ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a

Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation and activate BMP signal pathway. The constitutively active ACVR1 is also found to be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial cells, which may cause the formation of FOP lesions. MicroRNAs (miRNAs) play an essential role in regulating cell differentiation. Here, we verified that miR-148a directly targeted the 3′ UTR of ACVR1 mRNA by reporter gene assays and mutational analysis at the miRNA binding sites, and inhibited ACVR1 both at the protein level and mRNA level. Further, we verified that miR-148a could inhibit the mRNA expression of the Inhibitor of DNA binding (Id) gene family thereby suppressing the BMP signaling pathway. This study suggests miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against FOP

DeepSeek LLM: Scaling Open-Source Language Models with Longtermism

The rapid development of open-source large language models (LLMs) has been truly remarkable. However, the scaling law described in previous literature presents varying conclusions, which casts a dark cloud over scaling LLMs. We delve into the study of scaling laws and present our distinctive findings that facilitate scaling of large scale models in two commonly used open-source configurations, 7B and 67B. Guided by the scaling laws, we introduce DeepSeek LLM, a project dedicated to advancing open-source language models with a long-term perspective. To support the pre-training phase, we have developed a dataset that currently consists of 2 trillion tokens and is continuously expanding. We further conduct supervised fine-tuning (SFT) and Direct Preference Optimization (DPO) on DeepSeek LLM Base models, resulting in the creation of DeepSeek Chat models. Our evaluation results demonstrate that DeepSeek LLM 67B surpasses LLaMA-2 70B on various benchmarks, particularly in the domains of code, mathematics, and reasoning. Furthermore, open-ended evaluations reveal that DeepSeek LLM 67B Chat exhibits superior performance compared to GPT-3.5

High-Throughput 3D Screening Reveals Differences in Drug Sensitivities between Culture Models of JIMT1 Breast Cancer Cells

Peer reviewe

Grazing Intensity and Phenotypic Plasticity in the Clonal Grass Leymus chinensis

Phenotypic plasticity enables plants to cope with changes in their environment. Plasticity in a population of Leymus chinensis, a common grass species in arid and semiarid temperate grasslands of northern China, was determined in a natural grassland grazed by large domestic herbivores. We measured shoot and bud characteristics monthly along a grazing intensity gradient indicated by distance from the village gate during two growing seasons. In addition, some plants along the gradient were removed to a common transplant garden and their growth was compared. Leaf characteristics (leaf angle, leaf length, and leaf number), growth form (tiller height and tiller clusters), bud proliferation, and plant fitness differed significantly in situ along the gradient. The expression of plasticity was grazing intensity dependent: the greatest increase in tiller density, tiller cluster, and bud number occurred at a moderate grazing intensity (2.5 km from the village gate). In the transplant garden, no evidence was found for distinct populations of L. chinensis within the grassland. Leaf characteristics, tiller growth form, and bud demography of tillers not grazed showed phenotypic plasticity in response to grazing of neighbor shoots because clonal reproduction is the main breeding system for this species in grazed natural grassland and defoliation of neighbor shoots is likely to affect the physiology and morphology of tillers that are not grazed. The observed overcompensation in vegetative reproduction may aid future survival and growth and could be achieved in a prudent grazing system designed to take into account the needs of this dominant grass in semiarid temperate steppes. (C) 2017 The Society for Range Management. Published by Elsevier Inc. All rights reserved

Effect of Al2O3 Content on High-Temperature Oxidation Resistance of Ti3SiC2/Al2O3

Considering the lack of an effective anti-oxidation protective layer for the oxidation process of Ti3SiC2, an in situ synthesis of Ti3SiC2 and Al2O3 was designed. Thermally stable Al2O3 was used to improve the high-temperature oxidation resistance of Ti3SiC2. Samples without TiC were selected for the oxidation test, and the oxidation morphology and weight gain curves of the oxidized surface in air at 1400 °C are reported. The change in the oxidation behavior occurred 4 h after oxidation. The addition of Al2O3 changed the composition of the oxide layer and compensated for the lack of a dense protective layer during Ti3SiC2 oxidation. Moreover, after 4 h of oxidation, the newly generated Al2TiO5 and the composite layer formed by diffusion were the main reasons for the large difference in the final weight gain between the two sets of samples

ZnS-embedded porous carbon for peroxydisulfate activation: Enhanced electron transfer for bisphenol A degradation

Transition metal sulfides have garnered increasing attention for their role in persulfate activation, a crucial process in environmental remediation. However, the function of metal sulfides without reversible valence changes, such as ZnS, remains largely unexplored in this context. Here we report ZnS-embedded porous carbon (ZnS-C), synthesized through the pyrolysis of Zn-MOF-74 and dibenzyl disulfide. ZnS-C demonstrates remarkable activity in activating peroxydisulfate (PDS) across a wide pH range, enabling the efficient mineralization removal of bisphenol A (BPA). Through electrochemical investigation and theoretical simulations of charge density distributions, we unveil that the electron transfer from BPA to PDS mediated by the ZnS-C catalyst governs the reaction. This study, both in theory and experiment, demonstrates metal sulfide as electron pump that enhances electron transfer efficiency in PDS activation. These findings redefine the role of metal sulfide catalysts, shedding new light on their potential for regulating reaction pathways in PDS activation processes

Aircraft Rotation Detection in Remote Sensing Image Based on Multi-Feature Fusion and Rotation-Aware Anchor

Due to the variations of aircraft types, sizes, orientations, and complexity of remote sensing images, it is still difficult to effectively obtain accurate position and type by aircraft detection, which plays an important role in intelligent air transportation and digital battlefield. Current aircraft detection methods often use horizontal detectors, which produce significant redundancy, nesting, and overlap of detection areas and negatively affect the detection performance. To address these difficulties, a framework based on RetinaNet that combines a multi-feature fusion module and a rotating anchors generation mechanism is proposed. Firstly, the multi-feature fusion module mainly realizes feature fusion in two ways. One is to extract multi-scale features by the feature pyramid, and the other is to obtain corner features for each layer of feature map, thereby enriching the feature expression of aircraft. Then, we add a rotating anchor generation mechanism in the middle of the framework to realize the arbitrary orientation detection of aircraft. In the last, the framework connects two sub-networks, one for classifying anchor boxes and the other for regressing anchor boxes to ground-truth aircraft boxes. Compared with state-of-the-art methods by conducting comprehensive experiments on a publicly available dataset to validate the proposed method performance of aircraft detection. The detection precision (P) of proposed method achieves 97.06% on the public dataset, which demonstrates the effectiveness of the proposed method