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Abstract Background Although several transcriptome-wide association studies (TWASs) have been performed to identify genes associated with overall breast cancer (BC) risk, only a few TWAS have explored the differences in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer. Additionally, these studies were based on gene expression prediction models trained primarily in breast tissue, and they did not account for alternative splicing of genes. Methods In this study, we utilized two approaches to perform multi-tissue TWASs of breast cancer by ER subtype: (1) an expression-based TWAS that combined TWAS signals for each gene across multiple tissues and (2) a splicing-based TWAS that combined TWAS signals of all excised introns for each gene across tissues. To perform this TWAS, we utilized summary statistics for ER + BC from the Breast Cancer Association Consortium (BCAC) and for ER- BC from a meta-analysis of BCAC and the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). Results In total, we identified 230 genes in 86 loci that were associated with ER + BC and 66 genes in 29 loci that were associated with ER- BC at a Bonferroni threshold of significance. Of these genes, 2 genes associated with ER + BC at the 1q21.1 locus were located at least 1 Mb from published GWAS hits. For several well-studied tumor suppressor genes such as TP53 and CHEK2 which have historically been thought to impact BC risk through rare, penetrant mutations, we discovered that common variants, which modulate gene expression, may additionally contribute to ER + or ER- etiology. Conclusions Our study comprehensively examined how differences in common variation contribute to molecular differences between ER + and ER- BC and introduces a novel, splicing-based framework that can be used in future TWAS studies.

Abstract The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction

Objective In China, there is a unique type of second marriage (SM) family where the woman is remarried, and the man is experiencing his first marriage. Additionally, the woman is older than the man. Therefore, these families experience many challenges: psychological, emotional, and societal pressure. Such family is a typical sample for studying sociocultural and psychological stress influencing on outcome of assisted reproductive technology (ART). This study aimed to investigate the impact of social psychological stress on the live birth outcomes AR.Methods In this retrospective cohort, second marriage (SM) families who visited the Second Hospital of Hebei Medical University reproductive center between January 2012 to December 2022 were screened, and 561s marriage families (the SM group) with 5600 first marriage (FM) families (the FM group) were included undergoing their first ART cycles. The primary outcome of this study was the live birth rate (LBR).Results The live birth rate (LBR) of SM group (30.7%) is lower than that of the FM group (43.6%) (p

Cables are critical in engineering structures for load‐bearing, electronic connection, and mechanical transmission. Various cable‐crawling robots (CCRs) have been developed to perform scheduled inspection or convey supplies. Most existing CCRs are often actuated by motors and used in large‐scaled engineering structures. The heavy bodies of these CCRs can cause damage or even casualties once slippage or drop occurs. A small and lightweight CCR that can crawl on thin cables is highly demanded for safety inspection in narrow and confined inner spaces of engineering structures. Herein, a soft CCR (weight, 2.1 g; length, 43 mm) is developed by utilizing multilayered dielectric elastomer actuators. Compared with existing solutions, this CCR achieves crawling on thin cables (diameter:

BackgroundPrevious studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles.MethodsThis study involved 8,516 adult participants (aged 18–74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index.ResultsIn this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50–74 (except for hypertriglyceridemia, where the highest risk was among men aged 50–74 years), during winter/spring or under low/middle ultraviolet index environments.ConclusionsNonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D

Background and objectives: The intercornual distance in the sacral hiatus has yet to be studied precisely in children. This age-stratified, observational study aimed to clarify the changes in sacral hiatus dimensions and to quantify the correlations between the intercornual distance of the sacral hiatus and age, height, weight, and head circumference by using real-time ultrasonography. Methods: The patients were stratified into three groups: neonates and infants, toddlers, and schoolchildren. In the operating room, the ultrasonic probe was placed at the sacral cornua to obtain a transverse view of the sacral hiatus, and the intercornual distance was measured three times in millimetres. Results: The study included a total of 156 patients. The mean ± SD (95%CI) of intercornual distance in neonates and infants (36 months).The mean values of neonates and infants were different from those of toddlers and schoolchildren (p 0.05, 95 % CI mean difference −1.10 to 0.95).Intercornual distance was correlated with age, height, weight, and head circumference before one year of age (Spearman's R values > 0.7), but there was no correlation thereafter (Spearman's p value > 0.05). Conclusion: In the first year after birth, the intercornual distance increases rapidly with body growth; after one year of age, the sacral hiatus dimension changes significantly. Ultrasound is superior for assessing the gradually ossified cartilage components in older children.

Ribosomal DNA (rDNA) contains highly conserved, specifically organized sequences encoding ribosomal RNAs (rRNAs) separated by variable non-transcribed intergenic spacers (NTSs) and is abundant in eukaryotic genomes. These characteristics make the rDNA an informative molecular target to study genome organization, molecular evolution, and phylogenetics. In this study, we characterized the 5S rDNA repeats in the greater duckweed Spiroldela polyrhiza, a species known for its small size, rapid growth, highly conserved genome organization, and low mutation rate. Sequence analysis of at least 12 individually cloned PCR fragments containing the 5S rDNA units for each of six ecotypes that originated from Europe (Ukraine) and Asia (China) revealed two distinct types of 5S rDNA repeats containing NTSs of different lengths and nucleotide compositions. The shorter 5S rDNA repeat units had a highly homogeneous 400-bp NTS, with few ecotype- or region-specific single-nucleotide polymorphisms (SNPs). The longer 5S rDNA units had NTSs of 1056–1084 bp with characteristic intra- and inter-genomic variants due to specific SNPs and insertions/deletions of 4–15-bp DNA elements. We also detected significant variability in the ratio of short/long 5S rDNA variants between ecotypes of S. polyrhiza. The contrasting dynamics of the two types of 5S rDNA units, combined with the unusually low repeat copy number (for plants) in S. polyrhiza (46–220 copies per genome), shows that this species could serve as an excellent model for examining the mechanisms of concerted evolution and functional significance of rDNA variability.

Abstract History courses are an essential part of a national education. The application of traditional courseware's media forms in education still requires further development and refinement. Herein, we report on a history courseware mode that integrates various historical teaching media, including 360-degree VR, paintings, maps, infographics, text, audio, and videos, based on the SCORM standard. These media elements are used to provide learners with a multimodal learning experience in history courses. We monitor the learning effects using EEG and questionnaires. The results show a significant improvement in our multimodal courseware technology compared to traditional courseware.

In order to investigate the effect of different counts of carbon fiber protofilaments on the impact resistance of C/C-SiC composites, two types of C/C-SiC composites (3K-C/C-SiC and 12K-C/C-SiC) were produced through the ceramic substrate densification of 2.5D carbon fiber needled preforms with different counts of carbon fiber protofilaments (K) via a two-step chemical vapor infiltration (CVI) method. The density and open porosity of two kinds of C/C-SiC omposites were determined by the volumetric method and mercury porosimeter. The structure and morphology of C/C-SiC composites were characterized through characterization methods such as X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS). Results showed that the counts of carbon fiber protofilaments were found to have a significant impact on the structure and properties of C/C-SiC composites. Pyrolytic carbon (PyC) and SiC were uniformly deposited on the surfaces of two kinds of carbon fibers for C/C-SiC composites prepared by two-step CVI. The weight gain for the 3K carbon fiber 2.5D needled preform was approximately 30%, while it was about 25% for the 12K carbon fiber 2.5D needled preform. The 3K-C/C-SiC composites had a density of approximately 0.89 g/cm3 and an open porosity of about 52.87%. The 12K-C/C-SiC composites had a density of approximately 0.74 g/cm3 and an open porosity of about 56.53%. These differences were attributed to the lower fiber content, lower density, and greater porosity of the 3K carbon fiber 2.5D needled preform, which facilitated greater deposition of PyC and SiC on the surfaces of fibers. At the same time, the density of SiC was greater than that of C, resulting in a higher density and lower porosity of 3K-C/C-SiC composites. By characterizing the structure and morphology of two types of C/C-SiC composites, it was found that the SiC contents in 3K-C/C-SiC and 12K-C/C-SiC composites were about 27.2% and 11.1%, respectively, and the C contents were about 72.8% and 88.9%, respectively. The thicknesses of PyC layer in a single fiber bundle were about 2.162 and 2.145 μm, respectively. The thicknesses of SiC layers were approximately 1.890 and 1.284 μm, respectively. 3K-C/C-SiC composite material had a higher SiC content and lower C content. This was due to the lower carbon fiber content and higher porosity of the 3K carbon fiber 2.5D needle preform, which could cause more PyC and SiC to deposit on the surfaces of the carbon fibers. Through the impact resistance test, it was determined that the impact toughness of 3K-C/C-SiC and 12K-C/C-SiC composites was approximately 25.624 kJ/m2 and 14.310 kJ/m2, respectively, with absorbed energy values of about 1.52 J and 1.09 J, respectively. Results of pendulum impact tests showed that the 3K-C/C-SiC composites had superior impact resistance compared to the 12K-C/C-SiC composites. This enhanced impact resistance was mainly due to the thicker SiC layer on the surface of 3K-C/C-SiC composites, which required more fracture work, and PyC possessed excellent toughness, which enhanced the fibers’ impact resistance. Furthermore, the toughness of the 3K carbon fiber preform was superior to that of the 12K carbon fiber preform. As a result, fracturing the fiber bundles in the 3K-C/C-SiC required more fracture work.

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome–lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1–Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate.ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD.MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors.ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P

Abstract In recent years, the conservation and protection of ancient cultural heritage have received increasing attention, and non-destructive testing (NDT), which can minimize the damage done to the test subject, plays an integral role therein. For instance, NDT through active infrared thermal imaging can be applied to ancient polyptychs, which can realize accurate detection of damage and defects existing on the surface and interior of the polyptychs. In this study, infrared thermography is used for non-invasive investigation and evaluation of two polyptych samples with different pigments and artificial defects, but both reproduced based on a painting by Pietro Lorenzetti (1280/85–1348) using the typical tempera technique of the century. It is noted that, to avoid as far as possible secondary damages done to the ancient cultural heritages, repeated damage-detection experiments are rarely carried out on the test subjects. To that end, numerical simulation is used to reveal the heat transfer properties and temperature distributions, as to perform procedural verification and reduce the number of experiments that need to be conducted on actual samples. Technique-wise, to improve the observability of the experimental results, a total variation regularized low-rank tensor decomposition algorithm is implemented to reduce the background noise and improve the contrast of the images. Furthermore, the efficacy of image processing is quantified through the structural-similarity evaluation.

Background: There is limited research providing an overall understanding of bone mineral density (BMD) changes throughout different stages of life. This study aimed to investigate the pattern of BMD changes across childhood, adolescence, adulthood, and old age, as well as exploring the critical time of peak BMD (PBMD). Methods: Participants of three major ethnicities from National Health and Nutrition Examination Survey 1999 to 2018 were involved: 46,381 and 20,944 participants aged 8–85 years old were included in the Lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD) studies, respectively. BMD was measured using dual-energy X-ray absorptiometry. The generalized additive model was used to construct smoothed percentile curves. Results: Both males and females experienced a sharp increase in LSBMD during puberty, with females reaching their PBMD earlier than males. Females’ LSBMD remained higher than males’ before the age of approximately 50, except for Non-Hispanic Blacks. For males, LSBMD reached a plateau at around 30 years old after reaching the peak value. Females exhibited two peak points on the fitted curves, with the second PBMD occurring around 36–37 years old. Ethnic variations were observed, with Non-Hispanic Blacks displaying the highest BMD levels at all ages. Non-Hispanic Whites and Mexican Americans had lower BMD levels, with Mexican Americans generally exhibiting the lowest BMD. FNBMD reached its peak earlier than LSBMD, and males consistently had higher FNBMD than females. Conclusions: This nationally representative study contributes to the understanding of BMD changes across the lifespan, and might provide guidance for bone health interventions in different population groups.