Dysfunction of degradation machineries causes cancers, including hepatocellular carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We previously reported that autophagy ...preferentially recruits and degrades the oncogenic microRNA (miR)‐224 to prevent HCC. Therefore, in the present study, we attempted to clarify whether cyclin D1 is another oncogenic factor selectively regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse correlation between low autophagic activity and high cyclin D1 expression in tumors of 147 HCC patients and three murine models, and these results taken together revealed a correlation with poor overall survival of HCC patients, indicating the importance of these two events in HCC development. We found that increased autophagic activity leads to cyclin D1 ubiquitination and selective recruitment to the autophagosome (AP) mediated by a specific receptor, sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation. Autophagy‐selective degradation of ubiquitinated cyclin D1 through SQSTM1 was confirmed using cyclin D1/ubiquitin binding site (K33‐238R) and phosphorylation site (T286A) mutants, lentivirus‐mediated silencing autophagy‐related 5 (ATG5), autophagy‐related 7 (ATG7), and Sqstm1 knockout cells. Functional studies revealed that autophagy‐selective degradation of cyclin D1 plays suppressive roles in cell proliferation, colony, and liver tumor formation. Notably, an increase of autophagic activity by pharmacological inducers (amiodarone and rapamycin) significantly suppressed tumor growth in both the orthotopic liver tumor and subcutaneous tumor xenograft models. Our findings provide evidence of the underlying mechanism involved in the regulation of cyclin D1 by selective autophagy to prevent tumor formation. Conclusion: Taken together, our data demonstrate that autophagic degradation machinery and the cell‐cycle regulator, cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of value in the development of alternative therapeutics for HCC patients. (Hepatology 2018;68:141‐154).
Medical professionals in thoracic medicine routinely analyze chest X-ray images, often comparing pairs of images taken at different times to detect lesions or anomalies in patients. This research ...aims to design a computer-aided diagnosis system that enhances the efficiency of thoracic physicians in comparing and diagnosing X-ray images, ultimately reducing misjudgments. The proposed system encompasses four key components: segmentation, alignment, comparison, and classification of lung X-ray images. Utilizing a public NIH Chest X-ray14 dataset and a local dataset gathered by the Chiayi Christian Hospital in Taiwan, the efficacy of both the traditional methods and deep-learning methods were compared. Experimental results indicate that, in both the segmentation and alignment stages, the deep-learning method outperforms the traditional method, achieving higher average IoU, detection rates, and significantly reduced processing time. In the comparison stage, we designed nonlinear transfer functions to highlight the differences between pre- and post-images through heat maps. In the classification stage, single-input and dual-input network architectures were proposed. The inclusion of difference information in single-input networks enhances AUC by approximately 1%, and dual-input networks achieve a 1.2-1.4% AUC increase, underscoring the importance of difference images in lung disease identification and classification based on chest X-ray images. While the proposed system is still in its early stages and far from clinical application, the results demonstrate potential steps forward in the development of a comprehensive computer-aided diagnostic system for comparative analysis of chest X-ray images.
Abstract
Rationale for review
Young adults of childbearing age and pregnant women are travelling more frequently to tropical areas, exposing them to specific arboviral infections such as dengue, zika ...and chikungunya viruses, which may impact ongoing and future pregnancies. In this narrative review, we analyse their potential consequences on pregnancy outcomes and discuss current travel recommendations.
Main findings
Dengue virus may be associated with severe maternal complications, particularly post-partum haemorrhage. Its association with adverse fetal outcomes remains unclear, but prematurity, growth retardation and stillbirths may occur, particularly in cases of severe maternal infection. Zika virus is a teratogenic infectious agent associated with severe brain lesions, with similar risks to other well-known TORCH pathogens. Implications of chikungunya virus in pregnancy are mostly related to intrapartum transmission that may be associated with severe neonatal infections and long-term morbidity.
Travel recommendations
Few agencies provide specific travel recommendations for travelling pregnant patients or couples trying to conceive and discrepancies exist, particularly regarding Zika virus prevention. The risks significantly depend on epidemiological factors that may be difficult to predict. Prevention relies principally on mosquito control measures. Couples trying to conceive and pregnant women should receive adequate information about the potential risks. It seems reasonable to advise pregnant women to avoid unnecessary travel to Aedes spp. endemic regions. The current rationale to avoid travel and delay conception is debatable in the absence of any epidemic. Post-travel laboratory testing should be reserved for symptomatic patients.
The ionospheric total electron content (TEC) derived from dense ground‐based Global Navigation Satellite System receivers over the continental United States and those from global ionosphere maps are ...utilized to find the ionosphere response to the August 21, 2017 total solar eclipse. Maximum obscurations and their associated TEC major depressions appear simultaneously at midlatitudes, while major depressions elongate toward the magnetic equator with some delays in the equatorial ionization anomaly (EIA) region. The former is due to the photochemical loss process, while the latter is caused by the plasma transport of E×B drifts and lunar gravitation forces. TECs of predawn reductions, morning enhancements, afternoon reductions, and nighttime enhancements reveal that the semidiurnal lunar tide are essential. Since a solar eclipse always occurs on a new moon day, the lunar tide results in the early EIA appearance and major depressions being underestimated/diminished before and overestimated/enhanced after about 14:00 local time.
Plain Language Summary
Observations during an eclipse offer a special opportunity for studying the Earth's ionospheric response to changes in solar ionizing radiation. Although ionospheric solar eclipse signatures in many events have been studied, we report the lunar tide effect on the signatures for the first time. A total solar eclipse swept across the continental United States (CONUS) from the west to east coast on August 21, 2017. The total electron content (TEC) along seven longitudes of the US continent derived from more than 2,200 ground‐based Global Navigation Satellite System receivers in the CONUS and extracted from global ionosphere maps (GIMs) is employed to study ionospheric solar eclipse signatures. The most prominent solar eclipse signature is major depressions (MDs) in both the CONUS and GIM TECs, when the maximum obscuration occurs. TEC extrema of predawn reductions, morning enhancements, afternoon reductions, and nighttime enhancements reveal that the semidiurnal lunar tide of about 12.42‐h period is prominent. The lunar tide causes the early appearance of equatorial ionization anomalies, which further results in the MDs being weakened in the morning and enhanced in the afternoon on the solar eclipse day. The lunar tide has to be taken into consideration for studying ionospheric solar eclipse effects.
Key Points
The lunar tide results in the early appearance of the equatorial ionization anomaly on solar eclipse days
Total electron contents tend to enhance before and decrease after 14:00 local time (LT) on a solar eclipse day
The lunar tide causes major depressions being weakened before and enhanced after 14:00 LT
Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus ...infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive. Here, we show that glycoprotein E (gE) binds to the cellular protein, annexin A1 (Anx-A1) to enhance infection. Anx-A1 can be detected on the surface of cells permissive for HSV-1 before infection and on virions. Suppression of Anx-A1 or its receptor, formyl peptide receptor 2 (FPR2), on the cell surface and gE or Anx-A1 on HSV-1 envelopes reduced virus binding to cells. Importantly, Anx-A1 knockout, Anx-A1 knockdown, or treatments with the FPR2 antagonist reduced the mortality and tissue viral loads of infected mice. Our results show that Anx-A1 is a novel enhancing factor of HSV-1 infection. Anx-A1-deficient mice displayed no evident physiology and behavior changes. Hence, targeting Anx-A1 and FPR2 could be a promising prophylaxis or adjuvant therapy to decrease HSV-1 lethality.
In this study, a highly responsive humidity sensor is developed by printing gold nanoparticles (GNPs) grafted with a hygroscopic polymer. These GNPs are inkjet-printed to form a uniform thin film ...over an interdigitated electrode with a controllable thickness by adjusting the printing parameters. The resistance of the printed GNP thin film decreases significantly upon exposure to water vapor and exhibits a semi-log relationship with relative humidity (RH). The sensor can detect RH variations from 1.8 to 95% with large resistance changes up to 4 orders of magnitude with no hysteresis and small temperature dependence. In addition, with a small thickness, the sensor can reach absorption equilibrium quickly with response and recovery times of ≤1.2 and ≤3 s, respectively. The fast response to humidity changes also allows the GNP thin-film sensor to distinguish signals from intermittent humidification/dehumidification cycles with a frequency up to 2.5 Hz. The printed sensors on flexible substrates show little sensitivity to bending deformation and can be embedded in a mask for human respiratory detection. In summary, this study demonstrates the feasibility of applying printing technology for the fabrication of thin-film humidity sensors, and the methodology developed can be further applied to fabricate many other types of nanoparticle-based sensor devices.
Exposure to air pollution during pregnancy leads to adverse pregnancy outcomes. Few studies have evaluated the influences of air quality, including environmental tobacco smoke (ETS) and particulate ...matter (PM), on fetal development, which this study examined. This longitudinal correlation study used multiple linear regression data analysis of PM2.5/PM10, self-reported ETS exposure, urinary cotinine level, maternal characteristics, and birth parameters (gestational week, body weight, body length, head, and chest circumferences) with the effect of air quality on fetal growth. The study included 74 pregnant women (mean age 31.9 ± 4.2 years, body mass index 23.6 ± 3.8 kg/m2, average gestational duration 38.5 ± 0.8 weeks). ETS exposure decreased birth length by ≥1 cm, and potentially is an independent risk factor for fetal growth restriction, and pregnant women should avoid indoor and outdoor ETS. However, neither PM2.5/PM10 nor ETS was associated with low birth weight or small for gestational age. This study adds to the evidence base that ETS exposure of nonsmoking pregnant women affects the fetal birth length. Family members should refrain from smoking near expectant mothers, although smoking in the vicinity of their residential surroundings potentially exposes mothers and their fetuses to ETS. Public pollution and childbirth education classes should include details of indoor ETS.
Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and ...enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.
This study was conducted to investigate the β-carotene status in osteoarthritis (OA) patients and examine its relationships with the risk of inflammation and metabolic syndrome. OA patients were ...stratified by obesity based on body fat percentage (obese OA, n = 44; non-obese OA, n = 56), and sixty-nine subjects without OA or obesity were assigned as a non-obese control group. β-carotene, metabolic parameters, and inflammation status were assessed. Obese OA patients exhibited a significantly higher rate of metabolic syndrome (p = 0.02), abdominal obesity (p < 0.01), and lower β-carotene status (p < 0.01) compared with non-obese OA and non-obese controls. After adjusting for potential confounders, β-carotene status (≥0.8 µM) was significantly inversely correlated with the risk of metabolic syndrome (odds ratio = 0.27, p < 0.01), abdominal obesity (odds ratio = 0.33, p < 0.01), high blood pressure (odds ratio = 0.35, p < 0.01), hyperglycemia (odds ratio = 0.45, p < 0.05), and inflammation (odds ratio = 0.30, p = 0.01). Additionally, subjects who had a high β-carotene status with a low proportion of metabolic syndrome when they had a low-grade inflammatory status (p < 0.01). Obese OA patients suffered from a higher prevalence of metabolic syndrome and lower β-carotene status compared to the non-obese controls. A better β-carotene status (≥0.8 µM) was inversely associated with the risk of metabolic syndrome and inflammation, so we suggest that β-carotene status could be a predictor of the risk of metabolic syndrome and inflammation in patients with and without OA.
PDF
