Background:
Uterine corpus endometrial carcinoma (UCEC) is a common gynecological malignancy globally with high recurrence and mortality rates. Cuproptosis is a new type of programmed cell death ...involved in tumor cell proliferation and growth, angiogenesis, and metastasis.
Methods:
The difference in cuproptosis-related genes (CRGs) between UCEC tissues and normal tissues deposited in The Cancer Genome Atlas database was calculated using the “limma” R package. LASSO Cox regression analysis was conducted to construct a prognostic cuproptosis–related signature. Kaplan–Meier analysis was conducted to compare the survival of UCEC patients. A ceRNA network was constructed to identify the lncRNA–miRNA–mRNA regulatory axis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to verify CRG expression in UCEC.
Results:
The expression of FDX1, LIAS, DLAT, and CDKN2A were upregulated, whereas the expression of LIPT1, DLD, PDHB, MTF1, and GLS were downregulated in UCEC versus normal tissues. The genetic mutation landscape of CRGs in UCEC was also summarized. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these CRGs were enriched in the tricarboxylic acid (TCA) cycle, glycolysis, and HIF-1 signaling pathway. LASSO Cox regression analysis was performed and identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1). UCEC patients with high risk scores had a poor prognosis with an area under the curve of 0.782 and 0.764 on 3- and 5-year receiver operating characteristic curves. Further analysis demonstrated a significant correlation between CDKN2A and pTNM stage, tumor grade, immune cell infiltration, drug sensitivity, tumor mutational burden (TMB) score, and microsatellite instable (MSI) score. The data validation of qRT-PCR further demonstrated the upregulation of CDKN2A and the downregulation of LIPT1 and GLS in UCEC versus normal tissues. The ceRNA network also identified lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis for UCEC.
Conclusion:
The current study identified a cuproptosis-related prognostic signature including these three prognostic biomarkers (CDKN2A, GLS, and LIPT1) for UCEC. The ceRNA network also identified that lncRNA XIST/miR-125a-5p/CDKN2A regulatory axis may be involved in the progression of UCEC. Further
in vivo
and
in vitro
studies should be conducted to verify these results.
In this article, an adaptive dynamic terminal sliding-mode controller using a double hidden layer recurrent neural network (DHL-RNN) structure for a single-phase active power filter (APF) is proposed ...to improve harmonic compensation performance. First, a method combining dynamic sliding mode and terminal sliding mode is proposed to solve the chattering phenomenon in traditional sliding-mode control. Then, since the nonlinear dynamics of APF is difficult to obtain accurately, the DHL-RNN is used to approximate the proposed dynamic terminal sliding-mode controller. Meanwhile, an integral robust switching term is added to eliminate the approximation error of the neural network. Simulation and experimental results proved that the proposed controller has better compensation performance and tracking effect compared with a simple terminal sliding-mode controller.
In photoacoustic imaging, the second near-infrared (NIR-II) window is where tissue generates the least background signal. However, the large size of the few available contrast agents in this spectral ...range impedes their pharmacokinetics and decreases their thermal stability, leading to unreliable photoacoustic imaging. Here, we report the synthesis of miniaturized gold nanorods absorbing in the NIR-II that are 5-11 times smaller than regular-sized gold nanorods with a similar aspect ratio. Under nanosecond pulsed laser illumination, small nanorods are about 3 times more thermally stable and generate 3.5 times stronger photoacoustic signal than their absorption-matched larger counterparts. These unexpected findings are confirmed using theoretical and numerical analysis, showing that photoacoustic signal is not only proportional to the optical absorption of the nanoparticle solution but also to the surface-to-volume ratio of the nanoparticles. In living tumour-bearing mice, these small targeted nanorods display a 30% improvement in efficiency of agent delivery to tumours and generate 4.5 times greater photoacoustic contrast.
The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2 virus) has been sustained in China since December 2019, and has become a ...pandemic. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the factors influencing medical worker anxiety in China during the COVID-19 outbreak. We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff in China from 10 February 2020 to 20 February 2020 using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, with the criteria of normal (⩽49), mild (50-59), moderate (60-70) and severe anxiety (⩾70). We used multivariable linear regression to determine the factors (e.g. having direct contact when treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status. Of 512 medical staff in China, 164 (32.03%) had had direct contact treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers suffering from moderate (1.36%) and four workers suffering from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients experienced higher anxiety scores than those who had not had direct contact (β value = 2.33, confidence interval (CI) 0.65-4.00; P = 0.0068). A similar trend was observed in medical staff from Hubei province, compared with those from other parts of China (β value = 3.67, CI 1.44-5.89; P = 0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (β value = 4.44, CI 1.55-7.33; P = 0.0028). In this survey of hospital medical workers during the COVID-19 outbreak in China, we found that study participants experienced anxiety symptoms, especially those who had direct clinical contact with infected patients; as did those in the worst affected areas, including Hubei province; and those who were suspect cases. Governments and healthcare authorities should proactively implement appropriate psychological intervention programmes, to prevent, alleviate or treat increased anxiety.
BACKGROUND:The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These ...areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.
METHODS:To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.
RESULTS:Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.
CONCLUSIONS:Gut microbiota–derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
Observation of surface water is a functional requirement for studying ecological and hydrological processes. Recent advances in satellite‐based optical remote sensors have promoted the field of ...sensing surface water to a new era. This paper reviews the current status of detecting, extracting, and monitoring surface water using optical remote sensing, especially progress in the last decade. It also discusses the current status and challenges in this field, including spatio‐temporal scale issues, integration with in situ hydrological data and elevation data, obscuration caused by clouds and vegetation, and the growing need to map surface water at a global scale. Historically, sensors have exhibited a contradiction in resolutions. Techniques including pixel unmixing and reconstruction, and spatio‐temporal fusion have been developed to alleviate this contradiction. Spatio‐temporal dynamics of surface water have been modeled by combining remote sensing data with in situ river flow. Recent studies have also demonstrated that the river discharge can be estimated using only optical remote sensing imagery, providing valuable information for hydrological studies in ungauged areas. Another historical issue for optical sensors has been obscuration by clouds and vegetation. An effective approach of reducing this limitation is to combine with synthetic aperture radar data. Digital elevation model data have also been employed to eliminate cloud/terrain shadows. The development of big data and cloud computation techniques makes the increasing demand of monitoring global water dynamics at high resolutions easier to achieve. An integrated use of multisource data is the future direction for improved global and regional water monitoring.
Plain Language Summary
Observing surface water is essential for ecological and hydrological studies. This paper reviews the current status of detecting, extracting, and monitoring surface water using optical remote sensing, especially progress in the last decade. It also discusses the current status and challenges in this field. For example, it was found that pixel unmixing and reconstruction, and spatio‐temporal fusion are two common and low‐cost approaches to enhance surface water monitoring. Remote sensing data have been integrated with in situ river flow to model spatio‐temporal dynamics of surface water. Recent studies have also proved that the river discharge can be estimated using only optical remote sensing imagery. This will be a breakthrough for hydrological studies in ungauged areas. Optical sensors are also easily obscured by clouds and vegetation. This limitation can be reduced by integrating optical data with synthetic aperture radar data and digital elevation model data. There is increasing demand of monitoring global water dynamics at high resolutions. It is now easy to achieve with the development of big data and cloud computation techniques. Enhanced global or regional water monitoring in the future requires integrated use of multiple sources of remote sensing data.
Key Points
Satellite‐based optical sensors are an efficient means for observing surface water regionally and globally
Pixel unmixing and reconstruction, and spatio‐temporal fusion are two common and low‐cost approaches to enhance surface water monitoring
The potential to estimate flow using only optical remote sensing has greatly enriched the data source of hydrological studies
2019-nCoV is a newly identified coronavirus with high similarity to SARS-CoV. We performed a structural analysis of the receptor binding domain (RBD) of spike glycoprotein responsible for entry of ...coronaviruses into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. However, 2019-nCoV has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.
•Spike glycoprotein of 2019-nCoV may confer a strong ACE2 receptor binding.•Conserved expression of ACE2 suggests a wide range of natural hosts for 2019-nCoV.•Tissue expression of ACE2 suggests multiple routes of 2019-nCoV transmission.
Pedestrian detection is an initial step to perform outdoor scene analysis, which plays an essential role in many real-world applications. Although having enjoyed the merits of deep learning ...frameworks from the generic object detectors, pedestrian detection is still a very challenging task due to heavy occlusions, and highly crowded group. Generally, the conventional detectors are unable to differentiate individuals from each other effectively under such a dense environment. To tackle this critical problem, we propose an attribute-aware pedestrian detector to explicitly model people's semantic attributes in a high-level feature detection fashion. Besides the typical semantic features, center position, target's scale, and offset, we introduce a pedestrian-oriented attribute feature to encode the high-level semantic differences among the crowd. Moreover, a novel attribute-feature-based Non-Maximum Suppression (NMS) is proposed to distinguish the person from a highly overlapped group by adaptively rejecting the false-positive results in a very crowd settings. Furthermore, an enhanced ground truth target is designed to alleviate the difficulties caused by the attribute configuration, and to ease the class imbalance issue during training. Finally, we evaluate our proposed attribute-aware pedestrian detector on three benchmark datasets including CityPerson, CrowdHuman, and EuroCityPerson, and achieves the state-of-the-art results.
Quantum key distribution (QKD)1,2 offers a long-term solution to secure key exchange. Due to photon loss in transmission, it was believed that the repeaterless key rate is bounded by a linear ...function of the transmittance, O(η) (refs. 3,4), limiting the maximal secure transmission distance5,6. Recently, a novel type of QKD scheme has been shown to beat the linear bound and achieve a key rate performance of O(η) (refs. 7–9). Here, by employing the laser injection technique and the phase post-compensation method, we match the modes of two independent lasers and overcome the phase fluctuation. As a result, the key rate surpasses the linear bound via 302 km and 402 km commercial-fibre channels, over four orders of magnitude higher than existing results5. Furthermore, our system yields a secret key rate of 0.118 bps with a 502 km ultralow-loss fibre. This new type of QKD pushes forward long-distance quantum communication for the future quantum internet.Phase-matching quantum key distribution is implemented with a 502 km ultralow-loss optical fibre. The fluctuations of the laser initial phases and frequencies are suppressed by the laser injection technique and the phase post-compensation method.
Reported herein is a new iron‐catalyzed diastereoselective olefin diazidation reaction which occurs at room temperature (1–5 mol % of catalysts and d.r. values of up to >20:1). This method tolerates ...a broad range of both unfunctionalized and highly functionalized olefins, including those that are incompatible with existing methods. It also provides a convenient approach to vicinal primary diamines as well as other synthetically valuable nitrogen‐containing building blocks which are difficult to obtain with alternative methods. Preliminary mechanistic studies suggest that the reaction may proceed through a new mechanistic pathway in which both Lewis acid activation and iron‐enabled redox‐catalysis are crucial for selective azido‐group transfer.
With iron hand: The title reaction proceeds at room temperature and tolerates a broad range of both unfunctionalized and highly functionalized olefins. It also provides a convenient synthetic approach to a variety of nitrogen‐containing building blocks. Preliminary mechanistic studies suggest both Lewis acid activation and iron‐enabled redox catalysis are crucial for the selective azido‐group transfer.
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