White light generation by mixing red, green, and blue laser diodes (RGB LDs) was demonstrated with Commission International de l'Eclairage coordinates of (0.2928, 0.2981), a correlated color ...temperature of 8382 K, and a color rendering index of 54.4 to provide a maximal illuminance of 7540 lux. All the white lights generated using RGB LDs were set within the risk group-1 criterion to avoid the blue-light hazard to human eyes. In addition, the RGB-LD mixed white light was diffused using a frosted glass to avoid optical aberration and to improve the performance of the lighting source. In addition, visible light communication (VLC) by using RGB-LD mixed white-light carriers and a point-to-point scheme over 1 m was performed in the directly modulated 16-QAM OFDM data format. In back-to-back transmission, the maximal allowable data rate at 10.8, 10.4, and 8 Gbps was determined for R, G, and B LDs, respectively. Moreover, the RGB-LD mixed white light-based indoor wavelength-division multiplexing (WDM)-VLC system yielded a total allowable transmission data rate of 8.8 Gbps over 0.5 m in free space. Such a high-speed RGB-LD mixed WDM-VLC system without any channel interference can be used to simultaneously provide data transmission and white lighting in an indoor environment.
To enable high-speed underwater wireless optical communication (UWOC) in tap-water and seawater environments over long distances, a 450-nm blue GaN laser diode (LD) directly modulated by pre-leveled ...16-quadrature amplitude modulation (QAM) orthogonal frequency division multiplexing (OFDM) data was employed to implement its maximal transmission capacity of up to 10 Gbps. The proposed UWOC in tap water provided a maximal allowable communication bit rate increase from 5.2 to 12.4 Gbps with the corresponding underwater transmission distance significantly reduced from 10.2 to 1.7 m, exhibiting a bit rate/distance decaying slope of -0.847 Gbps/m. When conducting the same type of UWOC in seawater, light scattering induced by impurities attenuated the blue laser power, thereby degrading the transmission with a slightly higher decay ratio of 0.941 Gbps/m. The blue LD based UWOC enables a 16-QAM OFDM bit rate of up to 7.2 Gbps for transmission in seawater more than 6.8 m.
Mitochondrial Ca(2+) uptake, a process crucial for bioenergetics and Ca(2+) signaling, is catalyzed by the mitochondrial calcium uniporter. The uniporter is a multi-subunit Ca(2+)-activated Ca(2+) ...channel, with the Ca(2+) pore formed by the MCU protein and Ca(2+)-dependent activation mediated by MICU subunits. Recently, a mitochondrial inner membrane protein EMRE was identified as a uniporter subunit absolutely required for Ca(2+) permeation. However, the molecular mechanism and regulatory purpose of EMRE remain largely unexplored. Here, we determine the transmembrane orientation of EMRE, and show that its known MCU-activating function is mediated by the interaction of transmembrane helices from both proteins. We also reveal a second function of EMRE: to maintain tight MICU regulation of the MCU pore, a role that requires EMRE to bind MICU1 using its conserved C-terminal polyaspartate tail. This dual functionality of EMRE ensures that all transport-competent uniporters are tightly regulated, responding appropriately to a dynamic intracellular Ca(2+) landscape.
We report a protocol for alkene hydroxyalkenylation. Using a persulfate anion as a one‐electron‐oxidation reagent and 1,2‐bis(phenylsulfonyl)ethylene as a radical acceptor in the presence of water, ...alkenes were converted into the corresponding 1‐phenylsulfonyl‐4‐hydroxyalkenes in good to high yields. The hydroxyalkenylation process involves the nucleophilic hydroxylation of alkene radical cations to give β‐hydroxyalkyl radicals, which, after a radical addition/β‐elimination sequence, provide the products. We also report a photocatalytic protocol for alkoxyalkenylation.
A simple protocol for alkene hydroxyalkenylation by 1,2‐bis(phenylsulfonyl)ethylene was developed using persulfate anion as a one‐electron oxidizing reagent. Regioselective hydroxyalkenylation was observed for a variety of substituted alkenes. A photocatalytic protocol for alkoxyalkenylation using an acridinium salt was also successful.
We report on a protocol for the hydroxyalkenylation of alkenes using an acridinium photoredox catalyst in combination with 1,2‐bis(phenylsulfonyl)ethylene and water. Using the protocol, alkenes could ...be converted into the corresponding 1‐phenylsulfonyl‐4‐hydroxyalkenes in good yields. The hydroxyalkenylation involves the nucleophilic hydroxylation of alkene‐derived radical cations to give β‐hydroxyalkyl radicals, which then undergo a radical addition/β‐elimination sequence. The catalytic cycle is likely sustained by electron transfer from the acridine radical to the benzenesulfonyl radical, which is formed via a radical addition/elimination sequence.
Hydroxyalkenylation of alkenes with 1,2‐bis(phenylsulfonyl)ethene and water was affected by photocatalytic electron‐transfer protocol using acridinium photocatalyst A.
Abstract The epithelial-mesenchymal transition (EMT) regulator, Slug, plays multifaceted roles in controlling lung cancer progression, but its downstream targets and mechanisms in promoting lung ...cancer progression have not been well defined. In particular, the miRNAs downstream of Slug in non-small cell lung cancer (NSCLC) remain undetermined. Here, we report that miR-137 is downstream of the EMT regulator, Slug, in lung cancer cells. Slug binds directly to the E-box of the miR-137 promoter and up-regulates its expression in lung cancer cells. Knockdown of miR-137 abolished Slug-induced cancer invasion and migration, whereas upregulation of miR-137 was found to trigger lung cancer cell invasion and progression by direct suppressing TFAP2C (transcription factor AP-2 gamma). Clinical data showed that lung adenocarcinoma patients with low-level expression of Slug and miR-137 but high-level expression of TFAP2C experienced significantly better survival. miR-137 is a Slug-induced miRNA that relays the pro-metastatic effects of Slug by targeting TFAP2C. Our findings add new components to the Slug-mediated regulatory network in lung cancer, and suggest that Slug, miR-137, and TFAP2C may be useful prognostic markers in lung adenocarcinoma.
CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated ...glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.
Asthma, a major non‐communicable disease, affects both adults and children and is associated with high morbidity compared with other chronic diseases. The glycolysis‐associated activation of type ...2 helper T (Th2) cells is the critical immunopathological mechanism involved in asthma deterioration. Long‐term use of steroids as a medical treatment for asthma induces side effects and resistance. Pterostilbene (PS), a stilbenoid compound found in blueberry and vines, exhibits antihyperglycemic and anti‐inflammatory properties. Thus, we hypothesized that the modulation of T cell immunity by PS may be an applicable intervention to treat asthma. Airway hyperresponsiveness, interleukin (IL)‐4 and IL‐13 levels, IgE, IgG, pulmonary infiltrated monocytes and eosinophils, and mucosubstances were measured in house dust mite (HDM)‐induced asthmatic mice under PS treatment. Bioenergetic metabolism, PI3K‐mTOR signalling, GATA3 expression and histone acetylation in PS‐treated Th2 cells were investigated. PS improved HDM‐induced pulmonary allergic airway inflammation by inhibiting Th2 cell and eosinophil accumulation in HDM asthmatic mice both in the preventive and therapeutic models. Targeting glycolysis resulted in IL‐4 inhibition via the downregulation of mTOR, GATA3 and histone acetylation in PS‐treated Th2 cells. Glucose supplementation reversed the inhibitory effect of PS on Th2 cells in vitro. Adoptive transfer with glucose‐treated Th2 cells enhanced Th2 activation and eosinophilic accumulation in PS‐treated asthmatic mice. Furthermore, PS significantly inhibited IL‐4 production of CD4+ T cells from the peripheral blood mononuclear cells of patients with asthma. PS attenuates HDM‐induced asthma via the inhibition of the Glut1/mTOR/GATA3 axis in Th2 cells, which supports the potential pharmaceutical application of PS treatment for asthma.
The inhibition of glycolysis by blocking glucose transportation is involved in pterostilbene's anti‐Th2 and anti‐eosinophil immune responses, which relieve bronchoconstriction. The downregulation of the mTOR‐GATA3 axis contributed to epigenetic changes through histone deacetylation in pterostilbene‐treated Th2 cells and ultimately led to a decrease in IL‐4 and IL‐13.
Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with an anti‐ vascular endothelial growth factor (VEGF) agent, bevacizumab or ramucirumab, is indicated for advanced ...lung adenocarcinoma harboring EGFR mutation. This study aimed to show the real‐world data of combination therapy and compare the effectiveness between bevacizumab and ramucirumab in combination with an EGFR‐TKI. This retrospective study enrolled 47 patients diagnosed of stage IV lung adenocarcinoma with exon 19 deletion or L858R point mutation, receiving a first‐line EGFR‐TKI with anti‐VEGF agent, including 34 (72%) and 13 (28%) patients receiving bevacizumab and ramucirumab, respectively. The response rate was similar in both groups (p = 0.38). Patients receiving bevacizumab had similar progression free survival (PFS) as those receiving ramucirumab (median PFS: 21.9 vs. 24.2 months, p = 0.4871); similar finding was noted in overall survival (OS) (median OS: 33.5 months vs. not reached, p = 0.4618). Patients receiving ramucirumab experienced a significantly high‐grade hypertension compared to those receiving bevacizumab (p = 0.0351). Multivariable Cox regression analysis found independent risk factors for worse PFS included poorer ECOG performance status, multiple (≥3) metastatic sites, brain metastasis, and pleural metastasis/effusion, while the type of anti‐VEGF agent was not a risk factor. Pericardial metastasis/effusion was the only one independent risk factor for worse OS. In summary, ramucirumab may have similar effectiveness as bevacizumab in combination with an EGFR‐TKI as first line therapy for advanced lung adenocarcinoma harboring susceptible EGFR mutation. Further large‐scale registry‐based cohort studies may be needed to validate our findings.
Our study aimed to explore the impact of different home‐ and community‐based service (HCBS) use patterns on older adults' physical function. The cohort data were drawn from two national datasets, the ...National Ten‐Year Long‐Term Care Plan 1.0 database and the National Health Insurance Program claims data. Participants were care recipients ages 65 and over, first evaluated and prescribed HCBS from 2010 through 2013 and evaluated again after 6 months (n = 32,392). Latent class analysis was used to identify subgroups with different HCBS use patterns. Multiple regression was used to examine the impact of different HCBS use patterns on change over time in disability related to activities of daily living (ADLs) and instrumental activities of daily living (IADLs). The analysis was stratified by respondents' levels of disability. Four subgroups of HCBS recipients were identified, with patterns of home‐based personal care, home‐based personal care and medical care, home‐based medical care and community care services. Older adults in the Home‐based MpC had significantly more improvement in both ADL (p < 0.05) and IADL (p < 0.001) scores compared with adults in the other three groups, while the community care group regressed the most. In the stratified analysis of the severely disabled, the IADL outcome of the Home‐based MC group was better than the home‐based PC group (p < 0.001). Study findings shed light on the benefits of promoting the use of integrated HCBS that combines personal and medical care, especially for community care services.
PDF
