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1.
Plant Cell Rep ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507055

RESUMO

KEY MESSAGE: Hydrogen sulfide positively regulates autophagy and the expression of hypoxia response-related genes under submergence to enhance the submergence tolerance of Arabidopsis. Flooding seriously endangers agricultural production, and it is quite necessary to explore the mechanism of plant response to submergence for improving crop yield. Both hydrogen sulfide (H2S) and autophagy are involved in the plant response to submergence. However, the mechanisms by which H2S and autophagy interact and influence submergence tolerance have not been thoroughly elucidated. Here, we reported that exogenous H2S pretreatment increased the level of endogenous H2S and alleviated plant cell death under submergence. And transgenic lines decreased in the level of endogenous H2S, L-cysteine desulfurase 1 (des1) mutant and 35S::GFP-O-acetyl-L-serine(thiol)lyase A1 (OASA1)/des1-#56/#61, were sensitive to submergence, along with the lower transcript levels of hypoxia response genes, LOB DOMAIN 41 (LBD41) and HYPOXIA RESPONSIVE UNKNOWN PROTEIN 43 (HUP43). Submergence induced the formation of autophagosomes, and the autophagy-related (ATG) mutants (atg4a/4b, atg5, atg7) displayed sensitive phenotypes to submergence. Simultaneously, H2S pretreatment repressed the autophagosome producing under normal conditions, but enhanced this process under submergence by regulating the expression of ATG genes. Moreover, the mutation of DES1 aggravated the sensitivity of des1/atg5 to submergence by reducing the formation of autophagosomes under submergence. Taken together, our results demonstrated that H2S alleviated cell death through regulating autophagy and the expression of hypoxia response genes during submergence in Arabidopsis.

2.
Sci Adv ; 8(18): eabm7665, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522739

RESUMO

There is an increasing trend of combining living cells with inorganic semiconductors to construct semi-artificial photosynthesis systems. Creating a robust and benign bio-abiotic interface is key to the success of such solar-to-chemical conversions but often faces a variety of challenges, including biocompatibility and the susceptibility of cell membrane to high-energy damage arising from direct interfacial contact. Here, we report living mineralized biofilms as an ultrastable and biocompatible bio-abiotic interface to implement single enzyme to whole-cell photocatalytic applications. These photocatalyst-mineralized biofilms exhibited efficient photoelectrical responses and were further exploited for diverse photocatalytic reaction systems including a whole-cell photocatalytic CO2 reduction system enabled by the same biofilm-producing strain. Segregated from the extracellularly mineralized semiconductors, the bacteria remained alive even after 5 cycles of photocatalytic NADH regeneration reactions, and the biofilms could be easily regenerated. Our work thus demonstrates the construction of biocompatible interfaces using biofilm matrices and establishes proof of concept for future sustainable photocatalytic applications.

3.
Int Immunopharmacol ; 109: 108783, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561479

RESUMO

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.

4.
Int J Mol Sci ; 23(9)2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35562896

RESUMO

The TALE gene family is an important transcription factor family that regulates meristem formation, organ morphogenesis, signal transduction, and fruit development. A total of 24 genes of the TALE family were identified and analyzed in tomato. The 24 SlTALE family members could be classified into five BELL subfamilies and four KNOX subfamilies. SlTALE genes were unevenly distributed on every tomato chromosome, lacked syntenic gene pairs, and had conserved structures but diverse regulatory functions. Promoter activity analysis showed that cis-elements responsive to light, phytohormone, developmental regulation, and environmental stress were enriched in the promoter of SlTALE genes, and the light response elements were the most abundant. An abundance of TF binding sites was also enriched in the promoter of SlTALE genes. Phenotype identification revealed that the green shoulder (GS) mutant fruits showed significantly enhanced chloroplast development and chlorophyll accumulation, and a significant increase of chlorophyll fluorescence parameters in the fruit shoulder region. Analysis of gene expression patterns indicated that six SlTALE genes were highly expressed in the GS fruit shoulder region, and four SlTALE genes were highly expressed in the parts with less-developed chloroplasts. The protein-protein interaction networks predicted interaction combinations among these SlTALE genes, especially between the BELL subfamilies and the KNOX subfamilies, indicating a complex regulatory network of these SlTALE genes in chloroplast development and green fruit shoulder formation. In conclusion, our result provides detailed knowledge of the SlTALE gene for functional research and the utilization of the TALE gene family in fruit quality improvement.

5.
Neuroimage Clin ; 34: 103021, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35500369

RESUMO

Iron mediated oxidative stress is involved in the process of brain injury after long-term ischemia. While increased iron deposition in the affected brain regions was observed in animal models of ischemic stroke, potential changes in the brain iron content in clinical patients with cerebral ischemia remain unclear. Quantitative susceptibility mapping (QSM), a non-invasive magnetic resonance imaging technique, can be used to evaluate iron content in the gray matter (GM) nuclei reliably. In this study, we aimed to quantitatively evaluate iron content changes in GM nuclei of patients with long-term unilateral middle cerebral artery (MCA) stenosis/occlusion-related cerebral ischemia using QSM. Forty-six unilateral MCA stenosis/occlusion patients and 38 age-, sex- and education-matched healthy controls underwent QSM. Clinical variables of history of hypertension, diabetes, hyperlipidemia, hyperhomocysteinemia, smoking, and drinking in all patients were evaluated. The iron-related susceptibility of GM nucleus subregions, including the bilateral caudate nucleus (CN), putamen (PU), globus pallidus (GP), thalamus, substantia nigra (SN), red nucleus, and dentate nucleus, was assessed. Susceptibility was compared between the bilateral GM nuclei in patients and controls. Receiver operating characteristic curve analysis was used to evaluate the efficacy of QSM susceptibility in distinguishing patients with unilateral MCA stenosis/occlusion from healthy controls. Multiple linear regression analysis was used to evaluate the relationship between ipsilateral susceptibility levels and clinical variables. Except for the CN, the susceptibility in most bilateral GM nucleus subregions was comparable in healthy controls, whereas for patients with unilateral MCA stenosis/occlusion, the ipsilateral PU, GP, and SN exhibited significantly higher susceptibility than the contralateral side (all P < 0.05). Compared with controls, susceptibility of the ipsilateral PU, GP, and SN and of contralateral PU in patients were significantly increased (all P < 0.05). The area under the curve (AUC) was greater for the ipsilateral PU than for the GP and SN (AUC = 0.773, 0.662 and 0.681; all P < 0.05). Multiple linear regression analysis showed that the increased susceptibility of the ipsilateral PU was significantly associated with hypertension, of the ipsilateral GP associated with smoking, and of the ipsilateral SN associated with diabetes (all P < 0.05). Our findings provide support for abnormal iron accumulation in the GM nuclei after chronic MCA stenosis/occlusion and its correlation with some cerebrovascular disease risk factors. Therefore, iron deposition in the GM nuclei, as measured by QSM, may be a potential biomarker for long-term cerebral ischemia.

6.
Cancer Sci ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524544

RESUMO

FAT atypical cadherin 1 (FAT1) is a mutant gene frequently found in human cancers and mainly accumulates at the plasma membrane of cancer cells. Emerging evidence has implicated FAT1 in the progression of gastric cancer (GC). This study intended to identify a regulatory network related to FAT1 in the GC development. Up-regulated expression of FAT1 was confirmed in GC tissues, and silencing FAT1 was observed to result in suppression of GC cell oncogenic phenotypes. Mechanistic investigation results demonstrated that FAT1 upregulated AP-1 expression by phosphorylating c-JUN and c-FOS, while LINC00857 elevated the expression of FAT1 by recruiting a transcription factor TFAP2C. Functional experiments further suggested that LINC00857 enhanced the malignant biological characteristics of GC cells through TFAP2C-mediated promotion of FAT1. More importantly, LINC00857 silencing delayed the tumor growth and blocked epithelial-mesenchymal transition in tumor-bearing mice, which was associated with downregulated expression of TFAP2C/FAT1. To conclude, LINC00857 plays an oncogenic role in GC through regulating the TFAP2C/FAT1/AP-1 axis. Hence, this study contributes to extended understanding of gastric carcinogenesis and LINC00857 may serve as a therapeutic target for GC.

7.
Adv Mater ; : e2200344, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524638

RESUMO

Advanced doped-silicon-layer-based passivating contacts have boosted the power conversion efficiency (PCE) of single-junction crystalline silicon (c-Si) solar cells to over 26%. However, the inevitable parasitic light absorption of the doped silicon layers impedes further PCE improvement. To this end, alternative passivating contacts based on wide-bandgap metal compounds (so-called dopant-free passivating contacts (DFPCs)) have attracted great attention, thanks to their potential merits in terms of parasitic absorption loss, ease-of-deposition, and cost. Intensive research activity has surrounded this topic with significant progress made in recent years. Various electron-selective and hole-selective contacts based on metal compounds have been successfully developed, and a champion PCE of 23.5% has been achieved for a c-Si solar cell with a MoOx -based hole-selective contact. In this work, the fundamentals and development status of DFPCs are reviewed and the challenges and potential solutions for enhancing the carrier selectivity of DFPCs are discussed. Based on comprehensive and in-depth analysis and simulations, the improvement strategies and future prospects for DFPCs design and device implementation are pointed out. By tuning the carrier concentration of the metal compound and the work function of the capping transparent electrode, high PCEs over 26% can be achieved for c-Si solar cells with DFPCs.

8.
J Pediatr Nurs ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537979

RESUMO

PURPOSE: To investigate the level of affiliate stigma among parents of children with autism spectrum disorder and to explore the mediating role of self-esteem and family functioning. DESIGN AND METHODS: A cross-sectional study was conducted in a large regional hospital and two childhood rehabilitation centers in Guangdong, China. Data related to demographics, parental self-esteem, family functioning, and affiliate stigma were collected from 180 parents of children diagnosed with ASD. We used t-tests, analysis of variance, and correlation analysis to explore the related factors of parental affiliate stigma. Path analysis was used to determine the mediating roles of self-esteem and family functioning in the relationship between symptom severity and affiliate stigma. RESULTS: Parents of children with autism spectrum disorder in China experienced low self-esteem, family functioning, and high affiliate stigma. Symptom severity was negatively correlated with self-esteem and family functioning. Self-esteem and family functioning were significantly negatively correlated with affiliate stigma. Symptom severity was positively correlated with affiliate stigma. Self-esteem and family functioning mediated the relationship between symptom severity and affiliate stigma. CONCLUSIONS: Symptom severity affects parental affiliate stigma among families with children with ASD. Self-esteem and family functioning are the two mediators in the relationship. We should take steps to improve self-esteem and family functioning in order to alleviate parental affiliate stigma. PRACTICE IMPLICATIONS: This study emphasizes the importance of the influence of ASD severity and family functioning on affiliate stigma. In clinical practice, psychological support should be provided for parents of children with ASD to improve their mental health.

9.
Org Lett ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549279

RESUMO

This study describes a regioselective ortho,ortho'-diborylation of aromatic triazenes catalyzed by [Ir(OMe)(cod)]2 in near-quantitative yields without an additional ligand. Aromatic triazenes act as both substrates and ligands. The X-ray structures of 2a and 2p indicate that the monoborylation products could promote the occurrence of diborylation. The synthesized triazene-substituted diboronate esters could undergo a variety of transformations including directing group removal. One-pot sequential modification provides a short entry to densely functionalized arenes.

10.
Ecotoxicol Environ Saf ; 238: 113597, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533448

RESUMO

The pollution of corn straw to the environment had attracted much attention. The preparation and alkali modification of corn straw biochar as the constructed wetland (CW) substrate was conducive to solving the environment pollution caused by straw and improving the purification effect of CW. The NaOH modification mechanism of corn straw biochar was analyzed by measuring the surface morphology, element content, specific surface area (SSA), pore volume, crystal structure, surface functional groups and CO2 adsorption. Biochar prepared under relatively optimal NaOH-modified conditions was used as the vertical flow CW substrate to treat city tail water. The results showed that controlling the modification condition of NaOH (< 1.0 mol·L-1, ≤ 24 h) was conducive to prevent the biochar structure destruction and C element reduction. The SSA and pore volume of NaOH (0.1 mol·L-1) modified biochar are 360 m2·g-1 and 0.109 cm3·g-1, respectively. The biochar adsorption for CO2 conformed to the Langmuir and Freundlich isothermal adsorption theoretical model (R2 > 0.9). The maximum adsorption capacity of CO2 by modified biochar with NaOH (0.1 mol·L-1) was 64.516 cm3·g-1 and increased by 10.3%. The city tail water treated by CW with plants showed that the removal rates of ammonia nitrogen, total nitrogen and nitrate nitrogen reached about 90%. The research results improved the utilization value of straw, realized straw carbon sequestration and promoted the progress of CW technology.

12.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556992

RESUMO

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be toxic, signifying a need for a synergistic drug combination. Resveratrol (RES) is a phenolic compound found in grapes shown to inhibit MM cell growth and induce apoptosis in these cells. We hypothesize that combining BTZ with a RES derivative at certain concentrations is synergistic in reducing viability and inducing apoptosis in MM cells. To address this hypothesis, we performed viability assays to assess the effects of increasing concentrations of RES derivatives and BTZ on human MM cell viability over time (24, 48, 72 hours) and western blots to assess the compounds' effects on inducing apoptosis in MM cells following 24 hour treatment. We found that BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins PARP1 and caspase-3 in a dose-dependent manner. We screened different combinations of RES derivatives with BTZ for synergistic effects on MM viability using CompuSyn and selected the combination of 5 nM BTZ and 5 µM PIN for further assessment as a synergistic treatment. In conclusion, a combination of low doses of BTZ and PIN synergistically decreases MM cell viability, possibly through inducing apoptosis.

13.
Int J Biol Macromol ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35569682

RESUMO

During wound healing process, it is essential to promote hemostasis and cell adhesion. Herein, we incorporated a scaffold with nanoparticles to improve the hemostatic properties and stimulate cell adhesion. The nanoparticles were prepared by self-assembling of silk fibroin, and the scaffold loaded nanoparticles were synthesized by crosslinking and freeze-drying. Macroscopical images showed that the nanoparticles distributed uniformly and increased the surface roughness of scaffold pore wall. The addition of nanoparticles decreased the pore size, enhanced the compression strength, lowered the degradation rate, and maintained the resilience and water uptake capacity. Compared with pure scaffold, the scaffold loaded nanoparticles revealed higher blood clotting index and promoted platelets adhesion. Furthermore, in vitro tests showed that scaffold loaded nanoparticles exhibited excellent biocompatibility, and stimulation effects on cell proliferation, migration, and adhesion for both L929 cells and HUVECs. Therefore, the scaffold loaded nanoparticles possessed great potential as a wound dressing for efficient hemostasis and subsequent wound healing.

14.
Acta Cardiol ; : 1-7, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501998

RESUMO

OBJECTIVE: To investigate the impact of shock index before Intra-Aortic Balloon Pump (IABP) implantation on recent prognosis of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 103 patients with CS complicating AMI admitted in our hospital from June 2014 to May 2019 who underwent primary PCI with IABP support were enrolled in the study. We collected the data according to the medical records and collected their clinical manifestation and laboratory examination, as well as 28-day mortality, and also calculated the shock index (ratio of heart rate to systolic blood pressure) before IABP implantation. RESULTS: Patients with higher SI at IABP insertion were associated with higher proportion of anterior infarction (81.5% vs. 61.2%, p = 0.022), previous history of PCI (24.1% vs. 8.16%, p = 0.030), culprit leision at left main (31.5% vs. 12.2%, p = 0.019), and final TIMI flow ≤ 2(55.5% vs. 26.5%, p = 0.003), invasive ventilation(40.7% vs. 20.4%, p = 0.026) as well as 28-day-mortality (81.5% vs. 61.2%, p = 0.022). SI at insertion may help predict recent outcome, with a cutoff value of 1.625, a sensitivity of 0.655 and a specificity of 0.708, and areas under the receiver-operating characteristic curve (AUCROC) was 0.713. On multiple analysis, SI, together with final TIMI flow, arterial pH and creatinine were independent predictive factors of recent prognosis among this population. CONCLUSION: Among CS patients complicating AMI undergoing PCI with the support of IABP, higher SI before IABP implantation was associated with poorer prognosis, SI was an independent risk factor of 28-day mortality and may predict the 28-day outcome.

15.
Front Mol Biosci ; 9: 888983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573733

RESUMO

The Jumonji C (JmjC) domain-containing protein family, an important family of histone demethylase in plants, can directly reverse histone methylation and play important roles in various growth and development processes. In the present study, 51 JmjC genes (GhJMJs) were identified by genome-wide analysis in upland cotton (Gossypium hirsutum), which can be categorized into six distinct groups by phylogenetic analysis. Extensive syntenic relationship events were found between G. hirsutum and Theobroma cacao. We have further explored the putative molecular regulatory mechanisms of the JmjC gene family in cotton. GhJMJ24 and GhJMJ49 were both preferentially expressed in embryogenic callus compared to nonembryogenic callus in cotton tissue culture, which might be regulated by transcription factors and microRNAs to some extent. Further experiments indicated that GhJMJ24 and GhJMJ49 might interact with SUVH4, SUVH6, DDM1, CMT3, and CMT1 in the nucleus, potentially in association with demethylation of H3K9me2. Taken together, our results provide a foundation for future research on the biological functions of GhJMJ genes in cotton, especially in somatic embryogenesis in cotton tissue culture, which is crucial for the regeneration of transgenic plants.

16.
Int J Biol Macromol ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561861

RESUMO

Misfolding and aggregation of α-synuclein (α-syn) play a key role in the pathogenesis of Parkinson's disease (PD). Herein, the inhibitory effect of ulvan on α-syn fibrillogenesis was studied using thioflavin T fluorescence and atomic force microscope assays. It is shown that ulvan could inhibit α-syn fibrillogenesis in a dose-dependent manner. Based on the circular dichroism results, it is found that ulvan delays greatly the conformational transition from its initial random coil to ß-sheet rich structure. The protective effect of ulvan against celllular death induced by α-syn aggregates was investigated by MTT colorimetric and cellular staining methods. It is found that ulvan protects greatly PC12 cells from α-syn fibril-induced cytotoxicity. In addition, ulvan disaggregates preformed α-syn fibrils and reduces cytotoxicity in a dose-dependent manner. Thereafter, the inhibitory effects of ulvan against α-syn fibrillogenesis were probed using Caenorhabditis elegans model NL5901 overexpressing α-syn. It is found that ulvan extends the lifespan of NL5901 and recovers the lipid deposition by reducing the accumulation of α-syn. Finally, the molecular interactions between ulvan and α-syn pentamer was also explored using molecular docking. These findings suggest that ulvan can be pursued as a novel candidate drug for treatment of PD.

17.
NPJ Biofilms Microbiomes ; 8(1): 31, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477734

RESUMO

Deterministic and stochastic forces both drive microbiota assembly in animals, yet their relative contribution remains elusive, especially in wild aquatic-insect-associated fungal communities. Here, we applied amplicon sequencing to survey the assembly mechanisms of the fungal community in 155 wild stonefly individuals involving 44 species of 20 genera within eight families collected from multiple locations in China. Analysis showed that fungal diversity and network complexity differed significantly among the eight stonefly families, and that the fungal communities in stoneflies exhibited a significant distance-decay pattern across large spatial scales. Both a structural equation model and variance partitioning analysis revealed that environmental factors (e.g., geographical, climatic) outweigh host attributes in shaping the fungal community of stoneflies. Using neutral and null model analyses, we also find that deterministic processes play a larger role than stochasticity in driving the fungal community assembly. However, the relative contribution of ecological processes including dispersal, drift, and selection, varied strongly with host taxonomy. Furthermore, environmental conditions also significantly affect the strength of these ecological processes. Overall, our findings illustrate that variations in host attributes and environment factors may moderate the relative influence of deterministic and stochastic processes to fungal community composition in wild stoneflies, which provides new insights into mechanisms of microbial community assembly in aquatic arthropods.


Assuntos
Microbiota , Micobioma , Animais , China , Humanos , Insetos , Processos Estocásticos
18.
Drug Deliv ; 29(1): 1132-1141, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35380084

RESUMO

Sodium aescinate (SA) is often used for intravenous (IV) injection owing to its anti-inflammatory, anti-exudative, increasing venous tension, improving blood circulation and reducing swelling activities. However, the clinical application of SA is limited by strong irritation, short half-life and low bioavailability. To overcome these defects, we intended to modify SA by encapsualing it with liposomes . SA was mixed with a proper amount of phospholipid and lyophilized to prepare the liposome of sodium aescinate for injection (SA-Lip-I). Its physical properties, cumulative release and dilution stability were evaluated in vitro. Its pharmacodynamic characteristics were evaluated. Safety of SA-Lip-I was evaluated in terms of hemolysis, IV irritation and acute toxicity. The mean particle size of SA-Lip-I was 117.33±0.95 nm, polydispersity index (PDI) was 0.140±0.017, Zeta potential was -30.34±0.23 mv, The cumulative release of SA-Lip at 12 h was more than 80%, which met the release requirements of nanoparticles. SA-Lip-I was well stable in the four mediators and met the clinical medication requirements. In addition, SA-Lip-I had better efficacy than the SA-I and has a significant difference. Furthermore, SA-Lip-I did not induce hemolysis at 37°C, and produced by far milder venous irritation as compared with SA-I. In addition, LD50 of SA-Lip-I was 2.12 fold that of the commercial SA-I, with no obvious side effects.The modified SA-Lip-I is a promising preparation which can reduce the irritation and toxic side effects, improve the treatment effect to a certain extent, but greatly alleviate pain of the patient during treatment, achieving the optimal curative effect.


Assuntos
Saponinas , Triterpenos , Humanos , Lipossomos , Água
19.
Artigo em Inglês | MEDLINE | ID: mdl-35388303

RESUMO

Methods: The chemical ingredients of ANW were retrieved from TCMSP, TCMID, and literature. We predicted the potential targets of active ingredients by PubChem, Swiss Target Prediction, and STITCH databases. The targets related to ischemic stroke were retrieved using GeneCards, DisGeNET, DrugBank, TTD, and GEO databases. Subsequently, Venn diagrams were used to identify common targets of active ingredients and ischemic stroke. Protein-protein interaction (PPI) network was structured with STRING platform and Cytoscape 3.8.2. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of key targets were performed in the Metascape database. Finally, molecular docking was conducted by AutoDock Tools and PyMOL software. Results: A total of 2391 targets were identified for 230 active ingredients of ANW, and 1386 of them overlapped with ischemic stroke targets. The key active ingredients were mainly quercetin, ß-estradiol, berberine, wogonin, and ß-sitosterol, and the key targets were also identified, including IL-6, AKT1, MAPK3, PIK3CA, and TNF. The biological process (BP) results indicated that ANW may have therapeutic effects through response oxidative stress, inflammatory response, cellular response to lipid, and response to nutrient levels. Furthermore, the ingredients of ANW were predicted to have therapeutic effects on ischemic stroke via the HIF-1 signaling pathway, FoxO signaling pathway, chemokine signaling pathway, fluid shear stress and atherosclerosis, and neurotrophin signaling pathway. The molecular docking results all showed that the core ingredients were strong binding activity with the core targets. Conclusion: In conclusion, the bioinformatics and pharmacological results reveal that counteracting oxidative stress, suppressing inflammation, inhibiting the development of AS, and even protecting neurological function are critical pathways for ANW in the treatment of ischemic stroke. These results may help to elucidate the mechanism of ANW on ischemic stroke for experimental studies and clinical applications.

20.
Front Psychiatry ; 13: 796384, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432017

RESUMO

Evaluating the resolution of parents of ill children can help in taking measures to alleviate their distress in a timely manner and promote children's rehabilitation. This study aims to develop and validate a nomogram for predicting the unresolved risk of parents of adolescents with psychiatric diagnoses. The data for 130 parents (modeling dataset = 90; validation dataset = 40) were collected. A nomogram was first developed to predict the unresolved risk for parents based on the logistic regression analysis in the modeling dataset. The internal and external validation then were conducted through quantifying the performance of the nomogram with respect to discrimination and calibration, respectively, in the modeling and validation datasets. Finally, the clinical use was evaluated through decision curve analyses (DCA) in the overall dataset. In the results, the nomogram consisted of six risk factors and provided a good discrimination with areas under the curve of 0.920 (95% CI, 0.862-0.978) in internal validation and 0.886 (95% CI, 0.786-0.986) in external validation. The calibration with good consistency between the observed probability and predicted probability was also found in both internal and external validation. DCA showed that the nomogram had a good clinical utility. In conclusion, the proposed nomogram exhibited a favorable performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and, thus, can be used as a convenient and reliable tool for predicting the unresolved risk of parents of children with psychiatric diagnoses.

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