A pilot study of microRNAs expression profile in plasma of patients with hydatid disease: potential immunomodulation of hydatid disease.

Echinococcosis is a zoonotic disease, which seriously endangers human health. The immune game between parasite and host is not fully understood. Exosomes are thought to be one of the ways of information communication between parasite and host. In this study, we attempted to explore the communication between Echinococcus granulosus and its host through the medium of exosomes. We collected plasma from E. granulosus patients (CE-EXO) and healthy donors (HD-EXO) and extracted exosomes from the plasma. The expression profile of miRNA in plasma was determined by second generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to annotate the function of target genes of differential miRNAs. Meanwhile, we co-cultured plasma exosomes from healthy donors and plasma exosomes from E. granulosus patients with Jurkat T cells with or without phytohaemagglutinin (PHA) stimulation. The expression of CD69 on Jurkat T cells was detected by flow cytometry. The results showed that the miRNA of exosomes between healthy donors and E. granulosus patients was significantly different. GO and KEGG were used to annotate the function of target genes of differential miRNAs. The results indicate that many important pathways are involved in inflammation, metabolism, and immune response after parasite infection, such as p53 signaling pathway, PI3K-Akt signaling pathway, and glycolysis/gluconeogenesis. Flow cytometry showed that CE-EXO reduced the expression of CD69 + on Jurkat T cells. Our present results suggest that these differentially expressed miRNAs may be important regulators of parasite-host interactions. Meanwhile, functional prediction of its target genes provides valuable information for understanding the mechanism of host-parasite interactions. These results provide clues for future studies on E. granulosus escape from host immune attack, which could help control E. granulosus infection.

Numerical Investigation on the Influence of Turbine Rotor Parameters on the Eddy Current Sensor for the Dynamic Blade Tip Clearance Measurement.

Eddy current sensors are increasingly being used to measure the dynamic blade tip clearance in turbines due to their robust anti-interference capabilities and non-contact measurement advantages. However, the current research primarily focuses on enhancing the performance of eddy current sensors themselves, with few studies investigating the influence of turbine rotor parameters on the measurements taken by these sensors for dynamic blade tip clearance. Hence, this paper addresses this gap by using COMSOL Multiphysics 6.2 software to establish a finite model with circuit interfaces. Additionally, the model's validity was verified through experiments. This model is used to simulate the voltage output of the sensor and the measurement of dynamic blade tip clearance under various rotor parameters. The results indicate that the length and number of blades, as well as the hub radius, significantly affect the sensor voltage output in comparison to rotation speed. Furthermore, we show that traditional static calibration methods are inadequate for measuring dynamic blade tip clearance using eddy current sensors. Instead, it is demonstrated that incorporating rotor parameters into the calibration of eddy current sensors can enhance the accuracy of dynamic blade tip clearance measurements.

Experimental Investigation on the Effect of Coil Shape on Planar Eddy Current Sensor Characteristic for Blade Tip Clearance.

Given the increasing application of eddy current sensors for measuring turbine tip clearance in aero engines, enhancing the performance of these sensors is essential for improving measurement accuracy. This study investigates the influence of coil shape on the measurement performance of planar eddy current sensors and identifies an optimal coil shape to enhance sensing capabilities. To achieve this, various coil shapes-specifically circular, square, rectangular wave, and triangular wave-were designed and fabricated, featuring different numbers of turns for the experiment at room temperature. By employing a method for calculating coil inductance, the performance of each sensor was evaluated based on key metrics: measurement range, sensitivity, and linearity. Experimental results reveal that the square coil configuration outperforms other shapes in overall measurement performance. Notably, the square coil demonstrated a measurement range of 0 mm to 8 mm, a sensitivity of 0.115685 µH/mm, and an impressive linearity of 98.41% within the range of 0 mm to 2 mm. These findings indicate that the square coil configuration enhances measurement capabilities. The conclusions drawn from this study provide valuable insights for selecting coil shapes and optimizing the performance of planar eddy current sensors, thereby contributing to the advancement of turbine tip clearance measurement techniques in aero engines.

Damage and Recovery Behavior of Low-Replacement-Rate Fly Ash Concrete after Different High-Temperature Exposures.

This study focuses on investigating the strength recovery of fire-damaged fly ash concrete (FAC) with a low substitution rate of 10% through post-fire curing. The chemical and microstructural changes were analyzed using X-ray diffraction (XRD), derivative thermogravimetry (DTG), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), and nitrogen adsorption. The findings indicate that the incorporation of fly ash slightly enhanced the strength after exposure to 400 °C; this was attributed to improved pozzolanic reactions, which were not observed at higher temperatures of 600 °C and 800 °C. Moreover, a positive effect on the recovery of compressive strength was observed due to the pozzolanic reaction. However, due to the relatively low fly ash content, depletion occurred at a later age, resulting in the inability to inhibit microstructural damage caused by the production of portlandite, thereby weakening the compressive strength. Interestingly, fly ash influenced the morphology of calcium carbonate and calcium silicate hydrate crystals, which is potentially ascribed to the role of high aluminum content acting as a crystallization-guiding agent.

Cost-effectiveness of adjuvant icotinib versus chemotherapy for patients with stage II-IIIA EGFR-mutated non-small cell lung cancer in China.

OBJECTIVE: Icotinib has been approved for adjuvant treatment of stage II-IIIA non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations in China, yet the long-term costs and outcomes of this strategy are unknown. Thus, we examined the cost effectiveness of adjuvant icotinib, compared with adjuvant chemotherapy, for the treatment of resected stage II-IIIA EGFR-mutated NSCLC. DESIGN: We performed a cost-effectiveness analysis from the perspective of the Chinese healthcare system, comparing 2-year adjuvant icotinib with four cycles of adjuvant chemotherapy. Costs and quality-adjusted life years (QALYs) were estimated using a Markov model. Model inputs were obtained from local data and literature. The influence of model parameters and assumptions was explored in sensitivity analyses. All costs are expressed in 2022 US dollars, and costs and QALYs were discounted at a rate of 5% per year. The willingness-to-pay (WTP) threshold was set at three times the per capita gross domestic product. SETTING: The Chinese healthcare system perspective. PARTICIPANTS: A hypothetical Chinese cohort of patients with resected stage II-IIIA EGFR-mutated NSCLC. INTERVENTIONS: Icotinib versus chemotherapy. PRIMARY OUTCOME MEASURE: Costs, QALYs, incremental cost-effectiveness ratio. RESULTS: The incremental cost per QALY gained with the use of 2-year icotinib, from the Chinese healthcare system perspective, was $3440.66 compared with adjuvant chemotherapy. At a WTP threshold of $40 500, adjuvant icotinib was the optimal treatment in over 99% of replications. The interpretation of the results was insensitive to model and input assumptions. CONCLUSIONS: Compared with adjuvant chemotherapy, adjuvant icotinib may be a cost-effective treatment for resected stage II-IIIA EGFR-mutated NSCLC as the WTP threshold is set at $40 500 per QALY.

Association between neural prosody discrimination and language abilities in toddlers: a functional near-infrared spectroscopy study.

BACKGROUND: Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay. METHODS: In this study, all cases(n = 241) were enrolled from a tertiary women's hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children's neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities. RESULTS: Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687. CONCLUSIONS: Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.

Reduced inhibition control ability in children with ADHD due to coexisting learning disorders: an fNIRS study.

Introduction: Inhibition control, as the core component of executive function, might play a crucial role in the understanding of attention deficit/hyperactivity disorder (ADHD) and specific learning disorders (SLD). Inhibition control deficits have been observed in children with ADHD or SLD. This study sought to test in a multi-modal fashion (i.e., behavior and plus brain imaging) whether inhibition control abilities would be further deteriorated in the ADHD children due to the comorbidity of SLD. Method: A total number of 90 children (aged 6-12 years) were recruited, including 30 ADHD, 30 ADHD+SLD (children with the comorbidity of ADHD and SLD), and 30 typically developing (TD) children. For each participant, a 44-channel functional near infrared spectroscopy (fNIRS) equipment was first adopted to capture behavioral and cortical hemodynamic responses during a two-choice Oddball task (a relatively new inhibition control paradigm). Then, 50 metrics were extracted, including 6 behavioral metrics (i.e., OddballACC, baselineACC, totalACC, OddballRT, baselineRT, and totalRT) and 44 beta values in 44 channels based on general linear model. Finally, differences in those 50 metrics among the TD, ADHD, and ADHD+SLD children were analyzed. Results: Findings showed that: (1) OddballACC (i.e., the response accuracy in deviant stimuli) is the most sensitive metric in identifying the differences between the ADHD and ADHD+SLD children; and (2) The ADHD+SLD children exhibited decreased behavioral response accuracy and brain activation level in some channels (e.g., channel CH35) than both the ADHD and TD children. Discussion: Findings seem to support that inhibition control abilities would be further decreased in the ADHD children due to the comorbidity of SLD.

Decreased wrist rotation imitation abilities in children with autism spectrum disorder.

Introduction: While meaningless gross motor imitation (GMI) is a common challenge for children diagnosed with autism spectrum disorder (ASD), this topic has not attracted much attention and few appropriate test paradigms have been developed. Methods: The current study proposed a wrist rotation imitation (WRI) task (a meaningless GMI assignment), and established a WRI ability evaluation system using low-cost wearable inertial sensors, which acquired the simultaneous data of acceleration and angular acceleration during the WRI task. Three metrics (i.e., total rotation time, rotation amplitude, and symmetry) were extracted from those data of acceleration and angular acceleration, and then were adopted to construct classifiers based on five machine learning (ML) algorithms, including k-nearest neighbors, linear discriminant analysis, naive Bayes, support vector machines, and random forests. To illustrate our technique, this study recruited 49 ASD children (aged 3.5-6.5 years) and 59 age-matched typically developing (TD) children. Results: Findings showed that compared with TD children, those with ASD may exhibit shorter total rotation time, lower rotation amplitude, and weaker symmetry. This implies that children with ASD might exhibit decreased WRI abilities. The classifier with the naive Bayes algorithm outperformed than other four algorithms, and achieved a maximal classification accuracy of 88% and a maximal AUC value of 0.91. Two metrics (i.e., rotation amplitude and symmetry) had high correlations with the gross and fine motor skills [evaluated by Gesell Developmental Schedules-Third Edition and Psychoeducational Profile-3 (PEP-3)]. While, the three metrics had no significant correlation with the visual-motor imitation abilities (evaluated by the subdomain of PEP-3) and the ASD symptom severity [evaluated by the Childhood Autism Rating Scale (CARS)] . Discussion: The strengths of this study are associated with the low-cost measurement system, correlation between the WRI metrics and clinical measures, decreased WRI abilities in ASD, and high classification accuracy.

A Key regulatory protein QRICH2 governing sperm function with profound antioxidant properties, enhancing sperm viability.

Infertility poses a global health and social challenge, affecting approximately 15% of couples at childbearing age, with half of the cases attributed to male factors, wherein genetic factors exert a substantial role. In our prior investigation, we identified loss-of-function variants within the gene encoding glutamine-rich protein 2 (QRICH2) in two consanguineous families, leading to various morphological abnormalities in sperm flagella and male infertility. Moreover, our observations in Qrich2 knockout mice revealed a pronounced reduction in spermatozoa count. However, the underlying mechanism remains elusive, prompting further investigation in the current study. By conducting experiments such as Hematoxylin-eosin (HE) staining, immunofluorescence staining, flow cytometry, and single sperm metabolism analysis on the testes and spermatozoa of Qrich2 knockout mice, we found a strong antioxidant capacity mediated by QRICH2 both in vivo and in vitro. Qrich2 knockout led to elevated levels of ROS, consequently inducing DNA damage in spermatids, which in turn triggered increased autophagy and apoptosis, ultimately causing a significant decrease in spermatozoa count. Incubation with the N-terminal purified protein of QRICH2 exhibited potent strong antioxidant activity at the cell and spermatozoa levels in vitro, thereby enhancing spermatozoa viability and motility. Therefore, QRICH2 plays a crucial role in safeguarding spermatids from excessive ROS-induced damage by augmenting antioxidant capacity, thereby promoting spermatozoa survival and improving motility. Furthermore, the N-terminal purified protein of QRICH2 shows promise as an additive for protecting spermatozoa during preservation and cryopreservation.

Learning shared template representation with augmented feature for multi-object pose estimation.

Template matching pose estimation methods based on deep learning have made significant advancements via metric learning or reconstruction learning. Existing approaches primarily build distinct template representation libraries (codebooks) from rendered images for each object, which complicate the training process and increase memory cost for multi-object tasks. Additionally, they struggle to effectively handle discrepancies between the distributions of training and test sets, particularly for occluded objects, resulting in suboptimal matching accuracy. In this study, we propose a shared template representation learning method with augmented semantic features to address these issues. Our method learns representations concurrently using metric and reconstruction learning as similarity constraints, and augments response of network to objects through semantic feature constraints for better generalization performance. Furthermore, rotation matrices serve as templates for codebook construction, leading to excellent matching accuracy compared to rendered images. Notably, it contributes to the effective decoupling of object categories and templates, necessitating the maintenance of only a shared codebook in multi-object pose estimation tasks. Extensive experiments on Linemod, Linemod-Occluded and TLESS datasets demonstrate that the proposed method employing shared templates achieves superior matching accuracy. Moreover, proposed method exhibits robustness on a collected aircraft dataset, further validating its efficacy.

Systematic analyses of the factors influencing sperm quality in patients with SARS-CoV-2 infection.

To figure out how does SARS-CoV-2 affect sperm parameters and what influencing factors affect the recovery of sperm quality after infection? We conducted a prospective cohort study and initially included 122 men with SARS-CoV-2 infection. The longest time to track semen quality after infection is 112 days and 58 eligible patients were included in our study eventually. We subsequently exploited a linear mixed-effects model to statistically analyze their semen parameters at different time points before and after SARS-CoV-2 infection. Semen parameters were significantly reduced after SARS-CoV-2 infection, including total sperm count (211 [147; 347] to 167 [65.0; 258], P < 0.001), sperm concentration (69.0 [38.8; 97.0] to 51.0 [25.5; 71.5], P < 0.001), total sperm motility (57.5 [52.3; 65.0] to 51.0 [38.5; 56.8], P < 0.001), progressive motility (50.0 [46.2; 58.0] to 45.0 [31.5; 52.8], P < 0.001). The parameters displayed the greatest diminution within 30 days after SARS-CoV-2 infection, gradually recovered thereafter, and exhibited no significant difference after 90 days compared with prior to COVID-19 infection. In addition, the patients in the group with a low-grade fever showed a declining tendency in semen parameters, but not to a significant degree, whereas those men with a moderate or high fever produced a significant drop in the same parameters. Semen parameters were significantly reduced after SARS-CoV-2 infection, and fever severity during SARS-CoV-2 infection may constitute the main influencing factor in reducing semen parameters in patients after recovery, but the effect is reversible and the semen parameters gradually return to normal with the realization of a new spermatogenic cycle.

Understanding bovine embryo elongation: a transcriptomic study of trophoblastic vesicles.

Background: During the process of elongation, the embryo increases in size within the uterus, while the extra-embryonic tissues (EETs) develop and differentiate in preparation for implantation. As it grows, the ovoid embryo transforms into a tubular form first and then a filamentous form. This process is directed by numerous genes and pathways, the expression of which may be altered in the case of developmental irregularities such as when the conceptus is shorter than expected or when the embryo develops after splitting. In bovines, efforts to understand the molecular basis of elongation have employed trophoblastic vesicles (TVs)-short tubular EET pieces that lack an embryo-which also elongate in vivo. To date, however, we lack molecular analyses of TVs at the ovoid or filamentous stages that might shed light on the expression changes involved. Methods: Following in vivo development, we collected bovine conceptuses from the ovoid (D12) to filamentous stages (D18), sectioned them into small pieces with or without their embryonic disc (ED), and then, transferred them to a receptive bovine uterus to assess their elongation abilities. We also grew spherical blastocysts in vitro up to D8 and subjected them to the same treatment. Then, we assessed the differences in gene expression between different samples and fully elongating controls at different stages of elongation using a bovine array (10 K) and an extended qPCR array comprising 224 genes across 24 pathways. Results: In vivo, TVs elongated more or less depending on the stage at which they had been created and the time spent in utero. Their daily elongation rates differed from control EET, with the rates of TVs sometimes resembling those of earlier-stage EET. Overall, the molecular signatures of TVs followed a similar developmental trajectory as intact EET from D12-D18. However, within each stage, TVs and intact EET displayed distinct expression dynamics, some of which were shared with other short epithelial models. Conclusion: Differences between TVs and EET likely result from multiple factors, including a reduction in the length and signaling capabilities of TVs, delayed elongation from inadequate uterine signals, and modified crosstalk between the conceptus and the uterus. These findings confirm that close coordination between uterine, embryonic, and extra-embryonic tissues is required to orchestrate proper elongation and, based on the partial differentiation observed, raise questions about the presence/absence of certain developmental cues or even their asynchronies.

Improving Accuracy of ADHD Diagnosis with the Combination of Brain Imaging and Behavioral Measures.

Neuropsychological measures may improve Attention-deficit/hyperactivity disorder (ADHD) diagnostic accuracy and enhance treatment response detection. Highquality evaluation indicators are necessary for accurate diagnosis of ADHD. Due to the high complexity of the pathogenesis of ADHD, it may not be possible to accurately diagnose ADHD only by relying on behavioral assessment or brain imaging examination. Therefore, the authors propose a comprehensive index that combines brain imaging behavioral and measures. The results showed that the classification performance of the composite index was better than that of the single behavior or brain image index.Clinical Relevance- The results of this study help to remind practicing clinicians to consider the results of multiple clinical examinations when clinically diagnosing ADHD patients.

Using machine learning to explore the characteristics of eye movement patterns and relationship with cognition ability of Chinese children aged 1-6 years.

Researchers have begun to investigate the relationship between eye movement characteristics of gaze patterns and cognitive abilities, and have attempted to use eye-tracking technology as a new method to evaluate cognitive abilities. Traditional eye movement analysis methods typically separate spatial and temporal information of eye movements, mostly analyze averaged data, and consider individual differences as noise. In addition, current eye movement studies on gaze patterns mostly involve adults, while research on infants and toddlers is limited with small sample sizes and narrow age ranges. It is still unknown whether the conclusions drawn from adult-based research can be applied to children. Consequently, eye movement research on gaze patterns in children is necessary. To address the concerns stated above, this study used the Hidden Markov machine learning method to model gaze patterns of 330 children aged 1-6 years while observing faces freely, and analyzed characteristics of eye movement gaze patterns. Additionally, we analyzed the correlation between gaze patterns of 31 toddlers aged 1-3 years and 37 preschoolers aged 4-6 years, and the different dimensions of cognitive abilities. The findings indicated that children exhibited holistic and analytic gaze patterns while observing different faces freely. More children adopted a holistic gaze pattern, and there were age-specific gaze pattern characteristics and regularities. Gaze patterns of toddlers may be correlated with their adaptive abilities and gaze patterns of preschoolers may be correlated with their visual space abilities. Specifically, toddlers aged 1-3 years showed a moderate negative correlation between the H-A scale and the adaptive dimension, while preschoolers aged 4-6 years showed a low negative correlation between the H-A scale and the visual space dimension. This study may provide new insights into the characteristics of children's eye-movement gaze patterns during face observation, and potentially offer objective evidence for future research aimed at promoting the use of eye-tracking technology in the assessment of toddlers' adaptive abilities and preschoolers' visual space abilities in the field of face perception.

Single-cell profiling reveals immune disturbances landscape and HLA-F-mediated immune tolerance at the maternal-fetal interface in preeclampsia.

Background: Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed. Methods: Single-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte. Results: A total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation. Conclusions: We revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.

Fatigue-Induced HCP-to-FCC Phase Transformation Resulting in Two FCC-Zr Variants in Pure Zirconium.

This study utilized transmission electron microscopy (TEM) and on-axis transmission Kikuchi diffraction (TKD) to investigate the fatigue-induced HCP-to-FCC phase transformation in industrial pure zirconium under a stress ratio of R = 0.1. The results show that fatigue damages result from phase deformations during cyclic loadings. The fatigue-induced FCC-Zr phases exhibit a B-type orientation relationship with the HCP-Zr matrix. Notedly, due to the different growth directions of Shockley partial dislocations relative to nucleation points, there are two FCC-Zr variants after the HCP-to-FCC phase transformation. The content of these two variants accounts for 65% and 35% of the total FCC-Zr, respectively, appearing as lamellae morphology embedded parallelly within the matrix. The distribution of the two variants includes isolated distribution and adjacent distribution. For the adjacent distribution, a twinning relationship is observed between the two variants. Meanwhile, as an intermediate transition stage of the HCP-to-FCC phase transformation, stacking faults are observed at the boundaries of the FCC-Zr lamellae. These findings offer insights into the microstructural features and formation mechanisms of fatigue-induced HCP-to-FCC phase transformation.

CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with a poor prognosis and growing incidence. In this study, we explored the potential roles of CDK1, CDK2, CDK4, and CDK6 in the progression of early-stage PDAC. Clinicopathologic and mRNA expression data and treatment information of 140 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy were obtained from the Cancer Genome Atlas data set. Our bioinformatic analysis showed that higher CDK1, CDK2, CDK4, or CDK6 expression was associated with a shorter median survival of the early-stage PDAC patients. Of note, in the low-proliferating pancreatic cancer group, CDKs expressions were significantly associated with proteins functioning in apoptosis, metastasis, immunity, or stemness. Among the low-proliferating PDAC, higher expression of CDK1 was associated with the shorter survival of patients, suggesting that CDK1 may regulate PDAC progression through cell cycle-independent mechanisms. Our experimental data showed that CDK1 knockdown/inhibition significantly suppressed the expression levels of AHR and POU5F1, two critical proteins functioning in cancer cell metastasis and stemness, in low-proliferating, but not in high-proliferating pancreatic cancer cells. In all, our study suggests that CDKs regulate PDAC progression not only through cell proliferation but also through apoptosis, metastasis, immunity, and stemness.

Identification of biomarkers and sex differences in the placenta of fetal growth restriction.

AIM: Fetal growth restriction (FGR) can lead to short-term and long-term impairments in the fetus. The placenta functions as an exchanger for substance transport, playing a critical role in fetal growth. However, the mechanism from the placental standpoint is still not fully understood. In this study, we aimed to investigate the pathophysiological mechanisms in the placenta that mediated the development of FGR and sex differences. METHODS: We analyzed the gene expression profiles of GSE100415 containing specific normotensive FGR placental samples and GSE114691 with canonical samples using three different methods, differentially expressed gene analysis, weighted gene co-expression network analysis, and gene set enrichment analysis. Gene enrichment was performed, including the gene ontology and pathway from the Kyoto Encyclopedia of Genes and Genomes. The important process was then validated in pregnant Wistar rats subcutaneously administered dexamethasone (0.2 mg/kg/d) or saline from gestation Day 9 to 21. RESULTS: Our results revealed little difference between the comparison of normal and normotensive FGR placental samples but confirmed the sex difference. Further analyses of the canonical samples identified the occurrence of vascular dysfunction, which was validated by the calculation of the vascular lumen area, showing that the vascular lumen in the FGR group was more than in the control. We also discovered 17 significantly expressed genes from the involved eigengenes. CONCLUSION: Our study provides an important theoretical and experimental basis to reevaluate the development of FGR from the placental standpoint and suggests a series of biomarkers for future clinical use.

Complex network of eye movements during rapid automatized naming.

Introduction: Although the method of visualizing eye-tracking data as a time-series might enhance performance in the understanding of gaze behavior, it has not yet been thoroughly examined in the context of rapid automated naming (RAN). Methods: This study attempted, for the first time, to measure gaze behavior during RAN from the perspective of network-domain, which constructed a complex network [referred to as gaze-time-series-based complex network (GCN)] from gaze time-series. Hence, without designating regions of interest, the features of gaze behavior during RAN were extracted by computing topological parameters of GCN. A sample of 98 children (52 males, aged 11.50 ± 0.28 years) was studied. Nine topological parameters (i.e., average degree, network diameter, characteristic path length, clustering coefficient, global efficiency, assortativity coefficient, modularity, community number, and small-worldness) were computed. Results: Findings showed that GCN in each RAN task was assortative and possessed "small-world" and community architecture. Additionally, observations regarding the influence of RAN task types included that: (i) five topological parameters (i.e., average degree, clustering coefficient, assortativity coefficient, modularity, and community number) could reflect the difference between tasks N-num (i.e., naming of numbers) and N-cha (i.e., naming of Chinese characters); (ii) there was only one topological parameter (i.e., network diameter) which could reflect the difference between tasks N-obj (i.e., naming of objects) and N-col (i.e., naming of colors); and (iii) when compared to GCN in alphanumeric RAN, GCN in non-alphanumeric RAN may have higher average degree, global efficiency, and small-worldness, but lower network diameter, characteristic path length, clustering coefficient, and modularity. Findings also illustrated that most of these topological parameters were largely independent of traditional eye-movement metrics. Discussion: This article revealed the architecture and topological parameters of GCN as well as the influence of task types on them, and thus brought some new insights into the understanding of RAN from the perspective of complex network.

AXL upregulates c­Myc expression through AKT and ERK signaling pathways in breast cancers.

Breast cancer (BC) is common worldwide. c-Myc and AXL are both overexpressed in BC, promoting its progression. The present study aimed to investigate the role of AXL in c-Myc expression in BC. Overexpression of AXL increased c-Myc expression while knockdown of AXL decreased c-Myc expression as determined by western blot analysis. Pharmaceutical inhibition of AXL also suppressed c-Myc expression. AKT and ERK inhibitor LY294002 and U0126 suppressed c-Myc expression, respectively. AXL overexpression which activates AKT and ERK signaling, upregulates c-Myc expression, while kinase-dead AXL which cannot activate AKT and ERK signaling, does not upregulate c-Myc expression, emphasizing the important role of these two signaling pathways in c-Myc upregulation. Finally, expression data of BC tissues from The Cancer Proteome Atlas displayed an association between AXL and c-Myc. Taken together, the present study revealed that AXL upregulates c-Myc expression through AKT and ERK signaling pathways in BC.