PLHPP2 inhibits the stemness of colorectal cancer by inactivating the Nrf2 signaling pathway.

Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a critical regulator of cellular homeostasis and acts as a tumor suppressor in multiple human cancers. However, its exact biological function in colorectal cancer (CRC) and the underlying molecular mechanism remain poorly understood. The correlation between the transcription and protein abundance of PHLPP2 was analyzed using proteomic and corresponding transcriptional data. Immunohistochemistry was used to validate the protein expression and the role of PHLPP2 in patient prognosis. In addition, a series of experiments in vitro and in vivo were performed to investigate the underlying molecular mechanism. Immunohistochemical staining of a CRC tissue microarray revealed that PHLPP2 protein expression was significantly downregulated compared to that in adjacent normal tissues. Low expression of PHLPP2 was an independent prognostic risk factor for poor survival. A nomogram established by integrating PHLPP2 expression and traditional clinicopathological factors achieved more reliable prognostic assessment in CRC patients. Additionally, PHLPP2 overexpression suppressed CRC cell migration, invasion and stemness in vitro as well as tumorigenesis in vivo. Further experiments revealed that upregulation of PHLPP2 increased ROS levels by suppressing the Nrf2-ARE signaling pathway, which inhibited the stemness of CRC cells. Moreover, incubation with sulforaphane, a selective chemical agonist of Nrf2, reversed this inhibitory effect in CRC. PHLPP2 acts as a tumor suppressor gene in CRC by restraining the Nrf2-ARE signaling pathway and increasing ROS levels, affecting the stemness of CRC cells. These anticancer molecular mechanisms indicate PHLLPP2's significant clinical value in prognosis prediction and targeted therapy.

Herp knockout protects against nonalcoholic fatty liver disease in mice on a high fat diet.

This study aims to discover the role of Homocysteine-induced ER protein (Herp) deficiency in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). After 8 weeks of feeding with normal-fat diet (NFD) or HFD, WT (wild type) and Herp-/- mice were measured for the body weight, liver weight and serum biochemical parameters. HE, Oil Red O, and Sirius red stainings were used to evaluate the histopathological changes of liver tissues. QRT-PCR, Western blotting and Immunohistochemistry were employed to detect the mRNA and protein expression. TUNEL staining was used to observe the hepatocyte apoptosis. Herp knockout reduced the liver/body weight ratio of mice fed with HFD with the decreased serum levels of TG, TC, HDL, LDL, GGT, Hcy, ALT, and AST. Besides, WT mice fed with HFD presented obvious steatosis, inflammation and hepatocytes ballooning, which was relieved in Herp-/- mice. HFD-induce NFALD mice demonstrated increased Oil Red, Sirius red, and α-SMA staining than NFD-induced mice, but mice in the Herp-/- + HFD group was lower than the WT + HFD group. HFD-induce NFALD mice showed up-regulated expression of Grp78, Chop, and Atf4 in liver tissues when compared with NFD fed mice. However, regarding to the mice fed with HFD, Herp deficiency decrease in the expression of Grp78, Chop, and Atf4 in liver tissues with the reduced hepatocyte apoptosis. Herp was highly expressed in HFD-induced NAFLD mice. Herp knockout improved liver function and histopathological conditions with the decreased hepatocyte apoptosis and endoplasmic reticulum stress (ERS) of HFD-induce NFALD mice.

Joint Estimation of Source Range and Depth Using a Bottom-Deployed Vertical Line Array in Deep Water.

This paper presents a joint estimation method of source range and depth using a bottom-deployed vertical line array (VLA). The method utilizes the information on the arrival angle of direct (D) path in space domain and the interference characteristic of D and surface-reflected (SR) paths in frequency domain. The former is related to a ray tracing technique to backpropagate the rays and produces an ambiguity surface of source range. The latter utilizes Lloyd's mirror principle to obtain an ambiguity surface of source depth. The acoustic transmission duct is the well-known reliable acoustic path (RAP). The ambiguity surface of the combined estimation is a dimensionless ad hoc function. Numerical efficiency and experimental verification show that the proposed method is a good candidate for initial coarse estimation of source position.

Passive localization in the deep ocean based on cross-correlation function matching.

Passive localization of a sound source in the deep ocean is investigated in this study. The source can be localized by taking advantage of a cross-correlation function matching technique. When a two-sensor vertical array is used in the deep ocean, two types of side lobe curves appear in the ambiguity surface of the localization. The side lobe curves are analytically expressed and they are then used as indicators of the localization result instead of the scanning point with the maximum power. Simulation and experiment demonstrate the performance of the proposed passive localization method.

Localization of low-frequency coherent sound sources with compressive beamforming-based passive synthetic aperture.

The localization of low-frequency coherent sources requires a proper aperture to ensure a high spatial resolution. Attaining a large aperture is difficult in practice when the conditions involved are limited. This letter investigated a compressive beamforming-based passive synthetic aperture approach with a reference sensor in a fixed position. Localization findings on acoustic sources in a semi-anechoic chamber were compared with conventional beamforming, compressive beamforming, passive synthetic aperture, and compressive beamforming-based passive synthetic aperture. Results suggest that the proposed method can produce a higher spatial resolution and higher detection ability than the others.