bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Contact Evaluation of Deformation Characteristics on Automotive Steel Sheets
Authors: Ambriško Ľubomír , Pešek Ladislav
Published: May 2024

The work is focused on experimental research of deformation characteristics on three grades of hot-dip galvanized steels for the automotive industry. Deformation maps were obtained using the DIC (Digital Image Correlation) method. The map documents the development of longitudinal and transverse deformations under tensile stress. In addition to uniaxial tension, the investigated specimens were subjected to eccentric tension. The stable crack growth (SCG) was evaluated using a non-contact measurement technique on CT (compact tension) specimens. The deformation of steels, which affects the resistance to stable crack growth (confirmed by the Design of Experiments—DOE method), was manifested in the first stages of eccentric loading of specimens. The notch root radius varies considerably due to the blunting of the starting fatigue crack. The resistance to stable crack growth, which represents a safety reserve during a vehicle crash, was obtained.
Improving the Corrosion Resistance of Micro-Arc Oxidization Film on AZ91D Mg Alloy through Silanization
Authors: Liu Junchi , Yin Hang , Xu Zhengyi , Shao Yawei , Wang Yanqiu
Published: May 2024

The presence of inherent micro-pores and micro-cracks in the micro-arc oxidation (MAO) film of Mg alloys is a key factor contributing to substrate corrosion. A composite film layer with high corrosion resistance was achieved through silanizing the micro-arc oxidation film. The corrosion performance of the MAO films treated with various silane coupling agents was assessed through morphological characterization and electrochemical tests. SEM graphs depicted that the silane film can effectively seal the defects existing in micro-arc oxidation film, and electrochemical tests indicated the significant corrosion resistance improvement of MAO film after silanization treatment.
Influence of Ti Vacancy Defects on the Dissolution of O-Adsorbed Ti(0001) Surface: A First-Principles Study
Authors: Wang Xiaoting , Xie Dong , Jing Fengjuan , Ma Donglin , Leng Yongxiang
Published: May 2024

To investigate the dissolution mechanism of Ti metal, ab initio calculations were conducted to observe the impact of Ti vacancy defects on the O-adsorbed Ti(0001) surface, focusing on the formation energies of Ti vacancy, geometric structures, and electronic structures. The surface structures subsequent to Ti dissolution were simulated by introducing a Ti cavity on both clean and O-adsorbed Ti(0001) surfaces. Our findings indicated that Ti vacancy formation energies and electrochemical dissolution potential on the O-adsorbed Ti(0001) surface surpassed those on the clean surface, and they increased with increasing O coverage. This suggested that O adsorption inhibited Ti dissolution and enhanced O atom interaction with the Ti surface as O coverage increased. Furthermore, at higher O coverage, Ti vacancies contributed to the strengthening of Ti-O bonds on the O-adsorbed Ti(0001) surface, indicating that Ti dissolution aided in stabilizing the Ti surface. The formation of Ti vacancies brought the atomic ratio of Ti to O on the Ti surface closer to that of TiO2, potentially explaining the increased stability of the structure with Ti vacancies.
Thermomechanical Pathways for Accurate Microstructural Control of Ti–7Ag Alloy: Towards a New Generation of Antibacterial Materials for Medical Applications
Authors: Deya Julie , Delannoy Stéphanie , Vermaut Philippe , Prima Frédéric
Published: May 2024

This study delved into exploring microstructural states in a Ti–7Ag alloy to achieve targeted functional and structural properties. Specifically, the focus was on attaining a homogeneously precipitated state and a solid solution, known for their potential to combine functional traits like corrosion resistance and antibacterial activity with structural properties such as mechanical strength. However, obtaining these optimized microstructures presents challenges due to kinetic considerations. A key finding of this study was the crucial role of a pre-deformation stage, prior to heat treatment, to create an even distribution of fine Ti2Ag precipitates. Moreover, we demonstrated that starting from this precipitated state, a controlled dissolution step could yield a single-phase solid solution with similar grain size. Therefore, a tailored set of thermomechanical treatments was developed to achieve both microstructures, and these metallurgical states were fully characterized combining SEM (BSE imaging and EDS analysis), TEM, and XRD. Associated mechanical properties were also assessed by tensile testing. In addition, the process was proven to be robust enough to overcome potential industrial problems, such as slow cooling rates when water-quenching large ingots. Considering the limited existing documentation on microstructural features in Ti–Ag alloys, this work on this model alloy significantly advanced our current understanding of the broader Ti–Ag alloy system by providing new data and showcasing a tailored approach involving thermomechanical treatments.
Research on and Application of Feature Recognition and Intelligent Retrieval Method for Multi-Component Alloy Powder Injection Molding Gear Based on Partition Templates
Authors: Kong Yan , Cui Xiaoyi , Zhang Zhibing , Liu Yuqi
Published: May 2024

The forming process of multi-alloy gears by metal powder injection molding is tedious, and the current design process mainly depends on the experience of designers, which seriously affects the product development cycle and forming quality. In order to solve the problem of the gear feature expression being missing, which hinders the automatic retrieval of similar parts in the analogical design process, a feature recognition and intelligent retrieval method for a multi-alloy powder injection molding gear based on partition templates is proposed in this paper. The partition templates of the gear are defined, and gear digitization is completed by using the automatic recognition algorithm. Searching for similar gear parts in the knowledge base, designers can analogically design the forming process for new parts according to the mature process of the parts in the knowledge base. The automatic identification and intelligent retrieval system developed according to this method has been implemented in two MIM (metal injection molding) product manufacturing enterprises. Case studies and industrial applications have proved the effectiveness of the system, the efficiency of identification and retrieval has been improved by more than 97%, and the number of mold tests has been reduced by 60%.
Integrative BNN-LHS Surrogate Modeling and Thermo-Mechanical-EM Analysis for Enhanced Characterization of High-Frequency Low-Pass Filters in COMSOL
Authors: Davalos-Guzman Jorge , Chavez-Hurtado Jose L. , Brito-Brito Zabdiel
Published: May 2024

This paper pioneers a novel approach in electromagnetic (EM) system analysis by synergistically combining Bayesian Neural Networks (BNNs) informed by Latin Hypercube Sampling (LHS) with advanced thermal–mechanical surrogate modeling within COMSOL simulations for high-frequency low-pass filter modeling. Our methodology transcends traditional EM characterization by integrating physical dimension variability, thermal effects, mechanical deformation, and real-world operational conditions, thereby achieving a significant leap in predictive modeling fidelity. Through rigorous evaluation using Mean Squared Error (MSE), Maximum Learning Error (MLE), and Maximum Test Error (MTE) metrics, as well as comprehensive validation on unseen data, the model’s robustness and generalization capability is demonstrated. This research challenges conventional methods, offering a nuanced understanding of multiphysical phenomena to enhance reliability and resilience in electronic component design and optimization. The integration of thermal variables alongside dimensional parameters marks a novel paradigm in filter performance analysis, significantly improving simulation accuracy. Our findings not only contribute to the body of knowledge in EM diagnostics and complex-environment analysis but also pave the way for future investigations into the fusion of machine learning with computational physics, promising transformative impacts across various applications, from telecommunications to medical devices.
Mineral Assemblages and Ore-Forming Physicochemical Conditions of the La’erma and Qiongmo Au–Se Deposits in the Western Qinling Orogen, Central China
Authors: Liu Jiajun , Weng Guoming , Carranza Emmanuel John M. , Zhai Degao , Wang Yinhong , Zhang Fangfang , Gao Shen , Xu Lei
Published: May 2024

The La’erma and Qiongmo Au–Se deposits are characterized by a paragenetic Au–Se association hosted in the siliceous formation of the Cambrian Taiyangding Group in the western Qinling Orogen, central China. The La’erma and Qiongmo Au–Se deposits, which are considered to be the Carlin gold deposits, comprise a variety of selenides, native gold, and stibnite coexisting with baryte. Four stages have been recognized: sage I comprises pyrite and quartz with minor stibnite; stage II is composed mainly of sulfides; stage III is composed mainly of selenides; and stage IV is dominated by quartz–baryte–dickite. Stages II and III are the main metallogenic stages. Based on changes in mineral assemblages, combined with fluid inclusions and thermodynamic data, we evaluated the physicochemical conditions of the main metallogenic stages. The logfS2 values of ore-forming fluids at stage II ranged between −10.44 and −14.60 with logfSe2 being less than −10.70. Comparably, during stage III, which is characterized by numerous selenides, the logfS2 and logfSe2 ranged from −7.13 to −12.20 and −13.98 to −8.82, respectively. The occurrence of baryte during the mineralization suggests a consistently oxidizing condition, which can effectively remove Au from fluids. More importantly, this study emphasizes that the oxidizing condition was only a fundamental prerequisite for the deposition of selenides, and a high ∑Se/S ratio of the fluid ultimately controlled the precipitation of selenides. In the La’erma and Qiongmo deposits, intense water–rock reactions occurred as ore-forming fluids flowed into the Se-rich siliceous formations, resulting in an increase in the ∑Se/S ratio of the fluid and in the precipitation of selenides.
Characteristics and Genetic Mechanism of Granite Weathering Crust of Songnan Low Uplift, Qiongdongnan Basin, South China Sea
Authors: Li Zhiyu , Guo Jianhua , Wu Shiqing
Published: May 2024

Recently, a large-scale gas reservoir was discovered in granitic buried hills of the Songnan Low Uplift in the Qiongdongnan Basin. However, the strong heterogeneity of granite reservoirs limits further exploration and evaluation. Based on observations of sixty core samples and sixty thin sections, mineral composition, zircon dating, apatite fission tracks, physical properties, image logs, outcrop surveys and seismic interpretations, the characteristics of granite weathering crust of the Songnan Low Uplift are analyzed, and its controlling factors and evolution process are evaluated. The results show that weathered granite in the study area can be divided into several zones, from top to bottom: eluvium–slope zone, sandy zone, weathered fracture zone and horizontal undercurrent vuggy zone. The reservoirs in the eluvium–slope zone are dominated by microfissures and intergranular dissolution pores and have an average porosity of 4.68% and permeability of 2.34 md; the reservoirs in the sandy zone are composed of intergranular and intragranular dissolution pores and have an average porosity of 11.46% and permeability of 4.99 md; the reservoirs in the weathered fracture zone consist of various fractures and have an average porosity of 3.91% and permeability of 2.5 md; the reservoirs in the horizontal undercurrent vuggy zone are subhorizontal fractures and vugs and have an average porosity of 2.7% and permeability of 0.23 md. The development of granite reservoirs is jointly influenced by petrology and minerals, long-term exposure in a warm humid paleoclimate, faults, diverse topographies and shallow buried depth. Based on the above, our study establishes a development model of weathering crust and suggests that only the gentle slope and platform remain strongly weathered zones. After undergoing a complex evolution process of formation–destruction/denudation–regeneration–preservation, the current weathering crust of the Songnan Low Uplift is finally established. The results of this study have important theoretical and application value for the hydrocarbon exploration of buried hills in the Qiongdongnan Basin and provide a reference example for other granite reservoirs worldwide.
The Involvement of Ascorbic Acid in Cancer Treatment
Authors: Guo Di , Liao Yuan , Na Jintong , Wu Liangliang , Yin Yao , Mi Zhengcheng , Fang Shixu , Liu Xiyu , Huang Yong
Published: May 2024

Vitamin C (VC), also known as ascorbic acid, plays a crucial role as a water-soluble nutrient within the human body, contributing to a variety of metabolic processes. Research findings suggest that increased doses of VC demonstrate potential anti-tumor capabilities. This review delves into the mechanisms of VC absorption and its implications for cancer management. Building upon these foundational insights, we explore modern delivery systems for VC, evaluating its use in diverse cancer treatment methods. These include starvation therapy, chemodynamic therapy (CDT), photothermal/photodynamic therapy (PTT/PDT), electrothermal therapy, immunotherapy, cellular reprogramming, chemotherapy, radiotherapy, and various combination therapies.
Experimental and Machine-Learning-Assisted Design of Pharmaceutically Acceptable Deep Eutectic Solvents for the Solubility Improvement of Non-Selective COX Inhibitors Ibuprofen and Ketoprofen
Authors: Cysewski Piotr , Jeliński Tomasz , Przybyłek Maciej , Mai Anna , Kułak Julia
Published: May 2024

Deep eutectic solvents (DESs) are commonly used in pharmaceutical applications as excellent solubilizers of active substances. This study investigated the tuning of ibuprofen and ketoprofen solubility utilizing DESs containing choline chloride or betaine as hydrogen bond acceptors and various polyols (ethylene glycol, diethylene glycol, triethylene glycol, glycerol, 1,2-propanediol, 1,3-butanediol) as hydrogen bond donors. Experimental solubility data were collected for all DES systems. A machine learning model was developed using COSMO-RS molecular descriptors to predict solubility. All studied DESs exhibited a cosolvency effect, increasing drug solubility at modest concentrations of water. The model accurately predicted solubility for ibuprofen, ketoprofen, and related analogs (flurbiprofen, felbinac, phenylacetic acid, diphenylacetic acid). A machine learning approach utilizing COSMO-RS descriptors enables the rational design and solubility prediction of DES formulations for improved pharmaceutical applications.
Formation of Microporous Poly Acrylonitrile-Co-Methyl Acrylate Membrane via Thermally Induced Phase Separation for Immiscible Oil/Water Separation
Authors: Tan Linli , Wang Yuqi , Li Mingpu
Published: May 2024

An interconnected sponge structure and porous surface poly (acrylonitrile-co-methyl acrylate) (P(AN-MA)) microfiltration membranes (MF) were fabricated via thermally induced phase separation (TIPS) by using caprolactam (CPL), and acetamide (AC) as the mixed diluent. When the ternary system was composed of 15 wt.% P(AN-MA), 90 wt.% CPL, and 10 wt.% AC and formed in a 25 °C air bath, the membrane exhibited the highest water flux of 8107 L/m2·h. The P(AN-MA) membrane contained hydrophobic groups (-COOCH3) and hydrophilic groups (-CN), leading it to exhibit oleophobic properties underwater and hydrophobic properties in oil. The membrane demonstrates efficient separation of immiscible oil/water mixtures. The pure water flux of the petroleum ether/water mixture measured 870 L/m2·h, and the pure oil flux of the petroleum tetrachloride/water mixture measured 1230 L/m2·h under the influence of gravity. Additionally, the recovery efficiency of diluents through recrystallization was 85.3%, significantly reducing potential pollution and production costs.
Discovery of Nine Dipeptidyl Peptidase-4 Inhibitors from Coptis chinensis Using Virtual Screening, Bioactivity Evaluation, and Binding Studies
Authors: Zhao Zixi , Ma Ruonan , Ma Yuqing , Zhao Liqiang , Wang Lele , Fang Yuzhen , Zhang Yuxin , Wu Xia , Wang Xing
Published: May 2024

The objective of this study was to identify multiple alkaloids in Coptis chinensis that demonstrate inhibitory activity against DPP-4 and systematically evaluate their activity and binding characteristics. A combined strategy that included molecular docking, a DPP-4 inhibition assay, surface plasmon resonance (SPR), and a molecular dynamics simulation technique was employed. The results showed that nine alkaloids in Coptis chinensis directly inhibited DPP-4, with IC50 values of 3.44–53.73 μM. SPR-based binding studies revealed that these alkaloids display rapid binding and dissociation characteristics when interacting with DPP-4, with KD values ranging from 8.11 to 29.97 μM. A molecular dynamics analysis revealed that equilibrium was rapidly reached by nine DPP-4–ligand systems with minimal fluctuations, while binding free energy calculations showed that the ∆Gbind values for the nine test compounds ranged from −31.84 to −16.06 kcal/mol. The most important forces for the binding of these alkaloids with DPP-4 are electrostatic interactions and van der Waals forces. Various important amino acid residues, such as Arg125, His126, Phe357, Arg358, and Tyr547, were involved in the inhibition of DPP-4 by the compounds, revealing a mechanistic basis for the further optimization of these alkaloids as DPP-4 inhibitors. This study confirmed nine alkaloids as direct inhibitors of DPP-4 and characterized their binding features, thereby providing a basis for further research and development on novel DPP-4 inhibitors.
1-Acetoxypinoresinol, a Lignan from Olives: Insight into Its Characterization, Identification, and Nutraceutical Properties
Authors: Wijaya Ganesha Yanuar Arief , Cuffaro Doretta , Bertini Simone , Digiacomo Maria , Macchia Marco
Published: May 2024

Extra virgin olive oil (EVOO) is a symbol of the Mediterranean diet, constituting its primary source of fat. The beneficial effect of EVOO is strictly related to the presence of fatty acids and polyphenols, bioactive compounds endowed with nutraceutical properties. Among EVOO polyphenols, lignans possess a steroid-like chemical structure and are part of the phytoestrogen family, which is renowned for its health properties. The natural lignans (+)-pinoresinol and 1-acetoxypinoresinol (1-AP) are commonly present in olives and in EVOO. Although (+)-pinoresinol is found in different edible plants, such as flaxseed, beans, whole-grain cereals, sesame seeds, and certain vegetables and fruit, 1-AP was exclusively identified in olives in 2000. So far, the scientific literature has extensively covered different aspects of (+)-pinoresinol, including its isolation and nutraceutical properties. In contrast, less is known about the olive lignan 1-AP. Therefore, this review aimed to comprehensively evaluate the more important aspects of 1-AP, collecting all the literature from 2016 to the present, exploring its distribution in different cultivars, analytical isolation and purification, and nutraceutical properties.
The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy
Authors: Barbosa Priscila Oliveira , Tanus-Santos José E. , Cavalli Ricardo de Carvalho , Bengtsson Tore , Montenegro Marcelo F. , Sandrim Valéria Cristina
Published: May 2024

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5–10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal–fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.
Exogenous Ketone Supplement Administration Abrogated Isoflurane-Anesthesia-Induced Increase in Blood Glucose Level in Female WAG/Rij Rats
Authors: Rauch Enikő , Ari Csilla , D’Agostino Dominic P. , Kovács Zsolt
Published: May 2024

It has been demonstrated that isoflurane-induced anesthesia can increase the blood glucose level, leading to hyperglycemia and several adverse effects. The administration of a mix of ketone diester (KE) and medium-chain triglyceride (MCT) oil, named KEMCT, abolished the isoflurane-anesthesia-induced increase in blood glucose level and prolonged the recovery time from isoflurane anesthesia in a male preclinical rodent model, Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. While most preclinical studies use exclusively male animals, our previous study on blood glucose changes in response to KEMCT administration showed that the results can be sex-dependent. Thus, in this study, we investigated female WAG/Rij rats, whether KEMCT gavage (3 g/kg/day for 7 days) can change the isoflurane (3%)-anesthesia-induced increase in blood glucose level and the recovery time from isoflurane-evoked anesthesia using the righting reflex. Moreover, KEMCT-induced ketosis may enhance both the extracellular level of adenosine and the activity of adenosine A1 receptors (A1Rs). To obtain information on the putative A1R mechanism of action, the effects of an A1R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine; intraperitoneal/i.p. 0.2 mg/kg), on KEMCT-generated influences were also investigated. Our results show that KEMCT supplementation abolished the isoflurane-anesthesia-induced increase in blood glucose level, and this was abrogated by the co-administration of DPCPX. Nevertheless, KEMCT gavage did not change the recovery time from isoflurane-induced anesthesia. We can conclude that intragastric gavage of exogenous ketone supplements (EKSs), such as KEMCT, can abolish the isoflurane-anesthesia-induced increase in blood glucose level in both sexes likely through A1Rs in WAG/Rij rats, while recovery time was not affected in females, unlike in males. These results suggest that the administration of EKSs as an adjuvant therapy may be effective in mitigating metabolic side effects of isoflurane, such as hyperglycemia, in both sexes.
Relationship between Circulating 25-Hydroxyvitamin D and Metabolic Syndrome in Chinese Adults: A Large Nationwide Longitudinal Study
Authors: Shu Mi , Xi Yue , Wu Jie , Zhuo Lai-Bao , Yan Yan , Yang Yi-Duo , Feng Yue-Yue , Tan Hua-Qiao , Yang Hui-Fang , Chen Yu-Ming
Published: May 2024

Objective: This study investigated the association of circulating levels of 25-hydroxyvitamin D (25[OH]D) with the risk of metabolic syndrome (MetS) and its components in adults. Methods: This nationwide cohort involved 23,810 Chinese adults attending annual health evaluations. Serum 25(OH)D levels, MetS status, and covariates were determined at each examination. Among them, 8146, 3310, and 1971 completed two, three, and more than three evaluations, respectively. A hybrid mixed-effects and Cox regression model was employed to determine the cross-sectional and longitudinal relationships. Results: The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS were significantly lower in individuals within quartile 4 (vs. 1) of serum 25(OH)D for both between-individual (0.43 [0.35, 0.52]) and within-individual comparisons (0.60 [0.50, 0.73]), respectively (all p-trends < 0.001). Among the MetS components, the corresponding ORs (95% CI) in between- and within-individual comparisons were 0.40 (0.29, 0.54) and 0.26 (0.19, 0.36) for abdominal obesity, 0.49 (0.41, 0.58) and 0.78 (0.66, 0.93) for high triglycerides, 0.70 (0.59, 0.82) and 0.75 (0.64, 0.87) for hypertriglyceridemia, 0.48 (0.39, 0.59) and 0.87 (0.71, 1.07) for low HDL cholesterol, and 0.92 (0.76, 1.12) and 0.49 (0.41, 0.59) for hypertension, respectively. Decreased hazard ratios (95% CIs) in quartile 4 (vs. 1) of 25(OH)D were found for MetS (0.80 [0.65, 1.00]), high triglycerides (0.76 [0.62, 0.92]), abdominal obesity (0.77 [0.63, 0.96]), and low HDL cholesterol (0.64 [0.50, 0.81]). Conclusions: Decreased concentrations of serum 25(OH)D correlate significantly to a heightened MetS risk and specific components. Our findings underscore the potential preventive function of circulating vitamin D concerning metabolic disorders.
Biofortification of Plant- and Animal-Based Foods in Limiting the Problem of Microelement Deficiencies—A Narrative Review
Authors: Białowąs Wojciech , Blicharska Eliza , Drabik Kamil
Published: May 2024

With a burgeoning global population, meeting the demand for increased food production presents challenges, particularly concerning mineral deficiencies in diets. Micronutrient shortages like iron, iodine, zinc, selenium, and magnesium carry severe health implications, especially in developing nations. Biofortification of plants and plant products emerges as a promising remedy to enhance micronutrient levels in food. Utilizing agronomic biofortification, conventional plant breeding, and genetic engineering yields raw materials with heightened micronutrient contents and improved bioavailability. A similar strategy extends to animal-derived foods by fortifying eggs, meat, and dairy products with micronutrients. Employing “dual” biofortification, utilizing previously enriched plant materials as a micronutrient source for livestock, proves an innovative solution. Amid biofortification research, conducting in vitro and in vivo experiments is essential to assess the bioactivity of micronutrients from enriched materials, emphasizing digestibility, bioavailability, and safety. Mineral deficiencies in human diets present a significant health challenge. Biofortification of plants and animal products emerges as a promising approach to alleviate micronutrient deficiencies, necessitating further research into the utilization of biofortified raw materials in the human diet, with a focus on bioavailability, digestibility, and safety.
Metagenomics to Identify Viral Communities Associated with Porcine Respiratory Disease Complex in Tibetan Pigs in the Tibetan Plateau, China
Authors: Zhou Long , Zhou Han , Fan Yandi , Wang Jinghao , Zhang Rui , Guo Zijing , Li Yanmin , Kang Runmin , Zhang Zhidong , Yang Danjiao , Liu Jie
Published: May 2024

Tibetan pig is a unique pig breed native to the Qinghai–Tibet Plateau. To investigate viral communities associated with porcine respiratory disease complex (PRDC), 167 respiratory samples were collected from Tibetan pigs in the Ganzi Tibetan autonomous prefecture of Sichuan province. Following library construction and Illunima Novaseq sequencing, 18 distinct viruses belonging to 15 viral taxonomic families were identified in Tibetan pigs with PRDC. Among the 18 detected viruses, 3 viruses were associated with PRDC, including porcine circovirus type 2 (PCV-2), Torque teno sus virus (TTSuV), and porcine cytomegalovirus (PCMV). The genomic sequences of two PCV-2 strains, three TTSuV strains, and one novel Porprismacovirus strain were assembled by SOAPdenovo software (v2). Sequence alignment and phylogenetic analysis showed that both PCV-2 strains belonged to PCV-2d, three TTSuVs were classified to TTSuV2a and TTSuV2b genotypes, and the Porprismacovirus strain PPMV-SCgz-2022 showed a close genetic relationship with a virus of human origin. Recombination analysis indicated that PPMV-SCgz-2022 may have originated from recombination events between Human 16,806 × 66-213 strain and Porcine 17,668 × 82-593 strain. Furthermore, the high proportion of single infection or co-infection of PCV2/TTSuV2 provides insight into PRDC infection in Tibetan pigs. This is the first report of the viral communities in PRDC-affected Tibetan pigs in this region, and the results provides reference for the prevention and control of respiratory diseases in these animals.
Protective Effects of Dietary Vitamin D3, Turmeric Powder, and Their Combination against Gasoline Intoxication in Rats
Authors: Yestemirova Gulfira A. , Yessimsiitova Zura B. , Danilenko Michael
Published: May 2024

The inhalation of gasoline vapors (GV) is associated with developing various pathologies. Particularly, oil refinery and gas station workers are at a greater risk of developing lung cancer, kidney cancer, bladder cancer, and hematological disorders, including acute myeloid leukemia. Therefore, preventing the harmful effects of GV and alleviating their consequences appear to be important and timely issues. In this study, we investigated the potential of vitamin D3, turmeric powder, and their combination to ameliorate the toxicity of gasoline fumes in rats. Separate groups of animals fed with a standard rodent diet, with or without the supplementation of vitamin D3 (750 IU/kg body weight) and/or turmeric powder (0.5%, w/w, in food), were untreated or treated with GV (11.5 ± 1.3 cm3/h/m3/day) for 30, 60, or 90 days. Changes in the body weight were monitored weekly. Histological, biochemical, and hematological parameters were determined at the end of each treatment period. While the exposure of rats to GV resulted in a time-dependent reduction in body weight, supplementation with vitamin D3, but not with turmeric root powder or their combination, partially prevented weight loss. Macroscopical and histological analyses showed pronounced time-dependent changes in the organs and tissues of GV-treated rats. These included alveolar wall collapse in the lungs, the destruction of the lobular structure and hepatocytolysis in the liver, the shrinkage and fragmentation of glomeruli in the kidneys, and the disorganization of the lymphoid follicles in the spleen. However, co-treatment with the nutritional supplements tested, especially vitamin D3, noticeably alleviated the above conditions. This was accompanied by a significant improvement in the blood chemistry and hematological parameters. Collectively, our results demonstrate that the harmful effects of environmental exposure to GV can be reduced upon supplementation of vitamin D3. The fact that the protective activity of vitamin D3 alone was higher than that of turmeric root powder or the combined treatment suggests that combinations of these supplements may not always be more beneficial than each agent applied separately.
The Histone Deacetylase Family: Structural Features and Application of Combined Computational Methods
Authors: Curcio Antonio , Rocca Roberta , Alcaro Stefano , Artese Anna
Published: May 2024

Histone deacetylases (HDACs) are crucial in gene transcription, removing acetyl groups from histones. They also influence the deacetylation of non-histone proteins, contributing to the regulation of various biological processes. Thus, HDACs play pivotal roles in various diseases, including cancer, neurodegenerative disorders, and inflammatory conditions, highlighting their potential as therapeutic targets. This paper reviews the structure and function of the four classes of human HDACs. While four HDAC inhibitors are currently available for treating hematological malignancies, numerous others are undergoing clinical trials. However, their non-selective toxicity necessitates ongoing research into safer and more efficient class-selective or isoform-selective inhibitors. Computational methods have aided the discovery of HDAC inhibitors with the desired potency and/or selectivity. These methods include ligand-based approaches, such as scaffold hopping, pharmacophore modeling, three-dimensional quantitative structure–activity relationships, and structure-based virtual screening (molecular docking). Moreover, recent developments in the field of molecular dynamics simulations, combined with Poisson–Boltzmann/molecular mechanics generalized Born surface area techniques, have improved the prediction of ligand binding affinity. In this review, we delve into the ways in which these methods have contributed to designing and identifying HDAC inhibitors.
Synthesis and Evaluation of Novel 68Ga-Labeled [D-Phe6,Leu13ψThz14]bombesin(6-14) Analogs for Cancer Imaging with Positron Emission Tomography
Authors: Wang Lei , Chen Chao-Cheng , Zhang Zhengxing , Kuo Hsiou-Ting , Zhang Chengcheng , Colpo Nadine , Merkens Helen , Bénard François , Lin Kuo-Shyan
Published: May 2024

Gastrin-releasing peptide receptor (GRPR) is overexpressed in various cancers and is a promising target for cancer diagnosis and therapy. However, the high pancreas uptake and/or metabolic instability observed for most reported GRPR-targeted radioligands might limit their clinical applications. Our group recently reported a GRPR-targeted antagonist tracer, [68Ga]Ga-TacsBOMB2 ([68Ga]Ga-DOTA-Pip-D-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Leu13ψThz14-NH2), which showed a minimal pancreas uptake in a preclinical mouse model. In this study, we synthesized four derivatives with unnatural amino acid substitutions (Tle10-derived Ga-LW01158, NMe-His12-derived Ga-LW01160, α-Me-Trp8- and Tle10-derived Ga-LW01186, and Tle10- and N-Me-Gly11-derived Ga-LW02002) and evaluated their potential for detecting GRPR-expressing tumors with positron emission tomography (PET). The binding affinities (Ki(GRPR)) of Ga-LW01158, Ga-LW01160, Ga-LW01186, and Ga-LW02002 were 5.11 ± 0.47, 187 ± 17.8, 6.94 ± 0.95, and 11.0 ± 0.39 nM, respectively. [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 enabled clear visualization of subcutaneously implanted human prostate cancer PC-3 tumor xenografts in mice in PET images. Ex vivo biodistribution studies showed that [68Ga]Ga-LW01158 had the highest tumor uptake (11.2 ± 0.65 %ID/g) and good tumor-to-background uptake ratios at 1 h post-injection. Comparable in vivo stabilities were observed for [68Ga]Ga-LW01158, [68Ga]Ga-LW01186, and [68Ga]Ga-LW02002 (76.5–80.7% remaining intact in mouse plasma at 15 min post-injection). In summary, the Tle10 substitution, either alone or combined with α-Me-Trp8 or NMe-Gly11 substitution, in Ga-TacsBOMB2 generates derivatives that retained good GRPR binding affinity and in vivo stability. With good tumor uptake and tumor-to-background imaging contrast, [68Ga]Ga-LW01158 is promising for detecting GRPR-expressing lesions with PET.
Research Progress of Drug Delivery Systems Targeting the Kidneys
Authors: Huang Li-Feng , Ye Qiao-Ru , Chen Xiao-Cui , Huang Xiao-Rong , Zhang Qiao-Fei , Wu Chun-Yu , Liu Hua-Feng , Yang Chen
Published: May 2024

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment. However, due to off-target effects, conventional drugs for CKD typically require high doses to achieve adequate therapeutic effects, leading to long-term organ toxicity. Therefore, ideal treatments that completely cure the different types of kidney disease are rarely available. Several approaches for the drug targeting of the kidneys have been explored in drug delivery system research. Nanotechnology-based drug delivery systems have multiple merits, including good biocompatibility, suitable degradability, the ability to target lesion sites, and fewer non-specific systemic effects. In this review, the development, potential, and limitations of low-molecular-weight protein–lysozymes, polymer nanomaterials, and lipid-based nanocarriers as drug delivery platforms for treating AKI and CKD are summarized.
The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives
Authors: Tsoupras Alexandros , Gkika Despina A. , Siadimas Ilias , Christodoulopoulos Ioannis , Efthymiopoulos Pavlos , Kyzas George Z.
Published: May 2024

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists’ pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs’ side-effects on platelets’ functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.
Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats
Authors: de Morais Sebastião Vieira , Calado Gustavo Pereira , Carvalho Rafael Cardoso , Garcia João Batista Santos , de Queiroz Thyago Moreira , Cantanhede Filho Antonio José , Lopes Alberto Jorge Oliveira , Cartágenes Maria do Socorro de Sousa , Domingues Gerson Ricardo de Souza
Published: May 2024

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association’s efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.
The Synergistic Effect of N2 and N7 Modifications on the Inhibitory Efficacy of mRNA Cap Analogues
Authors: Kurpiejewski Karol , Piecyk Karolina , Lukaszewicz Maciej , Kamel Karol , Chmurski Kazimierz , Kmiecik Sebastian , Jankowska-Anyszka Marzena
Published: May 2024

In the fight against cancer, researchers have turned their attention to the eukaryotic initiation factor eIF4E, a protein whose increased level is strongly correlated with the development and progression of various types of cancer. Among the numerous strategies devised to tackle eIF4E overexpression, the use of 5′ end mRNA cap analogues has emerged as a promising approach. Here, we present new candidates as potent m7GMP analogues for inhibiting translation and interfacing with eIF4E. By employing an appropriate strategy, we synthesized doubly modified mono- and dinucleotide cap analogues, introducing simultaneous substituents at both the N7 and N2 positions of the guanine ring. This approach was identified as an effective and promising combination. Our findings reveal that these dual modifications increase the potency of the dinucleotide analogue, marking a significant advancement in the development of cancer therapeutics targeting the eIF4E pathway.
Lipid Nanoparticles in Lung Cancer Therapy
Authors: Omidian Hossein , Gill Erma J. , Cubeddu Luigi X.
Published: May 2024

This manuscript explores the use of lipid nanoparticles (LNPs) in addressing the pivotal challenges of lung cancer treatment, including drug delivery inefficacy and multi-drug resistance. LNPs have significantly advanced targeted therapy by improving the precision and reducing the systemic toxicity of chemotherapeutics such as doxorubicin and paclitaxel. This manuscript details the design and benefits of various LNP systems, including solid lipid–polymer hybrids, which offer controlled release and enhanced drug encapsulation. Despite achievements in reducing tumor size and enhancing survival, challenges such as manufacturing complexity, biocompatibility, and variable clinical outcomes persist. Future directions are aimed at refining targeting capabilities, expanding combinatorial therapies, and integrating advanced manufacturing techniques to tailor treatments to individual patient profiles, thus promising to transform lung cancer therapy through interdisciplinary collaboration and regulatory innovation.
A Visual Raman Nano−Delivery System Based on Thiophene Polymer for Microtumor Detection
Authors: Li Meng , Luo Aoxiang , Xu Wei , Wang Haoze , Qiu Yuanyuan , Xiao Zeyu , Cui Kai
Published: May 2024

A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor–acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of “Visualized Drug Delivery Systems”. Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.
SPECT Imaging of P. aeruginosa Infection in Mice Using 123I-BMIPP
Authors: Nishiyama Yuri , Mizutani Asuka , Kobayashi Masato , Muranaka Yuka , Sato Kakeru , Maki Hideki , Kawai Keiichi
Published: May 2024

Pseudomonas aeruginosa infection is an infectious disease that must be controlled because it becomes chronic and difficult to treat, owing to its unique system of toxin production/injection and elimination of other bacteria. Here, we noninvasively monitored P. aeruginosa using single-photon emission computed tomography (SPECT) imaging. Determining the amount and localization of the P. aeruginosa will enable making faster clinical diagnoses and selecting the most appropriate therapeutic agents and methods. Nonclinically, this information can be used for imaging in combination with biofilms and toxin probes and will be useful for discovering drugs targeting P. aeruginosa. To study P. aeruginosa accumulation, we conducted in vitro and in vivo studies using iodine-123 β-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP), which we previously reported using for Escherichia coli. In vitro, 123I-BMIPP accumulated in P. aeruginosa by being taken up into the bacteria and adsorbing to the bacterial surface. In vivo, 123I-BMIPP accumulated significantly more in infected sites than in noninfected sites and could be quantified by SPECT. These results suggest that 123I-BMIPP can be used as a probe for P. aeruginosa for SPECT. Establishing a noninvasive monitoring method using SPECT will allow further progress in studying P. aeruginosa.
Improved DeepLabV3+ Network Beacon Spot Capture Methods
Authors: Liu Jun , Ni Xiaolong , Yu Xin , Li Cong
Published: May 2024

In long-range laser communication, adaptive optics tracking systems are often used to achieve high-precision tracking. When recognizing beacon spots for tracking, the traditional threshold segmentation method is highly susceptible to segmentation errors in the face of interference. In this study, an improved DeepLabV3+ network is designed for fast and accurate capture of beacon spots in complex situations. In order to speed up the inference process, the backbone of the model was rewritten as MobileNetV2. This study improves the ASPP (Atrous Spatial Pyramid Pooling) module by splicing and fusing the outputs and inputs of its different layers. Meanwhile, the original convolution in the module is rewritten as a depthwise separable convolution with a dilation rate to reduce the computational burden. CBAM (Convolutional Block Attention Module) is applied, and the focus loss function is introduced during training. The network yields an accuracy of 98.76% mean intersection over union on self-constructed beacon spot dataset, and the segmentation consumes only 12 milliseconds, which realizes the fast and high-precision capturing of beacon spots.