bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Characterization of Corneal Epithelial and Stromal Cell-Derived Extracellular Vesicles
Authors: Yeung Vincent , Boychev Nikolay , Kanu Levi N. , Ng Veronica , Ross Amy E. , Hutcheon Audrey E. K. , Ciolino Joseph B.
Published: September 2024

Communication between the different layers of the cornea (epithelium and stroma) is a complex, yet crucial element in the corneal healing process. Upon corneal injury, it has been reported that the bi-directional cross talk between the epithelium and stroma via the vesicular secretome, namely, extracellular vesicles (EVs), can lead to accelerated wound closure upon injury. However, the distinct protein markers of EVs derived from human corneal epithelial (HCE) cells, keratocytes (HCKs), fibroblasts (HCFs), and myofibroblasts (HCMs) remain poorly understood. All EVs were enriched for CD81 and showed increased expression levels of ITGAV and FN1 in HCM-EVs compared to HCE- and HCF-EVs. All EVs were negative for GM130 and showed minimal differences in biophysical properties (particle concentration, median particle size, and zeta potential). At the proteomic level, we show that HCM-EVs are enriched with proteins associated with fibrosis pathways, such as COL6A1, COL6A2, MMP1, MMP2, TIMP1, and TIMP2, compared to HCE-, HCK-, and HCF-EVs. Interestingly, HCE-EVs express proteins involved with the EIF-2 signaling pathway (stress-induced signals to regulate mRNA translation), such as RPS21, RALB, EIF3H, RALA, and others, compared to HCK-, HCF-, and HCM-EVs. In this study, we isolated EVs from cell-conditioned media from HCE, HCKs, HCFs, and HCMs and characterized their biophysical and protein composition by Western blot, nanoparticle tracking analysis, and proteomics. This study supports the view that EVs from the corneal epithelium and stroma have a distinct molecular composition and may provide novel protein markers to distinguish the difference between HCE-, HCK-, HCF-, and HCM-EVs.
New Insights and Future Perspectives of APRIL in IgA Nephropathy
Authors: Muto Masahiro , Suzuki Hitoshi , Suzuki Yusuke
Published: September 2024

IgA nephropathy (IgAN) is characterized by immune-mediated glomerulonephritis, with the accumulation of galactose-deficient IgA1 (Gd-IgA1) in the glomeruli and increased levels of circulating Gd-IgA1 and Gd-IgA1-containing immune complexes. An incomplete understanding of the underlying mechanisms and differences in clinical and pathological features between individuals and ethnicities has contributed to the lack of established treatments for IgAN. A tumor necrosis factor (TNF) family member, a proliferation-inducing ligand (APRIL), is a crucial cytokine essential for the generation and survival of plasma cells. Recent studies demonstrated that APRIL is a pivotal mediator in the production of Gd-IgA1 in IgAN. As our understanding of the autoimmune pathogenesis underlying IgAN has improved, various pharmacological therapeutic targets, including APRIL antagonists, have emerged. Preliminary results showed that APRIL-targeting agents effectively reduced proteinuria and Gd-IgA1 levels without significantly increasing adverse events, indicating their potential as novel therapeutic agents for IgAN. In the present review, we discuss the current understanding of the role of APRIL in the pathogenesis of IgAN and novel therapeutic strategies focusing on APRIL-targeting agents for IgAN. APRIL inhibitors may offer new hope to patients with IgAN.
CDNF Exerts Anxiolytic, Antidepressant-like, and Procognitive Effects and Modulates Serotonin Turnover and Neuroplasticity-Related Genes
Authors: Tsybko Anton , Eremin Dmitry , Ilchibaeva Tatiana , Khotskin Nikita , Naumenko Vladimir
Published: September 2024

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor because it does not bind to a known specific receptor on the plasma membrane and functions primarily as an unfolded protein response (UPR) regulator in the endoplasmic reticulum. Data on the effects of CDNF on nonmotor behavior and monoamine metabolism are limited. Here, we performed the intracerebroventricular injection of a recombinant CDNF protein at doses of 3, 10, and 30 μg in C57BL/6 mice. No adverse effects of the CDNF injection on feed and water consumption or locomotor activity were observed for 3 days afterwards. Decreases in body weight and sleep duration were transient. CDNF-treated animals demonstrated improved performance on the operant learning task and a substantial decrease in anxiety and behavioral despair. CDNF in all the doses enhanced serotonin (5-HT) turnover in the murine frontal cortex, hippocampus, and midbrain. This alteration was accompanied by changes in the mRNA levels of the 5-HT1A and 5-HT7 receptors and in monoamine oxidase A mRNA and protein levels. We found that CDNF dramatically increased c-Fos mRNA levels in all investigated brain areas but elevated the phosphorylated-c-Fos level only in the midbrain. Similarly, enhanced CREB phosphorylation was found in the midbrain in experimental animals. Additionally, the upregulation of a spliced transcript of XBP1 (UPR regulator) was detected in the midbrain and frontal cortex. Thus, we can hypothesize that exogenous CDNF modulates the UPR pathway and overall neuronal activation and enhances 5-HT turnover, thereby affecting learning and emotion-related behavior.
Visual Detection of Dopamine with CdS/ZnS Quantum Dots Bearing by ZIF-8 and Nanofiber Membranes
Authors: Hu Jiadong , Li Jiaxin , Guo Qunqun , Du Guicai , Li Changming , Li Ronggui , Zhou Rong , He Hongwei
Published: September 2024

Dopamine (DA) is a widely present, calcium cholinergic neurotransmitter in the body, playing important roles in the central nervous system and cardiovascular system. Developing fast and sensitive DA detection methods is of great significance. Fluorescence-based methods have attracted much attention due to their advantages of easy operation, a fast response speed, and high sensitivity. This study prepared hydrophilic and high-performance CdS/ZnS quantum dots (QDs) for DA detection. The waterborne CdS/ZnS QDs were synthesized in one step using the amphiphilic polymer PEI-g-C14, obtained by grafting tetradecane (C14) to polyethyleneimine (PEI), as a template. The polyacrylonitrile nanofiber membrane (PAN-NFM) was prepared by electrospinning (e-spinning), and a metal organic frame (ZIF-8) was deposited in situ on the surface of the PAN-NFM. The CdS/ZnS QDs were loaded onto this substrate (ZIF-8@PAN-NFM). The results showed that after the deposition of ZIF-8, the water contact angle of the hydrophobic PAN-NFM decreased to within 40°. The nanofiber membrane loaded with QDs also exhibited significant changes in fluorescence in the presence of DA at different concentrations, which could be applied as a fast detection method of DA with high sensitivity. Meanwhile, the fluorescence on this PAN-NFM could be visually observed as it transitioned from a blue-green color to colorless, making it suitable for the real-time detection of DA.
Immunohistochemical Expression of p53 and FGFR3 Predicts Response to Enfortumab Vedotin in Metastatic Urothelial Carcinoma
Authors: Nagata Yujiro , Minato Akinori , Aono Hisami , Kimuro Rieko , Higashijima Katsuyoshi , Tomisaki Ikko , Harada Kenichi , Miyamoto Hiroshi , Fujimoto Naohiro
Published: September 2024

Locally advanced or metastatic urothelial carcinoma is a genomically and molecularly heterogeneous disease associated with various clinical outcomes. We aimed to evaluate the association between the status of p53/FGFR3 expression and the efficacy of enfortumab vedotin (EV) in metastatic urothelial carcinoma. We evaluated the association between p53 (abnormal vs. wild-type) or FGFR3 (high vs. low) expression determined by immunohistochemistry and response to EV in 28 patients with metastatic urothelial carcinoma. Overall, 60.7% showed abnormal p53, and 17.9% had high FGFR3 expression. The rates of objective response to EV were statistically higher in patients with abnormal p53 than in those with wild-type p53 (p = 0.038). Patients with pure urothelial carcinoma (n = 18) and low FGFR3 showed significantly better response to EV than those with high FGFR3. When the statuses of p53 and FGFR3 were combined, abnormal p53/low FGFR3 (vs. wild-type p53/high FGFR3) was strongly associated with favorable outcomes in both the entire cohort (p = 0.002) and in cases of pure urothelial carcinoma only (p = 0.023). Immunohistochemically abnormal p53 tumors were found to respond well to EV, while high FGFR3 tumors had a poorer response. Thus, p53 and FGFR3 are potential biomarkers for predicting response to EV treatment in patients with urothelial carcinoma.
Molecular Epidemiology and Phyloevolutionary Analysis of Porcine Parvoviruses (PPV1 through PPV7) Detected in Replacement Gilts from Colombia
Authors: Vargas-Bermudez Diana S. , Prandi Bruno Aschidamini , Souza Ueric José Borges de , Durães-Carvalho Ricardo , Mogollón José Darío , Campos Fabrício Souza , Roehe Paulo Michel , Jaime Jairo
Published: September 2024

Eight porcine parvovirus (PPV) species, designated as PPV1 through PPV8, have been identified in swine. Despite their similarities, knowledge about their distribution and genetic differences remains limited, resulting in a gap in the genetic classification of these viruses. In this study, we conducted a comprehensive analysis using PPV1 to PPV7 genome sequences from Colombia and others available in the GenBank database to propose a classification scheme for all PPVs. Sera from 234 gilts aged 180 to 200 days were collected from 40 herds in Colombia. Individual detection of each PPV (PPV1 through PPV7) was performed using end-point PCR. Complete nucleotide (nt) sequencing was performed on the PPV1 viral protein (VP), and near-complete genome (NCG) sequencing was carried out for novel porcine parvoviruses (nPPVs) (PPV2 through PPV7). Phylogenetic analyses were conducted by comparing PPV1-VP sequences to 94 available sequences and nPPVs with 565 NCG, 846 nPPV-VP, and 667 nPPV–nonstructural protein (NS) sequences. Bayesian phylogenetic analysis was used to estimate substitution rates and the time to the most recent common ancestor for each PPV. The highest prevalence was detected for PPV3 (40.1%), followed by PPV5 (20.5%), PPV6 (17%), PPV1 (14.5%), PPV2 (9.8%), PPV4 (4.2%), and PPV7 (1.3%). Notably, all tested sera were negative for PPV8 genomes. An analysis of the PPV1-VP sequences revealed two main clades (PPV1-I and PPV1-II), with the sequences recovered in this study grouped in the PPV1-II clade. Comparative analysis showed significant genetic distances for PPV2 to PPV7 at the NCG (>6.5%), NS (>6.3%), and VP (>7.5%) regions, particularly when compared to equivalent regions of PPV genomes recovered worldwide. This study highlights the endemic circulation of nPPVs in Colombian pig herds, specifically among gilts. Additionally, it contributes to the phylogenetic classification and evolutionary studies of these viruses. The proposed method aims to categorize and divide subtypes based on current knowledge and the genomes available in databanks.
Molecular Study of the Fukutin-Related Protein (FKRP) Gene in Patients from Southern Italy with Duchenne/Becker-like Phenotype
Authors: Qualtieri Antonio , De Benedittis Selene , Cerantonio Annamaria , Citrigno Luigi , Di Palma Gemma , Gallo Olivier , Cavalcanti Francesca , Spadafora Patrizia
Published: September 2024

Pathogenic variants localized in the gene coding for the Fukutin-Related Protein (FKRP) are responsible for Limb-Girdle Muscular Dystrophy type 9 (LGMDR9), Congenital Muscular Dystrophies type 1C (MDC1C), Walker–Warburg Syndrome (WWS), and Muscle–Eye–Brain diseases (MEBs). LGMDR9 is the fourth most common hereditary Limb Girdle Muscular Dystrophy in Italy. LGMDR9 patients with severe disease show an overlapping Duchenne/Becker phenotype and may have secondary dystrophin reduction on muscle biopsy. We conducted a molecular analysis of the FKRP gene by direct sequencing in 153 patients from Southern Italy (Calabria) with Duchenne/Becker-like phenotypes without confirmed genetic diagnosis. Mutational screening of the patients (112 men and 41 women, aged between 5 and 84 years), revealed pathogenic variants in 16 subjects. The most frequent variants identified were c.427C > A, p.R143S, and c.826C > A, p.L276I (NM_024301.5). The results obtained show that the Duchenne/Becker-like phenotype is frequently determined by mutations in the FKRP gene in our cohort and highlight the importance of considering LGMDR9 in the differential diagnosis of dystrophinopathies in Calabria. Finally, this study, which, to our knowledge, is the first conducted on Calabrian subjects, will contribute to the rapid identification and management of LGMDR9 patients.
In Vivo Evaluation of Nose-to-Brain Delivery of Liposomal Donepezil, Memantine, and BACE-1 siRNA for Alzheimer’s Disease Therapy
Authors: Lee David , Shen Andrew M. , Shah Milin , Garbuzenko Olga B. , Minko Tamara
Published: September 2024

Our study took an innovative approach by evaluating, in vivo, the efficacy of intranasal (IN) administration of liposomal formulations of donepezil, memantine, and beta-site amyloid precursor protein-cleaving enzyme (BACE-1) siRNA, and their combination as a “triple-drug therapy” in treating Alzheimer’s disease (AD). Female APP/PS1 homozygous, transgenic mice were used as an AD model. The spatial short-term memory of the APP/PS1 mice was evaluated by a Y-maze behavioral test. IN-administered formulations demonstrated better short-term memory recovery than oral administration. Triple-drug therapy induced short-term memory recovery and lowered beta-amyloid (Aβ) 40 and 42 peptide levels and BACE-1 mRNA expression. Additionally, inflammatory cytokine mRNA expression was downregulated. This innovative approach opens new possibilities for Alzheimer’s disease treatment and nose-to-brain delivery.
Mycovirus-Containing Aspergillus flavus Alters Transcription Factors in Normal and Acute Lymphoblastic Leukemia Cells
Authors: Tebbi Cameron K. , Yan Jiyu , Sahakian Eva , Mediavilla-Varela Melanie , Pinilla-Ibarz Javier , Patel Saumil , Rottinghaus George E. , Liu Rachel Y. , Dennison Clare
Published: September 2024

Transcription factors control genes to maintain normal hemopoiesis, and dysregulation of some factors can lead to acute lymphoblastic leukemia (ALL). Mycoviruses are known to alter the genetics of their fungal host. The present study evaluates the effects of the products of a mycovirus-containing Aspergillus flavus (MCAF), isolated from the home of a patient with ALL, on certain transcription factors of normal and ALL cell lines. Our published studies have shown that ALL patients have antibodies to MCAF, and that exposure of the mononuclear leukocytes of patients in complete remission to its products, unlike controls, results in the re-development of genetic and cell surface phenotypes characteristic of ALL. For the present study, normal, pre-B, and B-cell leukemia cell lines were exposed to the culture of MCAF. Pre- and post-exposure levels of PAX5, Ikaros, and NF-κB were assessed. Exposure to MCAF resulted in apoptosis, cell cycle changes, and complete downregulation of all transcription factors in normal cell lines. In acute leukemia cell lines, cellular apoptosis and alterations in the cell cycle were also noted; however, while there was downregulation of all tested transcription factors, residual levels were retained. The noted alterations in the transcription factors caused by MCAF are novel findings. The possible role of MCAF in leukemogenesis needs to be further investigated. Mycovirus-containing Aspergillus flavus was initially isolated from a leukemia patient’s home. Our prior published studies have illuminated intriguing associations of this organism with leukemia. Unlike controls, patients diagnosed with acute lymphoblastic leukemia (ALL) harbor antibodies to this organism. Furthermore, the exposure of mononuclear cells from patients with ALL in complete remission to the products of this organism reproduced genetic and cell phenotypes characteristic of ALL. These findings underscore the potential role of environmental factors in leukemogenesis and hint at novel avenues for therapeutic intervention and preventive strategies.
Betulonic Acid Inhibits Type-2 Porcine Reproductive and Respiratory Syndrome Virus Replication by Downregulating Cellular ATP Production
Authors: Long Feixiang , Su Lizhan , Zhang Mingxin , Wang Shuhua , Sun Qian , Liu Jinyi , Chen Weisan , Wang Haihong , Chen Jianxin
Published: September 2024

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV) infection, has been a serious threat to the pork industry worldwide and continues to bring significant economic loss. Current vaccination strategies offer limited protection against PRRSV transmission, highlighting the urgent need for novel antiviral approaches. In the present study, we reported for the first time that betulonic acid (BA), a widely available pentacyclic triterpenoids throughout the plant kingdom, exhibited potent inhibition on PRRSV infections in both Marc-145 cells and primary porcine alveolar macrophages (PAMs), with IC50 values ranging from 3.3 µM to 3.7 µM against three different type-2 PRRSV strains. Mechanistically, we showed that PRRSV replication relies on energy supply from cellular ATP production, and BA inhibits PRRSV infection by reducing cellular ATP production. Our findings indicate that controlling host ATP production could be a potential strategy to combat PRRSV infections, and that BA might be a promising therapeutic agent against PRRSV epidemics.
Transcriptome Profiling Associated with CARD11 Overexpression in Colorectal Cancer Implicates a Potential Role for Tumor Immune Microenvironment and Cancer Pathways Modulation via NF-κB
Authors: Alhosani Faisal , Ilce Burcu Yener , Alhamidi Reem Sami , Bhamidimarri Poorna Manasa , Hamad Alaa Mohamed , Alkhayyal Noura , Künstner Axel , Khandanpour Cyrus , Busch Hauke , Al-Ramadi Basel , Sayed Kadria , AlFazari Ali , Bendardaf Riyad , Hamoudi Rifat
Published: September 2024

The immune system plays a critical role in inflammation by initiating responses to infections or tissue damage. The nuclear factor-κB (NF-κB) pathway plays a key role in inflammation and innate immunity, as well as other cellular activities. Dysregulation of this well-choreographed pathway has been implicated in various diseases, including cancer. CARD11 is a key molecule in the BCL10-MALT1 complex, which is involved in transducing the signal downstream of the NF-κB pathway. This study aims to elucidate how CARD11 overexpression exacerbates the prognosis of colorectal cancer (CRC). To identify the cellular pathways influenced by CARD11, transcriptomic analysis in both CRC cell lines and patients was carried out on CARD11– overexpressed HCT-116 and HT-29 CRC cell lines alongside empty vector-transfected cell lines. Furthermore, a comparison of transcriptomic data from adenoma and carcinoma CRC patients with low- (CARD11–) and high-(CARD11+) CARD11 expression was carried out. Whole transcriptomics and bioinformatics analysis results indicate that CARD11 appears to play a key role in CRC progression. Absolute GSEA (absGSEA) on HCT-116 transcriptomics data revealed that CARD11 overexpression promotes cell growth and tissue remodeling and enhances immune response. Key genes co-expressed with CARD11, such as EP300, KDM5A, HIF1A, NFKBIZ, and DUSP1, were identified as mediators of these processes. In the HT-29 cell line, CARD11 overexpression activated pathways involved in chemotaxis and extracellular matrix (ECM) organization, marked by IL1RN, MDK, SPP1, and chemokines like CXCL1, CXCL3, and CCL22, which were shown to contribute to the more invasive stage of CRC. In patient samples, adenoma patients exhibited increased expression of genes associated with the tumor immune microenvironment, such as IL6ST, collagen family members, and CRC transition markers, such as GLI3 and PIEZO2, in CARD11+ adenoma patients. Carcinoma patients showed a dramatic increase in the expression of MAPK8IP2 in CARD11+ carcinoma patients alongside other cancer-related genes, including EMB, EPHB6, and CPEB4.
Targeting USP14/UCHL5: A Breakthrough Approach to Overcoming Treatment-Resistant FLT3-ITD-Positive AML
Authors: Nogami Ayako , Amemiya Hideki Jose , Fujiwara Hiroki , Umezawa Yoshihiro , Tohda Shuji , Nagao Toshikage
Published: September 2024

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in acute myeloid leukemia (AML) are associated with poor prognosis and therapy resistance. This study aimed to demonstrate that inhibiting the deubiquitinating enzymes ubiquitin-specific peptidase 14 (USP14) and ubiquitin C-terminal hydrolase L5 (UCHL5) (USP14/UCHL5) with b-AP15 or the organogold compound auranofin (AUR) induces apoptosis in the ITD-transformed human leukemia cell line MV4-11 and mononuclear leukocytes derived from patients with FLT3-ITD-positive AML. This study included patients diagnosed with AML at Tokyo Medical and Dental University Hospital between January 2018 and July 2024. Both treatments blocked downstream FLT3 pathway events, with the effects potentiated by USP14 knockdown. Both treatments inhibited FLT3 deubiquitination via K48 and disrupted translation initiation via 4EBP1, a downstream FLT3 target. FLT3 was downregulated in the leukemic cells, with the associated activation of stress-related MAP kinase pathways and increased NF-E2-related factor 2. Furthermore, the overexpression of B-cell lymphoma-extra-large and myeloid cell leukemia-1 prevented the cell death caused by b-AP15 and AUR. These results suggest that inhibiting USP14/UCHL5, which involves multiple regulatory mechanisms, is a promising target for novel therapies for treatment-resistant FLT3-ITD-positive AML.
Chitosan–Clay Mineral Nanocomposites with Antibacterial Activity for Biomedical Application: Advantages and Future Perspectives
Authors: Krajišnik Danina , Uskoković-Marković Snežana , Daković Aleksandra
Published: September 2024

Polymers of natural origin, such as representatives of various polysaccharides (e.g., cellulose, dextran, hyaluronic acid, gellan gum, etc.), and their derivatives, have a long tradition in biomedical applications. Among them, the use of chitosan as a safe, biocompatible, and environmentally friendly heteropolysaccharide has been particularly intensively researched over the last two decades. The potential of using chitosan for medical purposes is reflected in its unique cationic nature, viscosity-increasing and gel-forming ability, non-toxicity in living cells, antimicrobial activity, mucoadhesiveness, biodegradability, as well as the possibility of chemical modification. The intuitive use of clay minerals in the treatment of superficial wounds has been known in traditional medicine for thousands of years. To improve efficacy and overcome the ubiquitous bacterial resistance, the beneficial properties of chitosan have been utilized for the preparation of chitosan–clay mineral bionanocomposites. The focus of this review is on composites containing chitosan with montmorillonite and halloysite as representatives of clay minerals. This review highlights the antibacterial efficacy of chitosan–clay mineral bionanocomposites in drug delivery and in the treatment of topical skin infections and wound healing. Finally, an overview of the preparation, characterization, and possible future perspectives related to the use of these advancing composites for biomedical applications is presented.
Enhanced Photodynamic Therapy Efficacy through Solid Lipid Nanoparticle of Purpurin-18-N-Propylimide Methyl Ester for Cancer Treatment
Authors: Yeo Sooho , Wu Huiqiang , Yoon Il , Kim Hye-Soo , Song Young Kyu , Lee Woo Kyoung
Published: September 2024

Photodynamic therapy (PDT) is an innovative cancer treatment that utilizes light. When light irradiates, purpurin-18-N-propylimide methyl ester (P18 N PI ME) generates reactive oxygen species that destroy cancer cells. The hydrophobic nature of P18 N PI ME presents challenges regarding its aggregation in the body, which can affect its effectiveness. This study aimed to enhance the bioavailability and effectiveness of cancer treatment by synthesizing P18 N PI ME and formulating P18 N PI ME-loaded solid lipid nanoparticles (SLNs). The efficacy of PDT was estimated using the 1,3-diphenylisobenzofuran (DPBF) assay and photocytotoxicity tests on the HeLa (human cervical carcinoma) and A549 (human lung carcinoma) cell lines. The P18 N PI ME-loaded SLNs demonstrated particle sizes in the range of 158.59 nm to 248.43 nm and zeta potentials in the range of –15.97 mV to –28.73 mV. These SLNs exhibited sustained release of P18 N PI ME. DPBF analysis revealed enhanced PDT effects with SLNs containing P18 N PI ME compared with standalone P18 N PI MEs. Photocytotoxicity assays indicated toxicity under light irradiation but no toxicity in the dark. Furthermore, the smallest-sized formulation exhibited the most effective photodynamic activity. These findings indicate the potential of P18 N PI ME-loaded SLNs as promising strategies for PDT in cancer therapy.
Linoleic Acid Induces Metabolic Reprogramming and Inhibits Oxidative and Inflammatory Effects in Keratinocytes Exposed to UVB Radiation
Authors: Manosalva Carolina , Bahamonde Claudio , Soto Franco , Leal Vicente , Ojeda César , Cortés Carmen , Alarcón Pablo , Burgos Rafael A.
Published: September 2024

Linoleic acid (LA), the primary ω-6 polyunsaturated fatty acid (PUFA) found in the epidermis, plays a crucial role in preserving the integrity of the skin’s water permeability barrier. Additionally, vegetable oils rich in LA have been shown to notably mitigate ultraviolet (UV) radiation-induced effects, including the production of reactive oxygen species (ROS), cellular damage, and skin photoaging. These beneficial effects are primarily ascribed to the LA in these oils. Nonetheless, the precise mechanisms through which LA confers protection against damage induced by exposure to UVB radiation remain unclear. This study aimed to examine whether LA can restore redox and metabolic equilibria and to assess its influence on the inflammatory response triggered by UVB radiation in keratinocytes. Flow cytometry analysis unveiled the capacity of LA to diminish UVB-induced ROS levels in HaCaT cells. GC/MS-based metabolomics highlighted significant metabolic changes, especially in carbohydrate, amino acid, and glutathione (GSH) metabolism, with LA restoring depleted GSH levels post-UVB exposure. LA also upregulated PI3K/Akt-dependent GCLC and GSS expression while downregulating COX-2 expression. These results suggest that LA induces metabolic reprogramming, protecting against UVB-induced oxidative damage by enhancing GSH biosynthesis via PI3K/Akt signaling. Moreover, it suppresses UVB-induced COX-2 expression in HaCaT cells, making LA treatment a promising strategy against UVB-induced oxidative and inflammatory damage.
Assessing Medical Student Lifestyle Medicine Skills Using an Objective Structured Clinical Examination
Authors: Kay Denise , Pasarica Magdalena , Hernandez Caridad A. , Castiglioni Analia , Kauffman Christine A. , Daroowalla Feroza , Rahman Saleh M. M.
Published: September 2024

(1) The purpose of this project was to create and collect validity evidence for a lifestyle medicine objective structured clinical examination (OSCE) station to assess medical students’ performance related to lifestyle medicine competencies. (2) We developed a lifestyle medicine case/station with an associated observation checklist and rubric. We piloted the checklist and rubric in one lifestyle medicine OSCE station, securing triplicate scores of each student’s performance. For analysis, generalizability (G) theory was utilized for observation checklist data and interclass correlation coefficients (ICC) for patient encounter notes (PENs). (3) One hundred and fifteen third-year medical students completed the lifestyle medicine OSCE station in the Internal and Family Medicine Clerkship. The generalizability coefficient and Phi-coefficient based on the number of encounters (P = 115), facet 1 (nfacet1 = 10 assessment tool checklist items), and facet 2 (nfacet2 = two performance ratings in the live examination) were 0.71 and 0.69, respectively. The average interclass correlation coefficient (ICC) measure for PEN was 0.79 (CI = 0.69–0.85). (4) For this OSCE station, the G-coefficient provides positive indicators for the validity of the observation checklist items. Similarly, the ICC result provides validity evidence for the usefulness of the PEN rubric for capturing lifestyle medicine knowledge reflected in students’ PEN notes.
Unlocking the Puzzle: Investigating the Role of Interleukin 17 Genetic Polymorphisms, Circulating Lymphocytes, and Serum Levels in Venezuelan Women with Recurrent Pregnancy Loss
Authors: Garmendia Jenny Valentina , Blanca Isaac , Peña María Johanna , De Sanctis Claudia Valentina , De Sanctis Juan Bautista
Published: September 2024

In recurrent pregnancy loss (RPL), peripheral and local immune cells are activated, decreasing the leukocyte tolerogenic response in the uterus and decidua. The aim was to examine the role of IL-17 in RPL critically. The study included genetic polymorphism, the analysis of the number of circulating IL-17 lymphocyte populations, before and after cell priming, serum cytokine quantification, and the assessment of T-reg cells in a group of 50 RPL and 50 normal women from the admixed Venezuelan population. The study found no differences in the genetic polymorphisms rs2275913 and rs763780. However, when IL-17+ cell populations of controls and RPL patients were compared, a significant increase was observed in the cell populations CD3+ and CD4+ (p < 0.001), while the contrary was recorded in CD8+ and CD56+ cells. Upon cell priming, all IL-17+ populations were significantly decreased (p < 0.001) in RPL patients compared to controls. The increase in IL-17A in the serum of RPL patients may be due to the CD4+ population, while cell exhaustion after activation could be responsible for decreased CD8+ cell population. The number of CD4CD25 FoxP3+ cells was significantly reduced (p < 0.001), and the number of activated HLADR+ cells was significantly increased (p < 0.001) in RPL patients. The absence of differences in the genetic polymorphism compared to controls suggests that biological factors influence IL-17 levels in RPL patients. This finding has significant implications for the understanding and potential treatment of RPL.
On the Extended Adjacency Eigenvalues of a Graph
Authors: Altassan Alaa , Ganie Hilal A. , Shang Yilun
Published: September 2024

Let H be a graph of order n with m edges. Let di=d(vi) be the degree of the vertex vi. The extended adjacency matrix Aex(H) of H is an n×n matrix defined as Aex(H)=(bij), where bij=12didj+djdi, whenever vi and vj are adjacent and equal to zero otherwise. The largest eigenvalue of Aex(H) is called the extended adjacency spectral radius of H and the sum of the absolute values of its eigenvalues is called the extended adjacency energy of H. In this paper, we obtain some sharp upper and lower bounds for the extended adjacency spectral radius in terms of different graph parameters and characterize the extremal graphs attaining these bounds. We also obtain some new bounds for the extended adjacency energy of a graph and characterize the extremal graphs attaining these bounds. In both cases, we show our bounds are better than some already known bounds in the literature.
Evaluating the Effects of Epichloë Fungal Endophytes of Perennial Ryegrass on the Feeding Behaviour and Life History of Rhopalosiphum padi
Authors: Collinson Nicholas Paul , Giri Khageswor , Kaur Jatinder , Spangenberg German , Malipatil Mallik , Mann Ross Cameron , Valenzuela Isabel
Published: September 2024

The bird cherry-oat aphid, Rhopalosiphum padi (L.), is an economically significant pest of pasture grasses, the latter being capable of hosting several fungal endophyte–perennial ryegrass symbiota rich in alkaloids and toxic to vertebrates and invertebrates. Measuring aphid feeding behaviour can provide insights into the effectiveness and mode of action of different fungal endophytes. This study investigated the effects of different Epichloë–perennial ryegrass symbiota on the feeding behaviour of R. padi using the electrical penetration graph technique while also assessing the aphid life history. In most cases, endophytes had significant feeding deterrence and paired fecundity and mortality effects. But, in some instances, endophytes with the highest aphid mortality did not significantly deter feeding, suggesting a more complicated scenario of interactions between the relative concentration of metabolites, e.g., host plant defence response metabolites and alkaloids, and/or physical changes to leaf morphology. Overall, this study sheds light on the mode of action of Epichloë endophytes against aphids and highlights the importance of Epichloë–perennial ryegrass symbiota in the management of insect pests such as aphids in pasture-based grazing systems.
Relationship between Respiratory Function and the Strength of the Abdominal Trunk Muscles Including the Diaphragm in Middle-Aged and Older Adult Patients
Authors: Kurokawa Yuki , Kato Satoshi , Yokogawa Noriaki , Shimizu Takaki , Matsubara Hidenori , Kabata Tamon , Demura Satoru
Published: September 2024

Objectives: Respiration plays an important function in sustaining life. The diaphragm is the primary muscle involved in respiration, and plays an important role in trunk stabilization. Although it has been reported that respiratory function is important for trunk muscle stability, the correlation between respiratory function and abdominal trunk muscle strength remains undetermined. This study aimed to clarify this correlation among middle-aged and older patients. Methods: This observational study included 398 patients scheduled for surgery for degenerative conditions of the lower extremities. Respiratory function was evaluated using forced vital capacity and forced expiratory volume in 1 s measured using spirometry. Each patient underwent a physical function test before surgery, which included the assessment of the abdominal trunk muscle strength, grip power, knee extensor strength, one-leg standing time, and gait speed. Correlations between abdominal trunk muscle strength, respiratory function, and physical function were evaluated. Results: Abdominal trunk muscle strength was significantly correlated with forced vital capacity, forced expiratory volume in 1 s, grip power, knee extensor strength, one-leg standing time, and gait speed. Multiple linear regression analyses revealed that sex, forced vital capacity, forced expiratory volume in 1 s, and knee extensor strength were significant factors associated with abdominal trunk muscle strength. Conclusions: In middle-aged and older patients, abdominal trunk muscle strength including that of the diaphragm, is associated with forced vital capacity and forced expiratory volume in 1 s.
Evaluation of Rehabilitation Outcomes in Patients with Chronic Neurological Health Conditions Using a Machine Learning Approach
Authors: Santilli Gabriele , Mangone Massimiliano , Agostini Francesco , Paoloni Marco , Bernetti Andrea , Diko Anxhelo , Tognolo Lucrezia , Coraci Daniele , Vigevano Federico , Vetrano Mario , Vulpiani Maria Chiara , Fiore Pietro , Gimigliano Francesca
Published: September 2024

Background: Over one billion people worldwide suffer from neurological conditions that cause mobility impairments, often persisting despite rehabilitation. Chronic neurological disease (CND) patients who lack access to continuous rehabilitation face gradual functional decline. The International Classification of Functioning, Disability, and Health (ICF) provides a comprehensive framework for assessing these patients. Objective: This study aims to evaluate the outcomes of a non-hospitalized neuromotor rehabilitation project for CND patients in Italy using the Barthel Index (BI) as the primary outcome measure. The rehabilitation was administered through an Individual Rehabilitation Plan (IRP), tailored by a multidisciplinary team and coordinated by a physiatrist. The IRP involved an initial comprehensive assessment, individualized therapy administered five days a week, and continuous adjustments based on patient progress. The secondary objectives include assessing mental status and sensory and communication functions, and identifying predictive factors for BI improvement using an artificial neural network (ANN). Methods: A retrospective observational study of 128 CND patients undergoing a rehabilitation program between 2018 and 2023 was conducted. Variables included demographic data, clinical assessments (BI, SPMSQ, and SVaMAsc), and ICF codes. Data were analyzed using descriptive statistics, linear regressions, and ANN to identify predictors of BI improvement. Results: Significant improvements in the mean BI score were observed from admission (40.28 ± 29.08) to discharge (42.53 ± 30.02, p < 0.001). Patients with severe mobility issues showed the most difficulty in transfers and walking, as indicated by the ICF E codes. Females, especially older women, experienced more cognitive decline, affecting rehabilitation outcomes. ANN achieved 86.4% accuracy in predicting BI improvement, with key factors including ICF mobility codes and the number of past rehabilitation projects. Conclusions: The ICF mobility codes are strong predictors of BI improvement in CND patients. More rehabilitation sessions and targeted support, especially for elderly women and patients with lower initial BI scores, can enhance outcomes and reduce complications. Continuous rehabilitation is essential for maintaining progress in CND patients.
Evaluating the Impact of Synthesised Scent Enrichment on Behavioural and Endocrine Responses in Captive Alaotran Gentle Lemurs (Hapalemur alaotrensis)
Authors: Costantini Anna Beatrice , Glendewar Gale , Fontani Sara , Vaglio Stefano
Published: September 2024

The Alaotran gentle lemur (Hapalemur alaotrensis) is one of the world’s most endangered primates and shows low success rates in captive breeding programmes. This study tested biologically relevant scent enrichment using two synthesised mixtures likely to convey information about female fertility on the behaviour of three unsuccessful breeding pairs in captivity. Specifically, we compared the baseline and enrichment periods by combining behavioural observations (n = 240 h) with faecal endocrinology (n = 80 samples), focussing on cortisol and testosterone measurements via enzyme immunoassay techniques. Then, we tested two different mixtures to assess potential behavioural differences and evaluate the effectiveness of olfactory enrichment using scented and unscented cotton strips. Olfactory behaviours differed by sex and enrichment conditions, with both sexes exhibiting increased behaviours during enrichment compared to the baseline. Sexual behaviours increased during the enrichment period, with variations in frequency between males and females depending on the condition. No significant changes were observed in faecal cortisol levels. However, one male showed a significant increase in testosterone during the second enrichment mixture. Nevertheless, overall differences between baseline and enrichment were not significant. Our findings suggest that while the scent enrichment showed limited effectiveness, biologically meaningful scents may trigger species-specific behaviours.
Phosphatidylcholine in Intestinal Mucus Protects against Mucosal Invasion of Microbiota and Consequent Inflammation
Authors: Stremmel Wolfgang , Weiskirchen Ralf
Published: September 2024

Intestinal mucus serves as the first line barrier within the mucosa to protect against microbiota attack due to its water-repellent properties, which are the result of the high abundance of phosphatidylcholine bound to mucins. A deficiency of mucus phosphatidylcholine predisposes it to mucosal inflammation by the attack of commensal microbiota, as it is intrinsically low in ulcerative colitis. However, for precipitation of an acute inflammatory episode, mucus phosphatidylcholine has to fall below the critical level required for mucosal protection. Bacterial ectophospholipase could be a candidate for further thinning of the mucus phosphatidylcholine shield as shown, for example, with the ectophospholipase containing Helicobacter pylori bacterium. Despite supporting evidence for this mechanism in the intestine, the responsible ectophospholipase-carrying bacteria species are still to be defined. Applying phosphatidylcholine to the lumen can serve to fill up empty mucin-binding sites in ulcerative colitis as well as provide a substrate for the ectophospholipase-carrying bacteria preventing their attacks on the mucus phosphatidylcholine layer. Evidence supporting this concept comes from clinical trials in humans with ulcerative colitis as well as from colitis mouse models where phosphatidylcholine was substituted in the lumen. An alternative strategy could involve adding non-absorbable phospholipase inhibitors to the intestinal lumen, which has been shown to be effective in a mouse model of ulcerative colitis. Bacterial phospholipase should be considered a pathogenetic factor of the intestinal microbiota and therapeutic strategies should be developed to prevent their hyperactivity for clinical improvement of intestinal inflammation.
Thiazolylketol Acetates as Glycosyl Donors: Stereoselective Synthesis of a C-Ketoside
Authors: Ferrari Clark , Dondoni Alessandro , Marra Alberto
Published: September 2024

We have already proven that thiazolylketol acetates, synthetised by addition of 2-lithiothiazole to sugar lactones followed by acetylation, are efficient glycosyl donors in the presence of O-, N-, and P-nucleophiles. We describe here their first use in the C-glycosidation using trimetylsilyl cyanide as the acceptor in order to prepare, after thiazole-to-formyl unmasking and reduction, the corresponding C-ketosides.
(R)-2-Amino-1-hydroxyethylphosphonic Acid
Authors: Motevalli Majid , Abrahams Isaac , Blakskjær Peter , Wyatt Caroline E. , Wyatt Peter B.
Published: September 2024

(R)-2-Amino-1-hydroxyethylphosphonic acid 2 was prepared by hydrolytic kinetic resolution of rac-diethyl oxiran-2-ylphosphonate followed by reaction with benzylamine, acid hydrolysis, catalytic hydrogenolysis, and anion-exchange chromatography. Recrystallization from water-ethanol gave pure 2, which was characterized by IR, 1H NMR, 13C NMR, 31P NMR, polarimetry, elemental microanalysis, high-resolution mass spectrometry, and single-crystal X-ray diffraction. The acid 2 crystallized in the orthorhombic noncentrosymmetric space group P212121 with cell parameters a = 6.303 (2) Å, b = 7.104 (2) Å, c = 11.627 (3) Å. The X-ray crystal structure confirmed the (R)-configuration of 2 and revealed that 2 is zwitterionic in the solid state, with extensive intermolecular hydrogen bonding between the hydroxyl, ammonium cation, and phosphonate anion groups.
The Influence of Alloy Composition on Microstructure and Performance of Mixed-Smelting Alloy and Weld Metal
Authors: Ge Guangnan , Hu Jin , Hu Zongqiu , Li Haijun , Huo Yan , Tang Shawei , Liu Yi , Ding Junfeng , Hou Shipu , Gao Yunbao
Published: September 2024

In the present work, the Q345B low-alloy steel with different contents and ER309L stainless steel were melted together to obtain new alloys. The aim was to design the composition of weld metal (Q345B low-alloy steel as the base material and ER309L welding wire as the filler material) and improve the corrosion resistance of the weld metal. During the welding process, the composition of the weld metal was controlled to match the new alloys by changing the welding heat input. A relationship curve between fusion ration and welding heat input was obtained. The research focused on analyzing the effect of mixed-smelting ratio between Q345B and ER309L and welding heat input on the microscopic structure and corrosion performance of the prepared samples. The results show that the melted alloys containing 20% to 30% Q345B consist of a ferrite (δ) phase and austenite (A) phase, the samples containing 45% to 50% Q345B consist of a martensite (M) phase and austenite (A) phase, and the sample containing 40% Q345B consists of a martensite (M) phase, ferrite (δ) phase, and austenite (A) phase. As the mixed-smelting ratio of Q345B/ER309L increased, the corrosion resistance of samples decreased gradually. For the weld metal, the fusion ration between Q345B base material and ER309L welding wire increases with the welding heat input. When the heat input changed from 0.645 kJ/mm to 2.860 kJ/mm, the composition of the weld metal was consistent with the melted alloys containing 20–45% Q345B. The microstructure and corrosion resistance of the weld metal could be designed by the melting means, which has important guiding significance for engineering applications.
Tensile Constitutive Model of Engineered Cementitious Composites Reinforced by High-Strength Steel Wire Mesh
Authors: Li Jing , Gao Ruiyuan , Wang Ang , Li Ke , Wu Di , Li Hao , Li Yuxuan
Published: September 2024

The presentation of a constitutive model could help researchers to predict the mechanical behavior of a material, which also contributes to the further generalization of the material. This paper is to explore the tensile constitutive model of engineered cementitious composites (ECCs) reinforced by high-strength steel wire mesh based on experiments and numerical simulations. DIANA was used to simulate the tensile process of the specimens, and experiments were carried out to validate the numerical model. The effect of the ECCs’ tensile strength, reinforcement ratio and specimen size were considered during the specimen design process. The results showed that most of the errors of the simulated values compared to the experimental results were within 5%, which proved that the numerical model was quite accurate. The proposed constitutive model revealed the different roles played by ECCs and high-strength steel wires at different stress stages, and the calculation results were in high agreement with the simulation results, indicating the effectiveness of the constitutive model. The study in this paper could provide an important reference for the popularization and application of ECCs reinforced by high-strength steel wire mesh.
The Influence of Local Constraints on Solvent Motion in Polymer Materials
Authors: Hałagan Krzysztof , Duniec Przemysław , Kozanecki Marcin , Sikorski Andrzej
Published: September 2024

The influence of obstacles in the form of polymer chains on the diffusion of a low-molecular-weight solvent was the subject of this research. Studies were performed by computer simulations. A Monte Carlo model—the Dynamic Lattice Liquid algorithm—based on the idea of cooperative movements was used. The tested materials were polymer networks with an ideal structure (with a uniform mesh size) and real, irregular networks (with a non-uniform mesh size) obtained numerically by copolymerization. The diffusion of the solvent was analyzed in systems with a polymer concentration that did not exceed 16%. The influence of the polymer concentration and macromolecular architecture structure on the mobility and character of the motion of the solvent was discussed. The influence of irregular network morphology on solvent dynamics appeared to be significantly stronger than that of regular networks and star-like polymers.