bluuebunny/crossref_metadata_2025 huggingface dataset:
N-Acetylcysteine Administration Improves the Redox and Functional Gene Expression Levels in Spleen, Mesenteric Lymph Node and Gastrocnemius Muscle in Piglets Infected with Porcine Epidemic Diarrhea Virus
Authors: Zhang Yanyan , Tian Junjie , Wang Chao , Wu Tao , Yi Dan , Wang Lei , Zhao Di , Hou Yongqing
Published: January 2023

Our previous study reported that N-acetylcysteine (NAC) administration improved the function of intestinal absorption in piglets infected with porcine epidemic diarrhea virus (PEDV). However, the effects of NAC administration on the functions of other tissues and organs in PEDV-infected piglets have not been reported. In this study, the effects of NAC on the liver, spleen, lung, lymph node, and gastrocnemius muscle in PEDV-infected piglets were investigated. Thirty-two 7-day-old piglets with similar body weights were randomly divided into one of four groups: Control group, NAC group, PEDV group, and PEDV+NAC group (eight replicates per group and one pig per replicate). The trial had a 2 × 2 factorial design consisting of oral administration of 0 or 25 mg/kg body weight NAC and oral administration of 0 or 1.0 × 104.5 TCID50 PEDV. The trial lasted 12 days. All piglets were fed a milk replacer. On days 5–9 of the trial, piglets in the NAC and PEDV + NAC groups were orally administered NAC once a day; piglets in the control and PEDV groups were orally administered the same volume of saline. On day 9 of trial, piglets in the PEDV and PEDV+NAC groups were orally administrated 1.0 × 104.5 TCID50 PEDV, and the piglets in the control and NAC groups were orally administrated the same volume of saline. On day 12 of trial, samples, including of the liver, spleen, lung, lymph node, and gastrocnemius muscle, were collected. PEDV infection significantly increased catalase activity but significantly decreased the mRNA levels of Keap1, Nrf2, HMOX2, IFN-α, MX1, IL-10, TNF-α, S100A12, MMP3, MMP13, TGF-β, and GJA1 in the spleens of piglets. NAC administration ameliorated abnormal changes in measured variables in the spleens of PEDV-infected piglets. In addition, NAC administration also enhanced the antioxidant capacity of the mesenteric lymph nodes and gastrocnemius muscles in PEDV-infected piglets. Collectively, these novel results revealed that NAC administration improved the redox and functional gene expression levels in the spleen, mesenteric lymph nodes, and gastrocnemius muscle in PEDV-infected piglets.
Behind the Curtain: In Silico and In Vitro Experiments Brought to Light New Insights into the Anticryptococcal Action of Synthetic Peptides
Authors: Aguiar Tawanny K. B. , Neto Nilton A. S. , Silva Romério R. S. , Freitas Cleverson D. T. , Mesquita Felipe P. , Alencar Luciana M. R. , Santos-Oliveira Ralph , Goldman Gustavo H. , Souza Pedro F. N.
Published: January 2023

Cryptococcus neoformans is the pathogen responsible for cryptococcal pneumonia and meningitis, mainly affecting patients with suppressed immune systems. We have previously revealed the mechanism of anticryptococcal action of synthetic antimicrobial peptides (SAMPs). In this study, computational and experimental analyses provide new insights into the mechanisms of action of SAMPs. Computational analysis revealed that peptides interacted with the PHO36 membrane receptor of C. neoformans. Additionally, ROS (reactive oxygen species) overproduction, the enzymes of ROS metabolism, interference in the ergosterol biosynthesis pathway, and decoupling of cytochrome c mitochondrial membrane were evaluated. Three of four peptides were able to interact with the PHO36 receptor, altering its function and leading to ROS overproduction. SAMPs-treated C. neoformans cells showed a decrease in scavenger enzyme activity, supporting ROS accumulation. In the presence of ascorbic acid, an antioxidant agent, SAMPs did not induce ROS accumulation in C. neoformans cells. Interestingly, two SAMPs maintained inhibitory activity and membrane pore formation in C. neoformans cells by a ROS-independent mechanism. Yet, the ergosterol biosynthesis and lactate dehydrogenase activity were affected by SAMPs. In addition, we noticed decoupling of Cyt c from the mitochondria, which led to apoptosis events in the cryptococcal cells. The results presented herein suggest multiple mechanisms imposed by SAMPs against C. neoformans interfering in the development of resistance, thus revealing the potential of SAMPs in treating infections caused by C. neoformans.
Interconnected Set of Enzymes Provide Lysine Biosynthetic Intermediates and Ornithine Derivatives as Key Precursors for the Biosynthesis of Bioactive Secondary Metabolites
Authors: Liras Paloma , Martín Juan Francisco
Published: January 2023

Bacteria, filamentous fungi, and plants synthesize thousands of secondary metabolites with important biological and pharmacological activities. The biosynthesis of these metabolites is performed by networks of complex enzymes such as non-ribosomal peptide synthetases, polyketide synthases, and terpenoid biosynthetic enzymes. The efficient production of these metabolites is dependent upon the supply of precursors that arise from primary metabolism. In the last decades, an impressive array of biosynthetic enzymes that provide specific precursors and intermediates leading to secondary metabolites biosynthesis has been reported. Suitable knowledge of the elaborated pathways that synthesize these precursors or intermediates is essential for advancing chemical biology and the production of natural or semisynthetic biological products. Two of the more prolific routes that provide key precursors in the biosynthesis of antitumor, immunosuppressant, antifungal, or antibacterial compounds are the lysine and ornithine pathways, which are involved in the biosynthesis of β-lactams and other non-ribosomal peptides, and bacterial and fungal siderophores. Detailed analysis of the molecular genetics and biochemistry of the enzyme system shows that they are formed by closely related components. Particularly the focus of this study is on molecular genetics and the enzymatic steps that lead to the formation of intermediates of the lysine pathway, such as α-aminoadipic acid, saccharopine, pipecolic acid, and related compounds, and of ornithine-derived molecules, such as N5-Acetyl-N5-Hydroxyornithine and N5-anhydromevalonyl-N5-hydroxyornithine, which are precursors of siderophores. We provide evidence that shows interesting functional relationships between the genes encoding the enzymes that synthesize these products. This information will contribute to a better understanding of the possibilities of advancing the industrial applications of synthetic biology.
Evidence of Increased Oxidative Stress in the Placental Tissue of Women Who Suffered an Episode of Psychosis during Pregnancy
Authors: Ortega Miguel A. , Fraile-Martinez Oscar , García-Montero Cielo , Rodriguez-Martín Sonia , Funes Moñux Rosa M. , Bravo Coral , De Leon-Luis Juan A. , Saz Jose V. , Saez Miguel A. , Guijarro Luis G. , Lahera Guillermo , Monserrat Jorge , Mora Fernando , Quintero Javier , Bujan Julia , García-Honduvilla Natalio , Alvarez-Mon Melchor , Alvarez-Mon Miguel Angel
Published: January 2023

Psychosis is a complex clinical syndrome resulting in a loss of contact with reality and alterations in behavior and sensorial and motor functions. Although the onset of psychosis can be related to any medical condition, most cases of psychosis are not fully understood. Psychosis may manifest for the first time during pregnancy, which is detrimental to maternofetal well-being. The impact of having a first episode of psychosis during pregnancy on the placenta has not yet been explored. Oxidative stress is thought to take part in the etiopathogenesis of this complex disorder, and this condition can also affect the placenta as it is highly sensitive to changes in the maternal environment. In this sense, the aim of the present work was to study the gene and protein expression through RT–qPCR and immunohistochemistry, respectively, of oxidative stress markers (NOX-1, NOX-2, iNOS, eNOS and PARP) in the placental tissue of women who underwent a first episode of psychosis during pregnancy (FE-PW) in comparison to healthy pregnant women. Our results showed augmented gene and protein expression of NOX-1, NOX-2, iNOS and PARP in the placental tissue of FE-PW. For the first time, we demonstrated that oxidative stress may have an important pathophysiological role in this tissue, aiding in explaining the impact of psychosis on pregnancy and the need for future studies in this field to guide better clinical management of these patients.
Impact of Phenolic Acid Derivatives on the Oxidative Stability of β-Lactoglobulin-Stabilized Emulsions
Authors: Bock Alina , Kieserling Helena , Steinhäuser Ulrike , Rohn Sascha
Published: January 2023

Proteins, such as β-lactoglobulin (β-Lg), are often used to stabilize oil–water-emulsions. By using an additional implementation of phenolic compounds (PC) that might interact with the proteins, the oxidative stability can be further improved. Whether PC have a certain pro-oxidant effect on oxidation processes, while interacting non-covalently (pH-6) or covalently (pH.9) with the interfacial protein-film, is not known. This study aimed to characterize the impact of phenolic acid derivatives (PCDs) on the antioxidant efficacy of the interfacial β-Lg-film, depending on their structural properties and pH-value. Electron paramagnetic resonance (EPR) analyses were performed to assess the radical scavenging in the aqueous and oil phases of the emulsion, and the complexation of transition metals: these are well known to act as pro-oxidants. Finally, in a model linseed oil emulsion, lipid oxidation products were analyzed over storage time in order to characterize the antioxidant efficacy of the interfacial protein-film. The results showed that, at pH.6, PCDs can scavenge hydrophilic radicals and partially scavenge hydrophobic radicals, as well as reduce transition metals. As expected, transition metals are complexed to only a slight degree, leading to an increased lipid oxidation through non-complexed reduced transition metals. At pH.9, there is a strong complexation between PCDs and the transition metals and, therefore, a decreased ability to reduce the transition metals; these do not promote lipid oxidation in the emulsion anymore.
Isoscalar Giant Monopole Resonance in Spherical Nuclei as a Nuclear Matter Incompressibility Indicator
Authors: Gaidarov Mitko K. , Ivanov Martin V. , Katsarov Yordan I. , Antonov Anton N.
Published: January 2023

The incompressibility of both nuclear matter and finite nuclei is estimated by the monopole compression modes in nuclei in the framework of a nonrelativistic Hartree–Fock–Bogoliyubov method and the coherent density fluctuation model. The monopole states originate from vibrations of the nuclear density. The calculations in the model for the incompressibility in finite nuclei are based on the Brueckner energy–density functional for nuclear matter. Results for the energies of the breathing vibrational states and finite nuclei incompressibilities are obtained for various nuclei and their values are compared with recent experimental data. The evolution of the isoscalar giant monopole resonance (ISGMR) along Ni, Sn, and Pb isotopic chains is discussed. This approach can be applied to analyses of neutron stars properties, such as incompressibility, symmetry energy, slope parameter, and other astrophysical quantities, as well as for modelling dynamical behaviors within stellar environments.
Impact of Various Disturbance Sources on the Atmospheric Electric Field and Thunderstorm Activity of the Northern Tien-Shan
Authors: Antonova Valentina , Lutsenko Vadim , Gordiyenko Galina , Kryukov Sergey
Published: January 2023

Features of the manifestations of various sources of disturbances in the atmospheric electric field at the Tien-Shan high-mountain station have been studied, and the statistical relationship between solar and thunderstorm activity has been established. Air currents arising over the ocean, having overcome the mountain gorges of the Himalayas, carry moisture to the Northern Tien-Shan and determine the weather features and thunderstorm activity at the Tien-Shan high-mountain station. It was established that the maximum and minimum thunderstorm activity at the Tien-Shan high-mountain station corresponds to the distribution curve of daily thunderstorm activity for the Asia–Australia region. The investigation showed that coronal mass ejections (CMEs) affect the atmospheric electric field by increasing or decreasing its level or causing its fluctuations, depending on the features of manifestations in the near-Earth space and in the Earth’s magnetosphere. In at least 70% of cases, thunderstorm activity was observed with a 1–2-day delay after impact on the Earth’s magnetosphere by CMEs and HSSs. A number of cases were studied when thunderstorm activity was observed in a quiet geomagnetic field. In these cases, an increase in the values of fmin (the minimum frequency of reflection from the ionosphere) and foEs (the critical frequency of the sporadic E layer) was observed, which indicated an increase in the level of radio wave absorption in the ionospheric D-region and the level of electron density at altitudes of 100–120 km.
Investigation of Wind Characteristics and Cooling Effects of Crushed-Rock Embankment with Different Pavement Widths in Permafrost Region
Authors: Zhao Hongting , Li Xiaolin , Wu Xiaopeng
Published: January 2023

A crushed-rock embankment (CRE) with a high porous crushed-rock layer (CRL) can effectively cool the underlying permafrost through natural ventilation within the layer. However, in addition to the ambient conditions, the ventilation efficiency of the CRL and its cooling effect are significantly affected by the pavement width. In this study, the local wind flow around an embankment section was first analyzed based on field monitoring data. Then, considering climate warming, a 2-D coupled model of heat and mass transfer was established to investigate the wind characteristics and the cooling effects of the CRE with different pavement widths. The results showed that the pavement width exerted considerable impacts on the wind characteristics and cooling effects of the CRE. These impacts were evaluated via variations in the wind speed, the permafrost table, and the soil temperatures. An increase in pavement width can lower the wind speed within the CRL, which is adverse to the long-term thermal regimes of the embankment and the underlying permafrost. In addition, due to differential wind flows around the embankments, an asymmetric distribution of the soil temperatures beneath the windward and leeward sides of the embankments existed. Overall, it is hoped that the results of this study can provide informative references for the Qinghai–Tibet expressway that is constructed in permafrost regions.
Enhancing Performance of LiFePO4 Battery by Using a Novel Gel Composite Polymer Electrolyte
Authors: Wu Ke , Hu Naiqi , Wang Shuchan , Geng Zhiyuan , Deng Wenwen
Published: January 2023

Composite polymer electrolyte (CPE) is expected to have great prospects in solid-state batteries. However, their application is impeded due to the poor interfacial compatibility between CPE and electrodes that result in sluggish ionic transformation, especially at low temperatures. Here, on the basis of Poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) polymer electrolyte, gel composite polymer electrolyte (GCPE) with fast Li+ transport channel is prepared by in-situ polymerization with poly (ethylene glycol) methyl ether acrylate (PEGMEA) monomer and FEC as additive. Compared with CPE, GCPE increases the ionic conductivity by 10 times. It also achieves more uniform lithium precipitation and significantly inhibits the growth of lithium dendrites. The LFP/GCPE/Li battery has a capacity retention of over 99% at both room temperature and 0 °C after 100 cycles. In addition, the coulombic efficiency is above 99% during cycling. Our work provides a new technology to prepare GCPE with high ionic conductivity at both room temperature and low temperatures that has great potential in the application of solid-state lithium batteries.
Sex Differences in Microglia Activation in a Rodent Model of Preterm Hypoxic Ischemic Injury with Caffeine Treatment
Authors: McLeod Ruth Mae , Rosenkrantz Ted S. , Fitch Roslyn Holly , Koski Rachel R.
Published: January 2023

Preterm infants are often treated with caffeine as a respiratory stimulant. However, follow-up data shows caffeine may also have neuroprotective potential. There are several theories as to how caffeine might protect the brain, but none have been proven. This study looked at caffeine effects on microglial activation in rodent brains post hypoxic ischemic (HI) injury. Rat pups underwent either sham or HI surgery on P6, followed by treatment with either caffeine or saline. Forty-eight hours post-injury, brains were collected and underwent paraffin embedding and sectioning followed by immunofluorescence staining. Ionized calcium binding adaptor molecule 1 (Iba-1) was used to label microglia, and 4′,6-diamindino-2-phenylindole (DAPI) was used to label DNA. Cell size measurements of microglia were obtained to gauge microglia activation, and chromatin condensation (DAPI optical density) was used as an index of neuronal cell death. Results suggest that caffeine does offer protective effects, based on significantly increased levels of cell death in HI-saline animals not seen in caffeine-treated HI males and females. However, the mechanism of action may be different. Male HI animals showed marginally reduced microglial activation following caffeine treatment, whereas females did not. Results indicate that though caffeine may act protectively in both sexes by reducing cell death, the benefits may be mediated by different mechanisms.
Esterification of p-Coumaric Acid Improves the Control over Melanoma Cell Growth
Authors: Carmo-Martins Joana I. , Gonzatti Michelangelo B. , Varela Marina T. , Sousa Maria Eduarda P. , Costa Lucas V. S. , Rodrigues Elaine Guadelupe , Fernandes João Paulo S. , Keller Alexandre C.
Published: January 2023

Previous studies reported that p-coumaric acid modulates melanoma growth. Because the esterification of p-coumaric acid (p-CA) enhanced its activity as an antimelanogenic agent, we aimed to determine the antitumor potential of two derivatives, the ethyl and butyl esters, against the murine B16-F10 and the human SK-MEL-25 melanoma cells. Cell viability was determined in vitro by the lactate dehydrogenase release and violet crystal absorption assays. The cell proliferation rate and cell cycle behavior were determined by the colony formation assay and flow cytometry analysis. Although p-CA, at the concentration of 1 mM, failed to exert a significant antitumor activity, the ethyl and butyl ester derivatives caused substantial tumor cell death at doses < 1 mM. Despite a reduction in their direct cytotoxicity at minor doses, both products controlled the melanoma growth by arresting the cell cycle at the G0/G1 (B16-F10) or S/G2 (SK-MEL-25). Furthermore, the in vivo experiments showed that the butyl ester derivative suppressed the lung B16-F10 burden, compared to the p-CA-treated mice. Thus, the esterification of p-coumaric acid improved the control over the proliferation of murine and human melanoma cells and can be considered an approach for designing novel anticancer agents.
Efficacy of the Use of Wii Games in the Physical and Functional Training of the Elderly: Protocol of a Systematic Review
Authors: Lima Andreia , Moreira Maria Teresa , Ferreira Maria Salomé , Parola Vítor , Mendes Dárcio Tadeu , Nóbrega Maria do Perpétuo , Fernandes Carla
Published: January 2023

Background: Scientific and technological development has constituted a reality in the lives of populations, making it unimaginable to live without specific incentives that development has allowed. That said, given the increase in the longevity of people, it will be helpful to implement these resources in promoting health and disease prevention in the elderly. The objective of this study is to identify, in the scientific evidence, the effects of Wii games on the physical training of the elderly. Methods: A systematic review will be carried out according to the methodology recommended by the Joanna Briggs Institute. Relevant databases will be used for the research, where the words will be used: rehabilitation, exercise, physical activity, rehabilitation exercise; movement; therapeutic exercise; engine activity; rehabilitation, geriatric, gerontologic care, and aged. Results: This systematic review will include experimental and quasi-experimental studies, including randomised studies with and without a control group, pre- and post-assessment. Conclusions: To promote the autonomy of the elderly and consequently healthy and prosperous ageing, it is crucial to implement all available measures and resources. For this purpose, exergames have been shown to be effective, and it is necessary to know which ones are suitable for the physical training of the elderly. This one protocol is registered with the Open Science Framework.
Recent Advances in Electrochemical Immunosensors with Nanomaterial Assistance for Signal Amplification
Authors: Police Patil Avinash V. , Chuang Yu-Sheng , Li Chenzhong , Wu Ching-Chou
Published: January 2023

Electrochemical immunosensors have attracted immense attention due to the ease of mass electrode production and the high compatibility of the miniature electric reader, which is beneficial for developing point-of-care diagnostic devices. Electrochemical immunosensors can be divided into label-free and label-based sensing strategies equipped with potentiometric, amperometric, voltammetric, or impedimetric detectors. Emerging nanomaterials are frequently used on electrochemical immunosensors as a highly rough and conductive interface of the electrodes or on nanocarriers of immobilizing capture antibodies, electroactive mediators, or catalyzers. Adopting nanomaterials can increase immunosensor characteristics with lower detection limits and better sensitivity. Recent research has shown innovative immobilization procedures of nanomaterials which meet the requirements of different electrochemical immunosensors. This review discusses the past five years of advances in nanomaterials (metal nanoparticles, metal nanostructures, carbon nanotubes, and graphene) integrated into the electrochemical immunosensor. Furthermore, the new tendency and endeavors of nanomaterial-based electrochemical immunosensors are discussed.
Reduced Sleep Amount and Increased Sleep Latency in Prisoners: A Pilot Study in an Italian Jail
Authors: D’Aurizio Giulia , Tosti Beatrice , Tempesta Daniela , Avvantaggiato Lucia , Splendiani Alessandra , Sacco Simona , Mandolesi Laura , Curcio Giuseppe
Published: January 2023

Several previous subjective- or interview-based reports indicated a reduced sleep quality and quantity as well as a great incidence of insomnia troubles in prisoners living in jail. The aim of the present study is to assess the quality and quantity of sleep by using, for the first time, actigraphy. A total of thirty male prisoners and thirty male control volunteers accepted to participate in this study: to this end, they filled in some questionnaires to assess state and trait anxiety, depression, sleep quality, and insomnia severity. In addition, their sleep was actigraphically recorded for seven consecutive nights. The main results indicate a worsened mood in prisoners than in controls (with increased anxiety and depression) as well as a subjectively reported low sleep quality (higher scores at PSQI) with a clinical presence of insomnia complaints (as indicated by ISI scores). Moreover, objectively assessed sleep by means of actigraphy exhibited some worrying results, namely a longer sleep onset and a reduced total sleep time was seen in prisoners with respect to controls. The results have been discussed in the light of potential effects of sleep quality and quantity as well as of mood symptoms on cognitive functioning, as well as with respect to prisoners’ health and well-being.
Psychological Contract and Young Talent Retention in Vietnam: Development and Validation of a Hierarchical Reflective Structural Model
Authors: Dam Ngan , Hack-Polay Dieu , Rahman Mahfuzur , Mahmoud Ali B.
Published: January 2023

This research investigates the relationship between relational psychological contract and the retention of young talents in Vietnam. The study surveyed young employees pertaining to (Generations Y and Z) at BBB Company. The results show an equal weight of transactional and relational psychological contracts in the job satisfaction and retention of young Vietnamese employees. The research compared the relative importance of future growth potential against existing good practices. The results indicate that these two constructs have equal importance, as the value for r square is almost equal. This suggests that from a strategic standpoint Human Resource Management (HRM) ought to prioritise the development of practices that enhance both relational and transactional psychological contracts among young talents in Vietnam. This derives from a cultural transition, which means that both the weights of national culture and globalisation are influencing the choices and loyalty of the younger generations in the workplace. These findings have significant implications for the understanding of how generational differences and culture influence how a company retains their young talents and the importance of psychological contract for young employee commitment in Vietnam in an increasingly competitive environment.
Rectal Sparing Approaches after Neoadjuvant Treatment for Rectal Cancer: A Systematic Review and Meta-Analysis Comparing Local Excision and Watch and Wait
Authors: Bao Quoc Riccardo , Ferrari Stefania , Capelli Giulia , Ruffolo Cesare , Scarpa Marco , Agnes Amedea , Chiloiro Giuditta , Palazzari Elisa , Urso Emanuele Damiano Luca , Pucciarelli Salvatore , Spolverato Gaya
Published: January 2023

Local Excision (LE) or Watch and Wait (WW) for patients with complete clinical response or near-complete clinical response after neoadjuvant chemoradiotherapy (nCRT) were proposed to avoid morbidity and impairment of quality of life after rectal resection. The aim of this study is to perform a systematic review of the literature, and to compare rectal-sparing approaches, in terms of rectum-preservation rate, local control, and distant recurrences. A systematic review and meta-analysis were performed of studies published until July 2022 (PROSPERO, registration CRD42022341480), and the quality of evidence was assessed using a GRADE approach. Seven retrospective studies and one prospective trial were included. In six studies, patients were treated with standard long-course nCRT, and in two with Total Neoadjuvant Therapy (TNT). Overall, there were 213 and 188 patients in WW and LE group, respectively, and no difference was found between WW and LE when considering rectum-preservation rate (OR 0.80 95%CI 0.31–2.01, p = 0.63), local disease (OR 1.60 95%CI 0.75–3.42, p = 0.22), locoregional failure (OR 0.85 95%CI 0.20–3.66, p = 0.83) and distant recurrence (OR 0.76 95%CI 0.37–1.55, p = 0.45). Studies directly comparing WW and LE are still lacking, even though no differences between WW and LE in terms of rectum-preservation, local control, and distant recurrences have been found.
AT-101 Enhances the Antitumor Activity of Lenalidomide in Patients with Multiple Myeloma
Authors: Ailawadhi Sikander , Parrondo Ricardo D. , Dutta Navnita , Han Bing , Ciccio Gina , Cherukuri Yesesri , Alegria Victoria R. , LaPlant Betsy R. , Roy Vivek , Sher Taimur , Edwards Brett , Lanier Stephanie , Manna Alak , Heslop Keisha , Caulfield Thomas , Maldosevic Emir , Storz Peter , Manochakian Rami , Asmann Yan , Chanan-Khan Asher A. , Paulus Aneel
Published: January 2023

Bcl-2 and Mcl-1 proteins play a role in multiple myeloma (MM) cell survival, for which targeted inhibitors are being developed. AT-101 is an oral drug, which disrupts Bcl-2 and Mcl-1 function, impedes mitochondrial bioenergetic processes and induces apoptosis in MM cells. When combined with lenalidomide and dexamethasone (Rd), AT-101 significantly reduced tumor burden in an in vivo xenograft model of MM. These data provided rationale for a phase I/II study to establish the effective dose of AT-101 in combination with Rd (ARd regimen) in relapsed/refractory MM. A total of 10 patients were enrolled, most with high-risk cytogenetics (80%) and prior stem cell transplant (70%). Three patients were lenalidomide-refractory, 2 were bortezomib-refractory and 3 were daratumumab-refractory. The ARd combination was well tolerated with most common grade 3/4 adverse events being cytopenia’s. The overall response rate was 40% and clinical benefit rate was 90%. The median progression free survival was 14.9 months (95% CI 7.1-NE). Patients responsive to ARd showed a decrease in Bcl-2:Bim or Mcl-1:Noxa protein complexes, increased CD8+ T and NK cells and depletion of T and B-regulatory cells. The ARd regimen demonstrated an acceptable safety profile and promising efficacy in patients with relapsed/refractory MM prompting further investigation in additional patients.
Monoclonal Gammopathy of Thrombotic Significance
Authors: Gkalea Vasiliki , Fotiou Despina , Dimopoulos Meletios Athanasios , Kastritis Efstathios
Published: January 2023

The current review provides an overview of the thrombotic risk observed in patients with MG who do not otherwise require treatment. We discuss clinical and biomarker studies that highlight the heterogenous hemostatic profile observed in these patients and how knowledge has evolved over the past 20 years. Biomarker studies suggest shared biologic features between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), which involves both hypercoagulability and platelet activation. Hemostatic abnormalities identified in MGUS patients cannot be translated into clinical practice as they lack correlation to clinical events. The prothrombotic phenotype of MGUS patients has not been ascertained yet, but novel data on coagulation markers are promising. We also review rare conditions associated with the thrombogenic properties of the monoclonal protein that predispose to arterial, venous or microthrombotic events and demonstrate that the M-protein can be linked to clinically significant thrombotic events. Cryoglobulinemia, cryofibrinogenemia, cryo-crystaloglobulinemia and MG-related antiphospholipid syndrome are reviewed. We propose the new umbrella term “monoclonal gammopathy of thrombotic significance” (MGTS) to refer to significant, recurrent thrombotic events in patients with MGUS that provide a rationale for targeting the underlying plasma cell clone. Identifying MGUS patients at high risk for thrombotic events is currently a challenge.
A Promising Ash Supplementation Strategy in the Cultivation of Spirodela polyrrhiza Plants
Authors: Romanowska-Duda Zdzisława , Piotrowski Krzysztof , Stępiński Dariusz , Popłońska Katarzyna
Published: January 2023

An innovative approach to the management of waste in the form of ash obtained during biomass combustion is justified due to its specific properties, including the presence of macro- and microelements. The aim of the current study was to determine the concentration of ash obtained from Sorghum combustion regarding its fertilizer value and its effect on the cytological structures, physiological parameters, growth and development of Lemnaceae plants, thereby demonstrating the possibility of using this waste to supplement culture media. The analyses showed that the use of ash in the in vitro cultivation of Lemnaceae aquatic plants had a dose-dependent effect. The addition of 2% ash favorably affected the condition of plant roots, i.e., meristem elongation and an increase in nucleoli sizes as well as improving the chlorophyll content index, gas exchange parameters, chemical oxygen demand (COD) and plant vigor via PSII, which was confirmed by a chlorophyll fluorescence measurement. On the other hand, too high of a concentration, i.e., 10% ash, adversely affected the plant development and parameters studied. Concluding, the use of ash at a low concentration favorably affected the yielding of Spirodela polyrrhiza, whose biomass can be used for energy purposes in the production of bioethanol, plant biogas or the phytoremediation of industrial waters and leachate.
Chloroquine Enhances Death in Lung Adenocarcinoma A549 Cells Exposed to Cold Atmospheric Plasma Jet
Authors: Patrakova Ekaterina , Biryukov Mikhail , Troitskaya Olga , Gugin Pavel , Milakhina Elena , Semenov Dmitriy , Poletaeva Julia , Ryabchikova Elena , Novak Diana , Kryachkova Nadezhda , Polyakova Alina , Zhilnikova Maria , Zakrevsky Dmitriy , Schweigert Irina , Koval Olga
Published: January 2023

Cold atmospheric plasma (CAP) is an intensively-studied approach for the treatment of malignant neoplasms. Various active oxygen and nitrogen compounds are believed to be the main cytotoxic effectors on biotargets; however, the comprehensive mechanism of CAP interaction with living cells and tissues remains elusive. In this study, we experimentally determined the optimal discharge regime (or semi-selective regime) for the direct CAP jet treatment of cancer cells, under which lung adenocarcinoma A549, A427 and NCI-H23 cells demonstrated substantial suppression of viability, coupled with a weak viability decrease of healthy lung fibroblasts Wi-38 and MRC-5. The death of CAP-exposed cancer and healthy cells under semi-selective conditions was caspase-dependent. We showed that there was an accumulation of lysosomes in the treated cells. The increased activity of lysosomal protease Cathepsin D, the transcriptional upregulation of autophagy-related MAPLC3B gene in cancer cells and the changes in autophagy-related proteins may have indicated the activation of autophagy. The addition of the autophagy inhibitor chloroquine (CQ) after the CAP jet treatment increased the death of A549 cancer cells in a synergistic manner and showed a low effect on the viability of CAP-treated Wi-38 cells. Downregulation of Drp1 mitochondrial protein and upregulation of PINK1 protein in CAP + CQ treated cells indicated that CQ increased the CAP-dependent destabilization of mitochondria. We concluded that CAP weakly activated pro-survival autophagy in irradiated cells, and CQ promoted CAP-dependent cell death due to the destabilization of autophagosomes formation and mitochondria homeostasis. To summarize, the combination of CAP treatment with CQ could be useful for the development of cold plasma-based antitumor approaches for clinical application.
The Contribution of Tumor Derived Exosomes to Cancer Cachexia
Authors: Pitzer Christopher R. , Paez Hector G. , Alway Stephen E.
Published: January 2023

Cancer cachexia is defined as unintentional weight loss secondary to neoplasia and is associated with poor prognosis and outcomes. Cancer cachexia associated weight loss affects both lean tissue (i.e., skeletal muscle) and adipose tissue. Exosomes are extracellular vesicles that originate from multivesicular bodies that contain intentionally loaded biomolecular cargo. Exosome cargo includes proteins, lipids, mitochondrial components, and nucleic acids. The cargo carried in exosomes is thought to alter cell signaling when it enters into recipient cells. Virtually every cell type secretes exosomes and exosomes are known to be present in nearly every biofluid. Exosomes alter muscle and adipose tissue metabolism and biological processes, including macrophage polarization and apoptosis which contribute to the development of the cachexia phenotype. This has led to an interest in the role of tumor cell derived exosomes and their potential role as biomarkers of cancer cell development as well as their contribution to cachexia and disease progression. In this review, we highlight published findings that have studied the effects of tumor derived exosomes (and extracellular vesicles) and their cargo on the progression of cancer cachexia. We will focus on the direct effects of tumor derived exosomes and their cellular cross talk on skeletal muscle and adipose tissue, the primary sites of weight loss due to cancer cachexia.
Evaluating Changes in Perceived Enjoyment throughout a 12-Week School-Based Exergaming Intervention
Authors: Röglin Lisa , Stoll Oliver , Ketelhut Kerstin , Martin-Niedecken Anna Lisa , Ketelhut Sascha
Published: January 2023

This study assessed whether a high-intensity exergame represents an enjoyable training tool for children in the elementary school setting. Furthermore, it evaluated whether gender, body mass index (BMI), waist-to-height ratio (WHtR), fitness level, weekly physical activity level, and general interest in sports moderate perceived enjoyment during the 12-week intervention. Thirty fifth- and sixth-grade students (10.5 ± 0.7 years; 50% girls) participated in this study. During baseline assessments, anthropometric measurements and a shuttle run test were conducted. Throughout the intervention period, the students participated in 15–20-min exergaming sessions (ES) in the ExerCube twice a week during school hours. Enjoyment was assessed after an ES in weeks 2 and 12. Additionally, enjoyment was evaluated after a physical education (PE) class in week 2. The results reveal no significant changes in enjoyment (p = 0.164) over time. The modest changes over time were significantly affected by BMI (p = 0.027), WHtR (p = 0.007), and weekly activity level (p = 0.016). Compared to the PE class, enjoyment was significantly higher during the ES (p < 0.001). None of the covariates showed a significant effect. Mean HR during the ES reached 87.1 ± 1.9% of students’ individual maximum HR. In conclusion, the ExerCube provides a promising tool for schools to promote enjoyable moderate-to-vigorous physical activity.
Early Years Physical Activity and Motor Skills Intervention—A Feasibility Study to Evaluate an Existing Training Programme for Early Years Educators
Authors: Basterfield Laura , Machaira Theodora , Jones Dan , Rapley Tim , Araujo-Soares Vera , Cameron Neil , Azevedo Liane
Published: January 2023

A lack of fundamental motor skills (FMS) in the early years can lead to lower engagement with physical activity (PA), and track into adulthood. This study aimed to test the feasibility of an existing intervention for Early Years Educators (“Educators”) designed to increase knowledge, confidence and the ability to increase PA and FMS of children in a deprived area of England. Non-randomised design with wait-list control. Sixty-seven settings in Middlesbrough, North East England were invited. Recruitment target: 10 settings, 2 Educators per setting, four children per Educator. Intervention: one-day training course “Physical Literacy in the Early Years”, an age-appropriate theoretical and practical training course to support the development of physical literacy. Primary outcomes: recruitment, retention, acceptability of intervention and outcome measures. Secondary outcomes: change in Educators’ knowledge, intentions and behaviour, and change in children’s BMI z-score, PA and FMS. Eight settings were recruited; all Intervention Educators completed the training. Six settings participated at follow-up (four Intervention, two Control). The target for Educator recruitment was met (two per setting, total n = 16). Questionnaires were completed by 80% of Intervention Educators at baseline, 20% at follow-up. Control Educators completed zero questionnaires. No Educators took part in a process evaluation interview. Forty-eight children participated at baseline, 28 at follow-up. The intervention was deemed acceptable. The recruitment, retention and acceptability of measurements were insufficient to recommend proceeding. Additional qualitative work is needed to understand and surmount the challenges posed by the implementation of the trial.
Validation of the Arabic Version of Strengths and Difficulties Questionnaire in Early Childhood Education in Qatar
Authors: Al-Hendawi Maha
Published: January 2023

This study examined the validity of the Arabic version of the Strengths and Difficulties Questionnaire (SQD, teacher version) among a sample of young children in Qatar. Teachers rated 502 children aged four to five years from public preschools using the SDQ teacher version. The factor structure of the SDQ was analyzed using exploratory and confirmatory factor analyses. I calculated Cronbach’s alpha coefficient and item–total correlations to determine the reliability of the five subscales and overall SDQ. The findings showed acceptable reliability, with the exception of the Peer Problems Scale. Common fit statistics—including the comparative fit index, non-normed fit index, and goodness-of-fit index—were used for the confirmatory factor analysis. In general, satisfactory psychometric characteristics were observed for the preschool SDQ, suggesting that the questionnaire could be administered to preschool-age children in Qatar.
Evaluation of Solid Particle Erosion of EB-PVD TBCs under Thermal Cycling Conditions Based on a Stochastic Approach
Authors: Zhang Bochun , Chen Kuiying , Baddour Natalie
Published: January 2023

The solid particle erosion behavior of electron-beam physical vapor deposition (EB-PVD) thermal barrier coatings (TBCs) was numerically evaluated under thermal cycling conditions. The erosion rates were calculated based on the mechanics-based formulae where the model parameters are fitted to the temperature-process-dependent test data available in the literature. A stochastic approach was applied to simulate the erosion behavior toward service conditions. The mechanics-based formulae were then validated by experimentally measured temperature and sintering-dependent erosion rates from the literature. The pseudoductile erosion behavior is identified for silica particles in the EB-PVD topcoat (TC) erosion system above the intermediate temperatures (~220 °C) due to the softening of partial molten silica particles, thus leading to an increase in the cutting wear and a decrease in deformation wear. The erosion rates are found to decrease versus temperature but increase versus thermal cycles. Such erosion behavior could be attributed to propagation of sintering cracks induced at elevated temperatures. The parametric calculations show that both erosion and thermal cycling parameters have a profound effect on the erosion mechanism of EB-PVD TC. The erosion rate increases at higher solid particle velocity and accumulated mass but displays a pseudoductile erosion behavior versus variation of impacting angles. Two types of erosion mechanisms were evaluated under different thermal cycling conditions. Under the burner cycling test with a short high-temperature dwell period, the erosion mechanism of EB-PVD TBCs is governed by temperature, while under an isothermal cycling test with a high-temperature long dwell period, the erosion is determined by sintering time. The failure mechanisms of EB-PVD TBCs under solid particle erosion processes are discussed combining internal cracking within topcoat and external erosion on the surface of topcoat.
Experimental Research on Collapsibility of Xi’an Loess Improved by Calcium Lignosulfonate
Authors: Bai Zhentao , Li Dongbo , Zhao Dong , Lu Wei , Liu Jiaping
Published: January 2023

To improve the problem of collapsibility of loess, adding industrial materials such as cement is common engineering treatment, but this seriously damages the reclamation performance of soil. Calcium lignosulfonate (CLS) from paper plant waste fluids is a natural bio-based polymer with good application prospects as a soil improver. In this paper, the collapsibility and mechanical properties of CLS improved loess were investigated using a collapsibility test, gray correlation analysis, and an unconfined compressive strength test (UCS). In addition, the strengthening mechanism of CLS-improved loess was also explored based on scanning electron microscopy (SEM), microstructure parameters, and X-ray diffraction. The collapsibility coefficient decreased rapidly after CLS was admixed, and the single and double-oedometer methods showed the same change trend. The order of grey correlation degree of collapsibility on each index from large to small was: moisture content, pore ratio, dry density, and CLS content. The dosage of CLS greatly influenced the mechanical properties and collapsibility of stabilized loess. The optimum amount of CLS for Xi’an loess was 3%, at which the collapsibility coefficient was reduced by more than 95%, and the 28 d UCS increased by 180.01%. From the microstructure and mineral composition analysis perspective, CLS plays a role in filling pores and linking soil particles. After the protonation and ion exchange effect of CLS, the grain size and double electric layer thickness of mineral composition were reduced, and the structural compactness was increased. These research results are of great scientific significance for the ecological modification of soils.
Structure, Microstructure, and Dielectric Response of Polycrystalline Sr1-xZnxTiO3 Thin Films
Authors: Okhay Olena , Vilarinho Paula M. , Tkach Alexander
Published: January 2023

In a view of the research interest in the high-permittivity materials, continuous enhancement of the dielectric permittivity ε′ with Zn content was reported for conventionally prepared Sr1-xZnxTiO3 ceramics with x up to 0.009, limited by the solubility of Zn on Sr site. Here, we use a sol-gel technique and a relatively low annealing temperature of 750 °C to prepare monophasic Sr1-xZnxTiO3 thin films with higher x of 0.01, 0.05, and 0.10 on Pt/TiO2/SiO2/Si substrates. The incorporation of Zn on the Sr site is confirmed by the decrease of the lattice parameter, while the presence of Zn in the films is proven by energy dispersive spectroscopy. The film thickness is found to be ~330 nm by scanning electron microscopy, while the average grain size of 86–145 nm and roughness of 0.88–2.58 nm are defined using atomic force microscopy. ε′ measured on the films down to 10 K shows a decreasing trend with Zn content in contrast to that for weakly doped Sr1-xZnxTiO3 ceramics. At the same time, the temperature dependence of the dissipation factor tanδ reveals a peak, which intensity and temperature increase with Zn content.
HFCVO-DMN: Henry Fuzzy Competitive Verse Optimizer-Integrated Deep Maxout Network for Incremental Text Classification
Authors: Singh Gunjan , Nagpal Arpita
Published: January 2023

One of the effectual text classification approaches for learning extensive information is incremental learning. The big issue that occurs is enhancing the accuracy, as the text is comprised of a large number of terms. In order to address this issue, a new incremental text classification approach is designed using the proposed hybrid optimization algorithm named the Henry Fuzzy Competitive Multi-verse Optimizer (HFCVO)-based Deep Maxout Network (DMN). Here, the optimal features are selected using Invasive Weed Tunicate Swarm Optimization (IWTSO), which is devised by integrating Invasive Weed Optimization (IWO) and the Tunicate Swarm Algorithm (TSA), respectively. The incremental text classification is effectively performed using the DMN, where the classifier is trained utilizing the HFCVO. Nevertheless, the developed HFCVO is derived by incorporating the features of Henry Gas Solubility Optimization (HGSO) and the Competitive Multi-verse Optimizer (CMVO) with fuzzy theory. The proposed HFCVO-based DNM achieved a maximum TPR of 0.968, a maximum TNR of 0.941, a low FNR of 0.032, a high precision of 0.954, and a high accuracy of 0.955.