bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells
Authors: Lama Rati , Fose Joseph M. , Martín Diana , Muñoz Inés G. , Wang Eunice S. , Sung Pamela J. , Chemler Sherry R. , Wang Xinjiang
Published: January 2025

MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction. Inhibitors disrupting p53 interaction with MDM2/MDM4 are in clinical trials in patients bearing wild-type p53 cancers. However, these inhibitors are not designed to work for p53-null/mutant cancer cells. Owing to the importance of the E3 ligase of MDM2 in its p53-independent oncogenic activity, inhibitors targeting the E3 ligase activity of MDM2-MDM4 are desirable for p53-mutant cancer cells. Here, we report the development of such inhibitors with pro-apoptotic activity in p53-null leukemic cells. Among analogues of MDM2-MDM4 E3 ligase inhibitors, we initially identified MMRi36 as a potent pro-apoptotic compound in p53-null leukemic cells with acquired drug resistance. MMRi36 acts as an activator of MDM2-MDM4 E3 ligase by stabilizing MDM2-MDM4 heterodimers and promotes MDM2/MDM4 degradation in cells. Interestingly, replacement of the sulfur in 1,3,4-thiadiazole MMRi36 with a carbon led to identification of pyrazole MMRi36C that dissociates the MDM2-MDM4 RING heterodimers, inhibits the E3 ligase activity of the complex, and induces p53 protein accumulation, but retains the p53-independent pro-apoptotic activity. A brief SAR study identified a fluorine derivative of MMRi36C with improved pro-apoptotic activity. This study discovered a novel class of compound that targets MDM2-MDM4 ubiquitin E3 ligase activity for apoptosis induction in p53-mutant cancer cells.
Genistein Implications in Radiotherapy: Kill Two Birds with One Stone
Authors: Liu Xiongxiong , Zheng Tong , Bao Yanyu , Li Ping , Zhao Ting , Liu Yan , Wang Hui , Sun Chao
Published: January 2025

More than 70% of cancer patients receive radiotherapy during their treatment, with consequent various side effects on normal cells due to high ionizing radiation doses despite tumor shrinkage. To date, many radioprotectors and radiosensitizers have been investigated in preclinical studies, but their use has been hampered by the high toxicity to normal cells or poor tumor radiosensitization effects. Genistein is a naturally occurring isoflavone found in soy products. It selectively sensitizes tumor cells to radiation while protecting normal cells from radiation-induced damage, thus improving the efficacy of radiotherapy and consequent therapeutic outcomes while reducing adverse effects. Genistein protects normal cells by its potent antioxidant effect that reduces oxidative stress and mitigates radiation-induced apoptosis and inflammation. Conversely, genistein increases the radiosensitivity of tumor cells through specific mechanisms such as the inhibition of DNA repair, the arrest of the cell cycle in the G2/M phase, the generation of reactive oxygen species (ROS), and the modulation of apoptosis. These effects increase the cytotoxicity of radiation. Preclinical studies demonstrated genistein efficacy in various cancer models, such as breast, prostate, and lung cancer. Despite limited clinical studies, the existing evidence supports the potential of genistein in improving the therapeutic effect of radiotherapy. Future research should focus on dosage optimization and administration, the exploration of combination therapies, and long-term clinical trials to establish genistein benefits in clinical settings. Hence, the unique ability of genistein to improve the radiosensitivity of tumor cells while protecting normal cells could be a promising strategy to improve the efficacy and safety of radiotherapy.
Luminescent Iridium–Terpyridine Complexes with Various Bis-Cyclometalated Ligands
Authors: Ikeda Ko , Yano Natsumi , Handa Makoto , Kataoka Yusuke
Published: January 2025

A series of luminescent bis-cyclometalated iridium complexes with 2,2′:6′,2″-terpyridine (tpy), [Ir(C^N)2(tpy)]PF6 (C^N = 2-phenylpyridinate (ppy) for 1; benzo[h]quinolinate (bzq) for 2; 1-phenylisoquinolinate (piq) for 3; and 2-phenylbenzothiazolate (pbt) for 4), have been synthesized and structurally characterized. Single-crystal X-ray diffraction analyses reveal that the tpy ligands of 1–4 are coordinated to the iridium center in a bidentate fashion, and the uncoordinated pendant pyridine rings in the tpy ligands of 1–4 form intramolecular π-π stacking interactions with a phenyl moiety of C^N ligands. In addition, the pendant pyridine ring in the tpy ligand of 1 forms an intramolecular hydrogen bonding interaction, unlike in 2–4. Of interest, the photophysical properties of 1–4 are strongly influenced by the C^N ligands; 1 shows a luminescence band at 572 nm, with a short lifetime (τ) value of 80 nsec and a lower absolute luminescence quantum yield (Φ) of 3.72%, whereas 3 exhibits an intense luminescence band at 588 nm with a long τ value of 1965 nsec and a moderate Φ value of 9.57%. The density functional theory calculations revealed that the luminescence originates from the triplet metal–ligand to ligand charge transfer (3MLL′CT) excited state.
Cannabis sativa L. Extract Increases COX-1, COX-2 and TNF-α in the Hippocampus of Rats with Neuropathic Pain
Authors: Bartkowiak-Wieczorek Joanna , Jamka Małgorzata , Kujawski Radosław , Hołysz Marcin , Bienert Agnieszka , Czora-Poczwardowska Kamila , Szulc Michał , Mikołajczak Przemysław , Bogacz Anna , Wizner Anna-Maria , Wielgus Karolina , Słomski Ryszard , Mądry Edyta
Published: January 2025

Inflammation is the critical component of neuropathic pain; therefore, this study aimed to assess the potential anti-inflammatory effects of Cannabis sativa L. extracts in a vincristine-induced model of neuropathic pain. The effects of different doses (5.0–40.0 mg/kg) of two Cannabis sativa L. extracts (B and D) on COX-1, COX-2, TNF-α, and NF-κB mRNA and protein levels were examined in the rat hippocampus, cerebral cortex, and blood lymphocytes. There were statistically significant differences in COX-1, COX-2, and TNF-α mRNA and protein expression in the hippocampus and cerebral cortex, with significant differences in COX-2 and TNF-α in the lymphocytes. Extract D dose-dependently increased COX-1 mRNA and protein in the hippocampus and cortex. In contrast, Extract B dose-dependently increased COX-1 mRNA and decreased COX-2 mRNA (in a dose of 7.5 mg/kg) and TNF-α protein levels in the cortex. Cannabis sativa L. extracts significantly influenced the expression of inflammatory genes and proteins, with effects varying based on dose and tissue type. The increased expression of COX-1, COX-2, and TNF-α (in comparison to groups receiving NaCl, vincristine, and gabapentin) in the rat hippocampus and COX-1 in the cerebral cortex suggests that Cannabis may have a pro-inflammatory effect. Due to species specificity, the results of our research based on rats require confirmation in humans. However, Cannabis sativa should be recommended with caution for treating pain with an inflammatory component.
Physico-Chemical Properties of Granular Sorbents Based on Natural Bentonite Modified by Polyhydroxocations of Aluminum and Iron (III) by Co-Precipitation
Authors: Kussainova Bakytgul , Tazhkenova Gaukhar , Kazarinov Ivan , Burashnikova Marina , Ramazanova Raigul , Ivashchenko Yelena , Saurbayeva Bekzat , Tantybayeva Batima , Seitkan Ainur , Matniyazova Gulsim , Sadiyeva Khalipa , Nurlybayeva Aisha , Bazarkhankyzy Aidana
Published: January 2025

The physicochemical and adsorption properties of granular sorbents based on natural bentonite and modified sorbents based on it have been studied. It was found that modification of natural bentonite with iron (III) polyhydroxocations (mod. 1_Fe_5 GA) and aluminum (III) (mod. 1_Al_5 GA) by the “co-precipitation” method leads to a change in their chemical composition, structure, and sorption properties. It is shown that modified sorbents based on natural bentonite are finely porous (nanostructured) objects with a predominance of pores measuring 1.5–8.0 nm, with a specific surface area of 55–65 m2/g. Modification of bentonite with iron (III) and aluminum compounds by the “co-precipitation” method also leads to an increase in the sorption capacity of the obtained sorbents with respect to bichromate and arsenate anions and nickel cations by 5-10 times compared with natural bentonite. The obtained sorption isotherms were classified as Langmuir type isotherms. Kinetic analysis showed that at the initial stage the sorption process is controlled by an external diffusion factor, i.e. refers to the diffusion of sorbent from solution into a liquid film on the surface of the sorbent. Then the sorption process begins to proceed in a mixed diffusion mode, when it limits both the external diffusion factor and the internal diffusion factor (the diffusion of the sorbent to the active centers through the system of pores and capillaries). To determine the contribution of the chemical stage to the rate of adsorption of bichromate and arsenate anions and nickel(II) cations with the studied granular sorbents, kinetic curves were processed using the equations of chemical kinetics (pseudo-second-order model). As a result, it was found that the adsorption of the studied anions by modified sorbents based on natural bentonite is best described by a pseudo-second-order kinetic model. It is shown that the use of natural bentonite for the development of technology for the production of granular sorbents based on it has an undeniable advantage, firstly, in terms of its chemical and structural properties, it is easily and effectively modified, and secondly, having astringent properties, granules are easily made on its basis, which turn into ceramics during high-temperature firing. The result is a granular sorbent with high physical and mechanical properties. Since bentonite is an environmentally friendly product, the technology of recycling spent sorbents is also greatly simplified.
Thermal Characterization and Heat Capacities of Seven Polyphenols
Authors: Montenegro Iván , Pérez Carmen , González Begoña , Domínguez Ángeles , Gómez Elena
Published: January 2025

Polyphenolic compounds are key elements in sectors such as pharmaceutics, cosmetics and food; thus, their physicochemical characterization is a vital task. In this work, the thermal behavior of seven polyphenols (trans-resveratrol, trans-polydatin, kaempferol, quercetin, myricetin, hesperidin, and (−)-epicatechin) was investigated with DSC (differential scanning calorimetry) and TGA (thermogravimetric analysis). Melting temperatures, enthalpies of fusion and decomposition temperatures were determined, and heat capacities were measured in the temperature range from 283.15 K to 363.15 K. Results were compared to the scarce experimental data available in the literature, showing a satisfactory agreement. All compounds were found to be thermally stable until melting, upon which they rapidly decomposed. Myricetin was the only polyphenol that presented polymorphic behavior, exhibiting two phase transitions prior to melting. Heat capacities increased minimally with temperature in the studied range. In addition, the group contribution method developed by Marrero and Gani was used to estimate the thermal properties of the polyphenols, achieving high accuracy for melting temperatures.
Effectiveness of Different Organic Solvent Additions to Water Samples for Reducing the Adsorption Effects of Organic Pesticides Using Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry
Authors: Liu Yucan , Xu Xinyi , Wang Ying , Zhang Yan , Lu Jianbo , Liu Chengbin , Duan Jinming , Sun Hongwei
Published: January 2025

This study systematically investigated the effect of organic solvent addition on the detection signal intensity of 15 organic pesticides in water using ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UHPLC–ESI–MS/MS). The analysis of chromatographic peak area ratios in ultrapure water (UPW) versus 30% methanol (MeOH)–UPW showed that the adsorption effects (AEs, mainly from injection vials with weaker polarity) were the main factor influencing the detection intensity of the organic pesticides. The AEs varied with pesticide type and concentration, especially for those with high logKow values and longer retention times, such as malathion, triadimefon, prometryn, S–metolachlor, diazinon, and profenofos. Significant differences were observed in the ability of five organic solvents (MeOH, dimethyl sulfoxide, isopropanol, acetonitrile, and acetone) to reduce AEs, with MeOH being the most effective. Optimal solvent ratios were determined to minimize AEs in aqueous solutions. Additionally, plastic injection vials caused greater AEs than glass injection vials, but the addition of organic solvents increased the detection intensity of the analytes for vials of both materials. Density functional theory calculations of the binding energies between pesticides (diazinon, malathion, and S–metolachlor) and vial materials further confirmed the effect of AE on the detection intensity of the analytes. This study showed that the addition of MeOH to real water samples effectively reduced or eliminated the effects of AEs, achieving a good linearity of calibration curves (0.05/0.1–5 μg/L, R2 = 0.9853–0.9998), high sensitivity (LOD = 5–32 ng/L), precision (RSD = 1.4–14.5%), and accuracy (average recoveries = 80.6–121.8%). These results provide technical and methodological support for mitigating the effects of AEs on pesticide detection in water using UHPLC–ESI–MS/MS.
Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices
Authors: Isreb Abdullah , Alhnan Mohamed A. , Mkia Abdulrahman , Al-Jammal Khaled , Yaghi Abdallah , Oga Enoche Florence , Timmins Peter , Bonner Michael , Forbes Robert T.
Published: January 2025

Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system. This work studies the interaction between model drug combinations (two of ibuprofen, malonic acid, flurbiprofen, or naproxen) dispersed in a polymeric matrix of hypromellose acetate succinate (HPMCAS) using a solvent evaporation technique. Hildebrand and Hansen calculations were used to predict the miscibility of compounds as long as the difference in their solubility parameter values was not greater than 7 MPa1/2. It was observed that the selected APIs (malonic acid, ibuprofen, naproxen, and flurbiprofen) were miscible within the formed polymeric matrix. Adding the API caused depression in the Tg of the polymer to certain concentrations (17%, 23%, 13%) for polymeric matrices loaded with malonic acid, ibuprofen, and naproxen, respectively. Above this, large crystals started to form, and phase separation was seen. Adding two APIs to the same matrix resulted in reducing the saturation concentration of one of the APIs. A trend was observed and linked to Hildebrand and Hansen solubility parameters (HSP).
MoTe2 Photodetector for Integrated Lithium Niobate Photonics
Authors: Dong Qiaonan , Sun Xinxing , Gao Lang , Zheng Yong , Wu Rongbo , Cheng Ya
Published: January 2025

The integration of a photodetector that converts optical signals into electrical signals is essential for scalable integrated lithium niobate photonics. Two-dimensional materials provide a potential high-efficiency on-chip detection capability. Here, we demonstrate an efficient on-chip photodetector based on a few layers of MoTe2 on a thin film lithium niobate waveguide and integrate it with a microresonator operating in an optical telecommunication band. The lithium-niobate-on-insulator waveguides and micro-ring resonator are fabricated using the femtosecond laser photolithography-assisted chemical–mechanical etching method. The lithium niobate waveguide-integrated MoTe2 presents an absorption coefficient of 72% and a transmission loss of 0.27 dB µm−1 at 1550 nm. The on-chip photodetector exhibits a responsivity of 1 mA W−1 at a bias voltage of 20 V, a low dark current of 1.6 nA, and a photo–dark current ratio of 108 W−1. Due to effective waveguide coupling and interaction with MoTe2, the generated photocurrent is approximately 160 times higher than that of free-space light irradiation. Furthermore, we demonstrate a wavelength-selective photonic device by integrating the photodetector and micro-ring resonator with a quality factor of 104 on the same chip, suggesting potential applications in the field of on-chip spectrometers and biosensors.
Laser Synthesis of Platinum Single-Atom Catalysts for Hydrogen Evolution Reaction
Authors: Guo Hengyi , Wang Lingtao , Liu Xuzhao , Mativenga Paul , Liu Zhu , Thomas Andrew G.
Published: January 2025

Platinum (Pt)-based heterogeneous catalysts show excellent performance for the electrocatalytic hydrogen evolution reaction (HER); however, the high cost and earth paucity of Pt means that efforts are being directed to reducing Pt usage, whilst maximizing catalytic efficiency. In this work, a two-step laser annealing process was employed to synthesize Pt single-atom catalysts (SACs) on a MOF-derived carbon substrate. The laser irradiation of a metal–organic framework (MOF) film (ZIF67@ZIF8 composite) by rapid scanning of a ns pulsed infrared (IR; 1064 nm) laser across the freeze-dried MOF resulted in a metal-loaded graphitized film. This was followed by loading this film with chloroplatinic acid (H2PtCl6), followed by further irradiation with an ultraviolet (UV; 355 nm) laser, resulting in pyrolysis of H2PtCl6 to form the SAC, along with a further reduction of the MOF to form a Pt-decorated laser-induced annealed MOF (Pt-LIA-ZIF8@ZIF67). The Pt-LIA-ZIF8@ZIF67 catalyst with a Pt loading of 0.86 wt. % exhibited exceptionally high activity for the HER in acidic conditions. The atomically dispersed Pt on the carbon substrate exhibited a small overpotential of 68.8 mV at 10 mA cm−2 for the hydrogen evolution reaction with a mass activity 20.52 times that of a commercial Pt/C catalyst at an overpotential of 50 mV vs. RHE. Finally, we note that the synthesis method is simple, fast, and versatile, and potentially scalable for the mass production of SACs for electrocatalytic applications.
Associations of Serum Homocysteine with Bone Mineral Density and Osteoporosis Incidence in Chinese Middle-Aged and Older Adults: A Retrospective Cohort Study
Authors: Zou Jiupeng , Shu Mi , Chen Jiedong , Wusiman Maierhaba , Ye Jialu , Yang Sishi , Chen Si , Huang Zihui , Huang Bixia , Fang Aiping , Zhu Huilian
Published: January 2025

Objective: This research investigated the prospective association of serum homocysteine with lumbar bone mineral density (BMD) and the risk of osteoporosis in the Chinese population. Methods: In this cohort, 2551 Chinese individuals aged ≥50 years underwent annual health examinations. Among them, 2551, 1549, and 926 completed two, three, and more than three examinations, respectively. We used generalized estimating equations to analyze the connection between serum homocysteine and lumbar BMD. Additionally, we assessed the connection between serum homocysteine and the incidence of osteoporosis using Cox proportional hazard models. Subgroup analyses based on covariates were performed to identify important at-risk populations. Results: Participants with higher homocysteine levels showed decreased lumbar BMD compared to those with lower homocysteine levels (p-trend < 0.05). Specifically, lumbar BMD decreased by −0.002 (−0.003, −0.001) g/cm2 for every standard deviation increase in log-transformed serum homocysteine. Compared to the lowest quartile of homocysteine levels, lumbar BMD decreased by −0.006 (−0.010, −0.002) g/cm2 in the highest quartile in men. In smokers, lumbar BMD decreased by −0.007 (−0.012, −0.003) g/cm2 in the highest quartile. During the follow-up period, 175 incidences of osteoporosis were recorded. Serum homocysteine was linked to an increased risk of osteoporosis (p-trend < 0.05). Furthermore, for every standard deviation rise in log-transformed homocysteine, the HR for osteoporosis was 1.33 (95% CI, 1.12–1.58). Conclusions: Elevated homocysteine levels may be responsible for reduced lumbar BMD in middle-aged and older Chinese people, especially men and smokers. In addition, elevated homocysteine levels may be a risk factor for the development of osteoporosis.
The Glucose-Lowering Effect of Mesembryanthemum crystallinum and D-Pinitol: Studies on Insulin Secretion in INS-1 Cells and the Reduction of Blood Glucose in Diabetic Rats
Authors: Lee Dahae , Kim Sung Jin , Choi Yea Jung , Rho Young Ho , Kang Tae Seok , Kim Yoon Geol , Kang Ki Sung
Published: January 2025

Background: Ice plant (Mesembryanthemum crystallinum) is a vegetable with various therapeutic uses, one of which is its ability to prevent diabetes. The present study examined the insulin secretion effect related to the mechanism of action of ice plant extract (IPE) and its active compound D-pinitol in a rat insulin-secreting β-cell line, INS-1, as well as in diabetic rats. Methods: The glucose-stimulated insulin secretion (GSIS) test and Western blotting were used to measure GSIS. The glucose-stimulated index (GSI) and expression levels of insulin-related pathway factors, including insulin receptor substrate-2 (IRS-2), phosphoinositide 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1), were measured in INS-1 cells. Results: The results showed that the GSI values were found to be 8.17 ± 0.22 and 12.21 ± 0.22 for IPE (25 μg/mL) and D-pinitol (100 μM), respectively. GSI values increased statistically significantly. In addition, IPE and D-pinitol upregulated the expression of insulin-related pathway factors. These findings indicate that insulin secretion was significantly stimulated by IPE and D-pinitol in the INS-1 cells, partly by upregulating the expression of IRS-2, PI3K, Akt, and PDX-1. Additionally, IPE administration significantly reduced excessive weight gain and improved glucose tolerance by decreasing the OGTT-AUC. It demonstrated liver-function-improving and lipid-lowering effects by reducing serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), triglyceride levels, and total cholesterol levels. Mechanistically, IPE enhances insulin signaling by increasing insulin receptor substrate 1 (IRS-1) phosphorylation and improving glucose metabolism and insulin sensitivity. Conclusions: These results offer important new information on the potential of D-pinitol and IPE as functional foods for improving insulin secretion and managing metabolic dysregulation associated with diabetes.
The Novel Effect and Potential Mechanism of Lactoferrin on Organ Fibrosis Prevention
Authors: Yu Yonghui , Fang Juan , Li Yingying , Wang Xueli , Zhang Jingjie , Wang Jing , Sun Baoguo
Published: January 2025

Organ fibrosis is gradually becoming a human health and safety problem, and various organs of the body are likely to develop fibrosis. The ultimate pathological feature of numerous chronic diseases is fibrosis, and few interventions are currently available to specifically target the pathogenesis of fibrosis. The medical detection of organ fibrosis has gradually matured. However, there is currently no effective treatment method for these diseases. Therefore, we need to strive for developing effective and reliable drugs or substances to treat and prevent fibrotic diseases. Lactoferrin (LF) is a multifunctional glycoprotein with many pathological and physiologically active effects, such as antioxidant, anti-inflammatory and antimicrobial effects, and it protects against pathological and physiological conditions in various disease models. This review summarizes the effects and underlying mechanisms of LF in preventing organ fibrosis. As a naturally active substance, LF can be used as a promising and effective drug for the prevention and remission of fibrotic diseases.
High Prevalence of Salmonella spp. in Ready-to-Eat Artisanal Pork Sausages Sold at Food Outlets in Quindío, Colombia
Authors: Jaramillo-Bedoya Elizabeth , Flórez-Elvira Liliana Janeth , Ocampo-Ibáñez Iván Darío
Published: January 2025

Non-typhoidal salmonellosis is a foodborne disease caused by Salmonella spp. Most outbreaks of this disease are commonly associated with consuming contaminated meat products, hence the importance of monitoring ready-to-eat artisanal pork sausages for the presence of these bacteria. A total of 494 samples of grilled and smoked barbecue artisanal pork sausages were collected at food outlets from 12 municipalities of the Department of Quindío, Colombia, between 2017 and 2022. Salmonella spp. was identified using VIDAS® Easy SLM and confirmed through API® 20 E. Salmonella spp. was detected in 260 samples (52.6%), and the highest rates of contamination were found in Armenia (65.7%), Salento (65.2%), Circasia (57.7%), and Calarcá (56.4%). The highest proportion of these samples positive for Salmonella spp. was ready-to-eat smoked barbecue artisanal sausages (68.8%) sold by street vendors (58.4%) from 12 municipalities of the Department of Quindío. A significant association was observed between the municipality and contamination of samples with Salmonella spp. However, no link was found between the sampling year and the presence of the bacteria. This is the first study aimed at monitoring the presence of Salmonella spp. in artisanal pork sausages sold in the municipalities of the Department of Quindío over a 6-year period, and findings revealed very high percentages of contamination. Although Colombian legislation establishes sanitary and safety requirements for meat production, the presence of Salmonella spp. in artisanal sausages remains a persistent public health threat in developing countries.
Discovery of Novel Diagnostic Biomarkers for Common Pathogenic Nocardia Through Pan-Genome and Comparative Genome Analysis, with Preliminary Validation
Authors: Wang Chaohong , Jia Xinmiao , Wei Ming , Yan Jun , Sun Qing , Long Sibo , Zheng Maike , Shi Yiheng , Jiang Guanglu , Zhao Yan , Huang Hairong , Yang Xinting , Gu Li , Wang Guirong
Published: January 2025

The aim of this study was to reveal diagnostic biomarkers of considerable importance for common pathogenic Nocardia, utilizing pan-genomic and comparative genome analysis to accurately characterize clinical Nocardia infections. In this study, complete or assembled genome sequences of common pathogenic Nocardia and closely related species were obtained from NCBI as discovery and validation sets, respectively. Genome annotation was performed using Prokka software, and pan-genomic analysis and extraction of Nocardia core genes were performed using BPGA software. Comparative genome analysis of these core genes with the validation-set gene sequences was then performed using BLAT, with a threshold of 30% amino acid coverage and identity, in order to distinguish specific core genes. Finally, candidate gene-specific primers were designed using Snapgene software and DNA samples were obtained from clinical Nocardia strains and closely related species for validation. The analysis identified eighteen core genes specific to Nocardia spp., four core genes specific to N. farcinica, and forty-six core genes specific to N. cyriacigeorgica. After rigorous clinical validation, one gene from Nocardia spp. and five genes from N. cyriacigeorgica were confirmed to have high specificity and therefore can be used as reliable biomarkers for accurate diagnosis of Nocardia infection. This pioneering research reveals diagnostic biomarkers of considerable significance, with the potential to substantially enhance the precise diagnosis of common pathogenic Nocardia infections, thereby laying the groundwork for innovative diagnostic methodologies in subsequent studies.
Hydrogels of Poly(2-hydroxyethyl methacrylate) and Poly(N,N-dimethylacrylamide) Interpenetrating Polymer Networks as Dermal Delivery Systems for Dexamethasone
Authors: Simeonov Marin , Kostova Bistra , Mihaylova Rositsa , Vassileva Elena
Published: January 2025

Background/Objectives: This study is an attempt to reveal the potential of two types of interpenetrating polymer network (IPN) hydrogels based on poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(N,N-dimethylacrylamide) (PDMAM). These IPNs were evaluated for their potential for dermal delivery of the hydrophobic drug dexamethasone (DEX). Methods: The two types of IPNs were analyzed for their rheological behavior, swelling characteristics, and drug-loading capacity with DEX. Drug release profiles were studied in Franz diffusion cells in PBS media. Finally, the cytotoxicity of the PHEMA/PDMAM-based IPNs was studied against T-cell lymphoma cells (HUT-78) and a normal murine fibroblast cell line (CCL-1). Results: The rheological properties of these hydrogels show suitable mechanical properties for dermal application, with G′ values of ~10 kPa. From the rheological data, the mesh size of these hydrogels was found to be influenced by the type of the IPN and its composition, varying between 6.5 and 50 nm. The loading capacity of both IPN types and DEX entrapment efficiency were highly influenced by the IPN’s composition. The loading capacity of the IPNs can reach ~3.5%, with a DEX entrapment efficiency of ~35%. The PHEMA/PDMAM IPNs demonstrate an extended release profile with up to ~95% DEX released in 24 h, while PDMAM/PHEMA IPNs release no more than ~25% DEX in 24 h. The drug release profiles follow either non-Fickian diffusion (n~0.6) or case-II transport (n~0.9–1), depending on the IPN’s composition. The PHEMA/PDMAM-based materials were found to be non-cytotoxic against HUT-78 and CCL-1 cells. Conclusions: The study reveals that the IPNs of PHEMA and PDMAM appear to be suitable platforms for dermal delivery of dexamethasone as they have appropriate mechanical properties, providing tools to control drug loading and release, and they are biocompatible with human skin cells.
Research and Application of Interferogram Acquisition Method for Ground-Based Fourier-Transform Infrared Greenhouse Gas Spectrometer
Authors: Deng Yasong , Xu Liang , Jin Ling , Sun Yongfeng , Zhang Lei , Liu Jianguo , Liu Wenqing
Published: January 2025

A high-performance data acquisition and processing system within a spectrometer provides a powerful guarantee for obtaining high-precision data in ground-based Fourier-transform infrared greenhouse-gas spectroscopy. Addressing the challenge of accurate interferogram sampling in Fourier-transform spectroscopy, a dual-channel interferogram acquisition method was designed. Dual-channel analog-to-digital converters, acquiring interferograms at different gains, enable high dynamic range and high-resolution acquisition of infrared interferometric signals; the analog-to-digital converter channel of low-gain interferograms mainly captures data near the zero-optical-range-difference spike, and the analog-to-digital converter channel of high-gain interferograms mainly acquires the weak signals from the two flanks. The simulation results, circuit design, and correction method between the two channels of the method are given. Finally, in the ground-based Fourier-transform infrared greenhouse-gas spectrometer for experimental applications, the experiment shows that under the same measurement conditions, the carbon dioxide column concentration-measurement accuracy is improved by 2.096 times, and the dual-channel interferometric data acquisition method can significantly enhance the data retrieval accuracy.
Assessment of Fruit Traits and Antioxidant Capacity in Wild and Cultivated Genotypes of Ziziphus sp.
Authors: Șumălan Radu Liviu , Copolovici Dana Maria , Crișan Manuela , Stănică Florin , Șumălan Renata Maria , Lupitu Andreea , Vicas Simona Ioana , Mot Silvia , Copolovici Lucian , Ciulca Sorin
Published: January 2025

The genus Ziziphus includes numerous species, both cultivated and wild, offering significant genetic variability and economic potential that are often overlooked. Due to their high variability and ecological plasticity, jujube species and genotypes can be utilized in marginal areas and on land where few plants could be efficiently exploited. This study investigated variations in morphological characteristics (qualitative and quantitative), bioactive content (e.g., DPPH radicals), and antioxidant capacity in fruits, leaves, and stones of cultivated Z. jujuba genotypes (‘Hu Ping Zao’ and ‘Jun Zao’) and wild genotypes (Z. acido-jujuba and ‘Jurilovca’), using different solvents (water, ethanol, and methanol). The mass and dimensions of the fruits as well as their parameters (fresh and dry weight, length, width, and pulp-to-stone ratio) and the antioxidant potential of different plant organ types (leaves, fruit pulps, and stones) were determined. The results showed that the cultivated genotypes produced larger and heavier fruits with a higher pulp percentage than the wild forms of the same species. However, the wild forms exhibited higher antioxidant capacities than the cultivated genotypes, depending on the type of plant organ analyzed and the solvent used for extraction.
Methodological Impact on Curing Kinetics of Bone Cement Based on Poly (Styrene-co-Methyl Methacrylate)–2D Nanofiller Nanocomposites
Authors: Krishnan Mohan Raj , Alsharaeh Edreese Housni
Published: January 2025

Herein, we report the methodological impact on the curing kinetics of bone cement based on polymer nanocomposites prepared using different methods. Poly (styrene-co-methylmethacrylate)–2D nanofiller nanocomposites (P(S-MMA)–2D Nanofiller) were prepared using bulk and suspension polymerization methods to study the effect of the different methods. The prepared nanocomposites were well-characterized for chemical, thermal, mechanical, and structural characteristics using Fourier Transform Infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), nano-indentation, and scanning electron microscopy (SEM) techniques, respectively. The FT-IR results confirmed the successful formation of the polymer nanocomposites. The DSC results showed that the prepared nanocomposites have higher thermal stabilities than their copolymer counterparts. The nano-indentation results revealed that the elastic modulus of the copolymer nanocomposites (bulk polymerization) was as high as 7.89 GPa, and the hardness was 0.219 GPa. Incorporating the 2D nanofiller in the copolymer matrix synergistically enhances the thermo-mechanical properties of the bone cement samples. The polymer nanocomposites prepared using the suspension polymerization method exhibit faster-curing kinetics (15 min) than those prepared using the bulk polymerization (120–240 min) method.
A 3D-Printed Aqueous Drainage Tube with an Expandable Inner Diameter to Accommodate the Intraocular Pressure (IOP) Fluctuations After Glaucoma Surgery
Authors: Kim Jae-Seok , Jeong Hun-Jin , Park Ji-Woo , Gwak So-Jung , Han Jeong-Sun , Jung Kyoung In , Lee Seung-Jae
Published: January 2025

Glaucoma treatment involves reducing the intraocular pressure (IOP), which can damage the optic nerve, to a normal range. Aqueous drainage devices may be used for treatment, and a variety of devices have been proposed. However, they have a non-variable and uniform inner diameter, which makes it difficult to accommodate the IOP fluctuations that occur after glaucoma surgery. To ensure effective treatment in the early post-operative period with low IOP and the late post-operative period with high IOP, the inner diameter should be expandable over time to allow for smooth aqueous drainage. Here, we applied 3D printing technology with a tri-axial nozzle to develop an aqueous drainage tube that can expand its inner diameter. The distinct bilayer structure of the device allows it to expand its inner diameter through biodegradation, which can accommodate the IOP fluctuations that often occur after glaucoma surgery. The fabricated structure was evaluated in a series of tests, including leakage, cytotoxicity, and degradation experiments. The device did not show any leakage, was not toxic to cells, and demonstrated the expansion of the inner diameter through biodegradation. The device may provide a more effective post-operative solution for glaucoma patients by alleviating the effects of low IOP in the early post-operative period and high IOP in the late post-operative period.
Stress Analysis and Strength Prediction of Carbon Fiber Composite Laminates with Multiple Holes Using Cohesive Zone Models
Authors: Alharthi Hamzah , Abdellah Mohammed Y.
Published: January 2025

Composite materials play a crucial role in various industries, including aerospace, automotive, and shipbuilding. These materials differ from traditional metals due to their high specific strength and low weight, which reduce energy consumption in these industries. The damage behavior of such materials, especially when subjected to stress discontinuities such as central holes, differs significantly from materials without holes. This study examines this difference and predicts the damage behavior of carbon fiber composites with multiple holes using a progressive damage model through finite element analysis (FEM). Two holes were positioned along the central axis of symmetry in the longitudinal and transverse directions relative to the load. The presence of additional holes acts as a stress-relief factor, reducing stress by up to 17% when the holes are arranged in the longitudinal direction. A cohesive zone model with two parameters, including constant and linear shapes, was applied to develop a simple analytical model for calculating the nominal strength of multi-hole composite laminates, based on the unnotched plate properties of the material. The results closely match experimental findings. The data also provide design tables that can assist with material selection.
Investigation of the Sensitivity of Acoustic Emission to the Differentiation Between Mode I, II, and III Fracture in Bulk Polymer Materials
Authors: Shivaie Kojouri Ali , Aggelis Dimitrios G. , Karami Javane , Sharma Akash , Van Paepegem Wim , Van Hemelrijck Danny , Kalteremidou Kalliopi-Artemi
Published: January 2025

There is very limited research in the literature investigating the way acoustic emission signals change when polymer materials are undergoing different fracture modes. This study investigates the capability of acoustic emission to recognize the fracture mode through acoustic emission parameter analysis, and can be considered the first-ever study which examines the impact of different loading conditions, i.e., fracture mode I, mode II, and mode III, on the acoustic emission parameters in polymer materials. To accomplish this, prism-like pre-cracked polymer specimens were tested under the three different fracture modes. Acoustic emission parameters appeared sensitive to the different loading conditions of the pre-cracked specimens, indicating that acoustic emission can be used to distinguish the three fracture modes in polymer materials. Both frequency and time parameters reflect changes in the stress states at the crack tip. The duration and rise time of the waveforms were found to be the most sensitive acoustic emission parameters for identifying the fracture mode, while the average frequency variation can be employed to differentiate between in-plane and out-of-plane fracture modes. In order to interpret the experimental results in relation to wave mechanics, numerical wave propagation simulations for longitudinal and shear excitations were performed to simulate tensile and shear fracture modes and the corresponding emitted waves. An interesting correlation between the experimental and numerical results exists, showcasing acoustic emission’s potential for fracture identification.
Transformer–Gate Recurrent Unit-Based Hourly Purified Natural Gas Prediction Algorithm
Authors: Su Chang , Huang Jingcai , Dong Shasha , He Yuqi , Li Ji , Hu Luyao , Liu Xiao , Liao Yong
Published: January 2025

With the rapid development of industrial automation and intelligence, the consumption of resources and the environmental impact of production processes cannot today be ignored. Today, natural gas, as a commonly used energy source, produces significantly lower emissions of carbon dioxide, sulphur dioxide, and nitrogen oxides from combustion than coal and oil, and can be further purified to remove the small amount of impurities it contains, such as sulphur compounds. Therefore, purified natural gas (hereinafter referred to as purified gas), as a clean energy source, plays an important role in realising sustainable development. At the same time, It becomes more and more important to dispatch purified gas resources reasonably and accurately, and the paramount factor is that the load of purified gas needs to be predicted accurately. Therefore, this paper proposes a Transformer–GRU-based hourly prediction model for purified gas. The model uses the Transformer model for data fusion and feature extraction, and then combines the time series processing capability of the Gate Recurrent Unit (GRU) model to capture long-term dependencies and short-term dynamic changes in time series data. In this paper, the purified gas load data of Chongqing Municipality in 2020 was first preprocessed, and then divided into daily and hourly load datasets according to the measurement step. Meanwhile, considering the influence of temperature factor, the experimental dataset is subdivided according to whether it includes temperature data or not, and then the Transformer–GRU model was built for prediction, respectively. The results show that, compared with the Dual-Stage Attention-Based Recurrent Neural Network (DA-RNN) and the Transformer and GRU models alone, the Transformer–GRU model exhibits good performance in terms of the coefficient of determination, the average absolute percentage error, and mean square error, which can well meet the requirement of hourly prediction accuracy and has greater application value.
Will Dissolved Hydrogen Reveal the Instability of the Anaerobic Digestion Process?
Authors: Platošová Daniela , Rusín Jiří , Svoboda Radek , Vašinková Markéta
Published: January 2025

Dissolved hydrogen is a critical factor in maintaining the delicate balance among microbial species that drive anaerobic digestion. Since previous findings have demonstrated a correlation between dissolved hydrogen concentration and volatile fatty acid (VFA) levels, we propose to evaluate the use of dissolved hydrogen concentration in digestate as an alternative to traditional VFA measurements. The aim is to determine whether dissolved hydrogen could serve as a faster, more accurate, and more efficient indicator of process instability in anaerobic digestion. An integral part of this task also involves addressing the technical challenge of identifying a suitable sensor that meets our requirements. In this study, we evaluated the ratio of dissolved hydrogen concentration to Total Inorganic Carbon as a potential alternative to the traditional stability indicator, Volatile Fatty Acids/Total Inorganic Carbon (VFA/TIC), also referred to as Flüchtige Organische Säuren/Totales Anorganisches Carbonat (FOS/TAC). The single-stage anaerobic digestion process was carried out in a Terrafors IS rotary drum bioreactor for 150 days at an average temperature of 40 °C and an organic volatile load of 0.092 kg m−3 d−1. Corn silage was dosed on weekdays as the substrate. With a theoretical retention time of 45 days, a biogas production of 0.219 Nm3kgVs−1 with a CH4 content of 31.6% was achieved. The values of the determined VFA/TIC stability indicator ranged from 0.22 to 5.66, with the highest values obtained when the reactor was overloaded. The dissolved hydrogen concentration ranged 0.005–0.196 mg dm−3. The Pearson correlation coefficient was 0.337 and the Spearman correlation coefficient was 0.468. The amperometric microsensor has proven to be unsuitable for field applications due to its lack of sensitivity and short lifetime. The proposed ratio of dissolved hydrogen concentration to TIC did not prove to be significantly more effective than the established VFA/TIC indicator.
Energy Consumption Prediction and Optimization of the Electrical Submersible Pump Well System Based on the DA-RNN Algorithm
Authors: Sui Xianfu , Han Guoqing , Lu Xin , Xing Zhisheng , Liang Xingyuan
Published: January 2025

The electrical submersible pump (ESP) well system is widely used in the oil industry due to its advantages of high displacement and lift capability. However, it is associated with significant energy consumption. In order to conserve electrical energy and enhance the efficiency of petroleum companies, a deep learning-based energy consumption calculation method is proposed and utilized to optimize the most energy-efficient operating regime. The energy consumption of the ESP well system is precisely determined through the application of the Pearson correlation coefficient analysis method, which is utilized to examine the relationship between production parameters and energy usage. This process aids in identifying the input parameters of the model. Following this, an energy consumption prediction model is developed using the dual-stage attention-based recurrent neural network (DA-RNN) algorithm. To evaluate the accuracy of the DA-RNN model, a comparison of its errors is carried out in comparison to three other deep learning algorithms: Gated Recurrent Unit (GRU), Long Short-Term Memory (LSTM), and Transform. Lastly, an orthogonal experiment is executed using the chosen model to pinpoint the most energy-efficient operating regime. Analysis of 325 ESP wells in the Bohai PL oil field indicated that ten parameters, including choke diameter, casing pressure, pump inlet pressure, pump outlet pressure, motor temperature, frequency, oil production, gas production, water production, and GOR significantly impact the energy consumption of the ESP well system. Consequently, these parameters were selected as input variables for the deep learning model. Due to the attention mechanisms employed in the encoding and decoding stages, the DA-RNN algorithm achieved the best performance during model evaluation and was chosen for constructing the energy consumption prediction model. Furthermore, the DA-RNN algorithm demonstrates better model generalization capabilities compared to the other three algorithms. Based on the energy consumption prediction model, the operating regime of the ESP system was optimized to save up to 12% of the maximum energy. The energy consumption of the ESP well system is affected by numerous parameters, and it is difficult to comprehensively evaluate and predict quantitatively. Thus, this work proposes a data-driven model based on the DA-RNN algorithm, which has a dual-stage attention mechanism to rapidly and accurately predict the energy consumption of the ESP well system. Optimization of production parameters using this model can effectively reduce energy consumption.