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Preterm labor, a condition associated with various risk factors such as a history of prior preterm birth (PTB) and multiple pregnancies, has recently seen an increasing focus on its potential link with dyslipidemia. This study aims to investigate the relationship between dyslipidemia in expectant mothers and the risks of PTB. We studied 6963 mothers who gave birth at the International Peace Maternal and Child Health Hospital of Shanghai Jiaotong University School of Medicine in 2020, among which, 437 women had PTB. We extracted clinical and lipid data from electronic records, using multivariable logistic regression and restricted cubic spline models to explore the link between lipid concentrations (by quartiles) in pregnancy stages and PTB risk. The PTB rate was 6.3%. Early pregnancy in the PTB group showed elevated ApoA, ApoB, CHOL, LDL, and TG levels compared to controls (all P < 0.05). Late pregnancy showed no notable lipid differences. Multivariable analysis revealed elevated ApoA, TG, higher age, BMI ≥ 28 kg/m2, hypertension, assisted reproductive technology and gestational diabetes as PTB risk factors (all P < 0.05). After adjustments, higher ApoA, ApoB, CHOL and TG levels correlated with increased PTB risk. Using the lowest quartile, the adjusted ORs for early pregnancy's highest quartile of ApoA, ApoB, CHOL and TG were 1.348, 1.442, 1.442 and 2.156, respectively. Our findings indicate that dyslipemia in early pregnancy, including elevated levels of ApoA, ApoB, CHOL and TG, are associated with PTB. Managing lipid abnormalities during pregnancy may help reduce the risk of PTB. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2J2 (CYP2J2) is responsible for the epoxidation of endogenous arachidonic acid, and is involved in the metabolism of exogenous drugs. To date, no crystal structure of CYP2J2 is available, and the proposed structural basis for the substrate recognition and specificity in CYP2J2 varies with the structural models developed using different computational protocols. In this study, we developed a new structural model of CYP2J2, and explored its sensitivity to substrate binding by molecular dynamics simulations of the interactions with chemically similar fluorescent probes. Our results showed that the induced-fit binding of these probes led to the preferred active poses ready for the catalysis by CYP2J2. Divergent conformational dynamics of CYP2J2 due to the binding of each probe were observed. However, a stable hydrophobic clamp composed of residues I127, F310, A311, V380, and I487 was identified to restrict any substrate access to the active site of CYP2J2. Molecular docking of a series of compounds including amiodarone, astemizole, danazol, ebastine, ketoconazole, terfenadine, terfenadone, and arachidonic acid to CYP2J2 confirmed the role of those residues in determining substrate binding and specificity of CYP2J2. In addition to the flexibility of CYP2J2, the present work also identified other factors such as electrostatic potential in the vicinity of the active site, and substrate strain energy and property that have implications for the interpretation of CYP2J2 metabolism. [ABSTRACT FROM AUTHOR]

Neurodegeneration involves abnormal aggregation of intrinsically disordered amyloidogenic peptides (IDPs), usually mediated by hydrophobic protein-protein interactions. There is mounting evidence that formation of α-helical intermediates is an early event during self-assembly of amyloid-β42 (Aβ42) and α-synuclein (αS) IDPs in Alzheimer's and Parkinson's disease pathogenesis, respectively. However, the driving force behind on-pathway molecular assembly of partially folded helical monomers into helical oligomers assembly remains unknown. Here, we employ extensive molecular dynamics simulations to sample the helical conformational sub-spaces of monomeric peptides of both Aβ42 and αS. Our computed free energies, population shifts, and dynamic cross-correlation network analyses reveal a common feature of long-range intra-peptide modulation of partial helical folds of the amyloidogenic central hydrophobic domains via concerted coupling with their charged terminal tails (N-terminus of Aβ42 and C-terminus of αS). The absence of such inter-domain fluctuations in both fully helical and completely unfolded (disordered) states suggests that long-range coupling regulates the dynamicity of partially folded helices, in both Aβ42 and αS peptides. The inter-domain coupling suggests a form of intra-molecular allosteric regulation of the aggregation trigger in partially folded helical monomers. This approach could be applied to study the broad range of amyloidogenic peptides, which could provide a new path to curbing pathogenic aggregation of partially folded conformers into oligomers, by inhibition of sites far from the hydrophobic core. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. TNBC currently lacks a transplantation model that is suitable for clinical simulations of the tumor microenvironment. Intraductal injection of tumor cells into the mammary duct could mimic the occurrence and development of breast cancer. Herein, we injected 4T1 cells into the mammary ducts of BALB/C mice to build a preclinical model of TNBC and optimized the related construction method to observe the occurrence and spontaneous metastasis of tumors. We compared the effects of different cell numbers on tumorigenesis rates, times to tumorigenesis, and metastases to determine the optimal number of cells for modelling. We demonstrated that 4T1-MIND model mice injected with 20,000 cells revealed a suitable tumor formation rate and time, thus indicating a potential treatment time window after distant metastasis. We also injected 20,000 cells directly into the breast fat pad or breast duct for parallel comparison. The results still showed that the 4T1-MIND model provides sufficient treatment time for lung metastases in mice and that it is a more reliable model for early tumor development. The 4T1-MIND model requires continuous improvement and optimization. A suitable and optimized model for translational research and studies on the microenvironment in TNBC should be developed. [ABSTRACT FROM AUTHOR]

Wireless sensor network (WSN) location is a significant research area. In complex environments like forests, inaccurate signal intensity ranging is a major challenge. To address this issue, this paper presents a reliable WSN distance measurement-positioning algorithm for forest environments. The algorithm divides the positioning area into several sub-regions based on the discrete coefficient of the collected signal strength. Then, using the fitting method based on the signal intensity value of each sub-region, the algorithm derives the reference points of the logarithmic distance path loss model and path loss index. Finally, the algorithm locates target nodes using anchor nodes in different regions. Additionally, to enhance the positioning accuracy, weight values are assigned to the positioning result based on the discrete coefficient of the signal intensity in each sub-region. Experimental results demonstrate that the proposed WSN algorithm has high precision in forest environments. [ABSTRACT FROM AUTHOR]

Prognostic features in advanced perihilar cholangiocarcinoma (pCCA) patients who received first-line hepatic arterial infusion chemotherapy (HAIC) are unknown. The purpose of our study was to develop an applicable score based on serum inflammatory-tumor biomarkers to predict the survival of advanced pCCA patients who received first-line HAIC. In total, 106 advanced pCCA patients were enrolled as the training cohort. The optimal cutoff values of baseline variables were defined by the receiver operating characteristic method or according to previous publications. According to the results of Cox regression analysis, baseline neutrophil-to-lymphocyte ratio (NLR) > 3.19, carcinoembryonic antigen (CEA) > 10 ng/mL, and carbohydrate antigen 19-9 (CA19-9) > 200 U/mL were identified as independent survival predictors, which were used to develop the NLCECA score (NLR, CEA, and CA19-9). When including the NLCECA score in the multivariate analysis, the NLCECA score was the only independent predictor of survival. The risk of survival decreased by 111.9% for each 1-point increase in the NLCECA score. Additionally, the NLCECA score could also predict survival in another 33 patients in the validation cohort (P < 0.001). In summary, the NLCECA score is a potential biomarker system for predicting the survival of advanced pCCA patients who received first-line HAIC. [ABSTRACT FROM AUTHOR]

The Beijing Eye Study 2011 is a population-based cross-sectional study in Northern China, which enrolled 3468 participants whose age were more than 50 years. A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography with enhanced depth imaging for measurement of SFCT and fundus photography. Blood pressure, fundus photographs and choroidal OCT-images were available for 3237 (93.3%) subjects, with 1953 (56.3 ± 0.8%) of the study population fulfilled the diagnosis of hypertension and 1089 subjects having hypertensive retinopathy. For the hypertensive cases, the SFCT in patients with hypertensive retinopathy (286.48 ± 105.23 µm) was significantly thicker than subjects without hypertensive retinopathy (187.04 ± 78.80 µm, P < 0.001). SFCT was significantly associated with the stage of hypertensive retinopathy (P < 0.001), but not significantly associated with diastolic blood pressure (P = 0.94), history (P = 0.95) and years (P = 0.91) of hypertension. In conclusion, hypertension as systemic disease was not significantly affect the subfoveal choroidal thickness, but as ocular disease, hypertensive retinopathy was significantly related to changes of choroidal thickness. Lesions of choroid during chronic hypertension may play an important role in development of hypertensive retinopathy. [ABSTRACT FROM AUTHOR]

Middle Permian Qixia Formation in the southwestern region of Sichuan (SW China) has experienced multiphase fluidisation, resulting in an unclear understanding of the reservoir reconstruction effect. In this study, a systematic analysis of the Qi2 member in Wulong Town was carried out by combining field outcrop petrology and geochemistry. The results demonstrated that multiple sets of crystalline dolomite-bioclastic limestone cycles were stacked vertically in the Qi2 member, accompanied by the development of fractures and karst channels. The dolomite was mainly composed of silty-fine dolomite (D1) and recrystallised dolomite (D2). Furthermore, obvious multiphase dolomitic cements (Cd1-Cd2) were present in the fractures and pores. Early karst is known to have lithologic mutation surface development and karst channel development at the top of several secondary cycles. The vadose silt dolomites (Cd1) having karst channels developed dull luminescence under cathode luminescence (CL). Both the geochemical indicators of elements and rare earth element (REE) content indicated dysoxic-oxic environmental conditions. The hydrothermal solution displayed tectonic carniole characteristics in the strata burial stage. Fractures and pores were filled with hydrothermal minerals such as coarse dolomites-saddle dolomites (Cd2, with some caused by recrystallisation of the Cd1 hydrothermal solution) and fluorites. Coarse dolomites-saddle dolomites developed dull-red luminescence with a bright-red rim under CL and their δ18OVPDB values were more negative than those of middle Permian limestone samples. Both the geochemical indicators of elements and REE content indicated the suboxic-anoxic environmental conditions. Karstification had minor constructive impact on the reservoir of the Qi2 member in Baoxing in southwestern Sichuan. Most products of karstification were distributed as fillings in channels. Aside from creating certain networked fractures, the hydrothermal solution was mainly filled with hydrothermal minerals along the fractures, pores and early karst channels. Karst and the hydrothermal solution mainly damaged the middle and upper parts of the middle Permian Qixia Formation in Southwest Sichuan. The impact of episodic fluid on the restoration of the carbonate reservoir was mainly restricted by channels for fluid migration and thickness differences among the reservoir. However, certain thick-layered and massive crystalline dolomite may hold promise for exploration. [ABSTRACT FROM AUTHOR]

The effects of physiological integration on clonal plants growing in aquatic and terrestrial habitats have been extensively studied, but little is known about the role in the extension of amphibious clonal plants in the heterogeneous aquatic-terrestrial ecotones, especially when the water environments are polluted by heavy metals. Ramets of the amphibious clonal herb Alternanthera philoxeroides were rooted in unpolluted soil and polluted water at three concentrations of Cu. The extension of populations from unpolluted terrestrial to polluted aqueous environments mainly relied on stem elongation rather than production of new ramets. The absorbed Cu in the ramets growing in polluted water could be spread horizontally to other ramets in unpolluted soil via physiological integration and redistributed in different organs. The performances of ramets in both terrestrial and aquatic habitats were negatively correlated with Cu intensities in different organs of plants. It is concluded that physiological integration might lessen the fitness of connected ramets in heterogeneously polluted environments. The mechanical strength of the stems decreased with increasing Cu levels, especially in polluted water. We suggest that, except for direct toxicity to growth and expansion, heavy metal pollution might also increase the mechanical risk in breaking failure of plants. [ABSTRACT FROM AUTHOR]

Bioflocculation, being environmental-friendly and highly efficient, is considered to be a promising method to harvest microalgae. However, one limitation of this technology is high expense on substrates for bioflocculant bacteria cultivation. In this regard, we developed an innovative method for the inner-recycling of biomass that could harvest the typical microalgae, Microcystis aeruginosa, using a bioflocculant produced by Citrobacter sp. AzoR-1. In turn, the flocculated algal biomass could be reutilized as a substrate for Citrobacter sp. AzoR-1 cultivation and bioflocculant production. The experimental results showed that 3.4 ± 0.1 g of bioflocculant (hereafter called MBF-12) was produced by 10 g/L of wet biomass of M. aeruginosa (high-pressure steam sterilized) with an additional 10 g/L of glucose as an extra carbon source. The efficiency of MBF-12 for M. aeruginosa harvesting could reach ~95% under the optimized condition. Further analysis showed that MBF-12, dominated by ~270 kDa biopolymers, contributed the bioflocculation mechanisms of interparticle bridging and biosorption process. Bioflocculant synthesis by Citrobacter sp. AzoR-1 using microalga as a substrate, including the polyketide sugar unit, lipopolysaccharide, peptidoglycan and terpenoid backbone pathways. Our research provides the first evidence that harvested algae can be reutilized as a substrate to grow a bioflocculant using Citrobacter sp. AzoR-1. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play vital regulatory roles in plant growth and development. The phase transition from vegetative growth to flowering is crucial in the life cycle of plants. To date, miRNA-mediated flowering regulatory networks remain largely unexplored in radish. In this study, two small RNA libraries from radish leaves at vegetative and reproductive stages were constructed and sequenced by Solexa sequencing. A total of 94 known miRNAs representing 21 conserved and 13 non-conserved miRNA families, and 44 potential novel miRNAs, were identified from the two libraries. In addition, 42 known and 17 novel miRNAs were significantly differentially expressed and identified as bolting-related miRNAs. RT-qPCR analysis revealed that some miRNAs exhibited tissue- or developmental stage-specific expression patterns. Moreover, 154 target transcripts were identified for 50 bolting-related miRNAs, which were predominately involved in plant development, signal transduction and transcriptional regulation. Based on the characterization of bolting-related miRNAs and their target genes, a putative schematic model of miRNA-mediated bolting and flowering regulatory network was proposed. These results could provide insights into bolting and flowering regulatory networks in radish, and facilitate dissecting the molecular mechanisms underlying bolting and flowering time regulation in vegetable crops. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small noncoding RNAs that play pivotal roles in plant growth, development and stress response. Chromium (Cr) is one of common environmental contaminants possessing potential health hazards to living organisms. To date, little is known about the regulatory roles of miRNAs in response to Cr stress in radish. To systematically identify Cr-responsive miRNAs and their targets in radish, two sRNA libraries derived from Cr-free (CK) and Cr-treated (Cr200) roots were constructed. With Solexa sequencing, 81 known and 72 novel miRNAs were identified, from which 54 known and 16 novel miRNAs were significantly differentially expressed under Cr stress. Several target genes for Cr-responsive miRNAs encode different transcription factor (TF) families, including SPLs, MYBs, ERFs and bZIPs, might regulate corresponding HM-related transcriptional processes in plants. Notably, a few key responsive enzymes or proteins, including HMA, YSL1 and ABC transporter protein were involved in Cr uptake and homeostasis process. Furthermore, the expression patterns of some Cr-responsive miRNAs and their targets were validated by RT-qPCR. This study represents the first characterization of Cr-responsive miRNAs and their targets in radish. The outcomes of this study could provide novel insights into miRNA-mediated regulatory mechanisms underlying plant response to Cr stress in root vegetable crops. [ABSTRACT FROM AUTHOR]

High-speed rail (HSR) has recently expanded its networks globally, but its 350 km/h bridges have not yet been tested for high-level earthquakes. This study tests the typical HSR bridge on a shaking table to assess the seismic performance in high-level earthquakes such as Maximum Considered Earthquake. Based on the model similarity theory, it creates nine round-ended rectangular-shaped cross-section solid RC HSR bridge piers. It employs the orthogonal testing method to conduct experimental design considering four influential factors: aspect ratio, axial load ratio, longitudinal reinforcement rate, and volumetric stirrup ratio. Experimental research was conducted to examine the dynamic response of these piers subjected to varying seismic impacts and design parameters, and the implications of the four factors on the seismic performance of the piers were discussed. After all the earthquake circumstances, the test findings demonstrate that the concrete of the pier specimens has not cracked or spalled much. An earthquake with a peak acceleration of 0.96 g indicates that the pier body of the standard high-speed rail round-end solid pier retains its integrity and stability. The extent of the pier's earthquake damage is not immediately evident. HSR bridges' seismic design may benefit from this research, which examines the impact of dynamic characteristics, including aspect ratio, axial load ratio, and longitudinal reinforcement rate, on HSR bridge piers' seismic performance. [ABSTRACT FROM AUTHOR]

Epicardial adipose tissue (EAT) contributes to the pathophysiological process of coronary artery disease (CAD). The expression profiles of long non-coding RNAs (lncRNA) in EAT of patients with CAD have not been well characterized. We conducted high-throughput RNA sequencing to analyze the expression profiles of lncRNA in EAT of patients with CAD compared to patients without CAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. We confirmed a dysregulated intergenic lncRNA (lincRNA) (LINC00968) by real-time quantitative PCR (RT-qPCR). Subsequently, we constructed a ceRNA network associated with LINC00968, which included 49 mRNAs. Compared with the control group, lncRNAs and genes of EAT in CAD were characterized as metabolic active and pro-inflammatory profiles. The sequencing analysis detected 2539 known and 1719 novel lncRNAs. Then, we depicted both lncRNA and gene signatures of EAT in CAD, featuring dysregulation of genes involved in metabolism, nuclear receptor transcriptional activity, antigen presentation, chemokine signaling, and inflammation. Finally, we identified a ceRNA network as candidate modulator in EAT and its potential role in CAD. We showed the expression profiles of specific EAT lncRNA and mRNA in CAD, and a selected non-coding associated ceRNA regulatory network, which taken together, may contribute to a better understanding of CAD mechanism and provide potential therapeutic targets. Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024782. [ABSTRACT FROM AUTHOR]

Polycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds-ikarugamycin (1), capsimycin (2) and capsimycin B (3)-two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, have been identified. The absolute configurations of the tert/tert-diols moiety was determined in 4 by NMR spectroscopic analysis, CD spectral comparisons and semi-synthetic method. The post-modification mechanism of the carbocyclic ring at C-14/C-13 of compound 1 in the biosynthesis of an important intermediate 3 was investigated. A putative cytochrome P450 superfamily gene, SXIM_40690 (ikaD), which was proximally localized to the ikarugamycin biosynthetic pathway, was characterized. In vivo gene inactivation and complementation experiment confirmed that IkaD catalysed the epoxide-ring formation reaction and further hydroxylation of ethyl side chain to form capsimycin G (3′). Binding affinities and kinetic parameters for the interactions between ikarugamycin (1) and capsimycin B (3) with IkaD were measured with Surface Plasmon Resonance. The intermediate compound 3′ was isolated and identified as 30-hydroxyl-capsimycin B. The caspimycins 2 and 3, were transferred to methoxyl derivatives, 6 and 7, under acidic and heating conditions. Compounds 1-3 exhibited anti-proliferative activities against pancreatic carcinoma with IC50 values of 1.30-3.37 μM. [ABSTRACT FROM AUTHOR]

To study types and thickness of interdigitation zone band in adult Chinese subjects, we conducted a cross-sectional study. The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years. 263 people (263eyes) with a mean age of 64.8 years were randomly selected cases without macular diseases included in the study. A detailed ophthalmic examination was performed including SD-OCT for measurement of the thickness of interdigitation zone band. There are two types of interdigitation zone band; the type1 which can distinguish RPE-BM complex in 170 eyes; and the Type 2 which the two layers merged involved 93 eyes. In type1, the mean thickness of the interdigitation zone band was significantly thicker in the foveal center (16.46 ± 2.92 μm), then nasal macular region (16.19 ± 2.69 μm), temporal macular region (15.73 ± 2.68 . μm), superior region (15.72 ± 2.70 μm), and inferior macular region (14.84 ± 2.63 μm) (P all < 0.05). And the mean thickness of the interdigitation zone band in the foveal center associated with the subfoveal choroidal thickness (P = 0.025) and level of education (P = 0.033). The increase in the thickness of the interdigitation zone band may play a role in the pathophysiologic features of various age-related ocular conditions. [ABSTRACT FROM AUTHOR]

Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2−/−) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2−/− mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF. [ABSTRACT FROM AUTHOR]

Triptolide (TP) is the major active principle of Tripterygium wilfordii Hook f. and very effective in treatment of autoimmune diseases. However, TP induced hepatotoxicity limited its clinical applications. Our previous study found that TP was a substrate of P-glycoprotein and its hepatobiliary clearance was markedly affected by P-gp modulation in sandwich-cultured rat hepatocytes. In this study, small interfering RNA (siRNA) and specific inhibitor tariquidar were used to investigate the impact of P-gp down regulation on TP-induced hepatotoxicity. The results showed that when the function of P-gp was inhibited by mdr1a-1 siRNA or tariquidar, the systemic and hepatic exposures of TP were significantly increased. The aggravated hepatotoxicity was evidenced with the remarkably lifted levels of serum biomarkers (ALT and AST) and pathological changes in liver. The other toxicological indicators (MDA, SOD and Bcl-2/Bax) were also significantly changed by P-gp inhibition. The data analysis showed that the increase of TP exposure in mice was quantitatively correlated to the enhanced hepatotoxicity, and the hepatic exposure was more relevant to the toxicity. P-gp mediated clearance played a significant role in TP detoxification. The risk of herb-drug interaction likely occurs when TP is concomitant with P-gp inhibitors or substrates in clinic. [ABSTRACT FROM AUTHOR]