Enzymes play a key role in natural mineralization, but their function is disabling in bone metabolism when patients suffer severe degenerations like hypophosphatasia. To regulate bone homeostasis, a ...self‐activating phosphorus‐rich system is proposed on calcium glycerophosphate (CaGP) modified polyurethane (PU) fibrous substrate, wherein ample enzyme catalytic domains are imported with intestinal alkaline phosphatase (IALP) chelating and activating by calcium in situ that is testified by chemical potential evaluation. Therefore, Ca‐bonding IALP catalyzes organophosphate to phosphate locally to achieve a calcified symbiotic state, regulating mineralization and accelerating osteoinduction in vitro and in vivo. The self‐activating enzyme system promotes early osteogenic differentiation and angiogenesis, resulting in rapid healing of cranial defect with a “long‐tail” effect compared to an enzyme‐assisted system. Transcriptomic and metabolomic analyses demonstrate positive associations with neovascularization and calcium/phosphorus metabolism, specifically upregulated glycerophospholipids and calcium ions in favor of osteogenic differentiation under cytokine‐free conditions. These results provide a potential enzyme‐activating therapy in bone homeostasis and regeneration.
Inspired by natural bone mineralization, a self‐activating phosphorus‐rich system is proposed on calcium glycerophosphate (CaGP) modified polyurethane (PU) fibrous substrate, wherein ample enzyme catalytic domains are imported with intestinal alkaline phosphatase (IALP). Multi‐omics analysis reveals the mechanism of osteogenesis in vitro. In a rat ectopic bone formation and a rat skull defect model, PU‐CaGP@IALP exhibits excellent osteogenesis, osteoinductivity, and angiogenesis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Rostromedial tegmental nucleus (RMTg) GABA neurons exert a primary inhibitory drive onto midbrain dopamine neurons and are excited by a variety of aversive stimuli. There is, however, little evidence ...that the RMTg-ventral tegmental area (VTA)-nucleus accumbens shell (Acb) circuit plays a role in the aversive consequences of alcohol withdrawal. This study was performed in adult male Long-Evans rats at 48-h withdrawal from chronic alcohol drinking in the intermittent schedule. These rats displayed clear anhedonia and depression-like behaviors, as measured with the sucrose preference, and forced swimming tests. These aberrant behaviors were accompanied by a substantial increase in cFos expression in the VTA-projecting RMTg neurons, identified by a combination of immunohistochemistry and retrograde-tracing techniques. Pharmacological or chemogenetic inhibition of RMTg neurons mitigated the anhedonia and depression-like behaviors. Ex vivo electrophysiological data showed that chemogenetic inactivation of RMTg neurons reduced GABA release and accelerated spontaneous firings of VTA dopamine neurons. Finally, using a functional hemispheric disconnection procedure, we demonstrated that inhibition of unilateral RMTg, when combined with activation of D1 and D2 dopamine receptors in the contralateral (but not ipsilateral) Acb, mitigated the anhedonia and depression-like behaviors in alcohol-withdrawal rats. These data show that the integrity in the RMTg-VTA-Acb pathway in a single hemisphere is sufficient to elicit depression-like behavior during ethanol-withdrawal. Overall, the present results reveal that the RMTg-VTA-Acb pathway plays a crucial role in the depression-like behavior in animals undergoing alcohol withdrawal, further advocating the RMTg as a potential therapeutic target for alcoholism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diazinon (DZN) is a member of organophosphorus insecticides that has cytotoxic effects on different organs.
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-Acetyl cysteine (NAC) is a widely used antioxidant in clinical, in vivo and in vitro ...studies. We evaluated the protective role of NAC against DZN-induced toxicity in kidney tissue of Wistar rats. 30 male Wistar rats were divided into 5 groups of control, single dose of DZN, continuous dose of DZN, single doses of DZN + NAC and continuous doses of DZN + NAC. Kidney function test (blood urea nitrogen, creatinine and uric acid) was provided. Levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and total sulfhydryl (T-SH) were determined in renal tissues. Renal cells apoptosis was detected using TUNEL assay. The mRNA expressions of apoptosis, oxidative stress and inflammatory mediators, including B-cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (Bax), superoxide dismutase (SOD), catalase (CAT), Interleukin 10 (IL-10), Tumor necrosis factor-α (TNF-α), Caspase-3 and Caspase-8 were analyzed in kidney tissues using Real Time PCR method. Chronic exposure to DZN was associated with severe morphological changes in the kidney, as well as impairment of its function and decreased kidney weights. Continues treatment with DZN significantly decreased the percentage of renal apoptotic cells as compared to rats treated with continuous dose of DZN alone (17.69 ± 3.67% vs. 39.46% ± 2.44%;
p
< 0.001). Continuous exposure to DZN significantly decreased TAC and T-SH contents, as well as SOD and CAT expression, but increased MDA contents in the kidney tissues (
p
< 0.001). A significant increase was observed in mRNA expression of Bax, Caspase-3, Caspase-8, as well as TNF-α following exposure to DZN, but the expression of IL-10 and Bcl2 was significantly decreased. NAC can protect kidney tissue against DZN-induced toxicity by elevating antioxidants capacity, mitigating oxidative stress, inflammation and apoptosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The coexistence of nanoplastics (NPs) and various pollutants in the environment has become a problem that cannot be ignored. In order to identify the microcystin-LR (MCLR) bioaccumulation and the ...potential impacts on the early growth of F1 zebrafish (Danio rerio) offspring in the presence of polystyrene nanoplastics (PSNPs), PSNPs and MCLR were used to expose adult zebrafish for 21days. The exposure groups divided into MCLR (0, 0.9, 4.5 and 22.5μgL−1) alone groups and PSNP (100μgL−1) and MCLR co-exposure groups. F1 embryos were collected and developed to 120 h post-fertilization (hpf) in clear water. Compared with the exposure to MCLR only, the combined exposure increased the parental transfer of MCLR to the offspring and subsequently exacerbated the growth inhibition of F1 larvae. Further research clarified that combined exposure of PSNPs and MCLR could reduce the levels of thyroxine (T4) and 3, 5, 3′-triiodothyronine (T3) by altering the expression of hypothalamus–pituitary–thyroid (HPT) axis-related genes, eventually leading to growth inhibition of F1 larvae. Our results also exhibited combined exposure of PSNPs and MCLR could change the transcription of key genes of the GH/IGF axis compared with MCLR single exposure, suggesting the GH/IGF axis was a potential target for the growth inhibition of F1 larvae in PSNPs and MCLR co-exposure groups. The present study highlights the potential risks of coexistence of MCLR and PSNPs on development of fish offspring, and the environmental risks to aquatic ecosystems.
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•MCLR and PSNPs could accumulate in adult zebrafish and F1 larvae, through parental transmission.•PSNPs exposure exacerbated the toxic effects of MCLR on the growth of F1 larvae.•Combined exposure of PSNPs and MCLR caused thyroid endocrine disturbance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Three-dimensional (3D) printing offers great potential to customize sophisticated constructs for a myriad of applications. However, many thermosets require long-term curing under harsh conditions, ...which is not compatible with rapid 3D printing processing. 3D printing of these thermosets remains a challenge. Here, we report a new strategy for direct 3D printing of various thermosets via readily available extrusion-based technology using sacrificial sodium chloride particles as a removable thickener for printing and a reinforcer for curing, exemplified by crosslinked polyester, polyurethane and epoxy resins. Specifically, the 3D constructs exhibited hierarchical and porous architectures, which are highly desired for many applications, including regenerative medicine, sensors, actuators, catalyst supports, and energy absorbers. As a proof-of-concept demonstration, we 3D printed vapomechanical sensors and actuators featuring fast, large, robust, and gradient responsiveness, in addition to biodegradable scaffolds to promote vascularization and tissue ingrowth in vivo and elastic myocardial patches to efficiently treat myocardial infarction. We expect that this study will pave a new way to tailor sophisticated 3D structures of thermosets and will be very useful for diverse applications.
Although hundreds of studies have been conducted, our understanding of the pathogenesis, indications for surgical intervention, and disease markers of Takayasu arteritis (TAK) are still limited. ...Collection of biological specimens, clinical data and imaging data will facilitate translational research and clinical studies. In this study, we aim to introduce the design and protocol for the Beijing Hospital Takayasu Arteritis (BeTA) Biobank.
Based in the Department of Vascular Surgery of Beijing Hospital and Beijing Hospital Clinical Biological Sample Management Center, the BeTA Biobank is composed of clinical data and sample data from patients with TAK requiring surgical treatment. All clinical data of participants are collected, including demographic characteristics, laboratory tests, imaging results, operation information, perioperative complications, follow-up data, etc. Both blood samples including plasma, serum and cells, and vascular tissues or perivascular adipose tissue are collected and stored. These samples will promote the establishment of a multiomic database for TAK and help to identify disease markers and to explore potential targets for specific future drugs for TAK.
This study was designed to evaluate the efficacy of remote medication management of rivaroxaban by pharmacists for geriatric patients with nonvalvular atrial fibrillation during the COVID-19 ...pandemic.
A single-site, prospective cohort study was conducted among patients with non-valvular atrial fibrillation who received rivaroxaban therapy from July 2019 to December 2019. Patients in the pharmacist-led education and follow-up service (PEFS) group were managed remotely by a pharmacist. In contrast, those in the usual care (UC) group were managed by other providers. Data of routine blood tests, coagulation function tests, which also included cardiac function parameters were collected. The number and type of provider encounters, interventions related to rivaroxaban therapy, the occurrence of thromboembolism or bleeding, and the time of the first outpatient visit after discharge were recorded.
A total of 600 patients were recruited, and results of 381 patients were analyzed in the end, of which 179 patients were from the PEFS group and 202 were from the UC group. There was no significant difference between the two groups in terms of the occurrence ratio of systemic thrombosis, heart failure (LVEF < 40%), and left atrial dilation, which was defined as enlargement of left atrial diameter (LAD) > 40 mm. The cumulative incidences of bleeding complications, such as gastrointestinal tract and skin ecchymosis, were significantly higher in the UC group (12.4% vs. 6.1%, P=0.038; 4.5% vs. 0.6%, P=0.018). There was no significant difference after pharmacist intervention in terms of thrombosis occurrence ratio between the two groups (P = 0.338, HR: 0.722, 95% CI: 0.372-1.405). Remote instruction by a pharmacist reduced outpatient service frequency within the first 30 days after discharge (23.7% vs. 1.1%, P < 0.001). However, more patients in the PEFS group presented for the first outpatient revisit later than 40 days post-discharge (12.8% vs. 21.3%, P < 0.001).
Remote pharmacist-led medication instruction of rivaroxaban could reduce bleeding complications of the gastrointestinal tract and skin ecchymosis and postpone the first outpatient revisit after discharge.
Brassinosteroids (BRs) are a group of essential steroid hormones involved in diverse developmental and physiological processes in plants. The Brassinazole-resistant 1 (BZR1) transcription factors are ...key components of BR signaling and integrate a wide range of internal and environmental signals to coordinate plant development, growth, and resistance to abiotic and biotic stresses. Although the BZR1 family has been fully studied in Arabidopsis, celery BZR1 family genes remain largely unknown. Nine BZR1 genes were identified in the celery genome, and categorized into four classes based on phylogenetic and gene structure analyses. All the BZR1 proteins shared a typical bHLH (basic helix-loop-helix) domain that is highly conserved across the whole family in Arabidopsis, grape, lettuce, ginseng, and three Apiaceae species. Both duplications and losses of the BZR1 gene family were detected during the shaping of the celery genome. Whole-genome duplication (WGD) or segmental duplication contributed 55.56% of the BZR1 genes expansion, and the gamma as well as celery-omega polyploidization events made a considerable contribution to the production of the BZR1 paralogs in celery. Four AgBZR1 members (AgBZR1.1, AgBZR1.3, AgBZR1.5, and AgBZR1.9), which were localized both in the nucleus and cytoplasm, exhibit transcription activation activity in yeast. AgBZR1.5 overexpression transgenic plants in Arabidopsis showed curled leaves with bent, long petioles and constitutive BR-responsive phenotypes. Furthermore, the AgBZR1 genes possessed divergent expression patterns with some overlaps in roots, petioles, and leaves, suggesting an extensive involvement of AgBZR1s in the developmental processes in celery with both functional redundancy and divergence. Our results not only demonstrated that AgBZR1 played a conserved role in BR signaling but also suggested that AgBZR1 might be extensively involved in plant developmental processes in celery. The findings lay the foundation for further study on the molecular mechanism of the AgBZR1s in regulating the agronomic traits and environmental adaptation of celery, and provide insights for future BR-related genetic breeding of celery and other Apiaceae crops.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Although low-grade glioma (LGG) has a good prognosis, it is prone to malignant transformation into high-grade glioma. It has been confirmed that the characteristics of inflammatory ...factors and immune microenvironment are closely related to the occurrence and development of tumors. It is necessary to clarify the role of inflammatory genes and immune infiltration in LGG.
Methods:
We downloaded the transcriptome gene expression data and corresponding clinical data of LGG patients from the TCGA and GTEX databases to screen prognosis-related differentially expressed inflammatory genes with the difference analysis and single-factor Cox regression analysis. The prognostic risk model was constructed by LASSO Cox regression analysis, which enables us to compare the overall survival rate of high- and low-risk groups in the model by Kaplan–Meier analysis and subsequently draw the risk curve and survival status diagram. We analyzed the accuracy of the prediction model
via
ROC curves and performed GSEA enrichment analysis. The ssGSEA algorithm was used to calculate the score of immune cell infiltration and the activity of immune-related pathways. The CellMiner database was used to study drug sensitivity.
Results:
In this study, 3 genes (CALCRL, MMP14, and SELL) were selected from 9 prognosis-related differential inflammation genes through LASSO Cox regression analysis to construct a prognostic risk model. Further analysis showed that the risk score was negatively correlated with the prognosis, and the ROC curve showed that the accuracy of the model was better. The age, grade, and risk score can be used as independent prognostic factors (
p
< 0.001). GSEA analysis confirmed that 6 immune-related pathways were enriched in the high-risk group. We found that the degree of infiltration of 12 immune cell subpopulations and the scores of 13 immune functions and pathways in the high-risk group were significantly increased by applying the ssGSEA method (
p
< 0.05). Finally, we explored the relationship between the genes in the model and the susceptibility of drugs.
Conclusion:
This study analyzed the correlation between the inflammation-related risk model and the immune microenvironment. It is expected to provide a reference for the screening of LGG prognostic markers and the evaluation of immune response.
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