Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women with Obstructive Sleep Apnea.

The aim of this study was to identify serum diagnostic biomarkers associated with the severity of obstructive sleep apnea (OSA) during pregnancy. Differentially expressed proteins (DEPs) were identified in the control (C), mild (O), and moderate (MO) OSA groups (n = 3 in each group). Bioinformatics analysis was conducted to identify the underlying functions, pathways, and networks of the proteins. Receiver operating characteristic curves were used to assess the diagnostic value of the identified DEPs. The enzyme-linked immunoassay was performed to detect serum levels of the complement C1r subcomponent (C1R) and alpha-2-macroglobulin (A2M) in 79 pregnant women with OSA (mild OSA [n = 32]; moderate OSA [n = 29], and severe OSA [n = 18]) and 65 healthy pregnant women without OSA. Pearson's correlation analysis was conducted to analyze the correlation between C1R and A2M levels and OSA clinicopathological factors. In total, 141 DEPs, 29 DEPs, and 103 DEPs were identified in the three groups (i.e., the mild OSA vs control group, the moderate OSA vs mild apnea group, and the moderate OSA vs control group, respectively). C1R and A2M were identified as continuously up-regulated proteins, and the levels of C1R and A2M were associated with OSA severity. C1R and A2M were found to be correlated with body mass index, systolic blood pressure, apnea-hypopnea index, oxygen desaturation index, time with saturation below 90%, and lowest SaO2. Adverse maternal and neonatal outcomes were observed in pregnant women with OSA. C1R and A2M have been identified as diagnostic biomarkers and are associated with the severity of OSA during pregnancy.

Combinatorial interactions between viral proteins expand the potential functional landscape of the tomato yellow leaf curl virus proteome.

Viruses manipulate the cells they infect in order to replicate and spread. Due to strict size restrictions, viral genomes have reduced genetic space; how the action of the limited number of viral proteins results in the cell reprogramming observed during the infection is a long-standing question. Here, we explore the hypothesis that combinatorial interactions may expand the functional landscape of the viral proteome. We show that the proteins encoded by a plant-infecting DNA virus, the geminivirus tomato yellow leaf curl virus (TYLCV), physically associate with one another in an intricate network, as detected by a number of protein-protein interaction techniques. Importantly, our results indicate that intra-viral protein-protein interactions can modify the subcellular localization of the proteins involved. Using one particular pairwise interaction, that between the virus-encoded C2 and CP proteins, as proof-of-concept, we demonstrate that the combination of viral proteins leads to novel transcriptional effects on the host cell. Taken together, our results underscore the importance of studying viral protein function in the context of the infection. We propose a model in which viral proteins might have evolved to extensively interact with other elements within the viral proteome, enlarging the potential functional landscape available to the pathogen.

Mode of delivery and neonatal outcomes in preterm twins less than 32 weeks of gestation or birthweight under 1500 g: a systematic review and meta-analyses.

BACKGROUND: The mode of delivery for twins born before 32 weeks of gestation remains controversial. Our purpose is to conduct a meta-analysis of twin pregnancies less than 32 weeks or twin weight less than 1500 g, so as to find a suitable delivery mode. METHODS: We searched PubMed database, Cochrane Library database, and EMBASE database through December 2022. This protocol was registered with PROSPERO (CRD42023386946) prior to initiation. Studies that compared vaginal delivery to cesarean section for newborns less than 32 weeks of gestation or birthweight under 1500 g were included. The primary result was neonatal mortality rate. Secondary result was neonatal morbidity. The quality of literatures included in the research was evaluated in accordance with Newcastle-Ottawa Scale (NOS) literature quality evaluation scale. We use odds ratio (OR) as the effect index for binary variables. Point estimates and 95% confidence intervals (95% CI) were calculated. P < 0. 05 indicated statistically significant difference. RESULTS: Our search generated 5310 articles, and a total of 8 articles comprising a total of 14,703 newborns were included in the analysis. The odds ratios of neonatal mortality rate were for twins delivered by vaginal delivery compared to cesarean section were 0.84 (95% CI 0.57-1.24, P = 0.38). The 5-min Apgar score < 7 (95% CI 0.44-1.75, P = 0.72), necrotizing enterocolitis (95% CI 0.81-1.19, P = 0.82), intraventricular hemorrhage (95% CI 0.41-1.86, P = 0.71), periventricular leukomalacia (95% CI 0.16-4.52, P = 0.84), bronchopulmonary dysplasia (95% CI 0.88-1.36, P = 0.42), and respiratory distress syndrome (95% CI 0.23-2.01, P = 0.48) were not statistically significant between the two groups. CONCLUSION: We have observed that vaginal delivery does not confer an increased risk of neonatal morbidity and mortality in twins born before 32 weeks of gestation. However, the current results are affected by substantial heterogeneity and confounding factors. We still need high-quality randomized-controlled studies require to address this important question.

The preventive effects of different doses of atorvastatin on contrast-induced acute kidney injury after CT perfusion.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a severe complication among patients receiving intravascular contrast media. The purpose of this study was to investigate the preventive effects of pretreatment of atorvastatin at intensive doses on CI-AKI after computed tomography (CT) perfusion. METHODS: The levels of serum creatinine (SCR), blood urea nitrogen (BUN), Cystatin C (CysC), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in patients were compared between the observation group receiving 40 mg/kg atorvastatin and the control group receiving 20 mg/kg atorvastatin before and 72 h after CT examination. In addition, the incidence of CI-AKI was recorded. RESULTS: Compared with the control group, the incidence of renal injury in the observation group was significantly reduced, from 8% to 2% (χ2  = 6.62, p = 0.010). In addition, there was no notable difference in the levels of Scr, BUN, CysC, hs-CRP, and IL-6 before CT examination between two groups (p > 0.05). The levels of SCR, BUN, CysC, hs-CRP, and IL-6 were increased, while the levels of eGFR were decreased in the control group at 72 h after CT examination (p < 0.05). At 72 h after CT enhancement, the levels of BUN, CysC, and hs-CRP were prominently increased in the observation group (p < 0.05), while SCR, eGFR, and IL-6 did not change (p > 0.05). Compared with the control group, the levels of SCR, BUN, CysC, eGFR, hs-CRP, and IL-6 in the observation group were significantly decreased at 72 h after CT examination (p < 0.05). CONCLUSION: Intensive dose of atorvastatin pretreatment can prevent CI-AKI undergoing CT perfusion through lowering inflammation as well as renal function indexes SCR, CysC, BUN, and eGFR.

Efficiency comparison of B6(Cg)-Tyrc-2j /J and C57BL/6NTac embryos as hosts for the generation of knockout mice.

Careful selection of the host embryo is critical to the efficient production of knockout (KO) mice when injecting mouse embryonic stem (mES) cells into blastocysts. B6(Cg)-Tyrc-2j/J (B6 albino) and C57BL/6NTac (B6NTac) strains of mice are widely used to produce host blastocysts for such procedures. Here, we tested these two strains to identify an appropriate match for modified agouti C57BL/6N (JM8A3.N1) mES cells. When comparing blastocyst yield, super-ovulated B6NTac mice produced more injectable blastocysts per female than B6 albino mice (8.2 vs. 5.4). There was no significant difference in birth rate when injected embryos were transferred to the same pseudopregnant recipient strain. However, the live birth rate was significantly higher for B6NTac blastocysts than B6 albino blastocysts (62.7% vs. 50.2%). In addition, the proportion of pups exhibiting high-level and complete chimerism, as identified by coat color, was also significantly higher in the B6NTac strain. There was no obvious difference in the efficiency of germline transmission (GLT) when compared between B6NTac and B6 albino host embryos (61.5% vs. 63.3% for mES clones; 64.5% vs. 67.9% for genes, respectively), thus suggesting that an equivalent GLT rate could be obtained with only a few blastocyst injections for B6NTac embryos. In conclusion, our data indicate that B6NTac blastocysts are a better choice for the microinjection of JM8A3.N1 mES cells than B6 albino blastocysts.

Image and clinical analysis of common carotid web: a case report.

BACKGROUND: A carotid web is a very rare vascular disease of the carotid artery, leading to thrombosis and ischemic stroke. CASE PRESENTATION: A 65-year-old male patient was admitted due to left limb weakness. On arrival, he had moderate left hemiplegia, neglect, and sensory loss; the National Institutes of Health Stroke Scale score was 8. Computed tomography angiography (CTA) and magnetic resonance (MR) examination were performed to determine the cause of basal ganglia infarction. Thin-section axial CTA showed a membrane-like structure in the posterior wall of the right common carotid artery. The sagittal reconstruction image showed a membrane-like protrusion in the posterior wall of the right common carotid artery under the right carotid sinus. The MR axial T2 image showed a membrane-like high-signal protrusion into the carotid artery lumen, which was diagnosed as a right carotid web. The patient was treated with dual antihypertensive therapy by adjusting blood pressure, controlling brain edema, improving cerebral circulation, and nourishing the nerves. CONCLUSION: Careful comparison of axial thin-layer CTA and MR axial T2 images combined with sagittal reconstruction of CTA images can greatly improve the diagnostic rate of carotid web.

Pro-inflammatory role of cell-free mitochondrial DNA in cardiovascular diseases.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Inflammation contributes to the pathogenesis and progression of CVD. Circulating cell-free mitochondrial DNA (ccf-mtDNA) is that mtDNA fragments are released outside the cell and into the circulation by cell necrosis and secretion. The levels of ccf-mtDNA are increased in CVD and associated risk conditions, including hypercholesterolemia, diabetes mellitus, and arterial hypertension. MtDNA containing unmethylated CpG dinucleotides and can trigger inflammation that aggravates tissue injury by activating toll-like receptor 9, inflammasomes, and the stimulator of interferon genes pathway. Here, we review the expanding field of ccf-mtDNA-mediated inflammation and its role in the progression of CVD.

Surface and coherent contributions of plasmon fields to ultraviolet tip-enhanced coherent anti-Stokes Raman scattering.

Design of plasmonic substrates is of immense importance for high sensitivity and spatial resolution in plasmon-enhanced spectroscopy. In this study, the enhancement factors (EFs) of tip-enhanced coherent anti-Stokes Raman scattering (TECARS) contributed by surface and quantum coherent effects in the ultraviolet region are theoretically analyzed using three-dimensional finite-difference time-domain (3D-FDTD) method. In the multi-resonant TECARS configuration, surface and coherent EFs of 1018 and 109, respectively, can be achieved by considering the synthetic effect of surface and coherent enhancement mechanisms, providing the total TECARS EF of 1027 and sub-5 nm spatial resolution. Our theoretical results not only provide a deeper understanding of ultraviolet (UV)-TECARS but also can be used as a highly efficient reference for the experimental design of TECARS platform.

Deep ultraviolet tip-enhanced fluorescence.

Theoretical calculations were performed for the deep ultraviolet (DUV) tip-enhanced fluorescence (TEF) using Al@Al2O3 core-shell tips. Fluorescence enhancement, spatial resolution and surface plasmon coupled emission (SPCE) of DUV-TEF were quantitatively studied by finite-difference time-domain (FDTD) method. FDTD results demonstrate that the enhancement factor (EF) of TEF can be as high as 3 orders of magnitudes in the optimal TEF geometry. At the DUV excitation wavelength of 244 nm, the spatial resolution and SPCE angles are 6 nm and ±23°, respectively, showing maximum EF of 7.4 × 102. Our results not only help understanding the underlying physical mechanism for developing high-sensitivity and high-resolution DUV-TEF platform, but also contribute to expanding TEF technology from visible to UV range.

Long non-coding RNA TUG1 regulates the migration and invasion of trophoblast-like cells through sponging miR-204-5p.

Preeclampsia (PE) is a leading cause of maternal and perinatal death. Accumulated evidence suggests that many long non-coding RNAs (lncRNAs) are abnormally expressed in placentas from PE patients, and they may play functional roles in the development of PE. The present study aimed to investigate the functional role TUG1 in PE and explore the potential molecular mechanisms. Clinically, the expression of TUG1 in placental tissues from PE and normal controls was determined. In vitro, human trophoblast HTR-8/SVneo and JAR cells were employed for loss or gain-of-function assays. Our results demonstrate that TUG1 was downregulated in PE placental tissues compared with normal controls. Moreover, downregulation of TUG1 inhibited the migration and invasion of trophoblast-like cells. Bioinformatics analysis and functional assays showed that TUG1 interacted with miR-204-5p and negatively regulated the expression and function of miR-204-5p in trophoblast cells. Furthermore, TUG1-mediated migration and invasion of trophoblast cells was regulated by miR-204-5p. Together, our results suggested that TUG1 regulates trophoblast migration and invasion partly through sponging miR-204-5p, and the TUG1/miR-204-5p axis could be a potential therapeutic target for the treatment of PE.

Risk factors of postoperative valgus malalignment in mobile-bearing medial unicompartmental knee arthroplasty.

OBJECTIVE: The aim of this observational study was to investigate the risk factors of postoperative valgus malalignment after mobile-bearing medial unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively evaluated radiographic and surgical characteristics in 122 consecutive Oxford phase 3 UKAs. According to postoperative hip-knee-ankle angle (HKAA), 24 knees were sorted into group valgus with HKAA > 180° and 98 knees were sorted into group non-valgus with HKAA ≤ 180°. Logistic regression was performed to analyze risk factors including age, gender, BMI, side, preoperative limb alignment HKAA, preoperative LDFA, MPTA, FTFA, thickness of polyethylene bearing insert, tibial prothesis size, femoral prothesis size, medial tibial cut thickness, thickness of distal femoral mill, prothesis angle of coronal, and sagittal plane. RESULTS: The mean mechanical preoperative HKAA of 174.39°±4.23° was corrected to 178.18°±3.49° postoperatively (t = - 13.45, p = 0.000). The mean of postoperative HKAA in valgus group and non-valgus group was 183.45 ± 2.21° and 176.88 ± 2.35°, respectively (t = 12.44, p = 0.000). After statistical analysis with univariate analysis, eight risk factor variables among 16 independent variables were identified as potential predictors with p value ≤ 0.1. Multivariate logistic regression analysis for these eight potential predictors revealed that tibial cut (p = 0.046), LDFA (p = 0.003), MPTA (p = 0.011), and FTFA (p = 0.008) were significant risk factors predicting postoperative valgus malalignment after mobile-bearing UKA. CONCLUSIONS: Preoperative smaller LDFA, FTFA, larger MPTA and less medial tibial cut thickness were significantly associated with postoperative valgus malalignment in mobile-bearing UKA.

Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency.

BACKGROUND: A growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to identify gene expression and alternative splicing profiles to provide insights into the pathogenesis of severe MPP. METHODS: RNAs of bronchoalveolar lavage fluid (BALF) samples from three severe MPP children and three mild MPP children were analyzed respectively by deep sequencing followed by computational annotation and quantification. RESULTS: The gene expression analysis revealed 14 up-regulated and 34 down-regulated genes in severe MPP children comparing to mild MPP children. The top 10 most up-regulated genes were IGHV1-69, CH17-472G23.1, ATP1B2, FCER2, MUC21, IL13, FCRLB, CLEC5A, FAM124A, and INHBA. The top 10 most down-regulated genes were OSTN-AS1, IL22RA2, COL3A1, C1orf141, IGKV2-29, RP11-731F5.2, IGHV4-4, KIRREL, DNASE1L3, and COL6A2. Clustering analysis revealed similar expression pattern of CLEC5A, IL13, FCER2, and FLT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed changes related to primary immunodeficiency in severe MPP children comparing to mild MPP children; the pathway involves CD19, TNFRSF13C, CD79A, and AICDA genes. Among the differentially expressed genes, significant alternative splicing events were found in FCER2 and FCRLA. CONCLUSIONS: The current study on RNA sequencing provides novel insights into the pathogenesis of severe MPP in terms of gene expression and alternative splicing. The up-regulation of IL13, FCER2, FLT1, and CLEC5A and the down-regulation of CD79A, AICDA, CD19, and TNFRSF13C may contribute to the pathogenesis of severe MPP. The differential expressions of FCER2 and FCRLA could be due to their alternative splicing.

Porous Anatase-TiO2(B) Dual-Phase Nanorods Prepared from in Situ Pyrolysis of a Single Molecule Precursor Offer High Performance Lithium-Ion Storage.

To overcome the problems faced by TiO2 materials for lithium-ion batteries usage, such as easy nanoparticles agglomeration during cycling and poor cycling performance, in this study, TiO2 nanorods with the controlled phase compositions are prepared via direct pyrolysis of single molecule precursors in combination with a simple washing process. By tuning the external cations in the single source precursors, three TiO2 samples in a nanorod shape with the compositions of pure anatase, anatase-rutile dual phase, and anatase-TiO2(B) dual phase are synthesized successfully. High-resolution transmission electron microscopy, X-ray powder diffraction, and Raman measurements confirm the phase structures and compositions of the three prepared samples. The electrochemical results manifest that all the three nanorod-shaped TiO2 samples show the long-term cycling stability as negative materials for LIBs. Among them, the TiO2 sample with the combination of the anatase and TiO2-B phase shows the best performance, with the specific capacity of ∼184, 164, 140, 105, 80, and 60 mAh g-1 at 0.1, 0.3, 0.5, 1.5, 3.0, and 5.0 A g-1, respectively, and showing no capacity loss and low resistance after 1000 cycles at 1.5 A g-1. By the analysis of the cyclic voltammetry results recorded from different scan rates, the lithium-ion storage mechanism is clarified, which is dominated by the semi-infinite linear diffusion (anatase phase) in combination with the partial surface pseudocapacitive contribution [TiO2(B) phase]. As a result, this sample shows a great potential as a negative material for LIBs because of its electrochemical stability, high specific capacity, and superior rate capability. The proof-of-concept design of the anatase and TiO2-B dual phase may provide a new strategy for the synthesis of high performance TiO2-based anode material for LIBs.

Salting-out-enhanced ionic liquid microextraction with a dual-role solvent for simultaneous determination of trace pollutants with a wide polarity range in aqueous samples.

In real aquatic environments, many occupational pollutants with a wide range of polarities coexist at nanogram to milligram per liter levels. Most reported microextraction methods focus on extracting compounds with similar properties (e.g., polarity or specific functional groups). Herein, we developed a salting-out-enhanced ionic liquid microextraction based on a dual-role solvent (SILM-DS) for simultaneous detection of tetracycline, doxycycline, bisphenol A, triclosan, and methyltriclosan, with log K ow ranging from -1.32 to 5.40 in complex milk and environmental water matrices. The disperser in the ionic-liquid-based dispersive liquid-liquid microextraction was converted to the extraction solvent in the subsequent salting-out-assisted microextraction procedures, and thus a single solvent performed a dual role as both extractant and disperser in the SILM-DS process. Acetonitrile was selected as the dual-role solvent because of its strong affinity for both ionic liquids and water, as well as the extractant in the salting-out step. Optimized experimental conditions were 115 µL [C8MIM][PF6] as extractor, 1200 µL acetonitrile as dual-role solvent, pH 2.0, 5.0 min ultrasound extraction time, 3.0 g Na2SO4, and 3.0 min vortex extraction time. Under optimized conditions, the recoveries of the five pollutants ranged from 74.5 to 106.9%, and their LODs were 0.12-0.75 µg kg-1 in milk samples and 0.11-0.79 µg L-1 in environmental waters. Experimental precision based on relative standard deviation was 1.4-6.4% for intraday and 2.3-6.5% for interday analyses. Compared with previous methods, the prominent advantages of the newly developed method are simultaneous determination of pollutants with a wide range of polarities and a substantially reduced workload for ordinary environmental monitoring and food tests. Therefore, the new method has great application potential for simultaneous determination of trace pollutants with strongly contrasting polarities in several analytical fields. Graphical Abstract A salting-out-enhanced ionic liquid microextraction based on a dual-role solvent (SILM-DS) was developed for simultaneous detection of tetracycline, doxycycline, bisphenol A, triclosan and methyltriclosan, with log K ow ranging from -1.32 to 5.40. The novelty of SILM-DS method lies in (1) simultaneous quantification of pollutants with contrasting polarity; (2) microextraction based on a dual-role solvent (as a disperser and extractant); (3) giving high recoveries for analytes with a wide range of polarities; and (4) reducing workload for ordinary environmental monitoring and food tests.

Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse non-alcoholic steatohepatitis.

Dicer1 is an enzyme essential for microRNA (miRNA) maturation. The loss of miRNAs resulted from Dicer1 deficiency greatly contributes to the progression of many diseases, including lipid dysregulation, but its role in hepatic accumulation of free cholesterol (FC) that is critical in the development of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we used the liver-specific Dicer1-knockout mice to identify the miRNAs involved in hepatic FC accumulation. In a widely used dietary NASH model, mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, which resulted in significant increase in hepatic FC levels as well as decrease of Dicer1 mRNA levels in livers. The liver-specific Dicer1-knockout induced hepatic FC accumulation at 5-6 weeks, accompanied by increased mRNA and protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme of cholesterol synthesis in livers. Eleven predicted miRNAs were screened, revealing that miR-29a/b/c significantly suppressed HMGCR expression by targeting the HMGCR mRNA 3'-UTR. Overexpression of miR-29a in SMMC-7721 cells, a steatosis hepatic cell model, significantly decreased HMGCR expression and the FC level. Furthermore, the expression levels of miR-29a were inversely correlated with HMGCR expression levels in the MCD diet mouse model in vivo and in 2 steatosis hepatic cell models (SMMC-7721 and HL-7702 cells) in vitro. Our results show that Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse NASH, and miR-29 may serve as an important regulator of hepatic cholesterol homeostasis. Thus, miR-29a could be utilized as a potential therapeutic target for the treatment of non-alcoholic fatty liver disease as well as for other liver diseases associated with FC accumulation.

MicroRNA-1304 suppresses human non-small cell lung cancer cell growth in vitro by targeting heme oxygenase-1.

Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays. Cell apoptosis and cell cycle were examined using annexin V-PE/7-AAD and PI staining assays, respectively. The dual-luciferase reporter assay was used to verify post-transcriptional regulation of heme oxygenase-1 (HO-1) by miR-1304. CRISPR/Cas9 was used to deplete endogenous miR-1304. Overexpression of MiR-1304 significantly decreased the number and viability of NSCLC cells and colony formation, and induced cell apoptosis and G0/G1 phase cell cycle arrest. HO-1 was demonstrated to be a direct target of miR-1304 in NSCLC cells. Restoration of HO-1 expression by hemin (20 µmol/L) abolished the inhibition of miR-1304 on cell growth and rescued miR-1304-induced apoptosis in A549 cells. Suppression of endogenous miR-1304 with anti-1304 significantly increased HO-1 expression and promoted cell growth and survival in A549 cells. In 17 human NSCLC tissue samples, miR-1304 expression was significantly decreased, while HO-1 expression was significantly increased as compared to normal lung tissues. MicroRNA-1304 is a tumor suppressor and HO-1 is its direct target in NSCLC. The results suggest the potential for miR-1304 as a therapeutic target for NSCLC.

Synthesis and antitumor activity evaluation of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at C4-position.

A series of quinazoline derivatives bearing piperazine-1-carbodithioate moiety at the C4-position were synthesized using piperidine and 1-bromo-3-chloropropane as starting materials via eight steps. Final compounds 8a-q and 9a-i were evaluated for their antiproliferative activity against human lung cancer A549, breast adenocarcinoma MCF-7, and colorectal cancer HCT-116 cell lines. The results showed that fourteen of twenty-six final compounds inhibited the proliferation of three cancer cell lines with IC50 values less than 10µM. When treated with a representative compound 8n, HCT-116 cells were arrested at G0/G1 phase of the cell cycle. This provided a clue to further investigation of the mechanism of action.

Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives.

In this study, a series of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives were synthesized and evaluated for their antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassays indicated that most compounds demonstrated appreciable antibacterial bioactivities against Xoo and R. solanacearum. Among the title compounds, compound 4i demonstrated the best inhibitory effect against Xoo and R. solanacearum with half-maximal effective concentration (EC50) values of 14.69 and 15.14µg/mL, respectively, which were even better than those of commercial agents Bismerthiazol and Thiodiazole Copper. In vivo antibacterial activities tests under greenhouse conditions revealed that the control efficiency of compound 4i against rice bacterial leaf blight and tobacco bacterial wilt were better than those of Bismerthiazol and Thiodiazole Copper. Meanwhile, field trials also indicated that compound 4i demonstrated appreciable control efficiency against rice bacterial leaf blight and tomato bacterial wilt.

Hepatic cytochrome P450s play a major role in monocrotaline-induced renal toxicity in mice.

AIM: Monocrotaline (MCT) in plants of the genus Crotalaria induces significant toxicity in multiple organs including the liver, lung and kidney. Metabolic activation of MCT is required for MCT-induced toxicity. In this study, we attempted to determine whether the toxicity of MCT in kidney was a consequence of the metabolic activation of MCT in the liver. METHODS: Liver-specific cytochrome P450 reductase-null (Null) mice, wild-type (WT) mice and CYP3A inhibitor ketoconazole-pretreated WT (KET-WT) mice were examined. The mice were injected with MCT (300, 400, or 500 mg/kg, ip), and hepatotoxicity and nephrotoxicity were examined 24 h after MCT treatment. The levels of MCT and its metabolites in the blood, liver, lung, kidney and bile were determined using LC-MS analysis. RESULTS: Treatment of WT mice with MCT increased the serum levels of alanine aminotransferase, hyaluronic acid, urea nitrogen and creatinine in a dose-dependent manner. Histological examination revealed that MCT (500 mg/kg) caused severe liver injury and moderate kidney injury. In contrast, these pathological abnormalities were absent in Null and KET-WT mice. After injection of MCT (400 and 500 mg/kg), the plasma, liver, kidney and lung of WT mice had significantly lower MCT levels and much higher N-oxide metabolites contents in compared with those of Null and KET-WT mice. Furthermore, WT mice had considerably higher levels of tissue-bound pyrroles and bile GSH-conjugated MCT metabolites compared with Null and KET-WT mice. CONCLUSION: Cytochrome P450s in mouse liver play a major role in the metabolic activation of MCT and thus contribute to MCT-induced renal toxicity.