bluuebunny/crossref_metadata_2025 huggingface dataset:
The Association between the Type of Delivery and Factors Associated with Exclusive Breastfeeding Practice among Polish Women—A Cross-Sectional Study
Authors: Tracz Julia , Gajewska Danuta , Myszkowska-Ryciak Joanna
Published: October 2021

The type of delivery influences breastfeeding, both in terms of initiation and duration. The aim of the study was to determine the association between the type of delivery and factors associated with exclusive breastfeeding (EBF) practice among Polish women. Data on sociodemographic variables, pre-pregnancy weight, height, course of pregnancy, type of delivery and duration of breastfeeding were collected using a Computer-Assisted Web Interview. Of the 1024 breastfeeding women who participated in the study, 59.9% gave birth vaginally and 40.1% gave birth by caesarean section. The chance of starting EBF [OR: 0.478; 95% Cl: 0.274, 0.832] and continuing it for four months [OR: 0.836; 95% Cl: 0.569, 0.949] was lower in the case of caesarean delivery. Starting EBF was negatively affected by pre-pregnancy overweight status and obesity in the case of caesarean delivery. EBF practice for four months was negatively affected by age [18–24 years and 25–34 years], elementary education and average income [2001–4000 PLN] in the case of caesarean delivery. A negative impact on the chance of EBF for six months was also observed for younger age [18–24 years], elementary and secondary education and average income [2001–4000 PLN] in the case of caesarean delivery. There was no association between starting EBF and age, net income, place of living, pregnancy complications or the child′s birth weight category in the case of both subgroups, as well as between education and previous pregnancies in the case of vaginal delivery. These results suggest that women who deliver by caesarean section need additional breastfeeding support.
Heterogeneity of COVID-19 Risk Perception: A Socio-Mathematical Model
Authors: Gastelum-Strozzi Alfonso , Infante-Castañeda Claudia , Figueroa-Perea Juan Guillermo , Peláez-Ballestas Ingris
Published: October 2021

The perception of risk has been a key element in the experiences, containment and differential impact of the COVID-19 pandemic worldwide. The complexity of this phenomenon requires the interdisciplinary integration of theoretical and methodological aspects, as this integration informs the objective of developing a mathematical proposal based on a conceptual model located within the social theory of risk at the micro-social level. The mathematical risk model used here was developed from a secondary analysis of a study of 12,649 individuals on the experiences of the COVID-19 pandemic in a population in which the quantity and quality of the information made it possible to define a risk factor and its relationship to emotions and the sources of information used. Four sequential strategies were used to construct the model: choosing the variables for the questionnaire that theoretically corresponded to the conceptual model, constructing the risk vector and initial grouping of individuals by perception of risk, modeling by using principal component analysis and applying network methods. The theoretical model of risk, proposed and constructed through the analysis of groupings by quartiles and by networks in the studied population from a social and mathematical perspective, demonstrates the heterogeneity of risk perception as manifested by differences in perception by age, gender, expression of feelings and media consulted in a university community. The knowledge and methodology generated in these analyses contribute to the body of knowledge informing the response to future epidemiological contingencies.
Using Lean Six Sigma to Redesign the Supply Chain to the Operating Room Department of a Private Hospital to Reduce Associated Costs and Release Nursing Time to Care
Authors: O’Mahony Lisa , McCarthy Kerrie , O’Donoghue Josephine , Teeling Seán Paul , Ward Marie , McNamara Martin
Published: October 2021

Continuity of the supply chain is an integral element in the safe and timely delivery of health services. Lean Six Sigma (LSS), a continuous improvement approach, aims to drive efficiencies and standardisation in processes, and while well established in the manufacturing and supply chain industries, also has relevance in healthcare supply chain management. This study outlines the application of LSS tools and techniques within the supply chain of an Operating Room (OR) setting in a private hospital in Dublin, Ireland. A pre-/post-intervention design was employed following the Define, Measure, Analyse, Improve, Control (DMAIC) framework and applying LSS methodology to redesign the current process for stock management both within the OR storage area and within a pilot OR suite, through collaborative, inclusive, and participatory engagement with staff. A set of improvements were implemented to standardise and streamline the stock management in both areas. The main outcomes from the improvements implemented were an overall reduction in the value of stock held within the operating theatre by 17.7%, a reduction in the value of stock going out of date by 91.7%, and a reduction in the time spent by clinical staff preparing stock required for procedures by 45%, all demonstrating the effectiveness of LSS in healthcare supply chain management.
“It Is Like We Are Living in a Different World”: Health Inequity in Communities Surrounding Industrial Mining Sites in Burkina Faso, Mozambique, and Tanzania
Authors: Leuenberger Andrea , Cambaco Olga , Zabré Hyacinthe R. , Lyatuu Isaac , Utzinger Jürg , Munguambe Khátia , Merten Sonja , Winkler Mirko S.
Published: October 2021

Background: Health equity features prominently in the 2030 Agenda for Sustainable Development, yet there are wide disparities in health between and within countries. In settings of natural resource extraction (e.g., industrial mines), the health of surrounding communities is affected through myriad changes in the physical, social, and economic environment. How changes triggered by such projects translate into health inequities is poorly understood. Methods: This qualitative study explores potential layers of inequities by systematically coding perceived inequities of affected communities. Drawing on the framework method, we thematically analyzed data from 83 focus group discussions, which enrolled 791 participants from 10 study sites in Burkina Faso, Mozambique, and Tanzania. Results: Participants perceived inequities related to their individual characteristics, intermediate factors acting on the community level, and structural conditions. Due to environmental pollution and land loss, participants were concerned about unsecured livelihoods. Positive impacts, such as job opportunities at the mine, remained scarce for local communities and were claimed not to be equally distributed among community members. Conclusion: Extractive industries bear considerable risks to widen existing health gaps. In order to create equal opportunities among affected populations, the wider determinants of health must be considered more explicitly in the licensing process of resource extraction projects.
Chronic Rhinosinusitis and Alzheimer’s Disease—A Possible Role for the Nasal Microbiome in Causing Neurodegeneration in the Elderly
Authors: Harrass Sanaa , Yi Chenju , Chen Hui
Published: October 2021

Among millions of sufferers of chronic rhinosinusitis (CRS), the challenge is not only constantly coping with CRS-related symptoms, such as congested nose, sinus pain, and headaches, but also various complications, such as attention difficulties and possible depression. These complications suggest that neural activity in the central nervous system may be altered in those patients, leading to unexpected conditions, such as neurodegeneration in elderly patients. Recently, some studies linked the presence of CRS and cognitive impairments that could further develop into Alzheimer’s disease (AD). AD is the leading cause of dementia in the elderly and is characterised by progressive memory loss, cognitive behavioural deficits, and significant personality changes. The microbiome, especially those in the gut, has been recognised as a human organ and plays an important role in the development of various conditions, including AD. However, less attention has been paid to the microbiome in the nasal cavity. Increased nasal inflammatory responses due to CRS may be an initial event that changes local microbiome homeostasis, which may further affect neuronal integrity in the central nervous system resulting in AD. Evidence suggests a potential of β-amyloid deposition starting in olfactory neurons, which is then expanded from the nasal cavity to the central nervous system. In this paper, we reviewed currently available evidence that suggests this potential mechanism to advise the need to investigate the link between these two conditions.
Molecular Cytogenetic Analysis of the Introgression between Agropyron cristatum P Genome and Wheat Genome
Authors: Zhang Zhi , Zhou Shenghui , Liu Weihua , Song Liqiang , Zhang Jinpeng , Han Haiming , Yang Xinming , Lin Yida , Li Xiuquan , Li Lihui
Published: October 2021

Agropyron cristatum (2n = 4x = 28, PPPP) is an important wild relative of common wheat (Triticum aestivum L., 2n = 6x = 42). A previous report showed that the wheat-A. cristatum 6P translocation line WAT655 carrying A. cristatum 6PS (0.81–1.00) exhibited high resistance to prevalent physiological races of stripe rust (CYR32 and CYR33). In this study, three disease resistance-related transcripts, which were mapped to A. cristatum 6PS (0.81–1.00) through the analysis of specific molecular markers, were acquired from among A. cristatum full-length transcripts. The BC5F2 and BC5F2:3 genetic populations of the translocation line WAT655 were analyzed by using three disease resistance-related gene markers, A. cristatum P genome-specific markers, and fluorescence in situ hybridization (FISH). The results revealed that the introgression between A. cristatum P genome and wheat genome was observed in progenies of the genetic populations of the translocation line WAT655 and the physical positions of the three genes were considerably adjacent on A. cristatum 6PS (0.81–1.00) according to the FISH results. Additionally, kompetitive allele-specific PCR (KASP) markers of the three genes were developed to detect and acquire 24 breeding lines selected from the progenies of the distant hybridization of wheat and A. cristatum, which showed resistance to physiological races of stripe rust (CYR32 and CYR33) and other desirable agronomic traits according to the field investigation. In conclusion, this study not only provides new insights into the introgression between A. cristatum P genome and wheat genome but also provides the desirable germplasms for breeding practice.
New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists
Authors: Faúndez-Parraguez Manuel , Alarcón-Miranda Carlos , Cho Young Hwa , Pessoa-Mahana Hernán , Gallardo-Garrido Carlos , Chung Hery , Faúndez Mario , Pessoa-Mahana David
Published: October 2021

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.
Tension Stimulation of Tenocytes in Aligned Hyaluronic Acid/Platelet-Rich Plasma-Polycaprolactone Core-Sheath Nanofiber Membrane Scaffold for Tendon Tissue Engineering
Authors: Chen Chih-Hao , Li Dai-Ling , Chuang Andy Deng-Chi , Dash Banendu Sunder , Chen Jyh-Ping
Published: October 2021

To recreate the in vivo niche for tendon tissue engineering in vitro, the characteristics of tendon tissue underlines the use of biochemical and biophysical cues during tenocyte culture. Herein, we prepare core-sheath nanofibers with polycaprolactone (PCL) sheath for mechanical support and hyaluronic acid (HA)/platelet-rich plasma (PRP) core for growth factor delivery. Three types of core-sheath nanofiber membrane scaffolds (CSNMS), consisting of random HA-PCL nanofibers (Random), random HA/PRP-PCL nanofibers (Random+) or aligned HA/PRP-PCL (Align+) nanofibers, were used to study response of rabbit tenocytes to biochemical (PRP) and biophysical (fiber alignment) stimulation. The core-sheath structures as well as other pertinent properties of CSNMS have been characterized, with Align+ showing the best mechanical properties. The unidirectional growth of tenocytes, as induced by aligned fiber topography, was confirmed from cell morphology and cytoskeleton expression. The combined effects of PRP and fiber alignment in Align+ CSNMS lead to enhanced cell proliferation rates, as well as upregulated gene expression and marker protein synthesis. Another biophysical cue on tenocytes was introduced by dynamic culture of tenocyte-seeded Align+ in a bioreactor with cyclic tension stimulation. Augmented by this biophysical beacon from mechanical loading, dynamic cell culture could shorten the time for tendon maturation in vitro, with improved cell proliferation rates and tenogenic phenotype maintenance, compared to static culture. Therefore, we successfully demonstrate how combined use of biochemical/topographical cues as well as mechanical stimulation could ameliorate cellular response of tenocytes in CSNMS, which can provide a functional in vitro environmental niche for tendon tissue engineering.
Phytoestrogens (Resveratrol and Equol) for Estrogen-Deficient Skin—Controversies/Misinformation versus Anti-Aging In Vitro and Clinical Evidence via Nutraceutical-Cosmetics
Authors: Lephart Edwin D.
Published: October 2021

The overarching theme for this review is perspective. Superfoods (a marketing term for fruits and vegetables, etc.) have a positive connotation, while many superfoods contain phytoestrogens, a term that is alarming to the public and has a negative connotation because phytoestrogens are endocrine-disruptors, even though they are strong antioxidants that have many health benefits. To understand phytoestrogens, this paper provides a brief summary of the characteristics of: (a) estrogens, (b) estrogen receptors (ER), (c) estrogen-deficient skin, (d) how perspective(s) get off track, (e) phytoestrogen food sources, and (f) misconceptions of phytoestrogens and food safety, in general, that influence person(s) away from what is true. Finally, a brief history of cosmetics to nutraceuticals is covered plus the characteristics of phytoestrogens, resveratrol and equol on: (g) estrogen receptor binding, (h) topical and oral dosing, and (i) in vitro, molecular mechanisms and select clinical evidence, where both phytoestrogens (resveratrol and equol) demonstrate promising applications to improve skin health is presented along with future directions of nutraceuticals. Perspective is paramount in understanding the controversies associated with superfoods, phytoestrogens, and endocrine-disruptors because they have both positive and negative connotations. Everyone is exposed to and consumes these molecules everyday regardless of age, gender, or geographic location around the world, and how we understand this is a matter of perspective.
Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity
Authors: Marcuzzi Annalisa , Melloni Elisabetta , Zauli Giorgio , Romani Arianna , Secchiero Paola , Maximova Natalia , Rimondi Erika
Published: October 2021

Innate and adaptive immune responses have a well-known link and represent the distinctive origins of several diseases, many of which may be the consequence of the loss of balance between these two responses. Indeed, autoinflammation and autoimmunity represent the two extremes of a continuous spectrum of pathologic conditions with numerous overlaps in different pathologies. A common characteristic of these dysregulations is represented by hyperinflammation, which is an exaggerated response of the immune system, especially involving white blood cells, macrophages, and inflammasome activation with the hyperproduction of cytokines in response to various triggering stimuli. Moreover, hyperinflammation is of great interest, as it is one of the main manifestations of COVID-19 infection, and the cytokine storm and its most important components are the targets of the pharmacological treatments used to combat COVID-19 damage. In this context, the purpose of our review is to provide a focus on the pathogenesis of autoinflammation and, in particular, of hyperinflammation in order to generate insights for the identification of new therapeutic targets and strategies.
Macrophage-Dependent Interleukin-6-Production and Inhibition of IK Contributes to Acquired QT Prolongation in Lipotoxic Guinea Pig Heart
Authors: Chowdhury Md. Kamrul Hasan , Martinez-Mateu Laura , Do Jenny , Aromolaran Kelly A. , Saiz Javier , Aromolaran Ademuyiwa S.
Published: October 2021

In the heart, the delayed rectifier K current, IK, composed of the rapid (IKr) and slow (IKs) components contributes prominently to normal cardiac repolarization. In lipotoxicity, chronic elevation of pro-inflammatory cytokines may remodel IK, elevating the risk for ventricular arrythmias and sudden cardiac death. We investigated whether and how the pro-inflammatory interleukin-6 altered IK in the heart, using electrophysiology to evaluate changes in IK in adult guinea pig ventricular myocytes. We found that palmitic acid (a potent inducer of lipotoxicity), induced a rapid (~24 h) and significant increase in IL-6 in RAW264.7 cells. PA-diet fed guinea pigs displayed a severely prolonged QT interval when compared to low-fat diet fed controls. Exposure to isoproterenol induced torsade de pointes, and ventricular fibrillation in lipotoxic guinea pigs. Pre-exposure to IL-6 with the soluble IL-6 receptor produced a profound depression of IKr and IKs densities, prolonged action potential duration, and impaired mitochondrial ATP production. Only with the inhibition of IKr did a proarrhythmic phenotype of IKs depression emerge, manifested as a further prolongation of action potential duration and QT interval. Our data offer unique mechanistic insights with implications for pathological QT interval in patients and vulnerability to fatal arrhythmias.
Macrophage Polarization Related to Crystal Phases of Calcium Phosphate Biomaterials
Authors: Xiao Linghao , Shiwaku Yukari , Hamai Ryo , Tsuchiya Kaori , Sasaki Keiichi , Suzuki Osamu
Published: October 2021

Calcium phosphate (CaP) materials influence macrophage polarization during bone healing. However, the effect of the crystal phase of CaP materials on the immune response of bone remains unclear. In this study, the effect of the crystal phases of CaP materials on the regulation of macrophage polarization was investigated. Human THP-1 cells and mouse RAW 264 cells were cultured with octacalcium phosphate (OCP) and its hydrolyzed form Ca-deficient hydroxyapatite to assess the expression of pro-inflammatory M1 and anti-inflammatory M2 macrophage-related genes. OCP inhibited the excessive inflammatory response and switched macrophages to the anti-inflammatory M2 phenotype, which promoted the expression of the interleukin 10 (IL10) gene. In contrast, HL stimulated an excessive inflammatory response by promoting the expression of pro-inflammatory M1 macrophage-related genes. To observe changes in the microenvironment induced by OCP and HL, inorganic phosphate (Pi) and calcium ion (Ca2+) concentrations and pH value in the medium were measured. The expression of the pro-inflammatory M1 macrophage-related genes (tumor necrosis factor alpha (TNFα) and interlukin 1beta (IL1β)) was closely related to the increase in ion concentration caused by the increase in the CaP dose. Together, these results suggest that the microenvironment caused by the crystal phase of CaP materials may be involved in the immune-regulation capacity of CaP materials.
Perspectives on the Role of Enzymatic Biocatalysis for the Degradation of Plastic PET
Authors: Magalhães Rita P. , Cunha Jorge M. , Sousa Sérgio F.
Published: October 2021

Plastics are highly durable and widely used materials. Current methodologies of plastic degradation, elimination, and recycling are flawed. In recent years, biodegradation (the usage of microorganisms for material recycling) has grown as a valid alternative to previously used methods. The evolution of bioengineering techniques and the discovery of novel microorganisms and enzymes with degradation ability have been key. One of the most produced plastics is PET, a long chain polymer of terephthalic acid (TPA) and ethylene glycol (EG) repeating monomers. Many enzymes with PET degradation activity have been discovered, characterized, and engineered in the last few years. However, classification and integrated knowledge of these enzymes are not trivial. Therefore, in this work we present a summary of currently known PET degrading enzymes, focusing on their structural and activity characteristics, and summarizing engineering efforts to improve activity. Although several high potential enzymes have been discovered, further efforts to improve activity and thermal stability are necessary.
SOD2 Enhancement by Long-Term Inhibition of the PI3K Pathway Confers Multi-Drug Resistance and Enhanced Tumor-Initiating Features in Head and Neck Cancer
Authors: Hsueh Wei-Ting , Chen Shang-Hung , Chien Chia-Hung , Chou Shao-Wen , Chi Pei-I , Chu Jui-Mei , Chang Kwang-Yu
Published: October 2021

The phosphoinositide-3-kinase (PI3K) pathway has widely been considered as a potential therapeutic target for head and neck cancer (HNC); however, the application of PI3K inhibitors is often overshadowed by the induction of drug resistance with unknown mechanisms. In this study, PII3K inhibitor resistant cancer cells were developed by prolonged culturing of cell lines with BEZ235, a dual PI3K and mammalian target of rapamycin (mTOR) inhibitor. The drug resistant HNC cells showed higher IC50 of the proliferation to inhibitors specifically targeting PI3K and/or mTOR, as compared to their parental cells. These cells also showed profound resistance to drugs of other classes. Molecular analysis revealed persistent activation of phosphorylated AKT at threonine 308 in the drug resistant cells and increased expression of markers for tumor-initiating cells. Interestingly, increased intra-cellular ROS levels were observed in the drug resistant cells. Among anti-oxidant molecules, the expression of SOD2 was increased and was associated with the ALDH-positive tumor-initiating cell features. Co-incubation of SOD inhibitors and BEZ235 decreased the stemness feature of the cells in vitro, as shown by results of the spheroid formation assay. In conclusion, dysregulation of SOD2 might contribute to the profound resistance to PI3K inhibitors and the other drugs in HNC cells.
Mastocytosis and Mast Cell Activation Disorders: Clearing the Air
Authors: Jackson Clayton Webster , Pratt Cristina Marie , Rupprecht Chase Preston , Pattanaik Debendra , Krishnaswamy Guha
Published: October 2021

Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.
Oleanolic Acid’s Semisynthetic Derivatives HIMOXOL and Br-HIMOLID Show Proautophagic Potential and Inhibit Migration of HER2-Positive Breast Cancer Cells In Vitro
Authors: Lisiak Natalia Magdalena , Lewicka Izabela , Kaczmarek Mariusz , Kujawski Jacek , Bednarczyk-Cwynar Barbara , Zaprutko Lucjusz , Rubis Blazej
Published: October 2021

Approximately 20–30% of the diagnosed breast cancers overexpress the human epidermal growth factor receptor 2 (HER2). This type of cancer is associated with a more aggressive phenotype; thus, there is a need for the discovery of new compounds that would improve the survival in HER2-positive breast cancer patients. It seems that one of the most promising therapeutic cancer strategies could be based on the biological activity of pentacyclic triterpenes’ derivatives and the best-known representative of this group, oleanolic acid (OA). The biological activity of oleanolic acid and its two semisynthetic derivatives, methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate (HIMOXOL) and 12α-bromo-3-hydroxyimonoolean-28→13-olide (Br-HIMOLID), was assessed in SK-BR-3 breast cancer cells (HER2-positive). Viability tests, cell cycle assessment, evaluation of apoptosis, autophagy, and adhesion/migration processes were performed using MTT, clonogenic, cytofluorometry, Western blot, and qPCR. Both derivatives revealed higher cytotoxicity in studied breast cancer cells than the maternal compound, OA. They also decreased cell viability, induced autophagy, and (when applied in sub-cytotoxic concentrations) decreased the migration of SK-BR-3 cells.This study is the first to report the cytostatic, proautophagic (mTOR/LC3/SQSTM/BECN1 pathway), and anti-migratory (integrin β1/FAK/paxillin pathway) activities of HIMOXOL and Br-HIMOLID in HER2-positive breast cancer cells.
Functions of PPR Proteins in Plant Growth and Development
Authors: Li Xiulan , Sun Mengdi , Liu Shijuan , Teng Qian , Li Shihui , Jiang Yueshui
Published: October 2021

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.
Alveolar Regeneration in COVID-19 Patients: A Network Perspective
Authors: Gupta Shishir K. , Srivastava Mugdha , Minocha Rashmi , Akash Aman , Dangwal Seema , Dandekar Thomas
Published: October 2021

A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.
Sodium Butyrate Enhances Curcuminoids Permeability through the Blood-Brain Barrier, Restores Wnt/β-Catenin Pathway Antagonists Gene Expression and Reduces the Viability of Glioblastoma Cells
Authors: Majchrzak-Celińska Aleksandra , Kleszcz Robert , Stasiłowicz-Krzemień Anna , Cielecka-Piontek Judyta
Published: October 2021

Glioblastoma (GBM) is an extremely aggressive brain tumor awaiting novel, efficient, and minimally toxic treatment. Curcuminoids (CCM), polyphenols from Curcuma longa, and sodium butyrate (NaBu), a histone deacetylase inhibitor naturally occurring in the human body, await elucidation as potential anti-GBM agents. Thus, the aim of this study was to analyze CCM and NaBu both separately and as a combination treatment using three GBM cell lines. MTT was used for cytotoxicity evaluation, and the combination index was calculated for synergism prediction. Cell cycle, apoptosis, and reactive oxygen species (ROS) generation were analyzed using flow cytometry. DNA methylation was verified by MS-HRM and mRNA expression by qPCR. The permeability through the blood-brain barrier (BBB) and through the nasal cavity was evaluated using PAMPA model. The results of this study indicate that CCM and NaBu synergistically reduce the viability of GBM cells inducing apoptosis and cell cycle arrest. These effects are mediated via ROS generation and changes in gene expression, including upregulation of Wnt/β-catenin pathway antagonists, SFRP1, and RUNX3, and downregulation of UHRF1, the key epigenetic regulator. Moreover, NaBu ameliorated CCM permeability through the BBB and the nasal cavity. We conclude that CCM and NaBu are promising agents with anti-GBM properties.
Responses of Sphagneticola trilobata, Sphagneticola calendulacea and Their Hybrid to Drought Stress
Authors: Zhang Qilei , Huang Jundong , Ke Weiqian , Cai Minling , Chen Guangxin , Peng Changlian
Published: October 2021

Sphagneticola trilobata is an invasive plant in South China. A hybrid between S. trilobata and Sphagneticola calendulacea (a native related species) has also been found in South China. The drought resistance of S. calendulacea, S. trilobata and their hybrid was studied in this paper. Under drought stress, the leaves of S. trilobata synthesized more abscisic acid (ABA) than those of the other species to reduce stomatal opening and water loss. The activities of antioxidant enzymes were the highest in S. trilobata and the lowest in S. calendulacea. The leaves of S. calendulacea suffered the most serious damage, and their maximum photochemical efficiency was the lowest. RNA-sequencing ware used to analyze the expression levels of genes in ABA, antioxidant enzyme, sugar and proline synthesis and photosynthesis pathways. Further real-time PCR detection verified the RNA-sequence results, and the results were in accordance with the physiological data. The results showed that S. trilobata was the most drought tolerant, and the drought tolerance of the hybrid did not show heterosis but was higher than S. calendulacea. Therefore, compared with S. trilobata and the hybrid, the population number and distribution of S. calendulacea may be less in arid areas.
The Role of Emerin in Cancer Progression and Metastasis
Authors: Liddane Alexandra G. , Holaska James M.
Published: October 2021

It is commonly recognized in the field that cancer cells exhibit changes in the size and shape of their nuclei. These features often serve as important biomarkers in the diagnosis and prognosis of cancer patients. Nuclear size can significantly impact cell migration due to its incredibly large size. Nuclear structural changes are predicted to regulate cancer cell migration. Nuclear abnormalities are common across a vast spectrum of cancer types, regardless of tissue source, mutational spectrum, and signaling dependencies. The pervasiveness of nuclear alterations suggests that changes in nuclear structure may be crucially linked to the transformation process. The factors driving these nuclear abnormalities, and the functional consequences, are not completely understood. Nuclear envelope proteins play an important role in regulating nuclear size and structure in cancer. Altered expression of nuclear lamina proteins, including emerin, is found in many cancers and this expression is correlated with better clinical outcomes. A model is emerging whereby emerin, as well as other nuclear lamina proteins, binding to the nucleoskeleton regulates the nuclear structure to impact metastasis. In this model, emerin and lamins play a central role in metastatic transformation, since decreased emerin expression during transformation causes the nuclear structural defects required for increased cell migration, intravasation, and extravasation. Herein, we discuss the cellular functions of nuclear lamina proteins, with a particular focus on emerin, and how these functions impact cancer progression and metastasis.
Smart Vitamin Micelles as Cancer Nanomedicines for Enhanced Intracellular Delivery of Doxorubicin
Authors: Ko Na Re , Lee Sang Ju , Chandrasekaran Arun Pandian , Tyagi Apoorvi , Ramakrishna Suresh , Kim Seog-Young , Kim Do Won , Pack Chan-Gi , Oh Seung Jun
Published: October 2021

Chemotherapy is one of the most effective treatments for cancer. However, intracellular delivery of many anticancer drugs is hindered by their hydrophobicity and low molecular weight. Here, we describe highly biocompatible and biodegradable amphiphilic vitamin conjugates comprising hydrophobic vitamin E and hydrophilic vitamin B labeled with dual pH and glutathione-responsive degradable linkages. Vitamin-based micelles (vitamicelles), formed by self-assembly in aqueous solutions, were optimized based on their stability after encapsulation of doxorubicin (DOX). The resulting vitamicelles have great potential as vehicles for anticancer drugs because they show excellent biocompatibility (>94% after 48 h of incubation) and rapid biodegradability (>90% after 2.5 h). Compared with free DOX, DOX-loaded vitamicelles showed a markedly enhanced anticancer effect as they released the drug rapidly and inhibited drug efflux out of cells efficiently. By exploiting these advantages, this study not only provides a promising strategy for circumventing existing challenges regarding the delivery of anticancer drugs but also extends the utility of current DOX-induced chemotherapy.
Stimulus-Responsive Smart Nanoparticles-Based CRISPR-Cas Delivery for Therapeutic Genome Editing
Authors: Naeem Muhammad , Hoque Mubasher Zahir , Ovais Muhammad , Basheer Chanbasha , Ahmad Irshad
Published: October 2021

The innovative research in genome editing domains such as CRISPR-Cas technology has enabled genetic engineers to manipulate the genomes of living organisms effectively in order to develop the next generation of therapeutic tools. This technique has started the new era of “genome surgery”. Despite these advances, the barriers of CRISPR-Cas9 techniques in clinical applications include efficient delivery of CRISPR/Cas9 and risk of off-target effects. Various types of viral and non-viral vectors are designed to deliver the CRISPR/Cas9 machinery into the desired cell. These methods still suffer difficulties such as immune response, lack of specificity, and efficiency. The extracellular and intracellular environments of cells and tissues differ in pH, redox species, enzyme activity, and light sensitivity. Recently, smart nanoparticles have been synthesized for CRISPR/Cas9 delivery to cells based on endogenous (pH, enzyme, redox specie, ATP) and exogenous (magnetic, ultrasound, temperature, light) stimulus signals. These methodologies can leverage genome editing through biological signals found within disease cells with less off-target effects. Here, we review the recent advances in stimulus-based smart nanoparticles to deliver the CRISPR/Cas9 machinery into the desired cell. This review article will provide extensive information to cautiously utilize smart nanoparticles for basic biomedical applications and therapeutic genome editing.
The Spatiotemporal Coupling: Regional Energy Failure and Aberrant Proteins in Neurodegenerative Diseases
Authors: Virtuoso Assunta , Colangelo Anna Maria , Maggio Nicola , Fennig Uri , Weinberg Nitai , Papa Michele , De Luca Ciro
Published: October 2021

The spatial and temporal coordination of each element is a pivotal characteristic of systems, and the central nervous system (CNS) is not an exception. Glial elements and the vascular interface have been considered more recently, together with the extracellular matrix and the immune system. However, the knowledge of the single-element configuration is not sufficient to predict physiological or pathological long-lasting changes. Ionic currents, complex molecular cascades, genomic rearrangement, and the regional energy demand can be different even in neighboring cells of the same phenotype, and their differential expression could explain the region-specific progression of the most studied neurodegenerative diseases. We here reviewed the main nodes and edges of the system, which could be studied to develop a comprehensive knowledge of CNS plasticity from the neurovascular unit to the synaptic cleft. The future goal is to redefine the modeling of synaptic plasticity and achieve a better understanding of neurological diseases, pointing out cellular, subcellular, and molecular components that couple in specific neuroanatomical and functional regions.
Knockdown NRPC2, 3, 8, NRPABC1 and NRPABC2 Affects RNAPIII Activity and Disrupts Seed Development in Arabidopsis
Authors: Zhao Hailiang , Qin Yao , Xiao Ziyi , Liang Kun , Gong Dianming , Sun Qin , Qiu Fazhan
Published: October 2021

RNA polymerase III (RNAPIII) contains 17 subunits forming 4 functional domains that control the different stages of RNAPIII transcription and are dedicated to the synthesis of small RNAs such as 5S rRNA and tRNAs. Here, we identified 23 genes encoding these subunits in Arabidopsis (Arabidopsis thaliana) and further analyzed 5 subunits (NRPC2, NRPC3, NRPC8, NRPABC1, and NRPABC2) encoded by 6 genes with different expression patterns and belonging to different sub-complexes. The knockdown of these genes repressed the expression of 5S rRNA and tRNAs, causing seed developmental arrest at different stages. Among these knockdown mutants, RNA-seq analysis revealed 821 common differentially expressed genes (DEGs), significantly enriched in response to stress, abscisic acid, cytokinins, and the jasmonic acid signaling pathway. Weighted gene co-expression network analysis (WGCNA) revealed several hub genes involved in embryo development, carbohydrate metabolic and lipid metabolic processes. We identified numerous unique DEGs between the mutants belonging to pathways, including cell proliferation, ribosome biogenesis, cell death, and tRNA metabolic processes. Thus, NRPC2, NRPC3, NRPC8, NRPABC1, and NRPABC2 control seed development in Arabidopsis by influencing RNAPIII activity and, thus, hormone signaling. Reduced expression of these subunit genes causes an insufficient accumulation of the total RNAPIII, leading to the phenotypes observed following the genetic knockdown of these subunits.
Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
Authors: Rahman Noor , Khan Haroon , Zia Asad , Khan Asifullah , Fakhri Sajad , Aschner Michael , Gul Karim , Saso Luciano
Published: October 2021

Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy.
Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
Authors: Al-Ani Abdullah , Toms Derek , Sunba Saud , Giles Kayla , Touahri Yacine , Schuurmans Carol , Ungrin Mark
Published: October 2021

The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-µTs) that are suitable for scalable production and delivery via injection. RPE-µTs retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch’s membrane, suggesting that RPE-µTs may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery.
Robust and Precise Matching Algorithm Combining Absent Color Indexing and Correlation Filter
Authors: Tian Ying , Kaneko Shun’ichi , Sasatani So , Itoh Masaya , Fang Ming
Published: October 2021

This paper presents a novel method that absorbs the strong discriminative ability from absent color indexing (ABC) to enhance sensitivity and combines it with a correlation filter (CF) for obtaining a higher precision; this method is named ABC-CF. First, by separating the original color histogram, apparent and absent colors are introduced. Subsequently, an automatic threshold acquisition is proposed using a mean color histogram. Next, a histogram intersection is selected to calculate the similarity. Finally, CF follows them to solve the drift caused by ABC during the matching process. The novel approach proposed in this paper realizes robustness in distortion of target images and higher margins in fundamental matching problems, and then achieves more precise matching in positions. The effectiveness of the proposed approach can be evaluated in the comparative experiments with other representative methods by use of the open data.
Algebraic Fault Analysis of SHA-256 Compression Function and Its Application
Authors: Nakamura Kazuki , Hori Koji , Hirose Shoichi
Published: October 2021

Cryptographic hash functions play an essential role in various aspects of cryptography, such as message authentication codes, pseudorandom number generation, digital signatures, and so on. Thus, the security of their hardware implementations is an important research topic. Hao et al. proposed an algebraic fault analysis (AFA) for the SHA-256 compression function in 2014. They showed that one could recover the whole of an unknown input of the SHA-256 compression function by injecting 65 faults and analyzing the outputs under normal and fault injection conditions. They also presented an almost universal forgery attack on HMAC-SHA-256 using this result. In our work, we conducted computer experiments for various fault-injection conditions in the AFA for the SHA-256 compression function. As a result, we found that one can recover the whole of an unknown input of the SHA-256 compression function by injecting an average of only 18 faults on average. We also conducted an AFA for the SHACAL-2 block cipher and an AFA for the SHA-256 compression function, enabling almost universal forgery of the chopMD-MAC function.
Effects of Aqueous Extracts of Endophyte-Infected Grass Achnatherum inebrians on Growth and Development of Pea Aphid Acyrthosiphon pisum
Authors: Ma Yaling , Li Chunjie , White James F.
Published: October 2021

The pea aphid Acyrthosiphon pisum has a worldwide distribution and causes serious losses for agricultural production. Drunken horse grass Achnatherum inebrians is a widely distributed perennial poisonous grass on the grasslands of Northern and Northwestern China. The present study focused on contact toxicity activity of aqueous extracts of endophyte-infected (E+) and endophyte-free (E−) A. inebrians in different growth periods of pea aphids, and the growth and development of two color morphs of F1 generation nymphs. Both of the color morphs had development durations in E+ treatments that tended to be longer at 1st, 2nd, 3rd, and 4th instars than E− and control (CK). The E+ treated aphids also showed decreased weights at maturity with over all lower mean relative growth rates (MRGR). Aphid survival of E+ treated aphids was lower than that of E− and CK at all growth periods. Seeding stage E+ extracts showed a greater propensity for negatively affecting aphids than did E+ extract at maturity and the yellowing stage. These results show that extracts from endophyte-containing plants may contain compounds that may be used to control insects.