bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of the effects of P4ha1 and P4ha2 deletion on post-translational modifications of fibrillar collagens in mouse skin
Authors: Sarohi Vivek 
Published: February 2025

IntroductionCollagens, the most abundant proteins in mammals, play pivotal roles in maintaining tissue structure, functions, cell-to-cell communication, cellular migration, cellular behavior, and growth. Structures of collagens are highly complex due to the presence of dynamic post-translational modifications (PTMs), such as hydroxylations (on prolines and lysine residues) and O-glycosylation (on hydroxylysines) enzymatically catalyzed during biosynthesis in the endoplasmic reticulum. Collagen PTMs are essential for maintaining structural stability, elasticity, and different functions of collagens. The most prevalent modification in fibrillar collagens is prolyl 4-hydroxylation catalyzed by collagen prolyl 4-hydroxylases (C-P4Hs). Prolyl 4-hydroxylation on collagens plays a critical role in collagen biosynthesis, thermostability, and cell-collagen interactions. Collagens are large proteins. Different regions of collagen perform different functions, so the presence or absence of a PTM on a particular collagen site can affect its functioning. However, comprehensive site-specific identification of these PTMs on fibrillar collagen chains of mice skin has not been performed yet. Furthermore, the effects of prolyl 4-hydroxylase alpha 1 (P4HA1) and P4HA2 on 3-hydroxyproline, 5-hydroxylysine, and O-glycosylation sites of fibrillar collagen chains have not yet been explored.MethodologyThis study presents a comprehensive PTM analysis of fibrillar collagen chains extracted from the skin of different mutants of C-P4Hs (P4ha1+/−; P4ha2−/−, P4ha1+/+; P4ha2−/−, P4ha1+/−; P4ha2+/−, P4ha1+/+; P4ha2+/−) and wild-type mice. In this study, proteomics-based comprehensive PTM site identification by MS2 level ions from raw mass spectrometry data was performed, and MS1-level quantification was performed for PTM occupancy percentage analysis.Results and discussionA total of 421 site-specific PTMs were identified on fibrillar collagen chains (COL1A1, COL1A2, and COL3A1) extracted from wild-type mice skin. A total of 23 P4HA1-specific and seven P4HA2-specific 4-hydroxyproline sites on fibrillar collagen chains were identified. Moreover, it was found that the P4ha1 and P4ha2 deletion can affect the 3-hydroxyproline occupancy percentages in mice skin. Interestingly, increased levels of lysyl 5-hydroxylation were detected upon partial deletion of P4ha1 and full deletion of P4ha2. These findings show that the effects of deletion of prolyl 4-hydroxylases are not limited to less 4-hydroxylation on some specific proline sites, but it can also modulate the prolyl 3-hydroxylation, lysyl 5-hydroxylation, and O-glycosylation occupancy percentages in the fibrillar collagen chains in a site-specific manner.
Evaluating oxidative stress targeting treatments in in vitro models of placental stress relevant to preeclampsia
Authors: Afrose Dinara , Johansen Matt D. , Nikolic Valentina , Karadzov Orlic Natasa , Mikovic Zeljko , Stefanovic Milan , Cakic Zoran , Hansbro Philip M. , McClements Lana 
Published: February 2025

BackgroundPreeclampsia is a complex pregnancy disorder characterized by the new onset of hypertension and organ dysfunction, often leading to significant maternal and fetal morbidity and mortality. Placental dysfunction is a hallmark feature of preeclampsia, which is often caused by inappropriate trophoblast cell function in association with oxidative stress, inflammation and/or pathological hypoxia. This study explores the role of oxidative stress in trophoblast cell-based models mimicking the preeclamptic placenta and evaluates potential therapeutic strategies targeting these mechanisms.MethodsUric acid (UA) and malondialdehyde (MDA) concentrations were measured in human plasma from women with preeclampsia (n = 24) or normotensive controls (n = 14) using colorimetric assays. Custom-made first trimester trophoblast cell line, ACH-3P, was exposed to various preeclampsia-like stimuli including hypoxia mimetic (dimethyloxalylglycine or DMOG, 1 mM), inflammation (tumour necrosis factor or TNF-α, 10 ng/mL) or mitochondria dysfunction agent, (Rhodamine-6G or Rho-6G, 1 μg/mL), ± aspirin (0.5 mM), metformin (0.5 mM), AD-01 (100 nM) or resveratrol (15 µM), for 48 h. Following treatments, UA/MDA, proliferation (MTT), wound scratch and cytometric bead, assays, were performed.ResultsOverall, MDA plasma concentration was increased in the preeclampsia group compared to healthy controls (p &lt; 0.001) whereas UA showed a trend towards an increase (p = 0.06); when adjusted for differences in gestational age at blood sampling, MDA remained (p &lt; 0.001) whereas UA became (p = 0.03) significantly correlated with preeclampsia. Our 2D first trimester trophoblast cell-based in vitro model of placental stress as observed in preeclampsia, mimicked the increase in UA concentration following treatment with DMOG (p &lt; 0.0001), TNF-α (p &lt; 0.05) or Rho-6G (p &lt; 0.001) whereas MDA cell concentration increased only in the presence of DMOG (p &lt; 0.0001) or Rho-6G (p &lt; 0.001). Metformin was able to abrogate DMOG- (p &lt; 0.01), Rho-6G- (p &lt; 0.0001) or TNF-α- (p &lt; 0.01) induced increase in UA, or DMOG- (p &lt; 0.0001) or TNF-α- (p &lt; 0.05)induced increase in MDA. AD-01 abrogated UA or MDA increase in the presence of TNF-α (p &lt; 0.001) or Rho-6G (p &lt; 0.001)/DMOG (p &lt; 0.0001), respectively. The preeclampsia-like stimuli also mimicked adverse impact on trophoblast cell proliferation, migration and inflammation, most of which were restored with either aspirin, metformin, resveratrol, or AD-01 (p &lt; 0.05).ConclusionOur 2D in vitro models recapitulate the response of the first trimester trophoblast cells to preeclampsia-like stresses, modelling inappropriate placental development, and demonstrate therapeutic potential of repurposed treatments.
Exposure to polystyrene nanoplastics impairs sperm metabolism and pre-implantation embryo development in mice
Authors: Liu Yingdong , Hao Fengdan , Liang Haixin , Liu Wenqiang , Guo Yi 
Published: February 2025

IntroductionMicroplastics and nanoplastics are prevalent environmental contaminants. Recent reports indicate that polystyrene nanoparticles may adversely impact male reproductive health. This study aims to examine the effects of polystyrene exposure on sperm metabolism and the development of pre-implantation embryos.MethodsIn this study, male C57BL/6 mice were orally gavage-administered polystyrene nanoplastics (60 nm, 20 mg/kg/day) for 35 days to assess their impact on male reproduction and early embryonic development. Experiments included testicular transcriptome analysis, sperm metabolomics, sperm motility and fertilization assays, embryonic ROS detection, and RNA sequencing of 2-cell embryos, revealing the adverse effects of polystyrene exposure on sperm metabolism and embryo development.ResultsThe results revealed that oral gavage of polystyrene to male mice induced a pronounced immune-inflammatory response in testicular tissue, reduced sperm motility, and significantly lowered the fertilization rate. Notably, sperm from treated mice exhibited substantial metabolic disruptions, affecting key pathways, including glycerophospholipid biosynthesis and DNA repair. After fertilization, embryos at the 2-cell stage suffered damage in apoptotic and DNA repair pathways, subsequently impairing early embryo development.DiscussionIn conclusion, this study demonstrated that the oral gavage administration of polystyrene nanoplastics to male mice significantly affects male reproductive function, resulting in abnormalities in early embryonic development and alterations in associated gene expression profiles. These findings offer essential scientific insights for future research into sperm-mediated transgenerational effects and their impact on early embryonic development.
Design, synthesis, in silico studies and antiproliferative evaluation of some novel hybrids of pyrimidine-morpholine
Authors: Ataollahi Elaheh , Emami Leila , Al-Dies Al-Anood Mohammad , Zare Fateme , Poustforoosh Alireza , Emami Mina , Saadat Fateme , Motamen Fateme , Rezaei Zahra , Khabnadideh Soghra 
Published: February 2025

IntroductionCancer is a complex group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. These cells can invade nearby tissues and organs, or they may metastasize to other parts of the body through the bloodstream or lymphatic system.MethodsIn this study, eight novel pyrimidine-morpholine hybrides (2a-2h) were designed and synthesized based on molecular hybridization approach to identify potent cytotoxic agents. Spectroscopic methods, including infrared spectroscopy (IR), proton and carbon nuclear magnetic resonance (1HNMR &amp; 13CNMR), and mass spectrometry, were employed to confirm the structures of the compounds. The cytotoxic effects of the derivatives were evaluated against cancerous cell lines, including MCF-7 and SW480, using the MTT assay.Results and discussionIt was demonstrated that all derivatives had appropriate cytotoxic potential with IC50 in range of 5.12–117.04 μM. Compound 2g was identified as the most potent compound, exhibiting IC50 values of 5.10 ± 2.12 μM and 19.60 ± 1.13 μM toward the SW480 and MCF-7 cell lines, respectively. Cell cycle analysis showed that 2g could induces phase arrest in MCF-7 breast cancer cells. The apoptosis assay demonstrated the induction of apoptosis in the SW480 cell line. The biological activity of the compounds was confirmed by the docking studies. DFT analysis for compounds 2g and 2h was conducted at the B3LYP/6-31+G** level of theory. It was concluded that 2g is both thermodynamically and kinetically more stable than 2h. Moreover, the interpretation of ADME (Absorption, Distribution, Metabolism, and Excretion) indicates that these new series of compounds possess acceptable prognostic physicochemical properties. These synthesized compounds may serve as promising candidates for further investigation as anticancer agents.
Vertical porous 1D/2D hybrid aerogels with highly matched charge storage performance for aqueous asymmetric supercapacitors
Authors: Xu Panji , Quan Kunhua , Wei Xiyuan , Li Yubing , Xu Shuaikai 
Published: February 2025

Asymmetric supercapacitors (ASCs) have attracted widespread attention because of their high energy density, high power density and long cycle life. Nevertheless, the development of anodes and cathodes with complementary potential windows and synchronous energy storage kinetics represents a pivotal challenge. We propose to construct nanochannel-coupled vertically porous CNF/Ti3CNTx and CNF/rGO hybrid aerogel electrodes via a unidirectional bottom-up cryoprocess. The vertically porous structure will greatly shorten the ion diffusion path and enhance the charge/ion transfer/diffusion kinetics, and the inserted cellulose nanofibers (CNFs) will impede the re-stacking of the nanosheets and enlarge the interlayer nano-channels, thus improving the accessibility of electrolyte ions. Ultimately, all-solid-state ASCs assembled based on nanochannel-coupled vertically porous MXene and graphene aerogel can achieve an excellent energy density of 20.8 Wh kg−1 at 2.3 kW·kg−1, a high multiplicity performance, and retains 95.1% of energy density after 10,000 cycles. This work not only demonstrates the great superiority of nanochannel-coupled vertically porous hybrid aerogels, but also provides an effective strategy for designing asymmetric supercapacitor electrodes with matched structural and electrochemical properties.
Establishment of a novel double-antibody sandwich fluorescence microsphere immunochromatographic test strip for rapid detection of swine acute diarrhea syndrome coronavirus (SADS-CoV) infection
Authors: Cong Xiao , Tong Fei , Liu Huizhen , Zhu Yujun , Tan Ningxin , Gu Feng , Wang Huanan , Cong Feng 
Published: February 2025

IntroductionSwine acute diarrhea syndrome coronavirus (SADS-CoV) is an enveloped, positive-sense, single-stranded RNA virus that causes clinical symptoms such as vomiting and diarrhea in 10-day-old piglets. SADS-CoV has caused significant economic losses in the swine industry in southern China. Currently, no effective treatments or vaccines are available for this disease, making it crucial to establish a point-of-care testing (POCT) technology for early diagnosis and prevention.MethodsIn this study, we first validated the specificity and immunogenicity of four monoclonal antibodies (mAbs) targeting the nucleocapsid (N) protein of swine acute diarrhea syndrome coronavirus (SADS-CoV). The optimal antibody pair for constructing the fluorescent microsphere-based immunochromatographic assay (FM-ICA) was determined through systematic pairwise screening. Critical parameters of the FM-ICA test strip, including antibody labeling concentration, coating concentration, incubation time, and sample dilution ratio, were subsequently optimized. Analytical performance characteristics of the developed FM-ICA were then rigorously evaluated. Finally, clinical validation was conducted by parallel testing of 72 field samples using both FM-ICA and quantitative PCR (qPCR), followed by concordance rate analysis.ResultsFirst, we demonstrated that all four monoclonal antibodies exhibited favorable immunogenicity and specificity. Subsequently, mAb 12E1 was identified as the coating antibody, and mAb 5G12 was selected as the labeled antibody, forming the optimal combination for FM-ICA preparation. After optimization, the ideal parameters were determined: a labeling concentration of 200 μg/mg for antibodies, a coating concentration of 1 mg/mL, an incubation time of 10 min, and a dilution factor of 10. The FM-ICA exhibited outstanding specificity, sensitivity, reproducibility, and stability, achieving a maximum detectable dilution factor of 1280 and a limit of detection (LOD) of 78 PFU mL⁻¹. Finally, the concordance rate between FM-ICA and qPCR for clinical samples reached 97.22%.DiscussionThese results indicate that FM-ICA is an excellent POCT technology that can be used for the early diagnosis of SADS-CoV, providing support for disease prevention and treatment.
Characteristics and risk factors of type I or II endoleaks after thoracic endovascular aortic repair and open surgery
Authors: Zhu Fan , Chen Jia , Guo Yuanyuan , Shu Chang 
Published: February 2025

BackgroundType I endoleaks (T1ELs) and type II endoleaks (T2ELs) are among the most severe complications that occur after thoracic endovascular aortic repair (TEVAR) and open surgery. This investigation aimed to analyze the predictors and multiple risk factors of T1ELs and T2ELs, with a particular focus on the diameter of the false lumen and the pathology of the left subclavian artery (LSA).MethodsA total of 245 patients (mean age 57 ± 13 years) who had undergone open surgery or TEVAR were recruited and followed for a mean of 18 ± 10 months. Seven patients (2.8%) were classified into the T1EL group, and another seven (2.8%) were classified into the T2EL group. Contrast-enhanced computed tomography angiography of the entire aorta confirmed the diagnosis of aortic disease (e.g., thoracic aortic dissection, thoracic aortic aneurysm, and/or type B intramural hematoma) as well as the presence of T1ELs or T2ELs.ResultsReoperation was more common in the T1EL group (n = 4; 57%) than in the T2EL group (n = 2; 29%); also, reintervention for stenting of the thoracic endovascular graft was more frequent in the T1EL group (4 vs. 1). In T1EL group, four patients (57%) accepted reoperation due to progressive enlargement of the false lumen’s diameter (aneurysm size &gt; 55 mm) (n = 4; 100%) and sharp, persistent chest and back pain (n = 4; 100%). In the T2EL group, two patients (29%) required reintervention due to the false lumen’s growth rate (&gt;5 mm in diameter per half year) and symptoms of pulmonary vascular compression such as hemoptysis and dyspnea (n = 2; 100%). The median survival rate of patients in the T1EL and T2EL groups was 31 months [95% confidence interval (CI) 0.0937–11.4] and 30 months (95% CI: 0.08775–10.67), respectively. The proximal opening angle of the LSA (OR 3.141, 95% CI: 2.615–3.773) was significantly associated with the incidence of T1EL. Both the proximal opening angle of the LSA and its diameter were significantly associated with the occurrence of T2ELs.ConclusionsTo prevent the occurrence of T1ELs and T2ELs, appropriate stent grafts and the pathology of the LSA should be carefully considered.
Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and cardiovascular disease mortality in patients with type 2 diabetes mellitus and diabetic kidney disease
Authors: Li Zhiyu , Xu Hongyang 
Published: February 2025

PurposeNon-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) represents an essential lipid index and is closely related to the occurrence and development of diabetes and cardiovascular diseases (CVDs). Therefore, this study is intended to further investigate the association between the NHHR index and the mortality rate of CVDs in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD).MethodsThe research sample was selected from the NHANES (National Health and Nutrition Examination Survey) database, and 5136 individuals were categorized based on quartiles of the NHHR index. Restricted cubic plots and COX regression models were utilized to examine the thresholds and patterns of the NHHR index in relation to the risk of CVDs mortality among T2DM patients as well as those with DKD. Subgroup analyses and p-values were used to evaluate interactions between different variables.ResultsThe NHHR index shows a nonlinear association with cardiovascular mortality in two patient groups, following an L-shaped pattern. In individuals with T2DM, a lower NHHR index (&lt;1.68) correlates with an increased risk of death, demonstrating a 72.8% reduction in mortality risk for each unit increase in NHHR below this threshold. Similarly, among patients with DKD, a lower NHHR index (&lt;1.82) is associated with heightened cardiovascular mortality risk, indicating a 48.2% reduction in death risk for each unit increase in NHHR beneath the specified threshold. In patients diagnosed with T2DM, the third quartile of the NHHR index was significantly linked to reduced mortality risk; the association remained consistent even when additional variables were considered [Hazard Ratio (HR), 0.82; 95% Confidence Interval (CI) (0.69-0.97); P=0.019]. Among patients with DKD, cardiovascular mortality was notably higher in the third and fourth quartiles of the NHHR index [Quartile3 HR, 1.57; 95% CI (1.10-2.24), P=0.013; Quartile4 HR, 2.04; 95% CI (1.28-3.26), P=0.003].ConclusionsThe NHHR is below 1.68, and an increase in the NHHR index is associated with a reduced risk of CVD mortality in patients with T2DM. Similarly, when the NHHR falls below 1.82, an elevation in the NHHR index correlates with a decreased risk of CVD mortality in patients with DKD.
Association between life’s crucial 9 and severe abdominal aortic calcification in U.S. Adults: the mediating role of the systemic inflammatory response index
Authors: Tang Kaifeng , Wang Linping , Ye Jinming , Yuan Feng 
Published: February 2025

BackgroundLife’s Crucial 9 (LC9) is an emerging cardiovascular health scoring system that incorporates Life’s Essential 8 (LE8) alongside mental health factors. However, its relationship with severe abdominal aortic calcification (SAAC) remains poorly understood.ObjectivesThe objective of this study is to investigate the relationship between LC9 scores and the incidence of SAAC in the US population.MethodsData from 2,323 participants were analyzed, originating from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cycle. In exploring the dynamics of LC9, its constituents, and their relationship with SAAC, we employed advanced statistical methodologies, specifically multivariable logistic regression and weighted quantile sum regression. Subgroup interaction analyses were conducted to reinforce the conclusions, and mediation analysis was employed to investigate how the systemic inflammatory response index (SIRI) influences the connection between LC9 and SAAC.ResultsIn fully adjusted models, an increase of 10 points in LC9 scores was associated with a 26% reduction in the prevalence of SAAC, achieving statistical significance (P &lt; 0.001). As LC9 scores increased, a significant decline in SAAC prevalence was noted (P &lt; 0.05). The WQS analysis pinpointed strong links between the occurrence of SAAC and variables including exposure to tobacco, blood pressure levels, blood glucose concentrations, and mental health status, the odds ratio stood at 0.244, with the 95% CI extending from 0.119 to 0.495. SIRI was positively correlated with SAAC (P &lt; 0.05) and decreased with rising LC9 scores (β = -0.09, P &lt; 0.001). Mediation analysis revealed that the SIRI significantly influenced the linkage between LC9 and SAAC, accounting for 5.8% of the mediation effect, with a statistically significant p-value (P &lt; 0.001).ConclusionThis research highlights a robust inverse relationship between elevated LC9 scores and reduced SAAC incidence, suggesting the significant role of LC9 as a key factor in diminishing the frequency of SAAC. Furthermore, SIRI mediates this relationship.
Ultrasound radiomics and genomics improve the diagnosis of cytologically indeterminate thyroid nodules
Authors: Chen Lu , Zhang Mingbo , Luo Yukun 
Published: February 2025

BackgroundIncreasing numbers of cytologically indeterminate thyroid nodules (ITNs) present challenges for preoperative diagnosis, often leading to unnecessary diagnostic surgical procedures for nodules that prove benign. Research in ultrasound radiomics and genomic testing leverages high-throughput data and image or sequence algorithms to establish assisted models or testing panels for ITN diagnosis. Many radiomics models now demonstrate diagnostic accuracy above 80% and sensitivity over 90%, surpassing the performance of less experienced radiologists and, in some cases, matching the accuracy of experienced radiologists. Molecular testing panels have helped clinicians achieve accurate diagnoses of ITNs, preventing unnecessary diagnostic surgical procedures in 42%–61% of patients with benign nodules.ObjectiveIn this review, we examined studies on ultrasound radiomics and genomic molecular testing for cytological ITNs conducted over the past 5 years, aiming to provide insights for researchers focused on improving ITN diagnosis.ConclusionRadiomics models and molecular testing have enhanced diagnostic accuracy before surgery and reduced unnecessary diagnostic surgical procedures for ITN patients.