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1.
Plant Sci ; 312: 111052, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620447

RESUMO

Drought occurrence seriously affects the productivity and quality of apple crop worldwide. Autophagy, a conserved process for the degradation and recycling of unwanted cellular components, is considered to positively regulate the tolerance of various abiotic stresses in plants. In the current study, we isolated two ATG5 homologs genes, namely, MdATG5a and MdATG5b, from apple, demonstrating their responsiveness to drought and oxidative stresses. In addition to having the same cellular localization in the nucleus and cytoplasm, both MdATG5a and MdATG5b could interact with MdATG12. Transgenic apple plants overexpressing MdATG5a exhibited an improved drought tolerance, as indicated by less drought-related damage and higher photosynthetic capacities compared to wild-type (WT) plants under drought stress. The overexpression of MdATG5a improved antioxidant defenses in apple when exposed to drought via elevating both antioxidant enzyme activities and the levels of beneficial antioxidants. Furthermore, under drought stress, the overexpression of MdATG5a promoted the mobilization of starch to accumulate greater levels of soluble sugars, contributing to osmotic adjustments and supporting carbon skeletons for proline synthesis. Such changes in physiological responses may be associated with increased autophagic activities in the transgenic plants upon exposure to drought. Our results demonstrate that MdATG5a-mediated autophagy enhances drought tolerance of apple plants via improving antioxidant defenses and metabolic adjustments.

2.
Opt Express ; 29(15): 23258-23272, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34614593

RESUMO

High-resolution optical spectral analysis method is of significant importance for those who want to explore the physical world from the frequency domain. Aiming at the resolution degradation of classical coherent optical spectrum analysis (COSA) caused by the mirror phenomenon, this paper modifies the COSA system by introducing two homologous Brillouin scattering beams to serve as the pre-filter and local oscillator (LO), respectively. The central frequencies of the pre-filtered signal and the LO are locked by the Brillouin frequency shifts of those two Brillouin scattering beams. By means of this modification, the pre-filtered signal is located at either the upper-frequency-shifted side or the lower-frequency-shifted sides of the LO but could not exist on both sides of the LO. The proposed method could cancel the mirror phenomenon and thus improve the systematic resolution to 1.3 MHz in theory and 2 MHz in practice.

3.
Ultrason Sonochem ; 80: 105788, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34688142

RESUMO

In this work, the spraying of ethanol solution containing phenolic acid (ferulic acid or caffeic acid) was performed before subjecting to contact ultrasound-assisted air drying of blackberry. The mass transfer modeling results revealed that sonication intensified both internal water diffusion and external water exchange during drying, and ethanol pretreatment enhanced the effective diffusivity of water. Compared with air drying alone, the drying time for sequential ferulic acid pretreatment and drying with sonication was shortened by 89.2%. Owing to the co-pigmentation between phenolic acid and anthocyanins, the retention of anthocyanins was significantly enhanced after dehydration. At the end of drying, the total anthocyanin contents in the ultrasound-dried samples pretreated with ferulic acid and caffeic acid were 25.3% and 10.5% higher than the sonicated samples without pretreatments, respectively. Furthermore, drying simultaneously with sonication promoted the preservation of non-anthocyaninic soluble phenolics including catechin, phloretic acid, rutin in blackberry compared to air drying alone. Besides, bound phenolics in blackberry were less influences by the applied dehydration treatments. This study demonstrates that the combination of phenolic acid co-pigmentation pretreatment and ultrasound drying could be a promising method to protect anthocyanin pigments during dehydration of berry fruits.

4.
ACS Appl Mater Interfaces ; 13(39): 46361-46374, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34579526

RESUMO

Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.

5.
ACS Nano ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590820

RESUMO

Lithium-sulfur (Li-S) batteries are one of the most promising candidates for next-generation energy storage systems because of their high theoretical energy density. However, the shuttling behavior and sluggish conversion kinetics of lithium polysulfides (LiPSs) limit their practical application. Herein, B-doped MoS2 nanosheets are synthesized on carbon nanotubes (denoted as CNT@MoS2-B) to function as catalysts to boost the performance of Li-S batteries. The poor catalytic performance of the pristine MoS2 is revealed to be the result of unsuitable orbital orientation of the basal plane, which hinders the orbital overlap with sulfur species. B in CNT@MoS2-B is sp3 hybridized, and it has a vacant σ orbital perpendicular to the basal plane, which can maximize the head-on orbital overlap with S. The incorporation of B significantly increases the reactivity of MoS2 basal plane, which can facilitate the kinetics of Li2S formation and dissolution. With these merits, the S/CNT@MoS2-B cathodes deliver high rate capability and outstanding cycling stability, holding great promise for both scientific research and practical application. This work affords fresh insights for developing effective catalysts to accelerate LiPS conversion.

6.
J Colloid Interface Sci ; 606(Pt 2): 1340-1351, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34500150

RESUMO

The fabrication of stable and efficient catalysts for green and economic catalytic transformation is significant. Here, highly stable covalent triazine frameworks (CTF-1) were used as the supporting material for anchoring ultrafine Pd nanoparticles (NPs) via a facile impregnation process and a one-pot calcination-reduction strategy. The widespread dispersion of ultrafine Pd NPs was a result of the abundant high nitrogen-content triazine groups of CTF-1 that endowed the catalyst Pd@CTF-1 with high catalytic activity. The catalytic performance of Pd@CTF-1 was demonstrated by the one-pot N-alkylation of benzaldehyde with aniline (or nitrobenzene) under mild reaction conditions, and Pd@CTF-1 exhibited a wide range of general applicability for N-alkylation reactions. The reaction mechanism for the N-alkylation reaction was also studied in detail. In addition, the Pd@CTF-1 catalyst exhibited high thermal and chemical stability, maintaining good catalytic efficiency after multiple reaction cycles. This study provides new insights for the fabrication of organic supporting materials with highly dispersed active catalytic sites that can lead to excellent catalytic performance for efficient, economical, and green reactions.

7.
J Colloid Interface Sci ; 606(Pt 2): 1524-1533, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34500155

RESUMO

Heterogeneous noble metal-based catalysts with stable, precise structures and high catalytic performance are of great research interest for sustainable catalysis. Herein, we designed the novel sandwich-like metal-organic-framework composite nanocatalyst UiO-66-NH2@Pt@mSiO2 using UiO-66-NH2@Pt as the core, and mesoporous SiO2 as the shell. The obtained UiO-66-NH2@Pt@mSiO2 catalyst shows a well-defined structure and interface, and the protection of the mSiO2 shell can efficiently prevent Pt NPs from aggregating and leaching in the reaction process. In the one-pot cascade reaction of nitroarenes and aromatic aldehydes to secondary amines, UiO-66-NH2@Pt@mSiO2 shows excellent catalytic performance due to acid catalytic sites provided by UiO-66-NH2 and Pt hydrogenation catalytic sites. Furthermore, the porous structure of the UiO-66-NH2@Pt@mSiO2 catalyst also enhances reactant diffusion and improves the reaction efficiency. This work provides a new avenue to meticulously design well-defined nanocatalysts with superior catalytic performance and stability for challenging reactions.

8.
Nanoscale ; 13(36): 15267-15277, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34477185

RESUMO

Metastasis is a major sign of malignant tumors which plays a vital role in cancer-related death. Suppressing metastasis is an important way to improve the survival rate of cancer patients. Herein, multifunctional PEG-LAM-PPS nanoparticles (nPLPs) are fabricated as both nanocarriers and anti-metastatic agents for tumor treatment. In this system, laminarin sulfate (LAM) suppresses metastasis by reducing heparinase and protecting the extracellular matrix; the ROS-sensitive polypropylene sulfide (PPS) improves the release of the loaded drug in the tumor microenvironment. This is the first time that laminarin sulfate has been used as a carrier to inhibit the expression of heparinase and treat melanoma lung metastasis. The blank nanoparticles are excellently safe and showed high anti-metastatic efficacy in melanoma lung metastatic mouse models, reducing metastatic nodules by 60%. They significantly improved the anti-tumor efficacy of the loaded drug doxorubicin, provided ∼33% further reduction of the tumor volume and 50% further reduction of the metastatic nodule number compared with free doxorubicin. Thus, these simple and versatile micellar nanoparticles composed of biocompatible materials offer a promising vehicle for treating invasive solid tumors and metastases.


Assuntos
Antineoplásicos , Nanopartículas , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Regulação para Baixo , Doxorrubicina/farmacologia , Heparina Liase , Humanos , Camundongos , Micelas , Espécies Reativas de Oxigênio
9.
Inorg Chem ; 60(19): 14786-14792, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34543021

RESUMO

Rational design of transition-metal phosphide (TMPs)-based electrocatalysts can effectively promote oxygen evolution reaction (OER). Herein, the novel efficient Ni2P/Fe3O4 porous nanosheets arrays supported on Ni foam (Ni2P/Fe3O4/NF) as alkaline OER catalysts were synthesized using structural and interfacial engineering. The three-dimensional (3D) porous hierarchical structure of Ni2P/Fe3O4/NF provides abundant active sites for OER and facilitates the electrolyte diffusion of ions and O2 liberation. Furthermore, the strong interfacial coupling and synergistic effect between Ni2P and Fe3O4 modify the electronic structure, resulting in the enhanced intrinsic activity. Consequently, the optimized Ni2P/Fe3O4/NF exhibits excellent OER performance with low overpotentials of 213 and 240 mV at 60 and 100 mA cm-2 in 1.0 M KOH, respectively, better than the RuO2/NF and most Ni/Fe-based OER catalysts. Impressively, it can maintain its catalytic activity for at least 20 h at 60 mA cm-2. In addition, the relationship between the structure and performance is fully elucidated by the experimental characterizations, indicating that the metal oxyhydroxides in situ generated on the surface of catalysts are responsible for the high OER activity.

10.
Small ; : e2102962, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34520126

RESUMO

Polysulfide shuttling and sluggish sulfur redox kinetics hinder the cyclability and rate capability of lithium-sulfur (Li-S) batteries. The intrinsic redox kinetics of sulfur cathodes strongly depends on the interaction between catalysts and sulfur species. Herein, N-doped CoTe2 is proposed as an effective dual-anchoring electrocatalyst, which can simultaneously bind Li and S atoms in lithium polysulfides via ionic Te-Li/N-Li bonding and coordinate covalent Co-S bonding. The incorporated N not only serves as enhanced lithiophilic site, but also an agent to improve the sulfiphilicity of the Co site as revealed by a series of experimental and computational results. Benefiting from these superiorities, the use of N-doped CoTe2 as a catalytic interlayer enables efficient operation of Li-S batteries in terms of impressive rate capability of 758 mAh g-1 at 4 C and very low capacity decay of 0.021% per cycle over 1000 cycles. The material and strategy demonstrated in this work may open the door toward developing more advanced Li-S electrocatalysts.

11.
Adv Drug Deliv Rev ; 177: 113928, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34411689

RESUMO

Infectious diseases continue to inflict a high global disease burden. The consensus is that vaccination is the most effective option against infectious diseases. Oral vaccines have unique advantages in the prevention of global pandemics due to their ease of use, high compliance, low cost, and the ability to induce both systemic and mucosal immune responses. However, challenges of adapting vaccines for oral administration remain significant. Foremost among these are enzymatic and pH-dependent degradation of antigens in the stomach and intestines, the low permeability of mucus barrier, the nonspecific uptake of antigens at the intestinal mucosal site, and the immune suppression result from the elusive immune tolerance mechanisms. Innovative delivery techniques promise great potential for improving the flexibility and efficiency of oral vaccines. A better understanding of the delivery approaches and the immunological mechanisms of oral vaccine delivery systems may provide new scientific insight and tools for developing the next-generation oral vaccine. Here, an overview of the advanced technologies in the field of oral vaccination is proposed, including mucus-penetrating nanoparticle (NP), mucoadhesive delivery vehicles, targeting antigen-presenting cell (APC) nanocarriers and enhanced paracellular delivery strategies and so on. Meanwhile, the mechanisms of delivery vectors interact with mucosal barriers are discussed.

12.
Theranostics ; 11(17): 8517-8534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373756

RESUMO

Rationale: The progression of cancer cells depends on the soil and building an inhibitory soil might be a therapeutic option. We previously created tumor-suppressive secretomes by activating Wnt signaling in MSCs. Here, we examined whether the anti-tumor secretomes can be produced from tumor cells. Methods: Wnt signaling was activated in tumor cells by overexpressing ß-catenin or administering BML284, a Wnt activator. Their conditioned medium (CM) was applied to cancer cells or tissues, and the effects of CM were evaluated. Tumor growth in the mammary fat pad and tibia in C57BL/6 female mice was also evaluated through µCT imaging and histology. Whole-genome proteomics analysis was conducted to determine and characterize novel tumor-suppressing proteins, which were enriched in CM. Results: The overexpression of ß-catenin or the administration of BML284 generated tumor-suppressive secretomes from breast, prostate and pancreatic cancer cells. In the mouse model, ß-catenin-overexpressing CM reduced tumor growth and tumor-driven bone destruction. This inhibition was also observed with BML284-treated CM. Besides p53 and Trail, proteomics analysis revealed that CM was enriched with enolase 1 (Eno1) and ubiquitin C (Ubc) that presented notable tumor-suppressing actions. Importantly, Eno1 immunoprecipitated CD44, a cell-surface adhesion receptor, and its silencing suppressed Eno1-driven tumor inhibition. A pan-cancer survival analysis revealed that the downregulation of MMP9, Runx2 and Snail by CM had a significant impact on survival outcomes (p < 0.00001). CM presented a selective inhibition of tumor cells compared to non-tumor cells, and it downregulated PD-L1, an immune escape modulator. Conclusions: The tumor-suppressive secretome can be generated from tumor cells, in which ß-catenin presented two opposing roles, as an intracellular tumor promoter in tumor cells and a generator of extracellular tumor suppressor in CM. Eno1 was enriched in CM and its interaction with CD44 was involved in Eno1's anti-tumor action. Besides presenting a potential option for treating primary cancers and metastases, the result indicates that aggressive tumors may inhibit the growth of less aggressive tumors via tumor-suppressive secretomes.

13.
Arch Microbiol ; 203(9): 5397-5403, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34398306

RESUMO

A bacterial strain, designated M625T, was isolated from the surface of a marine red alga. Phylogenetic trees were reconstructed based on the 16S rRNA gene and RpoB protein sequences, which indicated that the strain belongs to the genus Aquimarina within the family Flavobacteriaceae. Strain M625T showed high sequence similarities to A. aggregata RZW4-3-2 T (95.7%), A. seongsanensis CBA3208T (95.3%) and A. versatilis CBA3207T (95.0%). The AAI and POCP values between strain M625T and A. muelleri DSM 19832 T were 71.8% and 57.9% respectively. The dDDH and ANI values between strain M625T and A. aggregata were 19.5% and 74.6% respectively. The strain was Gram-stain negative, strictly aerobic, non-motile and long rod-shaped, and positive for hydrolysis of starch, cellulose, alginate, DNA and Tween 20. The dominant respiratory quinone was MK-6. The major fatty acids were iso-C15:0, iso-C17:0 3-OH, and iso-C15:1 G, and the polar lipids consisted of phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids, and seven unidentified lipids. Based on the polyphasic comparisons, strain M625T is proposed to represent a novel species within the genus Aquimarina, for which the name Aquimarina algicola sp. nov. (type strain M625T = MCCC 1H00399T = KCTC 72685 T) was proposed.


Assuntos
Flavobacteriaceae , Rodófitas , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/análise , Flavobacteriaceae/genética , Filogenia , RNA Ribossômico 16S/genética , Rodófitas/genética , Água do Mar , Análise de Sequência de DNA , Vitamina K 2
14.
Int J Clin Pract ; : e14738, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399017

RESUMO

PURPOSE: Atrial fibrillation (AF) is one of the most common persistent arrhythmia, and its complications include cerebral embolism, arterial embolism and heart failure. Some studies have found that elevated Homocysteine (HCY) levels is a new risk factor for AF. Currently, there is no meta-analysis to explore whether the HCY levels is related to AF. Therefore, a meta-analysis was conducted to evaluate the relationship between the HCY levels and AF, in order to draw the attention of clinicians to the HCY levels. METHODS: A meta-analysis was performed in the study to evaluated the association between the HCY levels and AF. In order to identify eligible original articles, The EMBASE, PubMed, and web of science were systematically searched until November 2020. All data were analyzed with Review Manager 5.3. The meta-analysis results were evaluated depending on standardized mean differences (SMD) with 95% confidence intervals (CI). Moreover, the subgroup analysis and sensitivity analysis were also analyzed. RESULTS: The HCY levels was significantly associated with AF (WMD = 0.81, 95% CI: 0.58 to 1.03; P < .00001). In the analysis, there was a medium degree of heterogeneity (I2 = 73%). Subgroup analysis showed that female < 60, BMI≥25, BMI <25, age ≥60 and publication year ≥2010 were identified as possible sources of heterogeneity. Sensitivity analysis showed that the main results remained unchanged after omitting any single study or converting the random effects model (REM) to fixed effects model (FEM). CONCLUSIONS: The meta-analysis showed that there is a significant correlation between the HCY levels and AF, and the role of HCY in AF patients should not be ignored in clinical.

15.
Biomed Res Int ; 2021: 9933136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368360

RESUMO

Kidney transplantation is the promising treatment of choice for chronic kidney disease and end-stage kidney disease and can effectively improve the quality of life and survival rates of patients. However, the allograft rejection following kidney transplantation has a negative impact on transplant success. Therefore, the present study is aimed at screening novel biomarkers for the diagnosis and treatment of allograft rejection following kidney transplantation for improving long-term transplant outcome. In the study, a total of 8 modules and 3065 genes were identified by WGCNA based on the GSE46474 and GSE15296 dataset from the Gene Expression Omnibus (GEO) database. Moreover, the results of Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that these genes were mainly involved in the immune-related biological processes and pathways. Thus, 317 immune-related genes were selected for further analysis. Finally, 5 genes (including CD200R1, VAV2, FASLG, SH2D1B, and RAP2B) were identified as the candidate biomarkers based on the ROC and difference analysis. Furthermore, we also found that in the 5 biomarkers an interaction might exist among each other in the protein and transcription level. Taken together, our study identified CD200R1, VAV2, FASLG, SH2D1B, and RAP2B as the candidate diagnostic biomarkers, which might contribute to the prevention and treatment of allograft rejection following kidney transplantation.


Assuntos
Aloenxertos/patologia , Biomarcadores/metabolismo , Redes Reguladoras de Genes , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Aloenxertos/imunologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Rejeição de Enxerto/imunologia , Humanos , Anotação de Sequência Molecular , Mapas de Interação de Proteínas/genética , Curva ROC
16.
Dermatology ; : 1-11, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34455413

RESUMO

BACKGROUND: Current therapeutic options for atopic dermatitis (AD) are limited. Janus kinase (JAK) inhibitors may be viable alternatives. OBJECTIVES: To assess the efficacy and safety of JAK inhibitors for AD treatment. METHODS: We searched PubMed, Embase, the Cochrane Controlled Register of Trials, Web of Science, Global Resource of Eczema Trials database, and ClinicalTrials.gov from inception to September 1, 2020. Randomized clinical trials (RCTs) comparing JAK inhibitors with placebo/vehicle treatment for AD patients were included. The primary study outcomes included (1) the change (%) from the Eczema Area and Severity Index (EASI) baseline expressed as weighted mean difference (WMD) and 95% confidence interval (95% CI), and (2) the Investigator's Global Assessment (IGA) response and safety outcomes expressed as relative risk (RR) and 95% CI. RESULTS: We included 14 RCTs published in 13 studies (3,822 patients). Treatment with JAK inhibitors significantly improved IGA response (RR 2.83, 95% CI 2.25-3.56, p < 0.001) and EASI score (WMD -28.82, 95% CI -34.48 to -23.16, p < 0.001). JAK inhibitor treatment achieved the largest improvement in both IGA response (RR 3.59, 95% CI 2.66-4.84, p < 0.001) and EASI score (WMD -42.00, 95% CI -48.64 to -35.36, p < 0.001) by week 4 of treatment. Topical JAK inhibitors were significantly more efficacious than oral inhibitors. Upadacitinib treatment for 4 weeks was most effective in reducing EASI score (WMD -53.92, 95% CI -69.26 to -38.58, p < 0.001), while abrocitinib for 4 weeks led to the most effective IGA response (RR 5.47, 95% CI 2.74-10.93, p < 0.001). There was no difference in the frequency of adverse events (AEs) leading to discontinuation; however, JAK inhibitors use, especially abrocitinib, led to a higher incidence of treatment-emergent AEs (RR 1.25, 95% CI 1.10-1.42, p = 0.001). CONCLUSION: Our results imply that JAK inhibitors are an effective and safe AD treatment. Nevertheless, further trials with longer duration and head-to-head comparisons of different JAK inhibitors are needed.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34422078

RESUMO

Background: In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. Aim: This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. Materials and Methods: Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. Results: The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. Conclusions: These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways.

18.
RSC Chem Biol ; 2(3): 843-854, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34458813

RESUMO

Nonribosomal peptide synthetases (NRPSs) are multifunctional megaenzymes that govern the stepwise biosynthesis of pharmaceutically important peptides. In an ATP-dependent assembly-line mechanism dedicated domains are responsible for each catalytic step. Crystal structures have provided insight into several conformations of interacting domains. However, the complete picture in solution of how domain dynamics and the timing of conformational changes effect a directional biosynthesis remains only poorly understood and will be important for the efficient reprogramming of NRPSs. Here we dissect the multiple conformational changes associated with the adenylation and thiolation reactions of the aminoacylation pathway under catalytic conditions. We used pyrophosphate (PP i ) to biochemically drive the conformational changes backward and forward while performing an online monitoring with a Förster resonance energy transfer (FRET) didomain sensor, consisting of adenylation (A) and peptidyl-carrier protein (PCP) domains. Notably, we found aminoacyl thioester formation to efficiently occur in the presence of PP i even at millimolar concentrations, despite the chemically and conformationally reversing effect of this metabolite and by-product. This finding settles conflicting reports and explains why intracellular PP i concentrations do not impair NRP biosynthesis. A conserved amino acid was identified to be important for the mechanism under these conditions. FRET time-course analyses revealed that the directionality of the aminoacylation catalysis is correlated with conformational kinetics. Complemented by equilibrium hydrogen-deuterium exchange (HDX) analyses, our data uncovered the existence of at least one new intermediary conformation that is associated with the rate-determining step. We propose an expanded model of conformational changes in the NRPS aminoacylation pathway.

19.
CNS Neurosci Ther ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34415671

RESUMO

INTRODUCTION: The blood-brain barrier (BBB) disruption contributes to postoperative delirium, but cost-effective and non-invasive assessment of its permeability is not practicable in the clinical settings. Urine albumin to creatinine ratio (UACR), reflecting systemic vascular endothelial dysfunction, may be a prognostic and predictive factor associated with postoperative delirium. The aim was to analyze the relationship between UACR and postoperative delirium in elderly patients undergoing elective non-cardiac surgery. MATERIALS AND METHODS: Through stratified random sampling, a cohort of 408 individuals aged 60 years and older scheduled for elective non-cardiac surgery were included between February and August 2019 in the single-center, prospective, observational study. The presence of delirium was assessed using the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM-ICU) on the day of surgery, at 2 h after the surgery ending time and on the first 3 consecutive days with repeated twice-daily, with at least 6-h intervals between assessments. Urine samples were collected on one day before surgery, and 1st day and 3rd day after surgery. The primary outcome was the presence of postoperative delirium, and association of the level of UACR with postoperative delirium was evaluated with unadjusted/adjusted analyses and multivariable logistic regression. RESULTS: Postoperative delirium was observed in 26.75% (107 of 400) of patients within 3 days post-surgery. UACR-Pre (OR, 1.30; 95% CI, 1.14-1.49, p < 0.001), UACR-POD1 (OR, 1.20; 95% CI, 1.13-1.27, p < 0.001), and UACR-POD3 (OR, 1.14; 95% CI, 1.08-1.20, p < 0.001) between the delirium and non-delirium groups show a significant difference, even after adjusting for age, education levels, and other factors. CONCLUSION: As the marker of endothelial dysfunction, the high perioperative UACR value may be linked to the postoperative delirium in elderly patients undergoing elective non-cardiac surgery.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34339093

RESUMO

Metal-organic frameworks (MOFs) heterostructures with domain-controlled emissive colors have shown great potential for achieving high-throughput sensing, anti-counterfeit and information security. Here, a strategy based on steric-hindrance effect is proposed to construct lateral lanthanide-MOFs (Ln-MOFs) epitaxial heterostructures, where the channel-directed guest molecules are introduced to rebalance in-plane and out-of-plane growth rates of the Ln-MOFs microrods and eventually generate lateral MOF epitaxial heterostructures with controllable aspect ratios. A library of lateral Ln-MOFs heterostructures are acquired through a stepwise epitaxial growth procedure, from which rational modulation of each domain with specific lanthanide doping species allows for definition of photonic barcodes in a two-dimensional (2D) domain with remarkably enlarged encoding capacity. The results provide molecular-level insight into the use of modulators in governing crystallite morphology for spatially assembling multifunctional heterostructures.

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