportunities [...]
Microbiota in Pancreatic Diseases: A Review of the Literature
Authors: Schepis Tommaso , De Lucia Sara S. , Nista Enrico C. , Manilla Vittoria , Pignataro Giulia , Ojetti Veronica , Piccioni Andrea , Gasbarrini Antonio , Franceschi Francesco , Candelli Marcello
Published: December 2021

The gut microbiota is a critical element in the balance between human health and disease. Its impairment, defined as dysbiosis, is associated with gastroenterological and systemic diseases. Pancreatic secretions are involved in the composition and changes of the gut microbiota, and the gut microbiota may colonize the pancreatic parenchyma and be associated with the occurrence of diseases. The gut microbiota and the pancreas influence each other, resulting in a “gut microbiota-pancreas axis”. Moreover, the gut microbiota may be involved in pancreatic diseases, both through direct bacterial colonization and an indirect effect of small molecules and toxins derived from dysbiosis. Pancreatic diseases such as acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer are common gastroenterological diseases associated with high morbidity and mortality. The involvement of the microbiota in pancreatic diseases is increasingly recognized. Therefore, modifying the intestinal bacterial flora could have important therapeutic implications on these pathologies. The aim of this study is to review the literature to evaluate the alterations of the gut microbiota in pancreatic diseases, and the role of the microbiota in the treatment of these diseases.
The Uncertain Benefit of Adjuvant Chemotherapy in Advanced Low-Grade Serous Ovarian Cancer and the Pivotal Role of Surgical Cytoreduction
Authors: Johnson Racheal Louise , Laios Alexandros , Jackson David , Nugent David , Orsi Nicolas Michel , Theophilou Georgios , Thangavelu Amudha , de Jong Diederick
Published: December 2021

In our center, adjuvant chemotherapy is routinely offered in high-grade serous ovarian cancer (HGSOC) patients but less commonly as a standard treatment in low-grade serous ovarian cancer (LGSOC) patients. This study evaluates the efficacy of this paradigm by analysing survival outcomes and by comparing the influence of different clinical and surgical characteristics between women with advanced LGSOC (n = 37) and advanced HGSOC (n = 300). Multivariate analysis was used to identify independent prognostic features for survival in LGSOC and HGSOC. Adjuvant chemotherapy was given in 99.7% of HGSOC patients versus in 27% of LGSOC (p < 0.0001). The LGSOC patients had greater surgical complexity scores (p < 0.0001), more frequent postoperative ICU/HDU admissions (p = 0.0002), and higher peri-/post-operative morbidity (p < 0.0001) compared to the HGSOC patients. The 5-year OS and progression-free survival (PFS) was 30% and 13% for HGSOC versus 57% and 21.6% for LGSOC, p = 0.016 and p = 0.044, respectively. Surgical complexity (HR 5.3, 95%CI 1.2–22.8, p = 0.024) and complete cytoreduction (HR 62.4, 95% CI 6.8–567.9, p < 0.001) were independent prognostic features for OS in LGSOC. This study demonstrates no clear significant survival advantage of chemotherapy in LGSOC. It highlights the substantial survival benefit of dynamic multi-visceral surgery to achieve complete cytoreduction as the primary treatment for LGSOC patients.
Reference Ranges of Left Ventricular Hemodynamic Forces in Healthy Adults: A Speckle-Tracking Echocardiographic Study
Authors: Ferrara Francesco , Capuano Francesco , Cocchia Rosangela , Ranieri Brigida , Contaldi Carla , Lacava Graziella , Capone Valentina , Chianese Salvatore , Rega Salvatore , Annunziata Roberto , Sepe Chiara , Salzano Andrea , Citro Rodolfo , D’Andrea Antonello , Mauro Ciro , Cademartiri Filippo , Pedrizzetti Gianni , Bossone Eduardo
Published: December 2021

Background: The normal limits of left ventricular (LV) hemodynamic forces (HDFs) are not exactly known. The aim of this study was to explore the full spectrum of HDF parameters in healthy subjects and determine their physiologic correlates. Methods: 269 healthy subjects were enrolled (mean age: 43 ± 14 years; 123 (45.7%) men). All participants underwent an echo-Doppler examination. Tri-plane tissue tracking from apical views was used to measure 2D global endocardial longitudinal strain (GLS), circumferential strain (GCS), and LV HDFs. HDFs were normalized with LV volume and divided by specific weight. Results: LV systolic longitudinal HDFs (%) were higher in men (20.8 ± 6.5 vs. 18.9 ± 5.6, p = 0.009; 22.0 ± 6.7 vs. 19.8 ± 5.6, p = 0.004, respectively). There was a significant correlation between GCS (increased) (r = −0.240, p < 0.001) and LV longitudinal HDFs (reduced) (r = −0.155, p = 0.01) with age. In a multivariable analysis age, BSA, pulse pressure, heart rate and GCS were the only independent variables associated with LV HDFs (β coefficient = −0.232, p < 0.001; 0.149, p = 0.003; 0.186, p < 0.001; 0.396, p < 0.001; −0.328, p < 0.001; respectively). Conclusion: We report on the physiologic range of LV HDFs. Knowledge of reference values of HDFs may prompt their implementation into clinical routine and allow a more comprehensive assessment of the LV function.
Clinical Considerations in Orthodontically Forced Eruption for Restorative Purposes
Authors: Huang Grace , Yang Min , Qali Mohammad , Wang Tun-Jan , Li Chenshuang , Chang Yu-Cheng
Published: December 2021

For restorations on teeth involving invasion of the supracrestal tissue attachment (biological width), as well as for lack of ferrule effect, crown lengthening is required for long-term periodontal health and success of the restoration. In the same fashion, site development is often necessary prior to implant placement in order to provide optimal peri-implant soft and hard tissue architecture conducive to future esthetics and function. Orthodontic extrusion, also known as forced eruption, has been developed and employed clinically to serve the purposes of increasing the clinical crown length, correcting the periodontal defect, and developing the implant site. In order to provide comprehensive guidance on the clinical usage of this technique and maximize the outcome for patients who receive the dental restoration, the currently available literatures were summarized and discussed in the current review. Compared to traditional crown lengthening surgery, forced eruption holds advantages of preserving supporting bone, providing improved esthetics, limiting the involvement of adjacent teeth, and decreasing the negative impact on crown-to-root ratio compared to the traditional resective approach. As a non-invasive and natural technique capable of increasing the available volume of bone and soft tissue, forced eruption is also an attractive and promising option for implant site development. Both fixed and removable appliances can be used to achieve the desired extrusion, but patient compliance is a primary limiting factor for the utilization of removable appliances. In summary, forced eruption is a valuable treatment adjunct for patients requiring crown lengthening or implant restorations. Nonetheless, comprehensive evaluation and treatment planning are required for appropriate case selection based upon the known indications and contraindications for each purpose; major contraindications include inflammation, ankylosis, hypercementosis, vertical root fracture, and root proximity. Further studies are necessary to elucidate the long-term stability of orthodontically extruded teeth and the supporting bone and soft tissue that followed them.
Vascular Dysfunction Predicts Future Deterioration of Left Ventricular Ejection Fraction in Patients with Heart Failure with Mildly Reduced Ejection Fraction
Authors: Kishimoto Shinji , Maruhashi Tatsuya , Kajikawa Masato , Harada Takahiro , Yamaji Takayuki , Han Yiming , Mizobuchi Aya , Hashimoto Yu , Yoshimura Kenichi , Nakano Yukiko , Chayama Kazuaki , Goto Chikara , Yusoff Farina Mohamad , Nakashima Ayumu , Higashi Yukihito
Published: December 2021

The purpose of this study was to evaluate whether heart failure with mildly reduced ejection fraction (HFmrEF) is associated with vascular dysfunction and whether vascular function predicts future deterioration of LVEF in patients with HFmrEF. We evaluated endothelial function assessed by flow-mediated vasodilation (FMD) and vascular smooth muscle function assessed by nitroglycerine-induced vasodilation (NID) in 69 patients with HFmrEF and 426 patients without HF and evaluated the future deterioration of LVEF, defined as a decrease in LVEF to <40%, in 39 patients with HFmrEF for up to 3 years. Both FMD and NID were significantly lower in patients with HFmrEF than in patients without HF. We categorized patients into two groups based on low tertiles of NID: a low group (NID of <7.0%) and an intermediate and high group (NID of ≥7.0%). There were significant differences between the Kaplan–Meier curves for the deterioration of LVEF in the two groups (p < 0.01). Multivariate Cox proportional hazard analysis revealed that NID of <7.0% was an independent predictor of future deterioration of LVEF in patients with HFmrEF. Both endothelial function and vascular smooth muscle function are impaired in patients with HFmrEF compared with those in patients without HF. In addition, low NID of <7.0% predicts future deterioration of LVEF.
A Study on the Estimation of Source Bearing in an ASA Wedge: Diminishing the Estimation Error Caused by Horizontal Refraction
Authors: Zhou Jianbo , Tang Jun , Yang Yixin
Published: December 2021

The performance of warping transformation in diminishing the error in underwater source-bearing estimation, caused by horizontal refraction effects (also named 3D effects), is studied. First, the capability of warping transformation for separating the normal modes, as well as their direct and horizontally refracted paths, in a standard Acoustical Society of America (ASA) wedge is demonstrated. Second, the error values for source bearing estimation in three different manners, i.e., using the full signal, using its component corresponding to the first mode, and using the component of the latter corresponding only to the direct path are compared for the same wedge case. The results show that the estimation error can be significantly reduced by beamforming, with only the first mode, or using the direct path of the first mode in cases where there exists a horizontally refracted path of the first mode.
Factors Affecting Soil Organic Carbon Content between Natural and Reclaimed Sites in Rudong Coast, Jiangsu Province, China
Authors: Yang Peipei , Hu Zhou , Shu Qiang
Published: December 2021

The physical and chemical properties of coastal soils in China have changed due to the development of reclaimed stretches of coastline, which has a significant impact on the dynamics of organic carbon (OC) in the soils. We evaluated changes in the physical and chemical properties of soils in both a natural area and a reclaimed area along the coast of Rudong County, China, as well as the effects that these changes had on the OC content of the soils. A partial least squares regression (PLSR) model was used to determine which factors are most important for driving changes in soil OC at four sites from each area. According to dominant vegetation types, there were significant differences in soil physical and chemical properties and OC content between the reclaimed area and natural coastal area. The mean grain size and pH increased gradually with depth, and values were highest in reclaimed areas. Mean total N (TN), P, and S, salinity, water content, and soil OC were highest in natural areas and decreased with depth. The PLSR model determined that TN, silt content, and sand content were the most important factors affecting soil OC in the reclaimed area, whereas TN, clay content, and water content were important factors affecting soil OC dynamics in the natural coastal areas. This study provides important reference data for correctly assessing the role and status of coastal areas in the global carbon cycle.