bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Conjugated Nitrile Structures as Acceptor Moieties on the Photovoltaic Properties of Dye-Sensitized Solar Cells: DFT and TD-DFT Investigation
Authors: Tommalieh Maha J. , Aljameel Abdulaziz I. , Hussein Rageh K. , Al-heuseen Khalled , Alghamdi Suzan K. , Alrub Sharif Abu
Published: July 2024

A major challenge in improving the overall efficiency of dye-sensitized solar cells is improving the optoelectronic properties of small molecule acceptors. This work primarily investigated the effects of conjugation in nitriles incorporated as acceptor moieties into a newly designed series of D-A-A dyes. Density functional theory was employed to specifically study how single–double and single–triple conjugation in nitriles alters the optical and electronic properties of these dyes. The Cy-4c dye with a highly conjugated nitrile unit attained the smallest band gap (1.80 eV), even smaller than that of the strong cyanacrylic anchor group (2.07 eV). The dyes lacking conjugation in nitrile groups did not contribute to the LUMO, while LUMOs extended from donors to conjugated nitrile components, facilitating intramolecular charge transfer and causing a strong bind to the film surface. Density of state analysis revealed a considerable impact of conjugated nitrile on the electronic properties of dyes through an effective contribution in the LUMO, exceeding the role of the well-known strong 2,1,3-benzothiadiazole acceptor unit. The excited state properties and the absorption spectra were investigated using time-dependent density functional theory (TD-DFT). Conjugation in the nitrile unit caused the absorption band to broaden, strengthen, and shift toward the near-infrared region. The proposed dyes also showed optimum photovoltaic properties; all dyes possess high light-harvesting efficiency (LHE) values, specifically 96% for the dyes Cy-3b and Cy-4c, which had the most conjugated nitrile moieties. The dyes with higher degrees of conjugation had longer excitation lifetime values, which promote charge transfer by causing steady charge recombination at the interface. These findings may provide new insights into the structure of conjugated nitriles and their function as acceptor moieties in DSSCS, which may lead to the development of extremely effective photosensitizers for solar cells.
HMGB1-Mediated Cell Death—A Crucial Element in Post-Hepatectomy Liver Failure
Authors: Brunnthaler Laura , Hammond Thomas G. , Pereyra David , Santol Jonas , Probst Joel , Laferl Valerie , Resch Ulrike , Aiad Monika , Janoschek Anna Sofie , Gruenberger Thomas , Hackl Hubert , Starlinger Patrick , Assinger Alice
Published: July 2024

Liver resection (LR) is the primary treatment for hepatic tumors, yet posthepatectomy liver failure (PHLF) remains a significant concern. While the precise etiology of PHLF remains elusive, dysregulated inflammatory processes are pivotal. Therefore, we explored the theragnostic potential of extracellular high-mobility-group-box protein 1 (HMGB1), a key damage-associated molecular pattern (DAMP) released by hepatocytes, in liver recovery post LR in patients and animal models. Plasma from 96 LR patients and liver tissues from a subset of 24 LR patients were analyzed for HMGB1 levels, and associations with PHLF and liver injury markers were assessed. In a murine LR model, the HMGB1 inhibitor glycyrrhizin, was administered to assess its impact on liver regeneration. Furthermore, plasma levels of keratin-18 (K18) and cleaved cytokeratin-18 (ccK18) were quantified to assess suitability as predictive biomarkers for PHLF. Patients experiencing PHLF exhibited elevated levels of intrahepatic and circulating HMGB1, correlating with markers of liver injury. In a murine LR model, inhibition of HMGB1 improved liver function, reduced steatosis, enhanced regeneration and decreased hepatic cell death. Elevated levels of hepatic cell death markers K18 and ccK18 were detected in patients with PHLF and correlations with levels of circulating HMGB1 was observed. Our study underscores the therapeutic and predictive potential of HMGB1 in PHLF mitigation. Elevated HMGB1, K18, and ccK18 levels correlate with patient outcomes, highlighting their predictive significance. Targeting HMGB1 enhances liver regeneration in murine LR models, emphasizing its role in potential intervention and prediction strategies for liver surgery.
New Origins of Yeast, Plant and Bacterial-Derived Extracellular Vesicles to Expand and Advance Compound Delivery
Authors: Fernández-Rhodes María , Lorca Cristina , Lisa Julia , Batalla Iolanda , Ramos-Miguel Alfredo , Gallart-Palau Xavier , Serra Aida
Published: July 2024

Extracellular vesicles (EVs) constitute a sophisticated molecular exchange mechanism highly regarded for their potential as a next-generation platform for compound delivery. However, identifying sustainable and biologically safe sources of EVs remains a challenge. This work explores the emergence of novel sources of plant and bacterial-based EVs, such as those obtained from food industry by-products, known as BP-EVs, and their potential to be used as safer and biocompatible nanocarriers, addressing some of the current challenges of the field. These novel sources exhibit remarkable oral bioavailability and biodistribution, with minimal cytotoxicity and a selective targeting capacity toward the central nervous system, liver, and skeletal tissues. Additionally, we review the ease of editing these recently uncovered nanocarrier-oriented vesicles using common EV editing methods, examining the cargo-loading processes applicable to these sources, which involve both passive and active functionalization methods. While the primary focus of these novel sources of endogenous EVs is on molecule delivery to the central nervous system and skeletal tissue based on their systemic target preference, their use, as reviewed here, extends beyond these key applications within the biotechnological and biomedical fields.
Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Wang Yu , Tsukamoto Yoshiyuki , Hori Mitsuo , Iha Hidekatsu
Published: July 2024

Diffuse Large B-cell Lymphoma (DLBCL), with its intrinsic genetic and epigenetic heterogeneity, exhibits significantly variable clinical outcomes among patients treated with the current standard regimen. Disulfidptosis, a novel form of regulatory cell death triggered by disulfide stress, is characterized by the collapse of cytoskeleton proteins and F-actin due to intracellular accumulation of disulfides. We investigated the expression variations of disulfidptosis-related genes (DRGs) in DLBCL using two publicly available gene expression datasets. The initial analysis of DRGs in DLBCL (GSE12453) revealed differences in gene expression patterns between various normal B cells and DLBCL. Subsequent analysis (GSE31312) identified DRGs strongly associated with prognostic outcomes, revealing eight characteristic DRGs (CAPZB, DSTN, GYS1, IQGAP1, MYH9, NDUFA11, NDUFS1, OXSM). Based on these DRGs, DLBCL patients were stratified into three groups, indicating that (1) DRGs can predict prognosis, and (2) DRGs can help identify novel therapeutic candidates. This study underscores the significant role of DRGs in various biological processes within DLBCL. Assessing the risk scores of individual DRGs allows for more precise stratification of prognosis and treatment strategies for DLBCL patients, thereby enhancing the effectiveness of clinical practice.
Impact of Interleukin-6 Activation and Arthritis on Epidermal Growth Factor Receptor (EGFR) Activation in Sensory Neurons and the Spinal Cord
Authors: Roy Anutosh , Segond von Banchet Gisela , Gimeno-Ferrer Fátima , König Christian , Eitner Annett , Ebersberger Andrea , Ebbinghaus Matthias , Leuchtweis Johannes , Schaible Hans-Georg
Published: July 2024

In tumor cells, interleukin-6 (IL-6) signaling can lead to activation of the epidermal growth factor receptor (EGFR), which prolongs Stat3 activation. In the present experiments, we tested the hypothesis that IL-6 signaling activates EGFR signaling in peripheral and spinal nociception and examined whether EGFR localization and activation coincide with pain-related behaviors in arthritis. In vivo in anesthetized rats, spinal application of the EGFR receptor blocker gefitinib reduced the responses of spinal cord neurons to noxious joint stimulation, but only after spinal pretreatment with IL-6 and soluble IL-6 receptor. Using Western blots, we found that IL-6-induced Stat3 activation was reduced by gefitinib in microglial cells of the BV2 cell line, but not in cultured DRG neurons. Immunohistochemistry showed EGFR localization in most DRG neurons from normal rats, but significant downregulation in the acute and most painful arthritis phase. In the spinal cord of mice, EGFR was highly activated mainly in the chronic phase of inflammation, with localization in neurons. These data suggest that spinal IL-6 signaling may activate spinal EGFR signaling. Downregulation of EGFR in DRG neurons in acute arthritis may limit nociception, but pronounced delayed activation of EGFR in the spinal cord may be involved in chronic inflammatory pain.
Molecular Interactions and Mechanisms of COVID-19 Inhibition 2.0
Authors: Caruso Francesco , Rossi Miriam
Published: July 2024

Version 2 [...]
Reprogramming of Energy Metabolism in Human PKD1 Polycystic Kidney Disease: A Systems Biology Analysis
Authors: Song Xuewen , Pickel Lauren , Sung Hoon-Ki , Scholey James , Pei York
Published: July 2024

Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. We found gene expression profiles of PKD1 renal cysts were consistent with the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.
Alterations in the Structure, Composition, and Organization of Galactosaminoglycan-Containing Proteoglycans and Collagen Correspond to the Progressive Stages of Dupuytren’s Disease
Authors: Lenzi Luiz Guilherme S. , Gomes dos Santos João Baptista , Cavalheiro Renan P. , Mendes Aline , Kobayashi Elsa Y. , Nader Helena B. , Faloppa Flavio
Published: July 2024

Dupuytren’s disease (DD) is a prevalent fibroproliferative disorder of the hand, shaped by genetic, epigenetic, and environmental influences. The extracellular matrix (ECM) is a complex assembly of diverse macromolecules. Alterations in the ECM’s content, structure and organization can impact both normal physiological functions and pathological conditions. This study explored the content and organization of glycosaminoglycans, proteoglycans, and collagen in the ECM of patients at various stages of DD, assessing their potential as prognostic indicators. This research reveals, for the first time, relevant changes in the complexity of chondroitin/dermatan sulfate structures, specifically an increase of disaccharides containing iduronic acid residues covalently linked to either N-acetylgalactosamine 6-O-sulfated or N-acetylgalactosamine 4-O-sulfated, correlating with the disease’s severity. Additionally, we noted an increase in versican expression, a high molecular weight proteoglycan, across stages I to IV, while decorin, a small leucine-rich proteoglycan, significantly diminishes as DD progresses, both confirmed by mRNA analysis and protein detection via confocal microscopy. Coherent anti-Stokes Raman scattering (CARS) microscopy further demonstrated that collagen fibril architecture in DD varies importantly with disease stages. Moreover, the urinary excretion of both hyaluronic and sulfated glycosaminoglycans markedly decreased among DD patients.Our findings indicate that specific proteoglycans with galactosaminoglycan chains and collagen arrangements could serve as biomarkers for DD progression. The reduction in glycosaminoglycan excretion suggests a systemic manifestation of the disease.
Transcriptomic Characterization of Key Factors and Signaling Pathways for the Regeneration of Partially Hepatectomized Liver in Zebrafish
Authors: Song Guili , Feng Guohui , Li Qing , Peng Jinrong , Ge Wei , Long Yong , Cui Zongbin
Published: July 2024

Liver regeneration induced by partial hepatectomy (PHx) has attracted intensive research interests due to the great significance for liver resection and transplantation. The zebrafish (Danio rerio) is an excellent model to study liver regeneration. In the fish subjected to PHx (the tip of the ventral lobe was resected), the lost liver mass could be fully regenerated in seven days. However, the regulatory mechanisms underlying the liver regeneration remain largely unknown. In this study, gene expression profiles during the regeneration of PHx-treated liver were explored by RNA sequencing (RNA-seq). The genes responsive to the injury of PHx treatment were identified and classified into different clusters based on the expression profiles. Representative gene ontology (GO) enrichments for the early responsive genes included hormone activity, ribosome biogenesis and rRNA processing, etc., while the late responsive genes were enriched in biological processes such as glutathione metabolic process, antioxidant activity and cellular detoxification. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were also identified for the differentially expressed genes (DEGs) between the time-series samples and the sham controls. The proteasome was overrepresented by the up-regulated genes at all of the sampling time points. Inhibiting proteasome activity by the application of MG132 to the fish enhanced the expression of Pcna (proliferating cell nuclear antigen), an indicator of hepatocyte proliferation after PHx. Our data provide novel insights into the molecular mechanisms underlying the regeneration of PHx-treated liver.
Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders
Authors: Kisby Glen E. , Wilson David M. , Spencer Peter S.
Published: July 2024

Decades of research have identified genetic and environmental factors involved in age-related neurodegenerative diseases and, to a lesser extent, neuropsychiatric disorders. Genomic instability, i.e., the loss of genome integrity, is a common feature among both neurodegenerative (mayo-trophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease) and psychiatric (schizophrenia, autism, bipolar depression) disorders. Genomic instability is associated with the accumulation of persistent DNA damage and the activation of DNA damage response (DDR) pathways, as well as pathologic neuronal cell loss or senescence. Typically, DDR signaling ensures that genomic and proteomic homeostasis are maintained in both dividing cells, including neural progenitors, and post-mitotic neurons. However, dysregulation of these protective responses, in part due to aging or environmental insults, contributes to the progressive development of neurodegenerative and/or psychiatric disorders. In this Special Issue, we introduce and highlight the overlap between neurodegenerative diseases and neuropsychiatric disorders, as well as the emerging clinical, genomic, and molecular evidence for the contributions of DNA damage and aberrant DNA repair. Our goal is to illuminate the importance of this subject to uncover possible treatment and prevention strategies for relevant devastating brain diseases.
A Positive Feedback Loop Exists between Estradiol and IL-6 and Contributes to Dermal Fibrosis
Authors: Baker Frost DeAnna , Savchenko Alisa , Takamura Naoko , Wolf Bethany , Fierkens Roselyn , King Kimberly , Feghali-Bostwick Carol
Published: July 2024

Systemic sclerosis (SSc) is characterized by dermal fibrosis with a female predominance, suggesting a hormonal influence. Patients with SSc have elevated interleukin (IL)-6 levels, and post-menopausal women and older men also have high estradiol (E2) levels. In the skin, IL-6 increases the enzymatic activity of aromatase, thereby amplifying the conversion of testosterone to E2. Therefore, we hypothesized that an interplay between E2 and IL-6 contributes to dermal fibrosis. We used primary dermal fibroblasts from healthy donors and patients with diffuse cutaneous (dc)SSc, and healthy donor skin tissues stimulated with recombinant IL-6 and its soluble receptor (sIL-6R) or E2. Primary human dermal fibroblasts and tissues from healthy donors stimulated with IL-6+sIL-6R produced E2, while E2-stimulated dermal tissues and fibroblasts produced IL-6. Primary dermal fibroblasts from healthy donors treated with IL-6+sIL-6R and the aromatase inhibitor anastrozole (ANA) and dcSSc fibroblasts treated with ANA produced less fibronectin (FN), type III collagen A1 (Col IIIA1), and type V collagen A1 (Col VA1). Finally, dcSSc dermal fibroblasts treated with the estrogen receptor inhibitor fulvestrant also generated less FN, Col IIIA1, and Col VA1. Our data show that IL-6 exerts its pro-fibrotic influence in human skin in part through E2 and establish a positive feedback loop between E2 and IL-6.
Assessment of the Biocompatibility Ability and Differentiation Capacity of Mesenchymal Stem Cells on Biopolymer/Gold Nanocomposites
Authors: Hung Huey-Shan , Shen Chiung-Chyi , Wu Jyun-Ting , Yueh Chun-Yu , Yang Meng-Yin , Yang Yi-Chin , Cheng Wen-Yu
Published: July 2024

This study assessed the biocompatibility of two types of nanogold composites: fibronectin-gold (FN-Au) and collagen-gold (Col-Au). It consisted of three main parts: surface characterization, in vitro biocompatibility assessments, and animal models. To determine the structural and functional differences between the materials used in this study, atomic force microscopy, Fourier-transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to investigate their surface topography and functional groups. The F-actin staining, proliferation, migration, reactive oxygen species generation, platelet activation, and monocyte activation of mesenchymal stem cells (MSCs) cultured on the FN-Au and Col-Au nanocomposites were investigated to determine their biological and cellular behaviors. Additionally, animal biocompatibility experiments measured capsule formation and collagen deposition in female Sprague–Dawley rats. The results showed that MSCs responded better on the FN-Au and Col-AU nanocomposites than on the control (tissue culture polystyrene) or pure substances, attributed to their incorporation of an optimal Au concentration (12.2 ppm), which induced significant surface morphological changes, nano topography cues, and better biocompatibility. Moreover, neuronal, endothelial, bone, and adipose tissues demonstrated better differentiation ability on the FN-Au and Col-Au nanocomposites. Nanocomposites have a crucial role in tissue engineering and even vascular grafts. Finally, MSCs were demonstrated to effectively enhance the stability of the endothelial structure, indicating that they can be applied as promising alternatives to clinics in the future.
Integrative Analysis of Hepatopancreas Transcriptome and Proteome in Female Eriocheir sinensis under Thermal Stress
Authors: Pan Tingshuang , Li Tong , Yang Min , Jiang He , Ling Jun
Published: July 2024

The Chinese mitten crab (Eriocheir sinensis), an economically important crustacean that is endemic to China, has recently experienced high-temperature stress. The high thermal tolerance of E. sinensis points to its promise in being highly productive in an aquacultural context. However, the mechanisms underlying its high thermal tolerance remain unknown. In this study, female E. sinensis that were heat exposed for 24 h at 38.5 °C and 33 °C were identified as high-temperature-stressed (HS) and normal-temperature-stressed (NS) groups, respectively. The hepatopancreas of E. sinensis from the HS and NS groups were used for transcriptome and proteomic analyses. A total of 2350 upregulated and 1081 downregulated differentially expressed genes (DEGs) were identified between the HS and NS groups. In addition, 126 differentially expressed proteins (DEPs) were upregulated and 35 were downregulated in the two groups. An integrated analysis showed that 2641 identified genes were correlated with their corresponding proteins, including 25 genes that were significantly differentially expressed between the two omics levels. Ten Gene Ontology terms were enriched in the DEGs and DEPs. A functional analysis revealed three common pathways that were significantly enriched in both DEGs and DEPs: fluid shear stress and atherosclerosis, leukocyte transendothelial migration, and thyroid hormone synthesis. Further analysis of the common pathways showed that MGST1, Act5C, HSP90AB1, and mys were overlapping genes at the transcriptome and proteome levels. These results demonstrate the differences between the HS and NS groups at the two omics levels and will be helpful in clarifying the mechanisms underlying the thermal tolerance of E. sinensis.
Effect of Diets with the Addition of Edible Insects on the Development of Atherosclerotic Lesions in ApoE/LDLR−/− Mice
Authors: Hassen Hayat , Škvorová Petra , Pokhrel Kshitiz , Kulma Martin , Piątkowska Ewa , Kostogrys Renata B. , Kouřimská Lenka , Tarko Tomasz , Franczyk-Żarów Magdalena
Published: July 2024

Foods enriched with insects can potentially prevent several health disorders, including cardiovascular diseases, by reducing inflammation and improving antioxidant status. In this study, Tenebrio molitor and Gryllus assimilis were selected to determine the effect on the development of atherosclerosis in ApoE/LDLR−/− mice. Animals were fed AIN-93G-based diets (control) with 10% Tenebrio molitor (TM) and 10% Gryllus assimilis (GA) for 8 weeks. The nutritional value as well as antioxidant activity of selected insects were determined. The lipid profile, liver enzyme activity, and the fatty acid composition of liver and adipose tissue of model mice were evaluated. Quantitative analysis of atherosclerotic lesions in the entire aorta was performed using the en face method, and for aortic roots, the cross-section method was used. The antioxidant status of the GA cricket was significantly higher compared to the TM larvae. The results showed that the area of atherosclerosis (en face method) was not significantly different between groups. Dietary GA reduced plaque formation in the aortic root; additionally, significant differences were observed in sections at 200 and 300 µm compared to other groups. Furthermore, liver enzyme ALT activity was lower in insect-fed groups compared to the control group. The finding suggests that a diet containing edible insect GA potentially prevents atherosclerotic plaque development in the aortic root, due to its high antioxidant activity.
Characterisation of an Adult Zebrafish Model for SDHB-Associated Phaeochromocytomas and Paragangliomas
Authors: Miltenburg Jasmijn B. , Gorissen Marnix , van Outersterp Inge , Versteeg Iris , Nowak Alex , Rodenburg Richard J. , van Herwaarden Antonius E. , Olthaar Andre J. , Kusters Benno , Conrad Catleen , Timmers Henri J. L. M. , Dona Margo
Published: July 2024

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene succinate dehydrogenase subunit B (SDHB) are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available. The pathomechanism of SDHB-associated PPGL remains largely unknown, and the lack of suitable models hinders therapy development. Germline heterozygous SDHB pathogenic variants predispose to developing PPGLs with a life-long penetrance of around 50%. To mimic the human disease phenotype, we characterised adult heterozygous sdhb mutant zebrafish as a potential model to study SDHB-related PPGLs. Adult sdhb mutant zebrafish did not develop an obvious tumour phenotype and were anatomically and histologically like their wild-type siblings. However, sdhb mutants showed significantly increased succinate levels, a major hallmark of SDHB-related PPGLs. While basal activity was increased during day periods in mutants, mitochondrial complex activity and catecholamine metabolite levels were not significantly different. In conclusion, we characterised an adult in vivo zebrafish model, genetically resembling human carriers. Adult heterozygous sdhb mutants mimicked their human counterparts, showing systemic elevation of succinate levels despite the absence of a tumour phenotype. This model forms a promising basis for developing a full tumour phenotype and gaining knowledge of the pathomechanism behind SDHB-related PPGLs.
Biological Activity of Natural and Synthetic Peptides as Anticancer Agents
Authors: Bauso Luana Vittoria , La Fauci Valeria , Munaò Serena , Bonfiglio Desirèe , Armeli Alessandra , Maimone Noemi , Longo Clelia , Calabrese Giovanna
Published: July 2024

Cancer is one of the leading causes of morbidity and death worldwide, making it a serious global health concern. Chemotherapy, radiotherapy, and surgical treatment are the most used conventional therapeutic approaches, although they show several side effects that limit their effectiveness. For these reasons, the discovery of new effective alternative therapies still represents an enormous challenge for the treatment of tumour diseases. Recently, anticancer peptides (ACPs) have gained attention for cancer diagnosis and treatment. ACPs are small bioactive molecules which selectively induce cancer cell death through a variety of mechanisms such as apoptosis, membrane disruption, DNA damage, immunomodulation, as well as inhibition of angiogenesis, cell survival, and proliferation pathways. ACPs can also be employed for the targeted delivery of drugs into cancer cells. With over 1000 clinical trials using ACPs, their potential for application in cancer therapy seems promising. Peptides can also be utilized in conjunction with imaging agents and molecular imaging methods, such as MRI, PET, CT, and NIR, improving the detection and the classification of cancer, and monitoring the treatment response. In this review we will provide an overview of the biological activity of some natural and synthetic peptides for the treatment of the most common and malignant tumours affecting people around the world.
Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage
Authors: Du Qiran , Dickinson Anna , Nakuleswaran Pruthvi , Maghami Susan , Alagoda Savindu , Hook Andrew L. , Ghaemmaghami Amir M.
Published: July 2024

Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages’ functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.
Comprehensive Expression Analysis of the WRKY Gene Family in Phoebe bournei under Drought and Waterlogging Stresses
Authors: Wang Zhongxuan , You Limei , Gong Na , Li Can , Li Zhuoqun , Shen Jun , Wan Lulu , Luo Kaijin , Su Xiaoqing , Feng Lizhen , Chen Shipin , Lin Wenjun
Published: July 2024

In response to biotic and abiotic stresses, the WRKY gene family plays a crucial role in plant growth and development. This study focused on Phoebe bournei and involved genome-wide identification of WRKY gene family members, clarification of their molecular evolutionary characteristics, and comprehensive mapping of their expression profiles under diverse abiotic stress conditions. A total of 60 WRKY gene family members were identified, and their phylogenetic classification revealed three distinct groups. A conserved motif analysis underscored the significant conservation of motif 1 and motif 2 among the majority of PbWRKY proteins, with proteins within the same class sharing analogous gene structures. Furthermore, an examination of cis-acting elements and protein interaction networks revealed several genes implicated in abiotic stress responses in P. bournei. Transcriptomic data were utilized to analyze the expression patterns of WRKY family members under drought and waterlogged conditions, with subsequent validation by quantitative real-time PCR (RT-qPCR) experiments. Notably, PbWRKY55 exhibited significant expression modulation under drought stress; PbWRKY36 responded prominently to waterlogging stress; and PbWRKY18, PbWRKY38, and PbWRKY57 demonstrated altered expression under both drought and waterlogging stresses. This study revealed the PbWRKY candidate genes that potentially play a pivotal role in enhancing abiotic stress resilience in P. bournei. The findings have provided valuable insights and knowledge that can guide further research aimed at understanding and addressing the impacts of abiotic stress within this species.
Modifications of Nanobubble Therapy for Cancer Treatment
Authors: Terlikowska Katarzyna M. , Dobrzycka Bozena , Terlikowski Slawomir J.
Published: July 2024

Cancer development is related to genetic mutations in primary cells, where 5–10% of all cancers are derived from acquired genetic defects, most of which are a consequence of the environment and lifestyle. As it turns out, over half of cancer deaths are due to the generation of drug resistance. The local delivery of chemotherapeutic drugs may reduce their toxicity by increasing their therapeutic dose at targeted sites and by decreasing the plasma levels of circulating drugs. Nanobubbles have attracted much attention as an effective drug distribution system due to their non-invasiveness and targetability. This review aims to present the characteristics of nanobubble systems and their efficacy within the biomedical field with special emphasis on cancer treatment. In vivo and in vitro studies on cancer confirm nanobubbles’ ability and good blood capillary perfusion; however, there is a need to define their safety and side effects in clinical trials.
Stability and Motion Patterns of Two Interactive Oscillating Agents
Authors: Juang Jyh-Ching
Published: July 2024

This paper investigates the stability and motion of two interactive oscillating agents. Multiple agents can be controlled in a centralized and/or distributed manner to form specific patterns in cooperative tracking, pursuit, and evasion games, as well as environmental exploration. This paper studies the behavior of two oscillating agents due to their interaction. It shows that, through a combination of selecting oscillation centers and interaction gain, a variety of motions, including limit-cycles and stationary behavior, can be realized.
Bearing Capacity of Precast Concrete Joint Micropile Foundations in Embedded Layers: Predictions from Dynamic and Static Load Tests according to ASTM Standards
Authors: Omarov Abdulla , Sarsembayeva Assel , Zhussupbekov Askar , Nurgozhina Malika , Tleulenova Gulshat , Yeleussinova Akmaral , Isakulov Baizak
Published: July 2024

In this paper, joint precast piles with a cross-section of 400 × 400 mm and a pin-joined connection were considered, and their interaction with the soil of Western Kazakhstan has been analyzed. The following methods were used: assessment of the bearing capacity using the static compression load test (SCLT by ASTM) method, interpretation of the field test data, and the dynamic loading test (DLT) method for driving precast concrete joint piles, including Pile Driving Analyzer (PDA by ASTM) and Control and Provisioning of Wireless Access Points (CAPWAP) methods. According to the results, the composite piles tested by the PDA (by ASTM) method differ by 15 percent compared to the static load method, while the difference between the dynamic DLT (by ASTM) method and the static load (by ASTM) method was only 7 percent. So, according to the results, the alternative dynamic method DLT (by ASTM) is very effective and more accurate compared to other existing methods.
Correction: Cabral et al. Railway Bridge Geometry Assessment Supported by Cutting-Edge Reality Capture Technologies and 3D As-Designed Models. Infrastructures 2023, 8, 114
Authors: Cabral Rafael , Oliveira Rogério , Ribeiro Diogo , Rakoczy Anna M. , Santos Ricardo , Azenha Miguel , Correia José
Published: July 2024

In the original publication [...]
Effect of Impregnation of PEDOT:PSS in Etched Aluminium Electrodes on the Performance of Solid State Electrolytic Capacitors
Authors: Calabia Gascón Néstor , Wouters Benny , Terryn Herman , Hubin Annick
Published: July 2024

Electrolytic capacitors store larger amounts of energy thanks to their thin dielectric layers and enlarged surface area. However, the benefits of using a liquid electrolyte are at the expense of the possibility of leakage, evaporation, or rupture of the device over time. As a solution, solid electrolytes, such as conductive polymers, substitute the liquid ones decreasing the internal resistance and enlarging the lifetime of these devices. PEDOT:PSS is a widely used conductive polymer in the formation of solid electrolytic capacitors. However, using the enlarged surface of the porous electrodes efficiently requires industrial processes, the efficacy of which has not been explored. In this work, porous aluminium electrodes with dielectric layers of different thicknesses were coated with PEDOT:PSS at different levels of doping in order to study the efficiency of the production of solid electrolytic capacitors in industry. The combination of odd random phase electrochemical impedance spectroscopy (ORP-EIS) with surface characterization techniques (SEM-EDX, GDOES) formed a methodology that allowed the study of both the electrical properties and the level of impregnation for these model systems. All samples consisting of a porous aluminium electrode with an amount of PEDOT:PSS deposited on top resulted in an inefficient degree of penetration between the two electrodes. However, the electrochemical analysis proved that the use of dopants produces systems with the highest capacitive properties. Consequently, the evolution towards better solid electrolytic capacitors does not rely solely on the proper coverage of the porous electrodes, but on the proper electrical properties of the PEDOT:PSS within the pores.
Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity
Authors: Pérez Marina , Buey Berta , Corral Pilar , Giraldos David , Latorre Eva
Published: July 2024

Background: The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells. Methods: The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line. Results: Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs’ production could play a fundamental role in cancer immunotherapy.
A Finite Element Analysis Study of Influence of Femoral Stem Material in Stress Shielding in a Model of Uncemented Total Hip Arthroplasty: Ti-6Al-4V versus Carbon Fibre-Reinforced PEEK Composite
Authors: Ceddia Mario , Solarino Giuseppe , Giannini Giorgio , De Giosa Giuseppe , Tucci Maria , Trentadue Bartolomeo
Published: July 2024

Total hip arthroplasty is one of the most common and successful orthopaedic operations. Occasionally, periprosthetic osteolysis associated with stress shielding occurs, resulting in a reduction of bone density where the femur is not properly loaded and the formation of denser bone where stresses are confined. To enhance proximal load transfer and reduce stress shielding, approaches, including decreasing the stiffness of femoral stems, such as carbon fibre-reinforced polymer composites (CFRPCs), have been explored through novel modular prostheses. The purpose of the present study was to analyse, by the finite element analysis (FEA) method, the effect that the variation of material for the distal part of the femoral stem has on stress transmission between a modulable prosthesis and the adjacent bone. Methods: Through three-dimensional modelling and the use of commercially available FEA software Ansys R2023, the mechanical behaviour of the distal part of the femoral stem made of CFRPC or Ti-6Al-4V was obtained. A load was applied to the head of the femoral stem that simulates a complete walking cycle. Results: The results showed that the use of a material with mechanical characteristics close to the bone, like CFRPC, allowed for optimisation of the transmitted loads, promoting a better distribution of stress from the proximal to the distal part of the femur. This observation was also found in some clinical studies in literature, which reported not only an improved load transfer with the use of CFRPC but also a higher cell attachment than Ti-6Al-4V. Conclusions: The use of a material that has mechanical properties that are close to bone promotes load transfer from the proximal to the distal area. In particular, the use of CFRPC allows the material to be designed based on the patient’s actual bone characteristics. This provides a customised design with a lower risk of prosthesis loss due to stress shielding.
The Effect of Nanoclay Type on the Mechanical Properties and Antibacterial Activity of Chitosan/PVA Nanocomposite Films
Authors: Farrokhi Hadisehsadat , Koosha Mojtaba , Nasirizadeh Navid , Salari Mahshid , Abdouss Majid , Li Tianduo , Gong Yinghua
Published: July 2024

Nanoclays are a class of nanomaterials extensively used to prepare polymer nanocomposites. In this study, four types of common nanoclays were selected to prepare chitosan–polyvinyl alcohol (CP) nanocomposite films. Montmorillonite cloisite Na+ (MMT), organically modified montmorillonite (OMMT), and bentonite (BNT), as layered aluminosilicates, and halloysite nanotubes (HNT), as a tubular nanoclay, were blended with CP films at concentrations of 1.5, 3 and 4.5%. The nanocomposite films were characterized by FTIR, XRD, SEM/EDX, AFM, tensile strength, and antibacterial tests. SEM/EDX results showed a more uniform distribution of the OMMT and HNT nanoclays in the polymer matrix. AFM images showed a rougher surface for nanocomposite films compared to CP film. Increasing the nanoclay concentration in the films from 1.5 to 4.5% resulted in higher tensile strength for HNT and MMT while the trend was reversed for OMMT and BNT. Among the samples, nanocomposite films composed of OMMT and BNT showed the highest tensile strength at the lowest concentrations (CP-OMMT1.5 99 ± 3.7 MPa, CP-B1.5 81 ± 1.5 MPa). The nanocomposite films prepared from OMMT showed the highest antibacterial activity against E. coli and S. aureus with an inhibition zone of 15 and 19 mm, respectively. The results of this study showed that BNT and OMMT are promising nanoclays for enhancing the mechanical properties and antibacterial activity of hydrophilic polymers. The results of this research can provide new insights into selecting suitable nanoclays for different applications.
Correction: Petroll et al. Experimental Models for Investigating Intra-Stromal Migration of Corneal Keratocytes, Fibroblasts and Myofibroblasts. J. Funct. Biomater. 2012, 3, 183–198
Authors: Petroll Walter Matthew , Lakshman Neema , Ma Lisha
Published: July 2024

In the original publication [...]
Lifestyle as a Modulator of the Effects on Fitness of an Integrated Neuromuscular Training in Primary Education
Authors: Roman-Viñas Blanca , Vasileva Fidanka , Font-Lladó Raquel , Aznar-Laín Susana , Jiménez-Zazo Fabio , Lopez-Bermejo Abel , López-Ros Victor , Prats-Puig Anna
Published: July 2024

The objective was to evaluate changes in fitness after an integrated neuromuscular training (INT) intervention in primary school children and to evaluate how lifestyle behaviors and parental education modulate these changes. One hundred and seventy children (7.45 ± 0.34 years; 52% girls) were included. Cardiorespiratory fitness (half-mile run test), a 10 × 5 m shuttle run test, standing broad jump (SBJ), handgrip dynamometer, body mass index (BMI) and fat mass percentage (FM%) were assessed before and after the 3-month intervention (20 min of INT in the physical education class, twice per week). The Mediterranean diet (MD), sleep time and parental education level (PEL) were evaluated by questionnaires, and adherence to physical activity (PA) recommendations was measured with a triaxial accelerometer before the intervention. After the intervention, there were improvements in the 10 × 5 test and the SBJ. Only girls had improvements in the handgrip test, BMI SDS and FM%. After correcting for confounding variables, only BMI was significantly improved whereas strength improved in the participants non-compliant with the PA recommendations or pertaining to families of high PEL. The INT produced improvements in fitness in a brief period and in different subgroups of pupils (inactive and with diverse sociocultural environments).
Lagrangian Finite Element Model Formulation and Experimental Validation of the Laser Impact Weld Process for Ti/Brass Joining
Authors: Caruso Serafino , Sanguedolce Michela , Serratore Giuseppe , De Bartolo Carmine , Filice Luigino , Umbrello Domenico
Published: July 2024

Information on the flyer deformation during laser impact welding (LIW) is an important aspect to consider when high reliability of the welded components is required. For this reason, accurate numerical models simulating thermal and mechanical aspects are needed. In the present work, the cross-section morphology during LIW of Ti/Brass joints at varying laser pulse energies is modeled by a 2D finite element (FE) model. A hydrodynamic plasma pressure model able to describe the evolution of the pressure load step by step, taking into account the progressive deformation of the flyer, was implemented. Hence, this paper proposes an alternative method to the conventional node concentrated forces or predefined velocity as flyer boundary conditions. The levels of the equivalent plastic strain (PEEQ), shear stress, and critical flyer velocity at the collision point were used as reference parameters to predict the success of the welding bond, distinguishing the welded area from the unwelded area. The model was validated by comparison with the experimental data, which showed the effectiveness of the proposed FE code in predicting the cross-section morphology of the welded materials. Moreover, practical industrial information such as variation in the flyer impact velocity, collision angle, and process temperatures was predicted by varying the process laser pulse energy according to the basic principle of the process.
Enhancing Chronic Disease Management: Personalized Medicine Insights from Rural and Urban General Practitioner Practices
Authors: Duda-Sikuła Marta , Kurpas Donata
Published: July 2024

Health policies worldwide emphasize managing chronic conditions like diabetes and hypertension through medication and lifestyle modifications. However, translating guidelines into practical application remains challenging, leading to suboptimal care and poor health outcomes, particularly in low-resource settings. This study aims to reveal significant differences between rural and urban patients requiring personalized approaches to chronic disease management based on geographical location and demographic data, considering the impact of emergencies such as the COVID-19 pandemic. Data were collected from rural and urban general practitioner (GP) practices in Poland, covering four years from 2018 to the first quarter of 2021, focusing on diabetes and hypertension epidemiology, risk factors, comorbidities, resource consumption, and disease burden. The findings revealed significant differences between rural and urban patients regarding age, number of patient visits, gender distribution, and types of diagnoses and visit modalities. Rural patients tended to be older, had a higher median number of visits, and exhibited different patterns of diagnoses and visit types compared to urban patients. The study also investigated the impact of the COVID-19 pandemic on chronic disease treatment, finding that while age at visits increased during the pandemic, there were no significant changes in gender distribution, but a noticeable shift in diagnoses and visit modalities with an increase in remote visits and changes in the prevalence of specific diagnoses. These disparities highlight the need for tailored approaches to chronic disease management based on geographic location and patient demographics. The study underscores the importance of understanding the unique challenges and opportunities in managing chronic diseases across different settings and during public health crises like the COVID-19 pandemic, aiding healthcare providers and policymakers in developing targeted interventions to improve chronic disease prevention and management, ultimately leading to better health outcomes for individuals and communities. Further research is needed to explore the long-term effects of the pandemic on chronic disease treatment and assess the effectiveness of interventions to mitigate its impact.