Exploring the potential effect and mechanisms of protocatechuic acid on human hair follicle melanocytes

This study aims to evaluate the effect of Protocatechuic acid (PCA) on human hair follicle melanocytes (HFM). Normal primary HFM were isolated and cultured till logarithmic period of second passage, then treated with different concentrations of PCA (0.1~200 μmol L–1) to study the cell proliferation, melanin contents, tyrosinase activity and protein and mRNA expression of melanogenic genes (tyrosinase-related protein 1 (TRP-1), tyrosinase-related protein 2 (TRP-2), and microphthalmia-associated transcription factor (MITF)) in the cultured HFM. In addition, we have also measured the contents of superoxide dismutase (SOD) and glutathione (GSH) in PCA treated HFM. Vitamin C was used as a positive control. The result showed that PCA can decrease the synthesis of melanin and the tyrosinase activity with IC50 = 8.9 μmol L–1 and IC50 = 6.4 μmol L–1, respectively, at the treatment time of 24 hours, without inducing any cytotoxicity in HFM cells. In addition, the mRNA transcription and protein expression levels of TRP-1, TRP-2 and MITF significantly decreased with a dose-dependent manner after 24-hour PCA treated in HFM cells. Furthermore, PCA has significantly increased the SOD and GSH activity in a dose-dependent manner for 24-hour PCA treatment. This study suggested that PCA has an inhibitory effect on the production of melanin through down-regulation of the expression of melanogenesis-related protein and the effect of anti-oxidation, which could be useful for the therapy of melanin overproduction or skin whitening

Learning to Denoise Unreliable Interactions for Link Prediction on Biomedical Knowledge Graph

Link prediction in biomedical knowledge graphs (KGs) aims at predicting unknown interactions between entities, including drug-target interaction (DTI) and drug-drug interaction (DDI), which is critical for drug discovery and therapeutics. Previous methods prefer to utilize the rich semantic relations and topological structure of the KG to predict missing links, yielding promising outcomes. However, all these works only focus on improving the predictive performance without considering the inevitable noise and unreliable interactions existing in the KGs, which limits the development of KG-based computational methods. To address these limitations, we propose a Denoised Link Prediction framework, called DenoisedLP. DenoisedLP obtains reliable interactions based on the local subgraph by denoising noisy links in a learnable way, providing a universal module for mining underlying task-relevant relations. To collaborate with the smoothed semantic information, DenoisedLP introduces the semantic subgraph by blurring conflict relations around the predicted link. By maximizing the mutual information between the reliable structure and smoothed semantic relations, DenoisedLP emphasizes the informative interactions for predicting relation-specific links. Experimental results on real-world datasets demonstrate that DenoisedLP outperforms state-of-the-art methods on DTI and DDI prediction tasks, and verify the effectiveness and robustness of denoising unreliable interactions on the contaminated KGs

Mechanical Model of Underground Shaft Coal Pocket and Deformation of Silo Wall in Coal Mines

In order to provide a theoretical basis for the design of underground shaft coal pocket and support parameters in coal mines, a mechanical model and a dynamic analysis of the silo wall are established based on the engineering background of Ganhe Coal Mine. The numerical calculation is carried out by using the new model. The back analysis of the silo wall damage in the actual project is carried out, and the deformation law and fracture mechanism of the silo wall affected by different lateral pressure coefficients are analyzed and studied research. Based on the Mohr–Coulomb strength criterion, five sets of orthogonal simulation experiments were carried out for lateral pressure coefficients of 0.6, 0.8, 1.0, 1.2, and 1.4, respectively. The results show that the lateral pressure coefficient is the main factor affecting the deformation of the silo wall, the radial displacement of the silo wall increases gradually with the increase of the lateral pressure coefficient, and the displacement follows the quadratic polynomial function distribution. The maximum tensile stress area of the silo wall is located in the middle and lower part of the shaft coal pocket, which better explains the engineering phenomenon that the actual fracture location of the silo wall is mostly concentrated in the middle and lower part of the underground shaft coal pocket. The targeted repair technology can be used for reference in engineering

Extreme Environmental Stress-Induced Biological Responses in the Planarian

Planarians are bilaterally symmetric metazoans of the phylum Platyhelminthes. They have well-defined anteroposterior and dorsoventral axes and have a highly structured true brain which consists of all neural cell types and neuropeptides found in a vertebrate. Planarian flatworms are famous for their strong regenerative ability; they can easily regenerate any part of the body including the complete neoformation of a functional brain within a few days and can survive a series of extreme environmental stress. Nowadays, they are an emerging model system in the field of developmental, regenerative, and stem cell biology and have offered lots of helpful information for these realms. In this review, we will summarize the response of planarians to some typical environmental stress and hope to shed light on basic mechanisms of how organisms interact with extreme environmental stress and survive it, such as altered gravity, temperature, and oxygen, and this information will help researchers improve the design in future studies

Skarn Formation and Zn–Cu Mineralization in the Dachang Sn Polymetallic Ore Field, Guangxi: Insights from Skarn Rock Assemblage and Geochemistry

The Dachang is a world-class, super-giant Sn polymetallic ore field mainly composed of Zn–Cu ore bodies proximal to the granitic pluton and Sn polymetallic ore bodies distal to the granitic pluton. In this study, we used petrographic studies and major and trace element geochemistry with calc-silicates from the Zn–Cu ore bodies to constrain the physicochemical conditions of hydrothermal fluids during skarn rock formation and the evolution of ore-forming elements. Two skarn stages were identified based on petrographic observations: Prograde skarn rocks (Stage I), containing garnet, vesuvianite, pyroxene, wollastonite, and retrograde skarn rocks (Stage II), containing axinite, actinolite, epidote, and chlorite. The retrograde skarn rocks are closely associated with mineralization. The geochemical results show that the garnets in the Dachang ore field belong to the grossular–andradite solid solution, in which the early generation of garnet is mainly composed of grossular (average Gro72And25), while the later generation of garnet is mainly composed of andradite (average Gro39And59); the vesuvianites are Al-rich vesuvianites; the pyroxenes form a diopside–hedenbergite solid solution with a composition of Di3–86Hd14–96; the axinites are mainly composed of ferroaxinite; and the actinolites are Fe-actinolite. The mineral assemblage of the skarn rocks indicates that the ore-forming fluid was in a relatively reduced state in the early prograde skarn stage. As the ore-forming fluid evolved, the oxygen fugacity of the ore-forming fluid increased. During the final skarn stage, the ore-forming fluid changed from a relatively oxidized state to a reduced state. The skarn rocks have evolved from early Al-rich to late Fe-rich characteristics, indicating that the early ore-forming fluid was mainly magmatic exsolution fluid, which may mainly reflect the characteristics of magmatic fluids, and the late Fe-rich characteristics of the skarn rocks may indicate that the late hydrothermal fluid was strongly influenced by country rocks. Trace element analyses showed that the Sn content decreased from the prograde skarn stage to the retrograde skarn stage, indicating that Sn mineralization was not achieved by activating and extracting Sn from prograde skarn rocks by hydrothermal fluids. The significant enrichment of Sn in the magmatic hydrothermal fluid is a necessary condition for Sn mineralization. There are various volatile-rich minerals such as axinite, vesuvianite, fluorite, and tourmaline in the Dachang ore field, indicating that the ore-forming fluid contained extensive volatiles B and F, which may be the fundamental reason for the large-scale mineralization of the Dachang ore field

A Cross-Layer Route Discovery Framework for Mobile Ad Hoc Networks

<p/> <p>Most reactive routing protocols in MANETs employ a random delay between rebroadcasting route requests (RREQ) in order to avoid "broadcast storms." However this can lead to problems such as "next hop racing" and "rebroadcast redundancy." In addition to this, existing routing protocols for MANETs usually take a single routing strategy for all flows. This may lead to inefficient use of resources. In this paper we propose a cross-layer route discovery framework (CRDF) to address these problems by exploiting the cross-layer information. CRDF solves the above problems efficiently and enables a new technique: <it>routing strategy automation (RoSAuto)</it>. RoSAuto refers to the technique that each source node automatically decides the routing strategy based on the application requirements and each intermediate node further adapts the routing strategy so that the network resource usage can be optimized. To demonstrate the effectiveness and the efficiency of CRDF, we design and evaluate a macrobian route discovery strategy under CRDF.</p