Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Trichoderma harzianum prevents red kidney bean root rot by increasing plant antioxidant enzyme activity and regulating the rhizosphere microbial community.

Root rot is one of the main reasons for yield losses of red kidney bean (Phaseolus vulgaris) production. Pre-inoculation with Trichoderma harzianum can effectively lower the incidence of red kidney bean root rot. In this study, four treatments including CK (control), Fu13 (Fusarium oxysporum), T891 (T. harzianum) and T891 + Fu13 (T. harzianum + F. oxysporum) were arranged in a pot experiment to investigate how T891 affected the incidence and severity of root rot, plant growth, and changes of defense enzyme activity in red kidney bean plants. Community composition and diversity of the rhizosphere microbiota was evaluated through high-throughput sequencing, and co-occurrence network was analyzed. The results showed that when compared to the Fu13 treatment, pre-inoculation with T891 reduced the incidence and severity of red kidney bean root rot by 40.62 and 68.03% (p < 0.05), increased the root length, shoot length, total dry biomass by 48.63, 97.72, 122.17%. Upregulated activity of super-oxide dismutase (SOD), peroxidase (POD), catalase (CAT) by 7.32, 38.48, 98.31% (p < 0.05), and reduced malondialdehyde (MDA) by 23.70% (p < 0.05), respectively. Microbiological analyses also showed that F. oxysporum reduced alpha diversity resulting in alteration the composition of the rhizosphere microbial community in red kidney bean. T891 significantly reduced abundance of F. oxysporum, allowing the enrichment of potentially beneficial bacteria Porphyrobacter (ASV 46), Lysobacter (ASV 85), Microbacteriaceae (ASV 105), and Gemmatimonas (ASV 107), resulting in a more stable structure of the microbial network. The results of random forest analysis further revealed that ASV 46 (Porphyrobacter) was the primary influencing factor for the incidence of root rot after inoculation with T891, while ASV 85 (Lysobacter) was the primary influencing factor for the biomass of red kidney bean. In conclusion, T. harzianum promotes the growth of red kidney bean and inhibits root rot by improving plant antioxidant enzyme activity and regulating the rhizosphere microbial community.

HERVK-mediated regulation of neighboring genes: implications for breast cancer prognosis.

Human endogenous retroviruses (HERVs) are the remnants of ancient retroviral infections integrated into the human genome. Although most HERVs are silenced or rendered inactive by various regulatory mechanisms, they retain the potential to influence the nearby genes. We analyzed the regulatory map of 91 HERV-Ks on neighboring genes in human breast cancer and investigated the impact of HERV-Ks on the tumor microenvironment (TME) and prognosis of breast cancer. Nine RNA-seq datasets were obtained from GEO and NCBI SRA. Differentially expressed genes and HERV-Ks were analyzed using DESeq2. Validation of high-risk prognostic candidate genes using TCGA data. These included Overall survival (multivariate Cox regression model), immune infiltration analysis (TIMER), tumor mutation burden (maftools), and drug sensitivity analysis (GSCA). A total of 88 candidate genes related to breast cancer prognosis were screened, of which CD48, SLAMF7, SLAMF1, IGLL1, IGHA1, and LRRC8A were key genes. Functionally, these six key genes were significantly enriched in some immune function-related pathways, which may be associated with poor prognosis for breast cancer (p = 0.00016), and the expression levels of these genes were significantly correlated with the sensitivity of breast cancer treatment-related drugs. Mechanistically, they may influence breast cancer development by modulating the infiltration of various immune cells into the TME. We further experimentally validated these genes to confirm the results obtained from bioinformatics analysis. This study represents the first report on the regulatory potential of HERV-K in the neighboring breast cancer genome. We identified three key HERV-Ks and five neighboring genes that hold promise as novel targets for future interventions and treatments for breast cancer.

Structural Characterization and Immunobiological Activity of Polysaccharides from Astragalus Oyster Mushroom.

When added to mushroom growing substrates, edible and medicinal herbs affect the mushrooms' nutritional and medicinal value. In this study, polysaccharides (P0OP-I and P15OP-I) were extracted and purified from oyster mushrooms grown on substrates supplemented with 0% and 15% Astragalus roots (P0 and P15), respectively, and their chemical structure and immunobiological activities were compared. P15OP-I and P0OP-I were extracted using ultrasound-assisted hot water and deproteinized with the Sevage method, depigmented with 30% H2O2, desalted with dialysis, and purified using DEAE-52 cellulose and Sephadex G-100 dextran column chromatography. The molecular weight of P0OP-I and P15OP-I was 21,706.96 and 20,172.65 Da, respectively. Both were composed of monosaccharides D-mannose, galacturonic acid, D-glucose, D-galactose, and L-arabinose but in different molar ratios, and both were connected by a pyranoside linkage. P15OP-I consisted of higher contents of mannose, glucose, galactose and arabinose and lower content of galacturonic acid as compared to P0OP-I. Both P0OP-I and P15OP-I induced NO and TNF-α production but did not show cytotoxic effect or induce ROS generation in RAW264.7 cells. P15OP-I showed a stronger ability to promote NO and TNF-α production relative to P0OP-I. In vitro experiments showed that the immunomodulatory activity of P0OP-I and P15OP-I in RAW264.7 macrophages were mediated by the JNK/MAPK, Erk/MAPK, and NF-κB signaling pathways. The results would be helpful for elucidation of the health promoting mechanism of Astragalus oyster mushrooms as a source of neutraceuticals.

Humic acids enhance salt stress tolerance associated with pyrroline 5-carboxylate synthetase gene expression and hormonal alteration in perennial ryegrass (Lolium perenne L.).

Humic acid (HA) has been used as an important component in biostimulant formulations to enhance plant tolerance to salt stress, but the mechanisms underlying are not fully understood. This study was to investigate the physiological and molecular mechanisms of HA's impact on salt stress tolerance in perennial ryegrass (Lolium perenne L.). The two types of HA were extracted from weathered coal samples collected from Wutai County (WTH) and Jingle County (JLH) of Shanxi Province, China. The grass seedlings subjected to salt stress (250 mM NaCl) were treated with HA solutions containing 0.01% WTH (W/V) or 0.05% JLH (W/V), respectively. The HA treatments improved leaf photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs) and reduced leaf oxidative injury (lower malondialdehyde content) and Pro and intercellular CO2 concentrations in salt-stressed perennial ryegrass. The HA treatments also reversed the decline in antioxidative enzymes ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activity and improved growth and anti-senescence hormones indole-3-acetic acid (IAA) and brassinosteroid (BR). The HA treatments reduced the relative expression of P5CS and its downstream products proline (Pro) and the stress defense hormones abscisic acid (ABA), salicylic acid (SA), jasmonic acid (JA), and polyamines (PA). The results of this study indicate that the application of HAs may improve salt stress tolerance by regulating P5CS gene expression related to osmotic adjustment and increasing the activity of antioxidant enzymes and anti-senescence hormones in perennial ryegrass.

Ethyl pyruvate (EP) suppressed post-harvest blue mold of sweet cherry fruit by inhibiting the growth of Penicillium oxalicum.

BACKGROUND: The shelf-life of fresh sweet cherry is relatively short due to fungal decay during post-harvest storage. To investigate the effect and the mechanism of action of ethyl pyruvate (EP) against blue mold of sweet cherry fruit caused by Penicillium oxalicum, the spores were treated with 25 mg L-1 EP. The spore germination rate of P. oxalicum, the integrities of the cell wall and plasma membrane, reactive oxygen species (ROS) and malondialdehyde (MDA) were evaluated. RESULTS: EP treatment significantly suppressed post-harvest blue mold of sweet cherry fruit. We found that the treatment of 25 mg L-1 EP significantly suppressed blue mold of post-harvest sweet cherry fruit by directly inhibiting germination and the mycelial growth of P. oxalicum. After co-inoculation with EP for 30 min, the spore germination rate of P. oxalicum was reduced by 83.5%. In addition, the pH of the EP solution was found to affect its antimicrobial activity. After treatment with EP, the cell surface structures of the spores of P. oxalicum were much more incomplete, and higher ROS and MDA values were recorded in the spores. CONCLUSIONS: The results suggested that EP treatment destroyed the integrities of the cell surface structures and caused oxidative damage of the spores of P. oxalicum. © 2019 Society of Chemical Industry.

Nanoplasmonically Engineered Interfaces on Amorphous TiO2 for Highly Efficient Photocatalysis in Hydrogen Evolution.

The nanoplasmonic metal-driven photocatalytic activity depends heavily on the spacing between metal nanoparticles (NPs) and semiconductors, and this work shows that ethylene glycol (EG) is an ideal candidate for interface spacer. Controlling the synthetic systems at pH 3, the composite of Ag NPs with EG-stabilized amorphous TiO2 (Ag/TiO2-3) was synthesized by the facile light-induced reduction. It is verified that EG spacers can set up suitable geometric arrangement in the composite: the twin hydroxyls act as stabilizers to bind Ag NPs and TiO2 together and the nonconductive alkyl chains consisting only of two CH2 are able to separate the two building blocks completely and also provide the shortest channels for an efficient transfer of radiation energies to reach TiO2. Employed as photocatalysts in hydrogen evolution under visible light, amorphous TiO2 hardly exhibits the catalytic activity due to high defect density, whereas Ag/TiO2-3 represents a remarkably high catalytic efficiency. The enhancement mechanism of the reaction rate is proposed by the analysis of the compositional, structural, and optical properties from a series of Ag/TiO2 composites.

Phytochemicals of Euphorbia lathyris L. and Their Antioxidant Activities.

The objectives of this study were to characterize the antioxidant capacities and phytochemicals such as phenolics and flavonoids in four parts of Euphorbia lathyris L. HPLC was employed to detect the type and content of phenolic acids and flavonoids in the root, stem, seed, and testa of the plant. The total phenolic content (TPC) and total flavonoid content (TFC) were different among various parts of E. lathyris. The highest TPC were found in the testa (290.46 ± 15.09 mg of gallic acid equiv/100 g dry weight (DW)). However, the root contained the highest TFC (215.68 ± 3.10 mg of rutin equiv/g DW). Of the different antioxidant activities detected, DPPH free radical scavenging activity was highest in the testa (61.29 ± 0.29 mmol Trolox/100 g DW), but the highest FRAP antioxidant activity was found in the seed (1131.25 ± 58.68 mg FeSO4/100 g DW of free compounds and 1927.43 ± 52.13 mg FeSO4/100 g DW of bound compounds). There was a positive correlation between the total phenolic contents and DPPH free radical scavenging activity in different parts of E. lathyris.

Ethnopharmacological and bioactivity guided investigation of five TCM anticancer herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: Five herbs, Curcuma longa L. (CL), Scutellaria baicalensis Georgi (SBC), Scutellaria barbata D. Don (SBB), Hedyotis diffusa Willd. (HD) and Solanum nigrum L. (SN), are often prescribed in the polyherbal formulas for cancer treatment by traditional Chinese medicine (TCM) practitioners. The purpose of the present study was to identify important anticancer herbs used in TCM and carry out bioactivity-directed fractionation and isolation (BDFI) using six cancer cell lines as well as peripheral blood mononuclear cells (PBMCs), to identify constituents with anticancer activity but devoid of toxic effects against healthy immune cells. MATERIALS AND METHODS: Of 243 document anticancer TCM treatments, 199 anticancer TCM herbs were ranked by the number of literature reports for each herb. Five herbs were identified from the top 50 ranked herbs by at least two out of three TCM practitioners as frequently used in the TCM treatment of cancer. BDFI using MTS assay was applied to determine the active anticancer extracts, fractions, and finally discrete compounds. RESULTS: Five herbs were selected for study of their anticancer activities. The extracts of Curcuma longa L., Scutellaria barbata D. Don, and Hedyotis diffusa showed antiproliferative activity to various extents, extracts of Scutellaria baicalensis Georgi and Solanum nigrum L. showed little anticancer activity. Seven out of the 21 fractions obtained from Hedyotis diffusa Willd. showed anticancer activity. One new compound, ethyl 13(2) (S)-hydroxy-chlorophyllide a(1), along with 10 known compounds, i.e. 2-methyl-3-methoxyanthraquinone (2), 2-hydroxymethylanthraquinone(3), 2-hydroxy-3-methylanthraquinone(4), 2-hydroxymethy-1-hydroxyanthraquinone(5), 1-methoxy-2-hydroxyanthraquinone(6), 2-hydroxy-3-methyl-1-methoxyanthraquinone (7), oleanolic acid (8), ursolic acid (9), stigmasterol (10) and docosanoic acid (11), were isolated and identified. Compounds 2-6, 8 and 9 dose-dependently inhibited the cell viability of cancer cells within a concentration range of 1-200µM. Furthermore, compounds 2, 3, 5 and 9 showed significantly stronger inhibition of tested cancer cell lines than on that of PBMCs. CONCLUSION: This study identified anticancer herbs, extracts, fractions and eventually compounds from the documented anticancer TCM herbs by using BDFI. It also determined the antiproliferative activity in cancer and healthy immune cells of the isolated compounds from Hedyotis diffusa. The results will be useful in the validation of the clinical application of these herbs and the development of novel anticancer therapeutics.

Chemical and preclinical studies on Hedyotis diffusa with anticancer potential.

This paper presents the chemical and preclinical anticancer research on Hedyotis diffusa Willd. in detail, one of the most renowned herbs often prescribed in the polyherbal formulas for cancer treatment in traditional Chinese medicine. Anthraquinones, flavonoids, and terpenoids constitute the majority of the 69 compounds that have been isolated and identified from H. diffusa. The anticancer effects of the methanolic, ethanolic, and aqueous extracts in various preclinical cancer models have been described. This review also summarized the anticancer activity of constituents of the herb and the mechanisms of action. All the studies suggest that H. diffusa has enormous potential in the therapy of cancer and warrants further chemical and pharmacological investigation.

Caragana fabr. promotes revegetation and soil rehabilitation in saline-alkali wasteland.

To determine how plantations of Caragana microphylla shrubs affect saline-alkali soil amelioration and revegetation, we investigated the vegetation and sampled soils from saline-alkali wasteland (SAW), perennial Caragana forestland (PCF), Caragana forest after fire disturbance (CFF). Results showed that with the development of Caragana Fabr., highly dominant species of Poaceae family, including Elymus dahuricus, Thermopsis lanceolata, Stipa tianschanica, died out in PCF. Moreover, Papilionaceaefamily, including Lespedeza indica, Oxytropis psammocharis, and Astragalus scaberrimus, was established both in PCF and CFF. Phytoremediation of saline-alkali wasteland (SAW) was achieved by plantation, resulting in the reduced soil pH, sodium adsorption ratio, exchangeable sodium percentage, salinity, and Na+ concentration around Caragana shrubs. Greater amounts of soil organic, total nitrogen, ammonium nitrogen, available phosphorus, and available potassium were observed in PCF topsoil than in SAW topsoil The concentration of mineralized N in PCF soil was significantly lower than that in SAW soil at all sampled depths, indicating that Caragana shrubs were just using N and therefore less measured in soils. Fire disturbance resulted in decreased soil pH and salinity, but increased organic content, total nitrogen, and ammonium nitrogen. The improved soil parameters and self-recovery of shrubs indicated that Caragana shrubs were well established after burning event.

Ethnobotany, phytochemistry and pharmacology of the genus Caragana used in traditional Chinese medicine.

The genus Caragana is a member of the family Fabaceae, subfamily Faboideae and is native to arid and semi-arid areas of the temperate zones of Asia and Eastern Europe. Many species are cultured for dune-fixation, livestock forage and biological resources for fuel energy and fiber production. More than 10 species in this genus have a long history of use in traditional Chinese, Mongolian and Tibetan medicines and are believed to "nourish yin, invigorate the spleen, temper the blood and promote blood flow". They have been used for the treatment of a wide range of ailments including fevers, inflammation, wounds and infections, dizziness, headache, hypertension, female disorders, arthritis and cancer. Over 100 phytochemicals have been identified with flavonoids and stilbenoids being the major constituents of this genus. Clinical studies have demonstrated the pharmacological activities of different Caraganum species, e.g. Caragana sinica for the treatment of hypertension, and in vivo and/or in vitro studies have provided some support for other traditional uses, e.g. anti-cancer, anti-inflammatory, phytoestrogenic, immunostimulant and immunosuppressant activities. However, further studies to identify the active components and further verify the pharmacological activities are warranted. This review presents a comprehensive analysis of the ethnobotany, phytochemistry and pharmacology of the genus Caragana.