GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels.

Cancer initiation and progression are likely caused by the dysregulation of biological pathways. Gene set analysis (GSA) could improve the signal-to-noise ratio and identify potential biological insights on the gene set level. However, platforms exploring cancer multi-omics data using GSA methods are lacking. In this study, we upgraded our GSCALite to GSCA (gene set cancer analysis, http://bioinfo.life.hust.edu.cn/GSCA) for cancer GSA at genomic, pharmacogenomic and immunogenomic levels. In this improved GSCA, we integrated expression, mutation, drug sensitivity and clinical data from four public data sources for 33 cancer types. We introduced useful features to GSCA, including associations between immune infiltration with gene expression and genomic variations, and associations between gene set expression/mutation and clinical outcomes. GSCA has four main functional modules for cancer GSA to explore, analyze and visualize expression, genomic variations, tumor immune infiltration, drug sensitivity and their associations with clinical outcomes. We used case studies of three gene sets: (i) seven cell cycle genes, (ii) tumor suppressor genes of PI3K pathway and (iii) oncogenes of PI3K pathway to prove the advantage of GSCA over single gene analysis. We found novel associations of gene set expression and mutation with clinical outcomes in different cancer types on gene set level, while on single gene analysis level, they are not significant associations. In conclusion, GSCA is a user-friendly web server and a useful resource for conducting hypothesis tests by using GSA methods at genomic, pharmacogenomic and immunogenomic levels.

EVAtool: an optimized reads assignment tool for small ncRNA quantification and its application in extracellular vesicle datasets.

Extracellular vesicles (EVs) carrying various small non-coding RNAs (sncRNAs) play a vital roles in cell communication and diseases. Correct quantification of multiple sncRNA biotypes simultaneously in EVs is a challenge due to the short reads (<30 bp) could be mapped to multiple sncRNA types. To address this question, we developed an optimized reads assignment algorithm (ORAA) to dynamically map multi-mapping reads to the sncRNA type with a higher proportion. We integrated ORAA with reads processing steps into EVAtool Python-package (http://bioinfo.life.hust.edu.cn/EVAtool) to quantify sncRNAs, especially for sncRNA-seq from EV samples. EVAtool allows users to specify interested sncRNA types in advanced mode or use default seven sncRNAs (microRNA, small nucleolar RNA, PIWI-interacting RNAs, small nuclear RNA, ribosomal RNA, transfer RNA and Y RNA). To prove the utilities of EVAtool, we quantified the sncRNA expression profiles for 200 samples from cognitive decline and multiple sclerosis. We found that more than 20% of short reads on average were mapped to multiple sncRNA biotypes in multiple sclerosis. In cognitive decline, the proportion of Y RNA is significantly higher than other sncRNA types. EVAtool is a flexible and extensible tool that would benefit to mine potential biomarkers and functional molecules in EVs.

EVAtlas: a comprehensive database for ncRNA expression in human extracellular vesicles.

Extracellular vesicles (EVs) packing various molecules play vital roles in intercellular communication. Non-coding RNAs (ncRNAs) are important functional molecules and biomarkers in EVs. A comprehensive investigation of ncRNAs expression in EVs under different conditions is a fundamental step for functional discovery and application of EVs. Here, we curated 2030 small RNA-seq datasets for human EVs (1506 sEV and 524 lEV) in 24 conditions and over 40 diseases. We performed a unified reads dynamic assignment algorithm (RDAA) considering mismatch and multi-mapping reads to quantify the expression profiles of seven ncRNA types (miRNA, snoRNA, piRNA, snRNA, rRNA, tRNA and Y RNA). We constructed EVAtlas (http://bioinfo.life.hust.edu.cn/EVAtlas), a comprehensive database for ncRNA expression in EVs with four functional modules: (i) browse and compare the distribution of ncRNAs in EVs from 24 conditions and eight sources (plasma, serum, saliva, urine, sperm, breast milk, primary cell and cell line); (ii) prioritize candidate ncRNAs in condition related tissues based on their expression; (iii) explore the specifically expressed ncRNAs in EVs from 24 conditions; (iv) investigate ncRNA functions, related drugs, target genes and EVs isolation methods. EVAtlas contains the most comprehensive ncRNA expression in EVs and will be a key resource in this field.

Three Major Gastrointestinal Cancers Could Be Distinguished through Subclass-Specific IgG Glycosylation.

Esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC) are three major digestive tract tumors with higher morbidity and mortality due to significant molecular heterogeneity. Altered IgG glycosylation has been observed in inflammatory activities and disease progression, and the IgG glycome profile could be used for disease stratification. However, IgG N-glycome profiles in these three cancers have not been systematically investigated. Herein, subclass-specific IgG glycosylation in CRC, GC, and EC was comprehensively characterized by liquid chromatography-tandem mass spectrometry. It was found that IgG1 sialylation was decreased in all three cancers, and the alterations in CRC and EC may be subclass-specific. IgG4 mono-galactosylation was increased in all three cancers, which was a subclass-specific change in all of them. Additionally, glycopeptides of IgG1-H5N5, IgG2-H4N3F1, and IgG4-H4N4F1 could distinguish all three cancer groups from controls with fair diagnostic performance. Furthermore, bioinformatics verified the differential expression of relevant glycosyltransferase genes in cancer progression. Significantly, those three gastrointestinal cancers could be distinguished from each other using subclass-specific IgG glycans. These findings demonstrated the spatial and temporal diversity of IgG N-glycome among digestive cancers, increasing our understanding of the molecular mechanisms of EC, GC, and CRC pathogenesis.

Traceable and Integrated Pesticide Screening (TIPS), a Systematic and Retrospective Strategy for Screening 900 Pesticides and Unknown Metabolites in Tea.

Pesticide management is a crucial issue for sustainable agriculture and food safety. The high-resolution mass spectrometry (HRMS)-based screening method has become a popular choice to monitor pesticide residues in foods and the environment. Data-independent acquisition (DIA) was the first option allowing for this type of analysis due to the wide compound coverage compared to traditional targeted analysis using triple-quadrupole tandem mass spectrometry (QqQ). However, a higher false-positive detection rate is a critical shortcoming in DIA. To overcome this concern, a rigorous method is needed to determine the reliable information acquired from DIA screening. A systematic strategy, traceable and integrated pesticide screening (TIPS), was proposed in this study to comprehensively monitor pesticides and metabolites in a complex tea matrix, avoiding false-positive detection. A total of 900 pesticides were added to an in-house database and evaluated through precision tests, which showed good repeatability and reproducibility. One hundred pesticides and metabolites were detected and confirmed by TIPS in 98 commercial tea samples. In addition to the authorized pesticides that could be detected in TIPS, chlorfluazuron, diafenthiuron, and tolfenpyrad, which are pesticides not allowed to be used in tea farming, were frequently found in this study. In addition, dinotefuran DN and fenbuconazole metabolites RH-9129 and/or RH-9130 were tentatively identified in the archived data using retrospective analysis. The HRMS-based data in TIPS could be a record platform for tracing novel or emerging contaminants not initially targeted in samples. TIPS, a novel strategy, has great potential for rapidly conducting a risk assessment of unexpected pesticides in food.

FFLtool: a web server for transcription factor and miRNA feed forward loop analysis in human.

SUMMARY: Transcription factors (TFs) and microRNAs (miRNAs) are two kinds of important regulators for transcriptional and post-transcriptional regulations. Understanding cross-talks between the two regulators and their targets is critical to reveal complex molecular regulatory mechanisms. Here, we developed FFLtool, a web server for detecting potential feed forward loop (FFL) of TF-miRNA-target regulation in human. In FFLtool, we integrated comprehensive regulations of TF-target and miRNA-target, and developed two functional modules: (i) The 'FFL Analysis' module can detect potential FFLs and internal regulatory networks in a user-defined gene set. FFLtool also provides three levels of evidence to illustrate the reliability for each FFL and enrichment functions for co-target genes of the same TF and miRNA; (ii) The 'Browse FFLs' module displays FFLs comprised of differentially or specifically expressed TFs and miRNAs and their target genes in cancers. FFLtool is a valuable resource for investigating gene expression regulation and mechanism study in biological processes and diseases. AVAILABILITY AND IMPLEMENTATION: FFLtool is available on http://bioinfo.life.hust.edu.cn/FFLtool/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Acetylated Rhamnose Triterpenoid Saponins from Glechoma longituba Analyzed by LC-Q-TOFMS.

The aim of the present work is to isolate a series of triterpene derivatives with rhamnosyl linking acetyl groups from Glechoma longituba according to the structural characteristics of previously described triterpene saponins. The extract ion chromatography spectrum of the crude extract of G. longituba was detected and analyzed by HPLC-HR-ESI-MS to determine possible components, and these metabolites were traced and separated by combining high-resolution mass spectrometry and predicted liquid chromatography retention time. Three 11α, 12α-epoxypentacyclic oleanolic acid triterpene saponins (glechomanosides H-J) and one ursane triterpene aldehyde saponin with a C-28 aldehyde group were isolated from G. longituba. The structure of these compounds was confirmed by NMR and compared with those of previously characterized compounds. The strategy described in this report enables a rapid, reliable, and complete analysis of glycoside compounds containing different numbers of acetyl groups at different positions on the sugar.

Propofol Through Upregulating Caveolin-3 Attenuates Post-Hypoxic Mitochondrial Damage and Cell Death in H9C2 Cardiomyocytes During Hyperglycemia.

BACKGROUND/AIMS: Hearts from diabetic subjects are susceptible to myocardial ischemia reperfusion (I/R) injury. Propofol has been shown to protect against myocardial I/R injury due to its antioxidant properties while the underlying mechanism remained incompletely understood. Thus, this study aimed to determine whether or not propofol could attenuate myocardial I/R injury by attenuating mitochondrial dysfunction/damage through upregulating Caveolin (Cav)-3 under hyperglycemia. METHODS: Cultured rat cardiomyocyte H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in the absence or presence of propofol under high glucose (HG), and cell viability, lactate dehydrogenase (LDH) and mitochondrial viability as well as creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and intracellular adenosine triphosphate (ATP) content were measured with colorimetric Enzyme-Linked Immunosorbent Assays. Intracellular levels of oxidative stress was assessed using 2,7-dichlorodihydrofluorescein diacetate (DCF-DA) fluorescent staining and mitochondrial-dependent apoptosis was assessed by detecting mitochondrial membrane potential and the activation of apoptotic caspases 3 and 9. RESULTS: Exposure of cells to HG without or with H/R both significantly increased cell injury, cell apoptosis and enhanced oxidative stress that were associated with mitochondrial dysfunction and decreased Cav-3 protein expression. All these changes were further exacerbated following H/R under HG. Administration of propofol at concentrations from 12.5 to 50 µM but not 100 µM significantly attenuated H/R injury that was associated with increased Cav-3 expression and activation of the prosurvival proteins Akt and STAT3 with the optimal protective effects seen at 50 µM of propofol (P25). The beneficial effects of propofol(P25) were abrogated by Cav-3 disruption with ß-methyl-cyclodextrin. CONCLUSION: Propofol counteracts cardiomyocyte H/R injury by attenuating mitochondrial damage and improving mitochondrial biogenesis through upregulating Cav-3 during hyperglycemia.

Changing etiologies and outcome of liver failure in Southwest China.

BACKGROUND: The prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts. METHODS: We screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis. RESULTS: 97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three-month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001). CONCLUSION: Etiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female. 1. Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF. 2. The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis. 3. The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously. 4. Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF.

[Tranilast inhibits myocardial fibrosis in mice with viral myocarditis].

OBJECTIVE: To investigate the effect of tranilast on myocardial fibrosis in mice with viral myocarditis (VMC). METHODS: Male balb/c mice (n=72) were randomly divided into control, VMC and tranilast groups (n=24 each). In the VMC and tranilast groups, the mice were infected with Coxsackie virus B3 (CVB3) to prepare VMC model, while the control group was treated with Eagle's medium. After modeling, the tranilast group was administrated with tranilast [200 mg/(kg.d)] until the day before sampling. On days 7, 14 and 28 after CVB3 or Eagle's medium infection, heart specimens (n=8) were taken and examined after Toluidine blue staining and Nissl staining for counts of mast cells (MC), hematoxylin-eosin staining for myocardial pathological changes, and Masson staining for myocardial fibrosis. The expression of CTGF and type I collagen (Col I) in the myocardial tissue was measured by RT-PCR and Western blot. The correlations of CTGF mRNA expression with MC counts and Col I expression were analyzed. RESULTS: The myocardial pathological changes and collagen volume fraction in the VMC group were significantly higher than in the control group at all three time points (P<0.05). Tranilast treatment significantly decreased the myocardial pathological changes and collagen volume fraction compared with the VMC group (P<0.05). The mRNA and protein expression of CTGF and Col I increased in the VMC group compared with the control group, and the increases were reduced with tranilast treatment (P<0.05). The number of MC was positively correlated to CTGF mRNA expression on the 7th day and 14th day (r=0.439, P=0.049) in the VMC group. There were positive correlations between the mRNA expression of Col I and CTGF on the 7th day and 14th day (r=0.646, P=0.007) and the 28th day (r=0.326, P=0.031). CONCLUSIONS: Tranilast may inhibit the aggregation of MC and down-regulate the expression of CTGF, relieving myocardial fibrosis of mice with VMC.

Complete sequence and detailed analysis of the first indigenous plasmid from Xanthomonas oryzae pv. oryzicola.

BACKGROUND: Bacterial plasmids have a major impact on metabolic function and adaptation of their hosts. An indigenous plasmid was identified in a Chinese isolate (GX01) of the invasive phytopathogen Xanthomonas oryzae pv. oryzicola (Xoc), the causal agent of rice bacterial leaf streak (BLS). To elucidate the biological functions of the plasmid, we have sequenced and comprehensively annotated the plasmid. METHODS: The plasmid DNA was extracted from Xoc strain GX01 by alkaline lysis and digested with restriction enzymes. The cloned and subcloned DNA fragments in pUC19 were sequenced by Sanger sequencing. Sequences were assembled by using Sequencher software. Gaps were closed by primer walking and sequencing, and multi-PCRs were conducted through the whole plasmid sequence for verification. BLAST, phylogenetic analysis and dinucleotide calculation were performed for gene annotation and DNA structure analysis. Transformation, transconjugation and stress tolerance tests were carried out for plasmid function assays. RESULTS: The indigenous plasmid from Xoc strain GX01, designated pXOCgx01, is 53,206-bp long and has been annotated to possess 64 open reading frames (ORFs), including genes encoding type IV secretion system, heavy metal exporter, plasmid stability factors, and DNA mobile factors, i.e., the Tn3-like transposon. Bioinformatics analysis showed that pXOCgx01 has a mosaic structure containing different genome contexts with distinct genomic heterogeneities. Phylogenetic analysis indicated that the closest relative of pXOCgx01 is pXAC64 from Xanthomonas axonopodis pv. citri str. 306. It was estimated that there are four copies of pXOCgx01 per cell of Xoc GX01 by PCR assay and the calculation of whole genome shotgun sequencing data. We demonstrate that pXOCgx01 is a self-transmissible plasmid and can replicate in some Xanthomonas spp. strains, but not in Escherichia coli DH5α. It could significantly enhance the tolerance of Xanthomonas oryzae pv. oryzae PXO99A to the stresses of heavy metal ions. The plasmid survey indicated that nine out of 257 Xoc Chinese isolates contain plasmids. CONCLUSIONS: pXOCgx01 is the first report of indigenous plasmid from Xanthomonas oryzae pv. oryzicola, and the first completely sequenced plasmid from Xanthomonas oryzae species. It is a self-transmissible plasmid and has a mosaic structure, containing genes for macromolecule secretion, heavy metal exportation, and DNA mobile factors, especially the Tn3-like transposon which may provide transposition function for mobile insertion cassette and play a major role in the spread of pathogenicity determinants. The results will be helpful to elucidate the biological significance of this cryptic plasmid and the adaptive evolution of Xoc.

[The Application of Gold-immunochromatographic Test Strip Reader in Serum Antibody Detection in Echinococcosis].

One hundred and fifty-nine serum samples from hydatid disease patients and 80 serum samples from patients with other liver diseases were detected by gold-immunochromatographic assay, and read by naked eyes and the gold-immunochromatographic test strip reader. The sensitivity, specificity, and accuracy of eye-based method was 92.4% (147/159), 85.0% (68/80), and 89.9% (215/239), which was lower than that of the reader detection (95.6%, 93.7%, 95.0%, respectively). While, its false negative rate (7.5%, 12/159) and false positive rate (15.0%, 12/80) was higher than that of the reader detection (4.4% and 6.3%, respectively).

Hepatic resection associated with good survival for selected patients with intermediate and advanced-stage hepatocellular carcinoma.

OBJECTIVE: The efficacy and safety of hepatic resection (HR) to treat patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC) was retrospectively assessed. BACKGROUND: Although guidelines from the European Association for the Study of Liver Disease and the American Association for the Study of Liver Disease do not recommend HR for treating BCLC stage B/C HCC, several Asian and European studies have come to the opposite conclusions. METHODS: A consecutive sample of 1259 patients with BCLC stage B/C HCC who underwent HR (n = 908) or transarterial chemoembolization (TACE, n = 351) were included. Moreover, propensity score-matched patients were analyzed to adjust for any baseline differences. In parallel with this retrospective clinical study, the MEDLINE database was searched for studies evaluating the efficacy and safety of HR for BCLC stage B/C HCC. RESULTS: Among our patient sample, the 90-day mortality rate in the HR group was 3.1%. HR provided a survival benefit over TACE at 1, 3, and 5 years (88% vs 81%, 62% vs 33%, and 39% vs 16%, respectively; all P < 0.001). Propensity scoring and subgroup analyses based on tumor size, tumor number, presence or absence of macrovascular invasion, and portal hypertension (PHT) also showed that HR was associated with better long-term survival than TACE. All 36 studies identified in our literature search reported that HR is associated with good long-term survival and low morbidity. Multivariate analyses revealed that alpha-fetoprotein more than or equal to 400 ng/mL, diabetes mellitus, macrovascular invasion, and PHT are independent predictors of poor prognosis in patients with BCLC stage B/C HCC. CONCLUSIONS: Our clinical and literature analyses suggest that in patients with HCC with preserved liver function, the presence of large, solitary tumors, multinodular tumors, macrovascular invasion, or PHT are not contraindications for HR.

[Effect of tranilast on myocardial fibrosis in mice with viral myocarditis].

OBJECTIVE: To study the role of tranilast in the pathogenesis of myocardiac fibrosis in viral myocarditis. METHODS: Seventy-two BALB/C mice were randomly divided into control, model and intervention groups (n=24 each). Mice in the model and intervention groups were infected with Coxsackievirus B3 to induce viral myocarditis. The intervention group was given with tranilast (200 mg/kg) by gavage until sacrifice for sampling, while the other two groups were administered with the same volume of normal saline. Cardiac tissues were obtained from 8 mice on 7, 14 and 28 days after modeling. The mast cell number was observed by toluidine blue staining and thionine staining. The cardiac tissues were stained with hematoxylin and eosin as well as masson trichrome to observe the pathological changes in cardiac tissues. The mRNA and protein expression of osteopontin and transforming growth factor-ß1 was measured by RT-PCR and immunohistochemistry respectively. RESULTS: In the model group, the mRNA and protein expression of osteopontin reached the highest level on the 7th day, decreasing from the 14th day, and became to the least on the 28th day; while the expression of TGF-ß1 increased from the 7th day, reaching a peak on the 14th day, and decreased slightly on the 28th day. The mRNA and protein expression of TGF-ß1 and OPN was lower in the intervention group than the model group (P<0.05), but higher than the control group (P<0.05). The expression of OPN mRNA was positively correlated to the number of mast cells. CONCLUSIONS: Tranilast can reduce myocardial fibrosis by decreasing the number of mast cells, inhibiting the expression of TGF-ß1 and OPN.

Preoperative Antiviral Therapy and Long-Term Outcomes for Hepatitis B Virus-Related Hepatocellular Carcinoma After Curative Liver Resection: A Multicenter Analysis.

Background & Aims: To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy. Methods: Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR. Results: Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049-1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484-0.986). Conclusion: A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA.

A perspective demonstration on the importance of variable selection in inverse calibration for complex analytical systems.

Classical calibration and inverse calibration are two kinds of multivariate calibration in chemical modeling. They use strategies of modeling in component spectral space and in measured variable space, respectively. However, the intrinsic difference between these two calibration models is not fully investigated. Besides, in the case of complex analytical systems, the net analyte signal (NAS) cannot be well defined in inverse calibration due to the existence of uninformative and/or interfering variables. Therefore, application of the NAS cannot improve the predictive performance for this kind of calibration, since it is essentially a technique based on the full-spectrum. From our perspective, variable selection can significantly improve the predictive performance through removing uninformative and/or interfering variables. Although the need for variable selection in the inverse calibration model has already been experimentally demonstrated, it has not aroused so much attention. In this study, we first clarify the intrinsic difference between these two calibration models and then use a new perspective to intrinsically prove the importance of variable selection in the inverse calibration model for complex analytical systems. In addition, we have experimentally validated our viewpoint through the use of one UV dataset and two generated near infrared (NIR) datasets.

Transient inhibition of mitochondrial function by chrysin and apigenin prolong longevity via mitohormesis in C. elegans.

Mild inhibition of mitochondrial function leads to longevity. Genetic disruption of mitochondrial respiratory components either by mutation or RNAi greatly extends the lifespan in yeast, worms, and drosophila. This has given rise to the idea that pharmacologically inhibiting mitochondrial function would be a workable strategy for postponing aging. Toward this end, we used a transgenic worm strain that expresses the firefly luciferase enzyme widely to evaluate compounds by tracking real-time ATP levels. We identified chrysin and apigenin, which reduced ATP production and increased the lifespan of worms. Mechanistically, we discovered that chrysin and apigenin transiently inhibit mitochondrial respiration and induce an early ROS, and the lifespan-extending effect is dependent on transient ROS formation. We also show that AAK-2/AMPK, DAF-16/FOXO, and SKN-1/NRF-2 are required for chrysin or apigenin-mediated lifespan extension. Temporary increases in ROS levels trigger an adaptive response in a mitohormetic way, thereby increasing oxidative stress capacity and cellular metabolic adaptation, finally leading to longevity. Thus, chrysin and apigenin represent a class of compounds isolated from natural products that delay senescence and improve age-related diseases by inhibiting mitochondrial function and shed new light on the function of additional plant-derived polyphenols in enhancing health and delaying aging. Collectively, this work provides an avenue for pharmacological inhibition of mitochondrial function and the mechanism underlining their lifespan-extending properties.

[Spatio-temporal Characteristics of Organic Aggregates and the Driving Factors in Typical Lakes].

Organic aggregates (OA) are the important circulation hub of matter and energy in aquatic ecosystems. However, the comparison studies on OA in lakes with different nutrient levels are limited. In this study, spatio-temporal abundances of OA and OA-attached bacteria (OAB) in oligotrophic Lake Fuxian, mesotrophic Lake Tianmu, middle-eutrophic Lake Taihu, and hyper-eutrophic Lake Xingyun were investigated in different seasons during 2019-2021 using a scanning electron microscope, epi-fluorescence microscope, and flow cytometry. The results showed that:① the annual average abundances of OA in Lake Fuxian, Lake Tianmu, Lake Taihu, and Lake Xingyun were 1.4×104, 7.0×104, 27.7×104, and 16.0×104 ind·mL-1, whereas the annual average abundances of OAB in the four lakes were 0.3×106, 1.9×106, 4.9×106, and 6.2×106 cells·mL-1. The ratios of OAB:total bacteria (TB) in the four lakes were 30%, 31%, 50%, and 38%, respectively. ② OA abundance in summer was significantly higher than that in autumn and winter; however, the ratio of OAB:TB in summer was approximately 26%, which was significantly lower than that in the other three seasons. ③ Lake nutrient status was the most important environmental factor that affected the abundance variations of OA and OAB, accounting for 50% and 68% of the spatio-temporal variations in OA and OAB abundances. ④ Nutrient and organic matters were enriched in OA, especially in Lake Xingyun; the proportions of particle phosphorous, particle nitrogen, and organic matters in this lake were as high as 69%, 59%, and 79%, respectively. Under the circumstance of future climate change and the expansion of lake algal blooms, the effects of algal-originated OA in the degradation of organic matters and nutrient recycling would be increased.