bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of exogenous melatonin on antioxidant properties and fruit softening of ‘Fengtang’ plum fruit (Prunus salicina Lindl.) during storage at room temperature
Authors: Zhang Mingfei , Yang Xinxia , Yin Chunmei , Lin Xingyu , Liu Kexin , Zhang Kexin , Su Yujiao , Zou Xu , Liao Ling , Wang Xun , He Siya , He Ruiyuan , Sun Guochao , He Jiaxian , Xiong Bo , Wang Zhihui
Published: March 2024

‘Fengtang‘ plums soften quickly and lose flavor after harvest. This study comprehensively evaluated the effect of exogenous melatonin on the fruit quality of ‘Fengtang’ plums. According to our findings, exogenous melatonin prevented plum fruit from losing water, delayed the decline in firmness, and preserved a high TSS/TA level. Additionally, exogenous melatonin also enhanced the activity of antioxidant enzymes and increased the non-enzymatic antioxidants, thereby further increasing the antioxidant capacity of plum fruit. Notably, exogenous melatonin delayed the degradation of covalent soluble pectin (CSP), cellulose, and hemicellulose, as well as the rise in water-soluble pectin (WSP) concentration and the activity of cell wall degrading enzymes. Further investigation using atomic force microscopy (AFM) revealed that the chain-like structure of ionic-soluble pectin (ISP) and the self-assembly network structures of CSP were depolymerized, and melatonin treatment retarded the depolymerization of pectin structures. Our results showed that exogenous melatonin preserved the postharvest quality of plum fruits by controlling fruit softness and antioxidant capacity during storage.
Hexosamine biosynthesis and related pathways, protein N-glycosylation and O-GlcNAcylation: their interconnection and role in plants
Authors: Chen Ya-Huei , Cheng Wan-Hsing
Published: March 2024

N-Acetylglucosamine (GlcNAc), a fundamental amino sugar moiety, is essential for protein glycosylation, glycolipid, GPI-anchor protein, and cell wall components. Uridine diphosphate-GlcNAc (UDP-GlcNAc), an active form of GlcNAc, is synthesized through the hexosamine biosynthesis pathway (HBP). Although HBP is highly conserved across organisms, the enzymes involved perform subtly distinct functions among microbes, mammals, and plants. A complete block of HBP normally causes lethality in any life form, reflecting the pivotal role of HBP in the normal growth and development of organisms. Although HBP is mainly composed of four biochemical reactions, HBP is exquisitely regulated to maintain the homeostasis of UDP-GlcNAc content. As HBP utilizes substrates including fructose-6-P, glutamine, acetyl-CoA, and UTP, endogenous nutrient/energy metabolites may be integrated to better suit internal growth and development, and external environmental stimuli. Although the genes encoding HBP enzymes are well characterized in microbes and mammals, they were less understood in higher plants in the past. As the HBP-related genes/enzymes have largely been characterized in higher plants in recent years, in this review we update the latest advances in the functions of the HBP-related genes in higher plants. In addition, HBP’s salvage pathway and GlcNAc-mediated two major co- or post-translational modifications, N-glycosylation and O-GlcNAcylation, are also included in this review. Further knowledge on the function of HBP and its product conjugates, and the mechanisms underlying their response to deleterious environments might provide an alternative strategy for agricultural biofortification in the future.
Does the South African government have a duty to fund influenza vaccination of adults 65 years and older?
Authors: Sarangarajan Ruach , Ewuoso Cornelius
Published: March 2024

In this paper, we draw on the thinking about solidarity, reciprocity and distributive justice grounded in Afro-communitarian ethics from the Global South to argue for institutions, particularly the South African (SA) government, have a prima facie duty to foster influenza vaccine uptake for adults 65 years and older. Although we focus specifically on the South African government to defend our position, we believe that our argument extends to all governments. Notably, these duties are that the SA government ought to make influenza vaccines freely available for the older adult in both the public and private health facilities, provided financial allocation and their extant relationships allow for this. Further, the SA government has a duty to improve influenza vaccine procurement and availability in the country, preferably through increasing manufacturing capabilities. This paper is intrinsically valuable to promote epistemic justice, thereby contributing toward the decolonization of the global healthcare system. Moreover, this project has social significance in contributing to mitigation efforts against future public health challenges associated with population aging in resource-limited developing African nations, wherein the impact of population transition will be felt most.
On the impact of mass screening for SARS-CoV-2 through self-testing in Greece
Authors: Gilmour Samuel , Sapounas Spyros , Drakopoulos Kimon , Jaillet Patrick , Magiorkinis Gkikas , Trichakis Nikolaos
Published: March 2024

Background

Screening programs that pre-emptively and routinely test population groups for disease at a massive scale were first implemented during the COVID-19 pandemic in a handful of countries. One of these countries was Greece, which implemented a mass self-testing program during 2021. In contrast to most other non-pharmaceutical interventions (NPIs), mass self-testing programs are particularly attractive for their relatively small financial and social burden, and it is therefore important to understand their effectiveness to inform policy makers and public health officials responding to future pandemics. This study aimed to estimate the number of deaths and hospitalizations averted by the program implemented in Greece and evaluate the impact of several operational decisions.

Methods

Granular data from the mass self-testing program deployed by the Greek government between April and December 2021 were obtained. The data were used to fit a novel compartmental model that was developed to describe the dynamics of the COVID-19 pandemic in Greece in the presence of self-testing. The fitted model provided estimates on the effectiveness of the program in averting deaths and hospitalizations. Sensitivity analyses were used to evaluate the impact of operational decisions, including the scale of the program, targeting of sub-populations, and sensitivity (i.e., true positive rate) of tests.

Results

Conservative estimates show that the program reduced the reproduction number by 4%, hospitalizations by 25%, and deaths by 20%, translating into approximately 20,000 averted hospitalizations and 2,000 averted deaths in Greece between April and December 2021.

Conclusion

Mass self-testing programs are efficient NPIs with minimal social and financial burden; therefore, they are invaluable tools to be considered in pandemic preparedness and response.
Current methodologies of greenspace exposure and mental health research—a scoping review
Authors: Freymueller Julius , Schmid Hannah-Lea , Senkler Ben , Lopez Lumbi Susanne , Zerbe Stefan , Hornberg Claudia , McCall Timothy
Published: March 2024

Introduction

Greenspaces can provide an important resource for human mental health. A growing body of literature investigates the interaction and the influence of diverse greenspace exposures. In order to gain a comprehensive understanding of the complex connection between greenspace and mental health, a variety of perspectives and methodological combinations are needed. The aim of this review is to assess the current methodologies researching greenspace and mental health.

Methods

A scoping review was conducted. Four electronic databases (Pubmed, Embase, PsycInfo, Web of Science) were searched for relevant studies. A wide range of greenspace and mental health keywords were included to provide a comprehensive representation of the body of research. Relevant information on publication characteristics, types of greenspaces, mental health outcomes, and measurements of greenspace exposure and mental health was extracted and assessed.

Results

338 studies were included. The included studies encompassed a multitude of methods, as well as outcomes for both greenspace and mental health. 28 combinations were found between seven categories each for greenspace and mental health assessment. Some pairings such as geoinformation systems for greenspace assessment and questionnaires investigating mental health were used much more frequently than others, implying possible research gaps. Furthermore, we identified problems and inconsistences in reporting of greenspace types and mental health outcomes.

Discussion

The identified methodological variety is a potential for researching the complex connections between greenspace and mental health. Commonly used combinations can provide important insights. However, future research needs to emphasize other perspectives in order to understand how to create living environments with mental health benefits. For this purpose, interdisciplinary research is necessary.
“Machine replacement” or “job creation”: How does artificial intelligence impact employment patterns in China's manufacturing industry?
Authors: Huo Qingqing , Ruan Jing , Cui Yan
Published: March 2024

Artificial intelligence (AI), as an important engine for promoting high-quality economic development, should not be overlooked in terms of its impact on the employment of the labor force while promoting the digital and intelligent transformation of industries. In the face of the complex international environment and non-systemic shocks, it is of great significance to explore whether it is “machine replacement” or “job creation” in the process of the integration of AI and industry, as well as the impact of technological progress on the employment pattern of the labor force, in order to promote the economic development, respond to and solve the employment problem. It is of great significance to promote economic development and cope with and solve the employment problem. Based on the task model, this paper analyses the mechanism of the impact of AI on the employment pattern of manufacturing industry. Meanwhile, based on the provincial panel data of China's manufacturing industry from 2011 to 2020, it empirically examines the impact of AI on the total employment, employment structure and employment quality of the labor force, and analyses the multiple responses of AI on the employment pattern of the manufacturing industry. The study shows that: Firstly, the level of development of AI and the total amount of employment is a positive U-shaped relationship, the short term is dominated by the substitution effect, and the long term is dominated by the creation effect; Secondly, with regard to the employment structure, low-skilled labor is more likely to be replaced. The financial, accommodation and catering industries are relatively less affected by the spillover effects of the manufacturing industry; Third, with regard to the employment quality, the gap between urban and rural incomes has eased, with per capita net income of rural residents rising to a higher degree than per capita disposable income of urban residents. Thus, in order to further address the impact of AI on the employment patterns of the labor force, the level of AI development should be increased while expanding employment channels, paying attention to labor force skills training, reinforcing the leading role of developed regions, and accelerating regional integration and urban-rural integration, so as to share the dividends of technological progress.
X-shaped radio galaxies: probing jet evolution, ambient medium dynamics, and their intricate interconnection
Authors: Giri Gourab , Fendt Christian , Thorat Kshitij , Bodo Gianluigi , Rossi Paola
Published: March 2024

This review explores the field of X-shaped radio galaxies (XRGs), a distinctive subset of winged radio sources that are identified by two pairs of jetted lobes which aligned by a significant angle, resulting in an inversion-symmetric structure. These lobes, encompassing active (primary) and passive (secondary) phases, exhibit a diverse range of properties across the multiple frequency bands, posing challenges in discerning their formation mechanism. The proposed mechanisms can broadly be categorized into those related either to a triaxial ambient medium, into which the jet propagates, or to a complex, central AGN mechanism, where the jet is generated. The observed characteristics of XRGs as discovered in the most substantial sample to date, challenge the idea that there is universal process at work that produces the individual sources of XRGs. Instead, the observational and numerical results rather imply the absence of an universal model and infer that distinct mechanisms may be at play for the specific sources. By scrutinizing salient and confounding properties, this review intends to propose the potential direction for future research to constrain and constrict individual models applicable to XRGs.
Animal welfare at German abattoirs: insights into the occurrence of violations against laws and regulations from official veterinarians and judicial decisions
Authors: Schneidewind Stephanie Janet , Langforth Susann , Meemken Diana
Published: March 2024

Introduction

This study investigated the occurrence of various animal welfare violations at German abattoirs by analyzing the results of an anonymous online survey and relevant German court decisions.

Methods

The survey targeted official veterinarians (OVs) and other individuals responsible for enforcing animal welfare laws and regulations at German abattoirs. Participants were asked to report the five most common animal welfare violations in their workplaces during the past 3 years (2019–2021), and whether 22 specific given violations had occurred or not (in the same timeframe). The court decisions were examined to determine how many abattoirs were penalized for a specific animal welfare violation and the details about the number and species of affected animals.

Results

Overall, the violations examined throughout this study fell into one of the following categories: (1) use of prohibited driving aids (e.g., illicit use of electric prods, or hitting/beating animals); (2) inadequate husbandry in lairage; (3) inappropriate handling of animals with special care needs; (4) improper restraint, stunning, and bleeding of animals; and (5) unqualified task execution/inadequate administrative work (e.g., documentation of a violation). The violations analyzed in the scope of this study most frequently fell into categories 1, 2, and 4. Regarding the five violations that survey participants reported to be the most common in the years 2019–2021, 42.6% of responses (N = 277 reported violations) fell into category 4, followed closely by category 1 with 37.9%. Of the 22 violations surveyed in the second part of the survey, those reported by 50.0% or more participants were concentrated in categories 1, 2, and 4. Regarding the 16 relevant court rulings spanning from 2015 to 2022, the most frequently documented instances of misconduct primarily fell into category 1.

Discussion

The collected data suggest that there may be need for improvements regarding compliance with animal welfare legislation, especially concerning categories 1, 2, and 4. The authors suggest OVs to consider these findings when conducting monitoring activities at abattoirs and in the training and education of abattoir personnel.
Rapid hearing threshold assessment with modified auditory brainstem response protocols in dogs
Authors: Stanger Axel , Buhmann Gesine , Dörfelt Stefanie , Zablotski Yury , Fischer Andrea
Published: March 2024

Introduction

Auditory brainstem response (ABR) is the gold standard for hearing testing in dogs. ABR is commonly used in puppies to diagnose congenital sensorineural deafness. Long test times limit the use for a more comprehensive hearing screening in veterinary practice. This study aimed to establish a super-fast hearing screening protocol in dogs.

Methods

Hearing thresholds were routinely measured with a mobile device designed for newborn hearing screening in 90 dogs. We introduced modifications of the ABR protocol, e. g., a binaural test mode, higher stimulus rates, a broadband chirp stimulus, and an algorithm for automatic peak V detection in a stepwise fashion. Hearing thresholds were then measured with fast protocols utilizing either 30 Hz click or 90 Hz broadband chirp stimuli with 80, 60, 40, 30, 20, 10, 0 and −10 dBnHL stimulation intensities. Interrater reliability, agreement between click and chirp hearing thresholds and correlations with clinical characteristics of the dogs were assessed.

Results

Using all innovations, the test time for hearing threshold assessment in both ears was reduced to 1.11 min (mean). The chirp stimulus accentuated both, peak V and the subsequent trough, which are essential features for judgement of the hearing threshold, but preceding peaks were less conspicuous. Interrater reliability and agreement between click and chirp hearing threshold was excellent. Dogs >10 years of age and dogs with abnormal hearing score or otitis score had significantly higher hearing thresholds than younger dogs (p ≤ 0.001) or dogs without abnormalities (p < 0.001).

Conclusion

The results demonstrate that modifications in ABR protocols speed-up test times significantly while the quality of the recordings for hearing threshold assessment is maintained. Modified ABR protocols enable super-fast hearing threshold assessment in veterinary practice.
Modification of Layered Cathodes of Sodium-Ion Batteries with Conducting Polymers
Authors: Hidalgo M. Ángeles , Lavela Pedro , Tirado José L. , Aranda Manuel
Published: March 2024

Layered oxides exhibit interesting performance as positive electrodes for commercial sodium-ion batteries. Nevertheless, the replacement of low-sustainable nickel with more abundant iron would be desirable. Although it can be achieved in P2-Na2/3Ni2/9Fe2/9Mn5/9O2, its performance still requires further improvement. Many imaginative strategies such as surface modification have been proposed to minimize undesirable interactions at the cathode–electrolyte interface while facilitating sodium insertion in different materials. Here, we examine four different approaches based on the use of the electron-conductive polymer poly(3,4-ethylene dioxythiophene) (PEDOT) as an additive: (i) electrochemical in situ polymerization of the monomer, (ii) manual mixing with the active material, (iii) coating the current collector, and (iv) a combination of the latter two methods. As compared with pristine layered oxide, the electrochemical performance shows a particularly effective way of increasing cycling stability by using electropolymerization. Contrarily, the mixtures show less improvement, probably due to the heterogeneous distribution of oxide and polymer in the samples. In contrast with less conductive polyanionic cathode materials such as phosphates, the beneficial effects of PEDOT on oxide cathodes are not as much in rate performance as in inhibiting cycling degradation, due to the compactness of the electrodes without loss of electrical contact between active particles.
Extracellular Vesicles: Tiny Messengers for Mighty RNA Delivery
Authors: Das Alakesh
Published: March 2024

Extracellular vesicles (EVs) encompass a diverse array of cell-derived vesicles, originating either from the endosomal compartment (exosomes) or generated through shedding from the cell membrane. These lipid bilayer nanovesicles carry a diverse cargo consisting of nucleic acids, various macromolecules, and growth factors, capable of being assimilated by nearby or distant cells through biofluids, thereby triggering a wide range of cellular responses. Given their distinctive biological characteristics and crucial roles in intercellular communication, EVs have garnered significant attention, especially concerning potential clinical applications. Inheriting cargo from their parent cells, EVs present promising resources for diverse disease biomarkers. Research elucidating the specific impacts of cargo on target cells has sparked enthusiasm for their therapeutic potential. Compelling evidence indicates that RNA cargo housed within EVs can modulate gene expression and influence cellular functions in recipient cells. However, despite significant progress, numerous aspects of EV biology remain obscure, encompassing selective cargo-loading mechanisms that yield distinct compositions from source cells, variability in size and content, and undisclosed pathways governing uptake and cargo fate in recipient cells. A thorough understanding of core EV mechanisms—such as generation, trafficking, and payload delivery—is essential for their effective clinical utilization. This review explores the current understanding of RNA loading and transportation within EVs, shedding light on the advancements made toward clinical applications.
Transcriptomic, Proteomic, and Genomic Mutational Fraction Differences Based on HPV Status Observed in Patient-Derived Xenograft Models of Penile Squamous Cell Carcinoma
Authors: Zacharias Niki M. , Segarra Luis , Akagi Keiko , Fowlkes Natalie Wall , Chen Huiqin , Alaniz Angelita , de la Cerda Carolyn , Pesquera Pedro , Xi Yuanxin , Wang Jing , Chahoud Jad , Lu Xin , Rao Priya , Martinez-Ferrer Magaly , Pettaway Curtis A.
Published: March 2024

Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.
Monitoring Energy and Power Quality of the Loads in a Microgrid Laboratory Using Smart Meters
Authors: Isanbaev Viktor , Baños Raúl , Martínez Fernando , Alcayde Alfredo , Gil Consolación
Published: March 2024

Microgrids are local energy production and distribution networks that can operate independently when disconnected from the main power grid thanks to the integration of power generation systems, energy storage units and intelligent control systems. However, despite their advantages, the optimal energy management of real microgrids remains a subject that requires further investigation. Specifically, an effective management of microgrids requires managing a large number of electrical variables related to the power generated by the microgrid’s power supplies, the power consumed by the loads and the aspects of power quality. This study analyzes how we can monitor different variables, such as the active power, reactive power, power factor, total harmonic distortion and frequency in the loads of a microgrid, using high-precision power meters. Our empirical study, conducted using a functional microgrid comprising a hybrid wind–solar power system and several household appliances, demonstrates the feasibility of using low-cost and high-performance power meters with IoT functionality to collect valuable power quality and energy consumption data that can be used to control the microgrid operation.
Genome-Wide Identification and Drought Stress Response Pattern of the NF-Y Gene Family in Cymbidium sinense
Authors: Wang Linying , Zhao Xuewei , Zheng Ruiyue , Huang Ye , Zhang Cuili , Zhang Meng-Meng , Lan Siren , Liu Zhong-Jian
Published: March 2024

Cymbidium sinense, a type of orchid plant, is more drought-resistant and ornamental than other terrestrial orchids. Research has shown that many members of the NUCLEAR FACTOR Y (NF-Y) transcription factor family are responsive to plant growth, development, and abiotic stress. However, the mechanism of the NF-Y gene family’s response to abiotic stress in orchids has not yet been reported. In this study, phylogenetic analysis allowed for 27 CsNF-Y genes to be identified (5 CsNF-YAs, 9 CsNF-YBs, and 13 CsNF-YC subunits), and the CsNF-Ys were homologous to those in Arabidopsis and Oryza. Protein structure analysis revealed that different subfamilies contained different motifs, but all of them contained Motif 2. Secondary and tertiary protein structure analysis indicated that the CsNF-YB and CsNF-YC subfamilies had a high content of alpha helix structures. Cis-element analysis showed that elements related to drought stress were mainly concentrated in the CsNF-YB and CsNF-YC subfamilies, with CsNF-YB3 and CsNF-YC12 having the highest content. The results of a transcriptome analysis showed that there was a trend of downregulation of almost all CsNF-Ys in leaves under drought stress, while in roots, most members of the CsNF-YB subfamily showed a trend of upregulation. Additionally, seven genes were selected for real-time reverse transcription quantitative PCR (qRT-PCR) experiments. The results were generally consistent with those of the transcriptome analysis. The regulatory roles of CsNF-YB 1, 2, and 4 were particularly evident in the roots. The findings of our study may make a great contribution to the understanding of the role of CsNF-Ys in stress-related metabolic processes.
The Transcriptional Landscape of Immune-Response 3′-UTR Alternative Polyadenylation in Melanoma
Authors: Yang Xiao , Wu Yingyi , Chen Xingyu , Qiu Jiayue , Huang Chen
Published: March 2024

The prognosis of patients with malignant melanoma has been improved in recent decades due to advancements in immunotherapy. However, a considerable proportion of patients are refractory to treatment, particularly at advanced stages. This underscores the necessity of developing a new strategy to improve it. Alternative polyadenylation (APA), as a marker of crucial posttranscriptional regulation, has emerged as a major new type of epigenetic marker involved in tumorigenesis. However, the potential roles of APA in shaping the tumor microenvironment (TME) are largely unexplored. Herein, we collected two cohorts comprising melanoma patients who received immune checkpoint inhibitor (ICI) immunotherapy to quantify transcriptome-wide discrepancies in APA. We observed a global change in 3′-UTRs between responders and non-responders, which might involve DNA damage response, angiogenesis, PI3K-AKT signaling pathways, etc. Ten putative master APA regulatory factors for those APA events were detected via a network analysis. Notably, we established an immune response-related APA scoring system (IRAPAss), which exhibited a great performance of predicting immunotherapy response in multiple cohorts. Furthermore, we examined the correlation of APA with TME at the single-cell level using four single-cell immune profiles of tumor-infiltrating lymphocytes (TILs), which revealed an overall discrepancy in 3′-UTR length across diverse T cell populations, probably contributing to immunoregulation in melanoma. In conclusion, our study provides a transcriptional landscape of APA implicated in immunoregulation, which might lay the foundation for developing a new strategy for improving immunotherapy response for melanoma patients by targeting APA.
Identification and Validation of Key Genes Related to Preferred Flavour Profiles in Australian Commercial Papaya (Carica papaya L.)
Authors: Zhou Ziwei , Kanchana-udomkan Chutchamas , Ford Rebecca , Bar Ido
Published: March 2024

Commercial papaya varieties grown in Australia vary greatly in taste and aroma. Previous profiling has identified undesirable ‘off tastes’ in existing varieties, discouraging a portion of the population from consuming papayas. Our focus on enhancing preferred flavours led to an exploration of the genetic mechanisms and biosynthesis pathways that underlie these desired taste profiles. To identify genes associated with consumer-preferred flavours, we conducted whole RNA sequencing and de novo genome assembly on papaya varieties RB1 (known for its sweet flavour and floral aroma) and 1B (less favoured due to its bitter taste and musty aroma) at both ripe and unripe stages. In total, 180,368 transcripts were generated, and 118 transcripts related to flavours were differentially expressed between the two varieties at the ripe stage. Five genes (cpBGH3B, cpPFP, cpSUS, cpGES and cpLIS) were validated through qPCR and significantly differentially expressed. These genes are suggested to play key roles in sucrose metabolism and aromatic compound production pathways, holding promise for future selective breeding strategies. Further exploration will involve assessing their potential across broader germplasm and various growth environments.
The Specific Molecular Changes Induced by Diabetic Conditions in Valvular Endothelial Cells and upon Their Interactions with Monocytes Contribute to Endothelial Dysfunction
Authors: Tucureanu Monica Madalina , Ciortan Letitia , Macarie Razvan Daniel , Mihaila Andreea Cristina , Droc Ionel , Butoi Elena , Manduteanu Ileana
Published: March 2024

Aortic valve disease (AVD) represents a global public health challenge. Research indicates a higher prevalence of diabetes in AVD patients, accelerating disease advancement. Although the specific mechanisms linking diabetes to valve dysfunction remain unclear, alterations of valvular endothelial cells (VECs) homeostasis due to high glucose (HG) or their crosstalk with monocytes play pivotal roles. The aim of this study was to determine the molecular signatures of VECs in HG and upon their interaction with monocytes in normal (NG) or high glucose conditions and to propose novel mechanisms underlying valvular dysfunction in diabetes. VECs and THP-1 monocytes cultured in NG/HG conditions were used. The RNAseq analysis revealed transcriptomic changes in VECs, in processes related to cytoskeleton regulation, focal adhesions, cellular junctions, and cell adhesion. Key molecules were validated by qPCR, Western blot, and immunofluorescence assays. The alterations in cytoskeleton and intercellular junctions impacted VEC function, leading to changes in VECs adherence to extracellular matrix, endothelial permeability, monocyte adhesion, and transmigration. The findings uncover new molecular mechanisms of VEC dysfunction in HG conditions and upon their interaction with monocytes in NG/HG conditions and may help to understand mechanisms of valvular dysfunction in diabetes and to develop novel therapeutic strategies in AVD.
Different Patterns of Platinum Resistance in Ovarian Cancer Cells with Homologous Recombination Proficient and Deficient Background
Authors: Chiappa Michela , Guffanti Federica , Grasselli Chiara , Panini Nicolò , Corbelli Alessandro , Fiordaliso Fabio , Damia Giovanna
Published: March 2024

Platinum compounds are very active in first-line treatments of ovarian carcinoma. In fact, high rates of complete remission are achieved, but most patients eventually relapse with resistant disease. Many mechanisms underlying the platinum-resistant phenotype have been reported. However, there are no data in the same isogenic cell system proficient and deficient in homologous recombination (HR) on platinum-acquired resistance that might unequivocally clarify the most important mechanism associated with resistance. We generated and characterized cisplatin (DDP)-resistant murine ovarian ID8 cell lines in a HR-deficient and -proficient background. Specific upregulation of the NER pathway in the HR-proficient and -resistant cells and partial restoration of HR in Brca1−/−-resistant cells were found. Combinations of different inhibitors of the DNA damage response pathways with cisplatin were strongly active in both resistant and parental cells. The data from the ID8 isogenic system are in line with current experimental and clinical evidence and strongly suggest that platinum resistance develops in different ways depending on the cell DNA repair status (i.e., HR-proficient or HR-deficient), and the upregulation and/or restoration of repair pathways are major determinants of DDP resistance.
iBio-GATS—A Semi-Automated Workflow for Structural Modelling of Insect Odorant Receptors
Authors: Chidambara Thanu Vaanathi , Jabeen Amara , Ranganathan Shoba
Published: March 2024

Insects utilize seven transmembrane (7TM) odorant receptor (iOR) proteins, with an inverted topology compared to G-protein coupled receptors (GPCRs), to detect chemical cues in the environment. For pest biocontrol, chemical attractants are used to trap insect pests. However, with the influx of invasive insect pests, novel odorants are urgently needed, specifically designed to match 3D iOR structures. Experimental structural determination of these membrane receptors remains challenging and only four experimental iOR structures from two evolutionarily distant organisms have been solved. Template-based modelling (TBM) is a complementary approach, to generate model structures, selecting templates based on sequence identity. As the iOR family is highly divergent, a different template selection approach than sequence identity is needed. Bio-GATS template selection for GPCRs, based on hydrophobicity correspondence, has been morphed into iBio-GATS, for template selection from available experimental iOR structures. This easy-to-use semi-automated workflow has been extended to generate high-quality models from any iOR sequence from the selected template, using Python and shell scripting. This workflow was successfully validated on Apocrypta bakeri Orco and Machilis hrabei OR5 structures. iBio-GATS models generated for the fruit fly iOR, OR59b and Orco, yielded functional ligand binding results concordant with experimental mutagenesis findings, compared to AlphaFold2 models.
The Potential of Twendee X® as a Safe Antioxidant Treatment for Systemic Sclerosis
Authors: You Fukka , Nicco Carole , Harakawa Yoshiaki , Yoshikawa Toshikazu , Inufusa Haruhiko
Published: March 2024

Systemic sclerosis (SSc) is an autoimmune disease characterized by systemic skin hardening, which combines Raynaud’s phenomenon and other vascular disorders, skin and internal organ fibrosis, immune disorders, and a variety of other abnormalities. Symptoms vary widely among individuals, and personalized treatment is sought for each patient. Since there is no fundamental cure for SSc, it is designated as an intractable disease with patients receiving government subsidies for medical expenses in Japan. Oxidative stress (OS) has been reported to play an important role in the cause and symptoms of SSc. HOCl-induced SSc mouse models are known to exhibit skin and visceral fibrosis, vascular damage, and autoimmune-like symptoms observed in human SSc. The antioxidant combination Twendee X® (TwX) is a dietary supplement consisting of vitamins, amino acids, and CoQ10. TwX has been proven to prevent dementia in humans with mild cognitive impairment and significantly improve cognitive impairment in an Alzheimer’s disease mouse model by regulating OS through a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. We evaluated the effectiveness of TwX on various symptoms of HOCl-induced SSc mice. TwX-treated HOCl-induced SSc mice showed significantly reduced lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced highly oxidized protein products (AOPP) in serum and suppressed Col-1 gene expression and activation of B cells involved in autoimmunity. These findings suggest that TwX has the potential to be a new antioxidant treatment for SSc without side effects.
Early Increase in Blood–Brain Barrier Permeability in a Murine Model Exposed to Fifteen Days of Intermittent Hypoxia
Authors: Roche Frederic , Briançon-Marjollet Anne , Dematteis Maurice , Baldazza Marie , Gonthier Brigitte , Bertholon Frederique , Perek Nathalie , Pépin Jean-Louis
Published: March 2024

Obstructive sleep apnea (OSA) is characterized by intermittent repeated episodes of hypoxia–reoxygenation. OSA is associated with cerebrovascular consequences. An enhanced blood–brain barrier (BBB) permeability has been proposed as a marker of those disorders. We studied in mice the effects of 1 day and 15 days intermittent hypoxia (IH) exposure on BBB function. We focused on the dorsal part of the hippocampus and attempted to identify the molecular mechanisms by combining in vivo BBB permeability (Evans blue tests) and mRNA expression of several junction proteins (zona occludens (ZO-1,2,3), VE-cadherin, claudins (1,5,12), cingulin) and of aquaporins (1,4,9) on hippocampal brain tissues. After 15 days of IH exposure we observed an increase in BBB permeability, associated with increased mRNA expressions of claudins 1 and 12, aquaporins 1 and 9. IH seemed to increase early for claudin-1 mRNA expression as it doubled with 1 day of exposure and returned near to its base level after 15 days. Claudin-1 overexpression may represent an immediate response to IH exposure. Then, after 15 days of exposure, an increase in functional BBB permeability was associated with enhanced expression of aquaporin. These BBB alterations are possibly associated with a vasogenic oedema that may affect brain functions and accelerate neurodegenerative processes.
Automated Equations of State Tuning Workflow Using Global Optimization and Physical Constraints
Authors: Kanakaki Eirini Maria , Gaganis Vassilis
Published: March 2024

A computational model that can accurately describe the thermodynamics of a hydrocarbon system and its properties under various conditions is a prerequisite for running reservoir and pipeline simulations. Cubic Equations of State (EoS) are mathematical tools used to model the phase and volumetric behavior of reservoir fluids when compositional effects need to be considered. To anticipate uncertainty and enhance the quality of their predictions, EoS models must be adjusted to adequately match the available lab-measured PVT values. This task is challenging given that there are many potential tuning parameters, thus leading to various tuning results of questionable validity. In this paper, we present an automated EoS tuning workflow that employs a Generalized Pattern Search (GPS) optimizer for efficient tuning of a cubic EoS model. Specifically, we focus on the Peng–Robinson (PR) model, which is the oil and gas industry standard, to accurately capture the behavior of diverse multicomponent, complex hydrocarbon mixtures encountered in subsurface reservoirs. This approach surpasses the limitations of conventional gradient-based (GB) methods, which are susceptible to getting trapped in local optima. The proposed technique also allows physical constraints to be imposed on the optimization procedure. A gas condensate and an H2S-rich oil were used to demonstrate the effectiveness of the GPS algorithm in finding an optimized solution for high-dimensional search spaces, and its superiority over conventional gradient-based optimization was confirmed by automatically tracking globally optimal and physically sound solutions.
Marble Powder as a Soil Stabilizer: An Experimental Investigation of the Geotechnical Properties and Unconfined Compressive Strength Analysis
Authors: Umar Ibrahim Haruna , Lin Hang
Published: March 2024

Fine-grained soils present engineering challenges. Stabilization with marble powder has shown promise for improving engineering properties. Understanding the temporal evolution of Unconfined Compressive Strength (UCS) and geotechnical properties in stabilized soils could aid strength assessment. This study investigates the stabilization of fine-grained clayey soils using waste marble powder as an alternative binder. Laboratory experiments were conducted to evaluate the geotechnical properties of soil–marble powder mixtures, including Atterberg’s limits, compaction characteristics, California Bearing Ratio (CBR), Indirect Tensile Strength (ITS), and Unconfined Compressive Strength (UCS). The effects of various factors, such as curing time, molding water content, and composition ratios, on UCS, were analyzed using Exploratory Data Analysis (EDA) techniques, including histograms, box plots, and statistical modeling. The results show that the CBR increased from 10.43 to 22.94% for unsoaked and 4.68 to 12.46% for soaked conditions with 60% marble powder, ITS rose from 100 to 208 kN/m2 with 60–75% marble powder, and UCS rose from 170 to 661 kN/m2 after 28 days of curing, molding water content (optimum at 22.5%), and composition ratios (optimum at 60% marble powder). Complex modeling yielded R2 (0.954) and RMSE (29.82 kN/m2) between predicted and experimental values. This study demonstrates the potential of utilizing waste marble powder as a sustainable and cost-effective binder for soil stabilization, transforming weak soils into viable construction materials.
Preparation of CS-LS/AgNPs Composites and Photocatalytic Degradation of Dyes
Authors: Wu Jiabao , Chen Xinpeng , Li Aijing , Xing Tieling , Chen Guoqiang
Published: March 2024

Synthetic dyes are prone to water pollution during use, jeopardizing biodiversity and human health. This study aimed to investigate the adsorption and photocatalytic assist potential of sodium lignosulfonate (LS) in in situ reduced silver nanoparticles (AgNPs) and chitosan (CS)-loaded silver nanoparticles (CS-LS/AgNPs) as adsorbents for Rhodamine B (RhB). The AgNPs were synthesized by doping LS on the surface of chitosan for modification. Fourier transform infrared (FT-IR) spectrometry, energy-dispersive spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were used to confirm the synthesis of nanomaterials. The adsorption and photocatalytic removal experiments of RhB were carried out under optimal conditions (initial dye concentration of 20 mg/L, adsorbent dosage of 0.02 g, time of 60 min, and UV power of 250 W), and the kinetics of dye degradation was also investigated, which showed that the removal rate of RhB by AgNPs photocatalysis can reach 55%. The results indicated that LS was highly effective as a reducing agent for the large-scale production of metal nanoparticles and can be used for dye decolorization. This work provides a new catalyst for the effective removal of dye from wastewater, and can achieve high-value applications of chitosan and lignin.
Suitability of Gelatin Methacrylate and Hydroxyapatite Hydrogels for 3D-Bioprinted Bone Tissue
Authors: Stolarov Paul , de Vries Jonathan , Stapleton Sean , Morris Lauren , Martyniak Kari , Kean Thomas J.
Published: March 2024

Background: Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects; however, its limitations include donor-site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. In this experiment, gels composed of varying levels of gelatin methacrylate (GelMA) and hydroxyapatite (HA) and gelatin concentrations are explored. The objective was to increase the hydroxyapatite content and find the upper limit before the printability was compromised and determine its effect on the mechanical properties and cell viability. Methods: Design of Experiments (DoE) was used to design 13 hydrogel bioinks of various GelMA/HA concentrations. These bioinks were assessed in terms of their pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Three bioinks, one with the DoE-designed maximal stiffness, one with the experimentally defined maximal stiffness, and a literature-based control, were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. Results: The DoE ANOVA analysis indicated that the augmented three-level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% gelatin. There were no significant differences in the cell viability within the hydrogels from day 2 to day 7 (p > 0.05). There was, however, a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with a lower HA concentration (p < 0.05), showing that a higher HA content or print pressure may be cytotoxic within hydrogels. Conclusions: Extrusion-based 3DBP offers significant advantages for bone–tissue implants due to its high customizability. This study demonstrates that it is possible to create printable bone-like grafts from GelMA and HA with an increased HA content, favorable mechanical properties (145 kPa), and a greater than 80% cell viability.
Amino-Modified Graphene Oxide from Kish Graphite for Enhancing Corrosion Resistance of Waterborne Epoxy Coatings
Authors: Hao Shengle , Wan Siming , Hou Shiyu , Yuan Bowen , Luan Chenhui , Nan Ding , Huang Gen , Xu Deping , Huang Zheng-Hong
Published: March 2024

Waterborne epoxy (WEP) coatings with enhanced corrosion resistance were prepared using graphene oxide (GO) that was obtained from kish graphite, and amino-functionalized graphene oxide (AGO) was modified by 2-aminomalonamide. The structural characteristics of the GO and AGO were analyzed using X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). And the anti-corrosive performance of waterborne epoxy-cased composite coatings with different addition amounts of AGO was investigated using electrochemical measurements, pull-off adhesion tests, and salt spray tests. The results indicate that AGO15/WEP with 0.15 wt.% of AGO has the best anti-corrosive performance, and the lowest frequency impedance modulus increased from 1.03 × 108 to 1.63 × 1010 ohm·cm−2 compared to that of WEP. Furthermore, AGO15/WEP also demonstrates the minimal corrosion products or bubbles in the salt spray test for 200 h, affirming its exceptional long-term corrosion protection capability.