Increased generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of a variety of diseases such as cardiovascular diseases and cancer. NADPH oxidase (Nox), a ...multicomponent enzyme, has been identified as one of the key sources of ROS. Nox4, one of the seven members of Nox family (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2), has been extensively investigated in recent years. Its unique structures result in the constitutive generation of hydrogen peroxide (H
2
O
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) as the main product. As a key oxygen sensor, Nox4-derived H
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O
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plays diverse roles in cell proliferation, migration and death. Increased expression of Nox4 in cancer has been observed, which participates in metastasis, angiogenesis and apoptosis. Expression of Nox4 in endothelial cells actively mediated endothelial activation, dysfunction and injury, which contributes to the development of atherosclerosis, hypertension, cardiac hypertrophy and among others. This article explores the experimental studies related to the gene, structure, physiological function and pathological significance of Nox4. As Nox4 might serve as a potential target for the therapy of cardiovascular diseases and cancer, the Nox4 inhibitor is also discussed in this article.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Fungi produce millions of clonal asexual conidia (spores) that remain dormant until favourable conditions occur. Conidia contain abundant stable messenger RNAs but the mechanisms underlying the ...production of these transcripts and their composition and functions are unknown. Here, we report that the conidia of three filamentous fungal species (Aspergillus nidulans, Aspergillus fumigatus, Talaromyces marneffei) are transcriptionally active and can synthesize mRNAs. We find that transcription in fully developed conidia is modulated in response to changes in the environment until conidia leave the developmental structure. Environment-specific transcriptional responses can alter conidial content (mRNAs, proteins and secondary metabolites) and change gene expression when dormancy is broken. Conidial transcription affects the fitness and capabilities of fungal cells after germination, including stress and antifungal drug (azole) resistance, mycotoxin and secondary metabolite production and virulence. The transcriptional variation that we characterize in fungal conidia explains how genetically identical conidia mature into phenotypically variable conidia. We find that fungal conidia prepare for the future by synthesizing and storing transcripts according to environmental conditions present before dormancy.
Correlation between objects is prone to occur coincidentally, and exploring correlation or association in most situations does not answer scientific questions rich in causality. Causal discovery ...(also called causal inference) infers causal interactions between objects from observational data. Reported causal discovery methods and single-cell datasets make applying causal discovery to single cells a promising direction. However, evaluating and choosing causal discovery methods and developing and performing proper workflow remain challenges. We report the workflow and platform CausalCell (http://www.gaemons.net/causalcell/causalDiscovery/) for performing single-cell causal discovery. The workflow/platform is developed upon benchmarking four kinds of causal discovery methods and is examined by analyzing multiple single-cell RNA-sequencing (scRNA-seq) datasets. Our results suggest that different situations need different methods and the constraint-based PC algorithm with kernel-based conditional independence tests work best in most situations. Related issues are discussed and tips for best practices are given. Inferred causal interactions in single cells provide valuable clues for investigating molecular interactions and gene regulations, identifying critical diagnostic and therapeutic targets, and designing experimental and clinical interventions.
A precise evaluation of the fluid movability of coal sedimentary rock is crucial to the effective and secure utilization of coal measures gas reserves. Furthermore, its complex pore structure and ...diverse mineral components impact the flow properties of fluids in pore structures, causing accurate evaluation of fluid mobility to be extremely challenging. Nuclear magnetic resonance (NMR) technology is currently a prevalent technique to assess unconventional reservoirs due to its capacity to acquire abundant reservoir physical property data and determine fluid details. The free-fluid volume index (FFI) is a crucial factor in assessing fluid movability in the application of NMR technology, which can only be derived through intricate NMR saturation and centrifugation experiments This research utilized nuclear magnetic resonance (NMR) tests on 13 classic coal-measure sedimentary rock samples of three lithologies to reveal the FFI value. Moreover, the association between mineral components, pore structure parameters, and FFI was then extensively analyzed, and a prediction model for FFI was constructed. The results indicate that the T2 spectra of sandstone and shale own a bimodal distribution, with the principal point between 0.1 and 10 ms and the secondary peak between 10 and 100 ms. The majority of the T2 spectra of mudstone samples provide a unimodal distribution, with the main peak distribution range spanning between 0.1 and 10 ms, demonstrating that the most of the experimental samples are micropores and transition pores. The calculated results of the FFI range from 7.65% to 18.36%, and depict evident multifractal properties. Porosity, the content of kaolinite, multifractal dimension (Dq), and the FFI are linearly positively correlated. In contrast, the content of chlorite, illite, multifractal dimension subtraction (Dmin − Dmax), multifractal dimension proportion (Dmin/Dmax), and singularity strength (Δα) possess a negative linear correlation with the FFI, which can be further used for modeling. On the basis of the aforementioned influencing factors and the FFI experimental values of eight core samples, an FFI prediction model was constructed through multiple linear regression analysis. The accuracy of the prediction model was validated by utilizing this approach to five samples not included in the model development. It was revealed that the prediction model produced accurate predictions, and the research findings may serve as a guide for the classification and estimation of fluid types in coal reservoirs.
Transcription factors (TFs) play a crucial role in deciphering biological information from the DNA of living organisms. Improper regulation of their functions can disrupt cellular physiology and lead ...to diseases in humans. As one of the key regulatory mechanisms, some TFs control their own expression levels through autogenous regulation. However, identifying autogenous regulation events of TFs has been a tedious task. In this study, we present a straightforward approach that provides a reliable means to identify TF autogenous regulation events. Our method provides a valuable means for understanding the function of this important class of proteins in cells.
Abstract
2020 was an unprecedented year, with rapid and drastic changes in human mobility due to the COVID-19 pandemic. To understand the variation in commuting patterns among the Chinese population ...across stable and unstable periods, we used nationwide mobility data from 318 million mobile phone users in China to examine the extreme fluctuations of population movements in 2020, ranging from the Lunar New Year travel season (chunyun), to the exceptional calm of COVID-19 lockdown, and then to the recovery period. We observed that cross-city movements, which increased substantially in chunyun and then dropped sharply during the lockdown, are primarily dependent on travel distance and the socio-economic development of cities. Following the Lunar New Year holiday, national mobility remained low until mid-February, and COVID-19 interventions delayed more than 72.89 million people returning to large cities. Mobility network analysis revealed clusters of highly connected cities, conforming to the social-economic division of urban agglomerations in China. While the mass migration back to large cities was delayed, smaller cities connected more densely to form new clusters. During the recovery period after travel restrictions were lifted, the netflows of over 55% city pairs reversed in direction compared to before the lockdown. These findings offer the most comprehensive picture of Chinese mobility at fine resolution across various scenarios in China and are of critical importance for decision making regarding future public-health-emergency response, transportation planning and regional economic development, among others.
This article gives an overview of commuting patterns in China in 2020, offering the most comprehensive understanding on national mobility at fine resolution across various scenarios in China.
While incomplete non-medical data has been integrated into prediction models for epidemics, the accuracy and the generalizability of the data are difficult to guarantee. To comprehensively evaluate ...the ability and applicability of using social media data to predict the development of COVID-19, a new confirmed case prediction algorithm improving the Google Flu Trends algorithm is established, called Weibo COVID-19 Trends (WCT), based on the post dataset generated by all users in Wuhan on Sina Weibo. A genetic algorithm is designed to select the keyword set for filtering COVID-19 related posts. WCT can constantly outperform the highest average test score in the training set between daily new confirmed case counts and the prediction results. It remains to produce the best prediction results among other algorithms when the number of forecast days increases from one to eight days with the highest correlation score from 0.98 (P < 0.01) to 0.86 (P < 0.01) during all analysis period. Additionally, WCT effectively improves the Google Flu Trends algorithm's shortcoming of overestimating the epidemic peak value. This study offers a highly adaptive approach for feature engineering of third-party data in epidemic prediction, providing useful insights for the prediction of newly emerging infectious diseases at an early stage.
Electroacupuncture (EA) has a definite effect on the treatment of spinal cord injuries (SCIs), but its underlying molecular mechanism remains unclear. Meanwhile, MiR-106b-5p is an autophagy- and ...apoptosis-related micro-ribonucleic acid, but whether it regulates the progression of autophagy and apoptosis in SCIs is yet undetermined. As such, this study aimed to elucidate the involvement of miR-106b-5p in the EA treatment of an SCI.
The miR-106b-5p level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). In vitro, SH-SY5Y cells were transfected with miR-106b-5p mimics or inhibitors to regulate the miR-106b-5p expression, while in-vivo, SCI rats were treated with EA for 7 d at the bilateral Zusanli (ST36) and Jiaji (EX-B2) acupoints. The motor function was evaluated using the Basso-Beattie-Bresnahan (BBB) criteria. Further, autophagic vacuoles, pathological damage, and neuronal cell morphology were observed by transmission electron microscopy, as well as by hematoxylin and eosin and Nissl staining, respectively.
The miR-106b-5p level, which can interact directly with Beclin-1 by influencing its expression, as well as the expressions of P62, Caspase-3, and Bax, was upregulated after an SCI, but it decreased after EA. Moreover, the ratio of LC3-II to LC3-I was upregulated after EA. EA can enhance autophagy, reduce neuronal apoptosis, and minimize motor dysfunction and histopathological deficits after an SCI. More importantly, however, all the above effects induced by EA can be reversed after an injection of miR-106-5p agomir to produce an overexpression of miR-106b-5p.
EA treatment could downregulate miR-106b-5p to alleviate SCI-mediated injuries by promoting autophagy and inhibiting apoptosis.
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•Synthesis of structurally distinctive tetraarylphosphonium inner-salts (TAPIS).•TAPIS backbone could act as a Lewis base catalytic moiety.•TAPIS could act as phase tag to facilitate ...recycling and reuse of the catalyst.
Tetraarylphosphonium inner-salts (TAPIS) have been designed, synthesized and verified as recyclable and reusable Lewis base catalysts. The resulted TAPIS catalyst has been successfully applied in Michael addition, cyanation and trifluoromethylation reactions.
•The impacts of the TGD on downstream streamflow fluctuations are considered.•The GARCH model is used to capture heteroscedasticity in streamflow.•The joint fluctuations between streamflow series at ...different sites are analyzed.
The impacts of dams on the downstream streamflow is an important issue for the downstream flood control and water resources management. Most of the existing researches only focus on the impacts of dams on the first-order behavior of streamflow, i.e. its magnitude, but ignore the impacts on the second-order behavior of streamflow, i.e. its fluctuation. This study is aimed to study the impacts of the Three Gorges Dam (TGD) on the downstream flow in terms of not only their magnitudes but also fluctuations. The study method includes two steps, i.e. first to use the ARMAX-GARCH model to simulate the conditional mean and conditional variance of the single-site downstream streamflow series, and then to use the DCC-GARCH model to simulate the conditional covariance between streamflow series at different downstream sites. The method is applied to the downstream data series of the TGD for both the pre-dam period and post-dam period. By comparing the results of the two time periods, the conclusions are made as follows: (1) The TGD alleviates the extreme downstream streamflow, and this effect gradually weakens along the river; (2) the memory of single-site streamflow fluctuations in the mainstream of the middle reaches of the Yangtze River has been weakened by the TGD, the memory of streamflow fluctuations in the mainstream of the lower reaches has been enhanced; (3) the single-site streamflow fluctuations of Yichang and Datong have been enhanced by the TGD, and the streamflow fluctuations of the four sites between Yichang and Datong have been weakened; (4) the joint fluctuations (i.e. the covariance) and correlation between the streamflow series at different sites in the middle reaches of the Yangtze River have been weakened by the TGD, the joint fluctuations and correlation at different sites in the lower reaches have been enhanced. The results of this study are helpful for an improved understanding of the impacts of the dam on the downstream streamflow.
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