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Inspired by the biological processes of molecular recognition and transportation across membranes, nanopore techniques have evolved in recent decades as ultrasensitive analytical tools for individual molecules. In particular, nanopore-based single-molecule DNA/RNA sequencing has advanced genomic and transcriptomic research due to the portability, lower costs and long reads of these methods. Nanopore applications, however, extend far beyond nucleic acid sequencing. In this Review, we present an overview of the broad applications of nanopores in molecular sensing and sequencing, chemical catalysis and biophysical characterization. We highlight the prospects of applying nanopores for single-protein analysis and sequencing, single-molecule covalent chemistry, clinical sensing applications for single-molecule liquid biopsy, and the use of synthetic biomimetic nanopores as experimental models for natural systems. We suggest that nanopore technologies will continue to be explored to address a number of scientific challenges as control over pore design improves.This Review discusses the latest advances in nanopore technologies beyond DNA sequencing.

The new severe acute respiratory syndrome coronavirus 2 was initially discovered at the end of 2019 in Wuhan City in China and has caused one of the most serious global public health crises. A collection and analysis of studies related to the association between COVID-19 (coronavirus disease 2019) transmission and meteorological factors, such as humidity, is vital and indispensable for disease prevention and control. A comprehensive literature search using various databases, including Web of Science, PubMed, and Chinese National Knowledge Infrastructure, was systematically performed to identify eligible studies from Dec 2019 to Feb 1, 2021. We also established six criteria to screen the literature to obtain high-quality literature with consistent research purposes. This systematic review included a total of 62 publications. The study period ranged from 1 to 8 months, with 6 papers considering incubation, and the lag effect of climate factors on COVID-19 activity being taken into account in 22 studies. After quality assessment, no study was found to have a high risk of bias, 30 studies were scored as having moderate risks of bias, and 32 studies were classified as having low risks of bias. The certainty of evidence was also graded as being low. When considering the existing scientific evidence, higher temperatures may slow the progression of the COVID-19 epidemic. However, during the course of the epidemic, these climate variables alone could not account for most of the variability. Therefore, countries should focus more on health policies while also taking into account the influence of weather.

Protein nanopores offer an inexpensive, label-free method of analysing single oligonucleotides. The sensitivity of the approach is largely determined by the characteristics of the pore-forming protein employed, and typically relies on nanopores that have been chemically modified or incorporate molecular motors. Effective, high-resolution discrimination of oligonucleotides using wild-type biological nanopores remains difficult to achieve. Here, we show that a wild-type aerolysin nanopore can resolve individual short oligonucleotides that are 2 to 10 bases long. The sensing capabilities are attributed to the geometry of aerolysin and the electrostatic interactions between the nanopore and the oligonucleotides. We also show that the wild-type aerolysin nanopores can distinguish individual oligonucleotides from mixtures and can monitor the stepwise cleavage of oligonucleotides by exonuclease I. A wild-type aerolysin nanopore can resolve individual short oligonucleotides that are 2 to 10 bases long, and can monitor the stepwise cleavage of oligonucleotides by exonuclease I.

O-glycopeptides are highly expressed in various human cancers and play a key role in cancer progression and metastasis, making them promising biomarkers for early diagnostics. However, the inherent complexity and heterogeneity of glycans pose a major challenge for the simultaneous and precise analysis of multiple glycopeptides. Here, we developed a low-temperature nanopore technique capable of simultaneously discriminating 4 truncated O-glycopeptides with varied glycoforms. This method enables the direct identification and relative quantification of O-glycopeptides from a mixture, achieving a discrimination accuracy of 92.9%. This general strategy holds promise for the label-free analysis of glycopeptide biomarkers, with potential applications in cancer diagnostics.

SEE PDF] The presentations covered recent progress and new insights into nanopore electrochemical techniques toward life science and potential clinical applications, including sensitive protein analysis, selective nucleic acid testing, and small molecule detection at a single-molecule level. On October 19, 2020, Professor Ayumi Hirano-Iwata (Tohoku University, Japan) shared strategies for fabricating stable lipid bilayers onto the tapered apertures of Si chips to record single-channel activities and quantify the drug effect of the cell-free protein synthesized human ether-a-go-go-related gene (hERG) channel. Dr. Bingquan Luan (IBM T. J. Watson Research Center, USA) described molecular dynamics simulation of ssDNA stretching and transport through 2D and 3D heterostructure nanopores.

This prevalence of coronavirus disease 2019 (COVID-19) has become one of the most serious public health crises. Tree-based machine learning methods, with the advantages of high efficiency, and strong interpretability, have been widely used in predicting diseases. A data-driven interpretable ensemble framework based on tree models was designed to forecast daily new cases of COVID-19 in the USA and to determine the important factors related to COVID-19. Based on a hyperparametric optimization technique, we developed three machine learning algorithms based on decision trees, including random forest (RF), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM), and three linear ensemble models were used to integrate these outcomes for better prediction accuracy. Finally, the SHapley Additive explanation (SHAP) value was used to obtain the feature importance ranking. Our outcomes demonstrated that, among the three basic machine learners, the prediction accuracy was the following in descending order: LightGBM, XGBoost, and RF. The optimized LAD ensemble was the most precise prediction model that reduced the prediction error of the best base learner (LightGBM) by approximately 3.111%, while vaccination, wearing masks, less mobility, and government interventions had positive effects on the control and prevention of COVID-19.

Small activating RNAs （saRNAs） targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation （RNAa）. It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A （p21） as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters, saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation （RITA） complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAFI complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.

Background： The accurate measurement of the femoral anteversion （FA） angle is always a topic of much debate in the orthopedic surgery and radiology research. We aimed to explore a new FA measurement method to acquire accurate results without radiation damage using piglet model. Methods： A total of thirty piglets were assigned to two groups based on the age. Bilateral femora were imaged with 3.0-T magnetic resonance （MR） and 64-slice computed tomography （CT） examinations on all piglets. FA was measured on MR-three-dimensional （3D） postprocessing software with a four-step method： initial validation of the femoral condylar axis, validation of the condylar plane, validation of the femoral neck axis, and line-plane angle measurement of FA. After MR and CT examinations, all piglets were sacrificed and their degree of FA was measured using their excised, dried femora. MR, CT, and dried-femur measurement results were analyzed statistically; M R and CT measurements were compared for accuracy against each other and against the gold standard dried femur measurement. Results： In both groups, the mean FA value measured by MR was lower than that measured by CT. A statistically significant difference was observed between CT- and dried-femur measurements but not between MR- and dried-femur measurements. A higher correlation （0.783 vs. 0.408） and a higher consistency （0.863 vs. 0.578） with dried-femur measurement results were seen for MR measurements than CT measurements in the 1 -week age group. However, in the 8-week age group, similar correlations （0.707 vs. 0.669） and consistencies （0.864 vs. 0.82 l ） were observed. Conclusions： Noninvasive MR-3D-Cube reconstruction was able to accurately measure FA in piglets. Particularly in the 1-week age group with a larger proportion of cartilaginous structures, the correlation and consistency between MR- and dried-femur measurement results were higher than those between CT- and dried-femur measurements, suggesting that MR may be a new useful examination tool for FA-related diseases in children.

In this work, the piezotronic effect is investigated for the first time in external electric fields ranging from 0 V·cm-I to 2,000 V·cm-1 by using n-type ZnO nanowires supported by a flexible substrate. In the presence of an external electric field, the Schottky barrier height （SBH） is lowered by the image force, allowing more free carriers to pass through the metal-semiconductor junction and enhancing the screening effect on positive piezoelectric polarization charges. As the strength of the external electric field increases, the piezotronic effect is significantly suppressed and the metal-semiconductor contact finally exhibits Ohmic behavior. The experimental results show that devices can be classified into three groups, corresponding to low, moderate, and high carrier densities of the nanowires used. This work not only helps us to explicate the basic physical mechanism of the piezotronic effect in a harsh environment in an electric field but also provides guidelines for future design and fabrication of piezotronic devices.

The growth rates of bainite plates in an Fe-C-Mn-Si superbainitie steel were investigated by in situ observation. The lengthening rates of ferrite bainite during both cooling and isothermal holding processes were observed and the growth rates of bainite plates nucleating at grain boundaries, within grains and on preformed bainite were measured. It is indicated that the lengthening rates of bainite plates during the cooling and isothermal processes were different, and that the growth rates of bainite plates nucleating at different types of sites also demon- strated diversity. The bainite plates initiating at [vain boundaries during cooling grew the fastest, while the plates nucleating on preformed bainite did the slowest. However, the growth rate of the bainite plates nucleating at grain boundaries during isothermal transformation de- creased the most, whereas the bainite plates initiating within grains grew the fastest. In addition, the growth rate of ferrite bainite in the study supported the diffusion transformation mechanism of bainite from the viewooint of ~rowth rate.