Myeloid differentiation factor 88 (MyD88) and Toll or interleukin-1 receptor-domain-containing adaptor-inducing interferon-β (IFN-β) (TRIF) are two pivotal downstream adaptors of Toll-like receptors. ...Activation of MyD88 or TRIF signaling in cardiac immune pathology of severe inflammation negatively influences heart function. In the present study, severe septic cardiac injury was induced in C57BL/6 mice by cecum ligation and puncture (CLP). A total of 64 mice were divided randomly into the following four groups (n=16/group; 8 for observation of survival rate, 8 for heart sample analysis): Sham, CLP, anti-MyD88-CLP and anti-TRIF-CLP. Anti-MyD88 and anti-TRIF antibodies were administered to the respective mice through the tail veins 2 h before CLP. Measurements of cardiac function, including M-modes, velocity vector imaging and cardiac troponin I, were performed. Myocardial inflammatory cytokines were examined by reverse transcription-polymerase chain reaction (RT-PCR), myocardial neutrophil infiltration was measured by a myeloperoxidase activity assay, intracellular adhesion molecule and vascular cell adhesion molecule mRNA expression levels were investigated, and histopathological characteristics were evaluated. Levels of mRNA transcripts encoding genes for apoptosis production and MyD88, TRIF, nuclear factor-κB and IFN regulatory factor 3 were investigated by RT-PCR. Mice challenged with CLP demonstrated deleterious cardiac function, increased levels of interleukin-1β (IL-1β), IL-6β, and tumor necrosis factor-α mRNA, increased neutrophil infiltration, and increased apoptosis. In contrast, mice in the anti-MyD88 CLP and anti-TRIF CLP groups retained cardiac function with reduced cytokine release, decreased neutrophil infiltration, and reduced apoptosis. In addition, there was no significant difference between the anti-MyD88 CLP and anti-TRIF CLP groups. Thus, the present study indicated that MyD88 and TRIF blockades serve notable and equivalent roles in protecting cardiac deterioration from severe sepsis by attenuating cytokine release, reducing neutrophil infiltration and alleviating apoptosis.
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•Wenyujindiol A (1), a new sesquiterpene was isolated from Curcuma wenyujin.•Compound 1 possessed a novel natural skeleton with a rare 4/8 ring system.•Compound 1 exhibited moderate ...cytotoxicity against MCF-7 cancer cell lines.
Wenyujindiol A (1), a new sesquiterpene possessing a skeleton with a rare 4/8 ring system, together with the known compound (4S,5S)-germacrone-4,5-epoxide (2), were isolated from the rhizomes of Curcuma wenyujin. The structure of 1 was elucidated using spectroscopic measurements and single-crystal X-ray diffraction experiments. A plausible biogenetic pathway was also proposed for the biosynthesis of 1 from farnesyl diphosphate (FPP). Biological evaluation indicated that 1 exhibited moderate antitumor activity on the human breast cancer cell line MCF-7.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Triple‐negative breast cancer (TNBC) presents the most challenging subtype of all breast cancers because of its aggressive clinical phenotypes and absence of viable therapy targets. In ...order to identify effective molecular targets for treating patients with TNBC, we conducted an integration analysis of our recently published TNBC dataset of quantitative proteomics and RNA‐Sequencing, and found the abnormal upregulation of chromosome 9 open reading frame 142 (C9orf142) in TNBC. However, the functional roles of C9orf142 in TNBC are unclear.
Methods
In vitro and in vivo functional experiments were performed to assess potential roles of C9orf142 in TNBC. Immunoblotting, real‐time quantitative polymerase chain reaction (RT‐qPCR), and immunofluorescent staining were used to investigate the expression levels of C9orf142 and its downstream molecules. The molecular mechanisms underlying C9orf142‐regulated mouse double minute 2 (MDM2)‐binding protein (MTBP) were determined by chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assays.
Results
In TNBC tissues and metastatic lymph nodes, we observed that C9orf142 exhibited abnormal up‐regulation, and its elevated expression was indicative of unfavorable prognosis for TNBC patients. Both in vitro and in vivo functional experiments demonstrated that C9orf142 accelerated TNBC growth and metastasis. Further mechanism exploration revealed that C9orf142 transcriptionally activated MTBP, thereby regulating its downstream MDM2/p53/p21 signaling axis and the transition of cell cycle from G1 to S phase. Functional rescue experiment demonstrated that knockdown of MTBP attenuated C9orf142‐mediated tumour growth and metastasis. Furthermore, depletion of C9orf142 remarkably increased the responsiveness of TNBC cells to CDK4/6 inhibitor abemaciclib.
Conclusions
Together, these findings unveil a previously unrecognized effect of C9orf142 in TNBC progression and responsiveness to CDK4/6 inhibitor, and emphasize C9orf142 as a promising intervention target for TNBC treatment.
1. C9orf142 is elevated in TNBC patients and its elevation predicts unfavourable clinical outcome.
2. C9orf142 augments TNBC progression through transcriptional transaction of MTBP to regulate its downstream MDM2/p53/p21 signaling axis. 3. C9orf142 promotes resistance of TNBC cells to CDK4/6 inhibitor partially depend on MTBP/MDM2/p53/p21 signaling axis.
4. Knockdown of C9orf142 inhibits TNBC progression and enhances its sensitivity to CDK4/6 inhibitor.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the ...reference standard.
This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SI
- SI
)/(SI
- SI
), where SI
, SI
and SI
represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves.
The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001).
SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC.
The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC.
Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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•Arenecarboxylic acids were produced in high yields by oxidizing SCPs with ASHC.•The CAR structures in CPs suppress the formation of chlorine-substituted compounds.•O2− plays a ...crucial role in oxidizing ARs in SCPs to arenecarboxylic acids.•Conjugation effect and electron-withdrawing effect affect the product distribution.
Char powders (CPs) are a promising feedstock for producing benzenecarboxylic acids (BCAs) due to their abundant condensed aromatic rings. An innovative exploration on the related mechanisms for oxidation and chlorination was attempted to guide the production of target BCAs in higher yields. The results declare that Shenmu CPs were converted to valuable BCAs in the yield of 16.2%. According to the product distribution, the total relative content (4.3%) of chlorine-substituted alkanoic acids (CSAAs) is much higher than that (0.2%) of alkanoic acids, while the result of chlorine-substituted BCAs is just the opposite and no chlorine-substituted arenecarboxylic acids with multiple aromatic rings (ARs) were produced. All the CSAAs have only short-chains. Carboxylic groups (CGs) tend to be chlorinated, but the steric effect of benzene ring leads to the inertness of most BCAs towards chlorination. The conjugation effect between CGs and ARs facilitates degrading condensed aromatics by stabilizing aryl radical intermediates. Thereby, the activity towards chlorination decreases with increasing the number of CGs, condensation degree, and carbon numbers in the aliphatic chains.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A new fluorine-substituted benzyl triphenylphosphine tetrabromocobaltate(II) was synthesized and characterized.•The FT-IR and Raman spectra analysis were employed to identify the functional groups ...present in the molecule.•The HOMO-LUMO energy gap explains the interaction of charge transfer in molecules.•Non-linear optical properties were predicted by DFT calculations on the as-prepared crystal.
A new organic-inorganic hybrid 4FBzTPP2CoBr4(1) (4FBzTPP = 4-fluorobenzyltriphenylphosphonium) was synthesized and characterized by X-ray diffraction, DTA-TG measurement, FT-IR and Raman spectroscopies, Scanning Electron Microscope (SEM), Energy Dispersive Spectrometer (EDS) and UV–vis diffuse reflectance spectrum. 4FBzTPP2CoBr4 crystallized in monoclinic system with P21/c space group, consisting of two 4FBzTPP+ cations and one distorted tetrahedral CoBr42− anion. Powder X-ray diffraction analysis confirmed the bulk phase purity and homogeneity of the material. The UV–vis-DRS result indicated that the energy gap value of the electron transition was 1.60 eV, which was quite distant from the calculated value of 1.64 eV. The material showed fluorescent emission at 389 nm, 414 nm, 448 nm, and 495 nm under the excitation of UV light at 380 nm. Theoretical calculations were performed using the density functional theory method to derive the dipole moment and first hyperpolarizability of the as-synthesized molecule. The first hyperpolarizability value (βtot) was more than 11,600 times higher than those of standard KDP crystals, indicating that 4FBzTPP2CoBr4 was an excellent material for applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nitrogen doped carbon materials have been found to be a capable oxygen electrocatalyst for low-cost and highly durable metal-oxygen batteries. However, it is still a challenge to associate the ...precise working mechanism with their molecular structure, specific surface area and conductivity. By using first-principles calculations and experimental studies, for the first time, we clarify the higher catalyst activity of pyridinic-N than graphitic-N in highly conductive and porous carbon framework. Accordingly, an ultrahigh conductive three-dimensional doped carbon framework that consists of networked and hollow pipelines with nanometer-thick walls is prepared. Benefiting from such a unique structure, the as-made carbon framework as binder-free cathode for hybrid Li-O2 battery delivers 150 cycles at 1 A g−1 on deep (dis)charge. More importantly, based on the total mass of pyridinic nitrogen doped carbon framework, the capacity of the Li-O2 battery containing the binder-free carbon framework cathode amounts to 49.5 Ah g−1.
Catalytic activity of pyridinic-N of carbon framework can be improved by enhancing electron mobility and transport paths, and decreasing electron scattering interfaces, as proved by first-principles calculations and experimental studies. Accordingly, a three-dimensional N-doped carbon framework is fabricated via morphology-controlled solid-state pyrolysis of polyaniline foam, which successfully acts as a low-cost and highly catalytic active binder-free air cathode for hybrid electrolyte lithium-oxygen battery. Display omitted
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Self-healing system with ultrafast speed and heat-resistance is highly desired in development of intelligent high performance polymer composites. In this work, trifluoromethanesulfonic acid (TfOH), ...an ultra-strong Bronsted acid, is successfully encapsulated in silica microspheres, which cooperates with epoxy monomer, forming a group of novel self-healing agent having practical value. Impact and fatigue tests demonstrate that mechanical strength of epoxy composite filled with low loading level of microencapsulated epoxy monomer and TfOH can be recovered within seconds at room temperature without manual intervention. Moreover, the present healing system is low-toxic and has acquired significant thermal stability. It can survive the rigorous processing of high Tg epoxy (>240°C) during composite fabrication and provides the composite that was pre-treated at 180°C for 5h with the same healing efficiency as the untreated one. We believe that this work expands the spectrum of self-healing strategies and facilitates future applications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The first total synthesis of polycyclic Stemona alkaloid maistemonine has been achieved. The efficient approach features a stereoselective intramolecular Schmidt reaction, a ketone-ester ...condensation, and a Reformatsky reaction. Additionally, another Stemona alkaloid stemonamide was divergently synthesized from a common intermediate.
Isolated ventricular apical hypoplasia (IVAH) is a rare congenital cardiac anomaly, with clinical manifestations depending on the age of the patient, ranging from no symptoms in children to ...congestive heart failure or even malignant tachycardia in adults. Herein, we describe the clinical and anatomical findings in four cases with hypoplasia of the right or left ventricular apex, and we discuss the possible mechanisms and differential diagnosis of this malformation. Echocardiography is a rapidly accessible, low cost, noninvasive technique for the detection and evaluation of IVAH.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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