bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring a repurposed candidate with dual hIDO1/hTDO2 inhibitory potential for anticancer efficacy identified through pharmacophore-based virtual screening and in vitro evaluation
Authors: Aboomar Nourhan M. , Essam Omar , Hassan Afnan , Bassiouny Ahmad R. , Arafa Reem K.
Published: April 2024

Discovering effective anti-cancer agents poses a formidable challenge given the limited efficacy of current therapeutic modalities against various cancer types due to intrinsic resistance mechanisms. Cancer immunochemotherapy is an alternative strategy for breast cancer treatment and overcoming cancer resistance. Human Indoleamine 2,3-dioxygenase (hIDO1) and human Tryptophan 2,3-dioxygenase 2 (hTDO2) play pivotal roles in tryptophan metabolism, leading to the generation of kynurenine and other bioactive metabolites. This process facilitates the de novo synthesis of Nicotinamide Dinucleotide (NAD), promoting cancer resistance. This study identified a new dual hIDO1/hTDO2 inhibitor using a drug repurposing strategy of FDA-approved drugs. Herein, we delineate the development of a ligand-based pharmacophore model based on a training set of 12 compounds with reported hIDO1/hTDO2 inhibitory activity. We conducted a pharmacophore search followed by high-throughput virtual screening of 2568 FDA-approved drugs against both enzymes, resulting in ten hits, four of them with high potential of dual inhibitory activity. For further in silico and in vitro biological investigation, the anti-hypercholesterolemic drug Pitavastatin deemed the drug of choice in this study. Molecular dynamics (MD) simulations demonstrated that Pitavastatin forms stable complexes with both hIDO1 and hTDO2 receptors, providing a structural basis for its potential therapeutic efficacy. At nanomolar (nM) concentration, it exhibited remarkable in vitro enzyme inhibitory activity against both examined enzymes. Additionally, Pitavastatin demonstrated potent cytotoxic activity against BT-549, MCF-7, and HepG2 cell lines (IC50 = 16.82, 9.52, and 1.84 µM, respectively). Its anticancer activity was primarily due to the induction of G1/S phase arrest as discovered through cell cycle analysis of HepG2 cancer cells. Ultimately, treating HepG2 cancer cells with Pitavastatin affected significant activation of caspase-3 accompanied by down-regulation of cellular apoptotic biomarkers such as IDO, TDO, STAT3, P21, P27, IL-6, and AhR.
Evaluating tramway infrastructure on biodiversity and ecosystem services
Authors: Moroń Dawid , Beim Michał , Gudowska Agnieszka , Angeoletto Fabio , Celary Waldemar , Cwajna Aleksandra , Indykiewicz Piotr , Lenda Magdalena , Marjańska Emilia , Menzel Annette , Skórka Piotr , Tryjanowski Piotr
Published: April 2024

Tramways in urban areas for mass transit has been suggested to have a lower environmental footprint than roads. However, studies on the impact of tramways and the surrounding infrastructure on biodiversity is extremely rare despite the potential ecological effects associated with this anthropogenic feature. Surprisingly, we found fewer than 10 papers published on tramway-wildlife interactions, which is significantly lower (vs dozens of thousands) than that of other transportation methods. As tramways and stations may be managed sustainably by planting short vegetation on the track and roofs of tramway stations, they may be good examples of land-sharing policies in green urban planning, improving both biodiversity and people’s well-being. The potential environmental benefits of green practices for commercially available tramways should be strictly tested and applied, especially in the context of the growing popularity of tramway systems worldwide.
Reservoir ecosystems support large pools of fish biomass
Authors: Parisek Christine A. , De Castro Francine A. , Colby Jordan D. , Leidy George R. , Sadro Steve , Rypel Andrew L.
Published: April 2024

Humans increasingly dominate Earth’s natural freshwater ecosystems, but biomass production of modified ecosystems is rarely studied. We estimate potential fish total standing stock in USA reservoirs is 3.4 billion (B) kg, and approximate annual secondary production is 4.5 B kg y−1. We also observe varied and non-linear trends in reservoir fish biomass over time, thus previous assertions that reservoir fisheries decline over time are not universal. Reservoirs are globally relevant pools of freshwater fisheries, in part due to their immense limnetic footprint and spatial extent. This study further shows that reservoir ecosystems play major roles in food security and fisheries conservation. We encourage additional effort be expended to effectively manage reservoir environments for the good of humanity, biodiversity, and fish conservation.
A high-cholesterol diet promotes the intravasation of breast tumor cells through an LDL–LDLR axis
Authors: Magalhães Ana , Cesário Vanessa , Coutinho Diogo , Matias Inês , Domingues Germana , Pinheiro Catarina , Serafim Teresa , Dias Sérgio
Published: April 2024

Most metastases in breast cancer occur via the dissemination of tumor cells through the bloodstream. How tumor cells enter the blood (intravasation) is, however, a poorly understood mechanism at the cellular and molecular levels. Particularly uncharacterized is how intravasation is affected by systemic nutrients. High levels of systemic LDL-cholesterol have been shown to contribute to breast cancer progression and metastasis in various models, but the cellular and molecular mechanisms involved are still undisclosed. Here we show that a high- cholesterol diet promotes intravasation in two mouse models of breast cancer and that this could be reverted by blocking LDL binding to LDLR in tumor cells. Moreover, we show that LDL promotes vascular invasion in vitro and the intercalation of tumor cells with endothelial cells, a phenotypic change resembling vascular mimicry (VM). At the molecular level, LDL increases the expression of SERPINE2, previously shown to be required for both VM and intravasation. Overall, our manuscript unravels novel mechanisms by which systemic hypercholesterolemia may affect the onset of metastatic breast cancer by favouring phenotypic changes in breast cancer cells and increasing intravasation.
Proportioning optimization of transparent rock-like specimens with different fracture structures
Authors: Cui Jie , Hao Junshan , Li Ping , Li Chao , Zhang Youliang , Wang Kuilong
Published: April 2024

Clarifying the principles of proportioning optimization for brittle transparent rock-like specimens with differential fracture structures is crucial for the visualization study of the internal fracture and seepage evolution mechanisms in rock masses. This study, utilizing orthogonal experimental methods, uncovers the influence mechanisms, extents, and patterns by which the ratios of resin, hardener, and accelerator, along with the freezing duration, impact the mechanical characteristics of transparent rock-like specimens. Notably, it was observed that as the accelerator ratio and freezing time are increased, there’s a general decline in the uniaxial compressive strength, tensile strength, and elastic modulus of the specimens. In contrast, an increase in the hardener ratio initially leads to an enhancement in these mechanical properties, followed by a subsequent decrease. Under uniaxial compressive loading, the specimens exhibit four typical modes of failure: bursting failure, splitting failure, single inclined plane failure, and bulging failure. As the hardener and accelerator ratios increase, the mode of failure gradually shifts from bulging to bursting, with freezing time having a minor overall impact on the evolution of failure modes. The study proposes a method for inducing random three-dimensional closed fractures within the specimens and further clarifies the principles for optimizing the proportions of specimens with different fracture structures, such as intact, embedded regular, and random three-dimensional fractures. This research facilitates the in-depth application of transparent rock-like materials in various scenarios and provides theoretical guidance and technical support for visualizing the evolution of fracture and seepage characteristics within the fractured rock mass.
Comprehensive quantitative determination of aquifer confinement based on tidal response of well water level and its application in North China
Authors: Hu Chenyue , Liao Xin , Shi Yun , Liu Chunguo , Yan Rui , Lian Xiaoyang , Wang Zhenyu , Zhang Luming
Published: April 2024

Aquifer confinement represents a pivotal property that significantly influences the vulnerability and contamination risk of groundwater resources. Several methods have been proposed for determining aquifer confinement by analyzing the response of well water level to Earth tides and atmospheric tides. In this study, we evaluated the performance of the existing single methods and put forward an optimized comprehensive approach. We compared the determination results of the three single methods with those of a comprehensive method using water-level data from 39 earthquake precursor monitoring wells in North China. The results demonstrate that the comprehensive method effectively determined aquifer confinement, significantly reducing the uncertainty associated with the three single methods. The application of the comprehensive method in North China reveals that aquifer confinement may undergo temporal variations during long-term continuous observation, especially in areas where the confining properties of aquifers may vary due to human activities and earthquakes. In such areas, the comprehensive method facilitates accurate assessment of groundwater vulnerability, as well as the potential dispersion of underground pollutants.
An improved adaptive position tracking strategy for automatic shift actuator with uncertain parameters
Authors: Yin Chengqiang , Wang Shuai , Gao Jie , Xu Guangfei , Wu Jian
Published: April 2024

Realizing precise and fast position control of the gear is a challenging issue because of its nonlinearity, parameter uncertainty and external disturbance. Therefore, this paper researches the clutch position control considering the influence because of the factor on the system performance. By virtue of the traditional adaptive control method, an improved strategy based on finite time theory is proposed to further improve the convergence rate as well as the position tracking precision. First, a model of electromechanical clutch actuator system is established by theoretical analysis. Then, an enhanced adaptive controller is designed using finite time idea by introducing power function in the virtual control. And parameter update rate is adopted in the control action. Next, the stability of the control system is proved theoretically. Finally, Matlab simulations and experimental bench test are carried out to exhibit the effectiveness of the presented method. The results show that the satisfactory performance has been achieved with accurate position tracking and fast convergence speed.
Characterization of rotary valve control vibration system for vibration stress relief applications
Authors: Zhou Guoqiang , Zhao Guochao , Wang Hui
Published: April 2024

To enhance the vibration system characteristic distortion and pressure loss, we propose a novel rotary valve control vibration system. The paper presents the designed structural composition and generation mechanism of the rotary valve control vibration system. It also derives the mathematical model for the rotary valve distribution process and the overall system. The flow field inside the rotary valve is dynamically simulated using the multiple reference frame model, allowing for the determination of the change rule of the rotary valve’s output characteristics. An AMESim model was developed to analyze the vibration characteristics of the rotary valve control system. The effects of parameters such as inlet pressure, motor speed, and oil supply pump displacement were investigated. A rotary valve control vibration system experimental bench was constructed to experimentally verify the output characteristics of the rotary valve and the vibration characteristics of the system. The results indicate that the characteristic curve of the designed vibration system closely resembles a sinusoidal wave. Additionally, the rotary valve exhibits low pressure loss, making it more suitable for vibration stress relief applications. By appropriately increasing the inlet pressure and decreasing the motor speed, the vibration characteristics of the system can be improved.
The effect of continuous long-term illumination with visible light in different spectral ranges on mammalian cells
Authors: Dani Sophie , Schütz Kathleen , Dikici Ezgi , Bernhardt Anne , Lode Anja
Published: April 2024

One of the biggest challenges in tissue engineering and regenerative medicine is to ensure oxygen supply of cells in the (temporary) absence of vasculature. With the vision to exploit photosynthetic oxygen production by microalgae, co-cultivated in close vicinity to oxygen-consuming mammalian cells, we are searching for culture conditions that are compatible for both sides. Herein, we investigated the impact of long-term illumination on mammalian cells which is essential to enable photosynthesis by microalgae: four different cell types—primary human fibroblasts, dental pulp stem cells, and osteoblasts as well as the murine beta-cell line INS-1—were continuously exposed to warm white light, red or blue light over seven days. We observed that illumination with red light has no adverse effects on viability, metabolic activity and growth of the cells whereas exposure to white light has deleterious effects that can be attributed to its blue light portion. Quantification of intracellular glutathione did not reveal a clear correlation of this effect with an enhanced production of reactive oxygen species. Finally, our data indicate that the cytotoxic effect of short-wavelength light is predominantly a direct effect of cell illumination; photo-induced changes in the cell culture media play only a minor role.
A cAMP-biosensor-based assay for measuring plasma arginine–vasopressin levels
Authors: Doi Kosuke , Kawakami Kouki , Ikuta Tatsuya , Inoue Asuka
Published: April 2024

Arginine–vasopressin (AVP), a cyclic peptide hormone composed of nine amino acids, regulates water reabsorption by increasing intracellular cyclic adenosine monophosphate (cAMP) concentrations via the vasopressin V2 receptor (V2R). Plasma AVP is a valuable biomarker for the diagnosis of central diabetes insipidus (CDI) and is commonly measured using radioimmunoassay (RIA). However, RIA has several drawbacks, including a long hands-on time, complex procedures, and handling of radioisotopes with special equipment and facilities. In this study, we developed a bioassay to measure plasma AVP levels using HEK293 cells expressing an engineered V2R and a cAMP biosensor. To achieve high sensitivity, we screened V2R orthologs from 11 various mammalian species and found that the platypus V2R (pV2R) responded to AVP with approximately six-fold higher sensitivity than that observed by the human V2R. Furthermore, to reduce cross-reactivity with desmopressin (DDAVP), a V2R agonist used for CDI treatment, we introduced a previously described point mutation into pV2R, yielding an approximately 20-fold reduction of responsiveness to DDAVP while maintaining responsiveness to AVP. Finally, a comparison of plasma samples from 12 healthy individuals demonstrated a strong correlation (Pearson's correlation value: 0.90) between our bioassay and RIA. Overall, our assay offers a more rapid and convenient method for quantifying plasma AVP concentrations than existing techniques.
Loss of Y in regulatory T lymphocytes in the tumor micro-environment of primary colorectal cancers and liver metastases
Authors: Wójcik Magdalena , Juhas Ulana , Mohammadi Elyas , Mattisson Jonas , Drężek-Chyła Kinga , Rychlicka-Buniowska Edyta , Bruhn-Olszewska Bożena , Davies Hanna , Chojnowska Katarzyna , Olszewski Paweł , Bieńkowski Michał , Jankowski Michał , Rostkowska Olga , Hellmann Andrzej , Pęksa Rafał , Kowalski Jacek , Zdrenka Marek , Kobiela Jarek , Zegarski Wojciech , Biernat Wojciech , Szylberg Łukasz , Remiszewski Piotr , Mieczkowski Jakub , Filipowicz Natalia , Dumanski Jan P.
Published: April 2024

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.
Design, synthesis, and evaluation of novel arecoline-linked amino acid derivatives for insecticidal and antifungal activities
Authors: Pang Chaohai , Xu Yuan , Ma Xionghui , Li Shuhuai , Zhou Shengfu , Tian Hai , Wang Mingyue , Han Bingjun
Published: April 2024

A series of arecoline derivatives with amino acid moieties were designed and synthesised using an acylamide condensation strategy, taking arecoline as the foundational structure. The insecticidal efficacy of these compounds against Aphis craccivora and Tetranychus cinnabarinus was evaluated. Notably, derivatives 3h and 3i demonstrated superior insecticidal activity compared with arecoline. Additionally, 3h and 3i showed good fungicidal effectiveness against two types of plant fungi. Moreover, molecular docking analyses suggested that 3h and 3i could affect the nervous systems of A. craccivora and T. cinnabarinus by binding to neuronal nicotinic acetylcholine receptors. These findings suggest that compounds 3h and 3i represent promising leads for further development in insecticide and fungicide research.
Exploring hematological alterations and genetics linked to SNV rs10974944 in myeloproliferative neoplasms among Amazon patients
Authors: Paes Jhemerson F. , Torres Dania G. , Aquino Deborah C. , Alves Emanuela V. B. , Mesquita Erycka A. , Sousa Miliane A. , Fraiji Nelson Abrahim , Passos Leny N. M. , Abreu Rosângela S. , Silva George A. V. , Tarragô Andréa M. , de Souza Mourão Lucivana P.
Published: April 2024

BCR::ABL1-negative myeloproliferative neoplasms are hematopoietic disorders characterized by panmyelosis. JAK2 V617F is a frequent variant in these diseases and often occurs in the 46/1 haplotype. The G allele of rs10974944 has been shown to be associated with this variant, specifically its acquisition, correlations with familial cases, and laboratory alterations. This study evaluated the association between the 46/1 haplotype and JAK2 V617F in patients with myeloproliferative neoplasms in a population from the Brazilian Amazon. Clinical, laboratory and molecular sequencing analyses were considered. Carriers of the G allele of rs10974944 with polycythemia vera showed an increase in mean corpuscular volume and mean corpuscular hemoglobin, while in those with essential thrombocythemia, there was an elevation in red blood cells, hematocrit, and hemoglobin. Associations were observed between rs10974944 and the JAK2 V617F, in which the G allele (OR 3.4; p < 0.0001) and GG genotype (OR 4.9; p = 0.0016) were associated with JAK2 V617F + and an increase in variant allele frequency (GG: OR 15.8; p =  < 0.0001; G: OR 6.0; p = 0.0002). These results suggest an association between rs10974944 (G) and a status for JAK2 V617F, JAK2 V617F + _VAF ≥ 50%, and laboratory alterations in the erythroid lineage.
Experiencing beauty in everyday life
Authors: Knoll Anna Lena , Barrière Tristan , Weigand Rosalie , Jacobsen Thomas , Leder Helmut , Specker Eva
Published: April 2024

Beauty surrounds us in many ways every day. In three experience sampling (ESM) studies we investigated frequency, category of eliciting stimuli (natural vs human-made) and, the potential moderating role of several individual difference measures on such everyday experiences of beauty in an ecologically valid manner. Further, we explored the impact of such experiences on valence & arousal. Study 1 re-analysed data from a previous study, in line with the current aims. In Studies 2 and 3, we asked participants to report daily experiences of beauty using a mixed random and event-contingent sampling schedule. Mobile notifications (random sampling) prompted participants to take a photo and rate the beauty of their surroundings. Further, current valence and arousal were assessed. Notification frequency and total days of participation differed between these two studies. Participants were able to report additional experiences outside of the notification windows (event-contingent sampling). Our results indicate that we frequently encounter beauty in everyday life and that we find it in nature, in particular. Our results further suggest a mood-boosting effect of encounters with beauty. Lastly, our results indicate influences of individual differences however, these were inconclusive and require further attention.
The association of ALT to HDL-C ratio with type 2 diabetes in 50–74 years old adults: a population-based study
Authors: Emamian Abolfazl , Emamian Mohammad Hassan , Hashemi Hassan , Fotouhi Akbar
Published: April 2024

There is limited information about the relationship between diabetes mellitus (DM) and ALT to HDL-C ratio. This study aims to investigate this relationship for the first time in Iran. The data of this study were taken from the third phase of the Shahroud Eye Cohort Study, which was conducted in 2019 with the participation of 4394 people aged 50–74. ALT and HDL-C levels were measured using a BT-1500 autoanalyzer. The mean ALT/HDL-C ratio was reported along with 95% confidence intervals (CI). The multiple logistic regression was used to examine the association between this ratio and DM, while controlling for the effects of other independent variables. The mean and standard deviation of the ALT/HDL-C ratio in all participants were 16.62 ± 11.22 (95% CI 16.28–16.96). The prevalence of DM was 34.7% and individuals with DM had a mean ALT/HDL-C ratio that was 1.80 units higher than those without diabetes (P < 0.001). Also, in individuals with DM, the HDL-C was found to be 0.035 (mmol/L) lower (P < 0.001), while ALT was 1.13 (IU/L) higher (P < 0.001) compared to those without diabetes. Additionally, after controlling for confounding factors, the odds of developing DM increased in a non-linear manner with an increase in the ALT/HDL-C ratio. Abdominal obesity, advanced age, female gender, and hypertension were also found to be associated with increased odds of DM. In conclusion, an increase in the ALT/ HDL-C ratiowas associated with higher odds of DM. This ratio can serve as an important predictor for diabetes mellitus.
The influence of nanosunflower ash and nanowalnut shell ash on sustainable lightweight self-compacting concrete characteristics
Authors: Hilal Nahla , Hamah Sor Nadhim , Hadzima-Nyarko Marijana , Radu Dorin , Tawfik Taher A.
Published: April 2024

The absence of biodegradability exhibited by plastics is a matter of significant concern among environmentalists and scientists on a global scale. Therefore, it is essential to figure out potential pathways for the use of recycled plastics. The prospective applications of its utilisation in concrete are noteworthy. The use of recycled plastic into concrete, either as a partial or complete substitution for natural aggregates, addresses the issue of its proper disposal besides contributing to the preservation of natural aggregate resources. Furthermore, the use of agricultural wastes has been regarded as a very promising waste-based substance in the industry of concrete manufacturing, with the aim of fostering the creation of an environmentally sustainable construction material. This paper illustrates the impact of nano sunflower ash (NSFA) and nano walnut shells ash (NWSA) on durability (compressive strength and density after exposure to 800 °C and sulphate attack), mechanical properties (flexural, splitting tensile and compressive strength) and fresh characteristics (slump flow diameter, T50, V-funnel flow time, L-box height ratio, segregation resistance and density) of lightweight self-compacting concrete (LWSCC). The waste walnut shells and local Iraqi sunflower were calcinated at 700 ± 50 °C for 2 h and milled for 3 h using ball milling for producing NSFA and NWSA. The ball milling succeeded in reducing the particle size lower than 75 nm for NSFA and NWSA. The preparation of seven LWSCC concrete mixes was carried out to obtain a control mix, three mixtures were created using 10%, 20% and 30% NWSA, and the other three mixtures included 10%, 20% and 30% NSFA. The normal weight coarse aggregates were substituted by the plastic waste lightweight coarse aggregate with a ratio of 75%. The fresh LWSCC passing capacity, segregation resistance, and filling capability were evaluated. The hardened characteristics of LWSCC were evaluated by determining the flexural and splitting tensile strength at 7, 14 and 28 days and the compressive strength was measured at 7, 14, 28 and 60 days. Dry density and compressive strength were measured after exposing mixes to a temperature of 800 °C for 3 h and immersed in 10% magnesium sulphate attack. The results demonstrated that the LWSCC mechanical characteristics were reduced when the percentages of NWSA and NSFA increased, except for 10% NWSA substitution ratio which had an increase in splitting tensile strength test and similar flexural strength test to the control mixture. A minor change in mechanical characteristics was observed within the results of LWSCC dry density and compressive strength incorporating various NSFA and NWSA` contents after exposing to temperature 800 °C and immersed in 10% magnesium sulphate attack. Furthermore, according to the findings, it is possible to use a combination of materials consisting of 10–20% NSFA and 10–20% NWSA to produce LWSCC.
The effect of metabolism-related lifestyle and clinical risk factors on digestive system cancers in East Asian populations: a two-sample Mendelian randomization analysis
Authors: Cai Xianlei , Li Xueying , Liang Chao , Zhang Miaozun , Dong Zhebin , Yu Weiming
Published: April 2024

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93–0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05–1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53–0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34–0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37–0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves’ disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.
Markov chain-based impact analysis of the pandemic Covid-19 outbreak on global primary energy consumption mix
Authors: Ahmad Hussaan , Liaqat Rehan , Alhussein Musaed , Muqeet Hafiz Abdul , Aurangzeb Khursheed , Ashraf Hafiz Muhammad
Published: April 2024

The historic evolution of global primary energy consumption (GPEC) mix, comprising of fossil (liquid petroleum, gaseous and coal fuels) and non-fossil (nuclear, hydro and other renewables) energy sources while highlighting the impact of the novel corona virus 2019 pandemic outbreak, has been examined through this study. GPEC data of 2005–2021 has been taken from the annually published reports by British Petroleum. The equilibrium state, a property of the classical predictive modeling based on Markov chain, is employed as an investigative tool. The pandemic outbreak has proved to be a blessing in disguise for global energy sector through, at least temporarily, reducing the burden on environment in terms of reducing demand for fossil energy sources. Some significant long term impacts of the pandemic occurred in second and third years (2021 and 2022) after its outbreak in 2019 rather than in first year (2020) like the penetration of other energy sources along with hydro and renewable ones in GPEC. Novelty of this research lies within the application of the equilibrium state feature of compositional Markov chain based prediction upon GPEC mix. The analysis into the past trends suggests the advancement towards a better global energy future comprising of cleaner fossil resources (mainly natural gas), along with nuclear, hydro and renewable ones in the long run.
Synthesis and molecular docking studies of new aryl imeglimin derivatives as a potent antidiabetic agent in a diabetic zebrafish model
Authors: Khodakhah Aylin , Mohammadi Hassan , Abdoli Sina , Zarei Issa , Palimi Mahdie , Ekhtiari Zeinab , Talebi Meysam , Biglar Mahmood , Khorramizadeh Mohammad Reza , Amanlou Massoud
Published: April 2024

Diabetes mellitus (DM) is a persistent, progressive, and multifaceted disease characterized by elevated blood glucose levels. Type 2 diabetes mellitus is associated with a relative deficit in insulin mainly due to beta cell dysfunction and peripheral insulin resistance. Metformin has been widely prescribed as a primary treatment option to address this condition. On the other hand, an emerging glucose-reducing agent known as imeglimin has garnered attention due to its similarity to metformin in terms of chemical structure. In this study, an innovative series of imeglimin derivatives, labeled 3(a–j), were synthesized through a one-step reaction involving an aldehyde and metformin. The chemical structures of these derivatives were thoroughly characterized using ESI–MS, 1H, and 13C NMR spectroscopy. In vivo tests on a zebrafish diabetic model were used to evaluate the efficacy of the synthesized compounds. All compounds 3(a–j) showed significant antidiabetic effects. It is worth mentioning that compounds 3b (FBS = 72.3 ± 7.2 mg/dL) and 3g (FBS = 72.7 ± 4.3 mg/dL) have antidiabetic effects comparable to those of the standard drugs metformin (FBS = 74.0 ± 5.1 mg/dL) and imeglimin (82.3 ± 5.2 mg/dL). In addition, a docking study was performed to predict the possible interactions between the synthesized compounds and both SIRT1 and GSK-3β targets. The docking results were in good agreement with the experimental assay results.
Bacteriophage EPP-1, a potential antibiotic alternative for controlling edwardsiellosis caused by Edwardsiella piscicida while mitigating drug-resistant gene dissemination
Authors: Han Ganghua , Huang Ting , Liu Xinchun , Liu Ruyin
Published: April 2024

Edwardsiella piscicida causes significant economic losses to the aquaculture industry worldwide. Phage-based biocontrol methods are experiencing a renaissance because of the spread of drug-resistant genes and bacteria resulting from the heavy use of antibiotics. Here, we showed that the novel Edwardsiella phage EPP-1 could achieve comparable efficacy to florfenicol using a zebrafish model of Edwardsiella piscicida infection and could reduce the content of the floR resistance gene in zebrafish excreta. Specifically, phage EPP-1 inhibited bacterial growth in vitro and significantly improved the zebrafish survival rate in vivo (P = 0.0035), achieving an efficacy comparable to that of florfenicol (P = 0.2304). Notably, integrating the results of 16S rRNA sequencing, metagenomic sequencing, and qPCR, although the effects of phage EPP-1 converged with those of florfenicol in terms of the community composition and potential function of the zebrafish gut microbiota, it reduced the floR gene content in zebrafish excreta and aquaculture water. Overall, our study highlights the feasibility and safety of phage therapy for edwardsiellosis control, which has profound implications for the development of antibiotic alternatives to address the antibiotic crisis.
Safety and efficacy of fluoroscopy-guided urethral catheterization in case of failed blind or cystoscopy-assisted urethral catheterization
Authors: Kim Sang Woo , Nam In Chul , Kim Doo Ri , Lee Jeong Sub , Kim Jeong Jae , Kim Bong Su , Choi Guk Myung , Park Sung Eun
Published: April 2024

This retrospective study evaluated the safety and efficacy of fluoroscopy-guided urethral catheterization in patients who failed blind or cystoscopy-assisted urethral catheterization. We utilized our institutional database between January 2011 and March 2023, and patients with failed blind or cystoscopy-assisted urethral catheterization and subsequent fluoroscopy-guided urethral catheterization were included. A 5-Fr catheter was inserted into the urethral orifice, and the retrograde urethrography (RGU) was acquired. Subsequently, the operator attempted to pass a hydrophilic guidewire to the urethra. If the guidewire and guiding catheter could be successfully passed into the bladder, but the urethral catheter failed pass due to urethral stricture, the operator determined either attempted again with a reduced catheter diameter or performed balloon dilation according to their preference. Finally, an appropriately sized urethral catheter was selected, and an endhole was created using an 18-gauge needle. The catheter was then inserted over the wire to position the tip in the bladder lumen and ballooned to secure it. We reviewed patients’ medical histories, the presence of hematuria, and RGU to determine urethral abnormalities. Procedure-related data were assessed. Study enrolled a total of 179 fluoroscopy-guided urethral catheterizations from 149 patients (all males; mean age, 73.3 ± 13.3 years). A total of 225 urethral strictures were confirmed in 141 patients, while eight patients had no strictures. Urethral rupture was confirmed in 62 patients, and hematuria occurred in 34 patients after blind or cystoscopy-assisted urethral catheterization failed. Technical and clinical success rates were 100%, and procedure-related complications were observed in four patients (2.2%). The mean time from request to urethral catheter insertion was 129.7 ± 127.8 min. The mean total fluoroscopy time was 3.5 ± 2.5 min and the mean total DAP was 25.4 ± 25.1 Gy cm2. Balloon dilation was performed in 77 patients. Total procedure time was 9.2 ± 7.6 min, and the mean procedure time without balloon dilation was 7.1 ± 5.7 min. Fluoroscopy-guided urethral catheterization is a safe and efficient alternative in patients where blind or cystoscopy-assisted urethral catheterization has failed or when cystoscopy-urethral catheterization cannot be performed.
Skeletal muscle differentiation induces wide-ranging nucleosome repositioning in muscle gene promoters
Authors: Harris Sonalí , Anwar Iqra , Baksh Syeda S. , Pratt Richard E. , Dzau Victor J. , Hodgkinson Conrad P.
Published: April 2024

In a previous report, we demonstrated that Cbx1, PurB and Sp3 inhibited cardiac muscle differentiation by increasing nucleosome density around cardiac muscle gene promoters. Since cardiac and skeletal muscle express many of the same proteins, we asked if Cbx1, PurB and Sp3 similarly regulated skeletal muscle differentiation. In a C2C12 model of skeletal muscle differentiation, Cbx1 and PurB knockdown increased myotube formation. In contrast, Sp3 knockdown inhibited myotube formation, suggesting that Sp3 played opposing roles in cardiac muscle and skeletal muscle differentiation. Consistent with this finding, Sp3 knockdown also inhibited various muscle-specific genes. The Cbx1, PurB and Sp3 proteins are believed to influence gene-expression in part by altering nucleosome position. Importantly, we developed a statistical approach to determine if changes in nucleosome positioning were significant and applied it to understanding the architecture of muscle-specific genes. Through this novel statistical approach, we found that during myogenic differentiation, skeletal muscle-specific genes undergo a set of unique nucleosome changes which differ significantly from those shown in commonly expressed muscle genes. While Sp3 binding was associated with nucleosome loss, there appeared no correlation with the aforementioned nucleosome changes. In summary, we have identified a novel role for Sp3 in skeletal muscle differentiation and through the application of quantifiable MNase-seq have discovered unique fingerprints of nucleosome changes for various classes of muscle genes during myogenic differentiation.
An improved corner dealiasing and recognition algorithm for 2D Wadell roundness computation
Authors: Chen Jianhuang , Zhang Zhongjian , Lin Daming , Li Lihui , Xu Wenjie
Published: April 2024

This paper optimizes the 2D Wadell roundness calculation of particles based on digital image processing methods. An algorithm for grouping corner key points is proposed to distinguish each independent corner. Additionally, the cyclic midpoint filtering method is introduced for corner dealiasing, aiming to mitigate aliasing issues effectively. The relationships between the number of corner pixels (m), the central angle of the corner (α) and the parameter of the dealiasing degree (n) are established. The Krumbein chart and a sandstone thin section image were used as examples to calculate the 2D Wadell roundness. A set of regular shapes is calculated, and the error of this method is discussed. When α ≥ 30°, the maximum error of Wadell roundness for regular shapes is 5.21%; when 12° ≤ α < 30°, the maximum error increases. By applying interpolation to increase the corner pixels to the minimum number (m0) within the allowable range of error, based on the α-m0 relational expression obtained in this study, the error of the corner circle can be minimized. The results indicate that as the value of m increases, the optimal range interval for n also widens. Additionally, a higher value of α leads to a lower dependence on m. The study's results can be applied to dealiasing and shape analysis of complex closed contours.
The influence of hot isostatic pressing on precipitates, mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (wt.%) alloy manufactured by sand casting
Authors: Wang Dan , Ma Chao , Chen Ye , Gu Li , Yu Yangyang
Published: April 2024

Microstructures and mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (GZ1208K, wt.%) alloy under different treatments (as-cast: signed as nonHIP-GZ1208K, hot isostatic pressing (HIP): signed as HIP-GZ1208K) were characterized. Based on microstructure characterization, two prismatic precipitates, β′ and β1 precipitates, and one basal precipitate, γ′ precipitate, formed in both of nonHIP-GZ1208K and HIP-GZ1208K alloy. According to analysis, the area number density and the size of β′ precipitate could be adjusted through HIP treatment. The area number density of β′ precipitate increased after HIP treatment when aged at 32 h, and the size of β′ precipitate refined in both of the HIP-GZ1208K alloy aged at 8 h and 32 h. Except the influence of HIP treatment on microstructures, the ultimate tensile strength (UTS) and elongation of nonHIP-GZ1208K alloy also improved after HIP treatment. The UTS of the GZ1208K alloy aged at 8 h increased from 348 MPa (nonHIP-) to 371 MPa (HIP-) and the elongation increased from 2.6% to 4.7%. The density of the nonHIP-GZ1208K alloy increased after HIP treatment, that is to say the casting defects could be eliminated and the compactness of microstructures could be increased under the high pressure of HIP treatment.
Warming climate is helping human beings run faster, jump higher and throw farther through less dense air
Authors: Wang Shixin , Chen Tiexi , Luo Jing-Jia , Gao Meng , Zuo Hongchao , Ling Fenghua , Hu Jianlin , Yuan Chaoxia , Yang Yuanjian , Wang Lina , Huang Huaming , Wang Naiang , Li Yaojun , Yamagata Toshio
Published: April 2024

Understanding both positive and negative impacts of climate change is essential for comprehensively assessing and well adapting to the impacts of changing climate. Conventionally, climate warming is revealed to negatively impact human activities. Here, we reveal that human beings’ performance in anaerobic sports may benefit from climate warming. Using global weather observation and athletes’ performance datasets, we show that world-top athletes’ performances in nearly all athletics anaerobic events (i.e., sprints, jumps and throws) substantially improve as ambient temperature rises. For example, 100 m performance monotonically improves by 0.26 s as ambient temperature rises from 11.8° to 36.4 °C. Using Coupled Model Intercomparison Project Phase 6 datasets, we further show that global warming can substantially improve world-top athletes’ performance in eleven of the thirteen Olympics athletics anaerobic events by 0.27%–0.88% and 0.14–0.48% under high-emission and medium-emission scenarios, respectively, during 1979–2100. Among them, the improvements for 100 m are 0.59% (0.063 s) and 0.32% (0.034 s), respectively. Mechanism analysis shows that the warmed ambient atmosphere can improve competitors’ performance through expanding the air and thus reducing the air resistance to the competitors and throwing implements for hummer throw and all the sprints, hurdling and jumps. Quantitative analysis estimates that this thermodynamic process is essential for the impacts of warmed ambient atmosphere on the performances in these events as physiological processes are.
Assessing the feasibility of near-ambient conditions superconductivity in the Lu-N-H system
Authors: Fang Yue-Wen , Dangić Đorđe , Errea Ion
Published: April 2024

The report of near-ambient superconductivity in nitrogen-doped lutetium hydrides (Lu-N-H) has generated a great interest. However, conflicting results raised doubts regarding superconductivity. Here, we combine high-throughput crystal structure predictions with a fast predictor of superconducting critical temperature (Tc) based on electron localization function to shed light on the properties of Lu-N-H at 1 GPa. None of the predicted structures supports high-temperature superconductivity and the inclusion of nitrogen in the crystal structure predictions leads to more insulating structures than metallic ones in quantity. Despite the lack of near-ambient superconductivity, we consider alternative metastable templates and study their Tc and dynamical stability including quantum anharmonic effects. Lu4H11N exhibits a Tc of 100 K at only 20 GPa, a large increase compared to 30 K of its parent LuH3. Interestingly, it has a similar X-ray pattern to the experimental one. The LaH10-like LuH10 and CaH6-like LuH6 become high-temperature superconductors at 175 GPa and 100 GPa, with Tc of 286 K and 246 K, respectively. Our findings suggest that high-temperature superconductivity is not possible in stable phases at near-ambient pressure. However, at a slightly enhanced pressure of 20 GPa, high-Tc superconductivity emerges in Lu-H-N, and metastable room-temperature superconducting templates persist at high pressures.
Reframing trait trade-offs in marine microbes
Authors: Levine Naomi M. , Doblin Martina A. , Collins Sinéad
Published: April 2024

The oceans sequester a vast amount of carbon thus playing a central role in the global carbon cycle. Assessing how carbon cycling will be impacted by climate change requires an improved understanding of microbial dynamics, which are responsible for most carbon transformations in the oceans. Current numerical models used for predicting future states represent simplified microbial phenotypes and thus may not produce robust predictions of microbial communities. We propose reframing approaches for studying microbial trait change to allow for selection on multi-trait phenotypes. Integrating statistical approaches and trait-based models will allow for the incorporation of evolution into carbon cycle predictions.
In situ fabricating a Rh/Ga2O3 photothermal catalyst for dry reforming of methane
Authors: Li Yuqiao , Li Dezheng , Liu Huimin , Lei Yiming , Zhao Rongda , He Dehua , Zheng Ze , Luo Hui , Liu Aidi
Published: April 2024

Rh2O3/Ga2O3 is in situ reduced to Rh/Ga2O3−x during the photothermal DRM reaction. The Rh NPs and oxygen vacancies promote light absorption and reactant activation, respectively, thereby enhancing photothermal catalytic activity at 500 °C.
Impact of the sintering parameters on the microstructural and transport properties of 60 wt% Ce0.8Gd0.2O2−δ–40 wt% FeCo2O4 composites
Authors: Fischer Liudmila , Ran Ke , Sebold Doris , Behr Patrick , Baumann Stefan , Mayer Joachim , Nijmeijer Arian , Bouwmeester Henny , Guillon Olivier , Meulenberg Wilhelm A.
Published: April 2024

This article presents the connection between the sintering parameters and microstructural and functional transport properties of dual-phase composite.
Paper/GO/e-Au flexible SERS sensors for in situ detection of tricyclazole in orange juice and on cucumber skin at the sub-ppb level: machine learning-assisted data analysis
Authors: Nguyen Ha Anh , Mai Quan Doan , Nguyet Nga Dao Thi , Pham Minh Khanh , Nguyen Quoc Khanh , Do Trong Hiep , Luong Van Thien , Lam Vu Dinh , Le Anh-Tuan
Published: April 2024

Paper/GO/e-Au SERS substrates were fabricated to detect tricyclazole on cucumber skin and in orange juice. A machine learning model was developed for data analysis and to distinguish tricyclazole from 9 other organic compounds.
Recent advances in the functionalization, substitutional doping and applications of graphene/graphene composite nanomaterials
Authors: Narayan Jyoti , Bezborah Kangkana
Published: April 2024

Recently, graphene and graphene-based nanomaterials have emerged as advanced carbon functional materials with specialized unique electronic, optical, mechanical, and chemical properties.
Hydroxytyrosol ameliorates stress-induced liver injury through activating autophagy via HDAC1/2 inhibition
Authors: Fan Li , Zhao Lijuan , Zhu Yangbo , Li Lin , Yang Xueping , Ma Ping , Liu Jian , Zhao Qingwei , Li Xiaobo
Published: April 2024

The first evidence that HT induces autophagy in the hepatocytes by targeting HDAC1/2 for maintaining mitochondrial dysfunction, thus preventing inflammation and oxidative stress for exerting an anti-SLI effect.