miR-96/HBP1/Wnt/β-catenin regulatory circuitry promotes glioma growth

AbstractWe found that miR-96 is overexpressed in glioma, and its level inversely correlates with the survival of patients. The reduction in miR-96 abundance suppresses the proliferation and colony formation of glioma cells. The tumorigenicity of U-87 MG cells is reduced by miR-96 silencing. miR-96 contributes to the activation of Wnt/β-catenin pathway in glioma cells. HMG-box transcription factor 1 (HBP-1), a Wnt/β-catenin pathway inhibitor, is suppressed by miR-96. The reactivation of Wnt/β-catenin signaling causes an increase in the proliferation of glioma cells, and a decrease in miR-96 expression. On the other hand, HBP1 silencing promotes miR-96 expression. Collectively, miR-96 contributes to the progression of glioma by enhancing the activation of the Wnt/β-catenin pathway, and the miR-96/HBP1/Wnt/β-catenin regulatory circuitry promotes the proliferation of glioma cells

Improving Autonomous Driving Safety with POP: A Framework for Accurate Partially Observed Trajectory Predictions

Accurate trajectory prediction is crucial for safe and efficient autonomous driving, but handling partial observations presents significant challenges. To address this, we propose a novel trajectory prediction framework called Partial Observations Prediction (POP) for congested urban road scenarios. The framework consists of two key stages: self-supervised learning (SSL) and feature distillation. POP first employs SLL to help the model learn to reconstruct history representations, and then utilizes feature distillation as the fine-tuning task to transfer knowledge from the teacher model, which has been pre-trained with complete observations, to the student model, which has only few observations. POP achieves comparable results to top-performing methods in open-loop experiments and outperforms the baseline method in closed-loop simulations, including safety metrics. Qualitative results illustrate the superiority of POP in providing reasonable and safe trajectory predictions

IR-STP: Enhancing Autonomous Driving with Interaction Reasoning in Spatio-Temporal Planning

Considerable research efforts have been devoted to the development of motion planning algorithms, which form a cornerstone of the autonomous driving system (ADS). Nonetheless, acquiring an interactive and secure trajectory for the ADS remains challenging due to the complex nature of interaction modeling in planning. Modern planning methods still employ a uniform treatment of prediction outcomes and solely rely on collision-avoidance strategies, leading to suboptimal planning performance. To address this limitation, this paper presents a novel prediction-based interactive planning framework for autonomous driving. Our method incorporates interaction reasoning into spatio-temporal (s-t) planning by defining interaction conditions and constraints. Specifically, it records and continually updates interaction relations for each planned state throughout the forward search. We assess the performance of our approach alongside state-of-the-art methods in the CommonRoad environment. Our experiments include a total of 232 scenarios, with variations in the accuracy of prediction outcomes, modality, and degrees of planner aggressiveness. The experimental findings demonstrate the effectiveness and robustness of our method. It leads to a reduction of collision times by approximately 17.6% in 3-modal scenarios, along with improvements of nearly 7.6% in distance completeness and 31.7% in the fail rate in single-modal scenarios. For the community's reference, our code is accessible at https://github.com/ChenYingbing/IR-STP-Planner.Comment: 12 pages, 10 figures, accepted by IEEE-TITS at this Januar

Concept for a Future Super Proton-Proton Collider

Following the discovery of the Higgs boson at LHC, new large colliders are being studied by the international high-energy community to explore Higgs physics in detail and new physics beyond the Standard Model. In China, a two-stage circular collider project CEPC-SPPC is proposed, with the first stage CEPC (Circular Electron Positron Collier, a so-called Higgs factory) focused on Higgs physics, and the second stage SPPC (Super Proton-Proton Collider) focused on new physics beyond the Standard Model. This paper discusses this second stage.Comment: 34 pages, 8 figures, 5 table

MicroRNA-34a Attenuates Paclitaxel Resistance in Prostate Cancer Cells via Direct Suppression of JAG1/Notch1 Axis

Background/Aims: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. Methods: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. Results: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. Conclusion: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage

Tissue-based T cell activation and viral RNA persist for up to 2 years after SARS-CoV-2 infection.

The mechanisms of postacute medical conditions and unexplained symptoms after SARS-CoV-2 infection [Long Covid (LC)] are incompletely understood. There is growing evidence that viral persistence, immune dysregulation, and T cell dysfunction may play major roles. We performed whole-body positron emission tomography imaging in a well-characterized cohort of 24 participants at time points ranging from 27 to 910 days after acute SARS-CoV-2 infection using the radiopharmaceutical agent [18F]F-AraG, a selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the postacute COVID-19 group, which included those with and without continuing symptoms, was higher compared with prepandemic controls in many regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. T cell activation in the spinal cord and gut wall was associated with the presence of LC symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms specifically. Increased T cell activation in these tissues was also observed in many individuals without LC. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization of SARS-CoV-2 RNA and immunohistochemical studies in a subset of five participants with LC symptoms. We identified intracellular SARS-CoV-2 single-stranded spike protein-encoding RNA in rectosigmoid lamina propria tissue in all five participants and double-stranded spike protein-encoding RNA in three participants up to 676 days after initial COVID-19, suggesting that tissue viral persistence could be associated with long-term immunologic perturbations

Failure analysis and structural optimization for rotary mechanism of large sling based on thermal–mechanical coupling analysis

Rotary mechanism is the core part of the multi-functional sling for turning over and erecting the castings and forgings. The mechanical performance of a nail plate inside the structure determines the working safety. In this paper, the dangerous working condition of the rotary mechanism is first introduced when the castings and forgings with different diameters are clamped by the sling. Then, the temperature field and the thermal–mechanical coupling model for the nail plate are established, and the failure mode is analyzed. Next, the layout and shape of the nails on the nail plate are studied to improve the load-bearing performance. A mathematical model, taking the height and draft angle of the nail as the design variables, is established, and a new nail plate model is given. The comparison is carried out through simulation and experiment. The results show that the mechanical performances of the nail plate are significantly improved, and the failure problem of the rotary mechanism is solved