STROBE-GnRHa pretreatment in frozen-embryo transfer cycles improves clinical outcomes for patients with persistent thin endometrium: A case-control study.

The well-prepared endometrium with appropriate thickness plays a critical role in successful embryo implantation. The thin endometrium is the main factor of frozen-embryo transfer (FET), resulting in the failure of implantation undergoing FET. Hormone treatment is suggested to improve endometrium thickness; however, among the larger numbers of cases, it cannot reach the sufficient thickness, which leads to a high cancelation rate of embryo transfer as well as waste high-quality embryos. Thus, it increases the burden to patients in both economic and psychological perspectives. We performed a retrospective observational study, which was composed with 2 cohorts, either with the conventional hormone replacement therapy (HRT) protocol or HRT with gonadotrophin-releasing hormone agonist (GnRHa) pretreatment to prepare the endometrium before FET. The measurements of endometrium thickness, hormone level, transfer cycle cancelation rate, pregnancy rate, and implantation rate were retrieved from the medical records during the routine clinic visits until 1 month after embryo transfer. The comparisons between 2 cohorts were performed by t-test or Mann-Whitney U test depending on the different attributions of data. In total, 49 cycles were under HRT with GnRHa pretreatment and 84 cycles were under the conventional HRT protocol. HRT with GnRHa pretreatment group improved the endometrial thickness (8.13 ± 1.79 vs 7.51 ± 1.45, P = .031), decreased the transfer cancelation rate (P = .003), and increased clinical pregnancy rate and implantation rate significantly (both P = .001). Additionally, luteinizing hormone level in pretreatment group was consistently lower than conventional HRT group (P < .05). Our study revealed HRT with GnRHa pretreatment efficiently improved the endometrial thickness, therefore, decreased the FET cycle cancelation. It also elevated the embryo implantation rate and clinical pregnancy rate by improving endometrial receptivity

OmniSeg3D: Omniversal 3D Segmentation via Hierarchical Contrastive Learning

Towards holistic understanding of 3D scenes, a general 3D segmentation method is needed that can segment diverse objects without restrictions on object quantity or categories, while also reflecting the inherent hierarchical structure. To achieve this, we propose OmniSeg3D, an omniversal segmentation method aims for segmenting anything in 3D all at once. The key insight is to lift multi-view inconsistent 2D segmentations into a consistent 3D feature field through a hierarchical contrastive learning framework, which is accomplished by two steps. Firstly, we design a novel hierarchical representation based on category-agnostic 2D segmentations to model the multi-level relationship among pixels. Secondly, image features rendered from the 3D feature field are clustered at different levels, which can be further drawn closer or pushed apart according to the hierarchical relationship between different levels. In tackling the challenges posed by inconsistent 2D segmentations, this framework yields a global consistent 3D feature field, which further enables hierarchical segmentation, multi-object selection, and global discretization. Extensive experiments demonstrate the effectiveness of our method on high-quality 3D segmentation and accurate hierarchical structure understanding. A graphical user interface further facilitates flexible interaction for omniversal 3D segmentation

Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis.

Sepsis claims an estimated 30 million episodes and 6 million deaths per year, and treatment options are rather limited. Human neutrophil peptides 1-3 (HNP1-3) are the most abundant neutrophil granule proteins but their neutrophil content varies because of unusually extensive gene copy number polymorphism. A genetic association study found that increased copy number of the HNP-encoding gene DEFA1/DEFA3 is a risk factor for organ dysfunction during sepsis development. However, direct experimental evidence demonstrating that these risk alleles are pathogenic for sepsis is lacking because the genes are present only in some primates and humans. Here, we generate DEFA1/DEFA3 transgenic mice with neutrophil-specific expression of the peptides. We show that mice with high copy number of DEFA1/DEFA3 genes have more severe sepsis-related vital organ damage and mortality than mice with low copy number of DEFA1/DEFA3 or wild-type mice, resulting from more severe endothelial barrier dysfunction and endothelial cell pyroptosis after sepsis challenge. Mechanistically, HNP-1 induces endothelial cell pyroptosis via P2X7 receptor-mediating canonical caspase-1 activation in a NLRP3 inflammasome-dependent manner. Based on these findings, we engineered a monoclonal antibody against HNP-1 to block the interaction with P2X7 and found that the blocking antibody protected mice carrying high copy number of DEFA1/DEFA3 from lethal sepsis. We thus demonstrate that DEFA1/DEFA3 copy number variation strongly modulates sepsis development in vivo and explore a paradigm for the precision treatment of sepsis tailored by individual genetic information

Influence of temperature on the transmission performance of track circuit in high-speed railway

In order to explore the influence of temperature on track circuit, a mathematical simulation model of track circuit is established. Then, the influence mechanism of temperature on the key equipment of track circuit is analysed. Finally, the influence on the receiver voltage and the locomotive signal current are computed based on the simulation model

Attentive Mask CLIP

Image token removal is an efficient augmentation strategy for reducing the cost of computing image features. However, this efficient augmentation strategy has been found to adversely affect the accuracy of CLIP-based training. We hypothesize that removing a large portion of image tokens may improperly discard the semantic content associated with a given text description, thus constituting an incorrect pairing target in CLIP training. To address this issue, we propose an attentive token removal approach for CLIP training, which retains tokens with a high semantic correlation to the text description. The correlation scores are computed in an online fashion using the EMA version of the visual encoder. Our experiments show that the proposed attentive masking approach performs better than the previous method of random token removal for CLIP training. The approach also makes it efficient to apply multiple augmentation views to the image, as well as introducing instance contrastive learning tasks between these views into the CLIP framework. Compared to other CLIP improvements that combine different pre-training targets such as SLIP and MaskCLIP, our method is not only more effective, but also much more efficient. Specifically, using ViT-B and YFCC-15M dataset, our approach achieves $43.9\%$ top-1 accuracy on ImageNet-1K zero-shot classification, as well as $62.7/42.1$ and $38.0/23.2$ I2T/T2I retrieval accuracy on Flickr30K and MS COCO, which are $+1.1\%$, $+5.5/+0.9$, and $+4.4/+1.3$ higher than the SLIP method, while being $2.30\times$ faster. An efficient version of our approach running $1.16\times$ faster than the plain CLIP model achieves significant gains of $+5.3\%$, $+11.3/+8.0$, and $+9.5/+4.9$ on these benchmarks

Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension. METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia. RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group. CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo

ATM-Mediated Phosphorylation of Cortactin Involved in Actin Polymerization Promotes Breast Cancer Cells Migration and Invasion

Background/Aims: The ataxia-telangiectasia mutated (ATM) protein kinase is critical for the maintenance of genomic stability and acts as tumor suppressor. Although evidence shows that a DNA damage-independent ATM (oxidized ATM) may be involved in cancer progression, the underlying mechanism is still unclear. Methods: Immunohistochemistry, immunofluorescence and western blotting were applied to detect the levels of oxidized ATM. Transwell assay was used to detect the cell migration and invasion abilities in different treatments. Quantitative phosphoproteome analysis was performed using hypoxic BT549 cells, in the presence or absence of Ku60019, a specific inhibitor of ATM kinase. The phosphorylated cortactin, the target protein of oxidized ATM, was confirmed by immunoprecipitation-western blots and in vitro kinase assay. The functions of phosphorylated cortactin were studied by specific short hairpin RNA, site-directed mutation, transwell assay, and actin polymerization assay. Results: Enhanced oxidized ATM proteins were present not only in the advanced and invasive breast tumor tissues but also malignant hypoxic breast cancer cells, in the absence of DNA damage. Loss of ATM expression or inhibiting oxidized ATM kinase activity reduced breast cancer cell migration and invasion. Using quantitative phosphoproteomics approach, 333 oxidized ATM target proteins were identified, some of these proteins govern key signaling associated with gap junction, focal adhesion, actin cytoskeleton rearrangement. Cortactin, one of the biggest changed phospho-protein, is a novel oxidized ATM-dependent target in response to hypoxia. Mechanically, we reveal that hypoxia-activated ATM can enhance the binding affinity of cortactin with Arp2/3 complex by phosphorylating cortactin at serine 113, and as a result, in favor of breast cancer cell migration and invasion. Conclusion: Oxidized ATM can phosphorylate cortactin at serine 113, playing a critical role in promoting breast tumor cell mobility and invasion via actin polymerization