Despite the continued efforts, a batch-insensitive tool that can both infer and predict the developmental dynamics using single-cell genomics is lacking. Here, I present scTour, a novel deep learning ...architecture to perform robust inference and accurate prediction of cellular dynamics with minimal influence from batch effects. For inference, scTour simultaneously estimates the developmental pseudotime, delineates the vector field, and maps the transcriptomic latent space under a single, integrated framework. For prediction, scTour precisely reconstructs the underlying dynamics of unseen cellular states or a new independent dataset. scTour's functionalities are demonstrated in a variety of biological processes from 19 datasets.
This article reviews the current state of knowledge regarding the epidemiology of frailty by focusing on 6 specific areas: (1) clinical definitions of frailty, (2) evidence of frailty as a medical ...syndrome, (3) prevalence and incidence of frailty by age, gender, race, and ethnicity, (4) transitions between discrete frailty states, (5) natural history of manifestations of frailty criteria, and (6) behavior modifications as precursors to the development of clinical frailty.
The reprogramming of somatic cells with defined factors, which converts cells from one lineage into cells of another, has greatly reshaped our traditional views on cell identity and cell fate ...determination. Direct reprogramming (also known as transdifferentiation) refers to cell fate conversion without transitioning through an intermediary pluripotent state. Given that the number of cell types that can be generated by direct reprogramming is rapidly increasing, it has become a promising strategy to produce functional cells for therapeutic purposes. This Review discusses the evolution of direct reprogramming from a transcription factor-based method to a small-molecule-driven approach, the recent progress in enhancing reprogrammed cell maturation, and the challenges associated with in vivo direct reprogramming for translational applications. It also describes our current understanding of the molecular mechanisms underlying direct reprogramming, including the role of transcription factors, epigenetic modifications, non-coding RNAs, and the function of metabolic reprogramming, and highlights novel insights gained from single-cell omics studies.
Arabidopsis thaliana high-affinity potassium transporter 1 (AtHKT1) limits the root-to-shoot sodium transportation and is believed to be essential for salt tolerance in A. thaliana. Nevertheless, ...natural accessions with 'weak allele' of AtHKT1, e.g. Tsu-1, are mainly distributed in saline areas and are more tolerant to salinity. These findings challenge the role of AtHKT1 in salt tolerance and call into question the involvement of AtHKT1 in salinity adaptation in A. thaliana. Here, we report that AtHKT1 indeed drives natural variation in the salt tolerance of A. thaliana and the coastal AtHKT1, so-called weak allele, is actually hyper-functional in reducing flowers sodium content upon salt stress. Our data showed that AtHKT1 positively contributes to saline adaptation in a linear manner. Forward and reverse genetics analysis established that the single AtHKT1 locus is responsible for the variation in the salinity adaptation between Col-0 and Tsu-1. Reciprocal grafting experiments revealed that shoot AtHKT1 determines the salt tolerance of Tsu-1, whereas root AtHKT1 primarily drives the salt tolerance of Col-0. Furthermore, evidence indicated that Tsu-1 AtHKT1 is highly expressed in stems and is more effective compared to Col-0 AtHKT1 at limiting sodium flow to the flowers. Such efficient retrieval of sodium to the reproductive organ endows Tsu-1 with stronger fertility compared to Col-0 upon salt stress, thus improving Tsu-1 adaptation to a coastal environment. To conclude, our data not only confirm the role of AtHKT1 in saline adaptation, but also sheds light on our understanding of the salt tolerance mechanisms in plants.
Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some ...biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.
A transition‐metal‐free visible‐light‐promoted radical phosphorylation/cyclization of N‐allylbenzamides with phosphine oxides for the synthesis of phosphoryl‐substituted dihydroisoquinolones was ...developed under room temperature. This protocol features mild reaction conditions, simple operation, broad substrate scope as well as scale‐up ability.
In this paper, a chiral metastructure absorber (CMMA) is combined with a circularly polarized (CP) antenna array based on a sequential-phase feed network, and the differential absorption of ...left-handed circular polarization (LHCP) and right-handed circular polarization (RHCP) by CMMA unit is used to improve the axial ratio beamwidth (ARBW) of CP antenna array by absorbing the cross-polarization of the antenna array. The proposed CMMA unit achieves good circular dichroism at 4.9~5.2 GHz, which improves the ARBW of the antenna in this frequency band. In addition, the feed network of the antenna proposed in this paper is in three-dimensional (3D) form to reduce the coupling between the feed network and the radiation patches, so that higher gain can be obtained. The measured impedance bandwidth of the antenna is 80% (2.81~6.81 GHz), the axial ratio (AR) bandwidth is 70.8% (3.68 ~7.22 GHz) and the peak gain is 15.28 dBi.
Analysis of the hydrogenation and dehydrogenation behaviors by kinetic models is an efficient approach to the in-depth understanding of the kinetic mechanism for hydrogen storage materials. A large ...number of kinetic models as well as analysis methods based on these models have been extensively applied in hydrogen storage materials, and kinetic parameters with physical interpretations are determined to reveal the kinetic mechanism of hydrogenation and dehydrogenation reactions. However, the assumptions and derivation steps of these models are usually difficult to find, and the selection of analysis methods is sometimes confusing. Moreover, some recently proposed models and analysis methods have not been introduced to investigate the kinetic mechanism of hydrogen storage materials yet. These problems significantly prevent the kinetic models as well as analysis methods from further revealing the kinetic mechanism for hydrogen storage materials. Therefore, this review mainly focuses on the illustration of the assumptions and derivation steps of the kinetic models, summarization of corresponding analysis methods, and introduction of some recently proposed kinetic models and analysis methods for hydrogen storage materials.
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•Analysis of kinetic behaviors for hydrogen storage materials reveals mechanisms.•The assumptions and derivation steps of the kinetic models are illustrated.•The analysis methods on the basis of the kinetic models are summarized.•Some new proposed models and analysis methods are introduced.
Tau, an important pathological protein of Alzheimer's disease (AD), can mediate the toxicity of amyloid β (Aβ). Thus, reduction of Tau with chemical molecules may offer a novel strategy for treating ...AD. Here, we designed and synthesized a series of multifunctional molecules that contained Tau-recognition moieties and E3 ligase-binding moieties to enhance Tau degradation. Among these molecules, TH006 had the highest activity of inducing Tau degradation by increasing its poly-ubiquitination. The decrement in Tau induced by TH006 could decrease the cytotoxicity caused by Aβ. Furthermore, TH006 could regulate the Tau level in the brain of an AD mouse model. Therefore, partial reduction of Tau with such multifunctional peptides may open up a novel therapeutic strategy for AD treatment.
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•Synthesized multifunctional PROTACs peptide TH006 effectively induces Tau degradation•TH006 increases poly-ubiquitination of Tau depending on VHL E3 ligase•Decrement of Tau induced by TH006 reduces the cytotoxicity caused by Aβ•TH006 can promote Tau reduction in primary neuron cells and 3xTg-AD mice
Tau, involved in Alzheimer's disease, is an intrinsically disordered protein which is difficult to be regulated. Chu et al. design and synthesize a multifunctional PROTACs peptide, TH006, to induce intracellular Tau degraded by increasing its poly-ubiquitination. Partial reduction of Tau induced by TH006 prevents cytotoxicity caused by Aβ.
While the f0 realization of lexical tones vary extensively in contexts, little has been known on how listeners process the variation in lexical tones due to contextual effects such as tonal ...coarticulation in spoken word recognition. This study thus aims to fill the knowledge gap in tone perception with evidence from two types of anticipatory tonal coarticulation effects in Tianjin Mandarin, i.e., the slope raising effect due to a following low-falling tone and the overall-height raising effect due to a following low-dipping tone. An eye-tracking experiment with the Visual World Paradigm was carried out to compare participants' eye movements when they heard targets in three types of anticipatory raising conditions, i.e., the Slope Raising condition, the Overall-height Raising condition, as well as the No Raising condition (the baseline). The eye movement results showed significant differences in the proportion of looks to target between the Slope Raising condition versus the other two conditions, whereas the Overall-height Raising condition did not differ significantly from the No Raising condition. The findings thus suggest the facilitatory effect of tonal coarticulation cues in the anticipation of the upcoming tones, but listeners in this study seemed to be only sensitive to the raising in the f0 slope rather than the overall raising in the f0 height.
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