bluuebunny/crossref_metadata_2025 huggingface dataset:
Digitization Meets Energy Transition: Shaping the Future of Environmental Sustainability
Authors: Wang Lin , He Yugang , Wu Renhong
Published: February 2024

This paper presents an empirical investigation into the effects of energy transition and digitization on carbon dioxide emissions, serving as a proxy for environmental sustainability, across 28 Chinese provinces from 2000 to 2021. Utilizing both static and dynamic regression analyses, the study reveals a significant driving effect of the energy transition on environmental sustainability, primarily through a reduction in carbon dioxide emissions. Notably, this influence is more pronounced in the eastern region of China, followed by the central and western regions, indicating regional heterogeneity in the impact of the energy transition. Furthermore, digitization is found to have a substantial moderating effect, enhancing energy conservation and emission reductions. As digitization progresses, its capability to diminish the impact of energy transitions on carbon dioxide emissions becomes more apparent, particularly in the eastern region, while this effect is less marked in central and western China. The study also delves into the nonlinear relationship between energy transitions and carbon dioxide emissions, discovering that increased levels of digitization can exacerbate the negative effects of energy transitions on emissions. These findings offer valuable insights into the dynamics of energy transition and digitalization, highlighting their crucial roles in shaping environmental sustainability in China.
BYCFoam: An Improved Solver for Rotating Detonation Engines Based on OpenFOAM
Authors: Cheng Miao , Sheng Zhaohua , Wang Jian-Ping
Published: February 2024

A rotating detonation engine (RDE) is a highly promising detonation-based propulsion system and has been widely researched in recent decades. In this study, BYCFoam, the latest gaseous version of the BYRFoam family, is developed specifically for RDE simulations. It is based on the standard compressible flow solver rhoCentralFoam in OpenFOAM and incorporates several enhancements: improved reconstruction variables and flux schemes; detailed chemistry and transport properties; the utilization of an adaptive mesh refinement (AMR) and dynamic load balancing (DLB). A series of comprehensive numerical tests are conducted, including the shock-tube problem, shock-wave diffraction, homogeneous ignition delay, premixed flame, planar detonation, detonation cellular structure and rotating detonation combustor (RDC). The results demonstrate that BYCFoam can accurately and efficiently simulate the deflagration and detonation processes. This solver enhances the capability of the BYRFoam family for the in-depth exploration of RDE in future research.
Energy Transition: Semi-Automatic BIM Tool Approach for Elevating Sustainability in the Maputo Natural History Museum
Authors: Piras Giuseppe , Muzi Francesco
Published: February 2024

Mozambique is experiencing the consequences of a severe energy crisis with economic and social impacts. Its strict dependence on hydroelectric sources is being severely tested by recent droughts that have drastically reduced water levels in dams. However, Mozambique is addressing energy poverty by exploring renewable energy sources thanks to investments in the sector by the European Union. The research concerns an energy analysis profile of the country and the penetration of renewable energy, presenting an energy upgrading scope through a semi-automatic calculation methodology in a Building Information Modeling (BIM) environment. The building under study, located in Maputo, is the Natural History Museum, which plays an important role in biodiversity conservation. Therefore, this paper proposes a BIM methodology for sizing an environmental control system tailored to serve the museum. The proposed system replaces the previous one and includes a photovoltaic system that not only meets the museum’s load but also supplies electricity to the surrounding area. Energy production from renewable sources with a surplus of 30% has been achieved. The proposed digital methodology has identified a maximum gap of 1.5% between the dimensions of the BIM duct and those of a traditional plant design, meeting ASHRAE requirements for environmental control.
The Effects of Exterior Glazing on Human Thermal Comfort in Office Buildings
Authors: Song Bing , Bai Lujian , Yang Liu
Published: February 2024

As a major component of the building envelope, the energy-saving design of exterior windows is key to energy savings in office buildings. The conventional design of exterior windows mainly focused on their impact on heating and cooling energy but ignored the indoor thermal comfort problems caused by the direct solar radiation transmitted by windows and the fluctuation of their internal surface temperatures. This study analyzed the influence of exterior windows on the indoor thermal environment of office buildings by carrying out field experiments. The experiments were carried out in a typical office building in Xi’an during December and January. The impact of exterior windows on human thermal comfort was studied from two perspectives: longwave radiation from the surface of window glass and solar shortwave radiation. It was found that solar radiation was the main cause of temperature fluctuations on the internal surface of windows and created non-uniform thermal environments. The mean radiant temperature fluctuations in the near-window area could reach up to 7.8 °C due to outdoor solar radiation in winter. Solar radiation transmitted by windows directly affects thermal sensations. Since conventional thermal comfort models or indices underestimated the thermal sensations of occupants in the presence of solar radiation, the additional thermal loads caused by solar radiation needed to be taken into account. The allowable operative temperature range for maintaining thermal comfort should be reduced by 0.5 °C when occupants are exposed to solar radiation.
Research on Improvement of Data Synchronization Method for Distribution Network Differential Protection Based on 5G
Authors: Fan Haiqiang , Wang Weiqing , Cheng Jing , Yuan Zhi , Li Xiaozhu , Yan Sizhe , Zhu Jinlong
Published: February 2024

To enhance the reliability of traditional current protection systems in the evolving landscape of future power grids, this paper proposes a differential protection data synchronization approach that leverages satellite and 5G network timing. This method addresses the risk of inadvertent operation due to 5G communication jitter. It employs the BeiDou satellite system for synchronizing the timing of 5G base stations and terminals. This synchronization extends to the 5G terminal and the protection device, thereby mitigating time deviations caused by air interface delays and reducing the 5G network’s end-to-end delay by approximately 4 ms on average. A simulation was conducted to assess the reliability and effectiveness of the proposed method under normal satellite signal conditions. The results indicated a significant improvement in protection accuracy, with the method reducing the protection activation time by approximately 5–7 ms compared to the 5G timing data synchronization method. This advancement offers technical support for the safe and stable operation of new power systems.
Lithofacies Characteristics of Gulong Shale and Its Influence on Reservoir Physical Properties
Authors: Han Zongyan , Wang Guiwen , Wu Hongliang , Feng Zhou , Tian Han , Xie Yingyi , Wu Hao
Published: February 2024

The lithofacies characteristics of the Qingshankou Formation (K2qn) shale in the Gulong Depression are crucial for oil exploration and development. This study investigates the K2qn shale lithofacies characteristics and their impact on reservoir physical properties using scanning electron microscopy (SEM), high-pressure mercury injection (HPMI), and logging quantification. The results indicate that the main minerals in K2qn shale are quartz, plagioclase, and clay. The sedimentary structures are classified into three types: laminated, layered, and massive. The K2qn shale lithofacies can be categorized into 12 types based on a combination of lithology and sedimentary structure. The main types are laminated clayey shale, layered clayey shale, and layered felsic shale. The larger the average pore size of the K2qn lithofacies, the stronger the heterogeneity of pore size distribution in space and the better the pore-to-throat connectivity. The impact of K2qn shale lithofacies on reservoir physical properties is mainly due to differences in lithology, complemented by variations in the sedimentary structural model. Under certain diagenetic or tectonic conditions, a layered sedimentary structural model of lithofacies may not increase reservoir permeability. Generally, felsic and carbonate rocks in tidal flat environments promote the development of shale with high permeability and porosity, while lithofacies deposited in static water environments below the wave base in lake basins typically exhibit low permeability and porosity. The physical properties of a reservoir are primarily influenced by the differences in pore throat characteristics resulting from variations in lithology.
Thermal Ageing of Dry Cellulose Paper Impregnated with Different Insulating Liquids—Comparative Studies of Materials Properties
Authors: Przybylek Piotr
Published: February 2024

Natural and synthetic esters are increasingly being chosen instead of mineral oil for environmental and fire safety reasons. However, their use in power transformers is limited due to insufficiently well-understood ageing processes affecting their properties and the properties of cellulosic materials impregnated with them. The research results presented in many scientific papers prove that the use of esters slows the ageing process of cellulosic materials. This article presents the results of research aimed at answering the question of whether the effect of slowing the ageing process will also occur in the case of insulation with very low initial moisture. The answer to this question will allow us to better understand the role of water in the ageing process of the transformer’s insulation system. The thermal ageing process was carried out at a temperature of 150 °C in closed systems. The degree of cellulose polymerisation was taken as a measure of the degree of paper ageing. Great attention was paid to measuring the water content in both paper and electro-insulating liquids at various stages of their ageing. Furthermore, measurements of the properties of electro-insulating liquids were made, which are considered markers of ageing. The test results obtained indicate that in the case of a dry insulation system, corresponding to the initial moisture of the new units, the type of liquid used to impregnate the cellulosic material does not significantly affect its depolymerisation process. However, in the case of paper impregnated with natural esters, a lower dynamic of moisture increase in insulation was observed.
Field-Oriented Control of a Nine-Phase Cage Induction Generator with Large Speed Changes and Variable Load
Authors: Cholewa Dariusz , Drozdowski Piotr
Published: February 2024

This paper presents a voltage control system for multiphase squirrel-cage induction generators operating at a high variability of speed and variable load. Field-oriented vector control was used with a change in the sequence of the stator phase currents what changes the number of poles of the magnetic field produced by nine-phase stator winding. At low speeds, the current sequence is changed so that the number of poles increases allowing for the desired voltage to be obtained with greater efficiency. The task of the automatic control system was to control the DC voltage to a desired value at the output of the multiphase PWM converter. This is an alternative control method to the scalar control of voltage and frequency presented in a previous work. The control method and parameters of the automatic control system result from the mathematical model of the multiphase induction machine. The results of the laboratory tests were compared with the effects of the operation of the same nine-phase scalar controlled generator.
Fractional-Order Control Method Based on Twin-Delayed Deep Deterministic Policy Gradient Algorithm
Authors: Jiao Guangxin , An Zhengcai , Shao Shuyi , Sun Dong
Published: February 2024

In this paper, a fractional-order control method based on the twin-delayed deep deterministic policy gradient (TD3) algorithm in reinforcement learning is proposed. A fractional-order disturbance observer is designed to estimate the disturbances, and the radial basis function network is selected to approximate system uncertainties in the system. Then, a fractional-order sliding-mode controller is constructed to control the system, and the parameters of the controller are tuned using the TD3 algorithm, which can optimize the control effect. The results show that the fractional-order control method based on the TD3 algorithm can not only improve the closed-loop system performance under different operating conditions but also enhance the signal tracking capability.
The Impact of Cancer-Associated Fibroblasts on the Biology and Progression of Colorectal Carcinomas
Authors: Henrich Larissa Maria , Greimelmaier Kristina , Wessolly Michael , Klopp Nick Alexander , Mairinger Elena , Krause Yvonne , Berger Sophia , Wohlschlaeger Jeremias , Schildhaus Hans-Ulrich , Baba Hideo Andreas , Mairinger Fabian Dominik , Borchert Sabrina
Published: February 2024

(1) Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Cancer-associated fibroblasts (CAFs) are major components of CRC’s tumour microenvironment (TME), but their biological background and interplay with the TME remain poorly understood. This study investigates CAF biology and its impact on CRC progression. (2) The cohort comprises 155 cases, including CRC, with diverse localizations, adenomas, inflammations, and controls. Digital gene expression analysis examines genes associated with signalling pathways (MAPK, PI3K/Akt, TGF-β, WNT, p53), while next-generation sequencing (NGS) determines CRC mutational profiles. Immunohistochemical FAP scoring assesses CAF density and activity. (3) FAP expression is found in 81 of 150 samples, prevalent in CRC (98.4%), adenomas (27.5%), and inflammatory disease (38.9%). Several key genes show significant associations with FAP-positive fibroblasts. Gene set enrichment analysis (GSEA) highlights PI3K and MAPK pathway enrichment alongside the activation of immune response pathways like natural killer (NK)-cell-mediated cytotoxicity via CAFs. (4) The findings suggest an interplay between CAFs and cancer cells, influencing growth, invasiveness, angiogenesis, and immunogenicity. Notably, TGF-β, CDKs, and the Wnt pathway are affected. In conclusion, CAFs play a significant role in CRC and impact the TME throughout development.
Identification of Candidate Expansin Genes Associated with Seed Weight in Pomegranate (Punica granatum L.)
Authors: Liu Chunyan , Zhao Haoyu , Li Jiyu , Cao Zhen , Deng Bo , Liu Xin , Qin Gaihua
Published: February 2024

Seed weight is an important target trait in pomegranate breeding and culture. Expansins act by loosening plant cell walls and cellulosic materials, permitting turgor-driven cell enlargement. However, the role of expansin genes (EXPs) in pomegranate seed weight remains elusive. A total of 29 PgrEXPs were identified in the ‘Dabenzi’ genome. These genes were classified into four subfamilies and 14 subgroups, including 22 PgrEXPAs, 5 PgrEXPBs, 1 PgrEXPLA, and 1 PgrEXPLB. Transcriptome analysis of PgrEXPs in different tissues (root, leaf, flower, peel, and seed testa) in ‘Dabenzi’, and the seed testa of the hard-seeded pomegranate cultivar ‘Dabenzi’ and soft-seeded cultivar ‘Tunisia’ at three development stages showed that three PgrEXPs (PgrEXPA11, PgrEXPA22, PgrEXPA6) were highly expressed throughout seed development, especially in the sarcotesta. SNP/Indel markers of these PgrEXPs were developed and used to genotype 101 pomegranate accessions. The association of polymorphic PgrEXPs with seed weight-related traits (100-seed weight, 100-kernel weight, 100-sarcotesta weight, and the percentage of 100-sarcotesta to 100-seed weight) were analyzed. PgrEXP22 was significantly associated with 100-seed weight and 100-sarcotesta weight and is a likely candidate for regulating seed weight and sarcotesta development in particular. This study provides an effective tool for the genetic improvement of seed weight in pomegranate breeding programs.
More Help Was Offered—But Was It Effective? First Responders and Volunteers in the 2021 Flood Disaster in Germany
Authors: Fekete Alexander , Rhein Beate
Published: February 2024

The floods in 2021 in Germany laid bare the need to better integrate volunteers into official disaster management. An online survey with 1767 valid interviews after the floods in July 2021 reveals the shared experiences of professional and non-professional groups. Communication and coordination problems are the main results of the survey analysis. Overall satisfaction was a bit lower for the volunteers than for the professionals. The behavior of the superiors could have been more satisfactory. The preparation and opportunity for reflection could have been better after the operation. The information provision before and during the flood operation could have been more satisfactory. Worries were higher about elderly persons, and misinformation was a perceived danger. Problems experienced in the flood operations ranged from psychological stress to hygiene, self-endangerment, assignment of tasks, and misinformation, both from the media and official sources. Infrastructure-related problems included electricity, water, communication lines, roads, and rail. The suggestions for improvements ranged from communication and information about warnings and behavior to persons that transfer knowledge between organizations, digital exchange platforms, and exchange between countries.
Study on Long-Term Care Service Awareness, Needs, and Usage Intention of Older Adult Male Homosexuals in Taiwan and Their Ideal Long-Term Care Service Model
Authors: Hong Hong
Published: February 2024

As the significance of long-term care services for older adults becomes more pronounced in Taiwan, especially considering the intensifying trend of an aging population, there remains a lack of comprehensive attention to the long-term care needs and experiences of older adult individuals within the LGBTQ+ community. The present study examines the long-term care service awareness, needs, and usage intention of older adult male homosexuals in Taiwan and assesses their ideal long-term care service model. This study of five older adult male homosexual subjects aged 66 to 73 years is intended as a preliminary exploration. Interviews were used to collect data. The study determined that the five subjects displayed high awareness of long-term care services, as they possessed actual experience of these services or had even participated in care service staff training to obtain certificates. Some even had experience in applying for home care services and reported problems during use. The subjects perceived that they were very likely to require long-term care services in the future and tended to opt for home care services if they required long-term support. Due to their personal experiences, the subjects displayed negative awareness of long-term care services and expressed worry that long-term care service staff harbored poor attitudes toward homosexuals. The subjects considered the most important aspects of long-term care to be basic medical care and lifestyle care. However, they worried that long-term care staff would delay or refuse to provide such services due to the subjects’ sexual orientation or stereotypes related to it, and they were concerned above all about the “friendly attitude” of long-term care staff. They hoped that long-term care staff were friendly toward homosexuals and did not discriminate against them, feeling that it would be more appropriate for homosexual long-term care staff to provide assistance. In terms of vision, while preferring organizations with homosexual employees, the subjects worried that they would be stigmatized and discriminated against. Regarding ideal long-term care services, while considering institutions with homosexual staff to be ideal, the subjects also worried that these would be labeled as institutions that were dedicated to homosexuals, potentially resulting in discrimination. Therefore, they hoped that the sexuality sensitivity of long-term care staff could be improved and that they would undergo professional continuing education to learn about homosexuals, their situations, and care needs.
Effects of the Three-Direction Movement Control Focus Complex Pain Program and Neurodynamic Focus Complex Pain Program on Pain, Mechanosensitivity, and Body Function in Taekwondo Athletes with Non-Specific Low Back Pain: A Preliminary Study
Authors: Kim Hong-gil , Jung Ju-hyeon , Bae Song-ui
Published: February 2024

We aimed to determine the effects of three-direction movement control focus complex pain program (3D-MCE) and neurodynamic focus complex pain program (NDT) on pain, mechanosensitivity, and body function in Taekwondo athletes with non-specific low back pain. This study used a two-group pretest–posttest design and was conducted at a university physiotherapy lab and training center. It included 21 Taekwondo athletes with non-specific low back pain from a Taekwondo studio and a University in Busan. Participants were divided into a 3D-MCE group (n = 10) and an NDT group (n = 10). The numerical rating pain scale (NRPS), pain pressure threshold (PPT), movement analysis, and Oswestry Disability Index (ODI) were measured before and after the intervention. The intervention was performed for 45 min twice a week for 4 weeks. Each group performed movement control exercises and neurodynamic techniques. The NRPS, motion analysis, and ODI were significantly changed after the intervention in the 3-DMCE group. The NRPS, PPT, and ODI changed significantly after the intervention in the NDT group. Moreover, the PPT and motion analysis showed significant differences between the two groups. For Taekwondo athletes with non-specific low back pain, 3D-MCE improved the stability control ability of the lumbar spine. It was confirmed that neurodynamic techniques reduce muscle and nerve mechanosensitivity.
A Spatial Optimization Model for Delineating Metropolitan Areas
Authors: Wang Gusiyuan , Mu Wangshu
Published: February 2024

A metropolitan area comprises a collection of cities and counties bound by strong socioeconomic ties. Despite the pivotal role that metropolitan areas play in regional economics, their delineation remains a challenging task for researchers and urban planners. Current threshold-based delineation methods select counties based on their connection strength with prespecified core counties. Such an approach often neglects potential interactions among outlying counties and fails to identify polycentric urban structures. The delineation of a metropolitan area is fundamentally a spatial optimization problem, whose objective is to identify a set of counties with high interconnectivity while also meeting specific constraints, such as area, contiguity, and shape. In this study, we present a novel spatial optimization model designed for metropolitan area delineation. This model aims to maximize intercounty connection strength in terms of both industry and daily life. This approach ensures a more accurate representation of the multicore structure that is commonly seen in developed metropolitan areas. Additionally, our model avoids the possibility of holes in metropolitan area delineation, leading to more coherent and logical metropolitan boundaries. We provide a mixed-integer programming formulation for the proposed model. Its efficacy is demonstrated by delineating the boundaries of the Nanjing and Lhasa metropolitan areas. This study also delves into discussions and policy implications pertinent to both of these metropolitan areas.
Role of microRNAs in Immune Regulation with Translational and Clinical Applications
Authors: Gaál Zsuzsanna
Published: February 2024

MicroRNAs (miRNAs) are 19–23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. In this review, involvement of miRNAs is summarized in the differentiation and function of immune cells, in anti-infective immune responses, immunodeficiencies and autoimmune diseases. Roles of miRNAs in anticancer immunity and in the transplantation of solid organs and hematopoietic stem cells are also discussed. Major focus is put on the translational clinical applications of miRNAs, including the establishment of noninvasive biomarkers for differential diagnosis and prediction of prognosis. Patient selection and response prediction to biological therapy is one of the most promising fields of application. Replacement or inhibition of miRNAs has enormous therapeutic potential, with constantly expanding possibilities. Although important challenges still await solutions, evaluation of miRNA fingerprints may contribute to an increasingly personalized management of immune dysregulation with a remarkable reduction in toxicity and treatment side effects. More detailed knowledge of the molecular effects of physical exercise and nutrition on the immune system may facilitate self-tailored lifestyle recommendations and advances in prevention.
PgDDS Changes the Plant Growth of Transgenic Aralia elata and Improves the Production of Re and Rg3 in Its Leaves
Authors: Guo Wenhua , Zhao Yue , Xu Honghao , Xia Yuxin , Tao Lei , You Xiangling
Published: February 2024

Aralia elata (Miq.) Seem is a medicinal plant that shares a common pathway for the biosynthesis of triterpenoid saponins with Panax ginseng. Here, we transferred the dammarenediol-II synthase gene from P. ginseng (PgDDS; GenBank: AB122080.1) to A. elata. The growth of 2-year-old transgenic plants (L27; 9.63 cm) was significantly decreased compared with wild-type plants (WT; 74.97 cm), and the leaflet shapes and sizes of the transgenic plants differed from those of the WT plants. Based on a terpene metabolome analysis of leaf extracts from WT, L13, and L27 plants, a new structural skeleton for ursane-type triterpenoid saponins was identified. Six upregulated differentially accumulated metabolites (DAMs) were detected, and the average levels of Rg3 and Re in the leaves of the L27 plants were 42.64 and 386.81 μg/g, respectively, increased significantly compared with the WT plants (15.48 and 316.96 μg/g, respectively). Thus, the expression of PgDDS in A. elata improved its medicinal value.
Effects of Aerobic Treadmill Training on Oxidative Stress Parameters, Metabolic Enzymes, and Histomorphometric Changes in Colon of Rats with Experimentally Induced Hyperhomocysteinemia
Authors: Stojanović Marija , Todorović Dušan , Gopčević Kristina , Medić Ana , Labudović Borović Milica , Despotović Sanja , Djuric Dragan
Published: February 2024

The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752–10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562–5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels.
Enhanced Immunomodulatory Effects of Thymosin-Alpha-1 in Combination with Polyanionic Carbosilane Dendrimers against HCMV Infection
Authors: Espinar-Buitrago María de la Sierra , Magro-López Esmeralda , Vázquez-Alejo Elena , Muñoz-Fernández María Ángeles
Published: February 2024

Resistance and toxicity associated with current treatments for human cytomegalovirus (HCMV) infection highlight the need for alternatives and immunotherapy has emerged as a promising strategy. This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (Tα1) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that Tα1 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFNγ production in T cells and elevated Treg functionality and reduced senescence were evident with Tα1 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with Tα1 + G2S16 treatment. In summary, Tα1 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.
Modeling Spinal Muscular Atrophy in Zebrafish: Current Advances and Future Perspectives
Authors: Gonzalez David , Vásquez-Doorman Constanza , Luna Adolfo , Allende Miguel L.
Published: February 2024

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by degeneration of lower motor neurons (LMNs), causing muscle weakness, atrophy, and paralysis. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene and can be classified into four subgroups, depending on its severity. Even though the genetic component of SMA is well known, the precise mechanisms underlying its pathophysiology remain elusive. Thus far, there are three FDA-approved drugs for treating SMA. While these treatments have shown promising results, their costs are extremely high and unaffordable for most patients. Thus, more efforts are needed in order to identify novel therapeutic targets. In this context, zebrafish (Danio rerio) stands out as an ideal animal model for investigating neurodegenerative diseases like SMA. Its well-defined motor neuron circuits and straightforward neuromuscular structure offer distinct advantages. The zebrafish’s suitability arises from its low-cost genetic manipulation and optical transparency exhibited during larval stages, which facilitates in vivo microscopy. This review explores advancements in SMA research over the past two decades, beginning with the creation of the first zebrafish model. Our review focuses on the findings using different SMA zebrafish models generated to date, including potential therapeutic targets such as U snRNPs, Etv5b, PLS3, CORO1C, Pgrn, Cpg15, Uba1, Necdin, and Pgk1, among others. Lastly, we conclude our review by emphasizing the future perspectives in the field, namely exploiting zebrafish capacity for high-throughput screening. Zebrafish, with its unique attributes, proves to be an ideal model for studying motor neuron diseases and unraveling the complexity of neuromuscular defects.
Identification of Germline FOXE1 and Somatic MAPK Pathway Gene Alterations in Patients with Malignant Struma Ovarii, Cleft Palate and Thyroid Cancer
Authors: Pires Carolina , Saramago Ana , Moura Margarida M. , Li Jing , Donato Sara , Marques Inês J. , Belo Hélio , Machado Ana C. , Cabrera Rafael , Grünewald Thomas G. P. , Leite Valeriano , Cavaco Branca M.
Published: February 2024

Germline variants in the FOXE1 transcription factor have been associated with thyroid ectopy, cleft palate (CP) and thyroid cancer (TC). Here, we aimed to clarify the role of FOXE1 in Portuguese families (F1 and F2) with members diagnosed with malignant struma ovarii (MSO), an ovarian teratoma with ectopic malignant thyroid tissue, papillary TC (PTC) and CP. Two rare germline heterozygous variants in the FOXE1 promoter were identified: F1) c.-522G>C, in the proband (MSO) and her mother (asymptomatic); F2) c.9C>T, in the proband (PTC), her sister and her mother (CP). Functional studies using rat normal thyroid (PCCL3) and human PTC (TPC-1) cells revealed that c.9C>T decreased FOXE1 promoter transcriptional activity in both cell models, while c.-522G>C led to opposing activities in the two models, when compared to the wild type. Immunohistochemistry and RT-qPCR analyses of patients’ thyroid tumours revealed lower FOXE1 expression compared to adjacent normal and hyperplastic thyroid tissues. The patient with MSO also harboured a novel germline AXIN1 variant, presenting a loss of heterozygosity in its benign and malignant teratoma tissues and observable β-catenin cytoplasmic accumulation. The sequencing of the F1 (MSO) and F2 (PTC) probands’ tumours unveiled somatic BRAF and HRAS variants, respectively. Germline FOXE1 and AXIN1 variants might have a role in thyroid ectopy and cleft palate, which, together with MAPK pathway activation, may contribute to tumours’ malignant transformation.
Extracellular Vesicles in the Pathogenesis, Clinical Characterization, and Management of Dermatomyositis: A Narrative Review
Authors: Ricco Cristina , Eldaboush Ahmed , Liu Ming-Lin , Werth Victoria P.
Published: February 2024

Extracellular vesicles (EVs) are lipid-bilayer particles secreted from cells that primarily assist in cell-to-cell communication through the content of their cargo, such as proteins and RNA. EVs have been implicated in the pathogenesis of various autoimmune diseases, including dermatomyositis (DM), an inflammatory autoimmune disease characterized by distinct cutaneous manifestations, myopathy, and lung disease. We sought to review the role of EVs in DM and understand how they contribute to the pathogenesis and clinical characterization of the disease. We summarized the research progress on EVs in dermatomyositis based on recent publications. EV cargoes, such as double-stranded DNA, microRNA, and proteins, contribute to DM pathogenesis and mediate the proinflammatory response and cytokine release through signaling pathways such as the stimulator of interferon genes (STING) pathway. These nucleic acids and proteins have been proposed as disease-specific, stable biomarkers to monitor disease activity and responses to therapy. They also correlate with clinical parameters, inflammatory markers, and disease severity scores. Furthermore, some markers show an association with morbidities of DM, such as muscle weakness and interstitial lung disease. The continued study of EVs will help us to further elucidate our understanding of dermatomyositis.
Benzodiazepine Interference with Fertility and Embryo Development: A Preliminary Survey in the Sea Urchin Paracentrotus lividus
Authors: Fogliano Chiara , Carotenuto Rosa , Cirino Paola , Panzuto Raffaele , Ciaravolo Martina , Simoniello Palma , Sgariglia Ilaria , Motta Chiara Maria , Avallone Bice
Published: February 2024

Psychotropic drugs and benzodiazepines are nowadays among the primary substances of abuse. This results in a large and constant release into aquatic environments where they have potentially harmful effects on non-target organisms and, eventually, human health. In the last decades, evidence has been collected on the possible interference of benzodiazepines with reproductive processes, but data are few and incomplete. In this study, the possible negative influence of delorazepam on fertilization and embryo development has been tested in Paracentrotus lividus, a key model organism in studies of reproduction and embryonic development. Sperm, eggs, or fertilized eggs have been exposed to delorazepam at three concentrations: 1 μg/L (environmentally realistic), 5 μg/L, and 10 μg/L. Results indicate that delorazepam reduces the fertilizing capacity of male and female gametes and interferes with fertilization and embryo development. Exposure causes anatomical anomalies in plutei, accelerates/delays development, and alters the presence and distribution of glycoconjugates such as N-Acetyl-glucosamine, α-linked fucose, and α-linked mannose in both morulae and plutei. These results should attract attention to the reproductive fitness of aquatic species exposed to benzodiazepines and pave the way for further investigation of the effects they may exert on human fertility. The presence of benzodiazepines in the aquatic environment raises concerns about the reproductive well-being of aquatic species. Additionally, it prompts worries regarding potential impacts on human fertility due to the excessive use of anxiolytics.
Do DEEPER ROOTING 1 Homologs Regulate the Lateral Root Slope Angle in Cucumber (Cucumis sativus)?
Authors: Kiryushkin Alexey S. , Ilina Elena L. , Kiikova Tatyana Y. , Pawlowski Katharina , Demchenko Kirill N.
Published: February 2024

The architecture of the root system is fundamental to plant productivity. The rate of root growth, the density of lateral roots, and the spatial structure of lateral and adventitious roots determine the developmental plasticity of the root system in response to changes in environmental conditions. One of the genes involved in the regulation of the slope angle of lateral roots is DEEPER ROOTING 1 (DRO1). Its orthologs and paralogs have been identified in rice, Arabidopsis, and several other species. However, nothing is known about the formation of the slope angle of lateral roots in species with the initiation of lateral root primordia within the parental root meristem. To address this knowledge gap, we identified orthologs and paralogs of the DRO1 gene in cucumber (Cucumis sativus) using a phylogenetic analysis of IGT protein family members. Differences in the transcriptional response of CsDRO1, CsDRO1-LIKE1 (CsDRO1L1), and CsDRO1-LIKE2 (CsDRO1L2) to exogenous auxin were analyzed. The results showed that only CsDRO1L1 is auxin-responsive. An analysis of promoter–reporter fusions demonstrated that the CsDRO1, CsDRO1L1, and CsDRO1L2 genes were expressed in the meristem in cell files of the central cylinder, endodermis, and cortex; the three genes displayed different expression patterns in cucumber roots with only partial overlap. A knockout of individual CsDRO1, CsDRO1L1, and CsDRO1L2 genes was performed via CRISPR/Cas9 gene editing. Our study suggests that the knockout of individual genes does not affect the slope angle formation during lateral root primordia development in the cucumber parental root.
Genome-Wide Identification of B-Box Gene Family and Candidate Light-Related Member Analysis of Tung Tree (Vernicia fordii)
Authors: Shi Kai , Zhao Guang , Li Ze , Zhou Junqin , Wu Lingli , Tan Xiaofeng , Yuan Jun
Published: February 2024

Light is one of the most important environmental factors for plant growth. In the production process of tung oil tree cultivation, due to the inappropriate growth of shading conditions, the lower branches are often dry and dead, which seriously affects the yield of tung oil trees. However, little is known about the key factors of light-induced tree photomorphogenesis. In this study, a total of 22 VfBBX family members were identified to provide a reference for candidate genes in tung tree seedlings. All members of the VfBBX family have different numbers of highly conserved B-box domains or CCT domains. Phylogenetic evolution clustered the VfBBX genes into four categories, and the highest density of members was on chromosome 6. Interspecific collinearity analysis suggested that there were six pairs of duplicate genes in VfBBX members, but the expression levels of all family members in different growth and development stages of the tung tree were significantly divergent. After different degrees of shading treatment and physiological data determination of tung tree seedlings, the differential expression level and chlorophyll synthesis genes correlation analysis revealed that VfBBX9 was a typical candidate nuclear localization transcription factor that was significantly differentially expressed in light response. This study systematically identified the VfBBX gene family and provided a reference for studying its molecular function, enhanced the theoretical basis for tung tree breeding, and identified excellent varieties.
A Novel Hemocyte-Derived Peptide and Its Possible Roles in Immune Response of Ciona intestinalis Type A
Authors: Matsubara Shin , Iguchi Rin , Ogasawara Michio , Nakamura Hiroya , Kataoka Tatsuki R. , Shiraishi Akira , Osugi Tomohiro , Kawada Tsuyoshi , Satake Honoo
Published: February 2024

A wide variety of bioactive peptides have been identified in the central nervous system and several peripheral tissues in the ascidian Ciona intestinalis type A (Ciona robusta). However, hemocyte endocrine peptides have yet to be explored. Here, we report a novel 14-amino-acid peptide, CiEMa, that is predominant in the granular hemocytes and unilocular refractile granulocytes of Ciona. RNA-seq and qRT-PCR revealed the high CiEma expression in the adult pharynx and stomach. Immunohistochemistry further revealed the highly concentrated CiEMa in the hemolymph of the pharynx and epithelial cells of the stomach, suggesting biological roles in the immune response. Notably, bacterial lipopolysaccharide stimulation of isolated hemocytes for 1–4 h resulted in 1.9- to 2.4-fold increased CiEMa secretion. Furthermore, CiEMa-stimulated pharynx exhibited mRNA upregulation of the growth factor (Fgf3/7/10/22), vanadium binding proteins (CiVanabin1 and CiVanabin3), and forkhead and homeobox transcription factors (Foxl2, Hox3, and Dbx) but not antimicrobial peptides (CrPap-a and CrMam-a) or immune-related genes (Tgfbtun3, Tnfa, and Il17-2). Collectively, these results suggest that CiEMa plays roles in signal transduction involving tissue development or repair in the immune response, rather than in the direct regulation of immune response genes. The present study identified a novel Ciona hemocyte peptide, CiEMa, which paves the way for research on the biological roles of hemocyte peptides in chordates.
Special Issue “Molecular Immunology of the Male Reproductive System”
Authors: Haidl Gerhard
Published: February 2024

The immunological aspects of male infertility have gradually become the focus of both basic and clinical research [...]
Cellular Alterations Due to Direct and Indirect Interaction of Nanomaterials with Nucleic Acids
Authors: Encinas-Gimenez Miguel , Martin-Duque Pilar , Martín-Pardillos Ana
Published: February 2024

Deoxyribonucleic acid (DNA) represents the main reservoir of genetic information in the cells, which is why it is protected in the nucleus. Entry into the nucleus is, in general, difficult, as the nuclear membrane is a selective barrier to molecules longer than 40 kDa. However, in some cases, the size of certain nanoparticles (NPs) allows their internalization into the nucleus, thus causing a direct effect on the DNA structure. NPs can also induce indirect effects on DNA through reactive oxygen species (ROS) generation. In this context, nanomaterials are emerging as a disruptive tool for the development of novel therapies in a broad range of biomedical fields; although their effect on cell viability is commonly studied, further interactions with DNA or indirect alterations triggered by the internalization of these materials are not always clarified, since the small size of these materials makes them perfectly suitable for interaction with subcellular structures, such as the nucleus. In this context, and using as a reference the predicted interactions presented in a computational model, we describe and discuss the observed direct and indirect effects of the implicated nanomaterials on DNA.
Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?
Authors: Tomaszewska Ewa , Hułas-Stasiak Monika , Dobrowolski Piotr , Świątkiewicz Małgorzata , Muszyński Siemowit , Tomczyk-Warunek Agnieszka , Blicharski Tomasz , Donaldson Janine , Arciszewski Marcin B. , Świetlicki Michał , Puzio Iwona , Bonior Joanna
Published: February 2024

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP’s impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-β1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP’s systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.