bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Evaluation Model of Multi-Temporal Energy Storage for Flexibility Provision in Microgrids
Authors: Chai Zhe , Zhang Yihan , Wei Lanyi , Liu Junhui , Lu Yao , Tian Chunzheng , Wu Zhaoyuan
Published: April 2024

With the advancement of distributed power generation technology and the deepening of the low-carbon transformation of energy structure, a high proportion of renewable energy has become an inevitable trend in future energy systems, especially for microgrids. However, the volatility and uncertainty associated with renewable energy pose significant challenges to the secure and stable operation of power systems, necessitating the exploration of the flexible regulation of resources. Energy storage, as a crucial flexible resource characterized by technological diversity and a variety of regulation capabilities, has been extensively studied and applied. Nonetheless, the high investment costs and limited returns of energy storage technology, coupled with the ambiguous utility in different scenarios under the current electricity market’s framework, complicate its broader application. To thoroughly analyze the utility of energy storage in facilitating flexible adjustments in microgrids, this study developed a composite weight-TODIM (an acronym in Portuguese for interactive and multi-criteria decision making) model for assessing the utility of energy storage that incorporates heterogeneity in the risk preferences. This model enabled a comparative analysis of the utility of energy storage technology across multiple scenarios, taking the risk preferences of decision-makers into account, thereby providing strategic insights for the application of multi-temporal energy storage in microgrids. The feasibility and effectiveness of the model were validated through a case study analysis.
Optimising Ion Conductivity in NdBaInO4-Based Phases
Authors: Chen Manyu , Li Cheng , Zhu Kai , Wang Jieyu , Liu Sida , Kong Weina , Ban Zifa , Shen Chao
Published: April 2024

Based on the previous work conducted by Fujii et al., NdBaInO4 compounds present modest oxide-ion conductivities. Therefore, it has been an attractive system of significant interest. In this study, we attempted to partially substitute Ca for Nd and the total electrical conductivity was successfully improved due to the generation of oxygen vacancies. The synthesis, crystal structure, density, surface topography, and electrical properties of NdBaInO4 and Ca-doped NdBaInO4 have been studied, respectively. NdBaInO4 and 10% and 20% molar fractions of Ca-doped NdBaInO4 were synthesized through solid-state reactions. The crystal structure of them was obtained from Le Bail refinement of the XRD pattern, giving the result of the monoclinic structure, which belongs to P21/c space group. The highest total electrical conductivity of 4.91 × 10−3 S cm−1 was obtained in the Nd0.9Ca0.1BaInO3.95 sample at a temperature of 760 °C in the dry atmosphere and the activation energy was reduced from 0.68 eV to 0.58 eV when the temperature was above 464 °C (737 K) after doping the NdBaInO4 with a 0.1 molar fraction of Ca2+. Moreover, the total conductivity of Nd0.9Ca0.1BaInO3.95 in the wet atmosphere at moderate temperature was relatively higher than that in the dry atmosphere, which suggests that potential proton conduction may exist in wet atmospheres. In addition, the oxygen diffusion coefficients of Nd0.9Ca0.1BaInO3.95 (D* = 1.82 × 10−8 cm2/s, 850 °C) was about two times higher than that of Nd0.8Ca0.2BaInO3.90 (D* = 7.95 × 10−9 cm2/s, 850 °C) and was increased significantly by two orders of magnitude when compared with the oxygen diffusion coefficient of the undoped NdBaInO4 (D* = 8.25 × 10−11 cm2/s, 850 °C).
Energy Integration of Thermal Pretreatment in Anaerobic Digestion of Wheat Straw
Authors: García Álvaro Alfonso , Ruiz Palomar César , Díaz Villalobos Israel , Hermosilla Daphne , Muñoz Raúl , de Godos Ignacio
Published: April 2024

Cereal straw stands out as one of the most abundant and globally distributed agricultural residues. Traditional applications cope with a limited amount of production, leaving the remainder in the field for natural decomposition. Managing cereal straw through controlled biological transformation under anaerobic conditions holds the potential to generate added value in the form of bioenergy. However, the lignocellulosic composition of these substrates poses challenges for organic degradation, often requiring energy-intensive pretreatments. A detailed study with a comprehensive calculation of the overall energy balance of the integrated process is proposed, aiming to provide real added value and replicability. Three scenarios for wheat straw transformation were investigated, incorporating two preliminary pre-treatment stages—mechanical milling and physicochemical steam explosion. Three conditions of pretreatment were essayed, varying the time exposure of the steam explosion. The subsequent energy integration analysis revealed that the process was optimized by up to 15% in the final energy balance when the steam explosion was set to 10 min. The macromolecular composition determination revealed that the thermal pretreatment reduced the lag phase of the hydrolysis step through hemicellulose breakdown.
A Multi-Source Braking Force Control Method for Electric Vehicles Considering Energy Economy
Authors: Wang Yinhang , Zhou Liqing , Chu Liang , Zhao Di , Guo Zhiqi , Jiang Zewei
Published: April 2024

Advancements in electric vehicle technology have promoted the development trend of smart and low-carbon environmental protection. The design and optimization of electric vehicle braking systems faces multiple challenges, including the reasonable allocation and control of braking torque to improve energy economy and braking performance. In this paper, a multi-source braking force system and its control strategy are proposed with the aim of enhancing braking strength, safety, and energy economy during the braking process. Firstly, an ENMPC (explicit nonlinear model predictive control)-based braking force control strategy is proposed to replace the traditional ABS strategy in order to improve braking strength and safety while providing a foundation for the participation of the drive motor in ABS (anti-lock braking system) regulation. Secondly, a grey wolf algorithm is used to rationally allocate mechanical and electrical braking forces, with power consumption as the fitness function, to obtain the optimal allocation method and provide potential for EMB (electro–mechanical brake) optimization. Finally, simulation tests verify that the proposed method can improve braking strength, safety, and energy economy for different road conditions, and compared to other methods, it shows good performance.
The Future Design of Smart Energy Systems with Energy Flexumers: A Constructive Literature Review
Authors: Hu Jin-Li , Bui Nhi Ha Bao
Published: April 2024

From powering our homes to driving our economies, energy lies at the heart of humanity’s complex challenges in the modern era. This paper reviews the evolution of smart energy systems, examining their technological advancements and societal implications while proposing a future design framework emphasizing four key pillars: holistic resource optimization, adaptive intelligence, environmental harmony, and human-centered design. While they offer numerous benefits, such as enhanced energy efficiency and reduced carbon emissions, smart energy systems also face challenges. These include cybersecurity risks, the complexity of integrating diverse energy sources seamlessly, high upfront costs, and potential compatibility issues arising from evolving technologies. Overcoming these challenges will be crucial for unleashing the full potential of smart energy systems and facilitating their global adoption. Abundant opportunities for further research and development exist in this domain, awaiting exploration and advancement.
Silver Dendritic Gels with Luminescence and Aggregation-Induced Emission Effect
Authors: Iguarbe Verónica , Romero Pilar , Elduque Anabel , Giménez Raquel
Published: April 2024

This work reports on a novel family of silver metallogels based on discrete coordination complexes. Structurally, they consist of dendrimers containing a trinuclear silver metallacycle at the core, with the general formula [M(μ-pz)]3, and poly(benzyl)ether branched structures with different numbers or terminal alkoxy chains at the periphery. These silver metallodendrimers are able to gel low-polarity solvents such as dodecane or cyclohexane, giving rise to luminescent organogels at room temperature with the property of aggregation-induced emission (AIE). This property means that in solution or the sol state, they are weak emitters, but in the gel state, luminescence is considerably increased. In this particular case, they exhibit blue luminescence. Two different dendritic scaffolds have been studied, finding significant differences in solubility, gel formation and dependence of luminescence on temperature. The results show that properly tailored silver gelators can show luminescence in the gel state.
Biomedical Trends in Stimuli-Responsive Hydrogels with Emphasis on Chitosan-Based Formulations
Authors: Kruczkowska Weronika , Gałęziewska Julia , Grabowska Katarzyna , Liese Gabriela , Buczek Paulina , Kłosiński Karol Kamil , Kciuk Mateusz , Pasieka Zbigniew , Kałuzińska-Kołat Żaneta , Kołat Damian
Published: April 2024

Biomedicine is constantly evolving to ensure a significant and positive impact on healthcare, which has resulted in innovative and distinct requisites such as hydrogels. Chitosan-based formulations stand out for their versatile utilization in drug encapsulation, transport, and controlled release, which is complemented by their biocompatibility, biodegradability, and non-immunogenic nature. Stimuli-responsive hydrogels, also known as smart hydrogels, have strictly regulated release patterns since they respond and adapt based on various external stimuli. Moreover, they can imitate the intrinsic tissues’ mechanical, biological, and physicochemical properties. These characteristics allow stimuli-responsive hydrogels to provide cutting-edge, effective, and safe treatment. Constant progress in the field necessitates an up-to-date summary of current trends and breakthroughs in the biomedical application of stimuli-responsive chitosan-based hydrogels, which was the aim of this review. General data about hydrogels sensitive to ions, pH, redox potential, light, electric field, temperature, and magnetic field are recapitulated. Additionally, formulations responsive to multiple stimuli are mentioned. Focusing on chitosan-based smart hydrogels, their multifaceted utilization was thoroughly described. The vast application spectrum encompasses neurological disorders, tumors, wound healing, and dermal infections. Available data on smart chitosan hydrogels strongly support the idea that current approaches and developing novel solutions are worth improving. The present paper constitutes a valuable resource for researchers and practitioners in the currently evolving field.
Fruit Agronomic and Quality Traits of Tomato F1 Hybrids Derived from Traditional Varieties
Authors: Sánchez Alicia Sánchez , Flores Pilar , Hernández Virginia , Sánchez Elena , Molina Elia , López Nuria , Rodríguez-Burruezo Adrián , Fenoll José , Hellín Pilar
Published: April 2024

The high genetic diversity of the tomato and its high micronutrient content make this fruit very interesting from an economic and nutritional point of view. The genetic erosion suffered by this crop, due to breeding objectives based on yield and marketing, makes it necessary to return to the origins in search of the nutritional and organoleptic quality lost in traditional varieties. In this study, the agronomic, physical, organoleptic, and nutritional characteristics of eighteen F1 hybrids, obtained by crossing fourteen traditional varieties, previously selected for their quality, were studied in order to select genotypes of superior quality that could be candidates for new varieties. All the parameters studied were strongly influenced by genotype, with a wide range between varieties. Most of the experimental hybrids showed higher quality scores than the commercial hybrids used as controls, due to the extensive selection process carried out on the parents in previous work. Principal component analysis revealed the characteristics of each hybrid that distinguished it from the others. Some hybrids (H1, H2, and H4) stood out for their high concentration of active compounds, others (H14, H13, H8, H15, H7, and H9) for their agronomic performance and high β-carotene content, and H3 was the only one to contain chlorophyll in its ripe fruits. Finally, the evaluation index allowed the selection of five hybrids with interesting characteristics, combining good yield performance and high quality. The results of this work have allowed for the selection of a group of hybrids with high organoleptic and nutritional quality which will be used as parents in a breeding programme, in which their characteristics will be fixed and their resilience will be increased through the introduction of virus resistance.
Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation
Authors: Williams Demond , Hargrove-Wiley Ebony , Bindeman Wendy , Valent Daniel , Miranda Adam X. , Beckstead Jacob , Fingleton Barbara
Published: April 2024

Interleukin-4 (IL4) is a Th2 cytokine that can signal through two different receptors, one of which—the type II receptor—is overexpressed by various cancer cells. Previously, we have shown that type II IL4 receptor signaling increases proliferation and metastasis in mouse models of breast cancer, as well as increasing glucose and glutamine metabolism. Here, we expand on those findings to determine mechanistically how IL4 signaling links glucose metabolism and histone acetylation to drive proliferation in the context of triple-negative breast cancer (TNBC). We used a combination of cellular, biochemical, and genomics approaches to interrogate TNBC cell lines, which represent a cancer type where high expression of the type II IL4 receptor is linked to reduced survival. Our results indicate that type II IL4 receptor activation leads to increased glucose uptake, Akt and ACLY activation, and histone acetylation in TNBC cell lines. Inhibition of glucose uptake through the deletion of Glut1 ablates IL4-induced proliferation. Additionally, pharmacological inhibition of histone acetyltransferase P300 attenuates IL4-mediated gene expression and proliferation in vitro. Our work elucidates a role for type II IL4 receptor signaling in promoting TNBC progression, and highlights type II IL4 signaling, as well as histone acetylation, as possible targets for therapy.
Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway
Authors: Carbajal-García Abril , Reyes-García Jorge , Díaz-Hernández Verónica , Casas-Hernández María F. , Flores-Murrieta Francisco Javier , Montaño Luis M.
Published: April 2024

Numerous studies suggest the involvement of adenosine-5′-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5′-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.
Deciphering the Impact of Defecation Frequency on Gut Microbiome Composition and Diversity
Authors: Park Gwoncheol , Kim Seongok , Lee WonJune , Kim Gyungcheon , Shin Hakdong
Published: April 2024

This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1–3 times/week, n = 4), mid-frequent (4–6 times/week, n = 7), and frequent (daily, n = 9). Utilizing 16S rRNA gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The Ruminococcus genus was predominant in the infrequent group, but decreased with more frequent defecation, while the Bacteroides genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.
Altered Sweat Composition Due to Changes in Tight Junction Expression of Sweat Glands in Cholinergic Urticaria Patients
Authors: Daci Denisa , Altrichter Sabine , Grillet François Marie , Dib Selma , Mouna Ahmad , Suresh Kumar Sukashree , Terhorst-Molawi Dorothea , Maurer Marcus , Günzel Dorothee , Scheffel Jörg
Published: April 2024

In cholinergic urticaria (CholU), small, itchy wheals are induced by exercise or passive warming and reduced sweating has been reported. Despite the described reduced muscarinic receptor expression, sweat duct obstruction, or sweat allergy, the underlying pathomechanisms are not well understood. To gain further insights, we collected skin biopsies before and after pulse-controlled ergometry and sweat after sauna provocation from CholU patients as well as healthy controls. CholU patients displayed partially severely reduced local sweating, yet total sweat volume was unaltered. However, sweat electrolyte composition was altered, with increased K+ concentration in CholU patients. Formalin-fixed, paraffin-embedded biopsies were stained to explore sweat leakage and tight junction protein expression. Dermcidin staining was not found outside the sweat glands. In the secretory coils of sweat glands, the distribution of claudin-3 and -10b as well as occludin was altered, but the zonula occludens-1 location was unchanged. In all, dermcidin and tight junction protein staining suggests an intact barrier with reduced sweat production capability in CholU patients. For future studies, an ex vivo skin model for quantification of sweat secretion was established, in which sweat secretion could be pharmacologically stimulated or blocked. This ex vivo model will be used to further investigate sweat gland function in CholU patients and decipher the underlying pathomechanism(s).
New Mediators in the Crosstalk between Different Adipose Tissues
Authors: Gómez-Hernández Almudena , de las Heras Natalia , Gálvez Beatriz G. , Fernández-Marcelo Tamara , Fernández-Millán Elisa , Escribano Óscar
Published: April 2024

Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.
Rpt5-Derived Analogs Stimulate Human Proteasome Activity in Cells and Degrade Proteins Forming Toxic Aggregates in Age-Related Diseases
Authors: Cekała Katarzyna , Trepczyk Karolina , Witkowska Julia , Jankowska Elżbieta , Wieczerzak Ewa
Published: April 2024

Aging and age-related diseases are associated with a decline in the capacity of protein turnover. Intrinsically disordered proteins, as well as proteins misfolded and oxidatively damaged, prone to aggregation, are preferentially digested by the ubiquitin-independent proteasome system (UIPS), a major component of which is the 20S proteasome. Therefore, boosting 20S activity constitutes a promising strategy to counteract a decrease in total proteasome activity during aging. One way to enhance the proteolytic removal of unwanted proteins appears to be the use of peptide-based activators of the 20S. In this study, we synthesized a series of peptides and peptidomimetics based on the C-terminus of the Rpt5 subunit of the 19S regulatory particle. Some of them efficiently stimulated human 20S proteasome activity. The attachment of the cell-penetrating peptide TAT allowed them to penetrate the cell membrane and stimulate proteasome activity in HEK293T cells, which was demonstrated using a cell-permeable substrate of the proteasome, TAS3. Furthermore, the best activator enhanced the degradation of aggregation-prone α-synuclein and Tau-441. The obtained compounds may therefore have the potential to compensate for the unbalanced proteostasis found in aging and age-related diseases.
PKIB, a Novel Target for Cancer Therapy
Authors: Musket Anna , Moorman Jonathan P. , Zhang Jinyu , Jiang Yong
Published: April 2024

The serine-threonine kinase protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent intracellular protein with multiple roles in cellular biology including metabolic and transcription regulation functions. The cAMP-dependent protein kinase inhibitor β (PKIB) is one of three known endogenous protein kinase inhibitors of PKA. The role of PKIB is not yet fully understood. Hormonal signaling is correlated with increased PKIB expression through genetic regulation, and increasing PKIB expression is associated with decreased cancer patient prognosis. Additionally, PKIB impacts cancer cell behavior through two mechanisms; the first is the nuclear modulation of transcriptional activation and the second is the regulation of oncogenic AKT signaling. The limited research into PKIB indicates the oncogenic potential of PKIB in various cancers. However, some studies suggest a role of PKIB in non-cancerous disease states. This review aims to summarize the current literature and background of PKIB regarding cancer and related issues. In particular, we will focus on cancer development and therapeutic possibilities, which are of paramount interest in PKIB oncology research.
The Influence of the Variable Wettability Characteristics of Layers on the Transport of Nanoparticles in the Context of Drug Delivery in Skin Structures
Authors: Błaszczyk Mariola M. , Przybysz Łukasz , Budzyń Aleksandra
Published: April 2024

The rapid development of nanotechnology has offered the possibility of creating nanosystems that can be used as drug carriers. The use of such carriers offers real opportunities for the development of non-invasive drug delivery through skin structures. However, in addition to the ability to create suitable nanocarriers, it is also necessary to know how they move through dermal layers. The human skin consists of layers with different wettability characteristics, which greatly complicates how introduced substances move through it. In this work, an experimental study of the diffusion process of nanoparticles through partitions with different wettability properties was carried out. Conventional diffusion tests using Franz chambers were used for this purpose. We quantified how the wettability of the barrier, the number of layers, and their mutual configuration affect the transport of nanoparticles. Based on the results, an analysis of the phenomena taking place, depending on the wettability of the partition, was carried out. A model relationship was also proposed to determine the effective diffusion coefficient, taking into account the influence of the wettability and porosity of the barrier.
Generation of Slco1a4-CreERT2-tdTomato Knock-in Mice for Specific Cerebrovascular Endothelial Cell Targeting
Authors: Xu Chengfang , Li Shounian , Cai Yunting , Lu Jinjin , Teng Yan , Yang Xiao , Wang Jun
Published: April 2024

The cerebrovascular endothelial cells with distinct characteristics line cerebrovascular blood vessels and are the fundamental structure of the blood–brain barrier, which is important for the development and homeostatic maintenance of the central nervous system. Cre-LoxP system-based spatial gene manipulation in mice is critical for investigating the physiological functions of key factors or signaling pathways in cerebrovascular endothelial cells. However, there is a lack of Cre recombinase mouse lines that specifically target cerebrovascular endothelial cells. Here, using a publicly available single-cell RNAseq database, we screened the solute carrier organic anion transporter family member 1a4 (Slco1a4) as a candidate marker of cerebrovascular endothelial cells. Then, we generated an inducible Cre mouse line in which a CreERT2-T2A-tdTomato cassette was placed after the initiation codon ATG of the Slco1a4 locus. We found that tdTomato, which can indicate the endogenous Slco1a4 expression, was expressed in almost all cerebrovascular endothelial cells but not in any other non-endothelial cell types in the brain, including neurons, astrocytes, oligodendrocytes, pericytes, smooth muscle cells, and microglial cells, as well as in other organs. Consistently, when crossing the ROSA26LSL-EYFP Cre reporter mouse, EYFP also specifically labeled almost all cerebrovascular endothelial cells upon tamoxifen induction. Overall, we generated a new inducible Cre line that specifically targets cerebrovascular endothelial cells.
New Insights into the Genetic Basis of Lysine Accumulation in Rice Revealed by Multi-Model GWAS
Authors: He Liqiang , Sui Yao , Che Yanru , Liu Lihua , Liu Shuo , Wang Xiaobing , Cao Guangping
Published: April 2024

Lysine is an essential amino acid that cannot be synthesized in humans. Rice is a global staple food for humans but has a rather low lysine content. Identification of the quantitative trait nucleotides (QTNs) and genes underlying lysine content is crucial to increase lysine accumulation. In this study, five grain and three leaf lysine content datasets and 4,630,367 single nucleotide polymorphisms (SNPs) of 387 rice accessions were used to perform a genome-wide association study (GWAS) by ten statistical models. A total of 248 and 71 common QTNs associated with grain/leaf lysine content were identified. The accuracy of genomic selection/prediction RR-BLUP models was up to 0.85, and the significant correlation between the number of favorable alleles per accession and lysine content was up to 0.71, which validated the reliability and additive effects of these QTNs. Several key genes were uncovered for fine-tuning lysine accumulation. Additionally, 20 and 30 QTN-by-environment interactions (QEIs) were detected in grains/leaves. The QEI-sf0111954416 candidate gene LOC_Os01g21380 putatively accounted for gene-by-environment interaction was identified in grains. These findings suggested the application of multi-model GWAS facilitates a better understanding of lysine accumulation in rice. The identified QTNs and genes hold the potential for lysine-rich rice with a normal phenotype.
Olive Flounder By-Product Prozyme2000P Hydrolysate Ameliorates Age-Related Kidney Decline by Inhibiting Ferroptosis
Authors: Son Myeongjoo , Jeon You-Jin , Ryu Bomi , Kim Dae Yu
Published: April 2024

This study explores olive flounder by-product Prozyme2000P (OFBP) hydrolysate as a potential treatment for age-related kidney decline. Ferroptosis, a form of cell death linked to iron overload and oxidative stress, is increasingly implicated in aging kidneys. We investigated whether OFBP could inhibit ferroptosis and improve kidney health. Using TCMK-1 cells, we found that OFBP treatment protected cells from ferroptosis induced by sodium iodate (SI). OFBP also preserved the mitochondria health and influenced molecules involved in ferroptosis regulation. In aging mice, oral administration of OFBP significantly improved kidney health markers. Microscopic examination revealed reduced thickening and scarring in the kidney’s filtering units, a hallmark of aging. These findings suggest that OFBP hydrolysate may be a promising therapeutic candidate for age-related kidney decline. By inhibiting ferroptosis, OFBP treatment appears to improve both cellular and structural markers of kidney health. Further research is needed to understand how OFBP works fully and test its effectiveness in more complex models.
Special Issue “Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease”
Authors: Cardona Fernando , Pérez-Tur Jordi
Published: April 2024

We are pleased to present the first and second editions of this Special Issue, titled “Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease”, of the International Journal of Molecular Sciences [...]
Tumor Antigens beyond the Human Exome
Authors: Emilius Lisabeth , Bremm Franziska , Binder Amanda Katharina , Schaft Niels , Dörrie Jan
Published: April 2024

With the advent of immunotherapeutics, a new era in the combat against cancer has begun. Particularly promising are neo-epitope-targeted therapies as the expression of neo-antigens is tumor-specific. In turn, this allows the selective targeting and killing of cancer cells whilst healthy cells remain largely unaffected. So far, many advances have been made in the development of treatment options which are tailored to the individual neo-epitope repertoire. The next big step is the achievement of efficacious “off-the-shelf” immunotherapies. For this, shared neo-epitopes propose an optimal target. Given the tremendous potential, a thorough understanding of the underlying mechanisms which lead to the formation of neo-antigens is of fundamental importance. Here, we review the various processes which result in the formation of neo-epitopes. Broadly, the origin of neo-epitopes can be categorized into three groups: canonical, noncanonical, and viral neo-epitopes. For the canonical neo-antigens that arise in direct consequence of somatic mutations, we summarize past and recent findings. Beyond that, our main focus is put on the discussion of noncanonical and viral neo-epitopes as we believe that targeting those provides an encouraging perspective to shape the future of cancer immunotherapeutics.
Triptolide, a Cancer Cell Proliferation Inhibitor, Causes Zebrafish Muscle Defects by Regulating Notch and STAT3 Signaling Pathways
Authors: Lee Byongsun , Park Yongjin , Lee Younggwang , Kwon Seyoung , Shim Jaekyung
Published: April 2024

Triptolide is a natural compound in herbal remedies with anti-inflammatory and anti-proliferative properties. We studied its effects on critical signaling processes within the cell, including Notch1 and STAT3 signaling. Our research showed that triptolide reduces cancer cell proliferation by decreasing the expression of downstream targets of these signals. The levels of each signal-related protein and mRNA were analyzed using Western blot and qPCR methods. Interestingly, inhibiting one signal with a single inhibitor alone did not significantly reduce cancer cell proliferation. Instead, MTT assays showed that the simultaneous inhibition of Notch1 and STAT3 signaling reduced cell proliferation. The effect of triptolide was similar to a combination treatment with inhibitors for both signals. When we conducted a study on the impact of triptolide on zebrafish larvae, we found that it inhibited muscle development and interfered with muscle cell proliferation, as evidenced by differences in the staining of myosin heavy chain and F-actin proteins in confocal fluorescence microscopy. Additionally, we noticed that inhibiting a single type of signaling did not lead to any significant muscle defects. This implies that triptolide obstructs multiple signals simultaneously, including Notch1 and STAT3, during muscle development. Chemotherapy is commonly used to treat cancer, but it may cause muscle loss due to drug-related adverse reactions or other complex mechanisms. Our study suggests that anticancer agents like triptolide, inhibiting essential signaling pathways including Notch1 and STAT3 signaling, may cause muscle atrophy through anti-proliferative activity.
Edible Insects in Slavic Culture: Between Tradition and Disgust
Authors: Orkusz Agnieszka , Orkusz Martyna
Published: April 2024

Insects are a conventional food in many cultures worldwide. Why therefore are they treated with aversion by the majority of people in Western countries? The aim of this work is to understand cultural norms and historical practices related to insects that can explain why in the countries of the West it is so difficult to accept them as a foodstuff, and why the disgust that they arouse is more common than in other regions of the world. Insects in Western countries are associated with negative experiences resulting from cultural and religious beliefs, traditions, stories, myths and individual experiences. Although there are species of insect that have positive associations, the high number of negative terms popularized the negative image of these creatures in people’s minds, as a result of which the concept of insects as a foodstuff arouses disgust in the culture of the West. Understanding the aversion to insects will contribute to the broader understanding of consumer attitudes, cultural influences on consumption, or potential shifts in food choices. It also can help develop strategies or methods that will assist in changing this reluctance and encourage the utilization of insects as a food source.
Frequency, Prognosis, and Clinical Features of Unexpected versus Expected Cardiac Arrest in the Emergency Department: A Retrospective Analysis
Authors: Szaruta-Raflesz Karolina , Łopaciński Tomasz , Siemiński Mariusz
Published: April 2024

Background: Though out-of-hospital CA (OHCA) is widely reported, data on in-hospital CA (IHCA) and especially cardiac arrest (CA) in the emergency department (CAED) are scarce. This study aimed to determine the frequency, prevalence, and clinical features of unexpected CAED and compare the data with those of expected CAED. Methods: We defined unexpected CAED as CA occurring in patients in non-critical ED-care areas; classified as not requiring strict monitoring. This classification was the modified Japanese Triage and Acuity Scale and physician assessment. A retrospective analysis of cases from 2016 to 2018 was performed, in comparison to other patients experiencing CAED. Results: The 38 cases of unexpected CA in this study constituted 34.5% of CA diagnosed in the ED and 8.4% of all CA treated in the ED. This population did not differ significantly from other CAED regarding demographics, comorbidities, and survival rates. The commonest symptoms were dyspnoea, disorders of consciousness, generalised weakness, and chest pain. The commonest causes of death were acute myocardial infarction, malignant neoplasms with metastases, septic shock, pulmonary embolism, and heart failure. Conclusions: Unexpected CAED represents a group of potentially avoidable CA and deaths. These patients should be analysed, and ED management should include measures aimed at reducing their incidence.
Drug Optimization in Patients with Mild-to-Moderate Ulcerative Colitis: A Global Survey
Authors: D’Amico Ferdinando , Jairath Vipul , Paridaens Kristine , Peyrin-Biroulet Laurent , Danese Silvio
Published: April 2024

Background/Objectives: The treatment of patients with mild-to-moderate ulcerative colitis (UC) is challenging. Although there are commonly used guidelines, therapy optimization is not standardized. We conducted a survey to investigate the management and treatment of patients with mild-to-moderate UC. Methods: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between June and July 2023. The survey addressed various issues of patient care such as patient monitoring, treatment optimization, follow-up, treatment decision making, and therapy de-escalation. Results: The survey included 222 physicians (59.9% men; mean age = 50.4 years) from 66 countries worldwide. Gastroenterologists were the most represented specialists (89.6%), followed by surgeons (3.2%), and internal medicine doctors (2.7%). Two-thirds of the participants (66.7%) had >10 years of experience in the field of IBD. The combination of oral (≥4 g/day) and rectal 5-aminosalicylic acid (5-ASA) was the preferred choice when optimizing therapy. Budesonide MMX (41.8%) and systemic steroids (39.9%) were preferred in patients who failed 5-ASA. Treatment decisions were predominantly based on endoscopic (99.0%) or clinical (59.8%) activity. A significant percentage of clinicians did not optimize therapy in the case of increased fecal calprotectin alone (45.1%) or radiological/ultrasound activity (39.8%) alone. Conclusions: The guidelines for the management of mild-to-moderate UC are well accepted in clinical practice. Endoscopic remission remains the main therapeutic target, followed by clinical remission. Fecal calprotectin and intestinal ultrasound still elicit complaints from physicians.
Computer-Assisted Navigation in Reverse Shoulder Arthroplasty: Surgical Experience and Clinical Outcomes
Authors: Andriollo Luca , Pietramala Silvia , Polizzi Alberto , Niccoli Giuseppe , Zattoni Guido , Morea Vincenzo
Published: April 2024

Background: The primary cause of medium- to long-term complications in reverse shoulder arthroplasty (RSA) is the failure of the glenoid component. The purpose of this study was to evaluate both the achievement of planning through computer-assisted navigation and the clinical outcomes at a minimum follow-up (FU) of 12 months. Methods: From December 2019 to December 2022, 57 Equinoxe RSAs with computer-assisted navigation were performed. The average age was 72.8 ± 6.6 years. Using the Orthoblue software, the version and inclination of the glenoid were evaluated from a preoperative CT scan, and planning was performed. Intraoperative navigation data were evaluated, and the clinical outcomes were assessed at a minimum follow-up of 12 months. Results: The average follow-up was 30.7 ± 13.5 months. The planning was reproduced in all implants. No errors in the computer-assisted navigation system were detected. No intraoperative or postoperative complications were recorded. At the final FU, the average active anterior elevation was 143° ± 36°, external rotation was 34° ± 5°, QuickDASH score was 19 ± 16 points, and constant score was 77 ± 18. Conclusions: Computer-assisted navigation is a reliable system for positioning prosthetic implants on challenging glenoids. A longer follow-up period is necessary to confirm the reduction in postoperative complications and the increase in survival compared to traditional RSA.
Predictors of Remission or Combined Remission and Low Disease Activity in Rheumatoid Arthritis Patients in Taiwan: A Prospective Cohort Study
Authors: Tsai Ping-Han , Fang Yao-Fan , Chen Yen-Fu , Chen Chih-Chieh , Chiang Wen-Yu , Chang Che-Tzu , Huang Yun-Ju , Liou Lieh-Bang
Published: April 2024

Objectives: This study aimed to identify predictors of remission or low disease activity (LDA) in patients with rheumatoid arthritis (RA) and low-ultrasound inflammation. Methods: A total of 80 patients with RA who fulfilled the 1987 ACR criteria for RA with a disease activity score of 28 joints (DAS28) > 3.2 were recruited. Over 1 year of therapy, we conducted blood tests every 6 months to examine erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), neuraminidase 3 (Neu3), and α-2,3-sialyltrasnferse I (ST3Gal-1) levels in B cells and monocytes. Additionally, we evaluated physical function by using the Health Assessment Questionnaire–Disability Index (HAQ-DI). Data on demographic and clinical parameters were collected, and musculoskeletal ultrasonography was performed twice a year on 12 specific joints to assess synovial changes. One year later, we compared all collected data and laboratory or ultrasound results between patients achieving remission or LDA and those who did not in order to determine the predictors. Results: Age, the presence or absence of rheumatoid factor, and the number of conventional disease-modifying anti-rheumatic drugs used were not correlated with remission or LDA for DAS28 or Simplified Disease Activity Index formulas. However, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores were associated with a higher likelihood of achieving remission or LDA for DAS28-ESR. Negative anticyclic citrullinated peptide (CCP) and low HAQ-DI scores were predictors of remission or LDA for DAS28-MCP-1. Interestingly, having less than two comorbidities is a good predictor of a combined remission/low disease activity state for SDAI and DAS28-MCP-1. Furthermore, Neu3 and ST3Gal-1 levels and ST3Gal-1/Neu3 ratios in B cells and monocytes had no significant correlation with total ultrasound scores. Nevertheless, monocyte ST3Gal-1 and Neu3 correlated significantly with DAS28-ESR >5.1 and DAS-MCP-1 >4.8 (both categories belong to high disease activity), respectively (rho = 0.609 with p = 0.012, and rho = 0.727 with p = 0.011, respectively). Monocyte ST3Gal-1/Neu3 ratios connected with DAS28-ESR >5.1 and 3.3 < SDAI ≦ 11 (low disease activity), respectively (rho = 0.662 with p = 0.005, and rho = 0.342 with p = 0.048, respectively). Conclusions: In patients with RA in Taiwan, male sex, low CRP levels, low ESR levels, and low HAQ-DI scores are predictors of remission or LDA for DAS28-ESR, which differ from the predictors for DAS28-MCP-1. Moreover, monocyte ST3Gal-1, Neu3, and their ratios correlated with different disease activity categories of DAS28-ESR, DAS28-MCP-1, and SDAI scores.
Gender Differences in Patients with Gastric Adenocarcinoma
Authors: Xing Yujin , Hosaka Hiroko , Moki Fumitaka , Tomaru Shota , Itoi Yuki , Sato Keigo , Hashimoto Yu , Tanaka Hirohito , Kuribayashi Shiko , Takeuchi Yoji , Nagai Kazue , Uraoka Toshio
Published: April 2024

Background: Gastric cancer (GC) epidemiology and outcomes vary by gender. Methods: We reviewed 18,436 GC patients from 2008 to 2018 and looked for gender differences in clinical characteristics and survival. Results: The gender proportion was 71% male and 29% female. Males had a significantly (p < 0.001) higher proportion of differentiated GC (66.3%) and a lower proportion of undifferentiated GC (26.3%). Diagnosis through medical check-ups was more common in males (30.0% vs. 26.4%, p < 0.001). Clinical staging revealed 54.6% of males and 52.9% of females had localized disease without lymph node metastasis (LNM), while distant metastasis occurred in 17.4% of males and 16.9% of females (p < 0.001). Kaplan–Meier survival curves indicated females had a significantly higher overall survival (p = 0.0018). The survival advantage for females was evident in the early stages, with a significant difference in localized disease without LNM (p < 0.001) and localized disease with LNM (p = 0.0026, log-rank test) but not in the advanced stages. Multivariate Cox regression analysis showed a significantly reduced mortality risk in females (p < 0.001). Conclusions: Significant gender differences exist with regard to pathological type, presentation, clinical stage, and overall survival. These findings suggest gender-specific strategies for screening, diagnosis, and treatment.
Lentigo Maligna Treatment—An Update
Authors: Ungureanu Loredana , Vasilovici Alina Florentina , Trufin Ioana Irina , Apostu Adina Patricia , Halmágyi Salomea-Ruth
Published: April 2024

Lentigo maligna (LM) is a melanoma in situ that is prevalent in chronically sun-damaged skin. Characterized by a slow growth pattern and high mutation rates due to chronic UV exposure, LM poses diagnostic and therapeutic challenges, particularly given its tendency to mimic other skin lesions and its occurrence in cosmetically sensitive areas. Its diagnosis is based on an integrated approach using dermoscopy and reflectance confocal microscopy (RCM). Despite its slow progression, LM can evolve into lentigo maligna melanoma (LMM), making its treatment necessary. Treatment modalities encompass both surgical and non-surgical methods. Surgical treatments like Wide Local Excision (WLE) and Mohs Micrographic Surgery (MMS) aim for clear histological margins. WLE, a standard melanoma surgery, faces challenges from LM’s subclinical extensions, which increase the recurrence risk. MMS, effective for large or poorly defined lesions, is defined by precise margin control while considering cosmetic outcomes. Non-surgical options, including radiotherapy and imiquimod, are alternatives for non-surgical candidates. Radiotherapy has been effective since the 1950s, offering good control and cosmetic results, especially for older patients. Imiquimod, an immunomodulator, shows promise in treating LM, though its application remains off-label. The increasing incidence of LM/LMM necessitates a balance in treatment choices to minimize recurrence and maintain cosmetic integrity. A multidisciplinary approach, integrating clinical examination with dermoscopy and RCM and histological assessment, is essential for accurate diagnosis and effective LM management.