Using microRNA (miRNA) expression array, we identified that miR-7 was deregulated in colorectal cancer (CRC). We studied the biological role and molecular target of miR-7 in CRC. miR-7 was ...downregulated in six out of seven colon cancer cell lines. Ectopic expression of miR-7 suppressed colon cancer cell proliferation (P<0.05), induced apoptosis (P<0.05) and caused cell-cycle arrest in G1 phase (P<0.05). The tumor suppressive function of miR-7 was further confirmed in nude mice (P<0.05). The 3'-untranslated region (3'UTR) of Yin Yang 1 (YY1) mRNA contains an evolutionarily conserved miR-7 binding site using in silico searches, luciferase reporter assay and western blot analysis confirmed that miR-7 directly bound to YY1 3'UTR to negatively regulate the protein expression of YY1 in colon cancer cell lines HCT116 and LOVO. Intriguingly, knock-down of YY1 in three colon cancer cell lines (HCT116, LOVO and DLD1) consistently suppressed cell proliferation (P<0.01) and induced apoptosis (P<0.01), indicating the opposite functions of miR-7 and YY1 in CRC. Consistent with these data, ectopic expression of YY1 promoted cell growth by increasing proliferation (P<0.01) and suppressing apoptosis (P<0.001). The tumorigenic ability of YY1 was further confirmed in vivo in xenograft-nude mouse model (P<0.01). In addition, pathway analyses revealed that the oncogenic effect by YY1 was associated with inhibiting p53 and modulating its downstream effectors p15, caspase cascades and C-Jun, and activating Wnt signaling pathway through activating β-catenin, anti-apoptotic survivin and fibroblast growth factor 4. Furthermore, multivariate analysis revealed that patients with YY1 protein high expression had a significant decrease in overall survival, and Kaplan-Meier survival curves showed that these patients had significantly shorter survival than others (P<0.0001). In conclusion, MiR-7 is a novel miRNA with tumor suppressive function in colon cancer by targeting oncogenic YY1. YY1 promotes colon cancer growth through inhibiting p53 and promoting Wnt signaling pathways and serves as an independent prognostic biomarker for CRC patients.
Logical qubit encoding and quantum error correction (QEC) protocols have been experimentally demonstrated in various physical systems with multiple physical qubits, generally without reaching the ...break-even point, at which the lifetime of the quantum information exceeds that of the single best physical qubit within the logical qubit. Logical operations are challenging, owing to the necessary non-local operations at the physical level, making bosonic logical qubits that rely on higher Fock states of a single oscillator attractive, given their hardware efficiency. QEC that reaches the break-even point and single logical-qubit operations have been demonstrated using the bosonic cat code. Here, we experimentally demonstrate repetitive QEC approaching the break-even point of a single logical qubit encoded in a hybrid system consisting of a superconducting circuit and a bosonic cavity using a binomial bosonic code. This is achieved while simultaneously maintaining full control of the single logical qubit, including encoding, decoding and a high-fidelity universal quantum gate set with 97% average process fidelity. The corrected logical qubit has a lifetime 2.8 times longer than that of its uncorrected counterpart. We also perform a Ramsey experiment on the corrected logical qubit, reporting coherence twice as long as for the uncorrected case.Repeated error correction creates a logical qubit encoded in the hybrid state of a superconducting circuit and a bosonic cavity, which is shown to be fully controllable under a universal single-qubit gate set.
Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep ...convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods.
In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard.
For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886–0·936) in the internal dataset, 0·870 (95% CI 0·822–0·918) in external validation dataset 1, and 0·831 (95% CI 0·793–0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% 85·0–90·2 vs 78·3% 72·1–84·5, p<0·0001; 82·7% 78·5–86·9 vs 70·4% 59·1–81·7, p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05).
The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists’ accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials.
National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.
Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small-cell lung cancer (NSCLC). The aim of our study was to determine prognostic risk factors and establish a novel nomogram ...for lung adenocarcinoma patients. Methods: This retrospective cohort study is based on the Surveillance, Epidemiology, and End Results (SEER) database and the Chinese multicenter lung cancer database. We selected 22,368 eligible LUAD patients diagnosed between 2010 and 2015 from the SEER database and screened them based on the inclusion and exclusion criteria. Subsequently, the patients were randomly divided into the training cohort (n = 15,657) and the testing cohort (n = 6711), with a ratio of 7:3. Meanwhile, 736 eligible LUAD patients from the Chinese multicenter lung cancer database diagnosed between 2011 and 2021 were considered as the validation cohort. Results: We established a nomogram based on each independent prognostic factor analysis for 1-, 3-, and 5-year overall survival (OS) . For the training cohort, the area under the curves (AUCs) for predicting the 1-, 3-, and 5-year OS were 0.806, 0.856, and 0.886. For the testing cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.804, 0.849, and 0.873. For the validation cohort, AUCs for predicting the 1-, 3-, and 5-year OS were 0.86, 0.874, and 0.861. The calibration curves were observed to be closer to the ideal 45° dotted line with regard to 1-, 3-, and 5-year OS in the training cohort, the testing cohort, and the validation cohort. The decision curve analysis (DCA) plots indicated that the established nomogram had greater net benefits in comparison with the Tumor-Node-Metastasis (TNM) staging system for predicting 1-, 3-, and 5-year OS of lung adenocarcinoma patients. The Kaplan–Meier curves indicated that patients’ survival in the low-risk group was better than that in the high-risk group (P < .001). Conclusion: The nomogram performed very well with excellent predictive ability in both the US population and the Chinese population.
Quantum key distribution (QKD) is a quantum communication technology that promises unconditional communication security. High-performance and cost-effective QKD systems are essential for the ...establishment of quantum communication networks1–3. By integrating all the optical components (except the laser source) on a silicon photonic chip, we have realized a stable, miniaturized and low-cost system for continuous-variable QKD (CV-QKD) that is compatible with the existing fibre optical communication infrastructure4. Here, the integrated silicon photonic chip is demonstrated for CV-QKD. It implements the widely studied Gaussian-modulated coherent state protocol that encodes continuous distributed information on the quadrature of laser light5,6. Our proof-of-principle chip-based CV-QKD system is capable of producing a secret key rate of 0.14 kbps (under collective attack) over a simulated distance of 100 km in fibre, offering new possibilities for low-cost, scalable and portable quantum networks.
BRAF plays an indispensable role in activating the MEK/ERK pathway to drive tumorigenesis. Receptor tyrosine kinase and RAS-mediated BRAF activation have been extensively characterized, however, it ...remains undefined how BRAF function is fine-tuned by stimuli other than growth factors. Here, we report that in response to proinflammatory cytokines, BRAF is subjected to lysine 27-linked poly-ubiquitination in melanoma cells by the ITCH ubiquitin E3 ligase. Lysine 27-linked ubiquitination of BRAF recruits PP2A to antagonize the S365 phosphorylation and disrupts the inhibitory interaction with 14-3-3, leading to sustained BRAF activation and subsequent elevation of the MEK/ERK signaling. Physiologically, proinflammatory cytokines activate ITCH to maintain BRAF activity and to promote proliferation and invasion of melanoma cells, whereas the ubiquitination-deficient BRAF mutant displays compromised kinase activity and reduced tumorigenicity. Collectively, our study reveals a pivotal role for ITCH-mediated BRAF ubiquitination in coordinating the signals between cytokines and the MAPK pathway activation in melanoma cells.
Abstract Background Indoor exposure to fine particulate matter (PM2.5 ) from outdoor sources is a major health concern, especially in highly polluted developing countries such as China. Few studies ...have evaluated the effectiveness of indoor air purification on the improvement of cardiopulmonary health in these areas. Objectives This study sought to evaluate whether a short-term indoor air purifier intervention improves cardiopulmonary health. Methods We conducted a randomized, double-blind crossover trial among 35 healthy college students in Shanghai, China, in 2014. These students lived in dormitories that were randomized into 2 groups and alternated the use of true or sham air purifiers for 48 h with a 2-week washout interval. We measured 14 circulating biomarkers of inflammation, coagulation, and vasoconstriction; lung function; blood pressure (BP); and fractional exhaled nitric. We applied linear mixed-effect models to evaluate the effect of the intervention on health outcome variables. Results On average, air purification resulted in a 57% reduction in PM2.5 concentration, from 96.2 to 41.3 μg/m3 , within hours of operation. Air purification was significantly associated with decreases in geometric means of several circulating inflammatory and thrombogenic biomarkers, including 17.5% in monocyte chemoattractant protein-1, 68.1% in interleukin-1β, 32.8% in myeloperoxidase, and 64.9% in soluble CD40 ligand. Furthermore, systolic BP, diastolic BP, and fractional exhaled nitrous oxide were significantly decreased by 2.7%, 4.8%, and 17.0% in geometric mean, respectively. The impacts on lung function and vasoconstriction biomarkers were beneficial but not statistically significant. Conclusions This intervention study demonstrated clear cardiopulmonary benefits of indoor air purification among young, healthy adults in a Chinese city with severe ambient particulate air pollution. (Intervention Study on the Health Impact of Air Filters in Chinese Adults; NCT02239744 )
NiCo2S4 single-shelled hollow polyhedrons (SSHPs) and double-shelled hollow polyhedrons (DSHPs) were synthesized by the same metal-organic-framework-engaged strategy that took advantage of the unique ...reactions of zeolitic imidazolate framework-67 and Ni(NO3)2, H2O, thiacetamide. It was found by XRD, SEM, TEM that the synthesized NiCo2S4 materials showed the hollow polyhedron structure assembled with nanocrystalline (the size was around 10–15 nm), and numerous mesopores existed among these nanocrystalline. As anode materials for lithium-ion batteries, NiCo2S4 SSHPs and DSHPs exhibited excellent cycling stability, but DSHPs were remarkably superior to SSHPs in terms of capacity performance and rate capability. At 0.1C, DSHPs could deliver the discharge capacity of 770.3 mAh g−1 at the 100th cycle, and the average discharge capacity over 100 cycles reached 745.5 mAh g−1. When the current came back to 0.1C after rate measurements, NiCo2S4 DSHPs could stably deliver the discharging capacity of 712.0 mAh g−1, reaching 92.1% of that at the initial 0.1C. The superior Li-storage performance should be attributed to the nanocrystalline, mesopore, and multi-shelled hollow polyhedron structure. The unique NiCo2S4 multi-shelled hollow polyhedrons exhibit great potential as anode materials for high-performance lithium-ion batteries.
The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and ...transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naïve pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.
The aim of this study was to investigate the relationship between maternal body mass index and all congenital heart defects (CHDs) combined and 11 individual defects. PubMed, ELSEVIER ScienceDirect, ...and Springer Link (up to February 2013) were searched, and the reference list of retrieved articles was reviewed. Three authors independently extracted the data. The systematic review included 24 studies, 14 of which were included in a metaanalysis. Statistical software was used to perform all statistical analyses. Fixed-effects or random-effects model was used to pool the results of individual study (expressed as odds ratios ORs with 95% confidence intervals CIs). A dose-response effect was observed between overweight, moderate obesity, and severe obesity and a pregnancy with any CHD (the pooled ORs: OR, 1.08 95% CI, 1.02–1.15; OR, 1.15 95% CI, 1.11–1.20; and OR, 1.39 95% CI, 1.31–1.47, respectively) as well as some individual defects such as hypoplastic left heart syndrome, pulmonary valve stenosis, and outflow tract defects. When we excluded mothers with diabetes mellitus, the pooled ORs for all CHDs combined were 1.12 (95% CI, 1.04–1.20) and 1.38 (95% CI, 1.20–1.59) for moderately obese and severely obese, respectively. The highest increased risk was severely obese mothers for tetralogy of Fallot (OR, 1.94; 95% CI, 1.49–2.51). Being underweight did not increase the risk of any of the aforementioned CHDs but did increase the risk of aortic valve stenosis (OR, 1.47; 95% CI, 1.01–2.15). The results of our study showed that increasing maternal body mass index was associated with an increasing risk of CHDs; severe obesity was an even greater risk factor for the development of CHDs.
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