bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Scale-Up of Zero-Gap AEM Water Electrolysers for Hydrogen Production
Authors: Loh Adeline , Li Xiaohong , Sluijter Soraya , Shirvanian Paige , Lai Qingxue , Liang Yanyu
Published: May 2023

The design of a 10 cm2 (3.4 cm by 3.4 cm) and a 100 cm2 (10 cm by 10 cm) anion exchange membrane (AEM) water electrolyser cell for hydrogen production are described. The AEM cells are based on a zero-gap configuration where the AEM is sandwiched between the anode and cathode so as to minimise voltage drop between the electrodes. Nonprecious nickel-based metal alloy and metal oxide catalysts were employed. Various experiments were carried out to understand the effects of operating parameters such as current densities, electrolyte concentrations, and testing regimes on the performance of both 10 cm2 and 100 cm2 AEM electrolyser cells. Increasing electrolyte concentration was seen to result in reductions in overpotentials which were proportional to current applied, whilst the use of catalysts improved performance consistently over the range of current densities tested. Extended galvanostatic and intermittent tests were demonstrated on both 10 cm2 and 100 cm2 cells, with higher voltage efficiencies achieved with the use of electrocatalysts. Stability tests in the 100 cm2 AEM electrolyser cell assembled with catalyst-coated electrodes demonstrated that the cell voltages remained stable at 2.03 V and 2.17 V during 72 h operation in 4 M KOH and 1 M KOH electrolyte, respectively, at a current density of 0.3 A cm−2 at 323 K. The inclusion of cycling load tests in testing protocols is emphasized for rational evaluation of cell performance as this was observed to speed up the rate of degradation mechanisms such as membrane degradation.
Prevalence of Polypharmacy of Older People in a Large Brazilian Urban Center and its Associated Factors
Authors: Vitorino Luciano Magalhães , Lopes Mendes Jorge Henrique , de Souza Santos Gerson , Oliveira Cláudia , José Helena , Sousa Luís
Published: May 2023

Background: With the aging population comes greater risks associated with polypharmacy, a significant public health problem. Objective: This study aimed to identify the prevalence of polypharmacy and its associated factors through Comprehensive Geriatric Assessment (CGA) among older adults treated in primary health care (PHC) in a large Brazilian urban center. Methods: We conducted a cross-sectional study with a random sampling of 400 older adults using primary health care. Polypharmacy was defined as the cumulative use of five or more daily medications. An assessment of a sociodemographic and health survey, fear of falling, and physical disabilities affecting activities of daily living and instrumental activities of daily living was conducted. Results: The mean age was 75.23 (SD: 8.53) years. The prevalence of polypharmacy and hyperpolypharmacy was 37% (n = 148) and 1% (n = 4), respectively. The adjusted logistic regression showed that participants with chronic non-communicable diseases (CNCDs) (OR = 9.24; p = 0.003), diabetes (OR = 1.93; p = 0.003), and obesity (OR = 2.15; p = 0.005) were associated with a greater propensity to use polypharmacy. Conclusion: Our results show that older adults with CNCDs, diabetes, and obesity were more likely to use polypharmacy. The results reinforce the importance of using CGA in clinical practice in PHC.
Quantification of Giant Unilamellar Vesicle Fusion Products by High-Throughput Image Analysis
Authors: Caliari Adriano , Hanczyc Martin M. , Imai Masayuki , Xu Jian , Yomo Tetsuya
Published: May 2023

Artificial cells are based on dynamic compartmentalized systems. Thus, remodeling of membrane-bound systems, such as giant unilamellar vesicles, is finding applications beyond biological studies, to engineer cell-mimicking structures. Giant unilamellar vesicle fusion is rapidly becoming an essential experimental step as artificial cells gain prominence in synthetic biology. Several techniques have been developed to accomplish this step, with varying efficiency and selectivity. To date, characterization of vesicle fusion has relied on small samples of giant vesicles, examined either manually or by fluorometric assays on suspensions of small and large unilamellar vesicles. Automation of the detection and characterization of fusion products is now necessary for the screening and optimization of these fusion protocols. To this end, we implemented a fusion assay based on fluorophore colocalization on the membranes and in the lumen of vesicles. Fluorescence colocalization was evaluated within single compartments by image segmentation with minimal user input, allowing the application of the technique to high-throughput screenings. After detection, statistical information on vesicle fluorescence and morphological properties can be summarized and visualized, assessing lipid and content transfer for each object by the correlation coefficient of different fluorescence channels. Using this tool, we report and characterize the unexpected fusogenic activity of sodium chloride on phosphatidylcholine giant vesicles. Lipid transfer in most of the vesicles could be detected after 20 h of incubation, while content exchange only occurred with additional stimuli in around 8% of vesicles.
Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat
Authors: Lu Jian-He , Chueh Kuang-Shun , Juan Tai-Jui , Mao Jing-Wen , Lin Rong-Jyh , Lee Yi-Chen , Shen Mei-Chen , Sun Ting-Wei , Lin Hung-Yu , Juan Yung-Shun
Published: May 2023

Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS) enzymes, reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.
Cracking the Floral Quartet Code: How Do Multimers of MIKCC-Type MADS-Domain Transcription Factors Recognize Their Target Genes?
Authors: Käppel Sandra , Rümpler Florian , Theißen Günter
Published: May 2023

MADS-domain transcription factors (MTFs) are involved in the control of many important processes in eukaryotes. They are defined by the presence of a unique and highly conserved DNA-binding domain, the MADS domain. MTFs bind to double-stranded DNA as dimers and recognize specific sequences termed CArG boxes (such as 5′-CC(A/T)6GG-3′) and similar sequences that occur hundreds of thousands of times in a typical flowering plant genome. The number of MTF-encoding genes increased by around two orders of magnitude during land plant evolution, resulting in roughly 100 genes in flowering plant genomes. This raises the question as to how dozens of different but highly similar MTFs accurately recognize the cis-regulatory elements of diverse target genes when the core binding sequence (CArG box) occurs at such a high frequency. Besides the usual processes, such as the base and shape readout of individual DNA sequences by dimers of MTFs, an important sublineage of MTFs in plants, termed MIKCC-type MTFs (MC-MTFs), has evolved an additional mechanism to increase the accurate recognition of target genes: the formation of heterotetramers of closely related proteins that bind to two CArG boxes on the same DNA strand involving DNA looping. MC-MTFs control important developmental processes in flowering plants, ranging from root and shoot to flower, fruit and seed development. The way in which MC-MTFs bind to DNA and select their target genes is hence not only of high biological interest, but also of great agronomic and economic importance. In this article, we review the interplay of the different mechanisms of target gene recognition, from the ordinary (base readout) via the extravagant (shape readout) to the idiosyncratic (recognition of the distance and orientation of two CArG boxes by heterotetramers of MC-MTFs). A special focus of our review is on the structural prerequisites of MC-MTFs that enable the specific recognition of target genes.
SOCS3 Protein Mediates the Therapeutic Efficacy of Mesenchymal Stem Cells against Acute Lung Injury
Authors: Kim Young Eun , Sung Dong Kyung , Bang Yuna , Sung Se In , Yang Misun , Ahn So Yoon , Chang Yun Sil
Published: May 2023

Mesenchymal stem cells (MSCs) have been studied as novel therapeutic agents because of their immunomodulatory properties in inflammatory diseases. The suppressor of cytokine signaling (SOCS) proteins are key regulators of the immune response and macrophage modulation. In the present study, we hypothesized that SOCS in MCSs might mediate macrophage modulation and tested this in a bacteria-induced acute lung injury (ALI) mouse model. The macrophage phenotype was observed in RAW264.7 alveolar macrophages exposed to lipopolysaccharide (LPS) in an in vitro model, and in the ALI mouse model induced by tracheal administration of Escherichia coli (1 × 107 CFU in 0.05mL PBS). In LPS-exposed RAW264.7 cells, the levels of markers of M1 macrophages, such as CD86 and pro-inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α), significantly increased, but they significantly reduced after MSC treatment. Meanwhile, the levels of markers of M2 macrophages, such as CD204 and anti-inflammatory cytokines (IL-4 and IL-10), increased after LPS exposure, and further significantly increased after MSC treatment. This regulatory effect of MSCs on M1/M2 macrophage polarization was significantly abolished by SOCS3 inhibition. In the E. coli-induced ALI model, tissue injury and inflammation in the mouse lung were significantly attenuated by the transplantation of MSCs, but not by SOCS3-inhibited MSCs. The regulatory effect of MSCs on M1/M2 macrophage polarization was observed in the lung injury model but was significantly abolished by SOCS3 inhibition. Taken together, our findings suggest that SOCS3 is an important mediator for macrophage modulation in anti-inflammatory properties of MSCs.
Molecular Target and Action Mechanism of Anti-Cancer Agents
Authors: Lee Seok-Geun
Published: May 2023

Precision oncology, also known as personalized medicine, is an evolving approach to cancer treatment that aims to tailor therapies to individual patients based on their unique molecular profile, including genetic alterations and other biomarkers [...]
Signal Pathways in Cancer
Authors: Song Guanbin
Published: May 2023

Cancer is a major health-threatening disease and is the second leading cause of death worldwide; the prevention and treatment of cancer remains one of the most challenging problems clinically [...]
Vaginal and Cervical Microbiota Composition in Patients with Endometrial Cancer
Authors: Barczyński Bartłomiej , Frąszczak Karolina , Grywalska Ewelina , Kotarski Jan , Korona-Głowniak Izabela
Published: May 2023

According to recent data, changes in the vaginal microbiota could affect the risk of gynaecological cancers. Women suffering from endometrial cancer present significant changes in cervicovaginal microbiota composition. The objective of our study was to characterize the cervicovaginal microbiota of women undergoing hysterectomy due to benign disease, atypical hyperplasia, and endometrial cancer; The study included 96 patients, who undergone surgical treatment due to benign uterine disease, precancerous endometrial lesion, and endometrial cancer. Quantitative and qualitative real-time PCR analysis of DNA isolated from vaginal fornix and endocervical canal samples was performed to detect the 19 most commonly identified microorganisms, including different Lactobacillus spp., Atopobium, Bifidobacterium, Chlamydia, and Gardnerella; At least one of the tested microorganisms was identified in 88.5% of vaginal and 83.3% of cervical samples. Lactobacillus iners was significantly more frequent in patients with benign condition, whereas Dialister pneumosintes and Mobiluncus curtisii was more frequent in cancer patients; Mobiluncus curtisi and Dialister pneumosintes, which were identified as significantly more common in endometrial cancer vaginal samples, may be considered as potential endometrial cancer co-factors which promote/stimulate carcinogenesis. However, the exact mechanism of such activity remains unexplained and requires further investigations.
A Multifunctional and Highly Adaptable Reporter System for CRISPR/Cas Editing
Authors: Wettengel Jochen M. , Hansen-Palmus Lea , Yusova Sofiya , Rust Lauren , Biswas Sreya , Carson Julien , Ryu Junghyun , Bimber Benjamin N. , Hennebold Jon D. , Burwitz Benjamin J.
Published: May 2023

CRISPR/Cas systems are some of the most promising tools for therapeutic genome editing. The use of these systems is contingent on the optimal designs of guides and homology-directed repair (HDR) templates. While this design can be achieved in silico, validation and further optimization are usually performed with the help of reporter systems. Here, we describe a novel reporter system, termed BETLE, that allows for the fast, sensitive, and cell-specific detection of genome editing and template-specific HDR by encoding multiple reporter proteins in different open-reading frames. Out-of-frame non-homologous end joining (NHEJ) leads to the expression of either secretable NanoLuc luciferase, enabling a highly sensitive and low-cost analysis of editing, or fluorescent mTagBFP2, allowing for the enumeration and tissue-specific localization of genome-edited cells. BETLE includes a site to validate CRISPR/Cas systems for a sequence-of-interest, making it broadly adaptable. We evaluated BETLE using a defective moxGFP with a 39-base-pair deletion and showed spCas9, saCas9, and asCas12a editing as well as sequence-specific HDR and the repair of moxGFP in cell lines with single and multiple reporter integrants. Taken together, these data show that BETLE allows for the rapid detection and optimization of CRISPR/Cas genome editing and HDR in vitro and represents a state-of the art tool for future applications in vivo.
InDel and SCoT Markers for Genetic Diversity Analysis in a Citrus Collection from the Western Caucasus
Authors: Kulyan Raisa , Samarina Lidiia , Shkhalakhova Ruset , Kuleshov Alexandr , Ukhatova Yulia , Antonova Olga , Koninskaya Natalia , Matskiv Alexandra , Malyarovskaya Valentina , Ryndin Alexey
Published: May 2023

Citrus collections from extreme growing regions can be an important source of tolerant germplasms for the breeding of cold-tolerant varieties. However, the efficient utilization of these germplasms requires their genetic background information. Thus, efficient marker systems are necessary for the characterization and identification of valuable accessions. In this study, the efficiency of 36 SCoT markers and 60 InDel markers were evaluated as part of the broad citrus collection of the Western Caucasus. The interspecific and intraspecific genetic diversity and genetic structures were analyzed for 172 accessions, including 31 species and sets of the locally derived cultivars. Single markers, such as SCoT18 (0.84), SCoT20 (0.93), SCoT23 (0.87), SCoT31 (0.88), SCoT36 (0.87) и LG 1-4 (0.94), LG 4-3 (0.86), LG 7-11 (0.98), and LG 8-10 (0.83), showed a high discriminating power, indicating the good applicability of these markers to assess intraspecific diversity of the genus Citrus. Overall, SCoT markers showed a higher level of polymorphism than InDel markers. According to analysis of population structure, SCoT and InDel markers showed K = 9 and K = 5 genetic clusters, respectively. The lowest levels of genetic admixtures and diversity were observed among the locally derived satsumas and lemons. The highest level of genetic admixtures was observed in the lime group. Phylogenetic relationships indicated a high level of interspecific genetic diversity but a low level of intraspecific diversity in locally derived satsumas and lemons. The results provide new insight into the origin of citrus germplasms and their distribution in colder regions. Furthermore, they are important for implementing conservation measures, controlling genetic erosion, developing breeding strategies, and improving breeding efficiency.
Design, Synthesis, and Anti-PVY Biological Activity of 1,3,5-Triazine Derivatives Containing Piperazine Structure
Authors: Bai Lian , Wei Chunle , Zhang Jian , Song Runjiang
Published: May 2023

In this study, a commercial agent with antivirus activity and moroxydine hydrochloride were employed to perform a lead optimization. A series of 1,3,5-triazine derivatives with piperazine structures were devised and synthesized, and an evaluation of their anti-potato virus Y (PVY) activity revealed that several of the target compounds possessed potent anti-PVY activity. The synthesis of compound C35 was directed by a 3D-quantitative structure–activity relationship that used the compound’s structural parameters. The assessment of the anti-PVY activity of compound C35 revealed that its curative, protective, and inactivation activities (53.3 ± 2.5%, 56.9 ± 1.5%, and 85.8 ± 4.4%, respectively) were comparable to the positive control of ningnanmycin (49.1 ± 2.4%, 50.7 ± 4.1%, and 82.3 ± 6.4%) and were superior to moroxydine hydrochloride (36.7 ± 2.7%, 31.4 ± 2.0%, and 57.1 ± 1.8%). In addition, molecular docking demonstrated that C35 can form hydrogen bonds with glutamic acid at position 150 (GLU 150) of PVY CP, providing a partial theoretical basis for the antiviral activity of the target compounds.
Evaluation of the Different Nutritional and Environmental Parameters on Microbial Pyrene Degradation by Mangrove Culturable Bacteria
Authors: Ahmad Manzoor , Ling Juan , Yin Jianping , Chen Luxiang , Yang Qingsong , Zhou Weiguo , Zhang Yuhang , Huang Xiaofang , Khan Imran , Dong Junde
Published: May 2023

Mangrove ecosystems play curial roles in providing many ecological services and alleviating global climate change. However, they are in decline globally, mainly threatened by human activities and global warming, and organic pollutants, especially PAHs, are among the crucial reasons. Microbial remediation is a cost-effective and environmentally friendly way of alleviating PAH contamination. Therefore, understanding the effects of environmental and nutritional parameters on the biodegradation of polycyclic aromatic hydrocarbons (PAHs) is significant for the bioremediation of PAH contamination. In the present study, five bacterial strains, designated as Bp1 (Genus Rhodococcus), Sp8 (Genus Nitratireductor), Sp13 (Genus Marinobacter), Sp23 (Genus Pseudonocardia), and Sp24 (Genus Mycolicibacterium), have been isolated from mangrove sediment and their ring hydroxylating dioxygenase (RHD) genes have been successfully amplified. Afterward, their degradation abilities were comprehensively evaluated under normal cultural (monoculture and co-culture) and different nutritional (tryptone, yeast extract, peptone, glucose, sucrose, and NPK fertilizer) and environmental (cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS)) parameters, as well with different co-contaminants (phenanthrene and naphthalene) and heavy metals (Cd2+, Cu2+, Fe3+, Ni2+, Mg2+, Mn2+, and Co2+). The results showed that strain Sp24 had the highest pyrene degradation rate (85%) in the monoculture experiment after being cultured for 15 days. Adding nitrogen- and carbon-rich sources, including tryptone, peptone, and yeast extract, generally endorsed pyrene degradation. In contrast, the effects of carbon sources (glucose and sucrose) on pyrene degradation were distinct for different bacterial strains. Furthermore, the addition of NPK fertilizer, SDS, Tween-80, phenanthrene, and naphthalene enhanced the bacterial abilities of pyrene removal significantly (p < 0.05). Heavy metals significantly reduced all bacterial isolates’ degradation potentials (p < 0.05). The bacterial consortia containing high bio-surfactant-producing strains showed substantially higher pyrene degradation. Moreover, the consortia of three and five bacterial strains showed more degradation efficiency than those of two bacterial strains. These results provide helpful microbial resources for mangrove ecological remediation and insight into optimized culture strategies for the microbial degradation of PAHs.
Enhanced Antibacterial Activity of Novel Fluorescent Glutathione-Capped Ag Nanoclusters
Authors: Tumskiy Roman , Khlebtsov Boris , Tumskaia Anastasiia , Evstigneeva Stella , Antoshkina Evgeniya , Zakharevich Andrey , Khlebtsov Nikolai G.
Published: May 2023

Ag nanomaterials are promising candidates for the discovery of next-generation antibiotics with a high antibacterial effect against multi-drug resistant strains. This paper reports a simple synthesis of novel water-soluble glutathione-capped silver nanoclusters (GSH-Ag NCs) with an enhanced antibacterial activity. According to thin layer chromatography (TLC), the synthesized GSH-Ag NCs are an individual fraction of the same composition without any impurities. According to matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and energy dispersive X-ray (EDX) analyses, the silver core of the GSH-Ag NCs contains approximately 35 silver atoms, and the molecular weight of these nanoclusters is about 11 kDa. The fabricated silver nanoclusters have a reddish fluorescence (λex/λem = 509/645 nm), with a large Stokes shift (>130 nm), and ultra-small size (less than 2 nm) according to transmission electron microscopy (TEM) data and dynamic light scattering (DLS) analysis. The antibacterial activity and minimal inhibitory concentrations of the silver nanoclusters towards Escherichia coli, Staphylococcus aureus, Bacillus cereus and Enterobacter cloacae were evaluated using the agar well-diffusion method and resazurin metabolism assay. The antibacterial activity of chelated silver in the nanoclusters was found to be significantly higher compared to the activity of free silver ions. To explain the possible mechanisms underlying the antibacterial actions of the GSH-Ag nanoclusters, molecular docking was performed, and prospective bacterial targets were identified using AutoDock.
Recent Advances in Biomolecular Recognition
Authors: Zhu Qiang , Luo Ray
Published: May 2023

Living cells are extremely complicated systems and composed of hundreds of thousands of diverse biomolecules, such as proteins, nucleic acids, and carbohydrates [...]
Calcium Dynamics of the Ventrolateral Preoptic GABAergic Neurons during Spontaneous Sleep-Waking and in Response to Homeostatic Sleep Demands
Authors: Kostin Andrey , Alam Md. Aftab , Saevskiy Anton , Yang Chenyi , Golshani Peyman , Alam Md. Noor
Published: May 2023

The ventrolateral preoptic area (VLPO) contains GABAergic sleep-active neurons. However, the extent to which these neurons are involved in expressing spontaneous sleep and homeostatic sleep regulatory demands is not fully understood. We used calcium (Ca2+) imaging to characterize the activity dynamics of VLPO neurons, especially those expressing the vesicular GABA transporter (VGAT) across spontaneous sleep-waking and in response to homeostatic sleep demands. The VLPOs of wild-type and VGAT-Cre mice were transfected with GCaMP6, and the Ca2+ fluorescence of unidentified (UNID) and VGAT cells was recorded during spontaneous sleep-waking and 3 h of sleep deprivation (SD) followed by 1 h of recovery sleep. Although both VGAT and UNID neurons exhibited heterogeneous Ca2+ fluorescence across sleep-waking, the majority of VLPO neurons displayed increased activity during nonREM/REM (VGAT, 120/303; UNID, 39/106) and REM sleep (VGAT, 32/303; UNID, 19/106). Compared to the baseline waking, VLPO sleep-active neurons (n = 91) exhibited higher activity with increasing SD that remained elevated during the recovery period. These neurons also exhibited increased Ca2+ fluorescence during nonREM sleep, marked by increased slow-wave activity and REM sleep during recovery after SD. These findings support the notion that VLPO sleep-active neurons, including GABAergic neurons, are components of neuronal circuitry that mediate spontaneous sleep and homeostatic responses to sustained wakefulness.
Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate Lupus Disease in Fcgr2b-/- Mice by Mediating Antigen-Specific Immune Tolerance
Authors: Khiewkamrop Phuriwat , Kaewraemruaen Chamraj , Manipuntee Chonnavee , Saengruengrit Chalathan , Insin Numpon , Leelahavanichkul Asada , Kaewduangduen Warerat , Sonpoung Opor , Ariya-anandech Kasirapat , Hirankarn Nattiya , Ritprajak Patcharee
Published: May 2023

Dendritic cells (DCs) are the most potent antigen-presenting cells that have multifaceted functions in the control of immune activation and tolerance. Hyperresponsiveness and altered tolerogenicity of DCs contribute to the development and pathogenesis of system lupus erythematosus (SLE); therefore, DC-targeted therapies aimed at inducing specific immune tolerance have become of great importance for the treatment of SLE. This study developed a new nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for target-oriented delivery to DCs in situ. PDMAEMA-PLGA NPs provided sustained drug release and exhibited immunosuppressive activity in FLT3L and GM-CSF-derived bone marrow in conventional DCs (BM-cDCs). PDMAEMA-PLGA NPs improved dexamethasone capability to convert wild-type and Fcgr2b-/- BM-cDCs from an immunogenic to tolerogenic state, and BM-cDCs treated with dexamethasone-incorporated PDMAEMA-PLGA NPs (Dex-NPs) efficiently mediated regulatory T cell (Treg) expansion in vitro. Dex-NP therapy potentially alleviated lupus disease in Fcgr2b-/- mice by mediating Foxp3+ Treg expansion in an antigen-specific manner. Our findings substantiate the superior efficacy of DC-targeted therapy using the PDMAEMA-PLGA NP delivery system and provide further support for clinical development as a potential therapy for SLE. Furthermore, PDMAEMA-PLGA NP may be a versatile platform for DC-targeted therapy to induce antigen-specific immune tolerance to unwanted immune responses that occur in autoimmune disease, allergy, and transplant rejection.
Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays
Authors: Tesoriero Chiara , Greco Francesca , Cannone Elena , Ghirotto Francesco , Facchinello Nicola , Schiavone Marco , Vettori Andrea
Published: May 2023

Muscular dystrophies (MDs) are a heterogeneous group of myopathies characterized by progressive muscle weakness leading to death from heart or respiratory failure. MDs are caused by mutations in genes involved in both the development and organization of muscle fibers. Several animal models harboring mutations in MD-associated genes have been developed so far. Together with rodents, the zebrafish is one of the most popular animal models used to reproduce MDs because of the high level of sequence homology with the human genome and its genetic manipulability. This review describes the most important zebrafish mutant models of MD and the most advanced tools used to generate and characterize all these valuable transgenic lines. Zebrafish models of MDs have been generated by introducing mutations to muscle-specific genes with different genetic techniques, such as (i) N-ethyl-N-nitrosourea (ENU) treatment, (ii) the injection of specific morpholino, (iii) tol2-based transgenesis, (iv) TALEN, (v) and CRISPR/Cas9 technology. All these models are extensively used either to study muscle development and function or understand the pathogenetic mechanisms of MDs. Several tools have also been developed to characterize these zebrafish models by checking (i) motor behavior, (ii) muscle fiber structure, (iii) oxidative stress, and (iv) mitochondrial function and dynamics. Further, living biosensor models, based on the expression of fluorescent reporter proteins under the control of muscle-specific promoters or responsive elements, have been revealed to be powerful tools to follow molecular dynamics at the level of a single muscle fiber. Thus, zebrafish models of MDs can also be a powerful tool to search for new drugs or gene therapies able to block or slow down disease progression.
Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones
Authors: Maisto Maria , Schiano Elisabetta , Luccheo Gianni , Luccheo Luigi , Alfieri Ernesto , Piccolo Vincenzo , Iannuzzo Fortuna , Di Lorenzo Ritamaria , Tenore Gian Carlo
Published: May 2023

Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. In this scenario, the aim of the present work was the design of an innovative multi-component nutraceutical formulation (NF) for the management of urinary stones consisting of a synergistic combination of natural aqueous extracts of Oreganum vulgare L. (1% of saponin), Urtica dioica (0.8% of β-sitosterol), Phyllanthus niruri (15% of tannins w/w), and Ceterach officinarum in association with bromelain, K, and Mg citrate. To assess the potential of NF also in the treatment of uric acid (UA) stones, the effects on the expression of the cellular UA transporters OAT1 and URAT1 were investigated in a renal tubular cell line. In addition, the myorelaxant effect of NF was investigated in a human pulmonary artery smooth muscle cell (HPASMC) model resulting in a decreased muscle contractility of −49.4% (p < 0.01) compared to the control. The treatment with NF also showed a valuable inhibition of in vitro calcium-oxalate crystal formation, both in prevention (−52.3% vs. control, p < 0.01) and treatment (−70.8% vs. control, p < 0.01) experiments. Finally, an ischemic reperfusion rat model was used to evaluate the NF anti-edema effects, resulting in a reduction in the edema-related vascular permeability (Normalized Gray Levels, NGL = 0.40 ± 0.09, p < 0.01, −67.1% vs. untreated rats). In conclusion, the present NF has shown to be a promising natural alternative for managing urinary tract stones.
Numerical Analysis of the Flow by Using a Free Runner Downstream the Francis Turbine
Authors: Bosioc Alin Ilie , Szakal Raul-Alexandru , Stuparu Adrian , Susan-Resiga Romeo
Published: May 2023

The current requirements of industrialized countries require the use of as much renewable energy as possible. One significant problem with renewable energy is that the produced power fluctuates. Currently, the only method available for energy compensation in the shortest time is given by hydroelectric power plants. Instead, hydroelectric power plants (especially the plants equipped with hydraulic turbines with fixed blades) are designed to operate in the vicinity of the optimal operating point with a maximum ±10% deviation. The energy market requires that hydraulic turbines operate in an increasingly wide area between −35% to 20% from the optimum operating point. Operation of hydraulic turbines far from the optimum operating point involves the appearance downstream of the turbine of a decelerated swirling flow with hydraulic instabilities (known in the literature as the vortex rope). The main purpose of this paper is to investigate numerically a new concept by using a free runner downstream on the main hydraulic runner turbine more precisely in the draft tube cone. The free runner concept requires rotations at the runaway speed with vanishing mechanical torque. The main purpose is to redistribute the total pressure and the moment between the shaft and the periphery. In addition, the free runner does not modify the operating point of the main hydraulic turbine runner.
Analysis of Provincial Policies on the Development of Prefabricated Construction in China
Authors: Yan Kangkang , Shuang Huer , Tan Yongtao , Xiang Shuang , Gan Xiaolong
Published: May 2023

Currently, China has launched an ambitious governmental initiative to promote the development of prefabricated construction (PC). As the target of PC development has been allocated to lower-level government, the responsibility for PC development rests at the provincial level. Therefore, provincial policies are extremely crucial for the development of PC. Despite this, few studies have been conducted to examine the role of provincial policies in promoting the development of PC. With the aim of filling this knowledge gap, a comprehensive analysis of provincial policies on the development of PC was conducted in this study. Firstly, 443 provincial policies for PC development issued by 31 regions were collected and divided into different types according to the policy instrument framework, including environment instruments, demand instruments and supply instruments. By using the approach of content analysis, the spatial and temporal distribution of provincial policies was explored, as well as the similarities and differences in different regions. The results indicate that China initially developed a policy system for PC development with the characteristics of multiple levels, multiple stakeholders and multiple instruments; meanwhile, provincial policy relies heavily on environmental instruments, and the use of supply and demand instruments is grossly inadequate. The existing problems of each policy instrument for PC development have been discussed, and corresponding countermeasures have been put forward. The research findings provide valuable information for policy adjustments in the future and shed light on the effective delivery of policies to promote the development of PC in developing countries.
Tensile, Compressive, and Flexural Characterization of CFRP Laminates Related to Water Absorption
Authors: Sudarisman Sudarisman , Haniel Haniel , Taufik Angger Kaloka , Tiopan Muhammad , Himarosa Rela Adi , Muflikhun Muhammad Akhsin
Published: May 2023

CFRP structures are often exposed to humid environment resulting in water absorption and causing property degradation. Water swelling and its effect on tensile, compressive, and flexural properties were investigated according to ASTM standards. Fracture modes were evaluated by analyzing micrographs of fracture areas. The specimens were cut from twill wave CFRP composite plates fabricated using a vacuum infusion technique. Some of them were immersed in water prior to being mechanically tested. It was found that tensile strength, as well as compressive, and flexural strength and moduli decreased due to water swelling, but fracture strain was found to increase due to water swelling. The most severely affected by water swelling is flexural strength (decreased by 25.72%), and the least is compressive modulus (decreased by 1.89%). Tensile specimens underwent fibre breakage followed by matrix cracking, compressive and flexural specimens showed fibre buckling followed by kinking and crushing where flexural specimens failed in their compressive side. In conclusion, water absorption has a bad impact on the composite strength.
Engineered GO-Silk Fibroin-Based Hydrogel for the Promotion of Collagen Synthesis in Full-Thickness Skin Defect
Authors: Syromiatnikova Valeriia , Gupta Sharda , Zhuravleva Margarita , Masgutova Galina , Zakirova Elena , Aimaletdinov Alexander , Rizvanov Albert , Salafutdinov Ilnur , Naumenko Ekaterina , Bit Arindam
Published: May 2023

In order to improve the regeneration of full-layer skin defects, hydrogels were developed based on the combination of chitosan (Cs), Daba silk fibroin (DSF), and graphene oxide (GO): CS, DSF/Cs and DSF/Cs/GO. The biocompatibility of hydrogels with human dermis fibroblasts in vitro was evaluated using the MTS assay. To assess the regenerative potential of hydrogels, a model of a full-layer skin defect was reconstructed on the back of rats and closed the wound surface with CS, DSF/Cs and DSF/Cs/GO hydrogels. The morphological and morphometric characteristics of regenerate tissues were obtained by staining with hematoxylin-eosin, Heidengain azocarmine, and immunohistochemistry on days 7 and 14 of the experiment. It has been shown that the use of DSF/Cs and DSF/Cs/GO promotes enhanced healing and epithelization of a full-layer skin wound. The addition of GO to the hydrogel increased the synthetic activity of fibroblasts and improved the characteristics of the produced collagen fibers.
The Effect of Post-Activation Potentiation on Swimming Starts in Adolescent Swimmers
Authors: Georgogiannis Nikolaos , Tsalis George
Published: May 2023

Background: Post-activation potentiation (PAP) is a phenomenon in which there is an increase in induced momentum in sporting activities after muscle contractions. In swimming, the start of the race and the increase in speed in its first few meters are important. The aim of the present study was to investigate the effect of the PAP protocol, which included a simulated body weight start on the ground, on the swimming start and on the 25 m freestyle performance. Methods: The study included 14 male and 14 female swimmers, 14.9 ± 0.6 years old. All the swimmers performed three maximal attempts of 25 m freestyle swimming from the starting block on three different days in a randomly counterbalanced order. In each session, swimmers performed either a 25 m freestyle without any intervention before the swimming trial (CG), or performed four vertical simulated ground starts at maximal effort, 15 s before (15 sG) or 8 min before (8 minG) the swimming trial. The jump height, entry distance, flight time, and flight speed for each attempt were calculated. Results: The CG entry distance was significantly longer than that of the 15 sG and 8 minG (3.39 ± 0.20 vs. 3.31 ± 0.21 and 3.25 ± 0.25 m, respectively, p < 0.001). Conclusions: Four simulated swim starts on the ground, 15 s or 8 min before the swim sprint, had no positive effect on the swim start or swim performance, and it is up to the swimmer to perform these jumps.
Experimental Study on Hydrodynamic Characteristics of a Submerged Floating Tunnel under Freak Waves (I: Time-Domain Study)
Authors: Pan Wenbo , He Meng , Cui Cheng
Published: May 2023

The dynamic response characteristics of a two-dimensional submerged floating tunnel (SFT) under random and freak waves were investigated in the present study. The results demonstrate that (1) the dynamic responses of the SFT under the freak wave are significantly larger than those under the largest wave in the wave train excluding the freak wave, particularly for the motion response. The maximum values of the motion responses induced by the freak wave were several times larger than those induced by the largest wave in the wave train excluding the freak wave, far exceeding the proportion of the corresponding wave height. (2) The freak wave parameter α1 has a significant effect on the amplification coefficients of surge, heave and pitch; all increase nonlinearly as α1 increases. Within α1 = 1.90~2.59, the amplification coefficients of the surge, heave and pitch vary in the ranges of 1.91~6.46, 1.53~3.87 and 1.73~5.32, respectively. (3) Amplification coefficients of tension increase almost linearly as α1 increases. Additionally, the amplification effect of the freak wave on the mooring tension is much smaller than that on motion responses. Within α1 = 1.90~2.59, the amplification coefficients of tension vary from 1.15 to 1.35. (4) Generalised amplification coefficients of motion responses increase as α1 increases and are all greater than 1.0, indicating that growth rates for motion responses under the freak wave exceed the growth rates for maximum wave height. Moreover, motion responses show a significantly nonlinear growth as maximum wave height increases. The generalised amplification coefficients of the mooring tension decrease as α1 increases, and are all less than 1.0, indicating that the dynamic amplification effect of the freak wave on the mooring tension is much smaller than that on motions. On the other hand, growth rates of the mooring tension under freak waves are smaller than the linear growth rate of the height of freak waves.
Evaluating Changes in the Multiyear Predictability of the Pacific Decadal Oscillation Using Model Analogs since 1900
Authors: Wu Yanling , Yan Xiaoqin
Published: May 2023

In this study, we investigate the changes in the multiyear predictability of the Pacific decadal oscillation (PDO) since 1900. A newly developed method, the model-analog method, is used to hindcast the PDO from 1900 to 2015. Model-analog hindcast provides comparable PDO prediction skills with the traditional assimilation-initialized forecast but with much lower computational costs. Our results show that PDO prediction skills have significantly changed over time. Specifically, the PDO could skillfully be predicted up to 5 years in advance in 1910–1960, but it can only be predicted 2–3 years in advance after 1960. We attribute these changes to the strength of the re-emergence process, where deep oceanic mixed layer temperature anomalies from one winter reappear in the following winters. In the high-prediction-skill period, the stronger re-emergence process provides more predictable information, leading to enhanced multiyear prediction skills. Our study offers new insights into the multiyear predictability of the PDO over a long-time frame and sheds light on the reasons behind the low prediction skill of the PDO.
Aspergillus fumigatus Extracellular Vesicles Display Increased Galleria mellonella Survival but Partial Pro-Inflammatory Response by Macrophages
Authors: Freitas Mateus Silveira , Bitencourt Tamires Aparecida , Rezende Caroline Patini , Martins Nubia Sabrina , Dourado Thales de Mileto Henrique , Tirapelli Carlos R. , Almeida Fausto
Published: May 2023

Fungal extracellular vesicles (EVs) mediate intra- and interspecies communication and are critical in host–fungus interaction, modulating inflammation and immune responses. In this study, we evaluated the in vitro pro- and anti-inflammatory properties of Aspergillus fumigatus EVs over innate leukocytes. A. fumigatus EVs induced a partial proinflammatory response by macrophages, characterized by increased tumor necrosis factor-alpha production, and increased gene expression of induced nitric oxide synthase and adhesion molecules. EVs induce neither NETosis in human neutrophils nor cytokine secretion by peripheral mononuclear cells. However, prior inoculation of A. fumigatus EVs in Galleria mellonella larvae resulted in increased survival after the fungal challenge. Taken together, these findings show that A. fumigatus EVs play a role in protection against fungal infection, although they induce a partial pro-inflammatory response.
Census and Dynamics of Trees Outside Forests in Central Italy: Changes, Net Balance and Implications on the Landscape
Authors: Ottaviano Marco , Marchetti Marco
Published: May 2023

Trees outside forests (TOFs) are important landscape features that provide numerous functions (ecosystem services) that are not valued due to a lack of knowledge about these resources. The aim of this study was to evaluate the changes induced by the anthropogenic land use change in relation to their effects on TOFs. The dynamics of TOFs were examined through detailed photointerpretation mapping and characterization by land use/land cover and other environmental variables. The landscape function of TOFs and relative dynamics were analyzed, revealing landscape simplification due to the loss of TOFs, both in number and area, and a relative loss of connectivity. In 2000, TOFs accounted for 2.6% more forest area than mapped in the regional forest map; in fifteen years, about 30% of the total area has been lost, one-third of which has been converted to forest and the remainder permanently lost. The causes of the loss of TOFs are partly due to the abandonment of agricultural land, but also to the actions of farmers who remove these elements for various reasons. In protected areas (Natura 2000 network), the loss is less due to the different characteristics of land use/cover and land management.
Logistics and Supply Chain Resilience of Japanese Companies: Perspectives from Impacts of the COVID-19 Pandemic
Authors: Maharjan Rajali , Kato Hironori
Published: May 2023

Background: Enhancing the resilience of global supply chains has become of increasing priority in response to recent natural disasters and the COVID-19 pandemic. Methods: This paper presents findings from semi-structured interviews with five Japanese companies conducted between November 2020 and February 2021 to examine the impacts of the COVID-19 pandemic on different aspects of logistics and supply chain activities and resilience strategies implemented. The interviews focused on firms’ financial performance and the status of preparedness, response, and future plans from the perspective of logistics and supply chain resilience. Through interviews, we also investigated whether existing logistics and supply chain resilience strategies helped the companies avoid, withstand, respond to, or recover from the pandemic’s impacts. Results: The results indicated that the interviewed companies experienced both positive and negative impacts from the pandemic on their logistics and supply chain activities and experienced negative impacts mainly on their financial performance. Conclusions: A certain level of preparedness was observed; however, the levels of resilience preparedness, response, and future plans varied among companies with different attributes, such as industry type and organisation size.
Mechanical Energy Absorption Ability of Titanium-Based Porous Structures Produced by Various Powder Metallurgy Approaches
Authors: Markovsky Pavlo E. , Janiszewski Jacek , Stasiuk Oleksandr O. , Savvakin Dmytro G. , Oryshych Denys V. , Dziewit Piotr
Published: May 2023

Porous materials are very efficient in absorbing mechanical energy, for instance, in combined armor, in order to improve the anti-ballistic protection characteristics. In the present study, porous titanium-based structures were manufactured via three different powder metallurgy methods using titanium hydride (TiH2) powder, which provided activated sintering, owing to dehydrogenation. The emission of hydrogen and shrinkage of powder particles on dehydrogenation also added an additional potential to control the sintering process and create desirable porosities. TiH2 powder was sintered with additions of NaCl or ammonium carbide as pore holding removable agents, while highly porous Ti-Al structures were formed via liquid phase reactive sintering of TiH2 and Al powders. The microstructures and porosities of sintered dehydrogenated titanium and Ti-Al structures were comparatively studied. Mechanical characteristics were evaluated using compression testing with strain rates varying from quasi-static to high levels. The resonant frequency method was also employed to determine damping parameters and elastic modulus of these materials. All testing methods were aimed at characterizing the energy-absorbing ability of the obtained porous structures. The desired strength, plasticity and energy-absorbing characteristics of porous titanium-based structures were assessed, and the possibilities of their application were also discussed. Based on the obtained results, it was found that porous titanium materials produced with the use of ammonium carbonate showed promising energy absorption properties.