L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate ...is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
Members of the orchid family occupy many germination niches, in terrestrial, epiphytic and epilithic environments. How orchid seeds attach to their substrate and survive after dispersal is largely ...unknown. C-lignin is a recently discovered specialized lignin, found in seed coats of some plants, including orchid species, but its functional and biological significance is obscure. We studied seed coat ontogenesis in three species (Neuwiedia veratrifolia, Cypripedium formosanum and Phalaenopsis aphrodite) that represent basal and advanced branches in orchid phylogeny and divergent life forms. From each species, controlled pollination yielded several stages of seed development, from which seed coats (testa) were isolated and analysed by ATR-FT-IR spectroscopy. The use of the ATR set-up ensured that the chemical information originated only from the integral outer seed surface layers. The FT-IR bands of C-lignin are presented here for the first time, and distinguished from bands of G/S-lignin. In the seed coats, C-lignin developed after G/S-lignin in N. veratrifolia and C. formosanum, while only G/S-lignin developed in P. aphrodite. We discuss C-lignin properties and possible function in relation to seed coat properties. The species differed with respect to sequence and amounts of deposition, not only of lignins but also lipids, resulting in differences in mature seed coat compositions. Thus we revealed an unexpected and marked diversity among orchids with respect to seed surface chemistry, with possible implications for seed and germination ecology.
Despite the well-established role of oncogenic RAS in promoting tumor formation, whether and how wild-type (WT) Ras inhibits tumorigenesis under physiological conditions remains controversial. Here, ...we show that in a fraction of endogenous oncogenic Kras-induced hematopoietic malignancies, including acute T-cell lymphoblastic leukemia/lymphoma (T-ALL) and myeloproliferative neoplasm (MPN), WT Kras expression is lost through epigenetic or genetic mechanisms. Using conditional Kras(G12D/-) mice, we find that WT Kras deficiency promotes oncogenic Kras-induced MPN, but not T-ALL, in a cell-autonomous manner. Loss of WT Kras rescues oncogenic Kras-mediated hematopoietic stem cell depletion and further enhances granulocyte-macrophage colony-stimulating factor signaling in myeloid cells expressing oncogenic Kras. Quantitative signaling studies reveal that oncogenic Kras but not oncogenic Nras leads to cross-activation of WT Ras, whereas loss of WT Kras further promotes the activation of all Ras isoforms. Our results demonstrate the tumor suppressor function of WT Kras in oncogenic Kras-induced leukemogenesis and elucidate its underlying cellular and signaling mechanisms.
We compare the dust attenuation properties of two samples of galaxies purely selected in the Galaxy Evolution Explorer (GALEX) near-ultraviolet band (NUV; 1750-2750 Å, λmean=2310 Å) and in the ...far-infrared (FIR) at 60 μm. These samples are built using the GALEX and IRAS sky surveys over ~600 deg2. The NUV-selected sample contains 95 galaxies detected down to NUV=16 mag (AB system). Eighty-three galaxies in this sample are spiral or irregular, and only two of them are not detected at 60 μm. The FIR-selected sample is built from the IRAS PSCz survey, which is complete down to 0.6 Jy. Among the 163 sources, we select 118 star-forming galaxies that are well measured by IRAS; all but one are detected in NUV, and 14 galaxies are not detected in the far-ultraviolet band (FUV; 1350-1750 Å, λmean=1530 Å). The dust-to-ultraviolet (NUV and FUV) flux ratio is calibrated to estimate the dust attenuation at both wavelengths. The median value of the attenuation in NUV is found to be ~1 mag for the NUV-selected sample, versus ~2 mag for the FIR-selected one. Within both samples, the dust attenuation is found to correlate with the luminosity of the galaxies. Almost all the NUV-selected galaxies and two-thirds of the FIR-selected sample exhibit a lower dust attenuation than expected from the tight relation found previously for starburst galaxies between dust attenuation and the slope of the ultraviolet continuum. The situation is reversed for the remaining third of the FIR-selected galaxies: their extinction is higher than that deduced from their FUV-NUV color and the relation for starbursts.
Abstract
Study Objectives
To investigate the short- and longer-term impact of a 45-min delay in school start time on sleep and well-being of adolescents.
Methods
The sample consisted of 375 students ...in grades 7–10 (mean age ± SD: 14.6 ± 1.15 years) from an all-girls’ secondary school in Singapore that delayed its start time from 07:30 to 08:15. Self-reports of sleep timing, sleepiness, and well-being (depressive symptoms and mood) were obtained at baseline prior to the delay, and at approximately 1 and 9 months after the delay. Total sleep time (TST) was evaluated via actigraphy.
Results
After 1 month, bedtimes on school nights were delayed by 9.0 min, while rise times were delayed by 31.6 min, resulting in an increase in time in bed (TIB) of 23.2 min. After 9 months, the increase in TIB was sustained, and TST increased by 10.0 min relative to baseline. Participants also reported lower levels of subjective sleepiness and improvement in well-being at both follow-ups. Notably, greater increase in sleep duration on school nights was associated with greater improvement in alertness and well-being.
Conclusions
Delaying school start time can result in sustained benefits on sleep duration, daytime alertness, and mental well-being even within a culture where trading sleep for academic success is widespread.
This study is an epidemiologic investigation of nosocomial severe fever with thrombocytopenia syndrome virus (SFTSV) transmission among healthcare workers (HCWs) after contact with an index patient. ...The aim of this study was to determine whether exposure to blood or bloody respiratory secretion is associated with human-to-human transmission of SFTSV.
Eleven days after the index patient died, two HCWs who had close exposure to the patient presented with typical symptoms of SFTS. An epidemiological investigation was conducted on all 25 HCWs who had been in close contact with the index patient. Clinical and laboratory data were collected, and transmission rate before and after the index patient had haemorrhagic manifestations was analysed.
Among 25 HCWs who had direct contact with the index patient, five HCWs were confirmed to have SFTS. All five HCWs had contact to blood or bloody respiratory secretions of the index patient without adequate use of personal protective equipment (PPE). No HCW with contact before haemorrhagic manifestations of the index patient contracted SFTS. Overall, the transmission rate was higher for HCWs who had contact after the index patient had haemorrhagic manifestations (33.3%, five of 15 HCWs, vs. 0%, zero of ten HCWs, p 0.041).
In HCWs who are inadequately protected, person-to-person transmission of SFTSV may be associated with contact with blood or bloody respiratory secretions. Therefore, universal precaution and full PPE is highly recommended for protection against SFTSV when there are signs of bleeding.
Background
Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well ...established.
Methods
Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large‐volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities.
Results
Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non‐surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection.
Conclusion
Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.
For the select few
A low‐power antenna switch driver circuit with RF leakage suppression and fast switching time is implemented in a 0.25 μm silicon‐on‐insulator (SOI) CMOS process. It is composed of a three‐stage ...current starved ring oscillator with a clock buffer, a charge pump and a latch‐based three‐state logic driver. The negative voltage from the charge pump is fed into the latch‐based three‐state logic driver, and it generates three states of logic level (+VDD, GND and −VDD) according to the decoder signal without any reliability issue. In addition, the proposed three‐state logic driver with an optimal negative resistance value reduces the amount of the RF leakage coupling into the charge pump while maintaining its switching time fast. In the measurement, the designed switch driver circuit shows <0.1 V of voltage loss under 150 μA of current consumption. A single‐pole double‐throw antenna switch employing the proposed switch driver circuit is implemented in a 0.25 μm SOI CMOS process. The measurement shows higher than +38 dBm of 1 dB compression point (P1dB) and 140 ns of switching time while allowing <0.5 dB of insertion loss and >30 dB of isolation over 100 MHz to 3 GHz frequency range.
Magnetic biosensors, based on nanomaterials and miniature electronics, have emerged as a powerful diagnostic platform. Benefiting from the inherently negligible magnetic background of biological ...objects, magnetic detection is highly selective even in complex biological media. The sensing thus requires minimal sample purification and yet achieves a high signal-to-background contrast. Moreover, magnetic sensors are also well-suited for miniaturization to match the size of biological targets, which enables sensitive detection of rare cells and small amounts of molecular markers. We herein summarize recent advances in magnetic sensing technologies, with an emphasis on clinical applications in point-of-care settings. Key components of sensors, including magnetic nanomaterials, labeling strategies and magnetometry, are reviewed.
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