Miracle-dz/UniFAR-FTUs huggingface dataset:
Target of Rapamycin Regulates Genome Methylation Reprogramming to Control Plant Growth in Arabidopsis

DNA methylation is an indispensable epigenetic modification that dynamically regulates gene expression and genome stability during cell growth and development processes. The target of rapamycin (TOR) has emerged as a central regulator to regulate many fundamental cellular metabolic processes from protein synthesis to autophagy in all eukaryotic species. However, little is known about the functions of TOR in DNA methylation. In this study, the synergistic growth inhibition of Arabidopsis seedlings can be observed when DNA methylation inhibitor azacitidine was combined with TOR inhibitors. Global DNA methylation level was evaluated using whole-genome bisulfite sequencing (WGBS) under TOR inhibition. Hypomethylation level of whole genome DNA was observed in AZD-8055 (AZD), rapamycin (RAP) and AZD + RAP treated Arabidopsis seedlings. Based on functional annotation and KEGG pathway analysis of differentially methylated genes (DMGs), most of DMGs were enriched in carbon metabolism, biosynthesis of amino acids and other metabolic processes. Importantly, the suppression of TOR caused the change in DNA methylation of the genes associated with plant hormone signal transduction, indicating that TOR played an important role in modulating phytohormone signals in Arabidopsis. These observations are expected to shed light on the novel functions of TOR in DNA methylation and provide some new insights into how TOR regulates genome DNA methylation to control plant growth.
Pentameric Ligand-Gated Ion Channels as Pharmacological Targets Against Chronic Pain

Chronic pain is a common detrimental condition that affects around 20% of the world population. The current drugs to treat chronic pain states, especially neuropathic pain, have a limited clinical efficiency and present significant adverse effects that complicates their regular use. Recent studies have proposed new therapeutic strategies focused on the pharmacological modulation of G-protein-coupled receptors, transporters, enzymes, and ion channels expressed on the nociceptive pathways. The present work intends to summarize recent advances on the pharmacological modulation of pentameric ligand-gated ion channels, which plays a key role in pain processing. Experimental data have shown that novel allosteric modulators targeting the excitatory nicotinic acetylcholine receptor, as well as the inhibitory GABAA and glycine receptors, reverse chronic pain-related behaviors in preclinical assays. Collectively, these evidences strongly suggest the pharmacological modulation of pentameric ligand-gated ion channels is a promising strategy towards the development of novel therapeutics to treat chronic pain states in humans.
Dissection of Superior Alleles for Yield-Related Traits and Their Distribution in Important Cultivars of Wheat by Association Mapping

Uncovering the genetic basis of yield-related traits is important for molecular improvement of wheat cultivars. In this study, a genome-wide association study was conducted using the wheat 55K genotyping assay and a diverse panel of 384 wheat genotypes. The accessions used included 18 founder parents and 15 widely grown cultivars with annual maximum acreages of over 667,000 ha, and the remaining materials were elite cultivars and breeding lines from several major wheat ecological areas of China. Field trials were conducted in five major wheat ecological regions of China over three consecutive years. A total of 460 significant loci were detected for eight yield-related traits. Forty-five superior alleles distributed over 31 loci for which differences in phenotypic values grouped by single nucleotide polymorphism (SNP) reached significant levels (P < 0.05) in nine or more environments, were detected; some of these loci were previously reported. Eleven of the 31 superior allele loci on chromosomes 4A, 5A, 3B, 5B, 6B, 7B, 5D, and 7D had pleiotropic effects. For example, AX-95152512 on 5D was simultaneously related to increased grain weight per spike (GWS) and decreased plant height (PH); AX-109860828 on 5B simultaneously led to a high 1,000-kernel weight (TKW) and short PH; and AX-111600193 on 4A was simultaneously linked to a high TKW and GWS, and short PH. The favorable alleles in each accession ranged from 2 to 30 with an average of 16 at the thirty-one loci in the population, and six accessions (Zhengzhou683, Suzhou7829, Longchun7, Ningmai6, Yunmai35 and Zhen7630) contained more than 27 favorable alleles. A significant association between the number of favorable alleles and yield was observed (r = 0.799, p < 0.0001), suggesting that pyramiding multiple QTL with marker-assisted selection may effectively increase yield of wheat. Furthermore, distribution of superior alleles in founder parents and widely grown cultivars was also discussed here. This study is useful for marker-assisted selection for yield improvement and dissecting the genetic mechanism of important cultivars in wheat.
Additive-Free MXene Liquid Crystals and Fibers

The discovery of liquid crystalline (LC) phases in dispersions of two-dimensional (2D) materials has enabled the development of macroscopically aligned three-dimensional (3D) macrostructures. Here, we report the first experimental observation of self-assembled LC phases in aqueous Ti3C2Tx MXene inks without using LC additives, binders, or stabilizing agents. We show that the transition concentration from the isotropic to nematic phase is influenced by the aspect ratio of MXene flakes. The formation of the nematic LC phase makes it possible to produce fibers from MXenes using a wet-spinning method. By changing the Ti3C2Tx flake size in the ink formulation, coagulation bath, and spinning parameters, we control the morphology of the MXene fibers. The wet-spun Ti3C2Tx fibers show a high electrical conductivity of ∼7750 S cm–1, surpassing existing nanomaterial-based fibers. A high volumetric capacitance of ∼1265 F cm–3 makes Ti3C2Tx fibers promising for fiber-shaped supercapacitor devices. We also show that Ti3C2Tx fibers can be used as heaters. Notably, the nematic LC phase can be achieved in other MXenes (Mo2Ti2C3Tx and Ti2CTx) and in various organic solvents, suggesting the widespread LC behavior of MXene inks.
Altered Global Brain Functional Connectivity in Drug-Naive Patients With Obsessive-Compulsive Disorder

Abnormal functional connectivity (FC) within discrete brain networks is involved in the pathophysiology of obsessive-compulsive disorder (OCD) with inconsistent results. In the present study, we investigated the FC patterns of 40 drug-naive patients with OCD and 38 healthy controls (HCs) through an unbiased voxel-wise global brain FC (GFC) analysis at rest. Compared with HCs, patients with OCD showed decreased GFC within the default mode network (DMN) (i.e., left posterior cingulate cortex/lingual gyrus) and sensorimotor network (i.e., left precentral gyrus/postcentral gyrus) and increased GFC within the executive control network (ECN) (i.e., left dorsal lateral prefrontal cortex and left inferior parietal lobule). Receiver operating characteristic curve analyses further indicated that the altered GFC values within the DMN, ECN, and sensorimotor network may be used as neuroimaging markers to differentiate patients with OCD from HCs. These findings indicated the aberrant FC patterns of the DMN, ECN, and sensorimotor network associated with the pathophysiology of OCD and provided new insights into the changes in brain organization function in OCD.
Lava Flows Erupted in 1996 on North Gorda Ridge Segment and the Geology of the Nearby Sea Cliff Hydrothermal Vent Field From 1-M Resolution AUV Mapping

The northernmost segment of the Gorda mid-ocean ridge is the site of a small-volume eruption in 1996 and the persistent off-axis Sea Cliff hydrothermal vent field. To better understand the geologic setting and formation of these features, 1-m resolution bathymetric mapping using autonomous underwater vehicles was completed in 2016. The mapped region covers 35 km2 and 15.6 km of the volcanic axis from south of the 1996 lava flows, and a cross section for ∼4.5 km perpendicular to the axis, that extends beyond the Sea Cliff hydrothermal vent field. A proposed 1996 flow ∼7 km south of previously mapped flows is an artifact from a poor pre-eruption survey. The 1996 flows consist of three discrete steep hummocky mounds of pillows and syneruptive talus. The Sea Cliff hydrothermal field is located a few km north of the narrowest, shallowest section of the ridge segment, 2.6 km east of the center of the neovolcanic zone, and ∼370 m above the average depth of the axial graben on the largest offset ridge-parallel fault. No evidence supports the prior hypothesis that the site is located where two fault systems intersect. The axial graben is asymmetrical with larger fault offsets on the east side. The ridge axis below the hydrothermal field and to the south toward the 1996 flows is constructed dominantly of hummocky flows of pillow basalt, many unusually steep-sided, with syneruptive talus at the base of their steep slopes. Three channelized flows ponded between steep hummocky flows, and then partially drained. Some low-eruption-rate hummocky flows and high-eruption-rate channelized flows have nearly identical compositions, supporting the idea that eruption rates on mid-ocean ridges vary because of different dike widths. Four volcanic structures with volumes between 0.18 and 0.25 km3 occur in the axial graben south of the 1996 flows. Two are flat-topped cones, another is a 1.5-km diameter inflated hummocky flow with 7 pit craters that demonstrate that the flow had a molten interior during growth. The fourth voluminous structure is a steep ridge with abundant syneruptive talus on its lower slopes. The North Gorda segment is an end-member, structurally and volcanically, compared with other Pacific intermediate-rate spreading ridges.
Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants

Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other’s observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.
Fc-Linked IgG N-Glycosylation in FcγR Knock-Out Mice

Immunoglobulin G (IgG) is the most abundant immunoglobulin isotype in the blood and is involved in the pathogenesis and progression of various diseases. Glycosylation of the IgG fragment crystallizable (Fc) region is shown to vary in different physiological and pathological states. Fc N-glycan composition can alter the effector functions of IgG by modulating its affinity for ligands, such as Fcγ receptors (FcγRs). However, it is not known whether IgG glycosylation is affected by the available repertoire of FcγRs, and if the Fc-linked N-glycome can compensate for modulation of the IgG–FcγR interaction. To explore this, we examined the subclass-specific Fc IgG glycoprofiles of healthy male and female FcγR knock-out mice on C57BL/6 and BALB/c backgrounds. We observed slight changes in IgG Fc N-glycan profiles in different knock-outs; however, it seems that the strain background and sex have a stronger effect on N-glycosylation of IgG Fc regions than the FcγR repertoire.
Repositioning of Hypoglycemic Drug Linagliptin for Cancer Treatment

Background Drug repositioning, development of new uses for marketed drugs, is an effective way to discover new antitumor compounds. In this study, we used a new method, filtering compounds via molecular docking to find key targets combination. Methods The data of gene expression in cancer and normal tissues of colorectal, breast, and liver cancer were obtained from The Cancer Genome Atlas Project (TCGA). The key targets combination was obtained from the protein-protein interaction network (PPI network) and the correlation analysis of the targets. Molecular docking was used to reposition the drugs which were obtained from DrugBank. MTT proliferation assay and animal experiments were used to verify the activity of candidate compounds. Flow cytometric analysis of proliferation, cell cycle and apoptosis, slice analysis, gene regulatory network, and Western blot were performed to elucidate the mechanism of drug action. Results CDK1 and AURKB were identified as a pair of key targets by the analysis of different expression gene from TCGA. Three compounds, linagliptin, mupirocin, and tobramycin, from 12 computationally predicted compounds, were verified to inhibit cell viability in HCT116 (colorectal), MCF7 (breast), and HepG2 (liver) cancer cells. Linagliptin, a hypoglycemic drug, was proved to inhibit cell proliferation by cell cycle arrest and induce apoptosis in HCT116 cells, and suppress tumor growth in nude mice bearing HCT116 cells. Linagliptin reduced the tumor size and decreased the expression of Ki67, a nuclear protein expressed in all proliferative cells. Gene regulatory network and Western blot analysis suggested that linagliptin inhibited tumor cell proliferation and promoted cell apoptosis through suppressing the expression and phosphorylation of Rb, plus down-regulating the expression of Pro-caspase3 and Bcl-2, respectively. Conclusion The combination of key targets based on the protein-protein interaction network that were built by the different gene expression of TCGA data to reposition the marketed drugs turned out to be a new approach to discover new antitumor drugs. Hypoglycemic drug linagliptin could potentially lead to novel therapeutics for the treatment of tumors, especially for colorectal cancer. Gene regulatory network is a valuable method for predicting and explaining the mechanism of drugs action.
Effects of OsMSH6 Mutations on Microsatellite Stability and Homeologous Recombination in Rice

DNA mismatch repair (MMR) system is important for maintaining DNA replication fidelity and genome stability by repairing erroneous deletions, insertions and mis-incorporation of bases. With the aim of deciphering the role of the MMR system in genome stability and recombination in rice, we investigated the function of OsMSH6 gene, an import component of the MMR system. To achieve this goal, homeologous recombination and endogenous microsatellite stability were evaluated by using rice mutants carrying a Tos17 insertion into the OsMSH6 gene. Totally 60 microsatellites were analyzed and 15 distributed on chromosome 3, 6, 8, and 10 showed instability in three OsMSH6 mutants, D6011, NF7784 and NF9010, compared with the wild type MSH6WT (the control). The disruption of OsMSH6 gene is associated with modest increases in homeologous recombination, ranging from 2.0% to 32.5% on chromosome 1, 3, 9, and 10 in the BCF2 populations of the mutant ND6011 and NF9010. Our results suggest that the OsMSH6 plays an important role in ensuring genome stability and genetic recombination, providing the first evidence for the MSH6 gene in maintaining microsatellite stability and restricting homeologous recombination in plants.
Resilient Authentication and Authorization for the Internet of Things (IoT) Using Edge Computing

An emerging type of network architecture called edge computing has the potential to improve the availability and resilience of IoT services under anomalous situations such as network failures or denial-of-service (DoS) attacks. However, relatively little has been explored on the problem of ensuring availability even when edge computers that provide key security services (e.g., authentication and authorization) become unavailable themselves. This article proposes a resilient authentication and authorization framework to enhance the availability of IoT services under DoS attacks or failures. The proposed approach leverages a technique called secure migration, which allows an IoT device to migrate to another trusted edge computer when its own local authorization service becomes unavailable. Specifically, we describe the design of a secure migration framework and its supporting mechanisms, including (1) automated migration policy construction and (2) protocols for preparing and executing the secure migration. We formalize secure migration policy construction as an integer linear programming (ILP) problem and show its effectiveness using a case study on smart buildings, where the proposed solution achieves significantly higher availability under simulated attacks on authorization services.
MCC950, a Selective Inhibitor of NLRP3 Inflammasome, Reduces the Inflammatory Response and Improves Neurological Outcomes in Mice Model of Spinal Cord Injury

Spinal cord injury (SCI) is a serious condition that affects bodily function; however, there is no effective therapy in clinical practice. MCC950, a selective NOD-like receptor protein-3 (NLRP3) inflammasome inhibitor, has been reported to alleviate canonical and non-canonical NLRP3 inflammasome activation of the inflammatory response in vitro and in vivo. However, the effect of MCC950 treatment on neurological post-SCI recovery remains unclear. In this study, we assessed the pharmacological effect of MCC950 on an experimental SCI model in vivo and neuronal injury in vitro. We found that MCC950 improved the grip strength, hind limb movements, spinal cord edema, and pathological injury in the SCI mice. We demonstrated that it exerted this effect by blocking NLRP3 inflammasome assembly, including NLRP3-ASC and NLRP3-Caspase-1 complexes, as well as the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18. Moreover, we found that MCC950 reduced spinal neuron injury and NLRP3 inflammasome activation, which had been induced by oxygen–glucose deprivation (OGD) or lipopolysaccharides (LPS) in vitro. In conclusion, our findings indicate that MCC950 alleviates inflammatory response and improves functional recovery in the acute mice model of SCI by blocking NLRP3 inflammasome assembly and alleviating downstream neuroinflammation. Therefore, these findings could prove useful in the development of effective therapeutic strategies for the treatment and prognosis of SCI.
On the Face of It: No Differential Sensitivity to Internal Facial Features in the Dog Brain

Dogs are looking at and gaining information from human faces in a variety of contexts. Next to behavioral studies investigating the topic, recent fMRI studies reported face sensitive brain areas in dogs' temporal cortex. However, these studies used whole heads as stimuli which contain both internal (eyes, nose, mouth) and external facial features (hair, chin, face-outline). Behavioral studies reported that (1) recognition of human faces by dogs requires visibility of head contour and that (2) dogs are less successful in recognizing their owners from 2D pictures than from real human heads. In contrast, face perception in humans heavily depends on internal features and generalizes to 2D images. Whether putative face sensitive regions in dogs have comparable properties to those of humans has not been tested so far. In two fMRI experiments, we investigated (1) the location of putative face sensitive areas presenting only internal features of a real human face vs. a mono-colored control surface and (2) whether these regions show higher activity toward live human faces and/or static images of those faces compared to scrambled face images, all with the same outline. In Study 1 (n = 13) we found strong activity for faces in multiple regions, including the previously described temporo-parietal and occipital regions when the control was a mono-colored, homogeneous surface. These differences disappeared in Study 2 (n = 11) when we compared faces to scrambled faces, controlling for low-level visual cues. Our results do not support the assumption that dogs rely on a specialized brain region for processing internal facial characteristics, which is in line with the behavioral findings regarding dogs inability to recognize human faces based on these features.
Significant contribution of fibrils on pulp fiber surface to water retention value

Abstract The contribution of structural changes of softwood bleached kraft pulp (SBKP) fibers and partly dried SBKP handsheets to their water retention values (WRVs) was studied. Two factors related to mesopores and macropores, which were determined for super critical point (SCP)-dried SBKP sheet samples, should participate in the WRVs determined for wet SBKP sheet samples. The mesopores are formed during pulping/bleaching to remove lignin and a part of hemicelluloses that are present originally in wood cell walls. The combined volumes of mesopores and macropores (totally < ∼0.6 g g−1) in SBKP fibers after SCP drying were significantly lower than the entire WRV (∼1.6 g g−1) of the original never-dried SBKP. We hypothesize that external fibrils of SBKP fibers are formed during pulping, bleaching, washing, pressure-screening, and pressing processes at high and low solid contents in water under high shear forces. The WRV can be used as an indicator to evaluate such structural changes of external fibrils in pulp fibers and paper sheets during drying/wetting in papermaking process as well as in use under various conditions. In contrast, changes in mesopore and macropore volumes determined for SCP-dried sheets cannot properly detect such structural changes of external fibrils.