Semaphorin 4C accelerates disease progression and enables disease detection in breast cancer

Semaphorins constitute a diverse family of widely expressed transmembrane, diffusible, and GPI-linked proteins with versatile physiologic functions in orchestrating nerve system development, immune homeostasis, angiogenesis, and cell metabolism. Accumulating evidence highlights semaphorins as essential regulators of tumorigenesis by coordinating the cell-cell communications in the tumor microenvironment. Semaphorin 4C (SEMA4C) is a member of the fourth class of semaphorins with high affinity to Plexin-B2 and its interplay with cancer has long been a significant knowledge gap. Here, this perspective summarizes the recent progress in the understanding of SEMA4C in cancer and comprehensively delineates the discovery of SEMA4C in lymphatic vessels of breast cancer, the mechanisms by which SEMA4C promotes the invasiveness, proliferation, metastasis, and drug resistance of breast cancer, and the explorations of leveraging serum SEMA4C in breast cancer detection, highlighting SEMA4C as a critical driver of breast cancer progression, an effective biomarker for breast cancer diagnosis, and potential therapeutic target for breast cancer treatment

Stable Internal Reference Genes for Normalizing Real-Time Quantitative PCR in Baphicacanthus cusia under Hormonal Stimuli and UV Irradiation, and in Different Plant Organs

Baphicacanthus cusia (Nees) Bremek, the plant source for many kinds of drugs in traditional Chinese medicine, is widely distributed in South China, especially in Fujian. Recent studies about B. cusia mainly focus on its chemical composition and pharmacological effects, but further analysis of the plant's gene functions and expression is required to better understand the synthesis of its effective compounds. Real-time quantitative polymerase chain reaction (RT-qPCR) is a powerful method for gene expression analysis. It is necessary to select a suitable reference gene for expression normalization to ensure the accuracy of RT-qPCR results. Ten candidate reference genes were selected from the transcriptome datasets of B. cusia in this study, and the expression stability was assessed across 60 samples representing different tissues and organs under various conditions, including ultraviolet (UV) irradiation, hormonal stimuli (jasmonic acid methyl ester and abscisic acid), and in different plant organs. By employing different algorithms, such as geNorm, NormFinder, and BestKeeper, which are complementary approaches based on different statistical procedures, 18S rRNA was found to be the most stable gene under UV irradiation and hormonal stimuli, whereas ubiquitin-conjugating enzyme E2 was the best suitable gene for different plant organs. This novel study aimed to screen for suitable reference genes and corresponding primer pairs specifically designed for gene expression studies in B. cusia, in particular for RT-qPCR analyses

Long Noncoding RNA HOTTIP Promotes Mouse Hepatic Stellate Cell Activation via Downregulating miR-148a

Background/Aims: HOTTIP is a critical modulator in human diseases including liver cancer, but its role and molecular biological mechanisms in liver fibrosis are still unclear. Methods: The expression profile of HOTTIP during the progression of liver fibrosis was detected in human liver samples and in CCl4-treated mice using qRT-PCR. The expressing sh-HOTTIP adenoviral vector was used to reduce HOTTIP levels in vivo. Dual-Luciferase Reporter Assay was performed to validate the interaction between miR-148a and HOTTIP, TGFBR1, or TGFBR2. Results: HOTTIP expressions in fibrotic liver samples and cirrhotic liver samples were significantly upregulated compared with healthy liver controls, and cirrhotic samples exhibited the highest levels of HOTTIP. Moreover, HOTTIP expressions were substantially induced in the liver tissues and hepatic stellate cells (HSC) of CCl4-treated mice. Ad-shHOTTIP delivery could alleviate CCl4- induced liver fibrosis in mice. Down-regulation of HOTTIP inhibited the viability and activation of HSCs in vitro, and HOTTIP negatively regulated miR-148a expression in HSCs. miR-148a had a negative effect on HSC activation by targeting TGFBR1 and TGFBR2. Conclusion: HOTTIP is involved in the progression of liver fibrosis by promoting HSC activation. The high level of HOTTIP downregulates miR-148a, thus to increase the level of TGFBR1 and TGFBR2 and contribute to liver fibrosis

Transforming Growth Factor β Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function

The transforming growth factor β (TGFβ) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGFβ type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGFβ ligands. Tgfbr1 null mice die embryonically, precluding functional characterization of TGFBR1 postnatally. To study TGFBR1–mediated signaling in female reproduction, we generated a mouse model with conditional knockout (cKO) of Tgfbr1 in the female reproductive tract using anti-Müllerian hormone receptor type 2 promoter-driven Cre recombinase. We found that Tgfbr1 cKO females are sterile. However, unlike its role in growth differentiation factor 9 (GDF9) signaling in vitro, TGFBR1 seems to be dispensable for GDF9 signaling in vivo. Strikingly, we discovered that the Tgfbr1 cKO females develop oviductal diverticula, which impair embryo development and transit of embryos to the uterus. Molecular analysis further demonstrated the dysregulation of several cell differentiation and migration genes (e.g., Krt12, Ace2, and MyoR) that are potentially associated with female reproductive tract development. Moreover, defective smooth muscle development was also revealed in the uteri of the Tgfbr1 cKO mice. Thus, TGFBR1 is required for female reproductive tract integrity and function, and disruption of TGFBR1–mediated signaling leads to catastrophic structural and functional consequences in the oviduct and uterus

Evaluating the Influence of Fracture Roughness and Tortuosity on Fluid Seepage Based on Fluid Seepage Experiments

The roughness and tortuosity of fractures are essential parameters affecting the fluid flow in a jointed rock mass. This paper investigates the influence of fracture roughness and tortuosity on fluid seepage behavior. A rough fracture surface was characterized by means of three-dimensional scanning and three-reconstruction technology, and the roughness and tortuosity of rock fractures were calculated. Hydraulic tests were conducted on deformed sandstone fractures with a self-made fracture seepage device, and the variation in the seepage flow was analyzed in rough fractures. The experimental results showed that the seepage flow of fluid decreased non-linearly with the increase in fracture roughness. Under different normal pressures, the friction resistance coefficient and tortuous resistance coefficient decreased with the increase in the Reynolds number. The friction resistance coefficient model and tortuous resistance coefficient model were used to quantitatively analyze the influence of fracture tortuosity and roughness on fluid flow, respectively. A modified model of the frictional resistance coefficient, considering fracture tortuosity and roughness, was established, which clearly expresses the law that with the increase in fracture tortuosity and roughness, the seepage flow of fluid decreases, and the head loss increases. The results of this research can provide a theoretical and experimental basis for studying fluid seepage behavior in deformed sandstone fractures

A plastic-damage approach to the excavation response of a circular opening in weak rock

During opening construction, the accumulated wall displacement and the developing excavation damaged zone are the results of stress redistribution and inelastic behavior induced by both the microcracking damage and the irreversible plastic deformation. The current approach to predict ground response to excavation disturbance is usually based on the Convergence-Confinement Method, which fails to consider the rock damage and the plastic-damage coupled mechanism, resulting in inaccurate estimation of rock deformation, particularly in the case of the weak rock with high deformability. This study establishes a plastic-damage theoretical approach for a circular opening by a kinematic decomposition of strains into an elastic, plastic and damage parts within the framework of finite strain using a hypoelastic–plastic theory, in order to investigate the inelastic behavior-induced excavation response. In this regard, the damage model provides the effective stress to the plasticity model defining the yield criterion, in combination with the strength-stiffness degradation and damage evolution. The numerical implementation is given and two examples are considered for validation. Extensive works are then carried out to clarify some issues, including the capacity of the model to characterize the inelastic behavior, the role of rock damage and confining stress dependence on ground response, and the preliminary critical support pressure for the residual failure zone.This work is funded by the National Natural Science Foundation of China (Grant Nos. 52004053, U1906208 and 52074060), Natural Science Foundation of Liaoning Province (Grant No. 2021-BS-052), and Fundamental Research Funds for the Central Universities (Grant No. N2101028). These supports are gratefully acknowledged.Peer ReviewedPostprint (author's final draft

Rock Stability Assessment Based on the Chronological Order of the Characteristic Acoustic Emission Phenomena

Sudden inelastic deformations in rock are associated with acoustic emission (AE). Therefore, AE monitoring technique can be used to study the fracture processes of rock. In this paper, AE tests were conducted on the granitic gneiss specimens under the uniaxial compressive loading conditions. The temporal changes in AE hit parameters and spatial-temporal evolution of AE events during the failure process of the granitic gneiss specimens were studied, and several characteristic AE phenomena (i.e., dramatic increase in dominant frequency, AE energy, and hit rate, the AE event with a high energy level, and the through-going distribution of the AE events with intermediate energy levels) were statistically analyzed before the failure occurred. It was found that the chronological order of the characteristic AE phenomena was relatively certain and correspondingly had a close relationship with the crack development stage. Because of the difference of the stress level at each crack development stage, the stability at different crack development stages is different. Therefore, a rock stability assessment approach was established based on the chronological order of the characteristic AE phenomena, and then the rock stability was assessed using the proposed approach

Semaphorin 4C accelerates disease progression and enables disease detection in breast cancer

Semaphorins constitute a diverse family of widely expressed transmembrane, diffusible, and GPI-linked proteins with versatile physiologic functions in orchestrating nerve system development, immune homeostasis, angiogenesis, and cell metabolism. Accumulating evidence highlights semaphorins as essential regulators of tumorigenesis by coordinating the cell-cell communications in the tumor microenvironment. Semaphorin 4C (SEMA4C) is a member of the fourth class of semaphorins with high affinity to Plexin-B2 and its interplay with cancer has long been a significant knowledge gap. Here, this perspective summarizes the recent progress in the understanding of SEMA4C in cancer and comprehensively delineates the discovery of SEMA4C in lymphatic vessels of breast cancer, the mechanisms by which SEMA4C promotes the invasiveness, proliferation, metastasis, and drug resistance of breast cancer, and the explorations of leveraging serum SEMA4C in breast cancer detection, highlighting SEMA4C as a critical driver of breast cancer progression, an effective biomarker for breast cancer diagnosis, and potential therapeutic target for breast cancer treatment