Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Trends of Incidence, Mortality, and Risk Factors for Lower Respiratory Infections among Children under 5 Years in China from 2000 to 2019.

BACKGROUND: Understanding the temporal trends in the burden of lower respiratory tract infections (LRI) and their attributable risk factors in children under 5 years is important for effective prevention strategies. METHODS: We used incidence, mortality, and attributable risk factors of LRI among children under 5 years from the Global Burden of Diseases database to analyze health patterns in 33 provincial administrative units in China from 2000 to 2019. Trends were examined using the annual average percentage change (AAPC) by the joinpoint regression method. RESULTS: The rates of incidence and mortality for under-5 LRI in China were 18.1 and 4134.3 per 100,000 children in 2019, with an AAPC decrease of 4.1% and 11.0% from 2000, respectively. In recent years, the under-5 LRI incidence rate has decreased significantly in 11 provinces (Guangdong, Guangxi, Guizhou, Hainan, Heilongjiang, Jiangxi, Qinghai, Sichuan, Xinjiang, Xizang, and Zhejiang) and remained stable in the other 22 provinces. The case fatality ratio was associated with the Human Development Index and the Health Resource Density Index. The largest decline in risk factors of deaths was household air pollution from solid fuels. CONCLUSIONS: The burden of under-5 LRI in China and the provinces has declined significantly, with variation across provinces. Further efforts are needed to promote child health through the development of measures to control major risk factors.

Mussel-inspired magnetic adsorbent MnO2/PDA@Fe3O4 for removing heavy metal ions contaminants in single and mixed systems.

Heavy metal pollution has been a magnificent concern for a long period. A novel magnetic material, MnO2/PDA@Fe3O4, was prepared in this paper. With the assistance of multiple characterization methods, it was confirmed that polydopamine coated the magnetic nucleus and acted as a dense intermediate layer for MnO2 attachment. Having superior adsorption performance, MnO2/PDA@Fe3O4 could remove heavy metal cations efficiently no matter in single or mixed systems. The maximum adsorption capacities calculated by the Langmuir model for Pb(II), Cu(II), and Cd(II) were 295.01 mg/g, 130.30 mg/g, and 115.16 mg/g, respectively. In mixed systems, the adsorbent showed obvious selectivity for Pb(II). And the variation of Cu(II) concentration was more responsible for Pb(II) adsorption than that of Cd(II). The kinetic and thermodynamic data revealed that the polluted ions immobilizations by MnO2/PDA@Fe3O4 were chemisorption and were endothermic, entropy increase, spontaneous process. The presence of humic acid and coexisting ions induced only a very limited interference. In addition, MnO2/PDA@Fe3O4 maintained excellent adsorption performance and stability after five cycles of adsorption and removed 98.33% Pb(II) and 71.24% Cu(II) from actual water, respectively. This study confirmed that the MnO2/PDA@Fe3O4 had great potential and broad prospects to remediate the heavy metal contaminants in water.

Transport of functional group modified polystyrene nanoplastics in binary metal oxide saturated porous media.

Metal oxides exist in porous media in the form of composite metal oxides, which can significantly affect the transport and transformation of pollutants in the soil environment. In this study, binary metal oxide porous media were prepared to explore the effects of solution chemistry, and the presence of binary metal oxides on the transport of functional group modified polystyrene nanoplastics (PSNPs) in saturated porous media. The results show that the existence of binary metal oxides significantly affects the migration ability of PSNPs in saturated porous media. The increase of ionic strength and the presence of multivalent cations affect the transport capacity of PSNPs in porous media. The types of binary metal oxides affect the migration of PSNPs in saturated porous media. The surface roughness and electrostatic interaction are important factors affecting the retention of PSNPs on the surface of binary metal oxide saturated porous media. The surface morphology has a more far-reaching impact. In addition, DLVO theory cannot fully explain the interaction between PSNPs and saturated porous media in the presence of Al3+. This study's results help provide some theoretical support for the migration of microplastics in the soil environment.

Identifying pleiotropic genes for major psychiatric disorders with GWAS summary statistics using multivariate adaptive association tests.

BACKGROUND: Genome wide association studies (GWAS) have discovered a few of single nucleotide polymorphisms (SNPs) related to major psychiatric disorders. However, it is not completely clear which genes play a pleiotropic role in multiple disorders. The study aimed to identify the pleiotropic genes across five psychiatric disorders using multivariate adaptive association tests. METHODS: Summary statistics of five psychiatric disorders were downloaded from Psychiatric Genomics Consortium. We applied linkage disequilibrium score regression (LDSC) to estimate genetic correlation and conducted tissue and cell type specificity analyses based on Multi-marker Analysis of GenoMic Annotation (MAGMA). Then, we identified the pleiotropic genes using MTaSPUsSet and aSPUs tests. We ultimately performed the functional analysis for pleiotropic genes. RESULTS: We confirmed the significant genetic correlation and brain tissue and neuron specificity among five disorders. 100 pleiotropic genes were detected to be significantly associated with five psychiatric disorders, of which 55 were novel genes. These genes were functionally enriched in neuron differentiation and synaptic transmission. LIMITATIONS: The effect direction of pleiotropic genes couldn't be distinguished due to without individual-level data. CONCLUSION: We identified pleiotropic genes using multivariate adaptive association tests and explored their biological function. The findings may provide novel insight into the development and implementation of prevention and treatment as well as targeted drug discovery in practice.

Mechanism Study of Cinnamomi Ramulus and Paris polyphylla Sm. Drug Pair in the Treatment of Adenomyosis by Network Pharmacology and Experimental Validation.

Objective: To explore the molecular mechanism of the Cinnamomi ramulus and Paris polyphylla Sm. (C-P) drug pair in the treatment of adenomyosis (AM) based on network pharmacology and animal experiments. Methods: Via a network pharmacology strategy, a drug-component-target-disease network (D-C-T-D) and protein-protein interaction (PPI) network were constructed to explore the core components and key targets of C-P drug pair therapy for AM, and the core components and key targets were verified by molecular docking. Based on the results of network pharmacology, animal experiments were performed for further verification. The therapeutic effect of the C-P drug pair on uterine ectopic lesions was evaluated in a constructed AM rat model. Results: A total of 30 components and 45 corresponding targets of C-P in the treatment of AM were obtained through network pharmacology. In the D-C-T-D network and PPI network, 5 core components and 10 key targets were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K signaling pathway was the most significantly enriched nontumor pathway. Molecular docking showed that most of the core components and key targets docked completely. Animal experiments showed that the C-P drug pair significantly ameliorated the pathological changes of endometriotic lesions in AM model rats and inhibited PI3K and Akt gene expression, and PI3K and Akt protein phosphorylation. In addition, treatment with the C-P drug pair promoted AM cell apoptosis; upregulated the protein expression of Bax, Caspase-3, and cleaved Caspase-9; and restrained Bcl-2 expression. Conclusions: We propose that the pharmacological mechanism of the C-P drug pair in the treatment of AM is related to inhibition of the PI3K/Akt pathway and promotion of apoptosis in AM ectopic lesions.

Photocatalytic degradation of persistent organic pollutants by Co-Cl bond reinforced CoAl-LDH/Bi12O17Cl2 photocatalyst: mechanism and application prospect evaluation.

The widespread distribution of persistent organic pollutants (POPs) in natural waters has aroused global concern due to their potential threat to the aquatic environment. Photocatalysis represents a promising mean to remediate polluted waters with the simple assistance of solar energy. Herein, we fabricated a Co-Cl bond reinforced CoAl-LDH/Bi12O17Cl2 heterogeneous photocatalyst to investigate the feasibility of photocatalysis to treat POPs-polluted water under environmental conditions. The optimum CoAl-LDH/Bi12O17Cl2 (5-LB) composite photocatalyst exhibited excellent photocatalytic performance, which could degrade 92.47 % of ciprofloxacin (CIP) and 95 % of bisphenol A (BPA) with 2h of actual solar light irradiation in Changsha, China (N 28.12 °, E 112.59 °). In view of the synergistic influence of water constituents, various water matrices greatly affected the degradation rate of CIP (BPA), with the degradation efficiency of 82.17% (84.37%) in tap water, 69.67% (71.63%) in wastewater effluent, and 44.07% (67.7%) in wastewater inflow. The results of electron spin resonance, and chemical trapping experiment, HPLC-MS and density functional theory calculation reflected that the degradation of CIP was mainly attributed to h+ and 1O2 attacking the active atoms of CIP molecule with high Fukui index. Furthermore, the non-toxicity of both 5-LB photocatalyst and treated CIP solution was proved by E.coli and B.subtilis cultivation, which further demonstrated the feasibility of the 5-LB to treat POPs in real water under irradiation of solar light.

Removal of Pb (II) and V (V) from aqueous solution by glutaraldehyde crosslinked chitosan and nanocomposites.

In this paper, new adsorbents with high mechanical strength chitosan-graphene oxide (CS-GO) and chitosan-titanium dioxide (CS-TiO2) were synthesized by using glutaraldehyde as crosslinking agent, and the adsorption behavior of Pb (II) and V (V) on them were investigated. The materials were characterized by scanning electron microscopy (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The effects of initial metal ion concentration and contact time on the removal of V (V) and Pb (II) by CS-GO and CS-TiO2 were investigated. Characterization results showed that the hydroxyl group of GO/TiO2 reacted with the amino group of chitosan. A comparison of the kinetic models against experimental data showed that the kinetics react system was best described by the pseudo-second-order model. indicating that chemical adsorption was the main adsorption force. the Langmuir adsorption model and Freundlich model agreed well with the experimental data. The removal capacity of Pb (II) by CS-GO and CS-TiO2 were lower than those of V (V). The uncross-linked -OH and CO were the main adsorptive sites for Pb (II) removal, while uncross-linked -OH and -NH2 played an important role in removing V (V). These findings provided insights on the removing lead and vanadium pollution.

Selective graphene-like metal-free 2D nanomaterials and their composites for photocatalysis.

From the viewpoint of sustainability, graphene-like metal-free 2D nanomaterials (GMFs) hold great potential in different photocatalytic fields due to their distinct structures and properties. Although their lattice structures are highly similar, the properties of these nanomaterials are in vast diversity owing to the uniqueness of particular atomic arrangement, thus giving rise to their multi-faceted functionalities in photocatalytic process. In this review, we summarize the latest progress of GMFs and their hybrid composites in photocatalytic field, including graphene and its derivatives, hexagonal boron nitride (h-BN), graphitic carbon nitride (g-C3N4), black phosphorus (BP) and emerging 2D covalent organic frameworks (COFs). Their unique 2D structure and key photocatalytic properties are firstly briefly introduced. Then a critical discussion on their multiple roles in the activity enhancement of composite photocatalysts is emphasized, which in turn points out the direction of maximizing their functions and guides our efficient construction of hybrid photocatalysts based on above 2D nanomaterials. On this basis, a summary about the hybridization of above 2D metal-free materials is presented, and the merits of 2D/2D hybrid systems are elaborated. Last, we wrap up this review with some summative remarks, covering understanding their own unique strengths and weaknesses by comparison and proposing the major challenges and perspectives in this emerging field.

Physiological and morphological response of Aphanizomenon flos-aquae to watermelon (Citrullus lanatus) peel aqueous extract.

Natural algaecides are more likely to be specific and biodegradable, and may offer an environmentally friendly method for control of cyanobacterial blooms. We explored, for the first time, the potential for watermelon peel aqueous extract (WMPAE) to control the growth of the harmful blue-green alga Aphanizomenon flos-aquae. The growth inhibition and several physiological parameters of A. flos-aquae, in response to WMPAE, were analyzed. Results showed that WMPAE significantly inhibited the growth of A. flos-aquae in a concentration-dependent way. The highest inhibition reached 94 % after 3 days' treatment with 6 g L-1 of WMPAE and a significant effect was obtained with lower doses and shorter times as well. The cell viability decreased quickly, cell shape changed, and intracellular structural damage occurred. At the same time, the antioxidant enzymes (superoxide dismutase SOD, catalase CAT and peroxidase POD) and malondialdehyde (MDA) levels all increased significantly, indicating that WMPAE between 2-6 g L-1 induced severe oxidative stress and damage to A. flos-aquae. Moreover, production of the four pigments chlorophyll a (Chl a), carotenoids, phycocyanin (PC), and allophycocyanin (APC) were all stimulated, though photosynthesis of A. flos-aquae was clearly inhibited. The maximum quantum yield of photosystem II (Fv/Fm) and the effective quantum yield of photosystem II ( Fv'/Fm') declined sharply, suggesting the decreased photosystem capacity of A. flos-aquae to convert light energy into chemical energy. In addition, non-photochemical quenching (NPQ) of A. flos-aquae increased after a very short time exposure to WMPAE, and decreased significantly with prolonged exposure time, which indicated the failure of photo protection mechanisms. These results suggest that the loss of cell viability, and increases in oxidative stress, and damage to intracellular structure and photosynthetic systems might be the mechanisms for the inhibitory effects. Our results suggested that WMPAE could be a novel and effective approach for controlling the growth of A. flos-aquae in aquatic environments.

UPLC-G2Si-HDMS untargeted metabolomics for identification of metabolic targets of Yin-Chen-Hao-Tang used as a therapeutic agent of dampness-heat jaundice syndrome.

Yin-Chen-Hao-Tang (YCHT), the classic formulae of traditional Chinese medicine (TCM), is widely used to treat dampness-heat jaundice syndrome (DHJS) and various liver diseases. However, the therapeutic mechanism of YCHT is yet to have an integrated biological interpretation. In this work, we used metabolomics technology to reveal the adjustment of small molecule metabolites in body during the treatment of YCHT. Aim to discover the serum biomarkers which are associated with the treatment of DHJS against YCHT. Pathological results and biochemical indicators showed that the hepatic injury and liver index abnormalities caused by DHJS was effectively improve after treatment with YCHT. On the basis of effective treatment, ultra-high performance liquid chromatography (UPLC-G2Si-HDMS) combined with the multivariate statistical analysis method was utilized to analyze the serum samples. Finally, 22 biomarkers were identified by using mass spectrometry and illuminated the correlative metabolic pathways which play a significant role and as therapeutic targets in the treatment of DHJS. This work demonstrated that mass spectrometry metabolomics provides a new insight to elucidate the action mechanism of formulae.

Serum metabolomics strategy for understanding the therapeutic effects of Yin-Chen-Hao-Tang against Yanghuang syndrome.

Yin-Chen-Hao-Tang (YCHT), a classic Chinese herbal formula, is characterized by its strong therapeutic effects of liver regulation and relief of jaundice, especially Yanghuang syndrome (YHS). YHS is a type of jaundice with damp-heat pathogenesis, and it is considered a complicated Chinese medicine syndrome (CMS). The accurate mechanism for healing YHS has not yet been completely reported. The purpose of the current research is to investigate the expression of endogenous biomarkers in YHS mice and evaluate the clinical therapeutic effect of YCHT. Serum samples were analyzed using UPLC-Q/TOF-MS techniques in order to determine differential metabolites to elucidate the functional mechanism of YCHT on YHS through metabolite profiling combined with multivariate analysis. Simultaneously, the exact diversification of YHS mice was elucidated using blood biochemistry indexes and histopathological examination, and the results indicated that YHS is markedly improved by YCHT. Unsupervised principal component analysis (PCA) patterns were constructed to dissect the variances of metabolic profiling. Overall, 22 potential biomarkers were identified using a metabolomics approach based on an accurate MS/MS approach, clustering and distinguishing analysis. The present work demonstrates that the effectiveness of YCHT against YHS prompts distinct discrepancies in metabolic profiles by adjusting biomarkers and regulating metabolic disorders. A total of 15 metabolic pathways were involved in biological disturbance. This demonstrates that metabolomic techniques are powerful means to explore the pathogenesis of CMS and the therapeutic effects of traditional Chinese formulae.

Functional metabolomics discover pentose and glucuronate interconversion pathways as promising targets for Yang Huang syndrome treatment with Yinchenhao Tang.

Yinchenhao Tang (YCHT), a classic traditional Chinese medicine (TCM) formulae, plays an important role in the treatment of Yang Huang syndrome (YHS). With the emergence of new biomarkers of YHS uncovered via metabonomics, the underlying functional mechanisms are still not clear. Functional metabolomics aims at converting biomarkers derived from metabonomics into disease mechanisms. Here, an integrated non-target metabolomics and IPA strategy were used to investigate the YCHT intervention on YHS. Our metabolomics study has shown that the potential protective effect of YCHT on YHS mice leads to significant changes in the metabolic profile by modulating the biomarkers and regulating the metabolic disorders. Twenty two differential metabolite biomarkers and fifteen involved metabolic pathways were correlated with the regulation of YCHT treatment on YHS. Functional metabolomics identified a core biomarker, d-glucuronic acid in pentose and glucuronate interconversion pathways, which was directly related to the target prediction of UDP-glucuronosyltransferase 1A1 and eventually leaded to a series of disturbances. In conclusion, this study shows that functional metabolomics can discover metabolic pathways as promising targets.