Layered silicate clays are natural crystallites and are well recognized for their structures and industrial applications, but there are very few reports on their structural confinement properties and ...on the mechanisms that underlie their polymer interactions. In this review, we summarize the recent progress on clay modification via conventional ion exchange reactions, sol–gel linking, atom transfer radical polymerization, and polymer intercalation. The organic interaction of ionic clays involves different noncovalent bonding forces, such as amido acid five-membered ring chelation, carboxylic acid chelation, intermolecular hydrogen bonding, and double-layer hydrophobic alignment in a layered clay confinement. Controlling the organic species, their amounts and their self-assembled conformation in a clay confinement could lead to the tailoring of the silicate platelet interlayer distance and of their organophilic properties.
Furthermore, the layered structure could be totally exfoliated and structurally randomized into individual silicate platelets using different mechanisms, such as the phase inversion of amphiphilic copolymer emulsifiers and phase transitions that involve zigzag Mannich polyamines. For comparison, the organic modification of graphene/graphite plate-like carbonaceous materials is briefly reviewed. The self-organization of organics in clay interlayer galleries and the randomization of layered silicate stacks into platelets are reviewed to understand the noncovalent bonding interactions between the clays and various organics. Different intercalation and exfoliation strategies help the in-depth understanding of clay chemistry and indicate new clay applications.
Triple negative breast cancer (TNBC) possesses poor prognosis mainly due to lack of effective endocrine or targeted therapies, aggressive nature and high rate of chemoresistance. Cancer stem cells ...(CSCs) are considered to play critical roles in cancer recurrence and chemoresistance. THEMIS2 was identified as the sole common elevated gene in three triple negative breast cancer (TNBC) and two ovarian CSC lines. We discovered an intrinsic signaling scaffold function of THEMIS2, which acts as a novel regulator of cancer stemness in promoting multiple cancer stemness properties including sphere formation, stemness markers expression, chemoresistance and tumorigenicity with low numbers of cancer cells implantation. For the first time, we demonstrated that THEMIS2 specifically enhanced MET activating phosphorylation by suppressing the association of protein-tyrosine phosphatases 1B (PTP1B) with p-MET and MET, which accounted mainly for THEMIS2-mediated effect on cancer stemness and chemoresistance. Increased THEMIS2 expression was associated with poor survival in TNBC patients and in patients from our breast cancer cohort. We found that non-cytotoxic dosages of cryptotanshinone (CPT) could potently inhibit cancer stemness, chemoresistance and tumorigenicity by suppressing expression of THEMIS2. Notably, stable overexpression of THEMIS2 is associated with enhanced sensitivity toward Capmatinib and CPT treatment. Expression levels of THEMIS2 and p-MET protein were positively correlated in the 465 breast cancer specimens. Our study revealed the novel oncogenic role of THEMIS2 and its underlying mechanism via suppressing PTP1B association with MET and thus leading to its activation. Our findings suggest that THEMIS2 could be a biomarker for MET targeted therapy and also provide a potential clinical application using low dosages of CPT for treatment of THEMIS2 positive TNBC.
Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are ...limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories.
We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: < 5.4%, 5.4%-5.6%, 5.7%-5.9%, 6.0%-6.4%, 6.5%-6.9%, 7.0%-7.9%, and ≥ 8.0%. The risks of IS/SE and major bleeding were compared among the groups after adjusting for baseline stroke and bleeding risk factors.
Compared with the patients with HbA1c level < 5.4%, IS/SE risk significantly increased at HbA1c levels higher than 6.5% adjusted hazard ratio (HR): 1.20, 95% confidence interval (CI): 1.00-1.43 for HbA1c level 6.5%-6.9%; 1.32, (95% CI 1.11-1.57) for HbA1c level 7.0%-7.9%; and 1.48 (95% CI 1.25-1.76) for HbA1c level ≥ 8.0%. These results were generally consistent in AF patients without OACs (n = 24,931). However, among 9105 patients receiving OACs, IS/SE risk was not higher for patients having higher HbA1c levels. The risk of major bleeding was comparable across all HbA1c categories. Compared with warfarin, DOACs were associated with lower risks of IS/SE (adjusted HR: 0.61, 95% CI 0.49-0.75) and major bleeding (adjusted HR: 0.30, 95% CI 0.21-0.42) without interactions across different HbA1c categories (all P interactions > 0.05).
For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level < 6.5% may be considered for eligible AF patients and should be tested in further prospective studies.
•Mesoporous bioactive glass (MBG) codoped with Cu and Ag, AgCu/80S, were successfully synthesized via a sol–gel method.•Cu increased the Ag ion release ability of the material by 1.2–1.6 times.•The ...composition ratio of Ag to Cu was Ag1Cu4/80S showed the best bioactivity.
In this study, through combining the antibacterial ability of silver (Ag) and the angiogenesis-promoting properties of copper (Cu), 80SiO2–15CaO–5P2O5-(5-x)Ag-xCuO (x = 0, 1, 2, 3, 4, and 5), Ag/Cu mesoporous bioactive glass (MBG) (AgCu/80S) were prepared using a sol-gel method. X-ray diffraction (XRD) and inductively coupled plasma-mass spectrometry (ICP-MS) were used to analyze the crystal phase, composition, and metal ion release ability of AgCu/80S. In vitro bioactive assay was used to evaluate AgCu/80S ability to form hydroxyapatite (HA) in phosphate-buffered saline (PBS). Human umbilical vein endothelial cell (HUVEC) migration and tube formation assays were performed to evaluate the angiogenesis-promoting properties of AgCu/80S.
The results of this study indicate that AgCu/80S has good bioactivity, antibacterial ability, and angiogenesis-promoting properties and is a multifunctional material with significant potential in the field of biomedicine.
•We successfully synthesized a multi-functional bioactive material, namely AgCu/80S, where silver possesses antibacterial activity, copper enhances the silver releasing, and 80S promotes the ...hydroxyapatite formation.•According to our review of the literature, Ag1Cu4/80S in our work is the first silver-copper co-incorporated bioactive glass and might possess multiple bio-functions.•Ag1Cu4/80S possessed a compromising metallic release but the lowest cytotoxicity and the highest antibacterial activity.
In this study, the sol-gel method was used to prepare bioactive glass capable of co-releasing silver and copper, named AgCu/80S. The thermal, crystal structure, bond, and composition were characterized by thermogravimetric analysis, X-ray diffraction analysis, and inductively coupled plasma mass spectrometry analysis, respectively. Disk diffusion tests, bacterial growth curve tests, and colony-forming tests were performed to assess the antibacterial activity of the bioactive glass. The textural results confirmed that silver and copper were successfully incorporated into the bioactive glasses. Moreover, the copper in AgCu/80S could enhance silver release to inhibit the growth of methicillin-resistant Staphylococcus aureus. In conclusion, we successfully synthesized a multi-functional bioactive material, namely AgCu/80S, where silver possesses antibacterial activity, copper enhances the silver releasing, and 80S promotes the hydroxyapatite formation. According to our review of the literature, AgCu/80S was the first silver-copper co-incorporated bioactive glass, but further functional investigations are necessary for its development.
Studies related to air pollution exposure and neurocognitive disorders, specifically cognitive impairment, among older adults are limited. We investigated the association between short-term and ...long-term exposure to ambient air pollution (i.e., particulate matter with an aerodynamic diameter of <10 μm and ozone) and the effects of their interaction on cognitive function in a community-dwelling, free-living elderly population. Study participants were in a multiple-wave representative sample, namely the Taiwan Longitudinal Study on Aging (n = 2241). In four surveys between 1996 and 2007, their cognitive function was assessed using the Short Portable Mental Status Questionnaire (SPMSQ). We estimated air pollution from 1993 to 2007, including daily concentrations of PM
and O
from air quality monitoring stations, based on the administrative zone of each participant's residence. Generalized linear mixed models were used to examine these associations after adjusting for covariates. We found that long-term exposure to PM
and O
was significantly associated with cognitive impairment (OR = 1.094, 95% CI: 1.020, 1.174 for PM
; OR = 1.878, 95% CI: 1.363, 2.560 for O
). The joint effect of exposure to PM
and O
was associated with cognitive impairment (
< 0.001). Co-exposure to ambient PM
and O
may deteriorate cognitive function in older adults.
Papaya ringspot virus (PRSV) limits papaya production worldwide. Previously, we generated transgenic lines of hybrid Tainung No.2 (TN-2) carrying the coat protein (CP) gene of PRSV with broad ...resistance to PRSV strains. Unfortunately, all of them were female, unacceptable for growers and consumers in practical applications. With our reported flanking sequences and the newly released papaya genomic information, the CP-transgene insert was identified at a non-coding region in chromosome 3 of the papaya genome, and the flanking sequences were verified and extended. The female transgenic line 16-0-1 was first used for backcrossing with the parental Sunrise cultivar six times and then followed by selfing three times. With multi-level molecular markers developed from the PRSV CP transgene and the genomic flanking sequences, the presence and zygosity of the CP transgene were characterized at the seedling stage. Meanwhile, hermaphrodite genotype was identified by a sex-linked marker. With homozygotic transgene and horticultural properties of Sunrise, a selected hermaphrodite individual was propagated by tissue culture (TC) and used as maternal progenitor to cross with non-transgenic parental cultivar Thailand to generate a new hybrid cultivar TN-2 with a hemizygotic CP-transgene. Three selected hermaphrodite individuals of transgenic TN were micropropagated by TC, and they showed broad-spectrum resistance to different PRSV strains from Taiwan, Hawaii, Thailand, and Mexico under greenhouse conditions. The selected clone TN-2 #1, with excellent horticultural traits, also showed complete resistance to PRSV under field conditions. These selected TC clones of hermaphrodite transgenic TN-2 provide a novel cultivation system in Taiwan and elsewhere.
Despite antiretroviral therapy, HIV-1 persists in memory CD4+ T cells, creating a barrier to cure. The majority of HIV-1 proviruses are defective and considered clinically irrelevant. Using cells ...from HIV-1-infected individuals and reconstructed patient-derived defective proviruses, we show that defective proviruses can be transcribed into RNAs that are spliced and translated. Proviruses with defective major splice donors (MSDs) can activate novel splice sites to produce HIV-1 transcripts, and cells with these proviruses can be recognized by HIV-1-specific cytotoxic T lymphocytes (CTLs). Further, cells with proviruses containing lethal mutations upstream of CTL epitopes can also be recognized by CTLs, potentially through aberrant translation. Thus, CTLs may change the landscape of HIV-1 proviruses by preferentially targeting cells with specific types of defective proviruses. Additionally, the expression of defective proviruses will need to be considered in the measurement of HIV-1 latency reversal.
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•The HIV-1 proviral landscape is dynamic and can change over time•Defective HIV-1 proviruses are transcribed, bypassing major splice donor defects•Defective HIV-1 proviruses (HIV-1def) can be translated in vitro and ex vivo•Cells with HIV-1dMSD and HIV-1hypermut can be recognized by cytotoxic T lymphocytes
Defective HIV-1 proviruses (HIV-1def) are considered clinically irrelevant. Pollack and Jones et al. find that HIV-1def can be transcribed, spliced, and translated. Cells containing HIV-1def can be recognized by cytotoxic T lymphocytes (CTLs). Thus, CTLs shape the proviral landscape, and the scope of CTL targets is larger than previously thought.
•Ovulatory follicular fluid exerts a long-lasting transformation activity covering throughout the ovulation cycle.•The ovulation injury-coagulation proteases-hepatocyte growth factor (HGF) cascade is ...responsible for the sustained activity.•Ovulation sources HGF into the peritoneal cavity, then into the blood circulation.•This coagulation-HGF cascade promotes the transformation of fallopian tube epithelial cells and ovarian cancer cells.•Physiologically, it promotes the growth of the corpus luteum and injured epithelium after ovulation.
The fallopian tube fimbrial epithelium, which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma. Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of fallopian tube epithelium. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor–thrombin–HGF activator (HGFA)–HGF cleavage cascade confers a sustained transformation activity to fallopian tube epithelium, high-grade serous carcinoma. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.
Hutchinson–Gilford progeria syndrome (HGPS) is a rare laminopathy that produces a mutant form of prelamin A, known as Progerin, resulting in premature aging. HGPS cells show morphological ...abnormalities of the nuclear membrane, reduced cell proliferation rates, accumulation of reactive oxygen species (ROS), and expression of senescence markers. Lysophosphatidic acid (LPA) is a growth factor‐like lipid mediator that regulates various physiological functions via activating multiple LPA G protein‐coupled receptors. Here, we study the roles of LPA and LPA receptors in premature aging. We report that the protein level of LPA3 was highly downregulated through internalization and the lysosomal degradation pathway in Progerin‐transfected HEK293 cells. By treating Progerin HEK293 cells with an LPA3 agonist (OMPT, 1‐Oleoyl‐2‐O‐methyl‐rac‐glycerophosphothionate) and performing shRNA knockdown of the Lpa3r transcript in these cells, we showed that LPA3 activation increased expression levels of antioxidant enzymes, consequently inhibiting ROS accumulation and ameliorating cell senescence. LPA3 was shown to be downregulated in HGPS patient fibroblasts through the lysosomal pathway, and it was shown to be crucial for ameliorating ROS accumulation and cell senescence in fibroblasts. Moreover, in a zebrafish model, LPA3 deficiency was sufficient to cause premature aging phenotypes in multiple organs, as well as a shorter lifespan. Taken together, these findings identify the decline of LPA3 as a key contributor to the premature aging phenotypes of HGPS cells and zebrafish.
In normal cells, activation of LPA3 stabilizes Nrf2 and enhances antioxidants to prevent accumulation of reactive oxygen species (ROS) and cell senescence. In Hutchinson–Gilford progeria syndrome (HGPS) cells, LPA3 is shown to be downregulated through high internalization and subsequent lysosomal degradation. The decline of LPA3 contributes to ROS accumulation and cell senescence of HGPS cells.
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