bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods to Stimulate the Proactivity of Enterprises in Fulfilling Safety Responsibilities: A Fundamental Issue in Construction Safety Management
Authors: Chang Beining , Yu Xiaosi , Liu Yachen
Published: October 2024

Management factors are among the most significant causes of construction safety incidents, and there is an issue of insufficient supervision at present. The degree of diligence exhibited by relevant entities is crucial, and the payoff can influence the decision-making behaviors of involved parties. Based on this, the aim of this paper is to investigate how to enhance the initiative of enterprises in fulfilling their safety responsibilities during the construction process. By developing a tripartite evolutionary game model that involves supervision companies, general contractors, and labor subcontractors and conducting numerical simulation analysis, we reveal that simultaneous proactive investment in safety by all three parties is challenging, with labor subcontractors being relatively more prone to opt for active safety investment. Supervision companies and general contractors often struggle to fulfill their safety duties at the same time. Factors such as the rewards and penalties stipulated in a contract, rent-seeking amounts, and accident-related losses have a significant impact on the evolution of the system. Based on the findings, we propose recommendations for construction management, which include the management of labor subcontracting in construction, the control of rent-seeking behaviors, and the establishment of a cooperative safety culture during the construction process.
Overcoming Irinotecan Resistance by Targeting Its Downstream Signaling Pathways in Colon Cancer
Authors: Saurav Shashank , Karfa Sourajeet , Vu Trung , Liu Zhipeng , Datta Arunima , Manne Upender , Samuel Temesgen , Datta Pran K.
Published: October 2024

Among the most popular chemotherapeutic agents, irinotecan, regarded as a prodrug belonging to the camptothecin family that inhibits topoisomerase I, is widely used to treat metastatic colorectal cancer (CRC). Although immunotherapy is promising for several cancer types, only microsatellite-instable (~7%) and not microsatellite-stable CRCs are responsive to it. Therefore, it is important to investigate the mechanism of irinotecan function to identify cellular proteins and/or pathways that could be targeted for combination therapy. Here, we have determined the effect of irinotecan treatment on the expression/activation of tumor suppressor genes (including p15Ink4b, p21Cip1, p27Kip1, and p53) and oncogenes (including OPN, IL8, PD-L1, NF-κB, ISG15, Cyclin D1, and c-Myc) using qRT-PCR, Western blotting, immunofluorescence (IF), and RNA sequencing of tumor specimens. We employed stable knockdown, neutralizing antibodies (Abs), and inhibitors of OPN, p53, and NF-κB to establish downstream signaling and sensitivity/resistance to the cytotoxic activities of irinotecan. Suppression of secretory OPN and NF-κB sensitized colon cancer cells to irinotecan. p53 inhibition or knockdown was not sufficient to block or potentiate SN38-regulated signaling, suggesting p53-independent effects. Irinotecan treatment inhibited tumor growth in syngeneic mice. Analyses of allograft tumors from irinotecan-treated mice validated the cell culture results. RNA-seq data suggested that irinotecan-mediated activation of NF-κB signaling modulated immune and inflammatory genes in mice, which may compromise drug efficacy and promote resistance. In sum, these results suggest that, for CRCs, targeting OPN, NF-κB, PD-L1, and/or ISG15 signaling may provide a potential strategy to overcome resistance to irinotecan-based chemotherapy.
Ganglioneuroma in Head and Neck: A Case Report of a Laryngeal Ganglioneuroma and a Systematic Review of the Literature
Authors: Gasparini Angela , Jiang Serena , Mani Riccardo , Tatta Tiziana , Gallo Oreste
Published: October 2024

Introduction: Ganglioneuroma (GN) is a rare, benign tumor of the autonomic nervous system. It is seldom located in the head and neck (HN) region. GN typically presents as a slow-growing, painless mass, often leading to delayed diagnosis. Case report: We report a unique case of laryngeal-originating GN in a 43-year-old female who presented with worsening dysphonia and dyspnea. Imaging revealed a large mass originating from the larynx. Histological examination confirmed the diagnosis. The tumor was surgically excised with preservation of key structures in the neck. At the follow-up, the patient experienced a significant improvement in symptoms. Material and methods: A systematic literature review following PRISMA guidelines was conducted in January 2024 to investigate the common sites of GN in the HN region and the complications associated with its treatment. Results: In a total of 58 articles, we studied 65 patients, mostly under 30 years old. Surgical excision remains the primary treatment, and post-operative complications were mostly neurological. Discussion: GNs are generally slow-growing and asymptomatic, but they can reveal themselves when compressing nearby structures, especially in the HN region. In symptomatic cases or when the tumor exhibits significant growth or hormonal activity, surgical resection is required. The lateral cervical approach is the most common one. The risk of postoperative complications and recurrence underscores the need for careful surgical planning and long-term follow-up. Conclusion: This unique laryngeal GN case highlights the importance of considering GN in the differential diagnosis of HN masses. Further large-scale studies are warranted to establish evidence-based protocols for their management, especially in the HN region.
Multiparametric Approach to the Colorectal Cancer Phenotypes Integrating Morphofunctional Assessment and Computer Tomography
Authors: Guirado-Peláez Patricia , Fernández-Jiménez Rocío , Sánchez-Torralvo Francisco José , Mucarzel Suárez-Arana Fernanda , Palmas-Candia Fiorella Ximena , Vegas-Aguilar Isabel , Amaya-Campos María del Mar , Martínez Tamés Gema , Soria-Utrilla Virginia , Tinahones-Madueño Francisco , García-Almeida José Manuel , Burgos-Peláez Rosa , Olveira Gabriel
Published: October 2024

(1) Background: Accurate body composition assessment in CCR patients is crucial due to the high prevalence of malnutrition, sarcopenia, and cachexia affecting survival. This study evaluates the correlation between body composition assessed by CT imaging as a reference technique, BIVA, nutritional ultrasound, and handgrip strength in CCR patients. (2) Methods: This retrospective study included CCR patients assessed by the Endocrinology and Nutrition Services of Virgen de la Victoria in Malaga and Vall d’Hebron in Barcelona from October 2018 to July 2023. Assessments included anthropometry, BIVA, NU, HGS, and AI-assisted CT analysis at the L3 level for body composition. Pearson’s analysis determined the correlation of CT-derived variables with BIVA, NU, and HGS. (3) Results: A total of 267 CCR patients (mean age 68.2 ± 10.9 years, 61.8% men) were studied. Significant gender differences were found in body composition and strength. CT-SMI showed strong correlations with body cell mass (r = 0.65), rectus femoris cross-sectional area (r = 0.56), and handgrip strength (r = 0.55), with a Cronbach’s alpha of 0.789. CT-based adipose tissue measurements showed significant correlations with fat mass (r = 0.56), BMI (r = 0.78), A-SAT (r = 0.49), and L-SAT (r = 0.66). Regression analysis indicated a high predictive power for CT-SMI, explaining approximately 80% of its variance (R2 = 0.796). (4) Conclusions: Comprehensive screening of colorectal cancer patients through BIVA, NU, HGS, and CT optimizes the results of the evaluation. These methods complement each other in assessing muscle mass, fat distribution, and nutritional status in CCR. When CT is unavailable or bedside assessment is needed, HGS, BIVA, and NU provide an accurate assessment of body composition.
Intraoperative Allogeneic Blood Transfusion Has No Impact on Postoperative Short-Term Outcomes After Pancreatoduodenectomy for Periampullary Malignancies: A Propensity Score Matching Analysis and Mediation Analysis
Authors: Ukegjini Kristjan , Warschkow René , Petrowsky Henrik , Müller Philip C. , Oberholzer José , Tarantino Ignazio , Jonas Jan Philipp , Schmied Bruno M. , Steffen Thomas
Published: October 2024

Background/Objectives: The aim of this study was to investigate the association between intraoperative blood transfusion (BT) and the short-term outcomes of pancreatoduodenectomy (PD) for patients with periampullary malignancies. Methods: In a retrospective two-center cohort analysis, we utilized a logistic and mixed-effects ordinal regression, nonparametric partial correlation, and mediation analysis, complemented by propensity score matching (PSM) and weighting. Results: A total of 491 patients were included. Of these, 18 (3.7%) received an intraoperative BT. An intraoperative BT was associated with blood loss (odds ratio (OR) per 100 mL = 1.42; 95% CI 1.27 to 1.62; p < 0.001) and relatively high ASA classes (OR = 3.75; 95% CI 1.05 to 17.74; p = 0.041). Intraoperative blood loss (r = 0.27; p < 0.001) but not intraoperative BT (r = 0.015; p = 0.698) was associated with postoperative complications. Intraoperative BT was associated with postoperative complications according to the unadjusted regression (OR = 1.95; 95% CI 1.38–2.42, p < 0.001) but not the multivariable ordinal regression. In the mediation analysis for relative risk (RR), intraoperative BT was beneficial (RR = 0.51; 95% CI: 0.01–0.78), and blood loss (RR = 2.49; 95% CI: 1.75–177.34) contributed to the occurrence of major postoperative complications. After PSM, analyses revealed that an intraoperative BT did not have a significant impact on the rates of postoperative major complications (OR = 1.048; p = 0.919), clinically relevant postoperative pancreatic fistula (OR = 0.573; p = 0.439) or postoperative 90-day mortality (OR = 0.714; p = 0.439). Conclusions: When adjusting for intraoperative blood loss, intraoperative BT is not associated with postoperative complications.
Underwater Techniques in Gastrointestinal Endoscopy: Diving into the Depths
Authors: Sferrazza Sandro , Calabrese Giulio , Maselli Roberta , Morais Rui , Facciorusso Antonio , Mavrogenis Georgios , Di Mitri Roberto , Repici Alessandro , Maida Marcello
Published: October 2024

The endoscopic resection of gastrointestinal tract lesions embraces different types of techniques, ranging from conventional polypectomy/endoscopic mucosal resection (EMR) to the field of third-space endoscopy, including endoscopic submucosal dissection (ESD), full-thickness resection and peroral endoscopic myotomy (POEM). Parallelly, the advent of underwater techniques has served as an add-on for both basic and advanced procedures, since its first report in 2012. We aimed to provide a comprehensive update on the state of the art about the feasibility of underwater basic and advanced techniques for GI endoscopy. Underwater EMR (U-EMR) has proved effective and safe in treating > 10 mm sessile or flat or all-size recurrent colonic lesions. Conversely, although data show good effectiveness and safety for <10 mm lesions, it is preferred when high-grade dysplasia is suspected, favouring cold snare polypectomy for all other cases. Moreover, promising data are emerging regarding the feasibility of U-ESD for difficult-to-resect colonic lesions. U-EMR represents a standard of care for treating < 25 mm superficial non-ampullary duodenal epithelial tumours. Data regarding oesophageal, gastric and ampullary lesions remains limited to small cohorts. Finally, using water immersion for POEM has shown a reduction in procedure time compared to the CO2 insufflation technique for vessel coagulation, albeit in a single-centre experience. Based on these results, U-EMR has become a standard for treating intermediate-size colonic and non-ampullary duodenal lesions, as highlighted also in the European Society of Gastrointestinal Endoscopy guidelines. Promising results have been shown in third-space endoscopy studies, even though further prospective studies are awaited to standardise the technique for both ESD and POEM.
Bringing Hope to Improve Treatment in Pancreatic Ductal Adenocarcinoma—A New Tool for Molecular Profiling of KRAS Mutations in Tumor and Plasma Samples
Authors: Bravo Ana Catarina , Morão Bárbara , Luz André , Dourado Rúben , Oliveira Beatriz , Guedes Ana , Moreira-Barbosa Catarina , Fidalgo Catarina , Mascarenhas-Lemos Luís , Costa-Santos Maria Pia , Maio Rui , Paulino Jorge , Viana Baptista Pedro , Fernandes Alexandra R. , Cravo Marília
Published: October 2024

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) incidence is rising, and prognosis remains poor due to late diagnosis and limited effective therapies. Currently, patients are treated based on TNM staging, without molecular tumor characterization. This study aimed to validate a technique that combines the amplification refractory mutation system (ARMS) with high-resolution melting analysis (HRMA) for detecting mutations in codon 12 of KRAS in tumor and plasma, and to assess its prognostic value. Methods: Prospective study including patients with newly diagnosed PDAC with tumor and plasma samples collected before treatment. Mutations in codon 12 of KRAS (G12D, G12V, G12C, and G12R) were detected using ARMS–HRMA and compared to Sanger sequencing (SS). Univariate and multivariate analyses were used to evaluate the prognostic significance of these mutations. Results: A total of 88 patients, 93% with ECOG-PS 0–1, 57% with resectable disease. ARMS–HRMA technique showed a higher sensitivity than SS, both in tumor and plasma (77% vs. 51%; 25 vs. 0%, respectively). The most frequent mutation was G12D (n = 32, 36%), followed by G12V (n = 22, 25%). On multivariate analysis, patients with G12D and/or G12C mutations, either in tumor or plasma, had lower PFS (HR 1.792, 95% CI 1.061–3.028, p = 0.029; HR 2.081, 95% CI 1.014–4.272, p = 0.046, respectively) and lower OS (HR 1.757, 95% CI 1.013–3.049, p = 0.045; HR 2.229, 95% CI 1.082–4.594, p = 0.030, respectively). Conclusions: ARMS–HRMA is a rapid and cost-effective method for detecting KRAS mutations in PDAC patients, offering the potential for stratifying prognosis and guiding treatment decisions. The presence of G12D and G12C mutations in both tumor and plasma is associated with a poorer prognosis.
The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment
Authors: Gonzalez Agurto Maria , Olivares Nicolas , Canedo-Marroquin Gisela , Espinoza Daniela , Tortora Sofia C.
Published: October 2024

Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4–5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota–host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking—a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors’ quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.
Comparative Study of Cutaneous Squamous Cell Carcinogenesis in Different Hairless Murine Models
Authors: Gkikas Georgios , Katsiris Dimitrios , Vitsos Andreas , Gioran Anna , Ieronymaki Dimitra , Kostaki Maria , Ladopoulos Georgios , Ioannidou Vaya , Theodoraki Elisavet , Chondrogianni Niki , Sfiniadakis Ioannis , Papaioannou Georgios T. , Rallis Michail Christou
Published: October 2024

Background: In recent decades, a significant global increase in the incidence of non-melanoma skin cancer has been observed. To explore the pathogenesis of and potential therapeutic approaches for squamous cell carcinoma, various in vivo studies using mouse models have been conducted. However, investigations comparing different hairless mouse models, with or without melanin, as well as models with hypercholesterolemia and immunosuppression, in terms of their ability to induce squamous cell carcinoma have yet to be undertaken. Methods: Four mouse strains, namely SKH-hr1, SKH-hr2, SKH-hr2+ApoE, and immunodeficient Nude (Foxn1 knockout), were exposed to UVA and UVB radiation three times per week, initially to 1 Minimal Erythemal Dose (MED), incrementally increased weekly to a maximum dose of 3 MED. Clinical evaluation, photodocumentation, and biophysical parameters were monitored, along with proteasome protein activity and histopathological assessments. Results: The SKH-hr1 model primarily developed actinic keratosis without significant progression to invasive squamous cell carcinoma (SCC), while the SKH-hr2 and SKH-hr2+ApoE models exhibited a higher likelihood and intensity of papilloma and aggressive SCC formation, with the latter showing upregulated proteasome activity. Histopathological analysis confirmed the presence of poorly differentiated, invasive SCCs in the SKH-hr2 and SKH-hr2+ApoE models, contrasting with the less aggressive SCCs in the Nude mice and the mixed lesions observed in the SKH-hr1 mice. Conclusions: The SKH-hr2+ApoE and SKH-hr2 mice were identified as the most suitable for further exploration of squamous cell carcinogenesis. In contrast, the SKH-hr1 mice were found to be the least suitable, even though they are albino. Notably, proteasome analysis revealed a potential role of proteasome activity in squamous cell carcinogenesis.
Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection
Authors: Sawai Katsuji , Goi Takanori , Kimura Youhei , Koneri Kenji
Published: October 2024

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p < 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.
Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer
Authors: Zhang Xiaobo , Han Bo , Shen Danhua
Published: October 2024

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People’s Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number—low (CNL), microsatellite instability—high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.
Lewis Acid-Base Site-Assisted In Situ Transesterification Catalysis to Produce Biodiesel
Authors: Zhang Zhuangzhuang , Meng Pan , Luo Hangyu , Pei Zhengfei , Liu Xiaofang
Published: October 2024

Biodiesel, a potent replacement for petroleum diesel, is derived from fatty acids in biomass through transesterification, which is renewable, non-toxic, and biodegradable and is a powerful replacement for petroleum diesel. Lewis acid has been proven effective for esterification and transesterification. The Lewis base enhances the electrophilic and nucleophilic properties of the molecules that bind to it, leading to the remarkable versatility of the Lewis base catalytic reaction. Many studies have shown that Lewis acid/base catalyzed in situ transesterification is a fast and environmentally friendly method for producing biodiesel. The utilization of Lewis acid-base sites to catalyze transesterification has been shown to enhance their efficiency and utilization of acid-base active sites. This review explores biodiesel production by different catalysts using Lewis acid-base sites, the conditions for catalytic transesterification, the effects of different reaction parameters on biodiesel production, and the biodiesel production process.
Recent Progress on the Synthesis and Applications of Zeolites from Industrial Solid Wastes
Authors: Zhang Wentao , Zhang Ting , Lv Yinmei , Jing Tao , Gao Xu , Gu Ziqi , Li Shiyang , Ao Hailing , Fang De
Published: October 2024

Zeolites have been increasingly applied in various fields such as energy conversion, environmental remediation, chemical production, and so on, being used as membranes, catalysts, and supports due to their large specific areas and strong gas adsorption. And, developing low-cost strategies for the preparation of zeolites has attracted the extensive attention of researchers. Coal fly ash, waste glass, discard zeolites, and slags are typical industrial wastes and rich in Si and Al, indicating that these industrial wastes can be utilized as alternative raw materials of zeolite synthesis. Firstly, the chemical composition and properties of these industrial wastes are summarized. Then, the strategies involved in synthesizing different zeolites from various industrial wastes are discussed. In addition, the applications of these zeolites are comprehensively reviewed.
Electrode Materials for NO Electroreduction Based on Dithiolene Metal–Organic Frameworks: A Theoretical Study
Authors: Fan Jiake , Yang Lei , Ye Lixin , Mei Mengyun , Zhu Weihua
Published: October 2024

To quickly and efficiently screen catalytic materials with both activity and selectivity for the nitric oxide reduction reaction (NORR), we adopted a strategy that considers the activity of the side reaction hydrogen evolution reaction (HER) first. It can be seen that Fe3(THT)2 (THT = triphenylene-2,3,6,7,10,11-hexathiol) has extremely excellent HER activity, with a Gibbs free energy change (ΔG) of 0.007 eV. Based on the relationship between ΔG and theoretical exchange current density, all TM3(THT)2 can be divided into two regions: one is the absolute values of ΔG greater than 1 eV, the other is the absolute values of ΔG greater than 0 eV and less than 1eV. Obviously, the candidates with the absolute values of ΔG greater than 1 eV have poor HER performance, but this precisely provides the possibility of obtaining NORR catalytic materials with both excellent selectivity and activity. Subsequent calculation results show that the maximum ΔG change of the rate-determining step of Ta3(THT)2 is unexpectedly only 0.05 eV. Therefore, Ta3(THT)2 may be regarded as the NORR catalytic material with both excellent performance and selectivity. Based on the electron transfer and partial density of states (PDOS) analysis, it can be seen that Ta plays a crucial role in the activation stage of NO. The approach that considers the activity of the side reaction HER first may provide a new idea for rapidly screening highly selective and active NORR catalysts.
Multispectral Imaging of Collagen, NAD(P)H and Flavin Autofluorescence in Mesenchymal Stem Cells Undergoing Trilineage Differentiation
Authors: Campbell Jared M. , Mahbub Saabah B. , Anwer Ayad G. , Habibalahi Abbas , Gronthos Stan , Paton Sharon , Grey Shane T. , Wu Lindsay E. , Gilchrist Robert B. , Goldys Ewa M.
Published: October 2024

Understanding the molecular mechanisms of differentiation is important for regenerative medicine and developmental biology. This study aims to characterise the role of the glycolysis/oxidative phosphorylation balance as a driver of mesenchymal stem cell (MSC) differentiation. Cells were maintained in normal conditions or stimulated towards the MSC trilineage cell types over 21 days. Multispectral imaging of cell autofluorescence was applied as a non-invasive methodology to continuously image cultures in situ. Spectral signals for collagen, NAD(P)H, and flavins were unmixed. MSCs cultured under chondrogenic conditions exhibited increased collagen levels relative to controls. Following osteogenic induction, MSCs showed increased collagen levels relative to controls during the earlier stages of culture; however, control cells increased their collagen levels as they became confluent. MSCs cultured under adipogenic conditions exhibited lower levels of collagen than controls. The redox ratio (RR; NAD(P)H/flavins) immediately decreased during chondrogenesis, with this early effect persisting throughout the culture compared to control cells, which appeared to increase their RR, similar to osteogenesis. Adipogenesis resulted in a small increase in RR on day 2 relative to control cells, followed by a persistent decrease. Chondrogenic and adipogenic differentiation favoured oxidative phosphorylation, whereas osteogenesis and MSC overgrowth resulted in a glycolytic metabolism. Following consideration of these findings, as well as the diverse reports in the literature, it is concluded that neither enhanced oxidative phosphorylation nor glycolysis are fundamental to the canonical modes of differentiation, and researchers should avoid interpreting shifts as indicating differentiation.
Apolipoprotein-L1 (APOL1): From Sleeping Sickness to Kidney Disease
Authors: Pays Etienne
Published: October 2024

Apolipoprotein-L1 (APOL1) is a membrane-interacting protein induced by inflammation, which confers human resistance to infection by African trypanosomes. APOL1 kills Trypanosoma brucei through induction of apoptotic-like parasite death, but two T. brucei clones acquired resistance to APOL1, allowing them to cause sleeping sickness. An APOL1 C-terminal sequence alteration, such as occurs in natural West African variants G1 and G2, restored human resistance to these clones. However, APOL1 unfolding induced by G1 or G2 mutations enhances protein hydrophobicity, resulting in kidney podocyte dysfunctions affecting renal filtration. The mechanism involved in these dysfunctions is debated. The ability of APOL1 to generate ion pores in trypanosome intracellular membranes or in synthetic membranes was provided as an explanation. However, transmembrane insertion of APOL1 strictly depends on acidic conditions, and podocyte cytopathology mainly results from secreted APOL1 activity on the plasma membrane, which occurs under non-acidic conditions. In this review, I argue that besides inactivation of APOL3 functions in membrane dynamics (fission and fusion), APOL1 variants induce inflammation-linked podocyte toxicity not through pore formation, but through plasma membrane disturbance resulting from increased interaction with cholesterol, which enhances cation channels activity. A natural mutation in the membrane-interacting domain (N264K) abrogates variant APOL1 toxicity at the expense of slightly increased sensitivity to trypanosomes, further illustrating the continuous mutual adaptation between host and parasite.
Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis
Authors: Skapinker Elizabeth , Aucoin Emilyn B. , Kombargi Haley L. , Yaish Abdulrahman M. , Li Yunfan , Baghaie Leili , Szewczuk Myron R.
Published: October 2024

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.
DNA-Binding Protein A Is Actively Secreted in a Calcium-and Inflammasome-Dependent Manner and Negatively Influences Tubular Cell Survival
Authors: Hoppstock Gregor , Lindquist Jonathan A. , Willems Antonia , Becker Annika , Reichardt Charlotte , Morgenroth Ronnie , Stolze Saskia , Zhu Cheng , Brandt Sabine , Mertens Peter R.
Published: October 2024

DNA-binding protein A (DbpA) belongs to the Y-box family of cold shock domain (CSD) proteins that bind RNA/DNA and exert intracellular functions in cell stress, proliferation, and differentiation. Given the pattern of DbpA staining in inflammatory glomerular diseases, without adherence to cell boundaries, we hypothesized extracellular protein occurrence and specific functions. Lipopolysaccharide and ionomycin induce DbpA expression and secretion from melanoma and mesangial cells. Unlike its homologue Y-box-binding protein 1 (YB-1), DbpA secretion requires inflammasome activation, as secretion is blocked upon the addition of a NOD-like receptor protein-3 (NLRP3) inhibitor. The addition of recombinant DbpA enhances melanoma cell proliferation, migration, and competes with tumor necrosis factor (TNF) binding to its receptor (TNFR1). In TNF-induced cell death assays, rDbpA initially blocks TNF-induced apoptosis, whereas at later time points (>24 h), cells are more prone to die. Given that CSD proteins YB-1 and DbpA fulfill the criteria of alarmins, we propose that their release signals an inherent danger to the host. Some data hint at an extracellular complex formation at a ratio of 10:1 (DbpA:YB-1) of both proteins.
Comparative Analysis of Extracellular Vesicles from Cytotoxic CD8+ αβ T Cells and γδ T Cells
Authors: Griesel Lisa , Kaleja Patrick , Tholey Andreas , Lettau Marcus , Janssen Ottmar
Published: October 2024

Background: Although belonging to different branches of the immune system, cytotoxic CD8+ αβ T cells and γδ T cells utilize common cytolytic effectors including FasL, granzymes, perforin and granulysin. The effector proteins are stored in different subsets of lysosome-related effector vesicles (LREVs) and released to the immunological synapse upon target cell encounter. Notably, in activated cells, LREVs and potentially other vesicles are continuously produced and released as extracellular vesicles (EVs). Presumably, EVs serve as mediators of intercellular communication in the local microenvironment or at distant sites. Methods: EVs of activated and expanded cytotoxic CD8+ αβ T cells or γδ T cells were enriched from culture supernatants by differential and ultracentrifugation and characterized by nanoparticle tracking analyses and Western blotting. For a comparative proteomic profiling, EV preparations from both cell types were isobaric labeled with tandem mass tags (TMT10plex) and subjected to mass spectrometry analysis. Results: 686 proteins were quantified in EV preparations of cytotoxic CD8+ αβ T cells and γδ T cells. Both populations shared a major set of similarly abundant proteins, while much fewer proteins presented higher abundance levels in either CD8+ αβ T cells or γδ T cells. To our knowledge, we provide the first comparative analysis of EVs from cytotoxic CD8+ αβ T cells and γδ T cells.
Climate Change, Land Use, and the Decline in Traditional Fulani Cattle Practices: Drivers of Antimicrobial Resistance in Kwara, Nigeria
Authors: Cole Jennifer , Adetona Mutiat , Basiru Afisu , Jimoh Wasiu , Abdulsalami Somrat , Ade-Yusuf Rodhiat , Babalola Karimat , Adetunji Victoria , Ahmed Akeem , Adeyemo Ismail , Olajide Abiola , Aremu Abdulfatai , Odetokun Ismail , Eltholth Mahmoud
Published: October 2024

This paper presents a case study of Fulani herdsmen in Nigeria, whose traditional ethnoveterinary practices risk being lost as the country transitions to more intensive and enclosed livestock practices. We use a planetary health framing to make visible the value of indigenous practices that are less damaging to the environment, animal welfare, and human health. Through ethnographic observation, focus group discussions (FGDs), and key stakeholder interviews, we show that the Fulani use a complex system of herbal medicines and traditional herding practices to maintain herd health, and to manage and treat animal disease when it arises. However, their traditions often sit uncomfortably with commercial farming practices. As traditional Fulani grazing lands are eroded, dispossessed Fulani take employment from businessmen farmers. Both parties’ inexperience with shed hygiene, artificial feed, and less environmentally resilient crossbreeds leads to an increased incidence of infectious disease. This, in turn, drives the higher use of antibiotics. There is, thus, a ‘causal chain’ of underlying drivers that lead, through poorer environmental, animal, and human health, to the increased use of antibiotics. The antibiotic resistance that emerges from this chain threatens human health now and in the future. Through a planetary health framing, we advocate for a deeper understanding of the knowledge held by Fulani herdsmen and their traditional ethnoveterinary practices as an alternative to increasing antibiotic use (ABU).
SERS-Driven Ceftriaxone Detection in Blood Plasma: A Protein Precipitation Approach
Authors: Dwivedi Aradhana , Ryabchykov Oleg , Liu Chen , Farnesi Edoardo , Schmidt Michael Stenbæk , Bocklitz Thomas , Popp Jürgen , Cialla-May Dana
Published: October 2024

Accurate detection of antibiotics in biological samples is essential for clinical diagnoses and therapeutic drug monitoring. This research examines how proteins and other substances in blood plasma affect the detection of the antibiotic ceftriaxone using surface-enhanced Raman spectroscopy (SERS). We detected ceftriaxone spiked in blood plasma without sample preparation within the range of 1 mg/mL to 50 µg/mL. By employing a pretreatment approach involving methanol-based protein precipitation to eliminate interfering substances from a spiked blood plasma solution, we could detect ceftriaxone down to 20 µg/mL. The comparative analysis demonstrates that the protein precipitation step enhances the sensitivity of SERS-based detection of drugs in the matrix blood plasma. The insights derived from this study are highly beneficial and can prove advantageous in developing new antibiotic detection methods that are both sensitive and selective in complex biological matrices. These methods can have important implications for clinical treatments.
A Biomimetic Chip with Dendrimer-Encapsulated Platinum Nanoparticles for Enhanced Electrochemiluminescence Detection of Cardiac Troponin I
Authors: Hui Yun , Kong Weijun , Shu Weiliang , Peng Zhiting , Shen Fengshan , Jiang Mingyang , Xu Zhen , Wu Tianzhun , Zhou Wenhua , Yu Xue-Feng
Published: October 2024

The measurement of cardiac troponin I (cTnI) is of vital importance for the early diagnosis of acute myocardial infarction. In this study, an enhanced electrochemiluminescent immunoassay for the highly sensitive and precise determination of cTnI was reported. A biomimetic chip with nepenthes peristome surface microstructures to achieve single-layer microbead arrays and integrated microelectrode arrays (MEAs) for ECL detection was microfabricated. Ru@SiO2 nanoparticles were prepared as signal amplificators labeling immunomagnetic beads. Dendrimer-encapsulated platinum nanoparticles (Pt DENs) were electrochemically modified on ITO MEAs. The resulting Pt DEN-modified ITO MEAs preserved good optical transparency and exhibited an approximately 20-fold ECL signal amplification compared to that obtained from bare ITO. The method made full use of the biomimetic chip with Pt DENs to develop single-layer immunomagnetic bead arrays with increasingly catalyzed electrochemical oxidation of the [Ru(bpy)3]2+–TPA system. Consequently, a limit of detection calculated as 0.38 pg/mL (S/N = 3) was obtained with excellent selectivity, demonstrating significant potential for the detection of cTnI in clinical diagnostics.
Trends in Nutritional Status and Dietary Behavior in School-Aged Children with Congenital Heart Defects
Authors: Tobias Dominik , Helm Paul Christian , Bauer Ulrike Maria Margarethe , Niessner Claudia , Hahn Sigrid , Siaplaouras Jannos , Apitz Christian
Published: October 2024

Background: Malnutrition and poor weight gain has been reported in infants with congenital heart defects (CHDs); however data in older children with CHDs are limited. In order to obtain representative data on the nutritional status, dietary behavior, and potential influencing factors in school-aged children with CHDs, we performed a nationwide online survey. Methods: Patients aged 6 to 17 years registered in the German National Register for CHDs were asked to participate in this study by completing the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) eating study questionnaire in order to assess their self-reported dietary habits. The use of the same questionnaire enabled a comparison with a representative subset of 4569 participants of the KiGGS study. Results: A total of 894 patients (mean age 12.5 ± 3.0 years; 47.2% female) were enrolled. Patients were allocated according to anatomic complexity into simple (23.8%), moderate (37.8%), and complex CHDs (38.4%). The consumption of sugar-containing food (p < 0.001) and fast food (p < 0.05) was significantly lower among the CHD patients than in the healthy children. Children with CHDs showed significantly lower body mass index (BMI) percentiles (p < 0.001) compared with their healthy peers, while children with complex and moderate CHDs had the lowest BMI. While in CHD patients, the BMI percentiles were not related to unhealthy food, there was a strong correlation with the CHD severity and number of previous interventions (p < 0.01). Conclusions: According to this nationwide survey, school-aged children with complex CHD are at risk of undernutrition, which is not due to dietary habits but to CHD severity and repeated surgery.
Effects of Oregano on Lactation Performance, Nutrient Digestibility, Ruminal Fermentation Parameters, and Methane Emissions in Dairy Cows: A Meta-Analysis
Authors: Mahdavi Ali , Darabighane Babak
Published: October 2024

Growing concerns regarding antibiotic use in livestock, due to antibiotic resistance and potential human transmission, have led to increased interest in herbs and their derivatives, including essential oils, which possess antimicrobial properties that may enhance overall productivity and serve as a strategy for methane mitigation. The objective of this meta-analysis was to investigate the effects of adding oregano to the diet in different forms (essential oils, plant materials, or leaves) on the dry matter intake (DMI), milk yield (MY), milk components, nutrient digestibility, ruminal fermentation parameters, and methane (CH4) emissions of dairy cows. A literature search was conducted to identify papers published from 2000 to 2023. Effect size for all outcomes was reported as a standardized means difference (SMD) and raw means difference with 95% confidence intervals. Heterogeneity was determined using the Q test and I2 statistic. The results of the meta-analysis indicated that adding oregano had no effect on DMI (SMD = 0.081; p = 0.507) and MY (SMD = 0.060; p = 0.665). Milk fat percentage, milk protein percentage, and milk lactose percentage were not affected by oregano. The addition of oregano to the diet significantly decreased dry matter digestibility (SMD = −0.502; p = 0.013), crude protein digestibility (SMD = −0.374; p = 0.040), and neutral detergent fiber digestibility (SMD = −0.505; p = 0.014). Ruminal pH (SMD = −0.122; p = 0.411), total volatile fatty acids concentration (SMD = −0.038; p = 0.798), acetate (SMD = −0.046; p = 0.757), propionate (SMD = 0.007; p = 0.960), and butyrate (SMD = 0.037; p = 0.801) proportion were not affected by oregano. The addition of oregano to the diet tended to decrease CH4/DMI (SMD = −0.275; p = 0.095) but did not affect CH4 production (SMD = −0.156; p = 0.282). Heterogeneity (Q and I2) was non-significant for all parameters. We conclude that the inclusion of oregano in various forms (essential oils, plant materials, or leaves) in the diet of dairy cows reduces nutrient digestibility but does not significantly affect DMI, MY, milk components, ruminal fermentation parameters, or CH4 production. Future research should focus on optimizing the dosage of oregano (both EOs and plant materials) and exploring the impact of its form on lactation, nutrient digestibility, ruminal fermentation, and CH4 emissions in dairy cows.
Research Progress on Environmental Corrosion Resistance of Thermal Barrier Coatings: A Review
Authors: Hu Xiaoyuan , Xie Ying , Li Faguo , Yin Fucheng
Published: October 2024

With the development of marine science and technology, marine construction is entering a new period of modern ocean development and utilization. The scale of marine development is expanding constantly. The lifespan of aircraft engines faces new challenges in marine environments. This paper reviews recent progress in the development of high-temperature coatings for aero-engines designed to resist marine atmospheric corrosion, with a focus on corrosion mechanisms, detection technologies, current research on marine atmospheric corrosion, standards for evaluating coating resistance, and novel advancements in coating materials.
Mechanical Properties of Spunlace Non-Wovens with a Porous Structure
Authors: Sąsiadek Michał , Dobrzańska-Danikiewicz Anna D. , Niedziela Maciej , Woźniak Waldemar , Szota Michał
Published: October 2024

The paper describes the influence of the drum system construction of two modern carding machines on the porous structure of spunlace non-wovens composed of polyester and viscose. The non-woven fabric structure, including the number and size of the pores, determines the tensile strength of the composites obtained. The spunlace non-wovens were subjected to tensile strength tests in the machine, and cross-directions and microscopic observations of their structure were made. The results of the experiments were used to determine the relationship between the strength of the material and the porosity of its structure. This knowledge was used to prepare recommendations for the manufacturer of wet wipes in order to enable the selection of a carding machine for the mass production of final products with strength properties that meet market requirements and satisfy the end customer.