Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively. In this study we have reviewed several ...reports of cancer burden, including the Global cancer statistics 2018 and Cancer statistics in China, 2015, along with the GLOBCAN 2018 online database, to investigate the differences of cancer patterns between China, the United States (USA) and the United Kingdom (UK). An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018. Compared to the USA and UK, China has lower cancer incidence but a 30% and 40% higher cancer mortality than the UK and USA, among which 36.4% of the cancer‐related deaths were from the digestive tract cancers (stomach, liver, and esophagus cancer) and have relatively poorer prognoses. In comparison, the digestive cancer deaths only took up ≤ 5% of the total cancer deaths in either USA or UK. Other reasons for the higher mortality in China may be the low rate of early‐stage cancers at diagnosis and non‐uniformed clinical cancer treatment strategies performed by different regions. China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country, with a rapidly increase cancer burden of colorectal, prostate, female breast cancers in addition to a high occurrence of infection‐related and digestive cancers. The incidence of westernized lifestyle‐related cancers in China (i.e. colorectal cancer, prostate, bladder cancer) has risen but the incidence of the digestive cancers has decreased from 2000 to 2011. An estimated 40% of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries. Tobacco smoking is the single most important carcinogenic risk factor in China, contributing to ~ 24.5% of cancers in males. Chronic infection is another important preventable cancer contributor which is responsible for ~ 17% of cancers. Comprehensive prevention and control strategies in China should include effective tobacco‐control policy, recommendations for healthier lifestyles, along with enlarging the coverage of effective screening, educating, and vaccination programs to better sensitize greater awareness control to the general public.
Abstract
Catalytic reductive coupling of two electrophiles and one unsaturated bond represents an economic and efficient way to construct complex skeletons, which is dominated by transition-metal ...catalysis via two electron transfer. Herein, we report a strategy of visible-light photoredox-catalyzed successive single electron transfer, realizing dearomative arylcarboxylation of indoles with CO
2
. This strategy avoids common side reactions in transition-metal catalysis, including ipso-carboxylation of aryl halides and β-hydride elimination. This visible-light photoredox catalysis shows high chemoselectivity, low loading of photocatalyst, mild reaction conditions (room temperature, 1 atm) and good functional group tolerance, providing great potential for the synthesis of valuable but difficultly accessible indoline-3-carboxylic acids. Mechanistic studies indicate that the benzylic radicals and anions might be generated as the key intermediates, thus providing a direction for reductive couplings with other electrophiles, including D
2
O and aldehyde.
In order to explore the integration path of curriculum Civics in English teaching, this paper proposes the construction method of students’ Civics behavioral portrait based on big data technology to ...mine the behavioral data of English majors. The behavioral data of students were collected with the help of various information systems in universities, and the processed data were clustered and analyzed based on the K-means algorithm. For the uncertainty of the K-value and initial center, the PCA method is used to reduce the dimensionality of the initial data, and the density Canopy clustering replaces the pre-processing process in the K-means algorithm. The average purity of clusters reached 0.88. From the mining effect, in the teaching theme of “people and society”, the main Civics elements are social service, science and technology, with heat values of 0.407 and 0.352. Big data the technology has provided strong support for the integration of Civics and English teaching.
Protein-protein interactions (PPIs) hold significant importance in biology, with precise PPI prediction as a pivotal factor in comprehending cellular processes and facilitating drug design. However, ...experimental determination of PPIs is laborious, time-consuming, and often constrained by technical limitations.
We introduce a new node representation method based on initial information fusion, called FFANE, which amalgamates PPI networks and protein sequence data to enhance the precision of PPIs' prediction. A Gaussian kernel similarity matrix is initially established by leveraging protein structural resemblances. Concurrently, protein sequence similarities are gauged using the Levenshtein distance, enabling the capture of diverse protein attributes. Subsequently, to construct an initial information matrix, these two feature matrices are merged by employing weighted fusion to achieve an organic amalgamation of structural and sequence details. To gain a more profound understanding of the amalgamated features, a Stacked Autoencoder (SAE) is employed for encoding learning, thereby yielding more representative feature representations. Ultimately, classification models are trained to predict PPIs by using the well-learned fusion feature.
When employing 5-fold cross-validation experiments on SVM, our proposed method achieved average accuracies of 94.28%, 97.69%, and 84.05% in terms of Saccharomyces cerevisiae, Homo sapiens, and Helicobacter pylori datasets, respectively.
Experimental findings across various authentic datasets validate the efficacy and superiority of this fusion feature representation approach, underscoring its potential value in bioinformatics.
Reported herein is a novel visible‐light photoredox system with Pd(PPh3)4 as the sole catalyst for the realization of the first direct cross‐coupling of C(sp3)−H bonds in N‐aryl ...tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra‐ and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp3)−C(sp3) and C(sp2)−C(sp3) bonds in moderate to excellent yields. These redox‐neutral reactions feature broad substrate scope (>60 examples), good functional‐group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible‐light photocatalyst and radicals are involved in the process.
Pd, just do it! A novel visible‐light photoredox system with Pd(PPh3)4 as the sole catalyst leads to the direct alkylation of C−H bonds with unactivated alkyl bromides under mild reaction conditions. These redox‐neutral reactions feature high yields, broad substrate scope (>60 examples), facile generation of quaternary centers, and good functional‐group tolerance.
The limited knowledge of miRNA-lncRNA interactions is considered as an obstruction of revealing the regulatory mechanism. Accumulating evidence on Human diseases indicates that the modulation of gene ...expression has a great relationship with the interactions between miRNAs and lncRNAs. However, such interaction validation via crosslinking-immunoprecipitation and high-throughput sequencing (CLIP-seq) experiments that inevitably costs too much money and time but with unsatisfactory results. Therefore, more and more computational prediction tools have been developed to offer many reliable candidates for a better design of further bio-experiments.
In this work, we proposed a novel link prediction model based on Gaussian kernel-based method and linear optimization algorithm for inferring miRNA-lncRNA interactions (GKLOMLI). Given an observed miRNA-lncRNA interaction network, the Gaussian kernel-based method was employed to output two similarity matrixes of miRNAs and lncRNAs. Based on the integrated matrix combined with similarity matrixes and the observed interaction network, a linear optimization-based link prediction model was trained for inferring miRNA-lncRNA interactions.
To evaluate the performance of our proposed method, k-fold cross-validation (CV) and leave-one-out CV were implemented, in which each CV experiment was carried out 100 times on a training set generated randomly. The high area under the curves (AUCs) at 0.8623 ± 0.0027 (2-fold CV), 0.9053 ± 0.0017 (5-fold CV), 0.9151 ± 0.0013 (10-fold CV), and 0.9236 (LOO-CV), illustrated the precision and reliability of our proposed method.
GKLOMLI with high performance is anticipated to be used to reveal underlying interactions between miRNA and their target lncRNAs, and deciphers the potential mechanisms of the complex diseases.
Regulated necrosis (necroptosis) and apoptosis are crucially involved in severe cardiac pathological conditions, including myocardial infarction, ischemia-reperfusion injury and heart failure. ...Whereas apoptotic signaling is well defined, the mechanisms that underlie cardiomyocyte necroptosis remain elusive. Here we show that receptor-interacting protein 3 (RIP3) triggers myocardial necroptosis, in addition to apoptosis and inflammation, through activation of Ca(2+)-calmodulin-dependent protein kinase (CaMKII) rather than through the well-established RIP3 partners RIP1 and MLKL. In mice, RIP3 deficiency or CaMKII inhibition ameliorates myocardial necroptosis and heart failure induced by ischemia-reperfusion or by doxorubicin treatment. RIP3-induced activation of CaMKII, via phosphorylation or oxidation or both, triggers opening of the mitochondrial permeability transition pore and myocardial necroptosis. These findings identify CaMKII as a new RIP3 substrate and delineate a RIP3-CaMKII-mPTP myocardial necroptosis pathway, a promising target for the treatment of ischemia- and oxidative stress-induced myocardial damage and heart failure.
Abstract
Photoredox-mediated umpolung strategy provides an alternative pattern for functionalization of carbonyl compounds. However, general approaches towards carboxylation of carbonyl compounds ...with CO
2
remain scarce. Herein, we report a strategy for visible-light photoredox-catalyzed umpolung carboxylation of diverse carbonyl compounds with CO
2
by using Lewis acidic chlorosilanes as activating/protecting groups. This strategy is general and practical to generate valuable α-hydroxycarboxylic acids. It works well for challenging alkyl aryl ketones and aryl aldehydes, as well as for α-ketoamides and α-ketoesters, the latter two of which have never been successfully applied in umpolung carboxylations with CO
2
(to the best of our knowledge). This reaction features high selectivity, broad substrate scope, good functional group tolerance, mild reaction conditions and facile derivations of products to bioactive compounds, including oxypheonium, mepenzolate bromide, benactyzine, and tiotropium. Moreover, the formation of carbon radicals and carbanions as well as the key role of chlorosilanes are supported by control experiments.
Over the past decades, organometallic complexes with precious elements, such as ruthenium and iridium, are widely used as visible‐light photoredox catalysts. Recently, more and more complexes based ...on earth‐abundant and inexpensive elements have been used as sensitizers in photochemistry. Although the photoexcited state lifetimes of iron complexes are typically shorter than those of traditional photosensitizers, the utilization of iron catalysts in photochemistry has sprung up owing to their abundance, low price, nontoxicity, and novel properties, including exhibiting ligand to metal charge transfer states. This concept focuses on recent advances in light‐driven iron catalysis in organic transformations, including iron/photoredox dual catalysis, light‐induced iron photoredox catalysis and light‐induced generation of active iron catalysts. The prospect for the future of this field is also discussed.
Light runs across iron catalysts: This Concept summarizes the recent advances in iron/photoredox dual catalysis, photoactive iron catalysts in photochemistry, as well as light‐induced generation of active iron catalysts in organic transformations. Prospects for the future of the field are also discussed.
Sepsis is characterized by a severe inflammatory response throughout the whole body and can induce acute kidney injury (AKI). This research aimed to investigate the regulatory mechanisms underlying ...miR‐155‐5p in sepsis‐induced AKI. CLP‐treated mice were used as an in vivo model of sepsis‐induced AKI, and LPS‐treated HK‐2 and TCMK‐1 cells were used as in vitro models. Bioinformatics analyses and mechanistic assays were utilized to reveal the relationships between molecules. H&E staining was used to reveal morphological changes in kidney tissues. ELISAs were conducted to detect the concentrations of proinflammatory cytokines. We discovered that miR‐155‐5p was prominently upregulated in sepsis‐induced AKI in vivo and in vitro. MiR‐155‐5p inhibition alleviated kidney injury in mice. Moreover, WWC1 served as a direct target of miR‐155‐5p and was negatively regulated by miR‐155‐5p. WWC1 upregulation inhibited the productions of inflammatory cytokines and suppressed apoptosis in vivo and in vitro. In addition, rescue assays demonstrated that WWC1 knockdown counteracted the inhibitory effect of anti‐miR‐155‐5p on inflammation and apoptosis. Moreover, miR‐155‐5p could bind to XIST. XIST expression was downregulated in LPS‐stimulated HK‐2 and TCMK‐1 cells. XIST could negatively regulate miR‐155‐5p expression and positively regulate WWC1 expression. Rescue assays revealed that miR‐155‐5p overexpression significantly reversed the suppressive effects of XIST upregulation on inflammation and apoptosis. In conclusion, our study revealed that the XIST/miR‐155‐5p/WWC1 axis modulated sepsis‐induced AKI progression, providing promising insight into therapeutic targets for sepsis‐induced AKI.
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