Immune system plays a decisive role for defending various pathogenic microorganisms. Astragalus membranaceus (AM) and Panax ginseng (PG) are two tonic herbs used in traditional Chinese medicine (TCM) ...as immune booster and help to control diseases with their healthy synergistic effect on immune system.
This study was aimed to investigate the promote effect and molecular mechanisms of AM and PG on immune system as booster and to control the target diseases using animal and computational systematic study.
Computational models including absorption, distribution, metabolism, and elimination (ADME) with weighted ensemble similarity (WES) algorithm-based models and ClueGo network analysis were used to find the potential bioactive compounds targets and pathways, which were responsible for immune regulation. Viscera index analysis, proliferation activity of splenic lymphocytes and cytotoxic activity of NK cells assays were performed to validate the effect of AM and PG on immune system of long-term administrated mice. Metabonomic study of mice plasma was conducted to investigate effect of AM and PG on the endogenous metabolic perturbations, together with correlation analysis.
AM and PG simultaneously showed the ability to strengthen the immune system function including enhancement of spleen and thymus index, proliferation of splenic lymphocytes and cytotoxic activity of NK cells. Besides, the different molecular mechanisms of AM and PG on immune regulation were also investigated by analyzing the potential bioactive compounds, enzymes actions and pathways. Quercetin, formononetin and kaempferol were the main immune-related compounds in AM, while ginsenoside Ra1, ginsenoside Rh1 and kaempferol in PG. About 10 target proteins were found close to immune regulation, including acetylcholinesterase (ACHE, common target in AM and PG), sphingosine kinase 1(SPHK1), cytidine deaminase (CDA), and Choline O-acetyltransferase (CHAT). Glycerophospholipid metabolism was regulated in both AM and PG groups. Pyrimidine metabolism and sphingolipid metabolism were considered as the special pathway in AM groups. Energy metabolism and glycerolipid metabolism were the special pathways in PG groups.
A novel comprehensive molecular mechanism analysis method was established and applied to clarify the scientific connotation of AM and PG as immune regulation, with similar herbal tonic effect provided in clinical practice of TCM, which can provide a new line of research for drug development (immune booster) using AM and PG.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The WRKY transcription factor family plays significant roles in biotic and abiotic stress responses, which has been associated with various biological processes in higher plants. However, very little ...is known regarding the structure and function of WRKY genes in maize. In this study, a total of 140 ZmWRKY proteins encoded by 125 ZmWRKY genes were eventually identified in maize. On the basis of features of molecular structure and a comparison of phylogenetic relationships of WRKY transcription factor families from Arabidopsis, rice and maize, all 140 ZmWRKY proteins in maize were divided into three main groups (Groups I, II and III) and the Group II was further classified into five subgroups. The characteristics of exon-intron structure of these putative ZmWRKY genes and conserved protein motifs of their encoded ZmWRKY proteins were also presented respectively, which was in accordance with the group classification results. Promoter analysis suggested that ZmWRKY genes shared many abiotic stress-related elements and hormone-related elements. Gene duplication analysis revealed that the segmental duplication and purifying selection might play a significant role during the evolution of the WRKY gene family in maize. Using RNA-seq data, transcriptome analysis indicated that most of ZmWRKY genes displayed differential expression patterns at different developmental stages of maize. Further, by quantitative real-time PCR analysis, twenty-one ZmWRKY genes were confirmed to respond to two different abiotic stress treatments, suggesting their potential roles in various abiotic stress responses. In addition, RNA-seq dataset was used to conduct weighted gene co-expression network analysis (WGCNA) in order to recognize gene subsets possessing similar expression patterns and highly correlated with each other within different metabolic networks. Further, subcellular localization prediction, functional annotation and interaction analysis of ZmWRKY proteins were also performed to predict their interactions and associations involved in potential regulatory network. Taken together, the present study will serve to present an important theoretical basis for further exploring function and regulatory mechanism of ZmWRKY genes in the growth, development, and adaptation to abiotic stresses in maize.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Microwave ablation (MWA) has several advantages over radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). We aimed to compare the efficacy and safety of MWA ...with those of RFA for HCC from the perspectives of percutaneous and laparoscopic approaches.
Methods: PubMed/MEDLINE, Embase, the Cochrane library, and China Biology Medicine databases were searched. Studies comparing the efficacy and safety of MWA with those of RFA in patients with HCC were considered eligible. Complete ablation (CA), local recurrence (LR), disease-free survival (DFS), overall survival (OS), and the major complication rate were compared between MWA and RFA.
Results: Four randomized controlled trials and 10 cohort studies were included. For percutaneous ablation, no significant difference was found between MWA and RFA regarding CA, LR, DFS, OS, and the major complication rate. A subgroup analysis of tumors measuring ≥3 cm revealed no difference in CA and LR for percutaneous ablation. For laparoscopic ablation, a significantly lower LR rate and a non-significant trend toward a higher major complication rate were observed for the MWA group (odds ratio OR 2.16, 95% confidence interval CI 1.16-4.02, p = .01 for LR; OR 0.21, 95% CI 0.04-1.03, p = .05 for major complication rate). CA, DFS, and OS were similar between the two groups.
Conclusions: Percutaneous (P)-MWA had similar therapeutic effects compared with P-RFA for HCC. Patients undergoing laparoscopic MWA had a lower LR rate; however, their major complication rate appeared to be higher. The superiority of MWA over RFA remains unclear and needs to be confirmed by high-quality evidence.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circulating tumor DNA (ctDNA) has emerged as a useful diagnostic and prognostic biomarker in many cancers. Here, we conducted a study to investigate the potential use of ctDNA methylation markers for ...the diagnosis and prognostication of colorectal cancer (CRC) and used a prospective cohort to validate their effectiveness in screening patients at high risk of CRC. We first identified CRC-specific methylation signatures by comparing CRC tissues to normal blood leukocytes. Then, we applied a machine learning algorithm to develop a predictive diagnostic and a prognostic model using cell-free DNA (cfDNA) samples from a cohort of 801 patients with CRC and 1021 normal controls. The obtained diagnostic prediction model discriminated patients with CRC from normal controls with high accuracy (area under curve = 0.96). The prognostic prediction model also effectively predicted the prognosis and survival of patients with CRC (
< 0.001). In addition, we generated a ctDNA-based molecular classification of CRC using an unsupervised clustering method and obtained two subgroups of patients with CRC with significantly different overall survival (
= 0.011 in validation cohort). Last, we found that a single ctDNA methylation marker, cg10673833, could yield high sensitivity (89.7%) and specificity (86.8%) for detection of CRC and precancerous lesions in a high-risk population of 1493 participants in a prospective cohort study. Together, our findings showed the value of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of CRC.
Upper gastrointestinal cancers (including oesophageal cancer and gastric cancer) are the most common cancers worldwide. Artificial intelligence platforms using deep learning algorithms have made ...remarkable progress in medical imaging but their application in upper gastrointestinal cancers has been limited. We aimed to develop and validate the Gastrointestinal Artificial Intelligence Diagnostic System (GRAIDS) for the diagnosis of upper gastrointestinal cancers through analysis of imaging data from clinical endoscopies.
This multicentre, case-control, diagnostic study was done in six hospitals of different tiers (ie, municipal, provincial, and national) in China. The images of consecutive participants, aged 18 years or older, who had not had a previous endoscopy were retrieved from all participating hospitals. All patients with upper gastrointestinal cancer lesions (including oesophageal cancer and gastric cancer) that were histologically proven malignancies were eligible for this study. Only images with standard white light were deemed eligible. The images from Sun Yat-sen University Cancer Center were randomly assigned (8:1:1) to the training and intrinsic verification datasets for developing GRAIDS, and the internal validation dataset for evaluating the performance of GRAIDS. Its diagnostic performance was evaluated using an internal and prospective validation set from Sun Yat-sen University Cancer Center (a national hospital) and additional external validation sets from five primary care hospitals. The performance of GRAIDS was also compared with endoscopists with three degrees of expertise: expert, competent, and trainee. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of GRAIDS and endoscopists for the identification of cancerous lesions were evaluated by calculating the 95% CIs using the Clopper-Pearson method.
1 036 496 endoscopy images from 84 424 individuals were used to develop and test GRAIDS. The diagnostic accuracy in identifying upper gastrointestinal cancers was 0·955 (95% CI 0·952–0·957) in the internal validation set, 0·927 (0·925–0·929) in the prospective set, and ranged from 0·915 (0·913–0·917) to 0·977 (0·977–0·978) in the five external validation sets. GRAIDS achieved diagnostic sensitivity similar to that of the expert endoscopist (0·942 95% CI 0·924–0·957 vs 0·945 0·927–0·959; p=0·692) and superior sensitivity compared with competent (0·858 0·832–0·880, p<0·0001) and trainee (0·722 0·691–0·752, p<0·0001) endoscopists. The positive predictive value was 0·814 (95% CI 0·788–0·838) for GRAIDS, 0·932 (0·913–0·948) for the expert endoscopist, 0·974 (0·960–0·984) for the competent endoscopist, and 0·824 (0·795–0·850) for the trainee endoscopist. The negative predictive value was 0·978 (95% CI 0·971–0·984) for GRAIDS, 0·980 (0·974–0·985) for the expert endoscopist, 0·951 (0·942–0·959) for the competent endoscopist, and 0·904 (0·893–0·916) for the trainee endoscopist.
GRAIDS achieved high diagnostic accuracy in detecting upper gastrointestinal cancers, with sensitivity similar to that of expert endoscopists and was superior to that of non-expert endoscopists. This system could assist community-based hospitals in improving their effectiveness in upper gastrointestinal cancer diagnoses.
The National Key R&D Program of China, the Natural Science Foundation of Guangdong Province, the Science and Technology Program of Guangdong, the Science and Technology Program of Guangzhou, and the Fundamental Research Funds for the Central Universities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fungal infection is common and difficult to be diagnosed timely in clinical, for its various kinds and similar manifestations. The rare pulmonary fungal infection such as Schizophyllum commune was ...one of the harder ones and misdiagnosed in usual.
We report a 32-year-old female which was diagnosed with Metagenomic Next-Generation Sequencing (mNGS). She was hospitalized with the complaint of 4 months and more of repeated cough and expectorating. The chest computer tomography revealed left lower lobe pathological changes, but antibiotics were ineffective. No positive results were found in laboratory tests, including sputum culture and the pathology of lung puncture biopsy.
mNGS of lung biopsy was performed and detected the sequence number of Schizophyllum for 11.
The patient was treated with voriconazole and itraconazole successively.
She recovered to health. There was no recurrence during follow-up.
mNGS as a diagnostic method could quickly detect pathogens through the processing of fragment, synthesis, comparison, and analysis of sample genes. It is suitable for detecting especially rare and polymicrobial infections. To our best knowledge, infection of Schizophyllum commune have not been reported in English literature with diagnostic method of mNGS.
Thallium (Tl) is a trace metal of severe toxicity. Its health concerns via consumption of contaminated vegetables have often been overlooked or underestimated. This study was designed to gain insight ...into the actual level and distribution characteristics of Tl and metal (loid)s (Pb, Cd, Cr, Sb, Mn, Cu, Zn, Ni, and Co) in agricultural soils and common vegetables cultivated in different zones (upstream, midstream, and downstream) of a densely populated residential area in a typical mine city, which has been open-pit exploiting Tl-bearing pyrite minerals since 1960s. The results show that most of the agricultural soils exhibit contaminated levels of Tl, with Tl contents (upstream: 1.35–4.31 mg/kg, midstream: 2.43–5.19 mg/kg, and downstream: 0.65–2.33 mg/kg) mostly exceeding the maximum permissible level (MPL) for agricultural land use (1 mg/kg). Sequential extraction procedure indicates that even Tl is predominantly retained in the residual fraction, significant levels of Tl are still present in the geochemically mobile fractions. Besides, metals like Cu, Cd, Mn, and Co are mostly distributed in the labile fractions. Almost all metal (loid)s in edible parts of the vegetables exceed their corresponding MPL for consumption. The chronic daily intake (CDI) and hazard quotient (HQ) values calculated for inhabitants at different ages indicate non-negligible Tl risks via consumption of local vegetables, especially for children. Therefore, it is critical to establish effective measures for hazardous waste management and enforceable regulations in Tl-polluted area to mitigate potential severe impacts of Tl on human health through food chain.
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•Thallium distribution was studied in various zones of a typical pyrite mining city.•Excessive levels of Tl were detected in farmland soils and common vegetables.•Substantial Tl in soils can transfer to plants though most Tl in the stable fraction.•Consumption of these vegetables may pose potential health risks to residents.•Regulations towards Tl pollution in food chain should be initiated immediately.
Alarming levels of toxic thallium were widely detected in vegetables and soils in a typical pyrite mining city.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Single metal atoms and metal clusters have attracted much attention because of their high dispersity, special electronic structures, and uniformity of active sites as heterogeneous catalysts, but it ...is still challenging to generate stable single atoms and clusters with high metal loadings. Supports play a crucial role in determining particle morphology and maintaining dispersion. Herein we synthesize an amorphous alumina with 29% coordinatively unsaturated pentacoordinate Al3+ (Al3+ penta) sites, which can anchor atomically dispersed Ru species with 1 wt % loading. Strong interactions between Ru and Al3+ penta centers were detected, resulting in distinct Ru geometric and electronic features. When used in benzene hydrogenation reaction, fairly high specific activity (TOF = 5180 h–1) were obtained. The high catalytic performance is considered closely correlated with the high utilization of special Ru active sites.
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IJS, KILJ, NUK, PNG, UL, UM
The secondary instabilities of stationary cross-flow vortices in a Mach 6 swept wing flow are studied using Floquet theory. High-frequency secondary instability modes of ‘y’ mode on top of stationary ...cross-flow vortices, and ‘z’ mode concentrating on the shoulder of the stationary cross-flow vortex are found. The most unstable secondary instability mode is always the ‘z’ mode as in incompressible swept wing flows. A new secondary instability mode concentrating on the trough of the stationary cross-flow vortex is found. The balance analysis of disturbance kinetic energy shows that the new mode belongs to the class of ‘y’ mode. The growth rate of the new ‘y’ mode located on the trough of the stationary cross-flow vortex is significantly larger than that of the ‘y’ mode on top of the stationary cross-flow vortex, and is comparable with the growth rate of the ‘z’ mode. It is also found that the new ‘y’ mode with higher frequency can evolve into the ‘z’ mode further downstream. The role of the pressure fluctuation term, including the pressure diffusion and pressure dilatation, in the energy production of secondary instability modes, is also investigated. It is shown that the pressure diffusion will only enhance the growth rate of the ‘z’ mode with higher frequency, but has little influence on other types of secondary instability mode. However, the pressure dilatation term arising from non-vanishing velocity divergence will reduce the growth rates of all secondary instability modes.
Hyperlipidemia characterized by abnormal deposition of cholesterol in arteries can cause atherosclerosis and coronary artery occlusion, leading to atherosclerotic coronary heart disease. The body ...prevents atherosclerosis by reverse cholesterol transport to mobilize and excrete cholesterol and other lipids. Apolipoprotein A1, the major component of high-density lipoprotein, plays a key role in reverse cholesterol transport. Here, we reviewed the role of apolipoprotein A1-targeting molecules in antiatherosclerosis therapy, in particular ATP-binding cassette transporter A1, lecithin-cholesterol acyltransferase, and scavenger receptor class B type 1.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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