An n-Type Open-Shell Conjugated Polymer with High-Spin Ground-State and High Intrinsic Electrical Conductivity.

Open-shell conjugated polymers with a high intrinsic conductivity and high-spin ground state hold considerable promise for applications in organic electronics and spintronics. Herein, two novel acceptor-acceptor (A-A) conjugated polymers based on a highly electron-deficient quinoidal benzodifurandione unit have been developed, namely DPP-BFDO-Th and DPP-BFDO. The incorporation of the quinoidal moiety into the polymers backbones enables deeply aligned lower-lying lowest unoccupied molecular orbital (LUMO) levels of below -4.0 eV. Notably, DPP-BFDO exhibits an exceptionally low LUMO (-4.63 eV) and a high-spin ground state characterized by strong diradical characters. Moreover, a self-doping through intermolecular charge-transfer is observed for DPP-BFDO, as evidenced by X-ray photoelectron spectroscopy (XPS) studies. The high carrier concentration in combination with a planar and linear conjugated backbone yields a remarkable electrical conductivity (σ) of 1.04 S cm-1 in the "undoped" native form, ranking among the highest values reported for n-type radical-based conjugated polymers. When employed as an n-type thermoelectric material, DPP-BFDO achieves a power factor of 12.59 µW m-1 K-2. Furthermore, upon n-doping, the σ could be improved to 65.68 S cm-1. This study underscores the great potential of electron-deficient quinoidal units in constructing dopant-free n-type conductive polymers with a high-spin ground state and exceptional intrinsic conductivity.

Excavation method optimization and mechanical responses investigating of a shallow buried super large section tunnels: a case study in Zhejiang.

The construction of super large section (SLS) shallow buried tunnels involves challenges related to their large span, high flat rate, and complex construction process. Selecting an appropriate excavation method is crucial for ensuring stability, controlling costs, and managing the construction timeline. This study focuses on the selection of excavation methods and the mechanical responses of SLS tunnels in different types of surrounding rock. The research is based on the Yangjiashan tunnel project in Zhejiang Province, China, which is a four-line highway tunnel with a span of 21.3 m. Three sequential excavation methods were proposed and simulated using the three-dimensional finite difference method: the "upper first and lower later" side drift (SD) method, the central diaphragm method, and the top heading and bench (HB) method. The mechanical response characteristics of tunnel construction under these methods were investigated, including rock deformation, rock pressure, and the internal forces acting on the primary support. By comparing the performance of the three construction methods in rock masses of Grades III to V, the study aimed to determine the optimal construction method for SLS tunnels considering factors such as safety, cost, and schedule. Field tests were conducted to evaluate the effectiveness of the optimized construction scheme. The results of the field monitoring indicated that the "upper first and lower later" SD method in Grade V rock mass and the HB method in Grade III to IV rock mass are feasible and cost-effective under certain conditions. The research findings provide valuable insights for the design and construction of SLS tunnels in complex conditions, serving as a reference for engineers and project managers.

An n-Type Conjugated Polymer with Low Crystallinity for High-Performance Organic Thermoelectrics.

Conjugated polymers (CPs) with low crystallinity are promising candidates for application in organic thermoelectrics (OTEs), particularly in flexible devices, because the disordered structures of these CPs can effectively accommodate dopants and ensure robust resistance to bending. However, n-doped CPs usually exhibit poor thermoelectric performance, which hinders the development of high-performance thermoelectric generators. Herein, we report an n-type CP (ThDPP-CNBTz) comprising two acceptor units: a thiophene-flanked diketopyrrolopyrrole and a cyano-functionalized benzothiadiazole. ThDPP-CNBTz shows a low LUMO energy level of below -4.20 eV and features low crystallinity, enabling high doping efficiency. Moreover, the dual-acceptor design enhances polaron delocalization, resulting in good thermoelectric performance. After n-doping, ThDPP-CNBTz exhibits an average electrical conductivity (σ) of 50.6 S cm-1 and a maximum power factor (PF) of 126.8 µW m-1 K-2, which is among the highest values reported for solution-processed n-type CPs to date. Additionally, a solution-processed flexible OTE device based on doped ThDPP-CNBTz exhibits a maximum PF of 70 µW m-1 K-2; the flexible device also shows remarkable resistance to bending strain, with only a marginal change in σ after 600 bending cycles. The findings presented in this work will advance the development of n-type CPs for OTE devices, and flexible devices in particular.

Deep learning-based automatic segmentation of meningioma from T1-weighted contrast-enhanced MRI for preoperative meningioma differentiation using radiomic features.

BACKGROUND: This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery. MATERIALS: A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built. RESULTS: The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively. CONCLUSIONS: The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.

Integrated metabolomics and transcriptomics analysis reveals γ-aminobutyric acid enhances the ozone tolerance of wheat by accumulation of flavonoids.

Wheat is susceptible to atmospheric ozone (O3) pollution, thus the increasing O3 is a serious threat to wheat production. γ-aminobutyric acid (GABA) is found to play key roles in the tolerance of plants to stress. However, few studies elaborated the function of GABA in response of wheat to O3. Here, we incorporated metabolome and transcriptome data to provide a more comprehensive insight on the role of GABA in enhancing the O3-tolerance of wheat. In our study, there were 31, 23, and 32 differentially accumulated flavonoids in the carbon-filtered air with GABA, elevated O3 with or without GABA treatments compared to the carbon-filtered air treatment, respectively. Elevated O3 triggered the accumulation of dihydroflavone, flavonols, and flavanols. Exogenous GABA enhanced dihydroflavone and dihydroflavonol, and also altered the expression of genes encoding some key enzymes in the flavonoid synthesis pathway. Additionally, GABA stimulated proline accumulation and antioxidant enzyme activities under elevated O3, resulting in the less accumulation of H2O2 and malondialdehyde. Consequently, GABA alleviated the grain yield loss from 19.6% to 9.6% induced by elevated O3. Our study provided comprehensive insight into the role of GABA in the alleviating the detrimental effects of elevated O3 on wheat, and a new avenue to mitigate O3 damage to the productivity of crops.

Improving ocular bioavailability of hydrophilic drugs through dynamic covalent complexation.

The clinical benefits of diquafosol tetrasodium (DQS), a hydrophilic P2Y2 receptor agonist for dry eye, have been hindered by a demanding dosing regimen. Nevertheless, it is challenging to achieve sustained release of DQS with conventional drug delivery vehicles which are mainly designed for hydrophobic small molecule drugs. To address this, we developed an affinity hydrogel for DQS by taking advantage of borate-mediated dynamic covalent complexation between DQS and hydroxypropyl guar. The resultant formulation (3% DQS Gel) was characterized by sustained release, low corneal permeation, and extended ocular retention, which were desirable attributes for ocular surface drug delivery. Both in vitro and in vivo studies had been carried out to verify the biocompatibility of 3% DQS Gel. Using corneal fluorescein staining, the Schirmer's test, PAS staining, quantitative PCR and immunohistological analyses as outcome measures, the superior therapeutic effects of 3% DQS Gel over PBS, the hydrogel vehicle and free DQS were demonstrated in a mouse dry eye model. Our DQS delivery strategy reported herein is readily applicable to other hydrophilic small molecule drugs with cis-diol moieties, thus providing a general solution to improve clinical outcomes of numerous diseases.

Highly selective electrosynthesis of H2O2 by N, O co-doped graphite nanosheets for efficient electro-Fenton degradation of p-nitrophenol.

The activity and selectivity of the cathode towards electrosynthesis of H2O2 are critical for electro-Fenton process. Herein, nickel-foam modified with N, O co-doped graphite nanosheets (NO-GNSs/Ni-F) was developed as a cathode for highly efficient and selective electrosynthesis of H2O2. Expectedly, the accumulation of H2O2 at pH= 3 reached 494.2 mg L-1 h-1, with the selectivity toward H2O2 generation reaching 93.0%. The synergistic effect of different oxygen-containing functional groups and N species on the performance and selectivity of H2O2 electrosynthesis was investigated by density functional theory calculations, and the combination of epoxy and graphitic N (EP + N) was identified as the most favorable configuration with the lowest theoretical overpotential for H2O2 generation. Moreover, NO-GNSs/Ni-F was applied in the electro-Fenton process for p-nitrophenol degradation, resulting in 100% removal within 15 min with the kinetic rate constant of 0.446 min-1 and 97.6% mineralization within 6 h. The efficient removal was mainly attributed to the generation of bulk ·OH. Furthermore, NO-GNSs/Ni-F exhibited excellent stability. This work provides a workable option for the enhancement of H2O2 accumulation and the efficient degradation of pollutants in electro-Fenton system.

Elevated ozone decreases the multifunctionality of belowground ecosystems.

Elevated tropospheric ozone (O3 ) affects the allocation of biomass aboveground and belowground and influences terrestrial ecosystem functions. However, how belowground functions respond to elevated O3 concentrations ([O3 ]) remains unclear at the global scale. Here, we conducted a detailed synthesis of belowground functioning responses to elevated [O3 ] by performing a meta-analysis of 2395 paired observations from 222 publications. We found that elevated [O3 ] significantly reduced the primary productivity of roots by 19.8%, 16.3%, and 26.9% for crops, trees and grasses, respectively. Elevated [O3 ] strongly decreased the root/shoot ratio by 11.3% for crops and by 4.9% for trees, which indicated that roots were highly sensitive to O3 . Elevated [O3 ] impacted carbon and nitrogen cycling in croplands, as evidenced by decreased dissolved organic carbon, microbial biomass carbon, total soil nitrogen, ammonium nitrogen, microbial biomass nitrogen, and nitrification rates in association with increased nitrate nitrogen and denitrification rates. Elevated [O3 ] significantly decreased fungal phospholipid fatty acids in croplands, which suggested that O3 altered the microbial community and composition. The responses of belowground functions to elevated [O3 ] were modified by experimental methods, root environments, and additional global change factors. Therefore, these factors should be considered to avoid the underestimation or overestimation of the impacts of elevated [O3 ] on belowground functioning. The significant negative relationships between O3 -treated intensity and the multifunctionality index for croplands, forests, and grasslands implied that elevated [O3 ] decreases belowground ecosystem multifunctionality.

Protein kinase MtCIPK12 modulates iron reduction in Medicago truncatula by regulating riboflavin biosynthesis.

Iron (Fe) is an essential micronutrient, and deficiency in available Fe is one of the most important limiting factors for plant growth. In some species including Medicago truncatula, Fe deficiency results in accumulation of riboflavin, a response associated with Fe acquisition. However, how the plant's Fe status is integrated to tune riboflavin biosynthesis and how riboflavin levels affect Fe acquisition and utilization remains largely unexplored. We report that protein kinase CIPK12 regulates ferric reduction by accumulation of riboflavin and its derivatives in roots of M. truncatula via physiological and molecular characterization of its mutants and over-expressing materials. Mutations in CIPK12 enhance Fe accumulation and improve photosynthetic efficiency, whereas overexpression of CIPK12 shows the opposite phenotypes. The Calcineurin B-like proteins CBL3 and CBL8 interact with CIPK12, which negatively regulates the expression of genes encoding key enzymes in the riboflavin biosynthesis pathway. CIPK12 negatively regulates Fe acquisition by suppressing accumulation of riboflavin and its derivatives in roots, which in turn influences ferric reduction activity by riboflavin-dependent electron transport under Fe deficiency. Our findings uncover a new regulatory mechanism by which CIPK12 regulates riboflavin biosynthesis and Fe-deficiency responses in plants.

Reorganization of three-dimensional chromatin architecture in Medicago truncatula under phosphorus deficiency.

Emerging evidence reveals that the three-dimensional (3D) chromatin architecture plays a key regulatory role in various biological processes of plants. However, information on the 3D chromatin architecture of the legume model plant Medicago truncatula and its potential roles in the regulation of response to mineral nutrient deficiency are very limited. Using high-resolution chromosome conformation capture sequencing, we identified the 3D genome structure of M. truncatula in terms of A/B compartments, topologically associated domains (TADs) and chromatin loops. The gene density, expressional level, and active histone modification were higher in A compartments than in B compartments. Moreover, we analysed the 3D chromatin architecture reorganization in response to phosphorus (P) deficiency. The intra-chromosomal cis-interaction proportion was increased by P deficiency, and a total of 748 A/B compartment switch regions were detected. In these regions, density changes in H3K4me3 and H3K27ac modifications were associated with expression of P deficiency-responsive genes involved in root system architecture and hormonal responses. Furthermore, these genes enhanced P uptake and mobilization by increasing root surface area and strengthening signal transduction under P deficiency. These findings advance our understanding of the potential roles of 3D chromatin architecture in responses of plants in general, and in particular in M. truncatula, to P deficiency.

Tolerant mechanism of model legume plant Medicago truncatula to drought, salt, and cold stresses.

Legume plants produce one-third of the total yield of primary crops and are important food sources for both humans and animals worldwide. Frequent exposure to abiotic stresses, such as drought, salt, and cold, greatly limits the production of legume crops. Several morphological, physiological, and molecular studies have been conducted to characterize the response and adaptation mechanism to abiotic stresses. The tolerant mechanisms of the model legume plant Medicago truncatula to abiotic stresses have been extensively studied. Although many potential genes and integrated networks underlying the M. truncatula in responding to abiotic stresses have been identified and described, a comprehensive summary of the tolerant mechanism is lacking. In this review, we provide a comprehensive summary of the adaptive mechanism by which M. truncatula responds to drought, salt, and cold stress. We also discuss future research that need to be explored to improve the abiotic tolerance of legume plants.

Tandem Mass Tag Analysis of the Effect of the Anterior Cingulate Cortex in Nonerosive Reflux Disease Rats with Shugan Jiangni Hewei Granules Treatment.

Objective: The current study aims to analyze the improvement mechanism of visceral hypersensitivity (VH) and targets of Shugan Jiangni Hewei granules (SJHG) for nonerosive reflux disease (NERD) treatment as well as to offer an experimental foundation for its clinical use. Methods: Healthy male Sprague-Dawley rats (n = 36) were acquired in the current study that was further split into three groups: blank, model, and drug (SJHG). Subsequently, differentially expressed proteins and bioinformatics analysis were performed on the collected tissue samples acquired from the anterior cingulate cortex of the model and SJHG rat groups using a tandem mass tag- (TMT-) based proteomics. Eventually, the obtained data from the bioinformatic analysis was further verified through western blotting. Results: From the bioinformatics analysis, only 64 proteins were differentially expressed between the NC and SJHG groups. These molecules were found to be highly expressed in immunological response and neural signal transmission. Finally, we confirmed three therapeutic targets of SJHG, namely, kininogen 1 (Kng1), junctional adhesion molecule A (JAM-A), and the PI3K/Akt signaling pathway. Conclusions: SJHG is effective in treating VH, Kng1 and JAM-A may be therapeutic targets of SJHG, and the therapeutic mechanism of SJHG may be realized by influencing immune response or transmission of neural signals.

A topical fluorometholone nanoformulation fabricated under aqueous condition for the treatment of dry eye.

Fluorometholone (FMT) is a frequently prescribed drug for the alleviation of dry eye. However, due to low aqueous solubility, it has been routinely used as an ophthalmic suspension, which is characterized by low bioavailability, inconvenience of administration, and difficulty in delivering accurate dose. Furthermore, the opaque appearance of the ophthalmic suspension is not desirable for optical purpose. In the present study, a transparent FMT nanoformulation (FMT-CD NPs) was fabricated by the cyclodextrin (CD) nanoparticle technology without organic solvents. It was demonstrated that FMT was encapsulated in an amorphous form, which was associated with increased release rate and enhanced corneal penetration efficiency. The biocompatibility of FMT-CD NPs was confirmed by the Live/Dead assay, CCK-8 assay and the wound healing assay. Most importantly, FMT-CD NPs alleviated dry eye signs more efficiently than the commercial eye drop, with one-fifth the dosage of FMT in the latter. Collectively, our study provides a promising FMT formulation for improved management of dry eye while reducing drug related side effects.

A deep learning radiomics model may help to improve the prediction performance of preoperative grading in meningioma.

PURPOSE: This study aimed to investigate the clinical usefulness of the enhanced-T1WI-based deep learning radiomics model (DLRM) in differentiating low- and high-grade meningiomas. METHODS: A total of 132 patients with pathologically confirmed meningiomas were consecutively enrolled (105 in the training cohort and 27 in the test cohort). Radiomics features and deep learning features were extracted from T1 weighted images (T1WI) (both axial and sagittal) and the maximum slice of the axial tumor lesion, respectively. Then, the synthetic minority oversampling technique (SMOTE) was utilized to balance the sample numbers. The optimal discriminative features were selected for model building. LightGBM algorithm was used to develop DLRM by a combination of radiomics features and deep learning features. For comparison, a radiomics model (RM) and a deep learning model (DLM) were constructed using a similar method as well. Differentiating efficacy was determined by using the receiver operating characteristic (ROC) analysis. RESULTS: A total of 15 features were selected to construct the DLRM with SMOTE, which showed good discrimination performance in both the training and test cohorts. The DLRM outperformed RM and DLM for differentiating low- and high-grade meningiomas (training AUC: 0.988 vs. 0.980 vs. 0.892; test AUC: 0.935 vs. 0.918 vs. 0.718). The accuracy, sensitivity, and specificity of the DLRM with SMOTE were 0.926, 0.900, and 0.924 in the test cohort, respectively. CONCLUSION: The DLRM with SMOTE based on enhanced T1WI images has favorable performance for noninvasively individualized prediction of meningioma grades, which exhibited favorable clinical usefulness superior over the radiomics features.

Closed dumbbell mediated isothermal amplification of nucleic acids for DNA diagnostic assays.

Nucleic acid amplification tests have been widely applied in clinical diagnostics, food safety monitoring, and molecular biology. As a well-established isothermal amplification method, Loop-mediated isothermal amplification (LAMP) has gained recognition. However, the need for specifically designed four to six primers and non-specific amplification pose challenges for further application of LAMP based detection methods. Here, a novel isothermal amplification method, termed closed dumbbell mediated isothermal amplification (CDA) of nucleic acids, was developed. The primers are easily designed by adding two different parts of middle sequence to the canonical PCR primers at 5'-ends. CDA method was demonstrated in detecting MERS-CoV orf1a gene and H1N1 gene fragments with merits of short core primer, simple primer design process and high amplification efficiency. In addition, CDA showed excellent amplification efficacy over LAMP and competitive annealing mediated isothermal amplification (CAMP) by slight modification of primers targeting at same sequence. Furthermore, real-time and HNB based colorimetric CDA detection of Shigella were developed for practical application, both exhibited 100% success. In all, the developed CDA method with high specificity, simplicity, efficiency and rapidity has shown its great potential for point of care nucleic acids diagnostic.

Engineering Advanced Drug Delivery Systems for Dry Eye: A Review.

Dry eye disease (DED) is a widespread and frequently reported multifactorial ocular disease that not only causes ocular discomfort but also damages the cornea and conjunctiva. At present, topical administration is the most common treatment modality for DED. Due to the existence of multiple biological barriers, instilled drugs generally exhibit short action times and poor penetration on the ocular surface. To resolve these issues, several advanced drug delivery systems have been proposed. This review discusses new dosage forms of drugs for the treatment of DED in terms of their characteristics and advantages. Innovative formulations that are currently available in the market and under clinical investigation are elaborated. Meanwhile, their deficiencies are discussed. It is envisioned that the flourishing of advanced drug delivery systems will lead to improved management of DED in the near future.

Genome-wide analysis of the Glutathione S-Transferase family in wild Medicago ruthenica and drought-tolerant breeding application of MruGSTU39 gene in cultivated alfalfa.

KEY MESSAGE: Transformation of MruGSTU39 in M. ruthenica and alfalfa enhanced growth and survival of transgenic plants by up-regulating GST and glutathione peroxidase activity to detoxify ROS under drought stress. Glutathione S-transferases (GSTs) are ubiquitous supergene family which play crucial roles in detoxification of reactive oxygen species (ROS). Despite studies on GSTs, few studies have focused on them in perennial, wild plant species with high tolerance to environmental stress. Here, we identified 66 MruGST genes from the genome of Medicago ruthenica, a perennial legume species native to temperate grasslands with high tolerance to environmental stress. These genes were divided into eight classes based on their conserved domains, phylogenetic tree and gene structure, with the tau class being the most numerous. Duplication analysis revealed that GST family in M. ruthenica was expanded by segmental and tandem duplication. Several drought-responsive MruGSTs were identified by transcriptomic analyses. Of them, expression of MruGSTU39 was up-regulated much more in a tolerant accession by drought stress. Transformation of MruGSTU39 in M. ruthenica and alfalfa (Medicago sativa) enhanced growth and survival of transgenic seedlings than their wild-type counterparts under drought. We demonstrated that MruGSTU39 can detoxify ROS to reduce its damage to membrane by up-regulating activities of GST and glutathione peroxidase. Our findings provide full-scale knowledge on GST family in the wild legume M. ruthenica with high tolerance to drought, and highlight improvement tolerance of legume forages to drought using genomic information of M. ruthenica.

miR-F4-C12 Functions on the Regulation of Adipose Accumulation by Targeting PIK3R1 in Castrated Male Pigs.

MicroRNAs (miRNAs) constitute small regulatory molecules for a wide array of biological activities (18~24 nucleotides in length), including adipogenesis and adipose deposition. Their effect is, however, incompletely defined in inducing fat accumulation in castrated male pigs. Based on our study, four nine-times miRNAs were selected to examine their functions in adipose formation activities. In 3T3-L1 cells and backfat tissues of castrated and intact male pigs, miR-F4-C12 was identified as a factor in adipose development utilizing quantitative real-time PCR (qRT-PCR). Further, miR-F4-C12 was identified to promote fat development, suggesting that miR-F4-C12 was involved in adipogenesis. Moreover, phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was proposed by the TargetScan, miRDB and starBase as a target of miR-F4-C12 and verified through a two-luciferase reporter assay. The over-expression of miR-F4-C12 dramatically decreases the PIK3R1 protein level in 3T3-L1 cells. The mRNA and protein levels of PIK3R1 in castrated pigs are reduced relative to intact pigs, providing further evidence that PIK3R1 is involved in regulating adipose accumulation. These results suggest that miR-F4-C12 involves adipose development and may regulate subcutaneous adipose tissue accumulation by targeting PIK3R1 in castrated male pigs.

Artemether Attenuates Aß25-35-Induced Cognitive Impairments by Downregulating Aß, BACE1, mTOR and Tau Proteins.

BACKGROUND: Alzheimer's disease (AD) is clinically characterized as a progressive cognitive impairment and behavioral disorder. Pathological hallmarks of AD include extracellular senile plaques (SPs), intracellular neurofibrillary tangles (NFTs) and massive neuronal loss. Although the exact cause of AD is not well understood, a mounting body of evidence has demonstrated that the pathogenesis of AD is associated with oxidative stress, neu-roinflammation, and amyloid beta (Aß) induced neural apoptosis. Moreover, overexpression of ß-secretase 1 (BACE1), Aß, mammalian target of rapamycin (mTOR), and Tau proteins are closely related to cognitive symptoms in AD. Studies have demonstrated that artemether, an antimalarial drug with acceptable side effects, possesses protective effects against neuroinflammation and oxidative stress. Importantly, artemether can easily penetrate the blood brain barrier, thereby representing an ideal drug candidate for AD treatment. METHODS: The effect of artemether on memory protection and the associated molecular mechanisms were investigated in an Aß25-35 induced cognitive impairments rat model. RESULTS: Results of the in vivo study showed that oral administration of artemether significantly attenuated Aß25-35-induced cognitive impairment in rats. Results of the in vitro study revealed that artemether significantly downregulated the endogenous expression of Aß, BACE1, mTOR, and Tau proteins in N2a cells. CONCLUSIONS: The beneficial effect of artemether against Aß 25-35-induced cognitive impairments was attributable to the downregulation of the expression of Aß, BACE1, mTOR, and Tau proteins, suggesting the potential of artemether as an effective, neuronal protective, and multi-targeted drug candidate for AD treatment.

Plant 3D Chromatin Organization: Important Insights from Chromosome Conformation Capture Analyses of the Last 10 Years.

Over the past few decades, eukaryotic linear genomes and epigenomes have been widely and extensively studied for understanding gene expression regulation. More recently, the three-dimensional (3D) chromatin organization was found to be important for determining genome functionality, finely tuning physiological processes for appropriate cellular responses. With the development of visualization techniques and chromatin conformation capture (3C)-based techniques, increasing evidence indicates that chromosomal architecture characteristics and chromatin domains with different epigenetic modifications in the nucleus are correlated with transcriptional activities. Subsequent studies have further explored the intricate interplay between 3D genome organization and the function of interacting regions. In this review, we summarize spatial distribution patterns of chromatin, including chromatin positioning, configurations and domains, with a particular focus on the effect of a unique form of interaction between varieties of factors that shape the 3D genome conformation in plants. We further discuss the methods, advantages and limitations of various 3C-based techniques, highlighting the applications of these technologies in plants to identify chromatin domains, and address their dynamic changes and functional implications in evolution, and adaptation to development and changing environmental conditions. Moreover, the future implications and emerging research directions of 3D genome organization are discussed.