This work synthesizes a new bifunctional furan derivative (PDMS‐FBZ) through a sequence of hydrosilylation of nadic anhydride (ND) with polydimethylsiloxane (PDMS), reaction of the product with ...p‐aminophenol to form PDMS‐ND‐OH, and its subsequent Mannich reaction with furfurylamine and CH2O. Then, the main chain‐type copolymer PDMS‐DABZ‐DDSQ is prepared through a Diels–Alder (DA) cycloaddition of PDMS‐FBZ with the bismaleimide‐functionalized double‐decker silsesquioxane derivative DDSQ‐BMI. Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy confirm the structure of this PDMS‐DABZ‐DDSQ copolymer; differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic mechanical analysis (DMA) reveal it to have high flexibility and high thermal stability (Tg = 177 °C; Td10 = 441 °C; char yield = 60.1 wt%); contact angle measurements reveal a low surface free energy (18.18 mJ m−2) after thermal ring‐opening polymerization, because the inorganic PDMS and DDSQ units are dispersed well, as revealed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). This PDMS‐DABZ‐DDSQ copolymer possesses reversible properties arising from the DA and retro‐DA reactions, suggesting its possible application as a functional high‐performance material.
The PDMS‐DABZ‐DDSQ copolymer reveals high flexibility and high thermal stability (Tg = 177 °C; Td10 = 441 °C; char yield = 60.1 wt%) and a low surface free energy (18.18 mJ m−2) after thermal ring‐opening polymerization, because the inorganic polydimethylsiloxane (PDMS) and DDSQ units are dispersed well.
Background Ovarian cancer (OC) is the most lethal gynecological cancer due to the recurrence of drug-resistance. Cancer initiating cells (CICs) are proposed to be responsible for the aggressiveness ...of OC. The rarity and difficulty of in vitro long-term cultivation of CICs challenge the development of CIC-targeting therapeutics. Reprogramming cancer cells into induced cancer initiating cell (iCICs) could be an approach to solve these. Several inducible CICs have been acquired by activating the expression of stemness genes in different cancer cells. However, few reports have demonstrated the feasibility in OC. Methods Patients with primary OC receiving surgery were enrolled. Tumor tissue were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunohistochemistry (IHC) staining to investigate the association of stemness markers with overall survival (OS). An high-grade serous ovarian cancer (HGSOC) cell line, OVCAR-3 was reprogrammed by transducing Yamanaka four factors OCT4, SOX2, KLF4 and MYC (OSKM) to establish an iOCIC model, iOVCAR-3-OSKM. CIC characteristics of iOVCAR-3-OSKM were evaluated by RT-PCR, sphere formation assay and animal experiments. Drug-resistance and migration ability were accessed by dye-efflux activity assay, MTT assay and migration assay. Gene profile was presented through RNA-sequencing. Lineage differentiation ability and organoid culture were determined by in vitro differentiation assays. Results In OC patients, the co-expression of multiple stem-related transcription factors (OCT4, SOX2, and NANOG) was associated with worse OS. iOVCAR-3-OSKM cells generated by reprogramming successfully exhibited stemness characteristics with strong sphere-forming and tumorigenesis ability. iOVCAR-3-OSKM cells also showed malignant potential with higher drug resistance to chemodrug, Paclitaxel (PTX) and migration ability. iOVCAR-3-OSKM was maintainable and expandable on feeder-dependent culture condition, it also preserved ovarian lineage differentiation abilities, which could well differentiate into OC cells with CK-7 and CA125 expressions and develop into an organoid mimic poor prognostic OC histological feature. Conclusions The establishment of iOVCAR-3-OSKM not only allows us to fill the gap in the information on induced CICs in OC but also provides a potential strategy to develop personalized CICs and organoid models for treating OC in the near future. Keywords: Ovarian cancer (OC), Cancer-initiating cells (CICs), Induced ovarian cancer-initiating cells (iOCICs), Organoid and drug screening
The formation of PtSe2‐layered films is reported in a large area by the direct plasma‐assisted selenization of Pt films at a low temperature, where temperatures, as low as 100 °C at the applied ...plasma power of 400 W can be achieved. As the thickness of the Pt film exceeds 5 nm, the PtSe2‐layered film (five monolayers) exhibits a metallic behavior. A clear p‐type semiconducting behavior of the PtSe2‐layered film (≈trilayers) is observed with the average field effective mobility of 0.7 cm2 V−1 s−1 from back‐gated transistor measurements as the thickness of the Pt film reaches below 2.5 nm. A full PtSe2 field effect transistor is demonstrated where the thinner PtSe2, exhibiting a semiconducting behavior, is used as the channel material, and the thicker PtSe2, exhibiting a metallic behavior, is used as an electrode, yielding an ohmic contact. Furthermore, photodetectors using a few PtSe2‐layered films as an adsorption layer synthesized at the low temperature on a flexible substrate exhibit a wide range of absorption and photoresponse with the highest photocurrent of 9 µA under the laser wavelength of 408 nm. In addition, the device can maintain a high photoresponse under a large bending stress and 1000 bending cycles.
Phase‐engineered PtSe2‐layered films by a plasma‐assisted selenization process to highly sensitive, flexible, and wide‐spectrum photoresponse photodetectors are demonstrated. A full PtSe2 field effect transistor is also demonstrated where the thinner PtSe2, exhibiting a semiconducting behavior, is used as the channel material, and the thicker PtSe2, exhibiting a metallic behavior, is used as an electrode.
It is important to select appropriate targeted therapies for subgroups of patients with lung adenocarcinoma who have specific gene alterations.
This prospective study was a multicenter project ...conducted in Taiwan for assessment of lung adenocarcinoma genetic tests. Five oncogenic drivers, including EGFR, KRAS, BRAF, HER2 and EML4-ALK fusion mutations, were tested. EGFR, KRAS, BRAF and HER2 mutations were assessed by MALDI-TOF MS (Cohort 1). EML4-ALK translocation was tested by Ventana method in EGFR-wild type patients (Cohort 2).
From August 2011 to November 2013, a total of 1772 patients with lung adenocarcinoma were enrolled. In Cohort 1 analysis, EGFR, KRAS, HER2 and BRAF mutations were identified in 987 (55.7%), 93 (5.2%), 36 (2.0%) and 12 (0.7%) patients, respectively. Most of these mutations were mutually exclusive, except for co-mutations in seven patients (3 with EGFR + KRAS, 3 with EGFR + HER2 and 1 with KRAS + BRAF). In Cohort 2 analysis, 29 of 295 EGFR-wild type patients (9.8%) were positive for EML4-ALK translocation. EGFR mutations were more common in female patients and non-smokers and KRAS mutations were more common in male patients and smokers. Gender and smoking status were not correlated significantly with HER2, BRAF and EML4-ALK mutations. EML4-ALK translocation was more common in patients with younger age.
This was the first study in Taiwan to explore the incidence of five oncogenic drivers in patients with lung adenocarcinoma and the results could be valuable for physicians in consideration of targeted therapy and inclusion of clinical trials.
Junctional adhesion molecule 3 (JAM3) is involved in epithelial cell junction, cell polarity, and motility. The molecular mechanisms underlying the role of JAM3 in placental dysfunction remain ...unclear. We hypothesized that JAM3 expression regulates trophoblast fusion, differentiation, proliferation, and apoptosis. Our results revealed that JAM3 was expressed in the cytotrophoblasts and syncytiotrophoblasts of first-trimester and term placental villi. JAM3 expression in cell–cell junctions decreased with the formation of syncytiotrophoblasts. Using trophoblasts as an in vitro model, we observed that forskolin and JAM3 knockdown significantly reduced JAM3 expression and increased syncytium formation. JAM3 knockdown additionally inhibited trophoblast proliferation and increased the number of trophoblasts in the sub-G1 and G2/M phases, indicating cell-cycle disturbance and apoptosis. Cell-cycle arrest was associated with the engagement of checkpoint kinase 2-cell division cycle 25C-cyclin-dependent kinase 1/cyclin B1 signaling. Increased expression of BIM, NOXA, XAF1, cytochrome c, and cleaved caspase-3 further indicated trophoblast apoptosis. Overexpression of JAM3 or recombinant JAM3 protein enhanced trophoblast adhesion and migration, which were inhibited by JAM3 knockdown. JAM3 knockdown induced reactive oxygen species and syncytin 2 expression in trophoblasts. Furthermore, H2O2-induced oxidative stress reduced JAM3 expression in trophoblasts and cell culture supernatants. H2O2 simultaneously induced trophoblast apoptosis. JAM3 expression was significantly decreased in the plasmas and placentas of patients with early-onset severe preeclampsia. Thus, our results show that JAM3 may not only be a structural component of trophoblast cell junctions but also regulates trophoblast fusion, differentiation, proliferation, apoptosis, and motility. Dysregulated trophoblast JAM3 expression is crucial in preeclampsia development. Graphical Abstract
Single-cell proteomics can reveal cellular phenotypic heterogeneity and cell-specific functional networks underlying biological processes. Here, we present a streamlined workflow combining ...microfluidic chips for all-in-one proteomic sample preparation and data-independent acquisition (DIA) mass spectrometry (MS) for proteomic analysis down to the single-cell level. The proteomics chips enable multiplexed and automated cell isolation/counting/imaging and sample processing in a single device. Combining chip-based sample handling with DIA-MS using project-specific mass spectral libraries, we profile on average ~1,500 protein groups across 20 single mammalian cells. Applying the chip-DIA workflow to profile the proteomes of adherent and non-adherent malignant cells, we cover a dynamic range of 5 orders of magnitude with good reproducibility and <16% missing values between runs. Taken together, the chip-DIA workflow offers all-in-one cell characterization, analytical sensitivity and robustness, and the option to add additional functionalities in the future, thus providing a basis for advanced single-cell proteomics applications.
Objective
Huntington disease (HD) is an inherited neurodegenerative disease caused by the mutant huntingtin gene (mHTT), which harbors expanded CAG repeats. We previously reported that the brain ...vessel density is higher in mice and patients with HD than in controls. The present study determines whether vascular function is altered in HD and characterizes the underlying mechanism.
Methods
The brain vessel density and vascular reactivity (VR) to carbogen challenge of HD mice were monitored by 3D ΔR2‐mMRA and blood oxygenation level–dependent (BOLD)/flow‐sensitive alternating inversion recovery (FAIR) magnetic resonance imaging (MRI), respectively. The amount of vascular endothelial growth factor (VEGF)‐A and the pericyte coverage were determined by immunohistochemistry and enzyme‐linked immunosorbent assay in human and mouse brain sections, primary mouse astrocytes and pericytes, and human astrocytes derived from induced pluripotent stem cells.
Results
Expression of mHTT in astrocytes and neurons is sufficient to increase the brain vessel density in HD mice. BOLD and FAIR MRI revealed gradually impaired VR to carbogen in HD mice. Astrocytes from HD mice and patients contained more VEGF‐A, which triggers proliferation of endothelial cells and may be responsible for the augmented neurovascular changes. Moreover, an astrocytic inflammatory response, which reduces the survival of pericytes through an IκB kinase–dependent pathway, mediates the low pericyte coverage of blood vessels in HD brains.
Interpretation
Our findings suggest that the inflammation‐prone HD astrocytes provide less pericyte coverage by promoting angiogenesis and reducing the number of pericytes and that these changes can explain the inferior VR in HD mice. The resultant impaired VR might hinder cerebral hemodynamics and increase brain atrophy during HD progression. Ann Neurol 2015;78:178–192
Increasing reports on epidemiological, diagnostic, and clinical studies suggest that dysfunction of the inflammatory reaction results in chronic illnesses such as cancer, arthritis, arteriosclerosis, ...neurological disorders, liver diseases, and renal disorders. Chronic inflammation might progress if injurious agent persists; however, more typically than not, the response is chronic from the start. Distinct to most changes in acute inflammation, chronic inflammation is characterized by the infiltration of damaged tissue by mononuclear cells like macrophages, lymphocytes, and plasma cells, in addition to tissue destruction and attempts to repair. Phagocytes are the key players in the chronic inflammatory response. However, the important drawback is the activation of pathological phagocytes, which might result from continued tissue damage and lead to harmful diseases. The longer the inflammation persists, the greater the chance for the establishment of human diseases. The aim of this review was to focus on advances in the understanding of chronic inflammation and to summarize the impact and involvement of inflammatory agents in certain human diseases.
Chronic inflammation is a greater the chance for the establishment of human diseases.
Metal-organic frameworks (MOFs) have recently garnered consideration as an attractive solid substrate because the highly tunable MOF framework can not only serve as an inert host but also enhance the ...selectivity, stability, and/or activity of the enzymes. Herein, we demonstrate the advantages of using a mechanochemical strategy to encapsulate enzymes into robust MOFs. A range of enzymes, namely β-glucosidase, invertase, β-galactosidase, and catalase, are encapsulated in ZIF-8, UiO-66-NH
, or Zn-MOF-74 via a ball milling process. The solid-state mechanochemical strategy is rapid and minimizes the use of organic solvents and strong acids during synthesis, allowing the encapsulation of enzymes into three prototypical robust MOFs while maintaining enzymatic biological activity. The activity of encapsulated enzyme is demonstrated and shows increased resistance to proteases, even under acidic conditions. This work represents a step toward the creation of a suite of biomolecule-in-MOF composites for application in a variety of industrial processes.
Three new triterpenoids-spergulagenin B (
), spergulagenin C (
), and spergulagenin D (
)-were isolated from the aerial part of
, along with 17 known compounds (
-
). The structures of these new ...compounds were identified by spectroscopic and MS analyses. Compounds
,
,
, and
were evaluated for inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells with IC
values of 17.03, 18.21, 16.30, and 12.64 μM, respectively. Compounds
,
, and
exhibited inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 cells with IC
values of 18.35 ± 1.34, 17.56 ± 1.41, and 14.27 ± 1.29 μM, respectively.
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