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1.
Virus Res ; 324: 199038, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36599394

RESUMO

Enterovirus A71 (EV-A71) is neurotropic and one of the primary enteric pathogens responsible for severe central nervous system infection in infants and young children. Neonatal mice are ideal models for studying the pathogenesis of infection caused by EV-A71. In this study, we assessed the susceptibility of neonatal BALB/c, C57BL/6, ICR, Kunming, and NIH mice to a clinically isolated EV-A71 strain. One-day-old mice were challenged with a clinical isolate of EV-A71 via intraperitoneal injection, then observed for 13 days for mortality, body-weight changes, and limb paralysis. RT-qPCR was performed to quantify viral RNA in the brain, spinal cord, skeletal muscle, and lungs of BALB/c and C57BL/6 mice. The expression of murine scavenger receptor class B member 2 (mSCARB2) was measured by western blotting. Finally, lesions were assessed by histological examination. We found that neonatal BALB/c and C57BL/6 mice were both susceptible to EV-A71, leading to decreased survival rate, greater body weight loss, and prominent hind-limb paralysis. Tissue viral loads of C57BL/6J mice were markedly higher than those of BALB/c mice, indicating that EV-A71 replicated more efficiently in C57BL/6 mice. Increased expression of mSCARB2 was observed 5 days after infection in C57BL/6 mice, which coincided with the peak in EV-A71 replication. Histological examination indicated that infection caused obvious pathogenic lesions. In conclusion, C57BL/6 are most susceptible to infection caused by EV-A71 and can be used as a model for studying its pathogenesis and test therapeutic options.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Animais , Camundongos , Enterovirus/genética , Enterovirus Humano A/fisiologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Antígenos Virais/genética , Camundongos Endogâmicos BALB C
2.
Genomics ; 115(2): 110557, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36610559

RESUMO

Early bolting of Peucedanum praeruptorum Dunn severely affects its quality. In this study, we compared with the root structure of P. praeruptorum and its four coumarins content between early bolting (CT) and unbolting (WT) at different growth stages. We found that the proportion of area outside the root cambium (Rs) was higher in the WT plants than in the CT plants and correlated positively with the proximity to the root tip. Furthermore, the content of all four coumarins was also higher in the WT plants relative to the CT plants. In addition, we identified 15,524 differentially expressed genes (DEGs) between the two plant varieties. 11 DEGs are involved in the photoperiod and gibberellin pathways that regulate early bolting and 24 genes involved in coumarins biosynthesis were also identified. Nevertheless, early bolting of P. praeruptorum does affect its quality formation, and further studies are needed to confirm its mechanism.

3.
Int J Mol Sci ; 24(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36675225

RESUMO

SDF-1α, the most common isoform of stromal cell-derived factor 1, has shown vital effects in regulating chondrocyte proliferation, maturation, and chondrogenesis. Autophagy is a highly conserved biological process to help chondrocytes survive in harsh environments. However, the effect of SDF-1α on chondrocyte autophagy is still unknown. This study aims to investigate the effect of SDF-1α on chondrocyte autophagy and the underlying biomechanism. Transmission electron microscope assays and mRFP-GFP-LC3 adenovirus double label transfection assays were performed to detect the autophagic flux of chondrocytes. Western blots and immunofluorescence staining assays were used to detect the expression of autophagy-related proteins in chondrocytes. RNA sequencing and qPCR were conducted to assess changes in autophagy-related mRNA expression. SDF-1α upregulated the number of autophagosomes and autolysosomes in chondrocytes. It also increased the expression of autophagy-related proteins including ULK-1, Beclin-1 and LC3B, and decreased the expression of p62, an autophagy substrate protein. SDF-1α-mediated autophagy of chondrocytes required the participation of receptor CXCR4. Moreover, SDF-1α-enhanced autophagy of chondrocytes was through the inhibition of phosphorylation of mTOR signaling on the upstream of autophagy. Knockdown by siRNA and inhibition by signaling inhibitor further confirmed the importance of the CXCR4/mTOR signaling axis in SDF-1α-induced autophagy of chondrocytes. For the first time, this study elucidated that SDF-1α promotes chondrocyte autophagy through the CXCR4/mTOR signaling axis.


Assuntos
Quimiocina CXCL12 , Condrócitos , Condrócitos/metabolismo , Quimiocina CXCL12/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Receptores CXCR4/metabolismo , Autofagia/genética
5.
Small ; : e2207214, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670333

RESUMO

The exploitation of electrode materials with ability to balance capacity and kinetics between cathode and anode is a challenge for sodium-ion hybrid capacitors (SIHCs). Mn-based anode materials are limited by poor electrical conductivity, sluggish reaction kinetics, large volume variation, weak cycling stability, and inferior reversible capacity. Herein, MnS nanocubes encapsulated in S-doped porous carbon matrix (MSC) with strong sulfur-bridged bond interactions (CSMn) are successfully synthesized by solvent-free tactics. The CSMn bonds generated between MnS and carbon significantly inhibit the aggregation of nanostructural MnS cubes, restrict the volume expansion, and stabilize the nanostructure, which improves the Na+ storage reversibility and stability. Moreover, S-doped porous carbon enhances the electrical conductivity and electrons/ions diffusion rate, which boosts a fast kinetic reaction. As expected, MSC anode presents an outstanding reversible capacity of 600 mAh g-1 at 0.2 A g-1 and a long-term stable capacity of 357 mAh g-1 for 1000 cycles at a high current density of 10 A g-1 in sodium-ion batteries (SIBs). The as-assembled SIHCs deliver a high energy density of 109 W h kg-1 and a high power output of 98 W kg-1 , with 88% capacity retention at 2 A g-1 after 2000 cycles and practical applications (55 LEDs can be lighted for 10 min).

6.
Regen Biomater ; 10: rbac100, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683745

RESUMO

Mechanical stiffness is recognized as a key physical factor and directs cell function via a mechanotransduction process, from extracellular physical cues to intracellular signaling cascades that affect transcriptional activity. Cells continually receive mechanical signals from both the surrounding matrix and adjacent cells. However, how mechanical stiffness cue at cell-substrate interfaces coordinates cell-cell junctions in guiding mesenchymal stem cell behaviors is poorly understood. Here, polydimethylsiloxane substrates with different stiffnesses were used to study mechanosensation/transduction mechanisms in controlling odontogenic differentiation of dental papilla cells (DPCs). DPC phenotypes (morphology and differentiation) changed in response to the applied force derived from stiff substrates. Significantly, higher expression of paxillin on stiffer substrates promoted DPC dentinogenesis. Upon treatment with siRNA to knockdown paxillin, N-cadherin increased mainly in the cytomembrane at the area of cell-cell contacts, whereas ß-catenin decreased in the nuclei. The result of a double luciferase reporter assay showed that stiffness promoted ß-catenin binding to TCF, which could coactivate the target genes associated with odontogenic differentiation, as evidenced by bioinformatics analysis. Finally, we determined that the addition of a ß-catenin inhibitor suppressed DPC mineralization in all the stiffness groups. Thus, our results indicated that a mechanotransduction process from cell-substrate interactions to cell-cell adhesions was required for DPC odontogenic differentiation under the stimulation of substrate stiffness. This finding suggests that stem cell fate specification under the stimulus of stiffness at the substrates is based on crosstalk between substrate interactions and adherens junctions, which provides an essential mechanism for cell-based tissue engineering.

7.
J Investig Med ; : 10815589221150643, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695444

RESUMO

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587-0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE.

8.
Nanomicro Lett ; 15(1): 32, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624319

RESUMO

Efficient synthesis of transition metal hydroxides on conductive substrate is essential for enhancing their merits in industrialization of energy storage field. However, most of the synthetic routes at present mainly rely on traditional bottom-up method, which involves tedious steps, time-consuming treatments, or additional alkaline media, and is unfavorable for high-efficiency production. Herein, we present a facile, ultrafast and general avenue to synthesize transition metal hydroxides on carbon substrate within 13 s by Joule-heating method. With high reaction kinetics caused by the instantaneous high temperature, seven kinds of transition metal-layered hydroxides (TM-LDHs) are formed on carbon cloth. Therein, the fastest synthesis rate reaches ~ 0.46 cm2 s-1. Density functional theory calculations further demonstrate the nucleation energy barriers and potential mechanism for the formation of metal-based hydroxides on carbon substrates. This efficient approach avoids the use of extra agents, multiple steps, and long production time and endows the LDHs@carbon cloth with outstanding flexibility and machinability, showing practical advantages in both common and micro-zinc ion-based energy storage devices. To prove its utility, as a cathode in rechargeable aqueous alkaline Zn (micro-) battery, the NiCo LDH@carbon cloth exhibits a high energy density, superior to most transition metal LDH materials reported so far.

9.
Cell Signal ; : 110605, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36681291

RESUMO

Gap junction intercellular communication (GJIC) allows the transfer of material, message and energy between cells, which influences cell behaviors including cell proliferation, migration, differentiation and apoptosis and determines cell fate. Interleukin-10 (IL-10), a versatile cytokine, attracts more and more attention in the cartilage pathology such as osteoarthritis (OA) due to its potential in anti-inflammatory and wound repair. However, whether IL-10 can mediate GJIC in chondrocytes remains elusive. In the current study, we aimed to explore the role of IL-10 on GJIC and its underlying mechanism. We found that IL-10 can promote GJIC in living chondrocytes. IL-10-enhanced GJIC in chondrocytes was dependent on the up-regulation of connexin 43 (Cx43). Knockdown experiment based on siRNA interference then confirmed that IL-10-enhanced GJIC required participation of IL-10 receptor 1. IL-10 activated signal transducer and activator of transcription 3 (STAT3) signaling and promoted the nuclear accumulation of p-STAT3 through IL-10 receptor 1. Inhibitor experiment further confirmed the importance of STAT3 signaling in IL-10-mediated GJIC. Taking together, our results provided a thorough process of IL-10-modulated cell-to-cell communication in chondrocytes and established a bridge between inflammatory factor, IL-10, and GJIC, which can increase our understanding about the physiology and pathology of cartilage.

10.
Bone Res ; 11(1): 2, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36588106

RESUMO

Articular cartilage serves as a low-friction, load-bearing tissue without the support with blood vessels, lymphatics and nerves, making its repair a big challenge. Transforming growth factor-beta 3 (TGF-ß3), a vital member of the highly conserved TGF-ß superfamily, plays a versatile role in cartilage physiology and pathology. TGF-ß3 influences the whole life cycle of chondrocytes and mediates a series of cellular responses, including cell survival, proliferation, migration, and differentiation. Since TGF-ß3 is involved in maintaining the balance between chondrogenic differentiation and chondrocyte hypertrophy, its regulatory role is especially important to cartilage development. Increased TGF-ß3 plays a dual role: in healthy tissues, it can facilitate chondrocyte viability, but in osteoarthritic chondrocytes, it can accelerate the progression of disease. Recently, TGF-ß3 has been recognized as a potential therapeutic target for osteoarthritis (OA) owing to its protective effect, which it confers by enhancing the recruitment of autologous mesenchymal stem cells (MSCs) to damaged cartilage. However, the biological mechanism of TGF-ß3 action in cartilage development and OA is not well understood. In this review, we systematically summarize recent progress in the research on TGF-ß3 in cartilage physiology and pathology, providing up-to-date strategies for cartilage repair and preventive treatment.

11.
NPJ Biofilms Microbiomes ; 9(1): 1, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596826

RESUMO

Tibial dyschondroplasia (TD) with multiple incentives is a metabolic skeletal disease that occurs in fast-growing broilers. Perturbations in the gut microbiota (GM) have been shown to affect bone homoeostasis, but the mechanisms by which GM modulates bone metabolism in TD broilers remain unknown. Here, using a broiler model of TD, we noted elevated blood glucose (GLU) levels in TD broilers, accompanied by alterations in the pancreatic structure and secretory function and damaged intestinal barrier function. Importantly, faecal microbiota transplantation (FMT) of gut microbes from normal donors rehabilitated the GM and decreased the elevated GLU levels in TD broilers. A high GLU level is a predisposing factor to bone disease, suggesting that GM dysbiosis-mediated hyperglycaemia might be involved in bone regulation. 16S rRNA gene sequencing and short-chain fatty acid analysis revealed that the significantly increased level of the metabolite butyric acid derived from the genera Blautia and Coprococcus regulated GLU levels in TD broilers by binding to GPR109A in the pancreas. Tibial studies showed reduced expression of vascular regulatory factors (including PI3K, AKT and VEFGA) based on transcriptomics analysis and reduced vascular distribution, contributing to nonvascularization of cartilage in the proximal tibial growth plate of TD broilers with elevated GLU levels. Additionally, treatment with the total flavonoids from Rhizoma drynariae further validated the improvement in bone homoeostasis in TD broilers by regulating GLU levels through the regulation of GM to subsequently improve intestinal and pancreatic function. These findings clarify the critical role of GM-mediated changes in GLU levels via the gut-pancreas axis in bone homoeostasis in TD chickens.


Assuntos
Microbioma Gastrointestinal , Osteocondrodisplasias , Animais , Osteocondrodisplasias/terapia , Osteocondrodisplasias/veterinária , Osteocondrodisplasias/metabolismo , Tiram , Galinhas , RNA Ribossômico 16S , Homeostase , Glucose
12.
Eur Radiol ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648550

RESUMO

OBJECTIVES: To investigate the imaging features of unilateral pulsatile tinnitus (PT) with jugular bulb wall dehiscence (JBWD). METHODS: Computerized tomography angiography images of unilateral PT patients were reviewed between 2019 and 2021. Thirty-one symptomatic JBWD patients without sigmoid sinus wall dehiscence (SSWD) were included. Thirty-eight patients with SSWD were used as the control group. The prevalence of JBWD was calculated. The area and height of the jugular bulb, the extent of dehiscence, the presence of jugular bulb diverticulum, posterior condylar emissary vein (PCEV), oblique occipital sinus (OOS), venous outflow laterality (VOL), the degree of transverse sinus stenosis (TSS), and the pituitary height to sella turcica ratio were compared between the two groups. RESULTS: The prevalence of JBWD was 12.1%, and JBWD was established as a causative diagnosis in 5.0% of unilateral PT patients. There were no statistical differences in the gender, symptomatic side, or VOL between the two groups. The area of the jugular bulb was larger and the height was higher (parea < 0.001, pheight = 0.005). The prevalence of jugular bulb diverticulum was higher in the JBWD group (p = 0.002). The degree of symptomatic TSS was less severe (p < 0.001), and the prevalence of bilateral TSS was lower in the JBWD group (p < 0.001). The pituitary height to sella turcica ratio was greater (p = 0.004), the prevalence of PCEV (p = 0.014) was lower, and OOS (p = 0.015) was greater in the JBWD group. CONCLUSIONS: The correlating factors of PT with JBWD and PT with SSWD are significantly different. These findings can further facilitate early and efficient PT treatment. KEY POINTS: • The incidence of jugular bulb dehiscence (JBWD) accounted for approximately 12.1% in pulsatile tinnitus (PT) patients, and JBWD was established as a causative diagnosis in 5.0% of PT patients. • PT required large blood flows and abnormal flow patterns, whether in JBWD or sigmoid sinus wall dehiscence groups. • JBWD causing PT has some unique characteristic findings on CT.

13.
Endocrine ; 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36689171

RESUMO

PURPOSE: The dopamine agonists (DA) have been used widely to treat prolactinomas. However, it is difficult to predict whether the patient will be responsive to DA treatment. METHODS: We aimed to investigate whether the in vivo expression of DRD2 based on 18F-fallypride PET/MR could predict the therapeutic effect of DA on prolactinomas. Seven patients with prolactinomas completed 18F-fallypride PET/MR. Among them, three patients underwent surgery and further tumor immunohistochemistry. Imaging findings and immunohistochemical staining were compared with treatment outcomes. RESULTS: 18F-fallypride PET/MR was visually positive in 7 of 7 patients, and DRD2 target specificity could be confirmed by immunohistochemical staining. A significantly lower tracer standard uptake value (SUV) could be detected in the resistant patients (n = 3) than in the sensitive patients (n = 4; SUVmean, 4.67 ± 1.32 vs. 13.57 ± 2.42, p < 0.05). DRD2 expression determined by 18F-fallypride PET/MR corresponded with the DA treatment response. CONCLUSION: 18F-fallypride PET/MR may be a promising technique for predicting DA response in patients with prolactinoma.

14.
Vet Microbiol ; 277: 109635, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36563583

RESUMO

Duck adenovirus 3 (DAdV-3), identified as the causative agent of a disease characterized by swelling and hemorrhage of liver and kidney, has caused substantial economic losses to duck industry in China. However, the neutralizing epitopes and the infection mechanism of DAdV-3 have not been extensively elucidated. In this study, a novel monoclonal antibody (mAb) targeting Fiber-2 protein of DAdV-3 was generated and designated as mAb 3E7. Indirect immunofluorescence assay showed that mAb 3E7 specifically reacted with the Fiber-2 in LMH cells transfected with pcDNA3.1-Fiber-2 or infected with DAdV-3. Moreover, mAb 3E7 could immunoprecipitate the Fiber-2 and efficiently inhibit the infection of DAdV-3 in vitro. Further epitope mapping revealed mAb 3E7 recognized the epitope 108LALGDGLE115 in Fiber-2, which was highly conserved among DAdV-3 strains. These findings not only identified a novel neutralizing epitope in Fiber-2, but also paved the way for further elucidating the vital roles of Fiber-2 in the infection and pathogenesis of DAdV-3.


Assuntos
Anticorpos Antivirais , Aviadenovirus , Animais , Patos , Anticorpos Monoclonais , Epitopos , Mapeamento de Epitopos/veterinária
15.
Int J Biol Macromol ; 226: 102-110, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36495986

RESUMO

Starch microspherical aerogel (SMA) prepared by enzymatic hydrolysis of starch with α-amylase was demonstrated to be higher adsorption capacity for methylene blue. Proper cleavage of α-1,4 glycosidic bonds could enhance the adsorption capacity of SMA, while the cleavage of α-1,6 glycosidic bonds showed an opposite effect. Compared with tapioca starch (TS), α-amylase hydrolyzed starch exhibited a 9.46 % decrease in amylose content, a 25.40 % increase in adsorbability, and significant decreases in weight-average molecular weight (Mw) of different amylases. When the Mw of enzymolysis starch was 6.39 × 106 g/mol, it was suitable for the preparation of SMA, and could significantly increase its adsorption capacity. The adsorbability of the crosslinked starch microspherical aerogel (CSMA) was 1.816 ± 0.026 mg/g, which was increased by 100.60 % relative to that of native starch microspherical aerogel (NSMA). CSMA had the best adsorption effect on oil and could be applied to the adsorption and removal of vegetable oil.


Assuntos
Amido , alfa-Amilases , Amido/química , Adsorção , alfa-Amilases/química , Hidrólise , Amilose
16.
J Ethnopharmacol ; 303: 115997, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509256

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolius Linn. is one of the most valuable herbal medicine in the world for its broad health benefits, including anti-diabetes. Ginsenoside Rb1, the principal active constituent of Panax quinquefolius Linn., could attenuate insulin resistance and metabolic disorders. The dysfunction of gut microbiota and fecal metabolites plays an important role in the pathogenesis of Type 2 Diabetes mellitus (T2DM). However, whether ginsenoside Rb1's hypoglycemic effect is related to gut microbiota remains elusive. AIM OF THE STUDY: Our study aimed to explore the insulin-sensitizing and anti-diabetic effects of ginsenoside Rb1 as well as the underlying mechanisms. MATERIALS AND METHODS: The T2DM model were established by high fat diet (HFD)-induced Kkay mice. The anti-diabetic effect of ginsenoside Rb1 (200 mg/kg/day) was evaluated by random blood glucose (RBG), fasting blood glucose (FBG), glucose tolerance test (OGTT), serum insulin level, insulin resistance index (HOMA-IR), pancreatic histology analysis, liver indexes, total triglyceride (TG) and total cholesterol (TC). Subsequently, 16S rRNA sequencing and LC-MS-based untargeted metabolomics were applied to characterize the microbiome and metabolites profile in HFD-induced Kkay mice, respectively. Finally, antibiotic treatment was used to validate the potential mechanism of ginsenoside Rb1 by modulating gut microbiota. RESULTS: Our results showed that ginsenoside Rb1 reduced blood glucose, OGTT, serum insulin level, HOMA-IR, liver indexes as well as pancreatic injury. In addition, the ginsenoside Rb1 reversed the gut microbiota dysbiosis in diabetic Kkay mice, as indicated by the elevated abundance of Parasutterella, decreased population of Alistipes, f_Prevotellaceae_unclassified, Odoribacter, Anaeroplasma. Moreover, ginsenoside Rb1 altered free fatty acid (FFA) levels in fecal metabolites, such as decreased the level of α-linolenic acid, 13-OxoODE, oleic acid, 13-HODE, arachidonic acid, palmitic acid, stearic acid, while increased the level of PC (14:0/22:1(13Z)) and PC (16:0/16:0). Notably, ginsenoside Rb1 failed to improve HFD-induced diabetes in Kkay mice with antibiotics intervention. CONCLUSION: These findings suggested that ginsenoside Rb1 may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play essential roles in diabetes-associated metabolic disorders and insulin resistance.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistência à Insulina , Doenças Metabólicas , Camundongos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , RNA Ribossômico 16S , Insulina , Metaboloma , Antibacterianos/farmacologia , Dieta Hiperlipídica/efeitos adversos
17.
Phys Chem Chem Phys ; 25(3): 1947-1956, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36541372

RESUMO

Similar to microhydrated hydroperoxide anion HOO-(H2O)n, the HOO-(NH3)n=1-3 anion can induce alternative nucleophiles by proton transfer (PT) from the solvent molecule NH3. The PT-induced species NH2-(H2O2)(NH3)n-1 is higher in energy than HOO-(NH3)n, obeying the proton affinity (PA) prediction that HOO- has a higher PA than NH2-. The potential energy profile of HOO-(NH3)n reacting with CH3Cl shows that the transition states of the traditional HOO--SN2 pathway are ∼10 kcal mol-1 lower in energy than those of the PT-induced NH2--SN2 pathway, indicating the latter path is unlikely to compete. The differential solvation energy for reactants and transition states with incremental solvation increases the barrier height of both HOO--/NH2--SN2 pathways and makes the transition structures more product-like. For HOO-(sol)n + CH3Cl → CH3OOH + Cl-(sol)n reactions, the barrier heights for sol = H2O are higher than those for sol = NH3, because H2O is more polar than NH3, and the electrostatic interaction is strengthened, hence H2O molecules stabilize the microsolvated nucleophiles more. In addition, because the H2O molecule is a better proton donor than the NH3 molecule, the PT-induced HO-SN2 pathway is more likely to compete with the HOO-SN2 pathway. The HOMO level of nucleophiles, which negatively correlates with the SN2 barrier heights, is found to be a good descriptor to predict the SN2 barrier height of a microsolvated system with the same attacking nucleophile. This work adds to our understanding of the differential solvent effect on the prototype ion-molecule SN2 reactions.

18.
Blood Press ; 32(1): 6-15, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36495008

RESUMO

PURPOSE: We investigated plasma angiotensin-converting enzyme 2 (ACE2) concentration in a population sample and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue in patients who underwent lung surgery. MATERIALS AND METHODS: The study participants were recruited from a residential area in the suburb of Shanghai for the plasma ACE2 concentration study (n = 503) and the lung tissue samples were randomly selected from the storage in Ruijin Hospital (80 men and 78 age-matched women). RESULTS: In analyses adjusted for covariables, men had a significantly higher plasma ACE2 concentration (1.21 vs. 0.98 ng/mL, p = 0.027) and the mean intensity of ACE2 in the lung tissue (55.1 vs. 53.9 a.u., p = 0.037) than women. With age increasing, plasma ACE2 concentration decreased (p = 0.001), while the mean intensity of ACE2 in the lung tissue tended to increase (p = 0.087). Plasma ACE2 concentration was higher in hypertension than normotension, especially treated hypertension (1.23 vs. 0.98 ng/mL, p = 0.029 vs. normotension), with no significant difference between users of RAS inhibitors and other classes of antihypertensive drugs (p = 0.64). There was no significance of the mean intensity of ACE2 in the lung tissue between patients taking and those not taking RAS inhibitors (p = 0.14). Neither plasma ACE2 concentration nor the mean intensity of ACE2 in the lung tissue differed between normoglycemia and diabetes (p ≥ 0.20). CONCLUSION: ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics of patients.Plain language summary What is the context? • The primary physiological function of ACE2 is the degradation of angiotensin I and II to angiotensin 1-9 and 1-7, respectively. • ACE2 was found to behave as a mediator of the severe acute respiratory syndrome coronavirus (SARS) infection. • There is little research on ACE2 in humans, especially in the lung tissue. • In the present report, we investigated plasma ACE2 concentration and the ACE2 expression quantitated with the diaminobenzidine mean intensity in the lung tissue respectively in two study populations. What is new? • Our study investigated both circulating and tissue ACE2 in human subjects. The main findings were: • In men as well as women, plasma ACE2 concentration was higher in younger than older participants, whereas the mean intensity of ACE2 in the lung tissue increase with age increasing. • Compared with normotension, hypertensive patients had higher plasma ACE2 concentration but similar mean intensity of ACE2 in the lung tissue. • Neither plasma ACE2 concentration nor lung tissue ACE2 expression significantly differed between users of RAS inhibitors and other classes of antihypertensive drugs. What is the impact? • ACE2 in the plasma and lung tissue showed divergent changes according to several major characteristics, such as sex, age, and treated and untreated hypertension. • A major implication is that plasma ACE2 concentration might not be an appropriate surrogate for the ACE2 expression in the lung tissue, and hence not a good predictor of SARS-COV-2 infection or fatality.


Assuntos
COVID-19 , Hipertensão , Masculino , Humanos , Feminino , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/farmacologia , SARS-CoV-2/metabolismo , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/farmacologia , Anti-Hipertensivos/farmacologia , Sistema Renina-Angiotensina , China , Angiotensina I , Pulmão
19.
Int J Nanomedicine ; 17: 5661-5678, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457548

RESUMO

Background: Existing implant materials cannot meet the essential multifunctional requirements of repairing infected bone defects, such as antibacterial and osteogenesis abilities. A promising strategy to develop a versatile biomimicry composite of the natural bone structure may be accomplished by combining a multifunctional nanoparticle with an organic scaffold. Methods: In this study, a quaternary ammonium silane-modified mesoporous silica containing nano silver (Ag@QHMS) was successfully synthesized and further combined with silk fibroin (SF) to fabricate the multifunctional nano-reinforced scaffold (SF-Ag@QHMS) using the freeze-drying method. Furthermore, the antibacterial and osteogenic effects of this composite were evaluated in vitro and in vivo. Results: SF-Ag@QHMS inherited a three-dimensional porous structure (porosity rate: 91.90 ± 0.62%) and better mechanical characteristics (2.11 ± 0.06 kPa) than that of the SF scaffold (porosity rate: 91.62 ± 1.65%; mechanic strength: 2.02 ± 0.01 kPa). Simultaneously, the introduction of versatile nanoparticles has provided the composite with additional antibacterial ability against Porphyromonas gingivalis, which can be maintained for 15 days. Furthermore, the expression of osteogenic-associated factors was up-regulated due to the silver ions eluting from the composite scaffold. The in vivo micro-CT and histological results indicated that the new bone formation was not only localized around the border of the defect but also arose more in the center with the support of the composite. Conclusion: The multifunctional silver-loaded mesoporous silica enhanced the mechanical strength of the composite while also ensuring greater and sustained antibacterial and osteogenic properties, allowing the SF-Ag@QHMS composite to be used to repair infected bone defects.


Assuntos
Doenças Transmissíveis , Fibroínas , Nanopartículas Multifuncionais , Nanopartículas , Humanos , Osteogênese , Dióxido de Silício , Antibacterianos/farmacologia
20.
Food Chem ; 406: 134977, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36470083

RESUMO

The skin discoloration of squid subjected to frozen storage negatively affects market price. In this study, various alkali treatments were investigated for effects on red granules and yellow pigments of squid skin and corresponding mechanisms were investigated at the tissue, cellular and molecular level. A significant colour improvement was observed when subjected to a pH 12 treatment, supported by decreased Δb* and increased Δa* values. Neither lower nor harsher alkali treatments than pH 12 can not obtain such results. HE staining and the UV-vis spectrum suggest that the improved red colour in skin was ascribed to the release of red pigment granules from damaged chromatophores by alkaline treatment and the release of red pigments in alkaline aqueous solutions from granules. However, based on TEM and particle size analysis, an excessive alkali treatment of pH 13 would degrade granules into smaller particles. The degradation of yellowness pigments indicated high sensitivity to alkali environments according to HPLC results. This study provides a valuable reference for improving the colour appearance of squid skin subjected to frozen storage.

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