KGNMDA: A Knowledge Graph Neural Network Method for Predicting Microbe-Disease Associations.

Accumulated studies discovered that various microbes in human bodies were closely related to complex human diseases and could provide new insight into drug development. Multiple computational methods were constructed to predict microbes that were potentially associated with diseases. However, most previous methods were based on single characteristics of microbes or diseases, that lacked important biological information related to microorganisms or diseases. Therefore, we constructed a knowledge graph centered on microorganisms and diseases from several existed databases to provide knowledgeable information for microbes and diseases. Then, we adopted a graph neural network method to learn representations of microbes and diseases from the constructed knowledge graph. After that, we introduced the Gaussian kernel similarity features of microbes and diseases to generate final representations of microbes and diseases. At last, we proposed a score function on final representations of microbes and diseases to predict scores of microbe-disease associations. Comprehensive experiments on the Human Microbe-Disease Association Database (HMDAD) dataset had demonstrated that our approach outperformed baseline methods. Furthermore, we implemented case studies on two important diseases (asthma and inflammatory bowel disease), the result demonstrated that our proposed model was effective in revealing the relationship between diseases and microbes. The source code of our model and the data were available on https://github.com/ChangzhiJiang/KGNMDA_master.

Rhodiola rosea: A Therapeutic Candidate on Cardiovascular Diseases.

Cardiovascular diseases, also known as circulatory diseases, are diseases of the heart and blood vessels, and its etiology is hyperlipidemia, thick blood, atherosclerosis, and hypertension. Due to its high prevalence, disability, and mortality, it seriously threatens human health. According to reports, the incidence of cardiovascular disease is still on the rise. Rhodiola rosea is a kind of traditional Chinese medicine, which has the effects of antimyocardial ischemia-reperfusion injury, lowering blood fat, antithrombosis, and antiarrhythmia. Rhodiola rosea has various chemical components, and different chemical elements have the same pharmacological effects and medicinal values for various cardiovascular diseases. This article reviews the research on the pharmacological effects of Rhodiola rosea on cardiovascular diseases and provides references for the clinical treatment of cardiovascular diseases.

Site-Selective Synthesis of Aryl Sulfides via Oxidative Aromatization of Cyclohexanones with Thiophenols.

We have introduced a metal-free facile access for the thiolation/aromatization of cyclohexanones with thiophenols to the corresponding aryl sulfides. The dehydroaromatic reaction of non-aromatic cyclohexanones proceeded smoothly using oxygen as a green oxidant.

Prediction of Protein-Protein Interaction Sites Based on Stratified Attentional Mechanisms.

Proteins are the basic substances that undertake human life activities, and they often perform their biological functions through interactions with other biological macromolecules, such as cell transmission and signal transduction. Predicting the interaction sites between proteins can deepen the understanding of the principle of protein interactions, but traditional experimental methods are time-consuming and labor-intensive. In this study, a new hierarchical attention network structure, named HANPPIS, by adding six effective features of protein sequence, position-specific scoring matrix (PSSM), secondary structure, pre-training vector, hydrophilic, and amino acid position, is proposed to predict protein-protein interaction (PPI) sites. The experiment proved that our model has obtained very effective results, which was better than the existing advanced calculation methods. More importantly, we used the double-layer attention mechanism to improve the interpretability of the model and to a certain extent solved the problem of the "black box" of deep neural networks, which can be used as a reference for location positioning on the biological level.

Gasotransmitters: Potential Therapeutic Molecules of Fibrotic Diseases.

Fibrosis is defined as the pathological progress of excessive extracellular matrix (ECM), such as collagen, fibronectin, and elastin deposition, as the regenerative capacity of cells cannot satisfy the dynamic repair of chronic damage. The well-known features of tissue fibrosis are characterized as the presence of excessive activated and proliferated fibroblasts and the differentiation of fibroblasts into myofibroblasts, and epithelial cells undergo the epithelial-mesenchymal transition (EMT) to expand the number of fibroblasts and myofibroblasts thereby driving fibrogenesis. In terms of mechanism, during the process of fibrosis, the activations of the TGF-ß signaling pathway, oxidative stress, cellular senescence, and inflammatory response play crucial roles in the activation and proliferation of fibroblasts to generate ECM. The deaths due to severe fibrosis account for almost half of the total deaths from various diseases, and few treatment strategies are available for the prevention of fibrosis as yet. Recently, numerous studies demonstrated that three well-defined bioactive gasotransmitters, including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), generally exhibited anti-inflammatory, antioxidative, antiapoptotic, and antiproliferative properties. Besides these effects, a number of studies have reported that low-dose exogenous and endogenous gasotransmitters can delay and interfere with the occurrence and development of fibrotic diseases, including myocardial fibrosis, idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, diabetic diaphragm fibrosis, and peritoneal fibrosis. Furthermore, in animal and clinical experiments, the inhalation of low-dose exogenous gas and intraperitoneal injection of gaseous donors, such as SNAP, CINOD, CORM, SAC, and NaHS, showed a significant therapeutic effect on the inhibition of fibrosis through modulating the TGF-ß signaling pathway, attenuating oxidative stress and inflammatory response, and delaying the cellular senescence, while promoting the process of autophagy. In this review, we first demonstrate and summarize the therapeutic effects of gasotransmitters on diverse fibrotic diseases and highlight their molecular mechanisms in the process and development of fibrosis.

Cadmium-induced germline apoptosis in Caenorhabditis elegans: the roles of HUS1, p53, and MAPK signaling pathways.

The transition metal cadmium (Cd) has been shown to induce apoptosis in a variety of cell lines and tissues. Caspase activation of the tumor suppressor gene p53 and mitogen-activated protein kinase (MAPK) signaling cascades have been reported to be involved in Cd-induced apoptosis. However, the underlying pathways of Cd-induced apoptosis have not been clearly elucidated in the in vivo systems, primarily for the lack of appropriate animal models. The nematode Caenorhabditis elegans has been shown to be a good model to study basic biological processes, including apoptosis. In this study, we used the mutated alleles of C. elegans homologs of known mammalian genes that are involved in regulation of apoptosis. Sublethal doses of Cd exposure increased C. elegans germline apoptosis in a dose- and time-dependent manner. The loss-of-function mutations of DNA damage response (DDR) genes HUS1 and p53 exhibited significant increase in germline apoptosis under Cd exposure, and the depletion of p53 antagonist ABL1 significantly enhanced apoptosis. Cd-induced apoptosis was blocked in the loss-of-function alleles of both c-Jun N-terminal kinase (JNK) and p38 MAPK cascades, which behaved normally under gamma-irradiation. Our findings implicate that both JNK and p38 MAPK cascades participate in Cd-induced apoptosis. Together, the results of this study suggest the nonessential roles of the DDR genes hus1 and p53 in Cd-induced germline apoptosis and that the apoptosis occurs through the ASK1/2-MKK7-JNK and ASK1/2-MKK3/6-p38 signaling pathways in a caspase-dependent manner. Finally, our study demonstrates that C. elegans is a mammalian in vivo substitute model to study the mechanisms of Cd-induced apoptosis.