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1.
Diabetes Obes Metab ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248211

RESUMO

BACKGROUND: Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA). METHODS: In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted. RESULTS: Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality). CONCLUSIONS: The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.

2.
Cardiovasc Res ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288197

RESUMO

AIMS: ß3-AR (ß3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate ß3-AR activation-mediated PVAT function in AD/AA. METHODS AND RESULTS: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect ß3-AR expression in PVAT. ApoE-/- and ß-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a ß3-AR agonist. The results demonstrated an up-regulation of ß3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of ß3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes. CONCLUSIONS: Our findings illustrated the therapeutic potential of ß3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation.

3.
J Colloid Interface Sci ; 677(Pt B): 323-330, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39151225

RESUMO

RuO2 is an efficient electrocatalyst for the oxygen evolution reaction (OER). However, during the OER process, RuO2 is prone to oxidation into Rux+ (x > 4), leading to its dissolution in the electrolyte and resulting in poor stability of RuO2. Here, we report a bicomponent electrocatalyst, NiO and RuO2 co-loaded on carbon nanotubes (RuO2/NiO/CNT). The results demonstrate that the introduction of NiO suppresses the over-oxidation of RuO2 during the OER process, not only inheriting the excellent catalytic performance of RuO2, but also significantly enhancing the stability of the catalyst for OER at high current densities. In contrast to RuO2/CNT, RuO2/NiO/CNT shows no significant change in activity after 150 h of OER at a current density of 100 mA cm-2. Density functional theory (DFT) calculations indicate that NiO transfers a large number of electrons to RuO2, thereby reducing the oxidation state of Ru. In conclusion, this study provides a detailed analysis of the phenomenon where low-valent metal oxides have the ability to enhance the stability of RuO2 catalysts.

4.
J Colloid Interface Sci ; 676: 896-905, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39068834

RESUMO

The development of efficient, stable, and versatile hydrogen evolution electrocatalysts is of great meaning, but still faces challenging. Interface engineering and phase engineering have been immensely applied in the field of hydrogen evolution reaction (HER) because of their unique physicochemical properties. However, they are typically used separately, which limits their effectiveness. Herein, we propose an interface-engineered CoMo/CoTe electrocatalyst, consisting of an amorphous CoMo (a-CoMo) layer-encapsulated crystalline CoTe array, achieving the profound optimization of catalytic performance. The experimental results and density functional theory calculations show that the d-band center of the catalyst shifts further upward in contrast with its crystalline-crystalline counterpart, optimizing the electronic structure and the intermediate adsorption, thereby reducing the kinetic barrier of HER. The a-CoMo/CoTe with superhydrophilic/superaerophobic features shows excellent catalytic performance in alkaline, neutral, and simulated seawater environments.

5.
J Colloid Interface Sci ; 676: 425-434, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39033677

RESUMO

The design of low-cost, efficient, and stable multifunctional basic catalysts to replace the high-cost noble metal catalysts remains a challenge. In this work, we report a dual-component Co-W2C catalytic system which achieves excellent properties of hydrogen evolution reaction (HER, η10 = 63 mV), oxygen evolution reaction (OER, η10 = 259 mV) and overall water splitting (η10 = 1.53 V) by adjusting the interfacial electronic structure of the material. Further density functional theory (DFT) calculations indicate that the efficient electronic modulation at the W2C/Co interface leads to the generation of favorable hydroxyl and hydrogen species energetics on the hybrid surface. The results of the in-situ Raman spectra show that W2C can suppress the excessive oxidation of the active site during the OER process, and the existence of core-shell structure also protects the W2C substrate. The stable and efficient catalytic performance of Co-W2C is attributed to the common advantages of structural and interface manipulation.

6.
Microbiol Spectr ; 12(4): e0234223, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391229

RESUMO

Seed metabolites are the combination of essential compounds required by an organism across various potential environmental conditions. The seed metabolites screening framework based on the network topology approach can capture important biological information of species. This study aims to identify comprehensively the relationship between seed metabolites and pathogenic bacteria. A large-scale data set was compiled, describing the seed metabolite sets and metabolite sets of 124,192 pathogenic strains from 34 genera, by constructing genome-scale metabolic models. The enrichment analysis method was used to screen the specific seed metabolites of each species/genus of pathogenic bacteria. The metabolites of pathogenic microorganisms database (MPMdb) (http://qyzhanglab.hzau.edu.cn/MPMdb/) was established for browsing, searching, predicting, or downloading metabolites and seed metabolites of pathogenic microorganisms. Based on the MPMdb, taxonomic and phylogenetic analyses of pathogenic bacteria were performed according to the function of seed metabolites and metabolites. The results showed that the seed metabolites could be used as a feature for microorganism chemotaxonomy, and they could mirror the phylogeny of pathogenic bacteria. In addition, our screened specific seed metabolites of pathogenic bacteria can be used not only for further tapping the nutritional resources and identifying auxotrophies of pathogenic bacteria but also for designing targeted bactericidal compounds by combining with existing antimicrobial agents.IMPORTANCEMetabolites serve as key communication links between pathogenic microorganisms and hosts, with seed metabolites being crucial for microbial growth, reproduction, external communication, and host infection. However, the large-scale screening of metabolites and the identification of seed metabolites have always been the main technical bottleneck due to the low throughput and costly analysis. Genome-scale metabolic models have become a recognized research paradigm to investigate the metabolic characteristics of species. The developed metabolites of pathogenic microorganisms database in this study is committed to systematically predicting and identifying the metabolites and seed metabolites of pathogenic microorganisms, which could provide a powerful resource platform for pathogenic bacteria research.


Assuntos
Anti-Infecciosos , Sementes , Filogenia , Bactérias , Bases de Dados Factuais , Anti-Infecciosos/metabolismo
7.
Quant Imaging Med Surg ; 13(12): 8383-8394, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106324

RESUMO

Background: Intracranial atherosclerotic disease (ICAD) is one of the most common causes of ischemic stroke. The fetal-type posterior cerebral artery (FTP) affects intracranial collateral circulation, which is closely related to the occurrence and development of ICAD. Knowledge of the relationship between FTP and ICAD is important for developing treatment strategies for FTP patients diagnosed with atherosclerotic diseases. This study aims to quantitatively analyze the association between the FTP and intracranial atherosclerotic plaques using magnetic resonance vessel wall imaging (VW-MRI). Methods: This retrospective study enrolled patients with recent cerebrovascular symptoms (stroke or transient ischemic attack <2 weeks) who were diagnosed with atherosclerotic plaque(s) by VW-MRI in one hospital from October 2018 to March 2022. They were classified into the FTP group and the non-FTP group. Plaque characteristics and vascular-related parameters in intracranial arteries were compared between the two groups. Univariate and multivariate logistic regressions were performed to determine the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of the plaque characteristics between the two groups. Results: A total of 104 patients (mean age: 61.8±9.8 years, 57 males) were included for VW-MRI scan analysis. 40 (38.46%) and 64 (61.54%) were classified into the FTP and the non-FTP groups, respectively. The plaques of middle cerebral artery (MCA) in the FTP group were more likely to occur on the dorsal and superior walls of the lumen compared with the non-FTP group (37.50% vs. 17.19%, P=0.001). The remodeling index (RI) of MCA was statistically different between the two groups (1.071±0.267 vs. 0.886±0.235, P=0.007). No significant differences were found in vertebrobasilar artery (VBA) plaque distributions (17.50% vs. 9.38%, 10.00% vs. 12.50%, 20.00% vs. 17.19%, P>0.05) and characteristics between the two groups (RI: 1.095±0.355 vs. 0.978±0.251; eccentricity index: 0.539±1.622 vs. 0.550±0.171, P>0.05). Conclusions: The plaques in the FTP group were more likely to occur on the dorsal and superior walls of the MCA, and the presentence of FTP was found to be significantly correlated with vascular remodeling of MCA atherosclerotic plaques. The relationship between the severity of intracranial atherosclerosis and the presence of FTP can provide valuable information for clinicians to intervene early and prevent the occurrence of stroke.

8.
J Org Chem ; 88(23): 16400-16409, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37983977

RESUMO

A mild chlorocyclization of pyrrole-tethered indoles has been realized using POCl3 as the chlorine source and tetramethylene sulfoxide as the promoter. A variety of chlorinated indolizino[8,7-b]indole derivatives have been constructed efficiently under this reaction system in moderate to good yields (19 examples, up to 93% yield).

9.
Phytomedicine ; 121: 155119, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801894

RESUMO

BACKGROUND: Previous studies have reported that puerarin possesses cardioprotective, vasodilatory, anti-inflammatory, anti-apoptotic, and hypoglycemic properties. However, the impact of puerarin on sepsis-associated encephalopathy (SAE) remains unexplored. In this study, we explored whether puerarin can modulate microglia-mediated neuroinflammation for the treatment of SAE and delved into the underlying mechanisms. METHODS: We established a murine model of SAE through intraperitoneal injection of lipopolysaccharide (LPS). The puerarin treatment group received pretreatment with puerarin. For in vitro experiments, BV2 cells were pre-incubated with puerarin for 2 h before LPS exposure. We employed network pharmacology, the Morris Water Maze (MWM) test, Novel Object Recognition (NOR) test, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time PCR (qRT-PCR) to elucidate the molecular mechanism of underlying puerarin's effects in SAE treatment. RESULTS: Our findings demonstrate that puerarin significantly reduced the production of inflammatory cytokines (TNF-α and IL-6) in the peripheral blood of LPS-treated mice. Moreover, puerarin treatment markedly ameliorated sepsis-associated cognitive impairment. Puerarin also exhibited inhibitory effects on the release of TNF-α and IL-6 from microglia, thereby preventing hippocampal neuronal cell death. Network pharmacology analysis identified AKT1 as a potential therapeutic target for puerarin in SAE treatment. Subsequently, we validated these results in both in vitro and in vitro experiments. Our study conclusively demonstrated that puerarin reduced LPS-induced phosphorylation of AKT1, with the AKT activator SC79 reversing puerarin's anti-inflammatory effects through the activation of the AKT1 signaling pathway. CONCLUSION: Puerarin exerts an anti-neuroinflammatory effect against SAE by modulating the AKT1 pathway in microglia.


Assuntos
Encefalopatia Associada a Sepse , Camundongos , Animais , Encefalopatia Associada a Sepse/tratamento farmacológico , Encefalopatia Associada a Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Microglia , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
10.
Fa Yi Xue Za Zhi ; 39(4): 399-405, 2023 Aug 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37859480

RESUMO

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.


Assuntos
Microbiota , Mudanças Depois da Morte , Humanos , Inteligência Artificial , Autopsia , Cadáver
11.
J Colloid Interface Sci ; 652(Pt B): 1665-1672, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37666198

RESUMO

The rational design of electrocatalysts with exceptional performance and durability for hydrogen production in alkaline medium is a formidable challenge. In this study, we have developed in-situ activated ruthenium nanoparticles dispersed on Ni3N nanosheets, forming a bifunctional electrocatalyst for hydrogen evolution and urea oxidation. The results of experimental analysis and theoretical calculations reveal that the enhanced hydrogen evolution reaction (HER) performance of O-Ru-Ni3N stems primarily from the optimized hydrogen adsorption and hydroxyl adsorption on Ru sites. The O-Ru-Ni3N on nickel foam (NF) electrode exhibits excellent HER performance, requiring only 29 mV to reach 10 mA cm-2 in an alkaline medium. Notably, when this O-Ru-Ni3N/NF catalyst is employed for both HER and urea oxidation reaction (UOR) to create an integrated H2 production system, a current density of 50 mA cm-2 can be generated at the cell voltage of 1.41 V. This report introduces an energy-efficient catalyst for hydrogen production and proposes a viable strategy for anodic activation in energy chemistry.

12.
Eur J Radiol ; 168: 111107, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37776582

RESUMO

PURPOSE: To investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. METHOD: Eighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. RESULTS: Higher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). CONCLUSIONS: Culprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.


Assuntos
Isquemia Encefálica , Arteriosclerose Intracraniana , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Humanos , Artéria Cerebral Média/diagnóstico por imagem , Placa Aterosclerótica/complicações , Placa Aterosclerótica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/complicações , Hemoglobinas Glicadas , Constrição Patológica , Estudos Retrospectivos , AVC Isquêmico/complicações , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Angiografia por Ressonância Magnética/métodos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
13.
J Org Chem ; 88(19): 13598-13609, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37728513

RESUMO

Benzylation of pyrrolo[2,1-a]isoquinoline derivatives has been realized with various phenols by the use of ammonium acetate as a promoter (20 examples, up to 84% yield). DMSO served as the source of methylene and solvent. The employment of iron chloride as a catalyst can also afford the desired benzylated products in moderate to good yields (11 examples, up to a 74% yield).

14.
J Org Chem ; 88(16): 11935-11944, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37550603

RESUMO

We have developed an efficient chlorination of pyrrolo[2,1-a]isoquinoline derivatives using POCl3 as the chlorine source and tetramethylene sulfoxide as a promoter. A series of pyrrolo[2,1-a]isoquinolines, polysubstituted pyrroles, and naphthols have been readily chlorinated under mild reaction conditions (26 examples, up to >99% yield). AcCl can also act as the chlorine source competently in this chlorination reaction.

15.
J Colloid Interface Sci ; 651: 760-768, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37572613

RESUMO

Studying interfacial charge transfer is of great significance for the preparation of electrocatalysts with high activity for the hydrogen evolution reaction (HER). Particularly, exploring the in-depth catalytic mechanisms and facile fabrication methods of narrow bandgap metal phosphides remains worthwhile. This work successfully combined catalytically inert n-type Nb2O5 with p-type CoP to prepare a p-n heterojunction (CoP-Nb2O5). The self-supporting heterojunction was fabricated by gas-phase phosphorization of the Co(OH)2-Nb2O5 precursor obtained through hydrothermal-electrodeposition strategy. By analyzing the electronic and band structures of CoP and Nb2O5, it was found that there exists a built-in electric field (BEF) in the heterojunction. This BEF can modulate the electronic structure of CoP at the interface, enhance its intrinsic activity and accelerate charge migration. The subsequent experimental results also demonstrate that Nb2O5 can significantly enhance the activity and stability of CoP. Our findings can serve as a novel perspective on the application of p-n heterojunction in the field of energy storage and conversion.

16.
Comput Struct Biotechnol J ; 21: 2973-2984, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37235186

RESUMO

Transporters are the main determinant for pharmacokinetics characteristics of drugs, such as absorption, distribution, and excretion of drugs in humans. However, it is difficult to perform drug transporter validation and structure analysis of membrane transporter proteins by experimental methods. Many studies have demonstrated that knowledge graphs (KG) could effectively excavate potential association information between different entities. To improve the effectiveness of drug discovery, a transporter-related KG was constructed in this study. Meanwhile, a predictive frame (AutoInt_KG) and a generative frame (MolGPT_KG) were established based on the heterogeneity information obtained from the transporter-related KG by the RESCAL model. Natural product Luteolin with known transporters was selected to verify the reliability of the AutoInt_KG frame, its ROC-AUC (1:1), ROC-AUC (1:10), PR-AUC (1:1), PR-AUC (1:10) are 0.91, 0.94, 0.91 and 0.78, respectively. Subsequently, the MolGPT_KG frame was constructed to implement efficient drug design based on transporter structure. The evaluation results showed that the MolGPT_KG could generate novel and valid molecules and that these molecules were further confirmed by molecular docking analysis. The docking results showed that they could bind to important amino acids at the active site of the target transporter. Our findings will provide rich information resources and guidance for the further development of the transporter-related drugs.

17.
J Org Chem ; 88(11): 7347-7361, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37167603

RESUMO

We have developed a mild sulfenylation of pyrrolo[2,1-a]isoquinolines with acetyl bromide and dimethyl sulfoxide. A wide range of functionalized pyrrolo[2,1-a]isoquinolines could be prepared efficiently through the formation of a C-S bond with thiophenols (27 examples, 36-94% yields). The current strategy can also be utilized for functionalization of pyrrolo[1,2-a]quinolines and indole.

18.
Yi Chuan ; 45(4): 341-353, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37077167

RESUMO

Fracture healing is a rigorous and orderly process with multiple steps that are mediated by multiple cells. During this process, osteoclast-mediated bone remodeling plays a critical role, and its abnormal activity leads not only to fracture susceptibility but also to impaired fracture healing. However, few studies have focused on impaired healing caused by osteoclast defects, and clinical drugs for this type of impaired fracture healing are still lacking. The cell types and regulatory pathways in the zebrafish skeletal system are highly similar to those of mammals, making the zebrafish skeletal system being widely used for skeletal-related studies. To study the process of fracture healing disorders caused by osteoclast defects and discover potential therapeutic drugs, we established an in vivo osteoclast-deficient fracture model using a previously generated fms gene mutant zebrafish (fmsj4e1). The results showed that reduced functional osteoclasts could affect fracture repair in the early stages of fracture. Then we applied an in vitro scale culture system to screen for osteoclast-activating drugs. We found the small molecule compound allantoin (ALL) being able to activate osteoclasts. Subsequently, we verified the activation role of ALL on osteoclasts and the promotion of fracture repair in an in vivo fmsj4e1 fracture defect model. Finally, by examining the osteoclastogenesis and maturation process, we found that ALL may promote osteoclast maturation by regulating RANKL/OPG, thus promoting fmsj4e1 fracture healing. Our study provides a potential new approach for the future improvement of fracture healing disorders caused by osteoclast defects.


Assuntos
Osteoclastos , Peixe-Zebra , Animais , Osteoclastos/metabolismo , Consolidação da Fratura , Alantoína/metabolismo , Osteogênese , Diferenciação Celular/genética , Mamíferos
19.
Syst Appl Microbiol ; 46(3): 126419, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37030242

RESUMO

Two novel strains GSK1Z-4-2T and MQZ15Z-1 were isolated from branches of mangrove plants collected from Guangxi Zhuang Autonomous Region, China. Both strains were Gram-negative, aerobic, non-flagellated and non-spore-forming bacteria. The comparison of 16S rRNA gene sequences initially indicated that the two strains were assigned to the genus Ancylobacter with sharing the highest similarity to Ancylobacter pratisalsi DSM 102029T (97.3%). The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values between strains GSK1Z-4-2T and MQZ15Z-1 were 99.9%, 97.4% and 77.4%, respectively, which revealed that the two strains belonged to the same species. Phylogenetic analyses based on 16S rRNA gene sequences and the core proteome showed that the two strains formed a well-supported cluster with A. pratisalsi DSM 102029T. Moreover, the ANI and isDDH values between strain GSK1Z-4-2T and A. pratisalsi DSM 102029T were 83.0% and 25.8%, respectively, demonstrating that strain GSK1Z-4-2T was a previously undescribed species. Meanwhile, strains GSK1Z-4-2T and MQZ15Z-1 exhibited most of chemotaxonomic and phenotypic features consistent with the description of the genus Ancylobacter. Based on the polyphasic data, strains GSK1Z-4-2T and MQZ15Z-1 should represent a novel species of the genus Ancylobacter, for which the name Ancylobacter mangrovi sp. nov. is proposed. The type strain is GSK1Z-4-2T (=MCCC 1K07181T = JCM 34924T).


Assuntos
Ácidos Graxos , Filogenia , RNA Ribossômico 16S/genética , China , DNA Bacteriano/genética , Hibridização de Ácido Nucleico , Análise de Sequência de DNA , Técnicas de Tipagem Bacteriana
20.
Artigo em Inglês | MEDLINE | ID: mdl-36884384

RESUMO

A endospore-forming bacterium, designated strain KQZ6P-2T, was isolated from surface-sterilized bark of the mangrove plant Kandelia candel, collected from Maowei Sea Mangrove Nature Reserve in Guangxi Zhuang Autonomous Region, China. Strain KQZ6P-2T was able to grow at NaCl concentrations in the range of 0-3 % (w/v) with optimum growth at 0-1 % (w/v) NaCl. Growth occurred at 20-42 °C (optimal growth at 30-37 °C) and pH 5.5-6.5 (optimal growth at pH 6.5). The 16S rRNA gene sequence similarity between strain KQZ6P-2T and its closest phylogenetic neighbour Paenibacillus chibensis JCM 9905T was 98.2 %. Phylogenetic analyses using 16S rRNA gene sequences showed that strain KQZ6P-2T formed a distinct lineage with Paenibacillus chibensis JCM 9905T. The draft genome of strain KQZ6P-2T was 5 937 633 bp in size and its DNA G+C content was 47.2mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values among strain KQZ6P-2T and its related species were below the cut-off levels of 95, 70 and 95.5%, respec-tively. The cell-wall peptidoglycan of strain KQZ6P-2T contained meso-diaminopimelic acid as the diagnostic diamino acid. Major cellular fatty acids were anteiso-C15:0 and C16:0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified aminophospholipids, four unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. Based on phylogenetic, phenotypic and chemotaxonomic data, strain KQZ6P-2T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus mangrovi sp. nov. is proposed. The type strain is KQZ6P-2T (=MCCC 1K07172T =JCM 34931T).


Assuntos
Paenibacillus , Rhizophoraceae , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Cloreto de Sódio , Casca de Planta , DNA Bacteriano/genética , Composição de Bases , China , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos/química , Hibridização Genômica Comparativa
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