New Insight into the Anti-liver Fibrosis Effect of Multitargeted Tyrosine Kinase Inhibitors: From Molecular Target to Clinical Trials

Tyrosine kinases (TKs) is a family of tyrosine protein kinases with important functions in the regulation of a broad variety of physiological cell processes. Overactivity of TK disturbs cellular homeostasis and has been linked to the development of certain diseases, including various fibrotic diseases. In regard to liver fibrosis, several TKs, such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR) kinases, have been identified as central mediators in collagen production and potential targets for anti-liver fibrosis therapies. Given the essential role of TKs during liver fibrogenesis, multitargeted inhibitors of aberrant TK activity, including sorafenib, erlotinib, imatinib, sunitinib, nilotinib, brivanib and vatalanib, have been shown to have potential for treating liver fibrosis. Beneficial effects are observed by researchers of this field using these multitargeted TK inhibitors in preclinical animal models and in patients with liver fibrosis. The present review will briefly summarize the anti-liver fibrosis effects of multitargeted TK inhibitors and molecular mechanisms

Investigation of Tumor Suppressing Function of CACNA2D3 in Esophageal Squamous Cell Carcinoma.

Background: Deletion of 3p is one of the most frequent genetic alterations in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes (TSGs) within these regions. In this study, one TSG, CACNA2D3 at 3p21.1, was characterized. Methods: Expression of CACNA2D3 in ESCCs was tested by quantitative real-time PCR and tissue microarray. The mechanism of CACNA2D3 downregulation was investigated by methylation-specific polymerase chain reaction (MS-PCR). The tumor suppressive function of CACNA2D3 was characterized by both in vitro and in vivo tumorigenic assays, cell migration and invasion assays. Results: CACNA2D3 was frequently downregulated in ESCCs (24/48, 50%), which was significantly associated with promoter methylation and allele loss (P<0.05). Tissue microarray result showed that downregulation of CACNA2D3 was detected in (127/224, 56.7%) ESCCs, which was significantly associated with lymph node metastasis (P = 0.01), TNM staging (P = 0.003) and poor outcome of ESCC patients (P<0.05). Functional studies demonstrated that CACNA2D3 could inhibit tumorigenicity, cell motility and induce apoptosis. Mechanism study found that CACNA2D3 could arrest cell cycle at G1/S checkpoint by increasing expressions of p21 and p53 and decreasing expression of CDK2. In addition, CACNA2D3 could upregulate intracellular free cytosolic Ca2+ and subsequently induce apoptosis. Conclusion: CACNA2D3 is a novel TSG responsible to the 3p21 deletion event and plays a critical suppressing role in the development and progression of ESCC. © 2013 Li et al.link_to_OA_fulltex

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system

Detector modules and spectrometers for the TIME-Pilot [CII] intensity mapping experiment

This proceeding presents the current TIME-Pilot instrument design and status with a focus on the close-packed modular detector arrays and spectrometers. Results of laboratory tests with prototype detectors and spectrometers are discussed. TIME-Pilot is a new mm-wavelength grating spectrometer array under development that will study the Epoch of Reionization (the period of time when the first stars and galaxies ionized the intergalactic medium) by mapping the fluctuations of the redshifted 157:7 μm emission line of singly ionized carbon ([CII]) from redshift z ~ 5:2 to 8:5. As a tracer of star formation, the [CII] power spectrum can provide information on the sources driving reionization and complements 21 cm data (which traces neutral hydrogen in the intergalactic medium). Intensity mapping provides a measure of the mean [CII] intensity without the need to resolve and detect faint sources individually. We plan to target a 1 degree by 0.35 arcminute field on the sky and a spectral range of 199-305 GHz, producing a spatial-spectral slab which is 140 Mpc by 0.9 Mpc on-end and 1230 Mpc in the redshift direction. With careful removal of intermediate-redshift CO sources, we anticipate a detection of the halo-halo clustering term in the [CII] power spectrum consistent with current models for star formation history in 240 hours on the JCMT. TIME-Pilot will use two stacks of 16 parallel-plate waveguide spectrometers (one stack per polarization) with a resolving power R ~ 100 and a spectral range of 183 to 326 GHz. The range is divided into 60 spectral channels, of which 16 at the band edges on each spectrometer serve as atmospheric monitors. The diffraction gratings are curved to produce a compact instrument, each focusing the diffracted light onto an output arc sampled by the 60 bolometers. The bolometers are built in buttable dies of 8 (low freqeuency) or 12 (high frequency) spectral channels by 8 spatial channels and are mated to the spectrometer stacks. Each detector consists of a gold micro-mesh absorber and a titanium transition edge sensor (TES). The detectors (1920 total) are designed to operate from a 250 mK base temperature in an existing cryostat with a photon-noise-dominated NEP of ~2 * 10^(-17) WHz^(-1-2). A set of flexible superconducting cables connect the detectors to a time-domain multiplexing SQUID readout system

Insula Volume and Salience Network Are Associated with Memory Decline in Parkinson Disease: Complementary Analyses of Voxel-Based Morphometry versus Volume of Interest

Objective. We investigated structural brain change in subjects with a clinical diagnosis of Parkinson disease with mild cognitive impairment (PD-MCI) and examined its relationship with memory impairment. Methods. Twenty-three PD-MCI patients were enrolled and underwent cognitive evaluation and 3-dimensional T1-weighted imaging. Voxel-based morphometry (VBM) was used to assess brain-behavior correlations and examine the relationship between insula and memory score. VOI methods replicated results obtained from VBM. Results. VBM uncovered the notion that memory scores were positively correlated with the gray matter (GM) density in the insular cortex and a significant positive correlation between overall cognitive performance and concentration of GM within the lateral temporal cortex. In VOI analyses, our results suggested a positive correlation between the insula and composite free-recall verbal memory (ρ=0.617, P=0.003) and the delayed free-recall verbal memory subdomain (ρ=0.725, P<0.001). Furthermore, we found a positive correlation between the insula and caudate (σ=0.570, P=0.006) and putamen volume (σ=0.683, P<0.001). Conclusions. In patients with PD-MCI, atrophic changes in the insula may be related to memory deficits, and the brain-behavior correlation may be associated with atrophic change in the striatum within the salience network

Search for antihelium in cosmic rays

The Alpha Magnetic Spectrometer (AMS) was flown on the space shuttle Discovery during flight STS-91 in a 51.7 degree orbit at altitudes between 320 and 390 km. A total of 2.86 * 10^6 helium nuclei were observed in the rigidity range 1 to 140 GV. No antihelium nuclei were detected at any rigidity. An upper limit on the flux ratio of antihelium to helium of < 1.1 * 10^-6 is obtained.Comment: 18 pages, Latex, 9 .eps figure

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

Multi-scale network fusion for infrared and visible images based on base and detail features

Si, H-P., Zhao, W-R., Li, T-T., Li, F-T., Bação, F., Sun, C-X., & Li, Y-L. (2025). BDMFuse: Multi-scale network fusion for infrared and visible images based on base and detail features. Journal of Infrared and Millimeter Waves (Hongwai Yu Haomibo Xuebao), 44(2), 275-284. https://doi.org/10.11972/j.issn.1001-9014.2025.02.015 --- Supported by the Henan Province Key Research and Development Project（231111211300，the Central Government of Henan Province Guides Local Science and Technology Development Funds（Z20231811005，Henan Province Key Research and Development Project（231111110100，Henan Provincial Outstanding Foreign Scientist Studio（GZS2024006，and Henan Provincial Joint Fund for Scientific and Technological Research and Development Plan（Application and Overcoming Technical Barriers）（242103810028)The fusion of infrared and visible images should emphasize the salient targets in the infrared image while preserving the textural details of the visible images. To meet these requirements, an autoencoder-based method for infrared and visible image fusion is proposed. The encoder designed according to the optimization objective consists of a base encoder and a detail encoder, which is used to extract low-frequency and high-frequency information from the image. This extraction may lead to some information not being captured, so a compensation encoder is proposed to supplement the missing information. Multi-scale decomposition is also employed to extract image features more comprehensively. The decoder combines low-frequency, high-frequency and supplementary information to obtain multi-scale features. Subsequently, the attention strategy and fusion module are introduced to perform multi-scale fusion for image reconstruction. Experimental results on three datasets show that the fused images generated by this network effectively retain salient targets while being more consistent with human visual perception. --- 红外与可见光图像的融合结果应该突出红外图像的显著目标，保留可见光图像的纹理细节。为满足上述要求，提出一种基于自编码器的红外与可见光图像融合方法。编码器根据优化目标构建基础编码器和细节编码器，用于提取图像的低频信息与高频信息。这种提取方式可能会导致部分信息未被捕捉，因此提出补偿编码器来补充信息。同时，采取多尺度分解来更全面地提取图像特征。解码器将低频、高频和补充信息相加获取多尺度特征。随后，引入注意力策略与Fusion模块进行多尺度融合，实现图像重建。在三个数据集上的实验结果表明，该网络生成的融合图像能有效保留突出目标，同时更符合人类的视觉感知。publishersversionpublishe