Proteinuria may be an indicator of adverse pregnancy outcomes in patients with preeclampsia: a retrospective study.

BACKGROUND: Proteinuria is one of the common manifestations of patients with preeclampsia (PE), but whether the severity of proteinuria is related to the pregnancy outcome of patients with preeclampsia remains controversial. The present study aimed to determine the relationship between 24-h proteinuria and adverse outcomes in patients with preeclampsia. METHODS: The present retrospective study included 329 pregnant women in Chongqing, China. Patients were divided into PE group and non-PE group. PE group was stratified into three subgroups based on the level of 24-h proteinuria. Correlation analysis was used to analyze the correlation between biochemical indexes and adverse pregnancy outcome, and Logistic regression analysis was used to analyze the risk factors of adverse pregnancy outcome. The receiver operating characteristic curve (ROC) was used to evaluate the ability of 24-h urinary protein to distinguish the adverse pregnancy outcome in patients with preeclampsia. RESULTS: (1) Between PE and non-PE group, cesarean section rate in PE group was significantly higher than that in non-PE group (84.4% vs. 25.9%, p <  0.001). Laboratory findings such as uric acid and creatinine level in PE group were higher than those in non-PE group. (2) Among mild (proteinuria < 0.3 g/24 h), moderate (0.3 g/24 h ≦ proteinuria < 2 g/24 h) and massive (proteinuria ≧ 2 g/24 h) groups, the frequencies of induced labor (p = 0.006) and stillbirth (p = 0.002) increased with the increase of 24-h proteinuria. (3) Adverse outcomes were positively correlated with 24-h proteinuria (adverse maternal outcomes: r = 0.239, p = 0.002; adverse fetal outcomes: r = 0.336, p <  0.001). (4) The best 24-h proteinuria cutoff values to determine stillbirth, premature and fetal distress were 3965.0 mg/24 h, 984.75 mg/24 h and 1503.85 mg/24 h and their odds ratio (95% confidence interval) were 12.46 (3.46-44.88), 2.48 (1.15-5.37) and 10.02 (2.14-46.80), respectively. CONCLUSIONS: The severity of 24-h proteinuia may forecast adverse outcomes in women with preeclampsia. We suggest proteinuria should be retained as one of the monitoring indexes in patients with preeclampsia. TRIAL REGISTRATION: Retrospectively registered. (LTMCMTS202001).

The Direct Involvement of Dark-Induced Tic55 Protein in Chlorophyll Catabolism and Its Indirect Role in the MYB108-NAC Signaling Pathway during Leaf Senescence in Arabidopsis thaliana.

The chloroplast relies on proteins encoded in the nucleus, synthesized in the cytosol and subsequently transported into chloroplast through the protein complexes Toc and Tic (Translocon at the outer/inner membrane of chloroplasts). A Tic complex member, Tic55, contains a redox-related motif essential for protein import into chloroplasts in peas. However, Tic55 is not crucial for protein import in Arabidopsis. Here, a tic55-II-knockout mutant of Arabidopsis thaliana was characterized for Tic55 localization, its relationship with other translocon proteins, and its association with plant leaf senescence when compared to the wild type. Individually darkened leaves (IDLs) obtained through dark-induced leaf senescence were used to demonstrate chlorophyll breakdown and its relationship with plant senescence in the tic55-II-knockout mutant. The IDLs of the tic55-II-knockout mutant contained higher chlorophyll concentrations than those of the wild type. Our microarray analysis of IDLs during leaf senescence identified seven senescence-associated genes (SAGs) that were downregulated in the tic55-II-knockout mutant: ASP3, APG7, DIN2, DIN11, SAG12, SAG13, and YLS9. Real-time quantitative PCR confirmed the reliability of microarray analysis by showing the same expression patterns with those of the microarray data. Thus, Tic55 functions in dark-induced aging in A. thaliana by indirectly regulating downstream SAGs expression. In addition, the expression of four NAC genes, including ANAC003, ANAC010, ANAC042, and ANAC075 of IDL treated tic55-II-knockout mutant appeared to be downregulated. Yeast one hybrid assay revealed that only ANAC003 promoter region can be bound by MYB108, suggesting that a MYB-NAC regulatory network is involved in dark-stressed senescence.

Overexpression of Lilium formosanumMADS-box (LFMADS) Causing Floral Defects While Promoting Flowering in Arabidopsis thaliana, Whereas Only Affecting Floral Transition Time in Nicotiana tabacum.

The Formosa lily (Lilium formosanum) is one of the most common horticultural species in Taiwan. To explore gene regulation involved in this species, we used transcriptome analysis to generate PH-FB (mixed floral buds) and PH-LF (mature leaves) datasets. Combination of the PH-FB and PH-LF constructed a de novo assembly of the ALL dataset, including 18,041 contigs and 23,807 unigenes by Nr, GO, COG, and KEGG databases. The differential gene expression (DGE) analysis revealed 9937 genes were upregulated while 10,383 genes were downregulated in the developing floral buds compared to mature leaves. Seven putative genes (LFMADS1 to 7) encoding floral organ identity proteins were selected for further analysis. LFMADS1-6 genes were specifically expressed in the floral organ, while LFMADS7 in the floral buds and mature leaves. Phylogenetic analysis revealed that LFMADS1-3 is classified into B-class, LFMADS4 into C-class, LFMADS5 into D-class, and LFMADS6-7 into E-class, respectively. LFMADS-GFP fusion proteins appeared to localize in the nucleus, supporting their roles as transcription factors (TFs). Overexpression of the LFMADS2, LFMADS4, and LFMADS6 genes in Arabidopsis resulted in early flowering and floral defect, however, only early flowering in transgenic tobacco was observed. Highly expressed floral integrator genes, including AtFT, AtLFY, and AtFUL in transgenic Arabidopsis and NtFUL and NtSOC1 in transgenic tobacco, resulted in early flowering phenotype through qRT-PCR analysis. Yeast two-hybrid analysis suggested that LFMADSs may form higher order complexes with the B-, C-, D, and/or E-class proteins to determine the floral organ identity. Furthermore, E-class LFMADS proteins may function as a glue to mediate and strengthen the protein-protein interactions. Therefore, our de novo datasets would provide information for investigating other differentially expressed candidate transcripts. In addition, functional conservation of LFMADSs appears to be vital in floral transition and floral organ identity.

Identification of Heat Shock Transcription Factor Genes Involved in Thermotolerance of Octoploid Cultivated Strawberry.

Heat shock transcription factors (HSFs) are mainly involved in the activation of genes in response to heat stress as well as other abiotic and biotic stresses. The growth, development, reproduction, and yield of strawberry are strongly limited by extreme temperatures and droughts. In this study, we used Illumina sequencing and obtained transcriptome data set from Fragaria × ananassa Duchessne cv. Toyonoka. Six contigs and three unigenes were confirmed to encode HSF proteins (FaTHSFs). Subsequently, we characterized the biological functions of two particularly selected unigenes, FaTHSFA2a and FaTHSFB1a, which were classified into class A2 and B HSFs, respectively. Expression assays revealed that FaTHSFA2a and FaTHSFB1a expression was induced by heat shock and correlated well with elevated ambient temperatures. Overexpression of FaTHSFA2a and FaTHSFB1a resulted in the activation of their downstream stress-associated genes, and notably enhanced the thermotolerance of transgenic Arabidopsis plants. Besides, both FaTHSFA2a and FaTHSFB1a fusion proteins localized in the nucleus, indicating their similar subcellular distributions as transcription factors. Our yeast one-hybrid assay suggested that FaTHSFA2a has trans-activation activity, whereas FaTHSFB1a expresses trans-repression function. Altogether, our annotated transcriptome sequences provide a beneficial resource for identifying most genes expressed in octoploid strawberry. Furthermore, HSF studies revealed the possible insights into the molecular mechanisms of thermotolerance, thus rendering valuable molecular breeding to improve the tolerance of strawberry in response to high-temperature stress.

Exploring the genetic correlation of cardiovascular diseases and mood disorders in the UK Biobank.

AIMS: Cardiovascular diseases (CVDs) are the leading cause of deaths globally. Mortality and incidence of CVDs are significantly higher in people with mood disorders. About 81.1% of CVD patients were reported with comorbidities in 2019, where the second most common comorbidity was due to major depressive disorder (MDD). This study, therefore, aimed to evaluate the genetic correlation between CVDs and mood disorders by using data from the UK Biobank towards understanding the influence of genetic factors on the comorbidity due to CVDs and mood disorders. METHODS: The UK Biobank database provides genetic and health information from half a million adults, aged 40-69 years, recruited between 2006 and 2010. A total of 117,925 participants and 6,128,294 variants were included for analysis after applying exclusion criteria and quality control steps. This study focused on two CVD phenotypes, two mood disorders and 12 cardiometabolic-related traits to conduct association studies. RESULTS: The results indicated a significant positive genetic correlation between CVDs and overall mood disorders and MDD specifically, showing substantial genetic overlap. Genetic correlation between CVDs and bipolar disorder was not significant. Furthermore, significant genetic correlation between mood disorders and cardiometabolic traits was also reported. CONCLUSIONS: The results of this study can be used to understand that CVDs and mood disorders share a great deal of genetic liability in individuals of European ancestry.

How to implement inclusive design into distinctive feature hand tool? a design study on fine operation-aid screwdriver.

Hand tool design should integrate the concept of Inclusive Design to be accessible to most users. However, current Inclusive Design strategies of product development are mostly used in post-design evaluation. The retention of inclusive properties in product when new functions are incorporated is essential. Fine operation-aid screwdrivers are designed according to user requirements to address frequently-encountered problems when using screwdrivers namely-insufficient lighting and difficulty in properly installing screws respectively. TRIZ method is applied, comprised the improving parameters solving the problems and worsening parameters which prevents the original inclusive design factors from being damaged into the contradiction matrix, and obtains a set of innovation principles. Eight experts were consulted for their design ideas and developed two fine operation-aid screwdrivers embracing the concept of Inclusive Design. Furthermore, factors regarding the two major operating problems were added to an existing hand tools Inclusive Design Scale. After correlation analysis, the inclusive fine operation-aid screwdriver evaluation scale was established. In addition, two more screwdrivers were selected with the same functions and high reviews on the market as control samples, and 39 users were recruited using a quota sampling strategy to participate in Inclusive Design evaluations. The results revealed that the fine operation-aid screwdrivers evidently solved the two major operating problems in terms of the five dimensions including functionality, comfort, professionality, safety, and usability in the inclusive fine operation-aid screwdriver evaluation scale, thereby affirming the rationality and reliability of our hand tool development approach.

Prognostic value of Holliday junction-recognizing protein and its correlation with immune infiltrates in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is a disease with high morbidity and mortality rates globally. Holliday junction-recognizing protein (HJURP) has recently been shown to be a potentially useful biomarker for diagnosing and determining the progression and prognosis of different cancer types. The present study assessed the prognostic value of HJURP expression in LUAD and investigated the biological pathways related to HJURP that are involved in LUAD pathogenesis. It was found that high HJURP expression was significantly associated with stage (P=0.001), T grade (P=0.012) and N grade (P=0.012). Overall survival analysis demonstrated that patients with LUAD and high HJURP expression had a worse prognosis compared with those patients with low HJURP expression (P<0.001). Multivariate analysis using the Cox proportional hazards model indicated that the expression of HJURP [hazard ratio (HR), 1.32; 95% confidence interval (CI), 1.09-1.60; P=0.004] and stage (HR, 1.90; 95% CI, 1.19-3.03; P=0.007) were independent prognostic factors for patients with LUAD. Gene set enrichment analysis results showed that genes involved with 'basal transcription factors', the 'cell cycle', 'homologous recombination', 'non-small cell lung cancer' (NSCLC), 'oocyte meiosis', 'p53 signaling pathway', 'pathways in cancer', 'RNA degradation' and 'spliceosome' were differentially enriched in the high HJURP expression phenotype. Significant correlations were also found between HJURP and several tumor-infiltrating immune cells, immunomodulators and immune subtypes. Furthermore, western blotting and qPCR analyses confirmed that HJURP was significantly increased in cell lines of NSCLC. In summary, HJURP may be a potentially useful prognostic molecular biomarker of a poor prognosis in LUAD cases. Further experiments are needed to demonstrate the biological effects of HJURP.

Overexpression of Resistance-Nodulation-Division Efflux Pump Genes Contributes to Multidrug Resistance in Aeromonas hydrophila Clinical Isolates.

Aeromonas hydrophila is a Gram-negative bacterium that is a critical causative agent of infections in fish and is occasionally responsible for human infections following contact with contaminated water or food. Currently, the extensive use of antibiotics in clinical practice has led to increased number of isolates of multidrug-resistant (MDR) Aeromonas and has posed a serious public health challenge. The efflux pump system is a critical mechanism of antibiotic resistance in most Gram-negative bacteria. However, the role of resistance-nodulation-division (RND)-type efflux pumps in MDR A. hydrophila is not fully understood. We aimed to evaluate the contribution of the RND efflux pump system to MDR A. hydrophila clinical isolates. PCR results indicated a considerable variation in the presence of RND efflux pump genes in clinical isolates compared to that of the environmental reference strain ATCC7966T. Compared to non-MDR clinical isolates, the expression levels of three putative RND efflux pump genes, AHA0021, AHA1320, and AheB, were significantly elevated in MDR strains. The minimal inhibitory concentrations of piperacillin/tazobactam, imipenem, erythromycin, and polymyxin B were significantly reduced by phenylalanine-arginine ß-naphthylamide (PAßN), further supporting the contribution of the RND efflux system in MDR A. hydrophila. We provided evidence supporting the contribution of the RND efflux system to multidrug resistance in A. hydrophila clinical isolates. Further studies are warranted to elucidate the detailed mechanisms that confer intrinsic resistance to antimicrobials in A. hydrophila.

Synergistic Actions of Benzyl Isothiocyanate with Ethylenediaminetetraacetic Acid and Efflux Pump Inhibitor Phenylalanine-Arginine ß-Naphthylamide Against Multidrug-Resistant Escherichia coli.

The aim of this study was to assess the efficacy of benzyl isothiocyanate (BITC) in combination with efflux inhibitors and metal chelators against multidrug-resistant Escherichia coli. In vitro synergism between testing molecules was observed based on the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), fractional inhibitory concentration index (FICI), bactericidal kinetics, and growth inhibition assay. BITC alone exhibited moderate antibacterial activity against E. coli strains with MIC and MBC values of 0.625-1.25 µM and 1.25-2.5 µM, respectively. In contrast, double and triple combinations of BITC, ethylenediaminetetraacetic acid (EDTA), and phenylalanine-arginine ß-naphthylamide (PAßN) resulted in synergistic activities with FICI values between 0.18 and 0.5, whereas combination of BITC with carbonyl cyanide m-chlorophenyl hydrazone or 2, 2'-dipyridyl revealed additive or indifference effect with FICI values of 0.75-1.5 and 1-1.5, respectively. Results of bactericidal kinetics and growth inhibition assays also supported the synergistic effects of EDTA and PAßN with BITC against E. coli strains. Our data demonstrate the possible use of adjuvant agents, such as the chelating agent EDTA and the efflux inhibitor PAßN to improve the antibacterial potential of isothiocyanate and may help to develop an alternative strategy for reducing the occurrence of multidrug resistance.

Proton pump inhibitor pantoprazole abrogates adriamycin-resistant gastric cancer cell invasiveness via suppression of Akt/GSK-ß/ß-catenin signaling and epithelial-mesenchymal transition.

The effect of proton pump inhibitor (PPI) on cancer risk has received much attention recently. In this study, we investigated the mechanism underlying multidrug resistance and the effect of a PPI pantoprazole using an adriamycin-resistant gastric cancer cell model (SGC7901/ADR). Compared with the parental cell line, SGC7901/ADR cells showed reduced proliferation rate, but higher resistance to adriamycin under both anchorage-dependent and -independent conditions. Notably, SGC7901/ADR cells underwent epithelial to mesenchymal transition (EMT) and showed increased migrating and invading capabilities. At molecular level, SGC7901/ADR cells showed strong activation of Wnt/ß-catenin signaling pathway compared with parental sensitive cells. Interestingly, we found that a PPI pantoprazole can effectively reverse the aggressiveness and EMT marker expression of SGC7901/ADR cells. Furthermore, pantoprazole treatment resulted in a profound reduction of both total and phosphorylated forms of Akt and GSK-3ß, which in turn suppressed the adriamycin-induced Wnt/ß-catenin signaling in SGC7901/ADR cells. Taken together, we demonstrate that the aggressive phenotype of adriamycin-resistant SGC7901/ADR cells is mediated by induction of EMT and activation of the canonical Wnt/ß-catenin signaling pathway. And for the first time, we show that it is possible to suppress the invasiveness of SGC7901/ADR cells by pantoprazole which targets the EMT and Akt/GSK-3ß/ß-catenin signaling.