Research Progress in the Regulation of the ABA Signaling Pathway by E3 Ubiquitin Ligases in Plants.

E3 ubiquitin ligases (UBLs), as enzymes capable of specifically recognizing target proteins in the process of protein ubiquitination, play crucial roles in regulating responses to abiotic stresses such as drought, salt, and temperature. Abscisic acid (ABA), a plant endogenous hormone, is essential to regulating plant growth, development, disease resistance, and defense against abiotic stresses, and acts through a complex ABA signaling pathway. Hormone signaling transduction relies on protein regulation, and E3 ubiquitin ligases play important parts in regulating the ABA pathway. Therefore, this paper reviews the ubiquitin-proteasome-mediated protein degradation pathway, ABA-related signaling pathways, and the regulation of ABA-signaling-pathway-related genes by E3 ubiquitin ligases, aiming to provide references for further exploration of the relevant research on how plant E3 ubiquitin ligases regulate the ABA pathway.

Coupled physicochemical dual-crosslinking Ti3C2Tx composite aerogels for the selective adsorption of gallium ions in acid fly ash leaching.

Herein, in order to extract Ga3+ from acid fly ash leaching, we propose a functionalized Ti3C2Tx-based MXene composite aerogel adsorbent for Ga3+ adsorption. The prepared physicochemical dual-crosslinking network aerogel MPHG-40 possesses good Ga3+ adsorption performance (132.52 mg g-1) at the pH of 3 and Ga3+ initial concentration of 50 mg L-1 within 6 h. After five adsorption-desorption cycles, the material shows good mass retention and a 95.65 % retention of its initial adsorption capacity, compared to most reported adsorbents. The optimized adsorbent realized good selective adsorption of Ga3+ against Cu2+, Zn2+, Fe3+, and Al3+ in a simulated acid fly ash leaching with the selective coefficient of 8.63, 96.10, 4.49, and 28.30, respectively. The adsorption may comply with a combined mechanism of physical adsorption, electrostatic interactions, ion-exchange mechanism, and ligand chelation, dominated by chemical adsorption, as identified by theoretical calculations based on density functional theory and experimental data. The three-dimensional solid adsorbent constructed in this study provides a new strategy for selective adsorption of Ga3+, making it possible to be applied to solid waste utilization of fly ash.

Auto-loaded TRAIL-exosomes derived from induced neural stem cells for brain cancer therapy.

Transdifferentiation (TD), a somatic cell reprogramming process that eliminates pluripotent intermediates, creates cells that are ideal for personalized anti-cancer therapy. Here, we provide the first evidence that extracellular vesicles (EVs) from TD-derived induced neural stem cells (Exo-iNSCs) are an efficacious treatment strategy for brain cancer. We found that genetically engineered iNSCs generated EVs loaded with the tumoricidal gene product TRAIL at nearly twice the rate of their parental fibroblasts, and TRAIL produced by iNSCs was naturally loaded into the lumen of EVs and arrayed across their outer membrane (Exo-iNSC-TRAIL). Uptake studies in ex vivo organotypic brain slice cultures showed that Exo-iNSC-TRAIL selectively accumulates within tumor foci, and co-culture assays demonstrated that Exo-iNSC-TRAIL killed metastatic and primary brain cancer cells more effectively than free TRAIL. In an orthotopic mouse model of brain cancer, Exo-iNSC-TRAIL reduced breast-to-brain tumor xenografts by approximately 3000-fold compared to treatment with free TRAIL, with all Exo-iNSC-TRAIL treated animals surviving through 90 days post-treatment. In additional in vivo testing against aggressive U87 and invasive GBM8 glioblastoma tumors, Exo-iNSC-TRAIL also induced a statistically significant increase in survival. These studies establish a novel, easily generated, stable, tumor-targeted EV to efficaciously treat multiple forms of brain cancer.

Auto-loaded TRAIL-exosomes derived from induced neural stem cells for brain cancer therapy.

Transdifferentiation (TD), a somatic cell reprogramming process that eliminates pluripotent intermediates, creates cells that are ideal for personalized anti-cancer therapy. Here, we provide the first evidence that extracellular vesicles (EVs) from TD-derived induced neural stem cells (Exo-iNSCs) are an efficacious treatment strategy for brain cancer. We found that genetically engineered iNSCs generated EVs loaded with the tumoricidal gene product TRAIL at nearly twice the rate as their parental fibroblasts, and the TRAIL produced by iNSCs were naturally loaded into the lumen of EVs and arrayed across their outer membrane (Exo-iNSC-TRAIL). Uptake studies in ex vivo organotypic brain slice cultures showed Exo-iNSC-TRAIL selectively accumulates within tumor foci, and co-culture assays showed that Exo-iNSC-TRAIL killed metastatic and primary brain cancer cells more effectively than free TRAIL. In an orthotopic mouse model of brain cancer, Exo-iNSC-TRAIL reduced breast-to-brain tumor xenografts around 3000-fold greater than treatment with free TRAIL, with all Exo-iNSC-TRAIL treated animals surviving through 90 days post-treatment. In additional in vivo testing against aggressive U87 and invasive GBM8 glioblastoma tumors, Exo-iNSC-TRAIL also induced a statistically significant increase in survival. These studies establish a new easily generated, stable, tumor-targeted EV to efficaciously treat multiple forms of brain cancer.

Enhancing tendon-bone integration and healing with advanced multi-layer nanofiber-reinforced 3D scaffolds for acellular tendon complexes.

Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive in vivo evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.

A chitosan-coated PCL/nano-hydroxyapatite aerogel integrated with a nanofiber membrane for providing antibacterial activity and guiding bone regeneration.

A guided bone regeneration (GBR) membrane can act as a barrier to prevent the invasion and interference from foreign soft tissues, promoting infiltration and proliferation of osteoblasts in the bone defect area. Herein, a composite scaffold with dual functions of osteogenesis and antibacterial effects was prepared for GBR. A polycaprolactone (PCL)/nano-hydroxyapatite (n-HA) aerogel produced by electrospinning and freeze-drying techniques was fabricated as the loose layer of the scaffold, while a PCL nanofiber membrane was used as the dense layer. Chitosan (CS) solution served as a middle layer to provide mechanical support and antibacterial effects between the two layers. Morphological results showed that the loose layer had a porous structure with n-HA successfully dispersed in the aerogels, while the dense layer possessed a sufficiently dense structure. In vitro antibacterial experiments illustrated that the CS solution in the middle layer stabilized the scaffold structure and endowed the scaffold with good antibacterial properties. The cytocompatibility results indicated that both fibroblasts and osteoblasts exhibited superior cell activity on the dense and loose layers, respectively. In particular, the dense layer made of nanofibers could work as a barrier layer to inhibit the infiltration of fibroblasts into the loose layer. In vitro osteogenesis analysis suggested that the PCL/n-HA aerogel could enhance the bone induction ability of bone mesenchymal stem cells, which was confirmed by the increased expression of the alkaline phosphatase activity. The loose structure facilitated the infiltration and migration of bone mesenchymal stem cells for better osteogenesis. In summary, such a composite scaffold exhibited excellent osteogenic and antibacterial properties as well as the barrier effect, thus holding promising potential for use as GBR materials.

Long-term conservation tillage increase cotton rhizosphere sequestration of soil organic carbon by changing specific microbial CO2 fixation pathways in coastal saline soil.

Coastal saline soil is an important reserve resource for arable land globally. Data from 10 years of continuous stubble return and subsoiling experiments have revealed that these two conservation tillage measures significantly improve cotton rhizosphere soil organic carbon sequestration in coastal saline soil. However, the contribution of microbial fixation of atmospheric carbon dioxide (CO2) has remained unclear. Here, metagenomics and metabolomics analyses were used to deeply explore the microbial CO2 fixation process in rhizosphere soil of coastal saline cotton fields under long-term stubble return and subsoiling. Metagenomics analysis showed that stubble return and subsoiling mainly optimized CO2 fixing microorganism (CFM) communities by increasing the abundance of Acidobacteria, Gemmatimonadetes, and Chloroflexi, and improving composition diversity. Conjoint metagenomics and metabolomics analyses investigated the effects of stubble return and subsoiling on the reverse tricarboxylic acid (rTCA) cycle. The conversion of citrate to oxaloacetate was inhibited in the citrate cleavage reaction of the rTCA cycle. More citrate was converted to acetyl-CoA, which enhanced the subsequent CO2 fixation process of acetyl-CoA conversion to pyruvate. In the rTCA cycle reductive carboxylation reaction from 2-oxoglutarate to isocitrate, synthesis of the oxalosuccinate intermediate product was inhibited, with strengthened CO2 fixation involving the direct conversion of 2-oxoglutarate to isocitrate. The collective results demonstrate that stubble return and subsoiling optimizes rhizosphere CFM communities by increasing microbial diversity, in turn increasing CO2 fixation by enhancing the utilization of rTCA and 3-hydroxypropionate/4-hydroxybutyrate cycles by CFMs. These events increase the microbial CO2 fixation in the cotton rhizosphere, thereby promoting the accumulation of microbial biomass, and ultimately improving rhizosphere soil organic carbon. This study clarifies the impact of conservation tillage measures on microbial CO2 fixation in cotton rhizosphere of coastal saline soil, and provides fundamental data for the improvement of carbon sequestration in saline soil in agricultural ecosystems.

Glioblastoma stem cell-derived exosomal miR-374b-3p promotes tumor angiogenesis and progression through inducing M2 macrophages polarization.

Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk of GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) are essential mediators during tumor immune-microenvironment remodeling initiated by GSCs, resulting in M2 polarization of tumor-associated macrophages (TAMs) as we reported previously. Our data disclosed aberrant upregulation of miR-374b-3p in both clinical glioblastoma specimens and human cell lines of GSCs. MiR-374b-3p level was high in GSCs-exos and can be internalized by macrophages. Mechanistically, GSCs exosomal miR-374b-3p induced M2 polarization of macrophages by downregulating phosphatase and tensin expression, thereby promoting migration and tube formation of vascular endothelial cells after coculture with M2 macrophages. Cumulatively, these data indicated that GSCs exosomal miR-374b-3p can enhance tumor angiogenesis by inducing M2 polarization of macrophages, as well as promote malignant progression of glioblastoma. Targeting exosomal miR-374b-3p may serve as a potential target against glioblastoma.

Transformed astrocytes confer temozolomide resistance on glioblastoma via delivering ALKBH7 to enhance APNG expression after educating by glioblastoma stem cells-derived exosomes.

BACKGROUND: Glioblastoma is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against glioblastoma. Nevertheless, the therapeutic efficacy of TMZ appears to be remarkably limited, because of low cytotoxic efficiency against glioblastoma. Besides, various mechanical studies and the corresponding strategies fail to enhancing TMZ curative effect in clinical practice. Our previous studies have disclosed remodeling of glial cells by GSCs, but the roles of these transformed cells on promoting TMZ resistance have never been explored. METHODS: Exosomes were extracted from GSCs culture through standard centrifugation procedures, which can activate transformation of normal human astrocytes (NHAs) totumor-associated astrocytes (TAAs) for 3 days through detect the level of TGF-ß, CD44 and tenascin-C. The secretive protein level of ALKBH7 of TAAs was determined by ELISA kit. The protein level of APNG and ALKBH7 of GBM cells were determined by Western blot. Cell-based assays of ALKBH7 and APNG triggered drug resistance were performed through flow cytometric assay, Western blotting and colony formation assay respectively. A xenograft tumor model was applied to investigate the function of ALKBH7 in vivo. Finally, the effect of the ALKBH7/APNG signaling on TMZ resistance were evaluated by functional experiments. RESULTS: Exosomes derived from GSCs can activate transformation of normal human astrocytes (NHAs)to tumor-associated astrocytes (TAAs), as well as up-regulation of ALKBH7expression in TAAs. Besides, TAAs derived ALKBH7 can regulate APNG gene expression of GBM cells. After co-culturing with TAAs for 5 days, ALKBH7 and APNG expression in GBM cells were elevated. Furthermore, Knocking-down of APNG increased the inhibitory effect of TMZ on GBM cells survival. CONCLUSION: The present study illustrated a new mechanism of glioblastoma resistance to TMZ, which based on GSCs-exo educated TAAs delivering ALKBH7 to enhance APNG expression of GBM cells, which implied that targeting on ALKBH7/APNG regulation network may provide a new strategy of enhancing TMZ therapeutic effects against glioblastoma.

Glioma stem cell-derived exosomes induce the transformation of astrocytes via the miR-3065-5p/DLG2 signaling axis.

Tumor-associated astrocytes (TAAs) in the glioblastoma microenvironment play an important role in tumor development and malignant progression initiated by glioma stem cells (GSCs). In the current study, normal human astrocytes (NHAs) were cultured and continuously treated with GSC-derived exosomes (GSC-EXOs) induction to explore the mechanism by which GSCs affect astrocyte remodeling. This study revealed that GSC-EXOs can induce the transformation of NHAs into TAAs, with relatively swollen cell bodies and multiple extended processes. In addition, high proliferation, elevated resistance to temozolomide (TMZ), and increased expression of TAA-related markers (TGF-ß, CD44, and tenascin-C) were observed in the TAAs. Furthermore, GSC-derived exosomal miR-3065-5p could be delivered to NHAs, and miR-3065-5p levels increased significantly in TAAs, as verified by miRNA expression profile sequencing and Reverse transcription polymerase chain reaction. Overexpression of miR-3065-5p also enhanced NHA proliferation, elevated resistance to TMZ, and increased the expression levels of TAA-related markers. In addition, both GSC-EXO-induced and miR-3065-5p-overexpressing NHAs promoted tumorigenesis of GSCs in vivo. Discs Large Homolog 2 (DLG2, downregulated in glioblastoma) is a direct downstream target of miR-3065-5p in TAAs, and DLG2 overexpression could partially reverse the transformation of NHAs into TAAs. Collectively, these data demonstrate that GSC-EXOs induce the transformation of NHAs into TAAs via the miR-3065-5p/DLG2 signaling axis and that TAAs can further promote the tumorigenesis of GSCs. Thus, precisely blocking the interactions between astrocytes and GSCs via exosomes may be a novel strategy to inhibit glioblastoma development, but more in-depth mechanistic studies are still needed.

The cognitive appraisal path of stroke knowledge, coping traits, family functioning and stigma among stroke patients: A moderated parallel mediation model.

AIMS: To establish a cognitive appraisal path model that examines the impact of stroke knowledge on stigma with the parallel mediating effects of negative and positive coping traits, as well as the moderating effects of family functioning. BACKGROUND: Stroke-related stigma, a 'mixture' of negative emotions involving internal criticism and external judgement, has been shown to impair patients' health outcomes. However, the specific factors underlying cognitive appraisals and their pathways remain unknown. DESIGN: A cross-sectional design. METHODS: The cross-sectional sample was from two stroke centres in China. Questionnaires were administered to collect sociodemographic data, stroke knowledge, coping traits, family functioning and stigma. Hierarchical regression models and the moderated parallel mediation model were constructed to analyse influencing pathways. The study adhered to the strengthening the reporting of observational studies in epidemiology guideline. RESULTS: All 144 samples reported stigma symptoms with a moderate-to-high standardising score. The best hierarchical regression model explains 55.5% of the variance in stigma. The parallel mediation model indicated that negative and positive coping traits co-mediating the association of stroke knowledge and stigma. After adding the family functioning as a moderator, the moderated parallel mediation model was confirmed with adequate fit indices. CONCLUSION: Among the cognitive appraisal factors affecting stroke-related stigma, stroke knowledge reduces stigma by modifying coping traits, while poor family functioning may serve as an opposing moderator. Notably, when family support is insufficient, enhanced stroke knowledge might paradoxically exacerbate the stigma. RELEVANCE TO CLINICAL PRACTICE: This study contributes knowledge on transforming health education and emphasises the pivotal roles of clinical nursing practitioners. In similar global contexts, the study highlights integrating health education, psychological counselling and family support to advance systematic nursing practices. PATIENT OR PUBLIC CONTRIBUTION: None.

Incidence and risk factors for hypotension after carotid artery stenting: Systematic review and meta-analysis.

OBJECTIVE: Hypotension is recognized as a common complication after carotid artery stenting, but its incidence and the risk factors associated with it are uncertain. Therefore, we performed a systematic review and meta-analysis to investigate and identify risk factors for hypotension after surgery. METHODS: We retrieved risk factors from eight databases for case-control and cross-sectional studies of hypotension after carotid artery stenting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on 28 November 2022. Data were analyzed by using R4.2.1 and Review Manager 5.3. RESULTS: A total of 2843 samples were searched, and 17 publications were included in the analysis. The meta-analysis results showed that the incidence of hypotension after surgery was 28.6% (95% confidence interval [CI] (0.225, 0.347)). Age ⩾ 65 years (odds ratio [OR] = 4.55, 95% CI (2.50, 8.29), P < 0.00001), stenosis site (bulb) (OR = 4.41, 95% CI (2.50, 7.79), P < 0.00001), severe stenosis (OR = 3.56, 95% CI (1.62, 7.85), P = 0.002), stenosis proximity (⩽ 10 mm) to bifurcation (OR = 2.69, 95% CI (1.74, 4.15), P < 0.00001), calcified plaques (OR = 4.64, 95% CI (1.93, 11.14), P = 0.0006), post-balloon dilation (OR = 5.95, 95% CI (2.31, 15.31), P = 0.0002), bilateral carotid stenting (OR = 30.51, 95% CI (2.33, 399.89), P = 0.009), and intravenous fluid intake/mL on the first postoperative day (mean difference = 444.99, 95% CI (141.40, 748.59), P = 0.004) were risk factors for hypotension after surgery. CONCLUSIONS: A high incidence of hypotension was observed after carotid artery stenting. Age, stenosis site, severe stenosis, stenosis proximity to bifurcation, calcified plaques, post-balloon dilation, type of surgery, and intravenous fluid intake were identified as risk factors.

Study on the shielding effect of low resistance body when using transient electromagnetic to detect urban underground space.

Transient electromagnetic Method (TEM) is an efficient geophysical detection technology suitable for detection of urban near-surface space. However, its detection results are well affected by the low resistance anomaly, which interferes with the interpretation of the inversion results. This article used finite element method to simulate the entire process of urban underground pipeline under TEM detection. The causes of interference and the degree of interference under different working conditions were analyzed. The results demonstrate that low resistance anomaly in magnetic field will caused electromagnetic energy absorption and resulting eddy current losses, which lead to a distortion of the primary magnetic field in the vicinity of the pipeline, and formation of a weak field zone beneath the pipeline. The size and shape of the shielding zone are affected by burial depth, transmitter coil diameter, and anomaly size. When the burial depth exceeds 10 times the diameter of the coil or pipeline, the shielding range stabilizes at 1.5-2 times the pipeline's transverse diameter. Moreover, when the pipeline's transverse diameter exceeds twice the transmitter coil diameter, the weak field zone beneath the pipeline will transform into a strong field zone, this is due to the refractive and reflective effects of the electromagnetic field. Finally, experiments were conducted and the inverted results was found to be larger than the actual pipeline diameter, with an error margin similar to that explained by the simulation. These results have implications for high accuracy detecting underground pipelines in urban areas.

Complexity-based graph convolutional neural network for epilepsy diagnosis in normal, acute, and chronic stages.

Introduction: The automatic precision detection technology based on electroencephalography (EEG) is essential in epilepsy studies. It can provide objective proof for epilepsy diagnosis, treatment, and evaluation, thus helping doctors improve treatment efficiency. At present, the normal and acute phases of epilepsy can be well identified through EEG analysis, but distinguishing between the normal and chronic phases is still tricky. Methods: In this paper, five popular complexity indicators of EEG signal, including approximate entropy, sample entropy, permutation entropy, fuzzy entropy and Kolmogorov complexity, are computed from rat hippocampi to characterize the normal, acute, and chronic phases during epileptogenesis. Results of one-way ANOVA and principal component analysis both show that utilizing complexity features, we are able to easily identify differences between normal, acute, and chronic phases. We also propose an innovative framework for epilepsy detection based on graph convolutional neural network (GCNN) using multi-channel EEG complexity as input. Results: Combining information of five complexity measures at eight channels, our GCNN model demonstrate superior ability in recognizing the normal, acute, and chronic phases. Experiments results show that our GCNN model reached the high prediction accuracy above 98% and F1 score above 97% among these three phases for each individual rat. Discussion: Our research practice based on real data shows that EEG complexity characteristics are of great significance for recognizing different stages of epilepsy.

Investigation of the acicular aragonite growth behavior in AOD stainless steel slag during slurry-phase carbonation.

This study presents a novel method for producing acicular aragonite using argon oxygen decarburization (AOD) slag while controlling the reaction temperature, reaction time, stirring speed, and the magnesium-to­calcium stoichiometric ratio. This approach provides steel plants with an opportunity to decrease their CO2 emissions and promote efficient resource utilization and CO2 storage through the production of high-quality value-added products. The experimental results showed that reaction temperature was the most significant factor affecting the carbonation efficiency of AOD slag, followed by reaction time, stirring speed, CO2 partial pressure, and the liquid-to-solid ratio (L/S). The study also found that elevated temperature and prolonged reaction duration favored the preferential precipitation of aragonite. Additionally, raising the temperature and the magnesium-to­calcium stoichiometric ratio was shown to enhance the formation of aragonite, affecting its crystal growth orientation and dimensions. The optimal combination of reaction parameters for the preparation of acicular aragonite was found to be the reaction time of 8 h, the magnesium-to­calcium stoichiometric ratio of 0.8, the reaction temperature of 120 °C, and the stirring speed of 200 r·min-1. Under these conditions, the resulting acicular aragonite exhibited excellent overall uniformity, a large aspect ratio, and a smooth crystal surface, with a content of 91.49 %, a single crystal length ranging from 9.86 to 32.6 µm, and a diameter ranging from 0.63 to 2.15 µm. This study provides valuable insights into the efficient production of acicular aragonite from steel slag while reducing CO2 emissions and promoting the sustainable use of resources.

Promoting neurite outgrowth and neural stem cell migration using aligned nanofibers decorated with protrusions and galectin-1 coating.

Biomaterials integrated with both topological cues and biological modifications are urgently needed in regenerative medicine. Here, aligned nanofibrous scaffolds decorated with nanoscale SiO2 protrusions and galectin-1 coating are reported. Prospects in neurite outgrowth and neural stem cell migration are discussed for suitable use in neural tissue engineering.

Autonomic function may mediate the neuroprotection of remote ischemic postconditioning in stroke: A randomized controlled trial.

OBJECTIVES: To evaluate the effect of remote ischemic postconditioning (RIPostC) on the prognosis of acute ischemic stroke(AIS) patients and investigate the mediating role of autonomic function in the neuroprotection of RIPostC. MATERIALS AND METHODS: 132 AIS patients were randomized into two groups. Patients received four cycles of 5-min inflation to a pressure of 200 mmHg(i.e., RIPostC) or patients' diastolic BP(i.e., shame), followed by 5 min of deflation on healthy upper limbs once a day for 30 days. The main outcome was neurological outcome including the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel index(BI). The second outcome measure was autonomic function measured by heart rate variability(HRV). RESULTS: Compared with the baseline, the post-intervention NIHSS score was significantly reduced in both groups (P<0.001). NIHSS score was significantly lower in the control group than intervention group at day 7.[RIPostC:3(1,5) versus shame:2(1,4); P=0.030]. mRS scored lower in the intervention group compared with the control group at day 90 follow-up(RIPostC:0.5±2.0 versus shame:1.0±2.0;P=0.016). The goodness-of-fit test revealed a significant difference between the generalized estimating equation model of mRS and BI scores of uncontrolled-HRV and controlled-HRV(P<0.05, both). The results of bootstrap revealed a complete mediation effect of HRV between group on mRS[indirect effect: -0.267 (LLCI = -0.549, ULCI = -0.048), the direct effect: -0.443 (LLCI = -0.831, ULCI = 0.118)]. CONCLUSION: This is the first human-based study providing evidence for a mediation role of autonomic function between RIpostC and prognosis in AIS patients. It indicated that RIPostC could improve the neurological outcome of AIS patients. Autonomic function may play a mediating role in this association. TRIAL REGISTRATION: The clinical trials registration number for this study is NCT02777099 (ClinicalTrials.gov Identifier).

Exosomal miR-6733-5p mediates cross-talk between glioblastoma stem cells and macrophages and promotes glioblastoma multiform progression synergistically.

AIM: Exosomal miRNAs derived from glioblastoma stem cells (GSCs) are important mediators of immunosuppressive microenvironment formation in glioblastoma multiform (GBM), especially in M2-like polarization of tumor-associated macrophages (TAMs). However, the exact mechanisms by which GSCs-derived exosomes (GSCs-exo) facilitate the remodeling of the immunosuppressive microenvironment of GBM have not been elucidated. METHODS: Transmission electron microscopy (TME) and nanoparticle tracking analysis (NTA) were applied to verify the existence of GSCs-derived exosomes. Sphere formation assays, flow cytometry, and tumor xenograft transplantation assays were performed to identify the exact roles of exosomal miR-6733-5p. Then, the mechanisms of miR-6733-5p and its downstream target gene regulating crosstalk between GSCs cells and M2 macrophages were further investigated. RESULTS: GSCs-derived exosomal miR-6733-5p induce macrophage M2 polarization of TAMs by positively targeting IGF2BP3 to activate the AKT signaling pathway, which further facilitates the self-renewal and stemness of GSCs. CONCLUSION: GSCs secrete miR-6733-5p-rich exosomes to induce M2-like polarization of macrophages, as well as enhance GSCs stemness and promote malignant behaviors of GBM through IGF2BP3 activated AKT pathway. Targeting GSCs exosomal miR-6733-5p may provide a potential new strategy against GBM.

A living ex vivo platform for functional, personalized brain cancer diagnosis.

Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm that enable rapid engraftment, treatment, and analysis of uncultured patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point: high- and low-grade adult and pediatric tumor tissue rapidly establishes on OBSCs among endogenous astrocytes and microglia while maintaining the tumor's original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and OBSC toxicity, generating summarized drug sensitivity scores on the basis of therapeutic window and allowing us to normalize response profiles across a panel of U.S. Food and Drug Administration (FDA)-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment show positive associations to clinical outcomes, suggesting that the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.

Genome-wide identification and expression analysis of the HVA22 gene family in cotton and functional analysis of GhHVA22E1D in drought and salt tolerance.

The HVA22 family of genes, induced by abscisic acid and stress, encodes a class of stress response proteins with a conserved TB2/DP1/HVA22 domain that are unique among eukaryotes. Previous studies have shown that HVA22s play an important role in plant responses to abiotic stresses. In the present study, 34, 32, 16, and 17 HVA22s were identified in G. barbadense, G. hirsutum, G. arboreum, and G. raimondii, respectively. These HVA22 genes were classified into nine subgroups, randomly distributed on the chromosomes. Synteny analysis showed that the amplification of the HVA22s were mainly due to segmental duplication or whole genome replication (WGD). Most HVA22s promoter sequences contain a large number of drought response elements (MYB), defense and stress response elements (TC-rich repeats), and hormone response elements (ABRE, ERE, SARE, etc.), suggesting that HVA22s may respond to adversity stresses. Expression profiling demonstrated that most GhHVA22s showed a constitutive expression pattern in G. hirsutum and could respond to abiotic stresses such as salt, drought, and low temperature. Overexpression of GhHVA22E1D (GH_D07G0564) in Arabidopsis thaliana enhances salt and drought tolerance in Arabidopsis. Virus-induced gene silencing of GhHVA22E1D reduced salt and drought tolerance in cotton. This indicates that GhHVA22E1D plays an active role in the plant response to salt stress and drought stress. GhHVA22E1D may act in plant response to adversity by altering the antioxidant capacity of plants. This study provides valuable information for the functional genomic study of the HVA22 gene family in cotton. It also provides a reference for further elucidation of the functional studies of HVA22 in plant resistance to abiotic stress response.