Meta-analysis for systematic review of global micro/nano-plastics contamination versus various freshwater microalgae: Toxicological effect patterns, taxon-specific response, and potential eco-risks.

Micro/nano-plastics (MNPs), as emerging persistent pollutants, are threatening freshwater ecosystems worldwide. Microalgae are important primary producers at the base of trophic level and susceptible to MNPs contamination, possibly resulting in further contamination in higher trophic levels and water quality. This study conducted a systematic review of 1071 observations from 63 publications, utilizing meta-analysis and subgroup analysis to investigate the toxicological effect patterns of MNPs parameters (size, concentration, and type) on microalgae. We also explored the potential eco-risks of certain specific MNPs parameters and subtle variations in the response of various microalgae taxa to MNPs. Results suggested that microplastics significantly inhibited microalgal photosynthesis, while nano-plastics induced more severe cell membrane damage and promoted toxin-release. Within a certain range of concentrations (0∼50 mg/L), rising MNPs concentration progressively inhibited microalgal growth and chlorophyll-a content, and progressively enhanced toxin-release. Among MNPs types, polyamide caused higher growth inhibition and more severe lipid peroxidation, and polystyrene induced more toxin-release, whereas polyethylene terephthalate and polymethyl methacrylate posed minimal effects on microalgae. Moreover, Bacillariophyta growth was inhibited most significantly, while Chlorophyta displayed strong tolerance and Cyanophyta possessed strong adaptive and exceptional resilience. Particularly, Komvophoron, Microcystis, Nostoc, Scenedesmus, and Gomphonema were more tolerant and might dominate freshwater microalgal communities under MNPs contamination. These results are crucial for acquiring the fate of freshwater microalgae under various MNPs contamination, identifying dominant microalgae, and reasonably assessing and managing involved eco-risks.

Correlation Analysis of IL-17, IL-21, IL-23 with Non-Alcoholic Liver Fibrosis and Cirrhosis.

Objective: This research aimed to explore the involvement of interleukins (IL) - IL-6, IL-17, IL-21, and IL-23 - in the evolution and diagnosis of non-alcoholic liver fibrosis and cirrhosis. Methods: The study subjects were selected from the patients who visited the Department of Hepatology of X Hospital in Y City from August 2021 to April 2023. Peripheral blood samples were collected. All participants were divided into liver fibrosis, cirrhosis, hepatitis, and healthy subjects four groups. IL-21, IL-17, IL23, IL-6 were detected by double antibody sandwich. Results: The results showed that there was a significant difference in the levels of IL-17, IL-21, and IL-23 among the 4 groups (P<0.0001). ROC curve analysis showed that the AUC values of IL-17, IL-21 and liver fiber 4 items were >0.70, suggesting that the diagnostic efficacy of IL-17, IL-21 was similar to that of liver fiber 4 items. Spearman correlation analysis showed that IL-17 had a positive correlation with collagen type III N-peptide, type IV collagen, and Laminin (P < 0.05), and no correlation with Hyaluronic acid (P > 0.05). Conclusion: IL-17, IL-21, and IL-23 play a pivotal role in the inflammatory pathways associated with liver injuries, establishing themselves as potent auxiliary diagnostic markers in identifying liver fibrosis and cirrhosis.

Discovery of 2,8-dihydroxyadenine in HUA patients with uroliths and biomarkers for its associated nephropathy.

Currently, it is acknowledged that gout is caused by uric acid (UA). However, some studies have revealed no correlation between gout and UA levels, and growing evidence suggests that 2,8-dihydroxyadenine (2,8-DHA), whose structural formula is similar to UA but is less soluble, may induce gout. Hence, we hypothesized that uroliths from hyperuricemia (HUA) patients, which is closely associated with gout, may contain 2,8-DHA. In this study, 2,8-DHA in uroliths and serum of HUA patients were determined using HPLC. Moreover, bioinformatics was used to investigate the pathogenic mechanisms of 2,8-DHA nephropathy. Subsequently, a mouse model of 2,8-DHA nephropathy established by the gavage administration of adenine, as well as a model of injured HK-2 cells induced by 2,8-DHA were used to explore the pathogenesis of 2,8-DHA nephropathy. Interestingly, 2,8-DHA could readily deposit in the cortex of the renal tubules, and was found in the majority of these HUA patients. Additionally, the differentially expressed genes between 2,8-DHA nephropathy mice and control mice were found to be involved in inflammatory reactions. Importantly, CCL2 and IL-1ß genes had the maximum degree, closeness, and betweenness centrality scores. The expressions of CCL2 and IL-1ß genes were significantly increased in the serum of 24 HUA patients with uroliths, indicating that they may be significant factors for 2,8-DHA nephropathy. Further analysis illustrated that oxidative damage and inflammation were the crucial processes of 2,8-DHA renal injury, and CCL2 and IL-1ß genes were verified to be essential biomarkers for 2,8-DHA nephropathy. These findings revealed further insights into 2,8-DHA nephropathy, and provided new ideas for its diagnosis and treatment.

Novel ecological implications of non-toxic Microcystis towards toxic ecotype in population-promoting toxic ecotype dominance at various N levels and cooperative defense against luteolin-stress.

Microcystin (MC)-producing (MC+) and MC-free (MC-) Microcystis always co-exist and interact during Microcystis-dominated cyanobacterial blooms (MCBs), where MC+Microcystis abundance and extracellular MC-content (EMC) determine the hazard extent of MCBs. The current study elucidated intraspecific interaction between MC+ and MC-Microcystis at various nitrogen (N) levels (0.5-50 mg/L) and how such N-mediated interaction impacted algicidal and EMC-inhibiting effect of luteolin, a natural bioalgicide. Conclusively, MC+ and MC-Microcystis were inhibited mutually at N-limitation (0.5 mg/L), which enhanced the algicidal and EMC-inhibiting effects of luteolin. However, at N-sufficiency (5-50 mg/L), MC-Microcystis promoted MC+ ecotype growth and dominance, and such intraspecific interaction induced the cooperative defense of two ecotypes, weakening luteolin's algicidal and EMC-inhibiting effects. Mechanism analyses further revealed that MC+Microcystis in luteolin-stress co-culture secreted exopolymeric substances (EPSs) for self-protection against luteolin-stress and also released more EMC to induce EPS-production by MC-Microcystis as protectants, thus enhancing their luteolin-resistance and promoting their growth. This study provided novel ecological implications of MC-Microcystis toward MC+ ecotype in terms of assisting the dominant establishment of MC+Microcystis and cooperative defense with MC+ ecotype against luteolin, which guided the application of bioalgicide (i.e. luteolin) for MCBs and MCs pollution mitigation in different eutrophication-degree waters.

Inoculating exogenous bacterium Brevibacillus laterosporus ZR-11 at maturity stage accelerates composting maturation by regulating physicochemical parameters and indigenous bacterial community succession.

Brevibacillus laterosporus ZR-11, a bio-control strain, was innovatively inoculated at maturity stage of composting to clarify its effect on physicochemical parameters and indigenous bacterial community structure in compost pile. Results revealed that ZR-11 inoculum rapidly increased pile temperature to 52 ºC and raised germination index (GI) value to beyond 85% on day 3, thereby achieving higher pile temperature and GI in the inoculated group than the non-inoculated group almost along maturity stage, and also decreased C/N ratio of the inoculated group to below 20 by composting end (day 8). Also, ZR-11 succeeded in colonizing compost pile along maturity stage. These suggested that ZR-11 as inoculum at maturity stage could accelerate compost maturation and have a potential to participate in bio-fertilizer production. High-throughput sequencing indicated that bacterial community structure experienced substantial succession in the inoculated and non-inoculated groups, and Firmicutes, Proteobacteria, and Actinobacteria were the dominant phyla in the two groups during maturity stage, with their abundances higher in the inoculated group. Saccharomonospora and Ammoniibacillus abundance increased on day 3 while Actinomadura abundance increased on day 6 in the inoculated group. As verified statistically, pile temperature and pH were key factors closely linked to dominant genera abundance, where Saccharomonospora and Ammoniibacillus abundance were positively correlated to pile temperature, while Actinomadura abundance was positively correlated to pile pH. Thus, it was inferred that ZR-11 inoculum could improve parameters such as temperature and pH to modify dominant genera abundance, thus regulating indigenous bacterial community succession, which might in turn promote compost maturation.

Long-term tracking robust removal of Microcystis-dominated bloom and microcystin-pollution risk by luteolin continuous-release microsphere at different nitrogen levels-Mechanisms from proteomics and gene expression.

Luteolin continuous-release microsphere (CRM) has promising algicidal effect against Microcystis, but how nitrogen (N) level impacted CRM effects on Microcystis growth and microcystins (MCs) pollution was never tracked along long term. This study revealed that luteolin CRM exerted long-term and robust inhibitory effects on Microcystis growth and MC-pollution by sharply decreasing extracellular and total MCs content at each N level, with growth inhibition ratio of 88.18%-96.03%, 92.91%-97.17% and 91.36%-95.55% at 0.5, 5 and 50 mg/L N, respectively, during day 8-30. Further analyses revealed that CRM-stress inhibited transferase, GTPase and ATPase activities, ATP binding, metal ion binding, fatty acid biosynthesis, transmembrane transport and disrupted redox homeostasis to pose equally robust algicidal effect at each N level. At lower N level, CRM-stress tended to induce cellular metabolic mode towards stronger energy supply/acquisition but weaker energy production/consumption, while triggered a shift towards stronger energy production/storage but weaker energy acquisition/consumption as N level elevated, thus disturbing metabolic balance and strongly inhibiting Microcystis growth at each N level. Long-term robust algicidal effect of CRM against other common cyanobacteria besides Microcystis was evident in natural water. This study shed novel insights into inhibitory effects and mechanisms of luteolin CRM on Microcystis growth and MC-pollution in different N-level waters.

Hemolytic disease of the newborn due to anti-Jra from a Chinese mother with one novel and one classic heterozygous mutation.

OBJECTIVE: Investigation of a Jr(a-) family samples, identification of the mutant and assessment of the differences of Jr antigen density of the Jr(a-) family members, random adult and newborn individuals' RBCs. BACKGROUND: The anti-Jra antibody is generated when a Jr(a-) individual pregnant or transfused with Jr(a+) blood unit, which can lead to mild-to-moderate hemolytic disease of the foetus and newborn (HDFN) or hemolytic transfusion reaction (HTR). Several mutations had been identified. The anti-Jra caused HDFN is not rare in East Asia, but due to the lack of antibody and molecular background, it is likely to lead missed detection. METHODS AND MATERIALS: One G4P1 woman had been detected as IAT positive during prenatal examination. Suspected as anti-Jra after the laboratory serological testing, the maternal sample was further assessed by molecular analysis. The antigen density was detected by flow cytometry after reacting with anti-Jra serum in family members and the normal individuals. RESULTS: One novel frameshift mutation c.717delC and one previously identified mutation c.706C > T in ABCG2 was identified on proband. The infant haemoglobin(Hb) and bilirubin increased significantly after exchange transfusion and the severe HDFN was relieved. Flow cytometry results showed that the Jra antigens on adult RBCs were significantly less than those on the infant. CONCLUSION: The c.717delC mutation can lead to the shortening of protein ABCG2 in the site of p.Leu307Stop, result in the loss of Jra antigen. The difference in antigen density between adult and infant RBCs may be a possible reason that leads to severe HDFN but not transfusion reaction. Breastfeeding may lead to slower recovery from HDFN.

A Network-Pharmacology-Combined Integrated Pharmacokinetic Strategy to Investigate the Mechanism of Potential Liver Injury due to Polygonum multiflorum.

Polygonum multiflorum (PM) has been used as a tonic and anti-aging remedy for centuries in Asian countries. However, its application in the clinic has been hindered by its potential to cause liver injury and the lack of investigations into this mechanism. Here, we established a strategy using a network pharmacological technique combined with integrated pharmacokinetics to provide an applicable approach for addressing this issue. A fast and sensitive HPLC-QQQ-MS method was developed for the simultaneous quantification of five effective compounds (trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin-8-O-ß-d-glucoside, physcion-8-O-ß-d-glucoside, aloe-emodin and emodin). The method was fully validated in terms of specificity, linearity, accuracy, precision, extraction recovery, matrix effects, and stability. The lower limits of quantification were 0.125-0.500 ng/mL. This well-validated method was successfully applied to an integrated pharmacokinetic study of PM extract in rats. The network pharmacological technique was used to evaluate the potential liver injury due to the five absorbed components. Through pathway enrichment analysis, it was found that potential liver injury is primarily associated with PI3K-Akt, MAPK, Rap1, and Ras signaling pathways. In brief, the combined strategy might be valuable in revealing the mechanism of potential liver injury due to PM.

Research on weed identification method in rice fields based on UAV remote sensing.

Rice is the world's most important food crop and is of great importance to ensure world food security. In the rice cultivation process, weeds are a key factor that affects rice production. Weeds in the field compete with rice for sunlight, water, nutrients, and other resources, thus affecting the quality and yield of rice. The chemical treatment of weeds in rice fields using herbicides suffers from the problem of sloppy herbicide application methods. In most cases, farmers do not consider the distribution of weeds in paddy fields, but use uniform doses for uniform spraying of the whole field. Excessive use of herbicides not only pollutes the environment and causes soil and water pollution, but also leaves residues of herbicides on the crop, affecting the quality of rice. In this study, we created a weed identification index based on UAV multispectral images and constructed the WDVI NIR vegetation index from the reflectance of three bands, RE, G, and NIR. WDVI NIR was compared with five traditional vegetation indices, NDVI, LCI, NDRE, and OSAVI, and the results showed that WDVI NIR was the most effective for weed identification and could clearly distinguish weeds from rice, water cotton, and soil. The weed identification method based on WDVI NIR was constructed, and the weed index identification results were subjected to small patch removal and clustering processing operations to produce weed identification vector results. The results of the weed identification vector were verified using the confusion matrix accuracy verification method and the results showed that the weed identification accuracy could reach 93.47%, and the Kappa coefficient was 0.859. This study provides a new method for weed identification in rice fields.

Classification of rice leaf blast severity using hyperspectral imaging.

Rice leaf blast is prevalent worldwide and a serious threat to rice yield and quality. Hyperspectral imaging is an emerging technology used in plant disease research. In this study, we calculated the standard deviation (STD) of the spectral reflectance of whole rice leaves and constructed support vector machine (SVM) and probabilistic neural network (PNN) models to classify the degree of rice leaf blast at different growth stages. Average accuracies at jointing, booting and heading stages under the full-spectrum-based SVM model were 88.89%, 85.26%, and 87.32%, respectively, versus 80%, 83.16%, and 83.41% under the PNN model. Average accuracies at jointing, booting and heading stages under the STD-based SVM model were 97.78%, 92.63%, and 92.20%, respectively, versus 88.89%, 91.58%, and 92.20% under the PNN model. The STD of the spectral reflectance of the whole leaf differed not only within samples with different disease grades, but also among those at the same disease level. Compared with raw spectral reflectance data, STDs performed better in assessing rice leaf blast severity.

NLRP3 Inflammasome Simultaneously Involved in Autophagy and Phagocytosis of THP-1 Cells to Clear Aged Erythrocytes.

Autophagy and phagocytosis are two important processes that capture and digest materials found in cellular interiors and exteriors, respectively. Aged red blood cells (RBCs) are cleared by phagocytes in vivo. We focused on determining whether autophagy occurs after phagocytes swallow sunset erythrocytes, and whether the degree of autophagy is related to scavenging ability of phagocytes to erythrocytes. In addition, the ability of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome to regulate erythrocyte clearance by phagocytes and its association with autophagy-related protein 16-like protein 1 (ATG16L1) are confirmed. We constructed a stable and low-NLRP3 expression THP-1 cell line using CRISPR/Cas9 technology. The analysis of erythrocyte clearance and autophagy of THP-1 cells with low NLRP3 expression showed that autophagy changes together when THP-1 engulfs aged RBCs. The occurrence of autophagy was dominated by microtubule-associated protein 1A/1B-light chain 3- (LC3-) associated phagocytosis accompanied by canonical autophagy. A negative correlation exists between the clearance of RBCs by THP-1 cells and the degree of autophagy. Downregulating the expression of NLRP3 in THP-1 cells can simultaneously inhibit the scavenging ability of THP-1 to erythrocytes and the degree of autophagy. In addition, the autophagy inhibitor bafilomycin A1 (BafA1) can enhance the phagocytosis ability of THP-1 to erythrocytes and promote the NLRP3 activation in THP-1 cells, while the autophagy inducer rapamycin inhibits the phagocytosis ability of THP-1 to RBCs and downregulates the NLRP3 activation. Results showed that autophagy and phagocytosis may be dynamic balance processes that can provide sufficient nutrition and energy to cells. Choosing NLRP3 as a target may regulate the phagocytic ability and the degree of autophagy in the meantime. These findings may be a potential strategy for regulating the clearance rate of phagocytes to aged RBCs and the secretion of proinflammatory cytokines to ensure transfusion safety.

Research progress on application of single-cell TCR/BCR sequencing technology to the tumor immune microenvironment, autoimmune diseases, and infectious diseases.

Single-cell omics is the profiling of individual cells through sequencing and other technologies including high-throughput analysis for single-cell resolution, cell classification, and identification as well as time series analyses. Unlike multicellular studies, single-cell omics overcomes the problem of cellular heterogeneity. It provides new methods and perspectives for in-depth analyses of the behavior and mechanism of individual cells in the cell population and their relationship with the body, and plays an important role in basic research and precision medicine. Single-cell sequencing technologies mainly include single-cell transcriptome sequencing, single-cell assay for transposase accessible chromatin with high-throughput sequencing, single-cell immune profiling (single-cell T-cell receptor [TCR]/B-cell receptor [BCR] sequencing), and single-cell transcriptomics. Single-cell TCR/BCR sequencing can be used to obtain a large amount of single-cell gene expression and immunomics data at one time, and combined with transcriptome sequencing and TCR/BCR diversity data, can resolve immune cell heterogeneity. This paper summarizes the progress in applying single-cell TCR/BCR sequencing technology to the tumor immune microenvironment, autoimmune diseases, infectious diseases, immunotherapy, and chronic inflammatory diseases, and discusses its shortcomings and prospects for future application.

Nitrogen-dependent luteolin effect on Microcystis growth and microcystin-pollution risk - Novel mechanism insights unveiled by comparative proteomics and gene expression.

Phytogenic allelochemical luteolin has potential to mitigate Microcystis-dominated cyanobacterial blooms (MCBs), but its algicidal effect against toxigenic Microcystis may be impacted by natural factors, especially nitrogen (N) level in waters. This study innovatively explored N-dependent effect of luteolin on Microcystis growth and its microcystins (MCs) production/release, and elucidated underlying mechanisms from proteomics and gene expression views. Generally, at each N level, rising luteolin dose progressively inhibited Microcystis growth by inhibiting proteins syntheses and genes expression involving light-capturing, photosynthetic electron transfer, Calvin cycle and phosphorus (P) acquisition, according to comparative proteomics and gene expression. At higher luteolin dose and lower N level, Microcystis cell tended to increase microcystins (MCs) production and conservation ability, with the highest increase degree observed at 12 mg/L luteolin and 0.5 mg/L N on day 10, reaching 1.96 and 2.68 folds of luteolin-free control, respectively, but decrease MC-release as extracellular MCs content (EMC), with inhibition ratio of 72.86%, 73.57%, 74.45% and 40.58%, 45.28%, 60.00% at rising N level under 12 mg/L luteolin stress on day 10 and 16, respectively. These enabled cellular defensive response of Microcystis to stronger stress and N limitation. Under luteolin stress, higher N level more strongly up-regulated numerous processes (e.g., oxidoreductase activity, ATP binding and transmembrane transport, oxidative phosphorylation, tricarboxylic acid cycle, fatty acid biosynthesis, glycolysis/gluconeogenesis, pyruvate, amino acids metabolism, metal ion-binding, P acquisition) as compensative protective responses to progressively down-regulated photosynthetic and ribosomal processes at higher N level, thus causing faster Microcystis growth than lower N level. This study provided novel insights for N-dependent effect and mechanisms of luteolin on MCBs mitigation and MCs risk control, and guided algicidal application of luteolin in different eutrophic-degree waters.

The Role of Liquid Biopsy Analytes in Diagnosis, Treatment and Prognosis of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract worldwide and is a serious threat to human life and health. CRC occurs and develops in a multi-step, multi-stage, and multi-gene process, in which abnormal gene expression plays an important role. CRC is currently diagnosed via endoscopy combined with tissue biopsy. Compared with tissue biopsy, liquid biopsy technology has received increasingly more attention and applications in the field of molecular detection due to its non-invasive, safe, comprehensive, and real-time dynamic nature. This review article discusses the application and limitations of current liquid biopsy analytes in the diagnosis, treatment, and prognosis of CRC, as well as directions for their future development.

Circular RNAs and Their Role in Exosomes.

As a novel class of endogenous non-coding RNAs discovered in recent years, circular RNAs (circRNAs) are highly conserved and stable covalently closed ring structures with no 5'-end cap or 3'-end poly(A) tail. CircRNAs are formed by reverse splicing, mainly by means of a noose structure or intron complementary pairing. Exosomes are tiny discoid vesicles with a diameter of 40-100 nm that are secreted by cells under physiological and pathological conditions. Exosomes play an important role in cell-cell communication by carrying DNA, microRNAs, mRNAs, proteins and circRNAs. In this review, we summarize the biological functions of circRNAs and exosomes, and further reveal the potential roles of exosomal circRNAs in different diseases, providing a scientific basis for the diagnosis, treatment, and prognosis of a wide variety of diseases.

Joint effects and mechanisms of luteolin and kaempferol on toxigenic Microcystis growth-Comprehensive analysis on two isomers interaction in binary mixture.

Allelochemicals are widely accepted as promising algaecide to mitigate Microcystis-dominated cyanobacterial blooms (MCBs). Allelopathic algicidal effect of single luteolin or kaempferol against Microcystis had been confirmed, but their joint effect against Microcystis was unclear. This study comprehensively explored time-dependent joint effect and mechanisms of luteolin and kaempferol on Microcystis growth during 14 day-test. The 50%-inhibitory threshold of their mixture (IC50 mix) was verified as 4.872 and 5.211 mg/L at equitoxic ratio, and 5.167 and 4.487 mg/L at equivalent ratio, respectively, on day 8 and 14. Using toxicity unit, isobologram and predictive models, results revealed that luteolin and kaempferol at equivalent ratio interacted additively at lower, median and higher dosages, while at equitoxic ratio interacted additively at lower dosage but synergistically at median and higher dosages in Microcystis on day 8 and 14, implying that their equitoxic mixture posed better algicidal effect against Microcystis. Various dosages of equitoxic mixture concurrently decreased aqueous and total microcystins (MCs) contents along test. Thus, luteolin and kaempferol could be jointly applied as high-efficacy and eco-safe algaecide with declined MCs pollution risks. As mixture dosage elevated, more strongly weakened cellular MCs retention and inhibited cellular photosynthetic pigments content during late stage, as well as decreased aqueous MCs content long test, jointly explained increasing growth inhibition ratio with rising mixture dosage. Yet, cell damage was gradually repaired due to early stimulated antioxidant defense at each mixture dosage, thus cell damage might not be a major reason for inhibited growth under mixture stress. This study provided novel insights and guidance to coupled application of luteolin and kamepferol for mitigating MCBs and decreasing MCs pollution risks.

Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer.

Background: Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges. Methods: The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Results: Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.

Rapid identification of chemical constituents of Rhodiola crenulata using liquid chromatography-mass spectrometry pseudotargeted analysis.

Rhodiola crenulata (R. crenulata), is a famous traditional Chinese medicine, with observable effects such as anti-high-altitude illness and fatigue resistance. Nevertheless, comprehensive and systematic structural identification of its components remains a challenge. In this study, a pseudotargeted analytical method, involving key fragment filtering by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and ultra-high performance liquid chromatography-linear ion trap-Orbitrap mass spectrometry, was developed for rapid detection and identification of the chemical constituents of R. crenulata. The process consists of three steps: (i) acquiring sufficient mass spectral data, (ii) constructing a key fragments schedule and discovering the substructures rapidly by pseudotargeted key fragment filtering, and (iii) further identification of the compound structures based on accurate masses, fragment ions, related literatures, and authentic standards. As a result, 104 compounds were identified and divided into five categories, among which three potentially new and 59 ones were reported for the first time in R. crenulata. These results indicated that the major types of components are flavanols and gallic acid derivatives, organic acids, alcohols and their glycosides, flavonoids and their glycosides. This study enhances the understanding of R. crenulata and provides a reference for rapid and comprehensive identification of constituents in other herbal medicines.

Bioinformatics Analysis: The Regulatory Network of hsa_circ_0007843 and hsa_circ_0007331 in Colon Cancer.

OBJECTIVE: To analyze the molecular regulation network of circular RNA (circRNA) in colon cancer (CC) by bioinformatics method. METHODS: hsa_circ_0007843 and hsa_circ_0007331 proved to be associated with CC in previous studies were chosen as the research object. ConSite database was used to predict the transcription factors associated with circRNA, and the CC-associated transcription factors were screened out after intersection. The CircInteractome database was used to predict the RNA-binding proteins (RBPs) interacting with circRNAs and screen out the CC-associated RBPs after an intersection. Furthermore, the CircInteractome database was used to predict the miRNAs interrelated with circRNAs, and the HMDD v3.2 database was used to search for miRNAs associated with CC. The target mRNAs of miRNA were predicted by the miRWalk v3.0 database. CC-associated target genes were screened out from the GeneCards database, and the upregulated genes were enriched and analyzed by the FunRich 3.1.3 software. Finally, the molecular regulatory network diagram of circRNA in CC was plotted. RESULTS: The ConSite database predicted a total of 14 common transcription factors of hsa_circ_0007843 and hsa_circ_0007331, among which Snail, SOX17, HNF3, C-FOS, and RORα-1 were related to CC. The CircInteractome database predicted that the RBPs interacting with these two circRNAs were AGO2 and EIF4A3, and both of them were related to CC. A total of 17 miRNAs interacting with hsa_circ_0007843 and hsa_circ_0007331 were predicted by CircInteractome database. miR-145-5p, miR-21, miR-330-5p, miR-326, and miR-766 were associated with CC according to the HMDDv3.2 database. miR-145-5p and miR-330-5p, lowly expressed in CC, were analyzed in the follow-up study. A total of 676 common target genes of these two miRNAs were predicted by the miRWalk3.0 database. And 57 target genes were involved in the occurrence and development of CC from the GeneCards database, with 23 genes downregulated and 34 genes upregulated. Additionally, GO analysis showed that the 34 upregulated genes were mainly enriched in biological processes such as signal transduction and cell communication. KEGG pathway analysis showed that the upregulated genes were closely related to integrin, ErbB receptor, and ALK1 signal pathways. Finally, a complete regulatory network of hsa_circ_0007843 and hsa_circ_0007331 in CC was proposed, whereby each one of the participants was either directly or indirectly associated and whose deregulation may result in CC progression. CONCLUSION: Predicting the molecular regulatory network of circRNAs by bioinformatics provides a new theoretical basis for further occurrence and development pathogenesis of CC and good guidance for future experimental research.

Time- and dose-dependent allelopathic effects and mechanisms of kaempferol on toxigenic Microcystis growth.

This study determined time-dependent IC50 and confirmed 3.5 mg/L as IC50 value for kaempferol inhibiting toxigenic Microcystis growth, based on which algicidal effects and mechanisms against toxigenic Microcystis exposed to various kaempferol doses (0.5-2 × IC50) were explored along 14 day-test. Results showed that growth inhibition ratio (GIR) almost elevated with increasing kaempferol dose, and at each dose GIR elevated firstly and fluctuated around 17.8%- > 40%, 53.6%-65.6% and 84.8%-89.3% at 1.75, 3.5 and 7 mg/L kaempferol during mid-late stage, respectively. With rising kaempferol dose, photosynthetic pigments contents (chlorophyll-a, phycobiliproteins), antioxidant response (superoxide dismutase and catalase (CAT) activities, glutathione (GSH) contents) and microcystins (MCs) production were almost increasingly stimulated as cellular protective responses during early-mid stage. However, these parameters (excluding CAT and GSH) were almost increasingly inhibited at late stage by prolonged stress and Microcystis cell was still more severely damaged as dose elevated along test, which could be reasons for increasing GIR with rising kamepferol dose. Persistent stimulation of CAT and GSH at each dose could alleviate cell damage until late stage, thus GIR no longer increased at late stage at each kaempferol dose. Moreover, fewer MCs release under kaempferol stress than control suggested kaempferol as eco-safe algaecide for migrating toxigenic Microcystis-dominated blooms (MCBs) and decreasing MCs risks. Compared with our previous data for luteolin inhibiting toxigenic Microcystis, this study supported formerly-proposed 'flavonoids structure - algicidal activity' relationship that the only OH-location difference between kaempferol and luteolin could affect algicidal activity and mechanisms against toxigenic Microcystis. Also, kaempferol and luteolin was revealed to exert additive effect on toxigenic Microcystis growth at equitoxic ratio. Our findings gave novel algicidal scenario of flavonoids and were greatly implicated in eco-friendly migrating toxigenic MCBs.