bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermo-Acoustic Properties of Four Natural Fibers, Musa textilis, Furcraea andina, Cocos nucifera, and Schoenoplectus californicus, for Building Applications
Authors: Bravo-Moncayo Luis , Argotti-Gómez Marcelo , Jara Oscar , Puyana-Romero Virginia , Ciaburro Giuseppe , Guerrero Víctor H.
Published: July 2024

Natural and bio-based construction materials such as bamboo, cork, or natural fiber composites offer a promising solution for enhancing the environmental sustainability of buildings. In this sense, the paper presents an experimental thermo-acoustic characterization of four common Ecuadorian natural fibers, abaca (Musa textilis), cabuya (Furcraea andina), coir (Cocos nucifera), and totora (Schoenoplectus californicus). Different densities were considered, from 85 kg/m3 (Cabuya) to 244 kg/m3 (totora), to thermo-acoustically characterize the samples built with these fibers, by means of the guarded-hot-plate (GHP) and impedance tube methods in-lab experimental benches. The exhaustive original characterization of the evaluated natural fiber composites showed a promising overall thermo-acoustic behavior. The thermal conductivity of the fibers was around 0.04–0.06 W/m·K and, therefore, comparable to other materials such as polystyrene, polyurethane, or aerogel that are already utilized for similar applications. On the other hand, the sound-absorption properties of the evaluated fibers are also very competitive, but strongly affected by the thickness of the sample, with noise reduction coefficient NRC ranging from 0.12 to 0.53. Consequently, the production and distribution of these materials in the Ecuadorian market for thermal insulation and acoustic conditioning constitute an alternative characterized by good technical performance, which, compared to synthetic composites used in the construction industry for similar duties, is ecological, sustainable, and has low built-in energy consumption.
A Molecular Hypothesis on Malignant Transformation of Oral Lichen Planus: A Systematic Review and Meta-Analysis of Cancer Hallmarks Expression in This Oral Potentially Malignant Disorder
Authors: Keim-del Pino Carmen , Ramos-García Pablo , González-Moles Miguel Ángel
Published: July 2024

We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87–78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99–75.0), genome instability (48.44%, 95%CI = 13.54–84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93–90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27–74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.
Predicting the Diagnosis of Prostate Cancer with a Novel Blood-Based Biomarker: Comparison of Its Performance with Prostate-Specific Antigen
Authors: Sanders Johnmesha L. , Iczkowski Kenneth A. , Shah Girish V.
Published: July 2024

The purpose of this study was to assess the efficacy, specificity, and predictive value of a newly discovered biomarker, Zinc finger-like1 protein (referred to as neuroendocrine marker, NEM) for the detection of prostate cancer (PCa). We retrospectively analyzed banked plasma samples from 508 men, with a median age of 67 years (range 48–97), to compare the performance of NEM and PSA in predicting subsequent histologic PCa. The cohort consisted of four groups of patients visiting a urology clinic: (1) patients not diagnosed with either benign prostatic disease or prostate cancer (PCa) were defined as normal; (2) patients diagnosed with benign hyperplasia (BPH) but not PCa; (3) patients with confirmed PCa; and (4) patients with cancer other than PCa. The normal men displayed a mean NEM plasma level of 0.948 ± 0.051 ng/mL, which increased to 1.813 ± 0.315 ng/mL in men with BPH, 86.49 ± 15.51 ng/mL in men with PCa, and 10.47 ± 1.029 ng/mL in men with other Ca. The corresponding concentrations of prostate-specific antigen (PSA) in these subjects were 1.787 ± 0.135, 5.405 ± 0.699, 35.77 ± 11.48 ng/mL, and 8.036 ± 0.518, respectively. Receiver operating characteristic (ROC) curve analysis was performed to compare NEM and PSA performance, and the Jouden Index for each biomarker was calculated to determine cut-off points for each biomarker. The area under the ROC curve to predict PCa was 0.99 for NEM and 0.81 for PSA (p < 0.0001). The cut-off for NEM was at 1.9 ng/mL, with sensitivity of 98% and specificity of 97%. The corresponding PSA values were 4.4 ng/mL, with sensitivity of 76% and specificity of 95%. The predictive value of each biomarker in a patient was matched with his pathologic data to determine the accuracy of each biomarker. NEM was more accurate than PSA in differentiating cancer from benign conditions, such as BPH or prostatitis. In conclusion, NEM was a better predictor of PCa than PSA in patients visiting urology clinics. NEM tests, either alone or in conjunction with other biomarkers, provide a reliable, non-invasive, and inexpensive test to remarkably reduce false positives and thereby reduce the number of diagnostic biopsies and associated painful procedures and the loss of quality of life.
Three-Dimensional Cell Culture Micro-CT Visualization within Collagen Scaffolds in an Aqueous Environment
Authors: Tkachev Sergey , Chepelova Natalia , Galechyan Gevorg , Ershov Boris , Golub Danila , Popova Elena , Antoshin Artem , Giliazova Aliia , Voloshin Sergei , Efremov Yuri , Istranova Elena , Timashev Peter
Published: July 2024

Among all of the materials used in tissue engineering in order to develop bioequivalents, collagen shows to be the most promising due to its superb biocompatibility and biodegradability, thus becoming one of the most widely used materials for scaffold production. However, current imaging techniques of the cells within collagen scaffolds have several limitations, which lead to an urgent need for novel methods of visualization. In this work, we have obtained groups of collagen scaffolds and selected the contrasting agents in order to study pores and patterns of cell growth in a non-disruptive manner via X-ray computed microtomography (micro-CT). After the comparison of multiple contrast agents, a 3% aqueous phosphotungstic acid solution in distilled water was identified as the most effective amongst the media, requiring 24 h of incubation. The differences in intensity values between collagen fibers, pores, and masses of cells allow for the accurate segmentation needed for further analysis. Moreover, the presented protocol allows visualization of porous collagen scaffolds under aqueous conditions, which is crucial for the multimodal study of the native structure of samples.
Multi-Objective Optimization of Surface Integrity in the Grind-Hardening Process
Authors: Wang Chunyan , Wang Guicheng , Shen Chungen , Dai Xinyu
Published: July 2024

Grind-hardening machining is a new integrated manufacturing technology that integrates the theory of material surface quenching and grinding machining. The surface integrity of grind-hardening directly affects the performance and reliability of the parts. Improving the grind-hardening quality has always been the focus and difficulty in this field. Based on the surface integrity theory and the characteristics of the grind-hardening process, this paper proposed four optimization criteria for grinding parameters according to the engineering application requirements of materials. Using the expectation function, the burr cross-sectional area, depth of the effective hardened layer, and surface roughness were comprehensively analyzed under each optimization criterion to obtain an optimal combination of grinding parameters. The results revealed a significant inconsistency in the optimized grinding parameters under each optimization criterion. When considering the depth of the effective hardened layer as the primary optimization parameter and ignoring the surface roughness and burr cross-sectional area, the highest overall desirability was 0.926395. In practical application, the optimization criteria should be reasonably selected according to the actual engineering requirements.
Preparation of Highly Efficient and Stable All-Inorganic CsPbBr3 Perovskite Solar Cells Using Pre-Crystallization Multi-Step Spin-Coating Method
Authors: Zhang Yulong , Jiang Zhaoyi , Li Jincheng , Meng Guanxiong , Guo Jiajun , Zhang Weijia
Published: July 2024

All-inorganic CsPbBr3 perovskite solar cells have garnered extensive attention in the photovoltaic domain due to their remarkable environmental stability. Nevertheless, CsPbBr3 prepared using the conventional sequential deposition method suffers from issues such as inferior crystallinity, low phase purity, and poor film morphology. Herein, we propose a pre-crystallization methodology by introducing a minute quantity of CsBr into the PbBr2 precursor solution to generate a small amount of CsPb2Br5 crystals within the PbBr2 film, leading to a porous PbBr2 film with enhanced crystallinity. Under the influence of more pores and CsPb2Br5 crystals as nucleation sites for inducing growth, a CsPbBr3 film with a larger crystal size, lower grain boundary density, stronger crystallinity, and higher phase purity is formed. Compared with untreated devices, photovoltaic devices prepared using the pre-crystallization method achieved a champion photovoltaic conversion efficiency (PCE) of 8.62%. Furthermore, pre-crystallized devices demonstrate higher stability than untreated ones and can still retain 94% of the original PCE after being exposed to air for 1000 h without encapsulating.
Synthesis and Characterization of SiO2 Nanoparticles for Application as Nanoadsorbent to Clean Wastewater
Authors: Elizondo-Villarreal Nora , Gandara-Martínez Eleazar , García-Méndez Manuel , Gracia-Pinilla Miguel , Guzmán-Hernández Ana María , Castaño Víctor M. , Gómez-Rodríguez Cristian
Published: July 2024

By way of the sol–gel chemical synthesis method, it is possible to synthesize SiO2 nanoparticles with a defined specific particle size, a surface area, and a defined crystal structure that can be effectively used as a nanoadsorbent to remove various organic dyes. SiO2 nanoparticles were synthesized by the sol–gel method using sodium silicate (Na2SiO3) by a green method without using a tetraethyl orthosilicate (TEOS) precursor, which is very expensive and highly toxic. This sol–gel process involves the formation of a colloidal suspension (sol) and solid gelation to form a network in a continuous liquid phase (gel). In addition, it requires controlled atmospheres. XRD indicates the presence of an amorphous phase with a diffraction angle of 2θ = 23°, associated with SiO2. UV-Vis spectroscopy reveals an absorbance value in the region of 200 nm to 300 nm, associated with SiO2 nanoparticles. The application as a nanoadsorbent to remove dyes was measured, and it was found that the nanoparticles with the best performance were those that were synthesized with pH 7, showing a 97% removal with 20 mg of SiO2 nanoparticles in 60 min. Therefore, SiO2 nanoparticles can be used as a nanoadsorbent, using a low-cost and scalable method for application to remove methylene blue in an aqueous medium.
The Importance of the Type of Posterior Staphyloma in the Development of Myopic Maculopathy
Authors: Ruiz-Medrano Jorge , Puertas Mariluz , Flores-Moreno Ignacio , Almazán-Alonso Elena , García-Zamora María , Kudsieh Bachar , Ruiz-Moreno José M.
Published: July 2024

The objective of this paper was to determine how different types of posterior staphyloma (PS) may affect the appearance and degree of myopic maculopathy. A cross-sectional study was conducted, in which 467 eyes from 246 highly myopic patients [axial length (AL) ≥ 26 mm] were studied. A complete ophthalmic exploration was carried out on all patients, including imaging tests. The presence of macular PS was established as the main comparison variable between groups (macular PS vs. non-macular PS vs. non-PS). The variables analyzed included age, AL, decimal best-corrected visual acuity (BCVA), Atrophy (A)/Traction (T)/Neovascularization (N) components according to the ATN grading system, and the presence of severe pathologic myopia (PM). Out of the total, 179 eyes (38.3%) presented macular PS, 146 eyes presented non-macular PS (31.2%), and 142 eyes showed no PS (30.4%). The group without PS was significantly younger than macular PS and non-macular PS groups (53.85 vs. 66.57 vs. 65.20 years; p < 0.001 each, respectively). There were no age differences between PS groups. Eyes with macular PS (31.47 ± 2.30 mm) were significantly longer than those with non-macular PS (28.68 ± 1.78 mm, p < 0.001) and those without PS (27.47 ± 1.34 mm, p < 0.001). BCVA was significantly better in the non-PS group (0.75 ± 0.27) compared to the non-macular PS (0.56 ± 0.31) and macular PS groups (0.43 ± 0.33), with p < 0.001 each. Eyes without PS showed significantly lower A and T components (1.31 ± 0.96 and 0.30 ± 0.53, respectively) than non-macular PS (2.21 ± 0.75 and 0.71 ± 0.99, respectively, p < 0.001 each) and macular PS eyes (2.83 ± 0.64 and 1.11 ± 1.10, respectively, p < 0.001 each). The N component was lower in non-PS eyes vs. non-macular PS eyes (0.20 ± 0.59 vs. 0.47 ± 0.83, p < 0.001) and as compared to the macular PS group (0.68 ± 0.90, p < 0.01). Additionally, the N component was significantly lower in the non-macular PS group than in the macular PS one (p < 0.05). The prevalence of severe PM was different between groups (p < 0.001). It was higher among macular PS eyes (138/179) when compared to other groups (p < 0.001, each), followed by the non-macular PS eyes (40/146) and being the lowest in the non-PS group (20/142). To conclude, macular PS is associated with a more advanced maculopathy, worse vision, and higher rates of severe PM.
WI-TMLEGA: Weight Initialization and Training Method Based on Entropy Gain and Learning Rate Adjustment
Authors: Tang Hongchuan , Li Zhongguo , Wang Qi , Fan Wenbin
Published: July 2024

Addressing the issues of prolonged training times and low recognition rates in large model applications, this paper proposes a weight training method based on entropy gain for weight initialization and dynamic adjustment of the learning rate using the multilayer perceptron (MLP) model as an example. Initially, entropy gain was used to replace random initial values for weight initialization. Subsequently, an incremental learning rate strategy was employed for weight updates. The model was trained and validated using the MNIST handwritten digit dataset. The experimental results showed that, compared to random initialization, the proposed initialization method improves training effectiveness by 39.8% and increases the maximum recognition accuracy by 8.9%, demonstrating the feasibility of this method in large model applications.
Optimal Process Design for Wake-Up Free Hf0.5Zr0.5O2 Ferroelectric Capacitors: Toward Low-Power Devices with Enhanced Ferroelectric Performance
Authors: Wang Hui , Qi Jiabin , Xie Xinyu , Liu Zongfang , Wu Wenhao , Lee Choonghyun
Published: July 2024

Ferroelectric hafnium and zirconium oxides have recently garnered significant attention due to their potential applications in in-memory computing. In this study, we present an optimized process design for a wake-up free 15 nm thick Hf0.5Zr0.5O2 (HZO) ferroelectric capacitor by fine-tuning the dual-oxygen process and incorporating oxygen annealing after post-metallization annealing (PMA). The optimized approach resulted in a competitive polarization of 28.6 μC/cm2, consistently exceeding 25 μC/cm2 at 3 V after 2 × 107 cycles, showcasing a current density of 3.2 mA/cm2 at 2 V after 105 cycles. The synergistic effect of oxygen vacancies and grain properties (grain size, phase proportion) enables competitive ferroelectric polarization at lower voltages, while the generation of WOx near the top electrode and increased grain size further ensure the reliability of the HZO ferroelectric capacitor. This work presents innovative perspectives for the development of non-volatile devices characterized by low leakage current and low power consumption.
Learning Curves of Harvester Operators in a Simulator Environment
Authors: Polowy Krzysztof , Rutkowski Dariusz
Published: July 2024

Simulator training helps provide safe and cost-effective training for operators of modern forestry machines that require high motor skills, constant concentration, and proper planning. The aim of the study was to analyze the learning curves of the trainees in order to determine the period during which most development takes place. In this study, 11 trainees were trained on a John Deere harvester simulator for approximately 15 h each. In each case, a clear learning curve could be identified, despite high inter- and intra-person variability. Effective time showed a steady decrease during training, with a group minimum at the end of training (1.25 min). Crane tip distance per tree dropped rapidly in the first 3–4 h, followed by a more gradual decrease to reach a minimum of 23.8 m. Crane control showed a significant increase from an initial 0.63 to a maximum of 0.8 by the 9th hour of training. A number of crane functions used simultaneously increased more rapidly to almost a maximum value (1.8) already in the 5th hour. The individual curves for each trainee were highly variable, showing a wide range of values and shapes. In conclusion, most personal development occurs during the first phase of simulator training, which typically takes approximately 9–10 h. It is important to consider significant inter-personal variability and tailor the duration of simulator training to individual needs.
Utilizing the pH-Shift Method for Isolation and Nutritional Characterization of Mantis Shrimp (Oratosquilla nepa) Protein: A Strategy for Developing Value-Added Ingredients
Authors: Chumthong Kanchanaphon , Saelee Nisa , Panpipat Worawan , Panya Atikorn , Phonsatta Natthaporn , Thangvichien Sujichon , Mala-in Wannasa , Grossmann Lutz , Chaijan Manat
Published: July 2024

This study focused on the production of protein isolates from mantis shrimp (MS). The pH-shift method was investigated to understand its impact on the protein yield, quality, and properties of the produced isolates. The first step was determining how the pH affected the protein solubility profile, zeta potential, and brown discoloration. The pH-shift process was then established based on the maximum and minimum protein solubilization. The solubilization pH had a significant impact on the mass yield and color of the produced protein, with a pH of 1.0 producing the maximum mass in the acidic region, whereas a maximum was found at a pH of 12.0 in the alkaline region (p < 0.05). Both approaches yielded mantis shrimp protein isolates (MPIs) with precipitation at a pH of 4.0 and a mass yield of around 25% (dw). The TCA-soluble peptide and TBARS levels were significantly lower in the MPI samples compared to MS raw material (p < 0.05). The MPIs maintained essential amino acid index (EAAI) values greater than 90%, indicating a high protein quality, and the pH-shift procedure had no negative impact on the protein quality, as indicated by comparable EAAI values between the mantis shrimp protein isolate extract acid (MPI-Ac), mantis shrimp protein isolate extract alkaline (MPI-Al), and MS raw material. Overall, the pH-shift approach effectively produced protein isolates with favorable quality and nutritional attributes.
Knowledge and Practice toward DEXA Scan among Women in Jazan City, Saudi Arabia
Authors: Dhayihi Turki M. , Haqawi Nawaf F. , Hakami Sarah A. , Harthi Fahad M. , Moafa Sarah H. , Alawi Yahya M. , Abutaleb Yazeed B. , Areshy Nadim I. , Hendi Ali M.
Published: July 2024

Background: Osteoporosis, characterized by reduced bone mass and increased fracture risk, presents a significant public health challenge. Dual-energy X-ray Absorptiometry (DEXA) scans offer a reliable means of assessing bone mineral density (BMD) and detecting osteoporosis. The aim of this study is to assess awareness, attitude, and practice of women in the Jazan region toward DEXA scan. Methods: Data were collected through a self-administered online questionnaire. Statistical analysis was conducted using SPSS version 29.0. The total knowledge scores of participants were calculated to assess potential associations with sociodemographic data. A p-value of less than 0.05 was considered statistically significant. Results: Among 400 women, 230 (57.5%) had low knowledge scores primarily due to poor knowledge of the DEXA scan procedure. Merely 39 women had undergone a DEXA scan mainly due to medical prescription (n = 22, 56.4%). Total knowledge scores were significantly higher among women with high monthly incomes (p = 0.019) and those working in medical-related jobs (p = 0.017). Conclusions: This study underscores the need for targeted interventions to improve awareness of DEXA scans among women in Jazan City. Additionally, the findings suggest that socioeconomic factors may influence awareness levels, emphasizing the importance of tailored educational strategies to reach diverse demographics.
Impact of the Clinical Pharmacist in Rheumatology Practice: A Systematic Review
Authors: Barat Eric , Soubieux Annaelle , Brevet Pauline , Gerard Baptiste , Vittecoq Olivier , Lequerre Thierry , Chenailler Catherine , Varin Rémi , Lattard Claire
Published: July 2024

This is a systematic literature review on the impact of pharmacists in rheumatology, conducted using the PubMed®, CINAHL®, Cochrane Library®, and Web of science® databases and using the PRISMA 2020 checklist. This review was conducted from 2000 to June 2024. A quality analysis was performed. The selection of articles, as well as all analyses, including quality analyses, were conducted by a pair of pharmacists with experience in rheumatology, and included 24 articles. This study highlights the growth of clinical pharmacy activities in rheumatology and the positive influence of clinical pharmacists on patient care. The implementation of such initiatives has the potential to improve medication adherence, reduce medication-related risks, and optimize associated healthcare costs. All these pharmaceutical interventions aim to make the patient care journey smoother and safer. Additionally, the diversity of available pharmaceutical services caters to the varied needs of rheumatology. Furthermore, outpatient clinical pharmacy is also explored in this field and garners interest from patients. The vast majority of studies demonstrate significant improvement in patient care with promising performance outcomes when pharmacists are involved. This review highlights the diverse range of interventions by clinical pharmacists in rheumatology, which is very promising. However, to better assess the benefits of clinical pharmacists, this activity needs further development and evaluation through controlled and randomized clinical research programs.
The Leafy-Stem-Buried Etiolation Contributed to the High Efficiency of Rootstock Vegetative Propagation in Avocado (Persea americana)
Authors: Li Weiming , Ma Xiaowei , Wang Songbiao , Huang Wenshan , Jiang Mingguo
Published: July 2024

Because of their tolerance to root rot and many abiotic stresses, rootstocks are generally required for commercial avocado production. However, cutting and air-layering, which are popular methods of vegetative propagation for producing large numbers of uniform and genetically identical plants, have been unsuccessful for years. To develop a practical and efficient rooting procedure for selected avocado clonal rootstocks, the present research investigated the effects of various factors on rooting cutting. Shoots were divided into three groups (air layering, direct cutting, and stem-buried etiolation) and treated with different combinations (plant growth regulators, PGRs; soaking time; and culture media), in which orthogonal or randomized-block designs were used. The rooting rate, average root length, average root number, average root dry weight, and rooting quality (Q value) were used as evaluation indicators. The results show that etiolation treatment of the mother shoot is the requisite condition for avocado shoot rooting. In addition, the rooting effect of etiolated cuttings was strongly impacted by PGR type, concentration, and soaking time, whereas no significant differences were detected among the culture media. Among these factors, the roots and the survival rates of etiolated cuttings of two hard-to-root varieties were optimal under the following conditions: indolebutyric acid concentration of 2500 mg/L, dipping duration for 5 s, and perlite:vermiculite culture at 1:1. The rooting rate of ‘Dusa’ was generally greater than that of ‘Duke 7’ and reached 82%.
Castor Meal and Ground Hydrothermalized Phonolite Optimize Sweet Potato Nutrition, Yield, and Quality
Authors: Parecido Renan J. , Soratto Rogério P. , Fernandes Adalton M. , Blanes Mayara C. , Fidelis Luis G. , Gitari Harun I. , Dutra Sérgio G.
Published: July 2024

To assess the effect of pure castor meal and a mixture of castor meal with ground hydrothermalized phonolite rock (CM+HP mixture) in providing nutrients, particularly N and K, and optimizing yield and quality of sweet potato, a field experiment was conducted using a randomized block design. Treatments were the absence and presence of synthetic N and K fertilizers (ammonium nitrate and KCl) combined with rates of organic fertilizers (1.2 and 2.4 Mg ha−1 of castor meal, 2.25 and 4.5 Mg ha−1 of CM+HP mixture, plus a treatment without organic fertilizers). The CM+HP mixture maintained adequate N and K status in plant leaves. Organic fertilizers increased the number of storage roots per plant and the sweetness of the storage roots, while synthetic fertilizers increased the storage root mean weight. Castor meal combined with synthetic fertilizers improved soil health (increased organic matter and enzyme activity in the soil). The combined application of synthetic fertilizers with 2.4 Mg ha−1 of castor meal or 4.5 Mg ha−1 of CM+HP mixture had the greatest benefit on storage root yield, with an average increase of 128% (10.9 Mg ha−1) on marketable storage root yield, and the nutrient removal compared with the sole application of organic fertilizers.
Biochemical Studies on Human Ornithine Aminotransferase Support a Cell-Based Enzyme Replacement Therapy in the Gyrate Atrophy of the Choroid and Retina
Authors: Pampalone Gioena , Chiasserini Davide , Pierigè Francesca , Camaioni Emidio , Orvietani Pier Luigi , Bregalda Alessandro , Menotta Michele , Bellezza Ilaria , Rossi Luigia , Cellini Barbara , Magnani Mauro
Published: July 2024

The gyrate atrophy of the choroid and retina (GACR) is a rare genetic disease for which no definitive cure is available. GACR is due to the deficit of ornithine aminotransferase (hOAT), a pyridoxal 5′-phosphate-dependent enzyme responsible for ornithine catabolism. The hallmark of the disease is plasmatic ornithine accumulation, which damages retinal epithelium leading to progressive vision loss and blindness within the fifth decade. Here, we characterized the biochemical properties of tetrameric and dimeric hOAT and evaluated hOAT loaded in red blood cells (RBCs) as a possible enzyme replacement therapy (ERT) for GACR. Our results show that (i) hOAT has a relatively wide specificity for amino acceptors, with pyruvate being the most suitable candidate for ornithine catabolism within RBCs; (ii) both the tetrameric and dimeric enzyme can be loaded in RBC retaining their activity; and (iii) hOAT displays reduced stability in plasma, but is partly protected from inactivation upon incubation in a mixture mimicking the intracellular erythrocyte environment. Preliminary ex vivo experiments indicate that hOAT-loaded RBCs are able to metabolize extracellular ornithine at a concentration mimicking that found in patients, both in buffer and, although with lower efficiency, in plasma. Overall, our data provide a proof of concept that an RBC-mediated ERT is feasible and can be exploited as a new therapeutic approach in GACR.
A Bioinformatic Assay of Quercetin in Gastric Cancer
Authors: Zúñiga-Hernández Sergio Raúl , García-Iglesias Trinidad , Macías-Carballo Monserrat , Pérez-Larios Alejandro , Gutiérrez-Mercado Yanet Karina , Camargo-Hernández Gabriela , Rodríguez-Razón Christian Martín
Published: July 2024

Gastric cancer (GC) remains a significant global health challenge, with high mortality rates, especially in developing countries. Current treatments are invasive and have considerable risks, necessitating the exploration of safer alternatives. Quercetin (QRC), a flavonoid present in various plants and foods, has demonstrated multiple health benefits, including anticancer properties. This study investigated the therapeutic potential of QRC in the treatment of GC. We utilized advanced molecular techniques to assess the impact of QRC on GC cells, examining its effects on cellular pathways and gene expression. Our findings indicate that QRC significantly inhibits GC cell proliferation and induces apoptosis, suggesting its potential as a safer therapeutic option for GC treatment. Further research is required to validate these results and explore the clinical applications of QRC in cancer therapy.
Synergistic Enhancement of Chemotherapy-Induced Cell Death and Antitumor Efficacy against Tumoral T-Cell Lymphoblasts by IMMUNEPOTENT CRP
Authors: Rivera-Lazarín Ana Luisa , Calvillo-Rodríguez Kenny Misael , Izaguirre-Rodríguez Mizael , Vázquez-Guillén José Manuel , Martínez-Torres Ana Carolina , Rodríguez-Padilla Cristina
Published: July 2024

T-cell malignancies, including T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), present significant challenges to treatment due to their aggressive nature and chemoresistance. Chemotherapies remain a mainstay for their management, but the aggressiveness of these cancers and their associated toxicities pose limitations. Immunepotent CRP (ICRP), a bovine dialyzable leukocyte extract, has shown promise in inducing cytotoxicity against various cancer types, including hematological cancers. In this study, we investigated the combined effect of ICRP with a panel of chemotherapies on cell line models of T-ALL and T-LBL (CEM and L5178Y-R cells, respectively) and its impact on immune system cells (peripheral blood mononuclear cells, splenic and bone marrow cells). Our findings demonstrate that combining ICRP with chemotherapies enhances cytotoxicity against tumoral T-cell lymphoblasts. ICRP + Cyclophosphamide (CTX) cytotoxicity is induced through a caspase-, reactive oxygen species (ROS)-, and calcium-dependent mechanism involving the loss of mitochondrial membrane potential, an increase in ROS production, and caspase activation. Low doses of ICRP in combination with CTX spare non-tumoral immune cells, overcome the bone marrow-induced resistance to CTX cell death, and improves the CTX antitumor effect in vivo in syngeneic Balb/c mice challenged with L5178Y-R. This led to a reduction in tumor volume and a decrease in Ki-67 proliferation marker expression and the granulocyte/lymphocyte ratio. These results set the basis for further research into the clinical application of ICRP in combination with chemotherapeutic regimens for improving outcomes in T-cell malignancies.
Overcoming Vemurafenib Resistance in Metastatic Melanoma: Targeting Integrins to Improve Treatment Efficacy
Authors: Boz Er Asiye Busra , Sheldrake Helen M. , Sutherland Mark
Published: July 2024

Metastatic melanoma, a deadly form of skin cancer, often develops resistance to the BRAF inhibitor drug vemurafenib, highlighting the need for understanding the underlying mechanisms of resistance and exploring potential therapeutic strategies targeting integrins and TGF-β signalling. In this study, the role of integrins and TGF-β signalling in vemurafenib resistance in melanoma was investigated, and the potential of combining vemurafenib with cilengitide as a therapeutic strategy was investigated. In this study, it was found that the transcription of PAI1 and p21 was induced by acquired vemurafenib resistance, and ITGA5 levels were increased as a result of this resistance. The transcription of ITGA5 was mediated by the TGF-β pathway in the development of vemurafenib resistance. A synergistic effect on the proliferation of vemurafenib-resistant melanoma cells was observed with the combination therapy of vemurafenib and cilengitide. Additionally, this combination therapy significantly decreased invasion and colony formation in these resistant cells. In conclusion, it is suggested that targeting integrins and TGF-β signalling, specifically ITGA5, ITGB3, PAI1, and p21, may offer promising approaches to overcoming vemurafenib resistance, thereby improving outcomes for metastatic melanoma patients.
Gallic Acid Enhances the Efficacy of BCR::ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia through Inhibition of Mitochondrial Respiration and Modulation of Oncogenic Signaling Pathways
Authors: Xiang Wei , Sng Colin , Lam Yi-Hui , Kok Ze-Hui , Linn Yeh-Ching , Neo Soek-Ying , Siew Yin-Yin , Singh Deepika , Koh Hwee-Ling , Chuah Charles
Published: July 2024

While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography–electrospray ionization–mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34+ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient ρ0 cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.
Disparities in Genetic Diversity Drive the Population Displacement of Two Invasive Cryptic Species of the Bemisia tabaci Complex in China
Authors: Xue Yantao , Wang Yusheng , Chen Jiqiang , Zhang Guifen , Liu Wanxue , Wan Fanghao , Zhang Yibo
Published: July 2024

Within the whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) complex, two cryptic species, namely Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED), are important invasive pests affecting global agriculture and horticulture. They were introduced into China sequentially in the mid-1990s and around 2003, respectively. Subsequently, the latter invader MED has outcompeted the earlier invader MEAM1, becoming the dominant population in the field. Although extensive studies have explored the underlying mechanisms driving this shift, the contribution of population genetics remains notably underexplored. In this study, we analyzed the genetic diversity and structure of 22 MED and 8 MEAM1 populations from various regions of China using mitochondrial DNA sequencing and microsatellite genotyping. Our results indicate low and moderate levels of genetic differentiation among geographically separate populations of MED and MEAM1, respectively. Median-joining network analysis of mtCOI gene haplotypes revealed no clear geographic structuring for either, with common haplotypes observed across provinces, although MED had more haplotypes. Comparative analyses revealed that MED presented greater genetic diversity than MEAM1 on the basis of two markers. Furthermore, analysis of molecular variance supported these findings, suggesting that while some genetic variation exists between populations, a significant amount is also present within populations. These findings reveal the population genetics of the two invasive cryptic species of the B. tabaci complex in China and suggest that the disparities in genetic diversity drive the displacement of their populations in the field. This work also provides valuable information on the genetic factors influencing the population dynamics and dominance of these invasive whitefly species.
Genome-Wide Identification and Characterization of U-Box Gene Family Members and Analysis of Their Expression Patterns in Phaseolus vulgaris L. under Cold Stress
Authors: Wang Jiawei , Liu Zhiyuan , She Hongbing , Xu Zhaosheng , Zhang Helong , Fang Zhengwu , Qian Wei
Published: July 2024

The common bean (Phaseolus vulgaris L.) is an economically important food crop grown worldwide; however, its production is affected by various environmental stresses, including cold, heat, and drought stress. The plant U-box (PUB) protein family participates in various biological processes and stress responses, but the gene function and expression patterns of its members in the common bean remain unclear. Here, we systematically identified 63 U-box genes, including 8 tandem genes and 55 non-tandem genes, in the common bean. These PvPUB genes were unevenly distributed across 11 chromosomes, with chromosome 2 holding the most members of the PUB family, containing 10 PUB genes. The analysis of the phylogenetic tree classified the 63 PUB genes into three groups. Moreover, transcriptome analysis based on cold-tolerant and cold-sensitive varieties identified 4 differentially expressed PvPUB genes, suggesting their roles in cold tolerance. Taken together, this study serves as a valuable resource for exploring the functional aspects of the common bean U-box gene family and offers crucial theoretical support for the development of new cold-tolerant common bean varieties.
Computational Insights into Reproductive Toxicity: Clustering, Mechanism Analysis, and Predictive Models
Authors: Cui Huizi , He Qizheng , Li Wannan , Duan Yuying , Han Weiwei
Published: July 2024

Reproductive toxicity poses significant risks to fertility and progeny health, making its identification in pharmaceutical compounds crucial. In this study, we conducted a comprehensive in silico investigation of reproductive toxic molecules, identifying three distinct categories represented by Dimethylhydantoin, Phenol, and Dicyclohexyl phthalate. Our analysis included physicochemical properties, target prediction, and KEGG and GO pathway analyses, revealing diverse and complex mechanisms of toxicity. Given the complexity of these mechanisms, traditional molecule-target research approaches proved insufficient. Support Vector Machines (SVMs) combined with molecular descriptors achieved an accuracy of 0.85 in the test dataset, while our custom deep learning model, integrating molecular SMILES and graphs, achieved an accuracy of 0.88 in the test dataset. These models effectively predicted reproductive toxicity, highlighting the potential of computational methods in pharmaceutical safety evaluation. Our study provides a robust framework for utilizing computational methods to enhance the safety evaluation of potential pharmaceutical compounds.
Hypersensitivity of Intrinsically Photosensitive Retinal Ganglion Cells in Migraine Induces Cortical Spreading Depression
Authors: Nagata Eiichiro , Takao Motoharu , Toriumi Haruki , Suzuki Mari , Fujii Natsuko , Kohara Saori , Tsuda Akio , Nakayama Taira , Kadokura Ayana , Hadano Manaka
Published: July 2024

Migraine is a complex disorder characterized by episodes of moderate-to-severe, often unilateral headaches and generally accompanied by nausea, vomiting, and increased sensitivity to light (photophobia), sound (phonophobia), and smell (hyperosmia). Photophobia is considered the most bothersome symptom of migraine attacks. Although the underlying mechanism remains unclear, the intrinsically photosensitive retinal ganglion cells (ipRGCs) are considered to be involved in photophobia associated with migraine. In this study, we investigated the association between the sensitivity of ipRGCs and migraines and cortical spreading depression (CSD), which may trigger migraine attacks. The pupillary responses closely associated with the function of ipRGCs in patients with migraine who were irradiated with lights were evaluated. Blue (486 nm) light irradiation elicited a response from ipRGCs; however, red light (560 nm) had no such effect. Melanopsin, a photosensitive protein, phototransduces in ipRGCs following blue light stimulation. Hypersensitivity of ipRGCs was observed in patients with migraine. CSD was more easily induced with blue light than with incandescent light using a mouse CSD model. Moreover, CSD was suppressed, even in the presence of blue light, after injecting opsinamide, a melanopsin inhibitor. The hypersensitivity of ipRGCs in patients with migraine may induce CSD, resulting in migraine attacks.
A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A)
Authors: Oláh Attila , Barta Bálint András , Ruppert Mihály , Sayour Alex Ali , Nagy Dávid , Bálint Tímea , Nagy Georgina Viktória , Puskás István , Szente Lajos , Szőcs Levente , Sohajda Tamás , Zima Endre , Merkely Béla , Radovits Tamás
Published: July 2024

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension. Landrace pigs were divided into the following experimental groups: iNO (inhaled nitric oxide, n = 3), SIN-1A-5 (5 mg, n = 3), and SIN-1A-10 (10 mg, n = 3). Parallel insertion of a PiCCO system and a pulmonary artery catheter (Swan-Ganz) was performed for continuous hemodynamic monitoring. The impact of iNO (15 min) and SIN-1A inhalation (30 min) was investigated under physiologic conditions and U46619-induced acute pulmonary hypertension. Mean pulmonary arterial pressure (PAP) was reduced transiently by both substances. SIN-1A-10 had a comparable impact compared to iNO after U46619-induced pulmonary hypertension. PAP and PVR decreased significantly (changes in PAP: −30.1% iNO, −22.1% SIN-1A-5, −31.2% SIN-1A-10). While iNO therapy did not alter the mean arterial pressure (MAP) and systemic vascular resistance (SVR), SIN-1A administration resulted in decreased MAP and SVR values. Consequently, the PVR/SVR ratio was markedly reduced in the iNO group, while SIN-1A did not alter this parameter. The pulmonary vasodilatory impact of inhaled SIN-1A was shown to be dose-dependent. A larger dose of SIN-1A (10 mg) resulted in decreased PAP and PVR in a similar manner to the gold standard iNO therapy. Inhalation of the nebulized solution of the new SIN-1A formulation (stabilized by a cyclodextrin derivative) might be a valuable, effective option where iNO therapy is not available due to dosing difficulties or availability.
Investigating Expression Dynamics of miR-21 and miR-10b in Glioblastoma Cells In Vitro: Insights into Responses to Hypoxia and Secretion Mechanisms
Authors: Charbit Hanna , Lavon Iris
Published: July 2024

Glioblastoma poses significant challenges in oncology, with bevacizumab showing promise as an antiangiogenic treatment but with limited efficacy. microRNAs (miRNAs) 10b and 21 have emerged as potential biomarkers for bevacizumab response in glioblastoma patients. This study delves into the expression dynamics of miR-21 and miR-10b in response to hypoxia and explores their circulation mechanisms. In vitro experiments exposed glioma cells (A172, U87MG, U251) and human umbilical vein endothelial cells (HUVEC) to hypoxic conditions (1% oxygen) for 24 h, revealing heightened levels of miR-10b and miR-21 in glioblastoma cells. Manipulating miR-10b expression in U87MG, demonstrating a significant decrease in VEGF alpha (VEGFA) following miR-10b overexpression under hypoxic conditions. Size exclusion chromatography illustrated a notable shift towards miR-21 and miR-10b exosomal packaging during hypoxia. A proposed model suggests that effective bevacizumab treatment reduces VEGFA levels, heightening hypoxia and subsequently upregulating miR-21 and miR-10b expression. These miRNAs, released via exosomes, might impact various cellular processes, with miR-10b notably contributing to VEGFA level reduction. However, post-treatment increases in miR-10b and miR-21 could potentially restore cells to normoxic conditions through the downregulation of VEGF. This study highlights the intricate feedback loop involving miR-10b, miR-21, and VEGFA in glioblastoma treatment, underscoring the necessity for personalized therapeutic strategies. Further research should explore clinical implications for personalized glioma treatments.
Ribosome Pausing Negatively Regulates Protein Translation in Maize Seedlings during Dark-to-Light Transitions
Authors: Hou Mingming , Fan Wei , Zhong Deyi , Dai Xing , Wang Quan , Liu Wanfei , Li Shengben
Published: July 2024

Regulation of translation is a crucial step in gene expression. Developmental signals and environmental stimuli dynamically regulate translation via upstream small open reading frames (uORFs) and ribosome pausing. Recent studies have revealed many plant genes that are specifically regulated by uORF translation following changes in growth conditions, but ribosome-pausing events are less well understood. In this study, we performed ribosome profiling (Ribo-seq) of etiolated maize (Zea mays) seedlings exposed to light for different durations, revealing hundreds of genes specifically regulated at the translation level during the early period of light exposure. We identified over 400 ribosome-pausing events in the dark that were rapidly released after illumination. These results suggested that ribosome pausing negatively regulates translation from specific genes, a conclusion that was supported by a non-targeted proteomics analysis. Importantly, we identified a conserved nucleotide motif downstream of the pausing sites. Our results elucidate the role of ribosome pausing in the control of gene expression in plants; the identification of the cis-element at the pausing sites provides insight into the mechanisms behind translation regulation and potential targets for artificial control of plant translation.