Peptide set test: a peptide-centric strategy to infer differentially expressed proteins.

MOTIVATION: The clinical translation of mass spectrometry-based proteomics has been challenging due to limited statistical power caused by large technical variability and inter-patient heterogeneity. Bottom-up proteomics provides an indirect measurement of proteins through digested peptides. This raises the question whether peptide measurements can be used directly to better distinguish differentially expressed proteins. RESULTS: We present a novel method called the peptide set test, which detects coordinated changes in the expression of peptides originating from the same protein and compares them to the rest of the peptidome. Applying our method to data from a published spike-in experiment and simulations demonstrates improved sensitivity without compromising precision, compared to aggregation-based approaches. Additionally, applying the peptide set test to compare the tumor proteomes of tamoxifen-sensitive and tamoxifen-resistant breast cancer patients reveals significant alterations in peptide levels of collagen XII, suggesting an association between collagen XII-mediated matrix reassembly and tamoxifen resistance. Our study establishes the peptide set test as a powerful peptide-centric strategy to infer differential expression in proteomics studies. AVAILABILITY AND IMPLEMENTATION: Peptide set test (PepSetTest) is publicly available at https://github.com/JmWangBio/PepSetTest.

A multiple linear regression analysis identifies factors associated with fear of cancer recurrence in postoperative patients with gastric cancer.

To investigate the risk factors of fear of cancer recurrence (FCR) in postoperative patients with gastric cancer (GC) and provide references for targeted nursing intervention development. A total of 84 patients who underwent GC surgery were included in this study. The fear of progression questionnaire-short form and social support rating scale were conducted, and multiple linear regression was performed to identify risk factors of FCR. The score of the fear of progression questionnaire-short form in patients with GC surgery was 39.1 ±â€…7.6. The results of multiple linear regression showed that age, education level, occupational status, course of the disease, Tumor node metastasis staging, and social support were the influencing factors of FCR in patients with GC (P < .05). The current situation of FCR in patients with GC surgery is not optimistic. The medical staff should pay more attention to patients with low age, low education level, unemployment, short course, high tumor node metastasis staging, low social support level, and other high-risk groups, and provide social support resources to reduce the level of FCR.

Research progress, challenges and perspectives of phospholipids metabolism in the LXR­LPCAT3 signaling pathway and its relation to NAFLD (Review).

Phospholipids (PLs) are principle constituents of biofilms, with their fatty acyl chain composition significantly impacting the biophysical properties of membranes, thereby influencing biological processes. Recent studies have elucidated that fatty acyl chains, under the enzymatic action of lyso­phosphatidyl­choline acyltransferases (LPCATs), expedite incorporation into the sn­2 site of phosphatidyl­choline (PC), profoundly affecting pathophysiology. Accumulating evidence suggests that alterations in LPCAT activity are implicated in various diseases, including non­alcoholic fatty liver disease (NAFLD), hepatitis C, atherosclerosis and cancer. Specifically, LPCAT3 is instrumental in maintaining systemic lipid homeostasis through its roles in hepatic lipogenesis, intestinal lipid absorption and lipoprotein secretion. The liver X receptor (LXR), pivotal in lipid homeostasis, modulates cholesterol, fatty acid (FA) and PL metabolism. LXR's capacity to modify PL composition in response to cellular sterol fluctuations is a vital mechanism for protecting biofilms against lipid stress. Concurrently, LXR activation enhances LPCAT3 expression on cell membranes and elevates polyunsaturated PL levels. This activation can ameliorate saturated free FA effects in vitro or endoplasmic reticulum stress in vivo due to lipid accumulation in hepatic cells. Pharmacological interventions targeting LXR, LPCAT and membrane PL components could offer novel therapeutic directions for NAFLD management. The present review primarily focused on recent advancements in understanding the LPCAT3 signaling pathway's role in lipid metabolism related to NAFLD, aiming to identify new treatment targets for the disease.

N-acyl homoserine lactones lactonase est816 suppresses biofilm formation and periodontitis in rats mediated by Aggregatibacter actinomycetemcomitans.

Aims: The current study aimed to explore the adjuvant therapeutic effect of N-acyl homoserine lactones (AHLs)-lactonase est816 on Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) biological behaviors and periodontitis progression. Methods: The inhibitory properties of est816 were detected by live/dead bacterial staining, scanning electron microscope (SEM), crystal-violet staining and reverse-transcription quantitative PCR (RT-qPCR). Biocompatibility of est816 on human gingival fibroblasts (HGFs) and human gingival epithelial cells (HGEs) was evaluated by CCK8 and ELISA. The ligature-induced periodontitis model was established in rats. Micro computed tomography and immunohistochemical and histological staining served to evaluate the effect of est816 on the prevention of periodontitis in vivo. Results: est816 significantly attenuated biofilm formation, reduced the mRNA expression of cytolethal distending toxin, leukotoxin and poly-N-acetyl glucosamine (PNAG) and downregulated expressions of interleukin-6 and tumor necrosis factor-α with low cell toxicity. In vivo investigations revealed est816 decreased alveolar bone resorption, suppressed matrix metalloproteinase-9 expression and increased osteoprotegerin expression. Conclusion: est816 inhibited A. actinomycetemcomitans biofilm formation and virulence release, resulting in anti-inflammation and soothing of periodontitis in rats, indicating that est816 could be investigated in further research on periodontal diseases.

Post-synthetic modification of covalent organic framework for efficient adsorption of organochlorine pesticides from cattle's milk.

Analysis of organochlorine pesticides (OCPs) residues in milk faces a significant challenge. Herein, a sea urchin structured covalent organic framework bearing boric acid groups named COF-B(OH)2 was synthesized and applied as a coating material for solid-phase microextraction (SPME) of the OCPs in cattle's milk. Its performance was superior to that of three commonly used commercial SPME fibers, which could be due to the coexistence of hydrogen bonding, halogen bonding, π-stacking and electrostatic interactions. Besides, the fiber coating displayed good stability and reusability. After optimization, a COF-B(OH)2 based SPME coupled with gas chromatography-electron capture detection was established for the sensitive detection of the OCPs from milk samples. The limits of detection (S/N = 3) were between 0.04 and 1.00 µg kg-1. Satisfactory accuracy was achieved with the method recoveries in the range of 87.5 % to 112.5 %. These results manifest the feasibility of the COF-B(OH)2 coated fiber for the enrichment of the trace OCPs from milk samples.

An endophytic fungus interacts with the defensin-like protein OsCAL1 to regulate cadmium allocation in rice.

Defensin-like proteins are conserved in multicellular organisms and contribute to innate immune responses against fungal pathogens. In rice, defensins play a novel role in regulating cadmium (Cd) efflux from the cytosol. However, whether the antifungal activity of defensins correlates with Cd-efflux function remains unknown. In this study, we isolated an endophytic Fusarium, designed Fo10, by a comparative microbiome analysis of rice plants grown in a paddy contaminated with Cd. Fo10 is tolerant to high levels of Cd, but is sensitive to the defensin-like protein OsCAL1, which mediates Cd efflux to the apoplast. We found that Fo10 symbiosis in rice is regulated by OsCAL1 dynamics, and Fo10 coordinates multiple plant processes, including Cd uptake, vacuolar sequestration, efflux to the environment, and formation of Fe plaques in the rhizosphere. These processes are dependent on the salicylic acid signaling pathway to keep Cd levels low in the cytosol of rice cells and to decrease Cd levels in rice grains without any yield penalty. Fo10 also plays a role in Cd tolerance in the poaceous crop maize and wheat, but has no observed effects in the eudicot plants Arabidopsis and tomato. Taken together, these findings provide insights into the mechanistic basis underlying how a fungal endophyte and host plant interact to control Cd accumulation in host plants by adapting defense responses to promote the establishment of a symbiosis that permits adaptation to high-Cd environments.

A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation.

Human antigen R (HuR) is a ubiquitously expressed RNA-binding protein, which functions as an RNA regulator. Overexpression of HuR correlates with high grade tumours and poor patient prognosis, implicating it as an attractive therapeutic target. However, an effective small molecule antagonist to HuR for clinical use remains elusive. Here, a single domain antibody (VHH) that binds HuR with low nanomolar affinity was identified and shown to inhibit HuR binding to RNA. This VHH was used to engineer a TRIM21-based biological PROTAC (bioPROTAC) that could degrade endogenous HuR. Significantly, HuR degradation reverses the tumour-promoting properties of cancer cells in vivo by altering the HuR-regulated proteome, highlighting the benefit of HuR degradation and paving the way for the development of HuR-degrading therapeutics. These observations have broader implications for degrading intractable therapeutic targets, with bioPROTACs presenting a unique opportunity to explore targeted-protein degradation through a modular approach.

DOSE-L1000: unveiling the intricate landscape of compound-induced transcriptional changes.

MOTIVATION: The LINCS L1000 project has collected gene expression profiles for thousands of compounds across a wide array of concentrations, cell lines, and time points. However, conventional analysis methods often fall short in capturing the rich information encapsulated within the L1000 transcriptional dose-response data. RESULTS: We present DOSE-L1000, a database that unravels the potency and efficacy of compound-gene pairs and the intricate landscape of compound-induced transcriptional changes. Our study uses the fitting of over 140 million generalized additive models and robust linear models, spanning the complete spectrum of compounds and landmark genes within the LINCS L1000 database. This systematic approach provides quantitative insights into differential gene expression and the potency and efficacy of compound-gene pairs across diverse cellular contexts. Through examples, we showcase the application of DOSE-L1000 in tasks such as cell line and compound comparisons, along with clustering analyses and predictions of drug-target interactions. DOSE-L1000 fosters applications in drug discovery, accelerating the transition to omics-driven drug development. AVAILABILITY AND IMPLEMENTATION: DOSE-L1000 is publicly available at https://doi.org/10.5281/zenodo.8286375.

Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear. AIM OF THE STUDY: To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology. MATERIALS AND METHODS: The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology. RESULTS: A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC. CONCLUSION: Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.

Multiomics links global surfactant dysregulation with airflow obstruction and emphysema in COPD.

Rationale: Pulmonary surfactant is vital for lung homeostasis as it reduces surface tension to prevent alveolar collapse and provides essential immune-regulatory and antipathogenic functions. Previous studies demonstrated dysregulation of some individual surfactant components in COPD. We investigated relationships between COPD disease measures and dysregulation of surfactant components to gain new insights into potential disease mechanisms. Methods: Bronchoalveolar lavage proteome and lipidome were characterised in ex-smoking mild/moderate COPD subjects (n=26) and healthy ex-smoking (n=20) and never-smoking (n=16) controls using mass spectrometry. Serum surfactant protein analysis was performed. Results: Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, surfactant protein (SP)-B, SP-A and SP-D concentrations were lower in COPD versus controls (log2 fold change (log2FC) -2.0, -2.2, -1.5, -0.5, -0.7 and -0.5 (adjusted p<0.02), respectively) and correlated with lung function. Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D, napsin A and CD44 inversely correlated with computed tomography small airways disease measures (expiratory to inspiratory mean lung density) (r= -0.56, r= -0.58, r= -0.45, r= -0.36, r= -0.44, r= -0.37, r= -0.40 and r= -0.39 (adjusted p<0.05)). Total phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, SP-A, SP-B, SP-D and NAPSA inversely correlated with emphysema (% low-attenuation areas): r= -0.55, r= -0.61, r= -0.48, r= -0.51, r= -0.41, r= -0.31 and r= -0.34, respectively (adjusted p<0.05). Neutrophil elastase, known to degrade SP-A and SP-D, was elevated in COPD versus controls (log2FC 0.40, adjusted p=0.0390), and inversely correlated with SP-A and SP-D. Serum SP-D was increased in COPD versus healthy ex-smoking volunteers, and predicted COPD status (area under the curve 0.85). Conclusions: Using a multiomics approach, we demonstrate, for the first time, global surfactant dysregulation in COPD that was associated with emphysema, giving new insights into potential mechanisms underlying the cause or consequence of disease.

Lignans from the Roots and Rhizomes of Dysosma versipellis and Their Cytotoxic Activities.

One new dibenzyltyrolactone lignan dysoslignan A (1), three new arylnaphthalide lignans dysoslignan B-C (2-4), along with fourteen known metabolites (5-18), were isolated from the roots and rhizomes of Dysosma versipellis. Their structures and stereochemistry were determined from analysis of NMR spectroscopic and circular dichroism (CD) data. Compound 2 represents the first report of naturally occurring arylnaphthalide lignan triglycoside. The cytotoxic activities of all isolated compounds were evaluated against A-549 and SMMC-7721 cell lines. Compounds 7-10 and 14-16 were more toxic than cisplatin in two tumor cell lines. This investigation clarifies the potential effective substance basis of D. versipellis in tumor treatment.

Qinggan Huoxue Recipe attenuates Alcoholic Liver Disease by suppressing PI3K/AKT signaling pathway based on network pharmacology.

Qinggan Huoxue Recipe (QGHXR) is originated from Xiao Chaihu Decotion. Many experimental studies have confirmed that QGHXR can significantly alleviate the symptoms of alcoholic liver disease (ALD), but the detailed mechanism is still unclear. Using traditional Chinese medicine network pharmacology analysis system database and animal experiments, we found that 180 potentially chemical compositions and 618 potential targets were screened from the prescription, which shared 133 signal pathways with ALD. Through animal experiments, it was found that QGHXR could reduce the liver total cholesterol (TC), serum TC, alanine aminotransferase, aspartate aminotransferase of ALD mice, reduce the lipid droplets and inflammatory injury of liver tissue. Meanwhile, it can also increase PTEN, decrease PI3K and AKT mRNA levels. In this study, we obtained the targets and pathways of QGHXR in the treatment of ALD, and preliminatively verified that QGHXR may improve ALD through PTEN/PI3K/AKT signaling pathway.

Dual-function DEFENSIN 8 mediates phloem cadmium unloading and accumulation in rice grains.

Grain cadmium (Cd) is translocated from source to sink tissues exclusively via phloem, though the phloem Cd unloading transporter has not been identified yet. Here, we isolated and functionally characterized a defensin-like gene DEFENSIN 8 (DEF8) highly expressed in rice (Oryza sativa) grains and induced by Cd exposure in seedling roots. Histochemical analysis and subcellular localization detected DEF8 expression preferentially in pericycle cells and phloem of seedling roots, as well as in phloem of grain vasculatures. Further analysis demonstrated that DEF8 is secreted into extracellular spaces possibly by vesicle trafficking. DEF8 bound to Cd in vitro, and Cd efflux from protoplasts as well as loading into xylem vessels decreased in the def8 mutant seedlings compared with the wild type. At maturity, significantly less Cd accumulation was observed in the mutant grains. These results suggest that DEF8 is a dual function protein that facilitates Cd loading into xylem and unloading from phloem, thus mediating Cd translocation from roots to shoots and further allocation to grains, representing a phloem Cd unloading regulator. Moreover, essential mineral nutrient accumulation as well as important agronomic traits were not affected in the def8 mutants, suggesting DEF8 is an ideal target for breeding low grain Cd rice.

Metabolomics window into the diagnosis and treatment of inflammatory bowel disease in recent 5 years.

Inflammatory bowel disease (IBD) is a kind of chronic inflammation that occurs in gastrointestinal tract, including Ulcerative colitis (UC) and Crohn's disease (CD). Although UC and CD are associated with intestinal inflammation and epithelial damage, they are quite different. The etiology of IBD has not been fully determined, but there is extensive evidence that its pathogenesis involves environmental, genetic, immune and microbial factors. The diagnosis and treatment of IBD is challenging due to its recurrent episodes and complex evolution. Metabolomics, as a new developing technology, can be used to qualitatively and quantitatively study small metabolic molecules in samples of patients, which include stool, urine, serum, plasma and tissues, and is increasingly valued in the diagnosis and treatment of IBD. This article sums up the recent progress of metabolomics in helping to diagnose and treat IBD diseases, hoping to provide biomarkers and new targets for the diagnosis and treatment of IBD. In addition, we present the limitations of the current study of metabolomics and highlight some solutions.

Progress and challenges of multidrug resistance proteins in diseases.

Chemotherapy remains the first choice for patients with advanced cancers when other treatments are ineffective. Multidrug resistance (MDR) is an unavoidable factor that negatively affects the effectiveness of cancer chemotherapy drugs. Researchers are trying to reduce MDR, improve the effectiveness of chemotherapeutic drugs, and alleviate patient suffering to positively contribute to disease treatment. MDR also occurs in inflammation and genetic disorders, which increases the difficulty of clinically beneficial treatments. The ATP-binding cassette (ABC) is an active transporter that plays an important role in the barrier and secretory functions of many normal cells. As the C subfamily in the ABC family, multidrug resistance proteins (MRPs/ABCCs) export a variety of antitumour drugs and are expressed in a variety of cancers. The present review summarises the role of MRPs in cancer and other diseases and recent research progress of MRP inhibitors to better examine the mechanism and function of MRPs, and establish a good relationship with clinical treatment.

Kaempferol attenuates nonalcoholic steatohepatitis by regulating serum and liver bile acid metabolism.

Objective: Changes in bile acids (BAs) are increasingly recognized as potential targets for non-alcoholic steatohepatitis (NASH). Kaempferol has been proved to be anti-inflammatory and reduce the disorder of lipid metabolism. In order to analyze the BA profile in NASH mice and determine the predictive biomarkers of kaempferol treatment, serum-targeted metabolomics and liver tissue RNA sequencing (RNA-seq) were carried out. Design: Six normal control mice (NC group), eight HFD-fed mice (HFD group), and eight kaempferol-treated HFD-fed mice (HFD + KP group) were included in the present study. Ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC-MS/MS) was used to quantify serum and liver BAs, and RNA-seq was used to quantify liver differentially expressed genes related to BA metabolism. Results: The serum levels of CA, ßMCA, UDCA, and 12-DHCA, as well as ωMCA in both the serum and liver, were significantly decreased in the HFD group compared with those in the NC group, and kaempferol can increase the serum levels of ßMCA, UDCA, and ωMCA and the liver level of 12-DHCA. The serum levels of TDCA, THDCA, TUDCA, TDCA/CA, and TDCA/DCA were significantly increased in the HFD group compared with those of the NC group, and kaempferol can decrease them. Furthermore, NASH mice had a higher liver level of total CA%, total CDCA%, primary BAs/secondary BAs, 12α-OH BAs/non-12α-OH Bas, and conjugated BAs/unconjugated BAs, and all decreased after kaempferol treatment. According to the RNA-seq results, we found that compared with the NC group, the mRNA expression of cholesterol-7α-hydroxylase (CYP7A1) in the HFD group was significantly increased, and the mRNA expression of sterol 12α-hydroxylase (CYP8B1) and multidrug resistance-related protein 3 (MRP3) was significantly decreased, while kaempferol significantly promoted the mRNA expression of mitochondrial sterol 27-hydroxylase (CYP27A1) and Na+ -taurocholate cotransporting polypeptide (NTCP). Conclusion: ßMCA, CA, UDCA, 12-DHCA, ωMCA, CDCA, TωMCA, TDCA, THDCA, TCDCA, and TUDCA in the serum, as well as 6,7-diketoLCA, 12-DHCA, and ωMCA in the liver, may be potential biomarkers for kaempferol to improve NASH. HFD-induced NASH may be associated with the increase of CYP7A1 and the decrease of CYP8B1, leading to increased BA synthesis, and the decrease of MRP3 leading to decreased BA synthesis, and kaempferol may alleviate NASH by increasing CYP27A1 and NTCP to enhance BA transport.

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world, and it often coexists with insulin resistance-related diseases including obesity, diabetes, hyperlipidemia, and hypertension, which seriously threatens human health. Better prevention and treatment strategies are required to improve the impact of NAFLD. Although needle biopsy is an effective tool for diagnosing NAFLD, this method is invasive and difficult to perform. Therefore, it is very important to develop more efficient approaches for the early diagnosis of NAFLD. Traditional Chinese medicine (TCM) can play a certain role in improving symptoms and protecting target organs, and its mechanism of action needs to be further studied. Metabolomics, the study of all metabolites that is thought to be most closely associated with the patients' characters, can provide useful clinically biomarkers that can be applied to NAFLD and may open up new methods for diagnosis. Metabolomics technology is consistent with the overall concept of TCM, and it can also be used as a potential mechanism to explain the effects of TCM by measuring biomarkers by metabolomics. Based on PubMed/MEDLINE and other databases, this paper retrieved relevant literature NAFLD and TCM intervention in NAFLD using metabolomics technology in the past 5 years were searched, and the specific metabolites associated with the development of NAFLD and the potential mechanism of Chinese medicine on improving symptoms were summarized.

The mechanism of branched-chain amino acid transferases in different diseases: Research progress and future prospects.

It is well known that the enzyme catalyzes the first step of branched-chain amino acid (BCAA) catabolism is branched-chain amino transferase (BCAT), which is involved in the synthesis and degradation of leucine, isoleucine and valine. There are two main subtypes of human branched chain amino transferase (hBCAT), including cytoplasmic BCAT (BCAT1) and mitochondrial BCAT (BCAT2). In recent years, the role of BCAT in tumors has attracted the attention of scientists, and there have been continuous research reports that BCAT plays a role in the tumor, Alzheimer's disease, myeloid leukaemia and other diseases. It plays a significant role in the growth and development of diseases, and new discoveries about this gene in some diseases are made every year. BCAT usually promotes cancer proliferation and invasion by activating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway and activating Wnt/ß-catenin signal transduction. This article reviews the role and mechanism of BCAT in different diseases, as well as the recent biomedical research progress. This review aims to make a comprehensive summary of the role and mechanism of BCAT in different diseases and to provide new research ideas for the treatment, prognosis and prevention of certain diseases.

Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases.

Sphingosine 1-phosphate receptor (S1PR), as a kind of G protein-coupled receptor, has five subtypes, including S1PR1, S1PR2, S1PR3, S1PR4, and S1PR5. Sphingosine 1-phosphate receptor (S1P) and S1PR regulate the trafficking of neutrophils and some cells, which has great effects on immune systems, lung tissue, and liver tissue. Presently, many related reports have proved that S1PR has a strong effect on the migration of lymphocytes, tumor cells, neutrophils, and many other cells via the regulation of signals, pathways, and enzymes. In this way, S1PR can regulate the relative response of the organism. Thus, S1PR has become a possible target for the treatment of autoimmune diseases, pulmonary disease, liver disease, and cancer. In this review, we mainly focus on the research of the S1PR for the new therapeutic directions of different diseases and is expected to assist support in the clinic and drug use.

Amino-functionalized hypercrosslinked polymer as sorbent for effective extraction of nitroimidazoles from water, drink and honey samples.

The three hypercrosslinked polymers (HCP) materials, designated as OPD-HCP, MPD-HCP and PPD-HCP, were synthesized by using o-phenylenediamine (OPD), m-phenylenediamine (MPD) and p-phenylenediamine (PPD) as monomers. They were characterized by infrared spectroscopy, powder X-ray diffraction, nitrogen sorption isotherms, and scanning electron microscopy. Then, the HCPs were explored as solid-phase extraction (SPE) adsorbent for the extraction of five nitroimidazoles (NDZs) (metronidazole, ronidazole, secnidazole, dimetridazole and ornidazole). Among the three HCPs, the MPD-HCP has the best adsorption performance for the NDZs. With the help of high-performance liquid chromatography with ultraviolet detection (HPLC-UV), good linear response range (0.07-40.0 ng mL-1), high method recovery (86.8%-113.3%), low limits of detection (0.02-0.15 ng mL-1) and good precision with the relative standard deviations of less than 8.1% were achieved for the determination of the NDZs in water samples. The effective determination of the NDZs in peach juice, honey tea, and honey samples were also realized by the developed method with satisfactory results. Based on both the experimental results and density functional theory calculation, the adsorption mechanism can be attributed to multiple interactions between the MPD-HCP and the NDZs, including hydrogen bonding, hydrophilic, and electrostatic interactions. The method provides a new alternative of choice for the determination of some NDZs in real samples.