Rare genetic variants play a critical role in unprovoked pulmonary embolism (PE). However, the known risk genes only account a small proportion of patients with PE. The objective of this study was to ...investigate the relationship between the rare variants of gene encoding methylenetetrahydrofolate reductase (MTHFR) and the initiation and long-term clinical outcomes of PE.
The rare variants of MTHFR were detected by whole exome sequencing of DNA from 258 unprovoked PE cases and 11,451 controls. Correlation of genotype and clinical phenotype and outcome were evaluated at baseline and after follow-up.
MTHFR rare variants were found in 15 of 258 cases (5.81%) and 241 of 11,451 controls (2.10%), conferring 2.87-fold greater odds of the PE occurrence (OR = 2.87, 95% CI = 1.68–4.91, P = 5.6 × 10−5, chi-square test). The patients with MTHFR rare variants had higher plasma level of homocysteine than those without. During a follow-up of 3.0 years, a total of 84 events were identified. The recurrent PE (two or more events of PE) were significantly higher in patients carrying MTHFR rare variants (8/15, 53.3%) compared with those without (55/239, 23.0%) (P = 0.023).
We speculate that MTHFR rare variants may increase the occurrence and recurrence of PE.
•Patients carrying MTHFR rare variants had higher plasma Hcy level than those without rare variants.•Rare variants of MTHFR were not only associated with the occurrence, but also closely associated with recurrence of PE.
Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum ...albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 μA·mM
·cm
), wide calibration range (0.01-3.5 mM), and low detection limit (17 μM). The apparent Michaelis-Menten constant Kmapp is 119 μM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.
The histone demethylase lysine‐specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of ...H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48‐linked deubiquitin and stability. Interestingly, we found c‐Myc was a key downstream effector of the USP1‐KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.
This study identifies USP1 as a critical deubiquitinase for stabilizing KDM4A, thereby promoting prostate cancer growth and tumorigenesis. Targeting KDM4A stabilization through pharmacological inhibition of USP1 by ML323 could thus open an avenue for therapeutic intervention in prostate cancer patients.
Abstract In Data Release 9 of LAMOST, we present measurements of v sin i for a total of 121,698 stars measured using the Medium Resolution Spectrograph (MRS) and 80,108 stars using the Low Resolution ...Spectrograph (LRS). These values were obtained through a χ 2 minimization process, comparing LAMOST spectra with corresponding grids of synthetically broadened spectra. Due to the resolution and the spectral range of LAMOST, v sin i measurements are limited to stars with an effective temperature ( T eff ) ranging from 5000 to 8500 K for MRS and 7000 to 9000 K for LRS. The detectable v sin i for MRS is set between 27 and 350 km s −1 , and for LRS between 110 and 350 km s −1 . This limitation is because the convolved reference spectra become less informative beyond 350 km s −1 . The intrinsic precision of v sin i , determined from multiepoch observations, is approximately ∼4.0 km s −1 for MRS and ∼10.0 km s −1 for LRS at a signal-to-noise ratio greater than 50. Our v sin i values show consistency with those from APOGEE17, displaying a scatter of 8.79 km s −1 . They are also in agreement with measurements from the Gaia DR3 and Sun et al. catalogs. An observed trend in LAMOST MRS data is the decrease in v sin i with a drop in T eff , particularly transiting around 7000 K for dwarfs and 6500 K for giants, primarily observed in stars with near-solar abundances.
Copper-mediated selective mono- or diaryloxylation of benzamides has been achieved by using 2-aminopyridine 1-oxide as a new and removable N,O-bidentate directing group. The reaction system shows a ...broad substrate scope and provides a straightforward way for the synthesis of mono- and diaryloxylated benzoic acids.
Comprehensive Summary
A new class of m‐hydroxybenzyl alcohols has been designed as competent three‐carbon building blocks and achieved their application in 2‐indolylmethanol‐involved regioselective ...(3 + 3) cycloadditions under the catalysis of Brønsted acids. By this appoach, a series of indole‐fused six‐membered cycloadducts have been synthesized in overall good yields (up to 98%) with excellent regioselectivity (all >95: 5 rr), thus affording a powerful method for the construction of indole‐fused six‐membered rings. Moreover, a catalytic asymmetric version of this (3 + 3) cycloaddition has been preliminarily investigated, which revealed the potential of the reaction for constructing chiral indole‐fused six‐membered rings in an enantioselective manner. This work not only has accomplished the first design of m‐hydroxybenzyl alcohols as competent reactants, but also represents the first application of m‐hydroxybenzyl alcohols as three‐carbon building blocks in cycloadditions. In addition, this work provides a good example for regioselective and C3‐nucleophilic (3 + 3) cycloadditions of 2‐indolylmethanols, which will substantially enrich the chemistry of 2‐indolylmethanols.
A new class of m‐hydroxybenzyl alcohols has been designed as competent three‐carbon building blocks and achieved their application in 2‐indolylmethanol‐involved regioselective (3 + 3) cycloadditions under the catalysis of Brønsted acids. By this appoach, a series of indole‐fused six‐membered cycloadducts have been synthesized in overall good yields (up to 98%) with excellent regioselectivity (all >95: 5 rr), thus affording a powerful method for the construction of indole‐fused six‐membered rings. Moreover, a catalytic asymmetric version of this (3 + 3) cycloaddition has been preliminarily investigated, which revealed the potential of the reaction for constructing chiral indole‐fused six‐membered rings in an enantioselective manner.
Chemiluminescence resonance energy transfer (CRET) is a non-radiative transfer of energy from chemiluminescence (CL) reagent to energy acceptor during the CL reaction. The reaction process does not ...require excitation from external source, so CRET-based assays have low background and high sensitivity. Recently, efficient energy transfer systems have been proposed and a variety of nanomaterials with different functions have been presented as acceptors. Among them, the “signal-on” type acceptors (e.g., fluorescence dye, quantum dot and semiconducting polymer) can increase the CL intensity effectively, while the “signal-off” type acceptors (e.g., gold nanoparticle and carbon nanomaterials) have highly quenching efficiency. The development of acceptors has extended the applications of CRET ranging from biosensing and bioimaging to biomedicine and therapy. In this review, the CRET modes are divided according to the type of acceptors based on the energy transfer mechanisms. Their recent advances and future prospects are summarized and discussed.
•The mechanisms of CRET are summarized according to the type of acceptors.•The recent advances of CRET in analytical applications are introduced.•The present challenges and future prospect of CRET are highlighted.
Background
Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) is reported to be linked to cancers. This research aims to explore the role and possible mechanism of CASC9 in lung ...injury induced by sepsis.
Methods
Lipopolysaccharide (LPS) induced human small airway epithelial cells (HSAECs) were established in vitro to mimic sepsis-induced lung injury. The effects of CASC9 and miR-195-5p on HSAECs viability were studied by CCK-8 assay. Interactions between CASC9 and miR-195-5p were determined by bioinformatics analysis, RT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation assay. Pyruvate dehydrogenase kinase 4 (PDK4) and apoptosis-related molecules including Bcl2 and Bad were detected by western blot. Additionally, sepsis-induced lung injury model in rats was established by intraperitoneal injection of LPS in vivo to validate the demonstrations of in vitro studies
.
Results
CASC9 was markedly down-regulated while miR-195-5p was significantly up-regulated in HSAECs treated by LPS and lung tissues of rats with sepsis. CASC9 interacted with miR-195-5p, and negatively regulated its expression level. Overexpression of CASC9 or transfection of miR-195-5p inhibitors significantly promoted the viability of HSAECs. The transfection of miR-195-5p mimics effected oppositely. For mechanism, miR-195-5p targeted the 3′UTR of pyruvate dehydrogenase kinase 4 (PDK4) gene and depressed the protein level, and PDK4 was regulated indirectly by CASC9. Restoration of CASC9 in the lung tissues of rats with sepsis ameliorated lung injury.
Conclusion
CASC9 protects lung epithelial cells from sepsis-induced injury via regulating miR-195-5p/PDK4 axis.
A novel V-shaped grating grid with a composite structure comprised of two oppositely tilted tracks is firstly proposed, which can provide both asymmetry and high refractive index modulation (RIM) to ...support the bending vector sensing. A long-period fiber grating formed by the V-shaped grids is fabricated with a high-frequency-CO 2 laser on a single-mode fiber, and it provides different responses of wavelength shift in two-axis directions' bending. The V-shaped grid model is established to theoretically analyze the change of RIM caused by bending. The formula of bending sensitivity is deduced, and the values of sensitivity in two-axis directions are calculated. The experimental bending sensitivities are 16.315 and -23.085 nm/m -1 in the opposite directions within the plane perpendicular to the laser-irradiated direction, which can coincide with the theoretical expectation. Its temperature recycle characteristic is also provided.
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