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In plants, miR390 directs the production of tasiRNAs from TRANS-ACTING SIRNA3 (TAS3) transcripts to regulate AUXIN RESPONSIVE FACTOR (ARF) genes, critical for auxin signaling; these tasiRNAs are known as tasiARFs. To understand the evolution of this miR390-TAS3-ARF pathway, we characterized homologs of these three genes from thousands of plant species, from bryophytes to angiosperms. We found the lower-stem region of MIR390 genes, critical for accurate DICER-LIKE1 processing, is conserved in sequence in seed plants. We propose a model for the transition of functional tasiRNA sequences in TAS3 genes occurred at the emergence of vascular plants, in which the two miR390 target sites of TAS3 genes showed distinct pairing patterns. Based on the cleavability of miR390 target sites and the distance between target site and tasiARF, we inferred a potential bidirectional processing mechanism exists for some TAS3 genes. We also demonstrated a tight mutual selection between tasiARF and its target genes and that ARGONAUTE7, the partner of miR390, was specified later than other factors in the pathway. All these data illuminate the evolutionary path of the miR390-TAS3-ARF pathway in land plants and demonstrate the significant variation that occurs in this functionally important and archetypal regulatory circuit.

Trichoderma harzianum strain SQR-T037 is a biocontrol agent that has been shown to enhance the uptake of nutrients (macro- and microelements) by plants in fields. The objective of this study was to investigate the contribution of SQR-T037 to P and microelement (Fe, Mn, Cu and Zn) nutrition in tomato plants grown in soil and in hydroponic conditions. Inoculation with SQR-T037 significantly improved the biomass and nutrient uptake of tomato seedlings grown in a nutrient-limiting soil. So we investigated the capability of SQR-T037 to solubilise sparingly soluble minerals in vitro via four known mechanisms: acidification by organic acids, chelation by siderophores, redox by ferric reductase and hydrolysis by phytase. SQR-T037 was able to solubilise phytate, Fe2O3, CuO, and metallic Zn but not Ca3(PO4)2 or MnO2. Organic acids, including lactic acid, citric acid, tartaric acid and succinic acid, were detected by HPLC and LC/MS in two Trichoderma cultures. Additionally, we inoculated tomato seedlings with SQR-T037 using a hydroponic system with specific nutrient deficiencies (i.e., nutrient solutions deficient in P, Fe, Cu or Zn and supplemented with their corresponding solid minerals) to better study the effects of Trichoderma inoculation on plant growth and nutrition. Inoculated seedlings grown in Cu-deficient hydroponic conditions exhibited increases in dry plant biomass (92%) and Cu uptake (42%) relative to control plants. However, we did not observe a significant effect on seedling biomass in plants grown in the Fe- and Zn-deficient hydroponic conditions; by contrast, the biomass decreased by 82% in the P-deficient hydroponic condition. Thus, we demonstrated that Trichoderma SQR-T037 competed for P (phytate) and Zn with tomato seedlings by suppressing root development, releasing phytase and/or chelating minerals. The results of this study suggest that the induction of increased or suppressed plant growth occurs through the direct effect of T. harzianum on root development, in combination with indirect mechanisms, such as mineral solubilisation (including solubilisation via acidification, redox, chelation and hydrolysis).

Background Alzheimer’s disease (AD), as the most common cause of dementia, brings huge economic burden for patients and social health care systems, which motivates researchers to study multiple protective factors, among which physical activity and exercise have been proven to be both effective and economically feasible. Methods A systematic literature search was performed for eligible studies published up to November 1st 2018 on three international databases (PubMed, Cochrane Library, and Embase) and two Chinese databases (Wanfang Data, China National Knowledge Infrastructure). All analyses were conducted using Stata 14.0. Due to heterogeneity between studies, a random-effects model was used for this meta-analysis. Meta-analysis was used to explore if physical activity and exercise can exert positive effects on cognition of elderly with AD and subgroup analyses were conducted to find out if there are dose-response effects. Results A total of 13 randomized controlled trials were included with a sample size of 673 subjects diagnosed with AD. Intervention groups showed a statistically significant improvement in cognition of included subjects measured by the MMSE score (SMD = 1.12 CI:0.66~1.59) compared to the control groups. Subgroup analyses showed different amounts of physical activity and exercise can generate different effects. Conclusions As one of few meta-analyses comparing different quantities of physical activity and exercise interventions for AD in details, our study suggests that physical activity and exercise can improve cognition of older adults with AD. While the concomitant effects on cognition functions of high frequency interventions was not greater than that of low frequency interventions, the threshold remains to be settled. However, more RCTs with rigorous study design are needed to support our findings.

Abnormal function of suborganelles such as mitochondria and endoplasmic reticulum often leads to abnormal function of cardiomyocytes or vascular endothelial cells and cardiovascular disease (CVD). Mitochondria-associated membrane (MAM) is involved in several important cellular functions. Increasing evidence shows that MAM is involved in the pathogenesis of CVD. MAM mediates multiple cellular processes, including calcium homeostasis regulation, lipid metabolism, unfolded protein response, ROS, mitochondrial dynamics, autophagy, apoptosis, and inflammation, which are key risk factors for CVD. In this review, we discuss the structure of MAM and MAM-associated proteins, their role in CVD progression, and the potential use of MAM as the therapeutic targets for CVD treatment.

Spatially resolved omics technologies reveal the spatial organization of cells in various biological systems. Here we propose SLAT (Spatially-Linked Alignment Tool), a graph-based algorithm for efficient and effective alignment of spatial slices. Adopting a graph adversarial matching strategy, SLAT is the first algorithm capable of aligning heterogenous spatial data across distinct technologies and modalities. Systematic benchmarks demonstrate SLAT’s superior precision, robustness, and speed over existing state-of-the-arts. Applications to multiple real-world datasets further show SLAT’s utility in enhancing cell-typing resolution, integrating multiple modalities for regulatory inference, and mapping fine-scale spatial-temporal changes during development. The full SLAT package is available at https://github.com/gao-lab/SLAT . Spatial omics technologies reveal the organisation of cells in various biological systems. Here, authors propose SLAT, a graph-based algorithm for aligning heterogenous data across technologies, modalities and timepoints, enabling spatiotemporal reconstruction of complex developmental processes.

The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of glycocalyx in various pathological and physiological conditions, by reviewing the basic research findings pertaining to the detection of eGC and its clinical significance. We also explores different pharmacological agents used to protect and rebuild the glycocalyx. Anin-depthsearch was performed in the PubMed database, focusing on research published after 2003 with keywords including endothelial glycocalyx, permeability, glycocalyx and injuries, and glycocalyx protection. Several authoritative reviews and original studies, were identified and reviewed to summarize the characteristics of the eGC under physiological and pathological conditions as well as the detection and protection of the glycocalyx. The eGC degradation is closely associated with pathophysiological changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia and high Na as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. Disturbance of glycocalyx usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

STING (stimulator of interferon genes) also known as transmembrane protein 173 (TMEM173) is a cytoplasmic DNA sensor which can be activated by the upstream cyclic dinucleotides (CDNs). This activation produces cytokines such as interferons and pro-inflammatory factors via the downstream IRF3 and NF-κB pathways, triggering an innate immune response and adaptive immunity to maintain homeostasis. STING is mainly expressed and activated in non-parenchymal cells, thus exerting a corresponding effect to maintain the homeostasis of the liver. In viral hepatitis, interferons and pro-inflammatory factors produced after STING activation initiate the immune response to inhibit virus replication and assembly. In the case of metabolic diseases of the liver, the activation of STING in kupffer cells and hepatic stellate cells leads to inflammation, the proliferation of connective tissue, and metabolic disorders in the hepatocytes, promoting the occurrence and development of the disease. In hepatocellular carcinoma, STING has two contradictory roles. When STING is activated in dendritic cells and macrophages, a large number of cytokines can be produced to initiate innate immune effects directly and to exert adaptive immunity through the recruitment and activation of T cells; however, aberrant activation of the STING pathway leads to a weakening of immune function and promotes oncogenesis and metastasis. Here, we summarize the interactions between STING and liver disease that have currently been identified and how to achieve therapeutic goals by modulating the activity of the STING pathway.

Circos plots enable scientists to easily inspect big biological data genome‐widely on a macroscopic scale, but cumbersome preparation of input data and complex parameter configuration limits its application. We have developed the “Advanced Circos” function in TBtools, to provide a simple way to construct Circos plots. As an out‐of‐the‐box combo toolkit, TBtools has integrated a set of functions convenient for input data preparation. The “Advanced Circos” function is supplied with a user‐friendly interface for the customization of parameter settings and can be deployed to visualize all kinds of genomic data, such as genomic associations, alignment data, gene density, and QTL locations. In the present article, we introduce the main features of “Advance Circos” and the protocols of upstream data preparation, aiming to endow more users with the ability to use Circos plots in big genomic data exploration. Highlights An out‐of‐the‐box solution for genome‐scale data visualization A step‐by‐step protocol for Circos plot configuration Reproducible and resumable project management Coming with a handy toolkit, Advanced Circos in TBtools provides a painless way to construct Circos Plots starting from input file preparation. Tracks including associated regions, dot plots, line plots, bar plots, heatmap, feature tags, and so forth are all supported. Try it! Coordination transformation and graphics element manipulation are quite easy.

Small RNAs are key regulators in plant growth and development. One subclass, phased siRNAs (phasiRNAs) require a trigger microRNA for their biogenesis. In grasses, two pathways yield abundant phasiRNAs during anther development; miR2275 triggers one class, 24-nt phasiRNAs, coincident with meiosis, while a second class of 21-nt phasiRNAs are present in premeiotic anthers. Here we report that the 24-nt phasiRNA pathway is widely present in flowering plants, indicating that 24-nt reproductive phasiRNAs likely originated with the evolutionary emergence of anthers. Deep comparative genomic analyses demonstrated that this miR2275/24-nt phasiRNA pathway is widely present in eudicots plants, however, it is absent in legumes and in the model plant Arabidopsis, demonstrating a dynamic evolutionary history of this pathway. In Solanaceae species, 24-nt phasiRNAs were observed, but the miR2275 trigger is missing and some loci displaying 12-nt phasing. Both the miR2275-triggered and Solanaceae 24-nt phasiRNAs are enriched in meiotic stages, implicating these phasiRNAs in anther and/or pollen development, a spatiotemporal pattern consistent in all angiosperm lineages that deploy them. 24-nt phased siRNA (phasiRNA) regulate reproduction in grasses, yet are absent from Arabidopsis , and were thought to be monocot-specific. Here, Xia et al. show that 24-nt phasiRNAs are in fact broadly distributed among eudicots and are consistently enriched during meiosis, despite possibly arising from distinct biogenesis pathways.

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain. Gastric pain has limited treatment options and the nociceptive ascending pathway remains largely unclear. Here, the authors identify a glutamatergic tetra-synaptic NTS–LPB–PVT–PL circuit that provides a basis for the clinical treatment of gastric pain.