Taxol
, an antitumor drug with significant activity, is the first microtubule stabilizing agent described in the literature. This short review of the mechanism of action of Taxol
emphasizes the ...research done in the Horwitz' laboratory. It discusses the contribution of photoaffinity labeled analogues of Taxol
toward our understanding of the binding site of the drug on the microtubule. The importance of hydrogen/deuterium exchange experiments to further our insights into the stabilization of microtubules by Taxol
is addressed. The development of drug resistance, a major problem that arises in the clinic, is discussed. Studies describing differential drug binding to distinct β-tubulin isotypes are presented. Looking forward, it is suggested that the β-tubulin isotype content of a tumor may influence its responses to Taxol
.
•The COVID-19 emerged in Wuhan City and rapidly spread throughout China.•NLR exhibited the largest area under the curve, with the highest specificity and sensitivity.•Elevated NLR can be considered ...independent biomarkers for indicating poor clinical outcomes.
To accumulate evidence that indicated the key role played by virus-triggered inflammation in the 2019-novel coronavirus disease (COVID-19) which emerged in Wuhan City and rapidly spread throughout China.
Age, neutrophil(NEU)-to-lymphocyte (LYM) ratio (NLR), lymphocyte-to-monocyte (MON) ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) of 93 patients with laboratory confirmed COVID-19 were investigated and compared. The receiver operating characteristic curve was applied to determine the thresholds for five bio-markers, and their prognostic values were assessed via the Kaplan–Meier curve and multivariate COX regression models.
The median age was 46.4 years old, and 37cases were females. A total of 27.8% of patients had been to Wuhan, and 73.1% had contacted with people from Wuhan. Fever (83.8%) and cough (70.9%) were the two most common symptoms. Elevated NLR and age were significantly associated with illness severity. The binary logistic analysis identified elevated NLR (hazard risk HR 2.46, 95% confidence interval CI 1.98–4.57) and age (HR 2.52, 95% CI 1.65–4.83) as independent factors for poor clinical outcome of COVID-19. NLR exhibited the largest area under the curve at 0.841, with the highest specificity (63.6%) and sensitivity (88%).
Elevated age and NLR can be considered independent biomarkers for indicating poor clinical outcomes.
In order to improve the output visual effect, display clarity better, and restore the color levels and details in oil paintings, this paper proposes a digital media interactive oil painting art ...exhibition method based on visual communication. Firstly, the feature points of virtual images of oil paintings are extracted and matched. On this basis, the virtual images of oil paintings are spliced to realize the fusion of virtual images of oil paintings with digital media interaction, and the virtual images of oil paintings with digital media interaction are obtained. Then, the noise model of the virtual image of oil painting artworks is constructed so that it can be restored to a noise-free image while retaining the characteristics of the image, and the virtual image of oil painting artworks can be denoised by using the optimization formula of network parameters. Finally, based on visual communication, the three-dimensional display structure of oil painting works is constructed, and the application of oil painting works is completed by determining the coordinate rotation matrix. The experimental results show that the final resolution obtained by this method is controlled above 95%, and the output visual effect and display clarity are good, which can more accurately restore the color levels and details in the original oil paintings.
2D covalent organic frameworks (2D COFs) have been recognized as a novel class of photoactive materials owing to their extended π‐electron conjugation and high chemical stabilities. Herein, a new ...covalent organic framework (Tph‐BDP) is facilely synthesized by using a porphyrin derivative and an organic dye BODIPY derivative (5,5‐difluoro‐2,8‐diformyl‐1,3,7,9‐tetramethyl‐10‐phenyl‐5H‐dipyrrolo1,2‐c:2′,1′‐f1,3,2diazabori‐nin‐4‐ium‐5‐uide) as monomers for the first time, and their unique photosensitive properties endow them excellent simulated oxidase activity under 635 nm laser irradiation that can catalyze the oxidation of 3,3′,5,5′‐tetramethylbenzidine (TMB). Further findings demonstrate that the presence of uranium (UO22+) can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading. This research provides a preparation strategy for COFs with excellent photocatalytic properties and nanozyme activity, and broadens the applications of the simple colorimetric methods for sensitive and selective radionuclide detection.
A new covalent organic framework is facilely synthesized and its unique photosensitive property endows excellent simulated oxidase activity that can catalyze the oxidation of 3,3′,5,5′‐tetramethylbenzidine (TMB). The presence of uranium can coordinate with imines of the oxidation products of TMB, thus modulating the charge transfer process of the colored products accompanied with intensive aggregation and remarkable color fading.
Distributed network architecture of heterogeneous computing faces with such problems as strict performance constraints of network control, unpredictable mapping relationship between computing data ...algorithms of different mobile terminals and inconsistency between computing algorithms and link control of data networks. In order to solve the above problems, we begin with software definition network architecture and load balancing algorithm for heterogeneous computing, and gradually improve the real-time and reliability of heterogeneous computing. On the one hand, the heterogeneous computing data of fog node and cloud computing system are distributed. The centralized service of software-defined network combines with distributed computing of mobile edge terminal and its subnet. On the other hand, we define the centralized information and distributed scheduler of the network. In addition, we deploy the optimal assignment of data sharing and heterogeneous computing tasks in real time with ellipse-partitioned area as the object. A series of algorithms for classifying and assigning heterogeneous computing data streams in software-defined networks are designed to achieve the optimal balance among load balancing, minimum classification of large data streams, minimum resource occupation and time constraints. Experimental comparison compared and evaluated the Load Balancing with big data stream (LBBS), Load Balancing with Heterogeneous Computing (LBHC) and the proposed LBBHD. Compared with the other two algorithms, the proposed algorithm improves workload skewness, throughput and load balancing error respectively about 2.1%, 1.96%, 2.9%, 2.2%; 5.57%. 2.51%.
Primary lung cancer is very heterogeneous in its clinical presentation, histopathology, and treatment response; and like other diseases, the prognosis consists of two essential facets: survival and ...quality of life (QOL). Lung cancer survival is mostly determined by disease stage and treatment modality, and the 5-Year survival rate has been in a plateau of 15% for three decades. QOL is focused on life aspects that are affected by health conditions and medical interventions; the balance of physical functioning and suffering from treatment side effects has long been a concern of care providers as well as patients. Obviously needed are easily measurable biologic markers to stratify patients before treatment for optimal results in survival and QOL and to monitor treatment responses and toxicities. Targeted therapies toward the mechanisms of tumor development, growth, and metastasis are promising and actively translated into clinical practice. Long-term lung cancer (LTLC) survivors are people who are alive 5 Years after the diagnosis. Knowledge about the health and QOL in LTLC survivors is limited because outcome research in lung cancer has been focused mainly on short-term survival. The independent or combined effects of lung cancer treatment, aging, smoking and drinking, comorbid conditions, and psychosocial factors likely cause late effects, including organ malfunction, chronic fatigue, pain, or premature death among lung cancer survivors. New knowledge to be gained should help lung cancer survivors, their healthcare providers, and their caregivers by providing evidence for establishing clinical recommendations to enhance their long-term survival and health-related QOL.
COVID-19 has spread globally. Epidemiological susceptibility to COVID-19 has been reported in patients with cancer. We aimed to systematically characterise clinical features and determine risk ...factors of COVID-19 disease severity for patients with cancer and COVID-19.
In this multicentre, retrospective, cohort study, we included all adult patients (aged ≥18 years) with any type of malignant solid tumours and haematological malignancy who were admitted to nine hospitals in Wuhan, China, with laboratory-confirmed COVID-19 between Jan 13 and March 18, 2020. Enrolled patients were statistically matched (2:1) with patients admitted with COVID-19 who did not have cancer with propensity score on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, illness severity, and clinical interventions were compared between patients with COVID-19 with or without cancer as well as between patients with cancer with non-severe or severe COVID-19. COVID-19 disease severity was defined on admission on the basis of the WHO guidelines. Univariable and multivariable logistic regression, adjusted for age, sex, comorbidities, cancer type, tumour stage, and antitumour treatments, were used to explore risk factors associated with COVID-19 disease severity. This study was registered in the Chinese Clinical Trial Register, ChiCTR2000030807.
Between Jan 13 and March 18, 2020, 13 077 patients with COVID-19 were admitted to the nine hospitals in Wuhan and 232 patients with cancer and 519 statistically matched patients without cancer were enrolled. Median follow-up was 29 days (IQR 22–38) in patients with cancer and 27 days (20–35) in patients without cancer. Patients with cancer were more likely to have severe COVID-19 than patients without cancer (148 64% of 232 vs 166 32% of 519; odds ratio OR 3·61 95% CI 2·59–5·04; p<0·0001). Risk factors previously reported in patients without cancer, such as older age; elevated interleukin 6, procalcitonin, and D-dimer; and reduced lymphocytes were validated in patients with cancer. We also identified advanced tumour stage (OR 2·60, 95% CI 1·05–6·43; p=0·039), elevated tumour necrosis factor α (1·22, 1·01–1·47; p=0·037), elevated N-terminal pro-B-type natriuretic peptide (1·65, 1·03–2·78; p=0·032), reduced CD4+ T cells (0·84, 0·71–0·98; p=0·031), and reduced albumin–globulin ratio (0·12, 0·02–0·77; p=0·024) as risk factors of COVID-19 severity in patients with cancer.
Patients with cancer and COVID-19 were more likely to deteriorate into severe illness than those without cancer. The risk factors identified here could be helpful for early clinical surveillance of disease progression in patients with cancer who present with COVID-19.
China National Natural Science Foundation.
Western blotting is an important technique used in cell and molecular biology. By using a western blot, researchers are able to identify specific proteins from a complex mixture of proteins extracted ...from cells. The technique uses three elements to accomplish this task: (1) separation by size, (2) transfer to a solid support, and (3) marking target protein using a proper primary and secondary antibody to visualize. This paper will attempt to explain the technique and theory behind western blot, and offer some ways to troubleshoot.
Climate change has the potential to change the distribution of pests globally and their resistance to pesticides, thereby threatening global food security in the 21st century. However, predicting ...where these changes occur and how they will influence current pest control efforts is a challenge. Using experimentally parameterised and field-tested models, we show that climate change over the past 50 years increased the overwintering range of a global agricultural insect pest, the diamondback moth (Plutella xylostella), by ~2.4 million km
worldwide. Our analysis of global data sets revealed that pesticide resistance levels are linked to the species' overwintering range: mean pesticide resistance was 158 times higher in overwintering sites compared to sites with only seasonal occurrence. By facilitating local persistence all year round, climate change can promote and expand pesticide resistance of this destructive species globally. These ecological and evolutionary changes would severely impede effectiveness of current pest control efforts and potentially cause large economic losses.
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